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Management of brain tumors presenting in pregnancy: a case series and systematic review. American journal of obstetrics & gynecology MFM Rodrigues, A. J., Waldrop, A. R., Suharwardy, S. n., Druzin, M. L., Iv, M. n., Ansari, J. R., Stone, S. A., Jaffe, R. A., Jin, M. C., Li, G. n., Hayden-Gephart, M. n. 2021; 3 (1): 100256
Abstract

Patients who present with brain tumors during pregnancy require unique imaging and neurosurgical, obstetrical, and anesthetic considerations. Here, we review the literature and discuss the management of patients who present with brain tumors during pregnancy. Between 2009 and 2019, 9 patients were diagnosed at our institution with brain tumors during pregnancy. Clinical information was extracted from the electronic medical records. The median age at presentation was 29 years (range, 25-38 years). The most common symptoms at presentation included headache (n=5), visual changes (n=4), hemiparesis (n=3), and seizures (n=3). The median gestational age at presentation was 20.5 weeks (range, 11-37 weeks). Of note, 8 patients (89%) delivered healthy newborns, and 1 patient terminated her pregnancy. In addition, 5 patients (56%) required neurosurgical procedures during pregnancy (gestational ages, 14-37 weeks) because of disease progression (n=2) or neurologic instability (n=3). There was 1 episode of postneurosurgery morbidity (pulmonary embolism [PE]) and no surgical maternal mortality. The median length of follow-up was 15 months (range, 6-45 months). In cases demonstrating unstable or progressive neurosurgical status past the point of fetal viability, neurosurgical intervention should be considered. The physiological and pharmacodynamic changes of pregnancy substantially affect anesthetic management. Pregnancy termination should be discussed and offered to the patient when aggressive disease necessitates immediate treatment and the fetal gestational age remains previable, although neurologically stable patients may be able to continue the pregnancy to term. Ultimately, pregnant patients with brain tumors require an individualized approach to their care under the guidance of a multidisciplinary team.

View details for DOI 10.1016/j.ajogmf.2020.100256

View details for PubMedID 33451609
Changes in Seizure Frequency and Antiepileptic Therapy during Pregnancy. The New England journal of medicine Pennell, P. B., French, J. A., May, R. C., Gerard, E., Kalayjian, L., Penovich, P., Gedzelman, E., Cavitt, J., Hwang, S., Pack, A. M., Sam, M., Miller, J. W., Wilson, S. H., Brown, C., Birnbaum, A. K., Meador, K. J., MONEAD Study Group, Meador, K. J., Pennell, P. B., May, R., Birnbaum, A., Cohen, M. J., Druzin, M., Finnell, R., French, J., Loring, D. W., McElrath, T. F., Nelson, L., Stowe, Z., Van Marter, L., Wells, P., Yerby, M., Moore, E., Wilson, S. H., Brown, C., Ippolito, D., Nair, A., Ayre, B., Skinner, J., Davis, L., Hendrickson, L., Shah, N., Leung, B., Arias, M., Robalino, C., Birnbaum, A. K., Karanam, A., Strickland, S., Latif, E., Park, Y., Acosta-Cotte, D., Ray, P., Boyer, K., Hanson, E., Young, A., Hickey, P., Strauss, J., Madeiros, H., Pennell, P., McElrath, F. T., Walsh, A., Chen, L., Allien, S., Lee, T., Sheldon, Y., Weinau, T., Pack, A., Cleary, K., Echo, J., Zygmunt, A., Casadei, C., Irobunda, I., Gedzelman, E., Dolan, M., Ono, K., Bearden, D., Ghilian, C., Teagarden, D., Newman, M., McCabe, P., Paglia, M., Taylor, C., Delucca, R., Barkley, G. L., Spanaki-Varelas, M., Thomas, A., Constantinou, J., Anwar, T., Holmes, T., Johnson, E., Krauss, G., Lawson, S., Pritchard, A., Ryan, M., Coe, P., Penovich, P., Hanna, J., Reger, K., Meehan, S., Olson, A., Schweizer, W., Rosenberg, J., Smith, A., Hwang, S., Tam Tam, H. B., Cukier, Y., Meltzer, E., DiCarlo, G., Lau, C., Smith, B., Gerard, E., Grobman, W., Coda, J., Miller, E., Bellinski, I., Bachman, E., Meador, K., Krueger, C., Seliger, J., DeWolfe, J., Owen, J., Thompson, M., Hall, C., Willia, V., Labiner, D., Maciulla, J., Moon, J., Kunnaz, L., Cavitt, J., Privitera, M., Flood-Schaffer, K., Jewell, G., McElroy, B., Mendoza, L., Serrano, E., Salih, Y., Bermudez, C., Miranda, M., Velez-Ruiz, N., Figueredo, P., Bagic, A., Popescu Urban, A., Gedela, S., Patterson, C., Jeyabalan, A., Radonovich, K., Sutcliffe, M., Beers, S., Wiles, C., Mosovsky, S., Kalayjian, L., Stek, A., Perez, S., Sierra, R., Miller, J. W., Mao, J., Phatak, V., Kim, M., Cheng-Hakimian, A., Oliva, A., Sam, M., Parker, L., Morris, M., Dimos, J., Miller, D. 2020; 383 (26): 2547?56
Abstract

BACKGROUND: Among women with epilepsy, studies regarding changes in seizure frequency during pregnancy have been limited by the lack of an appropriate nonpregnant comparator group to provide data on the natural course of seizure frequency in both groups.METHODS: In this prospective, observational, multicenter cohort study, we compared the frequency of seizures during pregnancy through the peripartum period (the first 6 weeks after birth) (epoch 1) with the frequency during the postpartum period (the following 7.5 months after pregnancy) (epoch 2). Nonpregnant women with epilepsy were enrolled as controls and had similar follow-up during an 18-month period. The primary outcome was the percentage of women who had a higher frequency of seizures that impaired awareness during epoch 1 than during epoch 2. We also compared changes in the doses of antiepileptic drugs that were administered in the two groups during the first 9 months of epoch 1.RESULTS: We enrolled 351 pregnant women and 109 controls with epilepsy. Among the 299 pregnant women and 93 controls who had a history of seizures that impaired awareness and who had available data for the two epochs, seizure frequency was higher during epoch 1 than during epoch 2 in 70 pregnant women (23%) and in 23 controls (25%) (odds ratio, 0.93; 95% confidence interval [CI], 0.54 to 1.60). During pregnancy, the dose of an antiepileptic drug was changed at least once in 74% of pregnant women and in 31% of controls (odds ratio, 6.36; 95% CI, 3.82 to 10.59).CONCLUSIONS: Among women with epilepsy, the percentage who had a higher incidence of seizures during pregnancy than during the postpartum period was similar to that in women who were not pregnant during the corresponding epochs. Changes in doses of antiepileptic drugs occurred more frequently in pregnant women than in nonpregnant women during similar time periods. (Funded by the National Institutes of Health; MONEAD ClinicalTrials.gov number, NCT01730170.).

View details for DOI 10.1056/NEJMoa2008663

View details for PubMedID 33369356
Maternal and Infant Adverse Outcomes Associated with Mild and Severe Preeclampsia during the First Year after Delivery in the United States AMERICAN JOURNAL OF PERINATOLOGY Ton, T. N., Bennett, M. V., Incerti, D., Peneva, D., Druzin, M., Stevens, W., Butwick, A. J., Lee, H. C. 2020; 37 (4): 398?408
View details for DOI 10.1055/s-0039-1679916

View details for Web of Science ID 000519106200009
2019 American College of Rheumatology Reproductive Health in Rheumatic and Musculoskeletal Diseases Guideline. Arthritis care & research Sammaritano, L. R., Bermas, B. L., Chakravarty, E. E., Chambers, C., Clowse, M. E., Lockshin, M. D., Marder, W., Guyatt, G., Ware Branch, D., Buyon, J., Christopher-Stine, L., Crow-Hercher, R., Cush, J., Druzin, M., Kavanaugh, A., Laskin, C. A., Plante, L., Salmon, J., Simard, J., Somers, E. C., Steen, V., Tedeschi, S. K., Vinet, E., Whitney White, C., Yazdany, J., Barbhaiya, M., Bettendorf, B., Eudy, A., Jayatilleke, A., Aakash Shah, A., Sullivan, N., Tarter, L. L., Birru Talabi, M., Turgunbaev, M., Turner, A., D'Anci, K. E. 2020
Abstract

OBJECTIVE: To develop an evidence-based guideline for rheumatic and musculoskeletal disease (RMD) patients regarding contraception; assisted reproductive technology (ART); fertility preservation; pregnancy assessment, counseling, and management; medication use before, during and after pregnancy; and hormone replacement therapy (HRT).METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, pregnancy and lactation, and HRT in RMD populations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence, and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements (GPS) were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.RESULTS: This ACR guideline provides 12 ungraded GPS and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus (SLE), those positive for antiphospholipid antibody (aPL) and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and GPS support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while on pregnancy compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues given the overall low level of evidence available for RMD patients in this area.CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences and comorbidities.

View details for DOI 10.1002/acr.24130

View details for PubMedID 32090466
2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis & rheumatology (Hoboken, N.J.) Sammaritano, L. R., Bermas, B. L., Chakravarty, E. E., Chambers, C., Clowse, M. E., Lockshin, M. D., Marder, W., Guyatt, G., Branch, D. W., Buyon, J., Christopher-Stine, L., Crow-Hercher, R., Cush, J., Druzin, M., Kavanaugh, A., Laskin, C. A., Plante, L., Salmon, J., Simard, J., Somers, E. C., Steen, V., Tedeschi, S. K., Vinet, E., White, C. W., Yazdany, J., Barbhaiya, M., Bettendorf, B., Eudy, A., Jayatilleke, A., Shah, A. A., Sullivan, N., Tarter, L. L., Birru Talabi, M., Turgunbaev, M., Turner, A., D'Anci, K. E. 2020
Abstract

OBJECTIVE: To develop an evidence-based guideline on contraception, assisted reproductive technologies (ART), fertility preservation with gonadotoxic therapy, use of menopausal hormone replacement therapy (HRT), pregnancy assessment and management, and medication use in patients with rheumatic and musculoskeletal disease (RMD).METHODS: We conducted a systematic review of evidence relating to contraception, ART, fertility preservation, HRT, pregnancy and lactation, and medication use in RMD populations, using Grading of Recommendations Assessment, Development and Evaluation methodology to rate the quality of evidence and a group consensus process to determine final recommendations and grade their strength (conditional or strong). Good practice statements were agreed upon when indirect evidence was sufficiently compelling that a formal vote was unnecessary.RESULTS: This American College of Rheumatology guideline provides 12 ungraded good practice statements and 131 graded recommendations for reproductive health care in RMD patients. These recommendations are intended to guide care for all patients with RMD, except where indicated as being specific for patients with systemic lupus erythematosus, those positive for antiphospholipid antibody, and/or those positive for anti-Ro/SSA and/or anti-La/SSB antibodies. Recommendations and good practice statements support several guiding principles: use of safe and effective contraception to prevent unplanned pregnancy, pre-pregnancy counseling to encourage conception during periods of disease quiescence and while receiving pregnancy-compatible medications, and ongoing physician-patient discussion with obstetrics/gynecology collaboration for all reproductive health issues, given the overall low level of available evidence that relates specifically to RMD.CONCLUSION: This guideline provides evidence-based recommendations developed and reviewed by panels of experts and RMD patients. Many recommendations are conditional, reflecting a lack of data or low-level data. We intend that this guideline be used to inform a shared decision-making process between patients and their physicians on issues related to reproductive health that incorporates patients' values, preferences, and comorbidities.

View details for DOI 10.1002/art.41191

View details for PubMedID 32090480
Does Hydroxychloroquine Protect against Preeclampsia and Preterm Delivery in Systemic Lupus Erythematosus Pregnancies? American journal of perinatology Do, S. C., Rizk, N. M., Druzin, M. L., Simard, J. F. 2020
Abstract

?Systemic lupus erythematosus (SLE) increases the risk of complications in pregnancy. Hydroxychloroquine (HCQ) decreases flares and neonatal lupus syndrome. Limited evidence suggests that HCQ also reduces preeclampsia and preterm birth in SLE pregnancies. We studied whether HCQ was associated with lower odds of preeclampsia and preterm delivery in SLE pregnancies.?We conducted a retrospective cohort study of 129 deliveries of 110 patients with SLE delivered at a single institution (2000-2017). HCQ exposure and preeclampsia, along with other clinical data, were extracted from chart review. Crude and multivariable-adjusted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs).?A total of 41% were exposed to HCQ, of whom 13.5% were complicated by preeclampsia versus 26.3% unexposed to HCQ (adjusted OR?=?0.5; 95% CI: 0.2-1.4). The difference was pronounced for first pregnancies (7 vs. 44%), but power was limited. The difference in preterm deliveries was less pronounced comparing HCQ-exposed pregnancies with HCQ-unexposed pregnancies (34 vs. 40.8%; OR?=?0.3; 95% CI: 0.3-1.5).?Pregnant SLE patients trended toward less preeclampsia and preterm delivery when treated with HCQ. Future larger studies are needed to increase the statistical power, account for additional potential confounders, and more fully account for parity.

View details for DOI 10.1055/s-0039-3402752

View details for PubMedID 31899930
Vaginal progesterone treatment is associated with intrahepatic cholestasis of pregnancy Tsur, A., Kan, P., Datoc, I., Leonard, S. A., Girsen, A., Shaw, G. M., Stevenson, D. K., El-Sayed, Y. Y., Druzin, M. L., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2020: S58?S59
View details for DOI 10.1016/j.ajog.2019.11.084

View details for Web of Science ID 000504997300069
Multiomics Characterization of Preterm Birth in Low- and Middle-Income Countries. JAMA network open Jehan, F. n., Sazawal, S. n., Baqui, A. H., Nisar, M. I., Dhingra, U. n., Khanam, R. n., Ilyas, M. n., Dutta, A. n., Mitra, D. K., Mehmood, U. n., Deb, S. n., Mahmud, A. n., Hotwani, A. n., Ali, S. M., Rahman, S. n., Nizar, A. n., Ame, S. M., Moin, M. I., Muhammad, S. n., Chauhan, A. n., Begum, N. n., Khan, W. n., Das, S. n., Ahmed, S. n., Hasan, T. n., Khalid, J. n., Rizvi, S. J., Juma, M. H., Chowdhury, N. H., Kabir, F. n., Aftab, F. n., Quaiyum, A. n., Manu, A. n., Yoshida, S. n., Bahl, R. n., Rahman, A. n., Pervin, J. n., Winston, J. n., Musonda, P. n., Stringer, J. S., Litch, J. A., Ghaemi, M. S., Moufarrej, M. N., Contrepois, K. n., Chen, S. n., Stelzer, I. A., Stanley, N. n., Chang, A. L., Hammad, G. B., Wong, R. J., Liu, C. n., Quaintance, C. C., Culos, A. n., Espinosa, C. n., Xenochristou, M. n., Becker, M. n., Fallahzadeh, R. n., Ganio, E. n., Tsai, A. S., Gaudilliere, D. n., Tsai, E. S., Han, X. n., Ando, K. n., Tingle, M. n., Maric, I. n., Wise, P. H., Winn, V. D., Druzin, M. L., Gibbs, R. S., Darmstadt, G. L., Murray, J. C., Shaw, G. M., Stevenson, D. K., Snyder, M. P., Quake, S. R., Angst, M. S., Gaudilliere, B. n., Aghaeepour, N. n. 2020; 3 (12): e2029655
Abstract

Worldwide, preterm birth (PTB) is the single largest cause of deaths in the perinatal and neonatal period and is associated with increased morbidity in young children. The cause of PTB is multifactorial, and the development of generalizable biological models may enable early detection and guide therapeutic studies.To investigate the ability of transcriptomics and proteomics profiling of plasma and metabolomics analysis of urine to identify early biological measurements associated with PTB.This diagnostic/prognostic study analyzed plasma and urine samples collected from May 2014 to June 2017 from pregnant women in 5 biorepository cohorts in low- and middle-income countries (LMICs; ie, Matlab, Bangladesh; Lusaka, Zambia; Sylhet, Bangladesh; Karachi, Pakistan; and Pemba, Tanzania). These cohorts were established to study maternal and fetal outcomes and were supported by the Alliance for Maternal and Newborn Health Improvement and the Global Alliance to Prevent Prematurity and Stillbirth biorepositories. Data were analyzed from December 2018 to July 2019.Blood and urine specimens that were collected early during pregnancy (median sampling time of 13.6 weeks of gestation, according to ultrasonography) were processed, stored, and shipped to the laboratories under uniform protocols. Plasma samples were assayed for targeted measurement of proteins and untargeted cell-free ribonucleic acid profiling; urine samples were assayed for metabolites.The PTB phenotype was defined as the delivery of a live infant before completing 37 weeks of gestation.Of the 81 pregnant women included in this study, 39 had PTBs (48.1%) and 42 had term pregnancies (51.9%) (mean [SD] age of 24.8 [5.3] years). Univariate analysis demonstrated functional biological differences across the 5 cohorts. A cohort-adjusted machine learning algorithm was applied to each biological data set, and then a higher-level machine learning modeling combined the results into a final integrative model. The integrated model was more accurate, with an area under the receiver operating characteristic curve (AUROC) of 0.83 (95% CI, 0.72-0.91) compared with the models derived for each independent biological modality (transcriptomics AUROC, 0.73 [95% CI, 0.61-0.83]; metabolomics AUROC, 0.59 [95% CI, 0.47-0.72]; and proteomics AUROC, 0.75 [95% CI, 0.64-0.85]). Primary features associated with PTB included an inflammatory module as well as a metabolomic module measured in urine associated with the glutamine and glutamate metabolism and valine, leucine, and isoleucine biosynthesis pathways.This study found that, in LMICs and high PTB settings, major biological adaptations during term pregnancy follow a generalizable model and the predictive accuracy for PTB was augmented by combining various omics data sets, suggesting that PTB is a condition that manifests within multiple biological systems. These data sets, with machine learning partnerships, may be a key step in developing valuable predictive tests and intervention candidates for preventing PTB.

View details for DOI 10.1001/jamanetworkopen.2020.29655

View details for PubMedID 33337494
Evaluation of US State-Level Variation in Hypertensive Disorders of Pregnancy. JAMA network open Butwick, A. J., Druzin, M. L., Shaw, G. M., Guo, N. n. 2020; 3 (10): e2018741
Abstract

Hypertensive disorders of pregnancy are important causes of maternal and perinatal morbidity in the US. However, the extent of statewide variation in the prevalence of chronic hypertension, pregnancy-induced hypertension or preeclampsia, and eclampsia in the US remains unknown.To examine the extent of statewide variation in the prevalence of chronic hypertension, hypertensive disorders of pregnancy (including pregnancy-induced hypertension or preeclampsia), and eclampsia in the US.A cross-sectional study using 2017 US birth certificate data was conducted from September 1, 2019, to February 1, 2020. A population-based sample of 3?659?553 women with a live birth delivery was included.State-specific prevalence of chronic hypertension, hypertensive disorders of pregnancy, and eclampsia was assessed using multilevel multivariable logistic regression, with the median odds ratio (MOR) to evaluate statewide variation.Of the 3?659?553 women, 185?932 women (5.1%) were younger than 20 years, 727?573 women (19.9%) were aged between 20 and 24 years, 1?069?647 women (29.2%) were aged between 25 and 29 years, 1?037?307 women (28.3%) were aged between 30 and 34 years, 523?607 women (14.3%) were aged between 35 and 39 years, and 115?487 women (3.2%) were 40 years or older. Most women had Medicaid (42.8%) or private insurance (49.4%). Hawaii had the lowest adjusted prevalence of chronic hypertension (1.0%; 95% CI, 0.9%-1.2%), and Alaska had the highest (3.4%; 95% CI, 3.0%-3.9%). Massachusetts had the lowest adjusted prevalence of hypertensive disorders of pregnancy (4.3%; 95% CI, 4.1%-4.6%), and Louisiana had the highest (9.3%; 95% CI, 8.9%-9.8%). Delaware had the lowest adjusted prevalence of eclampsia (0.03%; 95% CI, 0.01%-0.09%), and Hawaii had the highest (2.8%; 95% CI, 2.2%-3.4%). The degree of statewide variation was high for eclampsia (MOR, 2.36; 95% CI, 1.88-2.82), indicating that the median odds of eclampsia were 2.4-fold higher if the same woman delivered in a US state with a higher vs lower prevalence of eclampsia. Modest variation between states was observed for chronic hypertension (MOR, 1.27; 95% CI, 1.20-1.33) and hypertensive disorders of pregnancy (MOR, 1.17; 95% CI, 1.13-1.21).The findings of this study suggest that after accounting for patient-level and state-level variables, substantial state-level variation exists in the prevalence of eclampsia. These data can inform future public-health inquiries to identify reasons for the eclampsia variability.

View details for DOI 10.1001/jamanetworkopen.2020.18741

View details for PubMedID 33001203
A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants AMERICAN JOURNAL OF PERINATOLOGY Spiegel, A. M., Li, J., Oehlert, J. W., Mayo, J. A., Quaintance, C. C., Girsen, A. I., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M., Stevenson, D. K., Gibbs, R. S. 2019; 36 (14): 1453?58
View details for DOI 10.1055/s-0038-1677503

View details for Web of Science ID 000499481500005
Development and validation of a machine learning model for prediction of shoulder dystocia. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology Tsur, A., Batsry, L., Toussia-Cohen, S., Rosenstein, M. G., Barak, O., Brezinov, Y., Yoeli-Ullman, R., Sivan, E., Sirota, M., Druzin, M. L., Stevenson, D. K., Blumenfeld, Y. J., Aran, D. 2019
Abstract

OBJECTIVE: We sought to develop a machine learning (ML) model for prediction of shoulder dystocia (ShD) and to externally validate the model accuracy and potential clinical efficacy in optimizing the use of cesarean delivery (CD) in the context of suspected macrosomia.STUDY DESIGN: We used electronic health records (EHR) from the Sheba Medical Center in Israel to develop the model (derivation cohort) and EHR from the University of California San Francisco Medical Center to validate the model accuracy and clinical efficacy (validation cohort). Subsequent to inclusion and exclusion criteria, the derivation cohort consisted of 686 deliveries [131 complicated by ShD], and the validation cohort of 2,584 deliveries [31 complicated by ShD]. For each of these deliveries, we collected maternal and neonatal delivery outcomes coupled with maternal demographics, obstetric clinical data and sonographic biometric measurements of the fetus. Biometric measurements and their derived estimated fetal weight were adjusted (aEFW) to the date of the delivery. A ML pipeline was utilized to develop the model.RESULTS: In the derivation cohort, the ML model provided significantly better prediction than the current paradigm: using nested cross validation the area under the receiver operator characteristics curve (AUC) of the model was 0.793 �0.041, outperforming aEFW and diabetes (0.745 �0.044, p-value =1e-16). The following risk modifiers had a positive beta >0.02 increasing the risk of ShD: aEFW (0.164), pregestational diabetes (0.047), prior ShD (0.04), female fetal sex (0.04) and adjusted abdominal circumference (0.03). The following risk modifiers had a negative beta < -0.02 protective of ShD: adjusted biparietal diameter (-0.08) and maternal height (-0.03). In the validation cohort the model outperformed aEFW and diabetes (AUC=0.866 vs. 0.784, p-value =0.00007). Additionally, in the validation cohort, among the subgroup of 273 women carrying a fetus with aEFW above 4,000 g, the aEFW had no predictive power (AUC=0.548), and the model performed significantly better (0.775, p-value =0.0002). A risk-score threshold of 0.5 stratified 42.9% of deliveries to the high-risk group that included 90.9% of ShD cases and all cases accompanied by maternal or newborn complications. A more specific threshold of 0.7 stratified only 27.5% of the deliveries to the high-risk groups that included 72.7% of ShD cases, and all those accompanied by newborn complications.CONCLUSION: We developed a ML model for prediction of ShD. We externally validated the model performance in a different cohort. The model predicted ShD better than EFW+ maternal diabetes and was able to stratify the risk of ShD and neonatal injury in the context of suspected macrosomia. This article is protected by copyright. All rights reserved.

View details for DOI 10.1002/uog.21878

View details for PubMedID 31587401
Preterm birth phenotypes in women with autoimmune rheumatic diseases: A population based cohort study. BJOG : an international journal of obstetrics and gynaecology Kolstad, K. D., Mayo, J. A., Chung, L., Chaichian, Y., Kelly, V. M., Druzin, M., Stevenson, D. K., Shaw, G. M., Simard, J. F. 2019
Abstract

OBJECTIVE: To investigate preterm birth (PTB) phenotypes in women with different autoimmune rheumatic diseases in a large population-based cohort.DESIGN: Retrospective cohort study.SETTING: California, USA.POPULATION: All live singleton births in California between 2007 and 2011 were analyzed. Patients with autoimmune disease at delivery were identified by ICD-9 codes for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), polymyositis/dermatomyositis (DM/PM), and juvenile idiopathic arthritis (JIA).METHODS: Maternally linked hospital and birth certificate records of 2,481,516 deliveries were assessed (SLE n=2,272, RA n=1,501, SSc n=88, JIA n=187, DM/PM n=38). Multivariable Poisson regression models estimated risk ratios (RRs) for different PTB phenotypes (relative to term deliveries) for each autoimmune disease compared to the general obstetric population adjusting for maternal age, race/ethnicity, body mass index, smoking, education, payer, parity, and prenatal care.MAIN OUTCOME MEASURES: PTB was assessed overall (20-36 weeks) and by subphenotype: pre-term premature rupture of membranes (PPROM), spontaneous, or medically indicated PTB. Risk of PTB overall and each phenotype was partitioned by gestational age: early (20-31 weeks) and late (32-36 weeks).RESULTS: Risks for PTB were elevated for each autoimmune disease evaluated: SLE (RR 3.27 95%CI 3.01-3.56), RA (RR 2.04 95%CI 1.79-2.33), SSc (RR 3.74 95%CI 2.51-5.58), JIA (RR 2.23 95%CI 1.54-3.23), and DM/PM (RR 5.26 95%CI 3.12-8.89). These elevated risks were observed for the majority of PTB phenotypes as well.CONCLUSIONS: Women with systemic autoimmune diseases appear to have an elevated risk of various PTB phenotypes. Therefore, preconception counseling and close monitoring during pregnancy is crucial.

View details for DOI 10.1111/1471-0528.15970

View details for PubMedID 31571337
Preterm Delivery Phenotypes in Systemic Lupus Erythematosus Pregnancies AMERICAN JOURNAL OF PERINATOLOGY Simard, J. F., Chaichian, Y., Rossides, M., Wikstrom, A., Shaw, G. M., Druzin, M. L. 2019; 36 (9): 964?68
View details for DOI 10.1055/s-0038-1675648

View details for Web of Science ID 000477661000014
Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia FRONTIERS IN IMMUNOLOGY Han, X., Ghaemi, M. S., Ando, K., Peterson, L. S., Ganio, E. A., Tsai, A. S., Gaudilliere, D. K., Stelzer, I. A., Einhaus, J., Bertrand, B., Stanley, N., Culos, A., Tanada, A., Hedou, J., Tsai, E. S., Fallahzadeh, R., Wong, R. J., Judy, A. E., Winn, V. D., Druzins, M. L., Blumenfeld, Y. J., Hlatky, M. A., Quaintance, C. C., Gibbs, R. S., Carvalho, B., Shaw, G. M., Stevenson, D. K., Angst, M. S., Aghaeepour, N., Gaudilliere, B. 2019; 10
View details for DOI 10.3389/fimmu.2019.01305

View details for Web of Science ID 000470999000001
Systolic Hypertension, Preeclampsia-Related Mortality, and Stroke in California. Obstetrics and gynecology Judy, A. E., McCain, C. L., Lawton, E. S., Morton, C. H., Main, E. K., Druzin, M. L. 2019; 133 (6): 1151?59
Abstract

OBJECTIVE: To describe the clinical characteristics of stroke and opportunities to improve care in a cohort of preeclampsia-related maternal mortalities in California.METHODS: The California Pregnancy-Associated Mortality Review retrospectively examined a cohort of preeclampsia pregnancy-related deaths in California from 2002 to 2007. Stroke cases were identified among preeclampsia deaths, and case summaries were reviewed with attention to clinical variables, particularly hypertension. Health care provider- and patient-related contributing factors were also examined.RESULTS: Among 54 preeclampsia pregnancy-related deaths that occurred in California from 2002 to 2007, 33 were attributed to stroke. Systolic blood pressure exceeded 160 mm Hg in 96% of cases, and diastolic blood pressure was 110 or higher in 65% of cases. Hemolysis, elevated liver enzymes, and low platelet count syndrome was present in 38% (9/24) of cases with available laboratory data; eclampsia occurred in 36% of cases. Headache was the most frequent symptom (87%) preceding stroke. Elevated liver transaminases were the most common laboratory abnormality (71%). Only 48% of women received antihypertensive treatment. A good-to-strong chance to alter outcome was identified in stroke cases 66% (21/32), with delayed response to clinical warning signs in 91% (30/33) of cases and ineffective treatment in 76% (25/33) cases being the most common areas for improvement.CONCLUSION: Stroke is the major cause of maternal mortality associated with preeclampsia or eclampsia. All but one patient in this series of strokes demonstrated severe elevation of systolic blood pressure, whereas other variables were less consistently observed. Antihypertensive treatment was not implemented in the majority of cases. Opportunities for care improvement exist and may significantly affect maternal mortality.

View details for DOI 10.1097/AOG.0000000000003290

View details for PubMedID 31135728
Systolic Hypertension, Preeclampsia-Related Mortality, and Stroke in California. Obstetrics and gynecology Judy, A. E., McCain, C. L., Lawton, E. S., Morton, C. H., Main, E. K., Druzin, M. L. 2019
Abstract

OBJECTIVE: To describe the clinical characteristics of stroke and opportunities to improve care in a cohort of preeclampsia-related maternal mortalities in California.METHODS: The California Pregnancy-Associated Mortality Review retrospectively examined a cohort of preeclampsia pregnancy-related deaths in California from 2002 to 2007. Stroke cases were identified among preeclampsia deaths, and case summaries were reviewed with attention to clinical variables, particularly hypertension. Health care provider- and patient-related contributing factors were also examined.RESULTS: Among 54 preeclampsia pregnancy-related deaths that occurred in California from 2002 to 2007, 33 were attributed to stroke. Systolic blood pressure exceeded 160 mm Hg in 96% of cases, and diastolic blood pressure was 110 or higher in 65% of cases. Hemolysis, elevated liver enzymes, and low platelet count syndrome was present in 38% (9/24) of cases with available laboratory data; eclampsia occurred in 36% of cases. Headache was the most frequent symptom (87%) preceding stroke. Elevated liver transaminases were the most common laboratory abnormality (71%). Only 48% of women received antihypertensive treatment. A good-to-strong chance to alter outcome was identified in stroke cases 66% (21/32), with delayed response to clinical warning signs in 91% (30/33) of cases and ineffective treatment in 76% (25/33) cases being the most common areas for improvement.CONCLUSION: Stroke is the major cause of maternal mortality associated with preeclampsia or eclampsia. All but one patient in this series of strokes demonstrated severe elevation of systolic blood pressure, whereas other variables were less consistently observed. Antihypertensive treatment was not implemented in the majority of cases. Opportunities for care improvement exist and may significantly affect maternal mortality.

View details for PubMedID 31083120
Systemic lupus erythematosus in pregnancy: high risk, high reward CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Do, S. C., Druzin, M. L. 2019; 31 (2): 120?26
View details for DOI 10.1097/GCO.0000000000000528

View details for Web of Science ID 000480728000006
Understanding health disparities JOURNAL OF PERINATOLOGY Stevenson, D. K., Wong, R. J., Aghaeepour, N., Angst, M. S., Darmstadt, G. L., DiGiulio, D. B., Druzin, M. L., Gaudilliere, B., Gibbs, R. S., Gould, J. B., Katzl, M., Li, J., Moufarrej, M. N., Quaintancel, C. C., Quake, S. R., Reiman, D. A., Shawl, G. M., Snyder, M. P., Wang, X., Wisel, P. H. 2019; 39 (3): 354?58
View details for DOI 10.1038/s41372-018-0298-1

View details for Web of Science ID 000459549600003
Preeclampsia and Preterm Birth Risk in Women Receiving Dialysis During Pregnancy: A Population-Based Cohort Study. Do, S. C., O'Shaughnessy, M. M., Mayo, J., Girsen, A. I., Shaw, G. M., Stevenson, D. K., Druzin, M. L. SAGE PUBLICATIONS INC. 2019: 178A?179A
View details for Web of Science ID 000459610400342
Maternal and Infant Adverse Outcomes Associated with Mild and Severe Preeclampsia during the First Year after Delivery in the United States. American journal of perinatology Ton, T. G., Bennett, M. V., Incerti, D., Peneva, D., Druzin, M., Stevens, W., Butwick, A. J., Lee, H. C. 2019
Abstract

BACKGROUND: The burden of preeclampsia severity on the health of mothers and infants during the first year after delivery is unclear given the lack of population-based longitudinal studies in the United States.METHODS: We assessed maternal and infant adverse outcomes during the first year after delivery using population-based hospital discharge information merged with vital statistics and birth certificates of 2,021,013 linked maternal-infant births in California. We calculated sampling weights using the National Center for Health Statistics data to adjust for observed differences in maternal characteristics between California and the rest of the United States. Separately, we estimated the association between preeclampsia and gestational age and examined collider bias in models of preeclampsia and maternal and infant adverse outcomes.RESULTS: Compared with women without preeclampsia, women with mild and severe preeclampsia delivered 0.66 weeks (95% confidence interval [CI]: 0.64, 0.68) and 2.74 weeks (95% CI: 2.72, 2.77) earlier, respectively. Mild preeclampsia was associated with an increased risk of having any maternal adverse outcome (relative risk [RR]=1.95; 95% CI: 1.93, 1.97), as was severe preeclampsia (RR=2.80; 95% CI: 2.78, 2.82). The risk of an infant adverse outcome was increased for severe preeclampsia (RR=2.15; 95% CI: 2.14, 2.17) but only marginally for mild preeclampsia (RR=0.99; 95% CI: 0.98, 1). Collider bias produced an inverse association for mild preeclampsia and attenuated the association for severe preeclampsia in models for any infant adverse outcome.CONCLUSION: Using multiple datasets, we estimated that severe preeclampsia is associated with a higher risk of maternal and infant adverse outcomes compared with mild preeclampsia, including an earlier preterm delivery.

View details for PubMedID 30780187
A Genome-Wide Analysis of Clinical Chorioamnionitis among Preterm Infants. American journal of perinatology Spiegel, A. M., Li, J., Oehlert, J. W., Mayo, J. A., Quaintance, C. C., Girsen, A. I., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M., Stevenson, D. K., Gibbs, R. S. 2019
Abstract

OBJECTIVE: To identify single nucleotide polymorphisms (SNPs) associated with clinical chorioamnionitis among preterm infants.STUDY DESIGN: We reanalyzed a genome-wide association study (GWAS) from preterm newborns at less than 30 weeks' gestation. Cases and control definitions were determined using administrative records. There were 213 clinical chorioamnionitis cases and 707 clinically uninfected controls. We compared demographic and clinical outcomes of cases and controls. We performed a GWAS and compared the distribution of SNPs from the background genes and from the immunome genes. We used a Wilcoxon's rank-sum test to compare the SNPs normalized odds ratio and used odds ratios and p-values to determine candidate genes.RESULTS: Infants affected by clinical chorioamnionitis were more likely to have periventricular leukomalacia, high-grade retinopathy, and high-grade intraventricular hemorrhage (IVH). Although a GWAS did not identify SNPs associated with clinical chorioamnionitis at the genome-wide significance level, a direct test on the exonic variants in the human immunome revealed their significant increase of risk in clinical chorioamnionitis.CONCLUSION: Among very preterm infants, clinical chorioamnionitis was associated with periventricular leukomalacia, high-grade retinopathy, and IVH. Our analysis of variants in the human immunome indicates an association with clinical chorioamnionitis in very preterm pregnancies.

View details for PubMedID 30674050
Systemic lupus erythematosus in pregnancy: high risk, high reward. Current opinion in obstetrics & gynecology Do, S. C., Druzin, M. L. 2019
Abstract

PURPOSE OF REVIEW: The aim of this study was to describe risks of systemic lupus erythematosus (SLE) in pregnancy and the importance of preconception counselling, medication optimization and close surveillance.RECENT FINDINGS: Advances in care for pregnant patients with SLE have led to improved obstetric outcomes, but maternal and foetal risks continue to be elevated. Conception during periods of disease quiescence and continuation of most medications decrease adverse pregnancy outcomes. Hydroxychloroquine (HCQ) appears protective against flares in pregnancy, neonatal congenital heart block and preterm birth.SUMMARY: SLE in pregnancy confers increased maternal and foetal risks, including disease flares, preeclampsia, preterm birth, foetal growth restriction, neonatal lupus erythematosus (NLE) and congenital heart block. Disease control on an effective medication regimen mitigates many of these risks, but pregnancy in women with SLE remains a high-risk condition requiring multidisciplinary care and an individualized approach to each patient.

View details for PubMedID 30676534
Fetal antiepileptic drug exposure and learning and memory functioning at 6?years of age: The NEAD prospective observational study. Epilepsy & behavior : E&B Cohen, M. J., Meador, K. J., May, R., Loblein, H., Conrad, T., Baker, G. A., Bromley, R. L., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W., NEAD Study Group 2019; 92: 154?64
Abstract

The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.

View details for PubMedID 30660966
Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy. Bioinformatics (Oxford, England) Ghaemi, M. S., DiGiulio, D. B., Contrepois, K., Callahan, B., Ngo, T. T., Lee-McMullen, B., Lehallier, B., Robaczewska, A., Mcilwain, D., Rosenberg-Hasson, Y., Wong, R. J., Quaintance, C., Culos, A., Stanley, N., Tanada, A., Tsai, A., Gaudilliere, D., Ganio, E., Han, X., Ando, K., McNeil, L., Tingle, M., Wise, P., Maric, I., Sirota, M., Wyss-Coray, T., Winn, V. D., Druzin, M. L., Gibbs, R., Darmstadt, G. L., Lewis, D. B., Partovi Nia, V., Agard, B., Tibshirani, R., Nolan, G., Snyder, M. P., Relman, D. A., Quake, S. R., Shaw, G. M., Stevenson, D. K., Angst, M. S., Gaudilliere, B., Aghaeepour, N. 2019; 35 (1): 95?103
Abstract

Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia.Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net (EN) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified.Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/.Supplementary information: Supplementary data are available at Bioinformatics online.

View details for PubMedID 30561547
Effects of periconceptional folate on cognition in children of women with epilepsy: NEAD study. Neurology Meador, K. J., Pennell, P. B., May, R. C., Brown, C. A., Baker, G. n., Bromley, R. n., Loring, D. W., Cohen, M. J. 2019
Abstract

Emerging evidence suggests potential positive neuropsychological effects of periconceptional folate in both healthy children and children exposed in utero to antiseizure medications (ASMs). In this report, we test the hypothesis that periconceptional folate improves neurodevelopment in children of women with epilepsy by re-examining data from the Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) study.The NEAD study was an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes in 311 children of 305 women with epilepsy treated with ASM monotherapy. Missing data points were imputed with Markov chain Monte Carlo methods. Multivariate analyses adjusted for multiple factors (e.g., maternal IQ, ASM type, standardized ASM dose, and gestational birth age) were performed to assess the effects of periconceptional folate on cognitive outcomes (i.e., Full Scale Intelligence Quotient [FSIQ], Verbal and Nonverbal indexes, and Expressive and Receptive Language indexes at 3 and 6 years of age, and executive function and memory function at 6 years of age).Periconceptional folate was associated with higher FSIQ at both 3 and 6 years of age. Significant effects for other measures included Nonverbal Index, Expressive Language Index, and Developmental Neuropsychological Assessment Executive Function at 6 years of age, and Verbal Index and Receptive Language Index at 3 years of age. Nonsignificant effects included Verbal Index, Receptive Index, Behavior Rating Inventory of Executive Function-Parent Questionnaire Executive Function, and General Memory Index at 6 years of age, and Nonverbal Index and Expressive Index at 3 years of age.Use of periconceptional folate in pregnant women with epilepsy taking ASMs is associated with better cognitive development.NCT00021866.

View details for DOI 10.1212/WNL.0000000000008757

View details for PubMedID 31871217
In Reply. Obstetrics and gynecology Judy, A. E., McCain, C. L., Lawton, E. S., Morton, C. H., Main, E. K., Druzin, M. L. 2019; 134 (4): 880?81
View details for DOI 10.1097/AOG.0000000000003494

View details for PubMedID 31568351
Readmission following discharge on labetalol or nifedipine for management of hypertensive disorders of pregnancy Do, S. C., Panelli, D. M., Girsen, A. I., Suharwardy, S., Estes, J., Gibbs, R. S., El-Sayed, Y., Lyell, D. J., Druzin, M. L., Bentley, J. MOSBY-ELSEVIER. 2019: S341
View details for DOI 10.1016/j.ajog.2018.11.530

View details for Web of Science ID 000454249401294
Outcomes of women with primary and secondary pulmonary hypertension during pregnancy Blumenfeld, Y. J., Girsen, A. I., Druzin, M. L., Lyell, D. J., Bianco, K. Y., Herrero, T., Bentley, J., Seckel, E., Zamanian, R. T., El-Sayed, Y. Y. MOSBY-ELSEVIER. 2019: S405
View details for DOI 10.1016/j.ajog.2018.11.633

View details for Web of Science ID 000454249402093
Obstetric outcomes for women receiving newer generation antiepileptic drugs: retrospective cohort study using claims database Herrero, T., Bentley, J. P., Girsen, A. I., Do, S., Suharwardy, S., Panelli, D. M., Lyell, D. J., El-Sayed, Y., Druzin, M. L. MOSBY-ELSEVIER. 2019: S344?S345
View details for Web of Science ID 000454249401299
Improving the prediction of shoulder dystocia using artificial intelligence - a novel approach Tsur, A., Batsry, L., Barak, O., Brezinov, Y., Toussia-Cohen, S., Yoeli-Ullman, R., Sivan, E., Blumenfeld, Y. J., Druzin, M. L., Stevenson, D. K., Aran, D. MOSBY-ELSEVIER. 2019: S435?S436
View details for DOI 10.1016/j.ajog.2018.11.679

View details for Web of Science ID 000454249402136
Pravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1 PLACENTA Tsur, A., Kalish, F., Burgess, J., Nayak, N. R., Zhao, H., Casey, K. M., Druzin, M. L., Wong, R. J., Stevenson, D. K. 2019; 75: 1?8
View details for DOI 10.1016/j.placenta.2018.11.001

View details for Web of Science ID 000457628400001
Pravastatin improves fetal survival in mice with a partial deficiency of heme oxygenase-1. Placenta Tsur, A. n., Kalish, F. n., Burgess, J. n., Nayak, N. R., Zhao, H. n., Casey, K. M., Druzin, M. L., Wong, R. J., Stevenson, D. K. 2019; 75: 1?8
Abstract

Statins induce heme oxygenase-1 (HO-1) expression in vitro and in vivo. Low HO-1 expression is associated with pregnancy complications, e.g. preeclampsia and recurrent miscarriages. Here, we investigated the effects of pravastatin on HO-1 expression, placental development, and fetal survival in mice with a partial HO-1 deficiency.At E14.5, untreated pregnant wild-type (WT, n=13-18), untreated HO-1+/- (Het, n=6-9), and Het mice treated with pravastatin (Het+Pravastatin, n=12-14) were sacrificed. Numbers of viable fetuses/resorbed concepti were recorded. Maternal livers and placentas were harvested for HO activity. Hematoxylin and eosin (H&E) and CD31 immunohistochemical staining were performed on whole placentas.Compared with WT, HO activity in Het livers (65�18%, P<0.001) and placentas (74�7%, P<0.001) were significantly decreased. Number of viable fetuses per dam was significantly lower in Untreated Het dams (6.0�2.2) compared with WT (9.1�1.4, P<0.01), accompanied by a higher relative risk (RR) for concepti resorption (17.1, 95% CI 4.0-73.2). In Hets treated with pravastatin, maternal liver and placental HO activity increased, approaching levels of WT controls (to 83�7% and 87�14%, respectively). The number of viable fetuses per dam increased to 7.7�2.5 with a decreased RR for concepti resorption (2.7, 95% CI 1.2-5.9). In some surviving Untreated Het placentas, there were focal losses of cellular architecture and changes suggestive of reduced blood flow in the labyrinth. These findings were absent in Het+Pravastatin placentas.Pravastatin induces maternal liver and placental HO activity, may affect placental function and improve fetal survival in the context of a partial deficiency of HO-1.

View details for PubMedID 30712660
Understanding health disparities. Journal of perinatology : official journal of the California Perinatal Association Stevenson, D. K., Wong, R. J., Aghaeepour, N., Angst, M. S., Darmstadt, G. L., DiGiulio, D. B., Druzin, M. L., Gaudilliere, B., Gibbs, R. S., B Gould, J., Katz, M., Li, J., Moufarrej, M. N., Quaintance, C. C., Quake, S. R., Relman, D. A., Shaw, G. M., Snyder, M. P., Wang, X., Wise, P. H. 2018
Abstract

Based upon our recent insights into the determinants of preterm birth, which is the leading cause of death in children under five years of age worldwide, we describe potential analytic frameworks that provides both a common understanding and, ultimately the basis for effective, ameliorative action. Our research on preterm birth serves as an example that the framing of any human health condition is a result of complex interactions between the genome and the exposome. New discoveries of the basic biology of pregnancy, such as the complex immunological and signaling processes that dictate the health and length of gestation, have revealed a complexity in the interactions (current and ancestral) between genetic and environmental forces. Understanding of these relationships may help reduce disparities in preterm birth and guide productive research endeavors and ultimately, effective clinical and public health interventions.

View details for PubMedID 30560947
Preterm Delivery Phenotypes in Systemic Lupus Erythematosus Pregnancies. American journal of perinatology Simard, J. F., Chaichian, Y., Rossides, M., Wikstrom, A., Shaw, G. M., Druzin, M. L. 2018
Abstract

OBJECTIVE: Women with systemic lupus erythematosus (SLE) are at a greater risk of preterm delivery, many of which may be medically indicated (iatrogenic). We investigated preterm delivery phenotypes in SLE and general population comparators and assessed the role of preeclampsia.STUDY DESIGN: We used population-based Swedish Register data (2001-2013) and defined maternal SLE as ?2 SLE-coded discharge diagnoses from the Patient Register with ?1 coded by an appropriate specialist. Women from the general population were identified using the Total Population Register. Preterm delivery was defined as <37 weeks and separated into spontaneous and iatrogenic, as well as later versus extremely preterm (32 to <37 weeks vs. <32 weeks). Maternal comorbidity was assessed, and the proportion mediated by preeclampsia was calculated examining first, subsequent, and all pregnancies.RESULTS: Preterm delivery was more common in SLE for the first (22 vs. 6%) and subsequent (15 vs. 4%) pregnancies among 781 SLE-exposed pregnancies and 11,271 non-SLE pregnancies. Of SLE-exposed first births, 27% delivered before 32 weeks, and 90% were iatrogenic (compared with 47% of non-SLE first births).CONCLUSION: Preterm delivery complicates a greater proportion of SLE pregnancies than general population pregnancies, and a considerable proportion of risk is mediated through preeclampsia.

View details for PubMedID 30477035
Maternal Height and Risk of Preeclampsia among Race/Ethnic Groups. American journal of perinatology Maric, I., Mayo, J. A., Druzin, M. L., Wong, R. J., Winn, V. D., Stevenson, D. K., Shaw, G. M. 2018
Abstract

OBJECTIVE: Shorter maternal height has been associated with preeclampsia risk in several populations. It has been less evident whether an independent contribution to the risk exists from maternal height consistently across different races/ethnicities. We investigated associations between maternal height and risk of preeclampsia for different races/ethnicities.STUDY DESIGN: California singleton live births from 2007 to 2011 were analyzed. Logistic regression was used to estimate adjusted odds ratios for the association between height and preeclampsia after stratification by race/ethnicity. To determine the contribution of height that is as independent of body composition as possible, we performed one analysis adjusted for body mass index (BMI) and the other for weight. Additional analyses were performed stratified by parity, and the presence of preexisting/gestational diabetes and autoimmune conditions.RESULTS: Among 2,138,012 deliveries, 3.1% preeclampsia/eclampsia cases were observed. The analysis, adjusted for prepregnancy weight, revealed an inverse relation between maternal height and risk of mild and severe preeclampsia/eclampsia. When the analysis was adjusted for BMI, an inverse relation between maternal height was observed for severe preeclampsia/eclampsia. These associations were observed for each race/ethnicity.CONCLUSION: Using a large and diverse cohort, we demonstrated that shorter height, irrespective of prepregnancy weight or BMI, is associated with an increased risk of severe preeclampsia/eclampsia across different races/ethnicities.

View details for PubMedID 30396225
Maternal Congenital Heart Disease in Pregnancy. Obstetrics and gynecology clinics of North America Foeller, M. E., Foeller, T. M., Druzin, M. 2018; 45 (2): 267?80
Abstract

Congenital heart disease comprises most maternal cardiac diseases in pregnancy and is an important cause of maternal, fetal, and neonatal morbidity and mortality worldwide. Pregnancy is often considered a high-risk state for individuals with structural heart disease as a consequence of a limited ability to adapt to the major hemodynamic changes associated with pregnancy. Preconception counseling and evaluation are of utmost importance, as pregnancy is contraindicated in certain cardiac conditions. Pregnancy can be safely accomplished in most individuals with careful risk assessment before conception and multidisciplinary care throughout pregnancy and the postpartum period.

View details for PubMedID 29747730
Maternal Congenital Heart Disease in Pregnancy OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA Foeller, M. E., Foeller, T. M., Druzin, M. 2018; 45 (2): 267-+
View details for DOI 10.1016/j.ogc.2018.01.011

View details for Web of Science ID 000434905200009
Pravastatin Induces Heme Oxygenase Activity and Enhances Placental Development in a Murine Model. Tsur, A., Kalish, F., Burgess, J., Zhao, H., Casey, K. M., Druzin, M. L., Wong, R. J., Stevenson, D. K. SAGE PUBLICATIONS INC. 2018: 155A?156A
View details for Web of Science ID 000429928200299
Hydroxychloroquine and Preeclampsia Risk in Pregnancies with Systemic Lupus Erythematosus. Do, S. C., Simard, J. F., Druzin, M. L. SAGE PUBLICATIONS INC. 2018: 239A?240A
View details for Web of Science ID 000429928200554
Pravastatin improves pregnancy outcome and placental development in heme oxygenase-1 deficient mice Tsur, A., Kalish, F., Burgess, J., Zhao, H., Casey, K., Druzin, M. L., Wong, R. J., Stevenson, D. K. MOSBY-ELSEVIER. 2018: S202
View details for Web of Science ID 000422946900324
Characteristics of women with multiple postpartum hospital admissions Girsen, A. I., Sie, L., Carmichael, S., Foeller, M. E., Druzin, M. L., Lee, H. C., Gibbs, R. S. MOSBY-ELSEVIER. 2018: S461?S462
View details for Web of Science ID 000423616600271
Preterm Birth Phenotypes in Women with Autoimmune Diseases Kolstad, K. D., Mayo, J. A., Chung, L., Chaichian, Y., Kelly, V. M., Druzin, M., Stevenson, D. K., Shaw, G. M., Simard, J. F. WILEY. 2017
View details for Web of Science ID 000411824102207
Preterm Delivery Phenotypes in SLE Pregnancies Simard, J. F., Chaichian, Y., Rossides, M., Wikstrom, A., Shaw, G. M., Druzin, M. WILEY. 2017
View details for Web of Science ID 000411824102208
Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING Bernstein, P. S., Martin, J. N., Barton, J. R., Shields, L. E., Druzin, M. L., Scavone, B. M., Frost, J., Morton, C. H., Ruhl, C., Slager, J., Tsigas, E. Z., Jaffer, S., Menard, M. 2017; 46 (5): 776?87
Abstract

Complications arising from hypertensive disorders of pregnancy are among the leading causes of preventable severe maternal morbidity and mortality. Timely and appropriate treatment has the potential to significantly reduce hypertension-related complications. To assist health care providers in achieving this goal, this patient safety bundle provides guidance to coordinate and standardize the care provided to women with severe hypertension during pregnancy and the postpartum period. This is one of several patient safety bundles developed by multidisciplinary work groups of the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care. These safety bundles outline critical clinical practices that should be implemented in every maternity care setting. Similar to other bundles that have been developed and promoted by the Partnership, the hypertension safety bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged. This commentary provides information to assist with bundle implementation.

View details for DOI 10.1016/j.jogn.2017.05.003

View details for Web of Science ID 000412698400017

View details for PubMedID 28709727
National Partnership for Maternal Safety Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period OBSTETRICS AND GYNECOLOGY Bernstein, P. S., Martin, J. N., Barton, J. R., Shields, L. E., Druzin, M. L., Scavone, B. M., Frost, J., Morton, C. H., Ruhl, C., Slager, J., Tsigas, E. Z., Jaffer, S., Menard, M. 2017; 130 (2): 347?57
Abstract

Complications arising from hypertensive disorders of pregnancy are among the leading causes of preventable severe maternal morbidity and mortality. Timely and appropriate treatment has the potential to significantly reduce hypertension-related complications. To assist health care providers in achieving this goal, this patient safety bundle provides guidance to coordinate and standardize the care provided to women with severe hypertension during pregnancy and the postpartum period. This is one of several patient safety bundles developed by multidisciplinary work groups of the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care. These safety bundles outline critical clinical practices that should be implemented in every maternity care setting. Similar to other bundles that have been developed and promoted by the Partnership, the hypertension safety bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged. This commentary provides information to assist with bundle implementation.

View details for PubMedID 28697093
National Partnership for Maternal Safety: Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period ANESTHESIA AND ANALGESIA Bernstein, P. S., Martin, J. N., Barton, J. R., Shields, L. E., Druzin, M. L., Scavone, B. M., Frost, J., Morton, C. H., Ruhl, C., Slager, J., Tsigas, E. Z., Jaffer, S., Menard, M. 2017; 125 (2): 540?47
Abstract

Complications arising from hypertensive disorders of pregnancy are among the leading causes of preventable severe maternal morbidity and mortality. Timely and appropriate treatment has the potential to significantly reduce hypertension-related complications. To assist health care providers in achieving this goal, this patient safety bundle provides guidance to coordinate and standardize the care provided to women with severe hypertension during pregnancy and the postpartum period. This is one of several patient safety bundles developed by multidisciplinary work groups of the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care. These safety bundles outline critical clinical practices that should be implemented in every maternity care setting. Similar to other bundles that have been developed and promoted by the Partnership, the hypertension safety bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged. This commentary provides information to assist with bundle implementation.

View details for PubMedID 28696959
Consensus Bundle on Severe Hypertension During Pregnancy and the Postpartum Period JOURNAL OF MIDWIFERY & WOMENS HEALTH Bernstein, P. S., Martin, J. N., Barton, J. R., Shields, L. E., Druzin, M. L., Scavone, B. M., Frost, J., Morton, C. H., Ruhl, C., Slager, J., Tsigas, E. Z., Jaffer, S., Menard, M. 2017; 62 (4): 493?501
Abstract

Complications arising from hypertensive disorders of pregnancy are among the leading causes of preventable severe maternal morbidity and mortality. Timely and appropriate treatment has the potential to significantly reduce hypertension-related complications. To assist health care providers in achieving this goal, this patient safety bundle provides guidance to coordinate and standardize the care provided to women with severe hypertension during pregnancy and the postpartum period. This is one of several patient safety bundles developed by multidisciplinary work groups of the National Partnership for Maternal Safety under the guidance of the Council on Patient Safety in Women's Health Care. These safety bundles outline critical clinical practices that should be implemented in every maternity care setting. Similar to other bundles that have been developed and promoted by the Partnership, the hypertension safety bundle is organized into four domains: Readiness, Recognition and Prevention, Response, and Reporting and Systems Learning. Although the bundle components may be adapted to meet the resources available in individual facilities, standardization within an institution is strongly encouraged. This commentary provides information to assist with bundle implementation.

View details for DOI 10.1111/jmwh.12647

View details for Web of Science ID 000406668800011

View details for PubMedID 28697534
Opportunities for maternal transport for delivery of very low birth weight infants JOURNAL OF PERINATOLOGY Robles, D., Blumenfeld, Y. J., Lee, H. C., Gould, J. B., Main, E., Profit, J., Melsop, K., Druzin, M. 2017; 37 (1): 32-35
Abstract

To assess frequency of very low birth weight (VLBW) births at non-level III hospitals.Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500?g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models.Of the 1?508?143 births, 13?919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24?h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively.Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.Journal of Perinatology advance online publication, 29 September 2016; doi:10.1038/jp.2016.174.

View details for DOI 10.1038/jp.2016.174

View details for Web of Science ID 000391517000007
Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. Proceedings of the National Academy of Sciences of the United States of America Callahan, B. J., DiGiulio, D. B., Goltsman, D. S., Sun, C. L., Costello, E. K., Jeganathan, P. n., Biggio, J. R., Wong, R. J., Druzin, M. L., Shaw, G. M., Stevenson, D. K., Holmes, S. P., Relman, D. A. 2017
Abstract

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality. Previous studies have suggested that the maternal vaginal microbiota contributes to the pathophysiology of PTB, but conflicting results in recent years have raised doubts. We conducted a study of PTB compared with term birth in two cohorts of pregnant women: one predominantly Caucasian (n = 39) at low risk for PTB, the second predominantly African American and at high-risk (n = 96). We profiled the taxonomic composition of 2,179 vaginal swabs collected prospectively and weekly during gestation using 16S rRNA gene sequencing. Previously proposed associations between PTB and lower Lactobacillus and higher Gardnerella abundances replicated in the low-risk cohort, but not in the high-risk cohort. High-resolution bioinformatics enabled taxonomic assignment to the species and subspecies levels, revealing that Lactobacillus crispatus was associated with low risk of PTB in both cohorts, while Lactobacillus iners was not, and that a subspecies clade of Gardnerella vaginalis explained the genus association with PTB. Patterns of cooccurrence between L. crispatus and Gardnerella were highly exclusive, while Gardnerella and L. iners often coexisted at high frequencies. We argue that the vaginal microbiota is better represented by the quantitative frequencies of these key taxa than by classifying communities into five community state types. Our findings extend and corroborate the association between the vaginal microbiota and PTB, demonstrate the benefits of high-resolution statistical bioinformatics in clinical microbiome studies, and suggest that previous conflicting results may reflect the different risk profile of women of black race.

View details for PubMedID 28847941
A Proteomic Clock of Human Pregnancy. American journal of obstetrics and gynecology Aghaeepour, N. n., Lehallier, B. n., Baca, Q. n., Ganio, E. A., Wong, R. J., Ghaemi, M. S., Culos, A. n., El-Sayed, Y. Y., Blumenfeld, Y. J., Druzin, M. L., Winn, V. D., Gibbs, R. S., Tibshirani, R. n., Shaw, G. M., Stevenson, D. K., Gaudilliere, B. n., Angst, M. S. 2017
Abstract

Early detection of maladaptive processes underlying pregnancy-related pathologies is desirable, as it will enable targeted interventions ahead of clinical manifestations. The quantitative analysis of plasma proteins features prominently among molecular approaches used to detect deviations from normal pregnancy. However, derivation of proteomic signatures sufficiently predictive of pregnancy-related outcomes has been challenging. An important obstacle hindering such efforts were limitations in assay technology, which prevented the broad examination of the plasma proteome.The recent availability of a highly-multiplexed platform affording the simultaneous measurement of 1,310 plasma proteins opens the door for a more explorative approach. The major aim of this study was to examine whether analysis of plasma collected during gestation of term pregnancy would allow identifying a set of proteins that tightly track gestational age. Establishing precisely-timed plasma proteomic changes during term pregnancy is a critical step in identifying deviations from regular patterns due to fetal and maternal maladaptations. A second aim was to gain insight into functional attributes of identified proteins, and link such attributes to relevant immunological changes.Pregnant women participated in this longitudinal study. In two subsequent subsets of 21 (training cohort) and 10 (validation cohort) women, specific blood specimens were collected during the first (7-14 wks), second (15-20 wks), and third (24-32 wks) trimesters, and 6 wks post-partum for analysis with a highly-multiplexed aptamer-based platform. An elastic net algorithm was applied to infer a proteomic model predicting gestational age. A bootstrapping procedure and piece-wise regression analysis was used to extract the minimum number of proteins required for predicting gestational age without compromising predictive power. Gene ontology analysis was applied to infer enrichment of molecular functions among proteins included in the proteomic model. Changes in abundance of proteins with such functions were linked to immune features predictive of gestational age at the time of sampling in pregnancies delivering at term.An independently validated model consisting of 74 proteins strongly predicted gestational age (p = 3.8x10-14, R = 0.97). The model could be reduced to eight proteins without losing its predictive power (p = 1.7x10-3, R = 0.91). The three top ranked proteins were glypican 3, chorionic somatomammotropin hormone, and granulins. Proteins activating the Janus kinase (JAK) and signal transducer and activator of transcription (STAT) pathway were enriched in the proteomic model, chorionic somatomammotropin hormone being the top ranked protein. Abundance of chorionic somatomammotropin hormone strongly correlated with STAT5 signaling activity in CD4 T cells, the endogenous cell-signaling event most predictive of gestational age.Results indicate that precisely timed changes in the plasma proteome during term pregnancy mirror a "proteomic clock". Importantly, the combined use of several plasma proteins was required for accurate prediction. The exciting promise of such a "clock" is that deviations from its regular chronological profile may assist in the early diagnoses of pregnancy-relate pathologies and point to underlying pathophysiology. Functional analysis of the proteomic model generated the novel hypothesis that somatomammotropin hormone may critically regulate T-cell function during pregnancy.

View details for PubMedID 29277631
Postpartum readmission and severe maternal morbidity in California Girsen, A., Lee, L. C., Carmichael, S. L., Foeller, M., Druzin, M. L., Gibbs, R. MOSBY-ELSEVIER. 2017: S112
View details for Web of Science ID 000414256401118
Risky Business: Meeting the Structural Needs of Transdisciplinary Science. The Journal of pediatrics Wise, P. H., Shaw, G. M., Druzin, M. L., Darmstadt, G. L., Quaintance, C. n., M�kinen, E. n., Relman, D. A., Quake, S. R., Butte, A. J., Angst, M. S., Muglia, L. J., Macones, G. n., Driscoll, D. n., Ober, C. n., Simpson, J. L., Katz, M. n., Howse, J. n., Stevenson, D. K. 2017; 191: 255?58
View details for PubMedID 29173314
An immune clock of human pregnancy. Science immunology Aghaeepour, N. n., Ganio, E. A., Mcilwain, D. n., Tsai, A. S., Tingle, M. n., Van Gassen, S. n., Gaudilliere, D. K., Baca, Q. n., McNeil, L. n., Okada, R. n., Ghaemi, M. S., Furman, D. n., Wong, R. J., Winn, V. D., Druzin, M. L., El-Sayed, Y. Y., Quaintance, C. n., Gibbs, R. n., Darmstadt, G. L., Shaw, G. M., Stevenson, D. K., Tibshirani, R. n., Nolan, G. P., Lewis, D. B., Angst, M. S., Gaudilliere, B. n. 2017; 2 (15)
Abstract

The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2-dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies.

View details for PubMedID 28864494
Opportunities for maternal transport for delivery of very low birth weight infants. Journal of perinatology Robles, D., Blumenfeld, Y. J., Lee, H. C., Gould, J. B., Main, E., Profit, J., Melsop, K., Druzin, M. 2016
Abstract

To assess frequency of very low birth weight (VLBW) births at non-level III hospitals.Retrospective cohort study using linked California birth certificate and discharge data of 2008 to 2010 for deliveries of singleton or first-born infant of multiple gestations with birth weight 400 to 1500?g. Delivery rates by neonatal level of care were obtained. Risk of delivery at non-level III centers was estimated in univariable and multivariable models.Of the 1?508?143 births, 13?919 (9.2%) were VLBW; birth rate at non-level III centers was 14.9% (8.4% in level I and 6.5% in level II). Median rate of VLBW births was 0.3% (range 0 to 4.7%) annually at level I and 0.5% (range 0 to 1.6%) at level II hospitals. Antepartum stay for >24?h occurred in 14.0% and 26.9% of VLBW births in level I and level II hospitals, respectively.Further improvement is possible in reducing VLBW infant delivery at suboptimal sites, given the window of opportunity for many patients.Journal of Perinatology advance online publication, 29 September 2016; doi:10.1038/jp.2016.174.

View details for DOI 10.1038/jp.2016.174

View details for PubMedID 27684426
Recurrence of Preterm Birth and Early Term Birth. Obstetrics and gynecology Yang, J., Baer, R. J., Berghella, V., Chambers, C., Chung, P., Coker, T., Currier, R. J., Druzin, M. L., Kuppermann, M., Muglia, L. J., Norton, M. E., Rand, L., Ryckman, K., Shaw, G. M., Stevenson, D., Jelliffe-Pawlowski, L. L. 2016; 128 (2): 364-372
Abstract

To examine recurrent preterm birth and early term birth in women's initial and immediately subsequent pregnancies.This retrospective cohort study included 163,889 women who delivered their first and second liveborn singleton neonates between 20 and 44 weeks of gestation in California from 2005 through 2011. Data from hospital discharge records and birth certificates were used for analyses. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression models adjusted for risk factors.Shorter gestational duration in the first pregnancy increased the risk of subsequent preterm birth (both early, before 32 weeks of gestation, and later, from 32 to 36 weeks of gestation) as well as early term birth (37-38 weeks of gestation). Compared with women with a prior term birth, women with a prior early preterm birth (before 32 weeks of gestation) were at the highest risk for a subsequent early preterm birth (58/935 [6.2%] compared with 367/118,505 [0.3%], adjusted OR 23.3, 95% CI 17.2-31.7). Women with a prior early term birth had more than a twofold increased risk for subsequent preterm birth (before 32 weeks of gestation: 171/36,017 [0.5%], adjusted OR 2.0, 95% CI 1.6-2.3; from 32 to 36 weeks of gestation: 2,086/36,017 [6.8%], adjusted OR 3.0, 95% CI 2.9-3.2) or early term birth (13,582/36,017 [37.7%], adjusted OR 2.2, 95% CI 2.2-2.3).Both preterm birth and early term birth are associated with these outcomes in a subsequent pregnancy. Increased clinical attention and research efforts may benefit from a focus on women with a prior early term birth as well as those with prior preterm birth.

View details for DOI 10.1097/AOG.0000000000001506

View details for PubMedID 27400000
Challenging the 4-to 5-minute rule: from perimortem cesarean to resuscitative hysterotomy AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Lipman, S. S., Cohen, S., Mhyre, J., Carvalho, B., Einav, S., Arafeh, J., Jeejeebhoy, F., Cobb, B., Druzin, M., Katz, V., Harney, K. 2016; 215 (1): 129-131
View details for DOI 10.1016/j.ajog.2016.03.043

View details for PubMedID 27040085
Temporal and geographic patterns of home births in California 1991-2010 Girsen, A., Mayo, J. A., Blumenfeld, Y. J., Lyell, D. J., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M. MOSBY-ELSEVIER. 2016: S395
View details for DOI 10.1016/j.ajog.2015.10.801

View details for Web of Science ID 000367092800744
Disseminated Intravascular Coagulation Complicating the Conservative Management of Placenta Percreta OBSTETRICS AND GYNECOLOGY Judy, A. E., Lyell, D. J., Druzin, M. L., Dorigo, O. 2015; 126 (5): 1016-1018
Abstract

Retention of the placenta is an option in the management of placenta percreta; however, it may be associated with significant morbidity.We present a case of conservative management of placenta percreta. Disseminated intravascular coagulation (DIC) developed 49 days after delivery. An urgent hysterectomy was performed, followed by rapid normalization of coagulation parameters.Disseminated intravascular coagulation may complicate the conservative management of placenta percreta and can manifest weeks after delivery in the absence of antecedent hemorrhage or infection. The time course and presentation of this case are similar to the development of DIC after prolonged retention of a fetal demise with a probable shared pathophysiology. Close follow-up may facilitate prompt diagnosis of DIC, thereby minimizing associated morbidity.

View details for DOI 10.1097/AOG.0000000000000960

View details for Web of Science ID 000363974000016

View details for PubMedID 26132459
Maternal serum markers, characteristics and morbidly adherent placenta in women with previa JOURNAL OF PERINATOLOGY Lyell, D. J., Faucett, A. M., Baer, R. J., Blumenfeld, Y. J., Druzin, M. L., El-Sayed, Y. Y., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2015; 35 (8): 570-574
Abstract

To examine associations with morbidly adherent placenta (MAP) among women with placenta previa.Women with MAP (cases) and previa alone (controls) were identified from a cohort of 236?714 singleton pregnancies with both first and second trimester prenatal screening, and live birth and hospital discharge records; pregnancies with aneuploidies and neural tube or abdominal wall defects were excluded. Logistic binomial regression was used to compare cases with controls.In all, 37 cases with MAP and 699 controls with previa alone were included. Risk for MAP was increased among multiparous women with pregnancy-associated plasma protein-A (PAPP-A) ?95th percentile (?2.63 multiple of the median (MoM); adjusted OR (aOR) 8.7, 95% confidence interval (CI) 2.8 to 27.4), maternal-serum alpha fetoprotein (MS-AFP) ?95th percentile (?1.79 MoM; aOR 2.8, 95% CI 1.0 to 8.0), and 1 and ?2 prior cesarean deliveries (CDs; aORs 4.4, 95% CI 1.5 to 13.6 and 18.4, 95% CI 5.9 to 57.5, respectively).Elevated PAPP-A, elevated MS-AFP and prior CDs are associated with MAP among women with previa.

View details for DOI 10.1038/jp.2015.40

View details for Web of Science ID 000358684100008
Early-onset severe preeclampsia by first trimester pregnancy-associated plasma protein A and total human chorionic gonadotropin. American journal of perinatology Jelliffe-Pawlowski, L. L., Baer, R. J., Currier, R. J., Lyell, D. J., Blumenfeld, Y. J., El-Sayed, Y. Y., Shaw, G. M., Druzin, M. L. 2015; 32 (7): 703-712
Abstract

This study aims to evaluate the relationship between early-onset severe preeclampsia and first trimester serum levels of pregnancy-associated plasma protein A (PAPP-A) and total human chorionic gonadotropin (hCG).The association between early-onset severe preeclampsia and abnormal levels of first trimester PAPP-A and total hCG in maternal serum were measured in a sample of singleton pregnancies without chromosomal defects that had integrated prenatal serum screening in 2009 and 2010 (n?=?129,488). Logistic binomial regression was used to estimate the relative risk (RR) of early-onset severe preeclampsia in pregnancies with abnormal levels of first trimester PAPP-A or total hCG as compared with controls.Regardless of parity, women with low first trimester PAPP-A or high total hCG were at increased risk for early-onset severe preeclampsia. Women with low PAPP-A (multiple of the median [MoM]???the 10th percentile in nulliparous or???the 5th percentile in multiparous) or high total hCG (MoM???the 90th percentile in nulliparous or???the 95th percentile in multiparous) were at more than a threefold increased risk for early-onset severe preeclampsia (RR, 4.2; 95% confidence interval [CI], 3.0-5.9 and RR, 3.3; 95% CI, 2.1-5.2, respectively).Routinely collected first trimester measurements of PAPP-A and total hCG provide unique risk information for early-onset severe preeclampsia.

View details for DOI 10.1055/s-0034-1396697

View details for PubMedID 25519199
Cross Functional Management of Women With Rheumatological and Gastrointestinal Conditions During Family Planning and Pregnancy Clowse, M., Khamashta, M., Nelson-Piercy, C., Druzin, M. L., Pushparajah, D., Chakravarty, E. SAGE PUBLICATIONS INC. 2015: 230A
View details for Web of Science ID 000351407202148
Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption. American journal of obstetrics and gynecology Blumenfeld, Y. J., Baer, R. J., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Faucett, A. M., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2014; 211 (2): 144 e1-9
Abstract

The objective of the study was to examine the association between placental abruption, maternal characteristics, and routine first- and second-trimester aneuploidy screening analytes.The study consisted of an analysis of 1017 women with and 136,898 women without placental abruption who had first- and second-trimester prenatal screening results, linked birth certificate, and hospital discharge records for a live-born singleton. Maternal characteristics and first- and second-trimester aneuploidy�screening analytes were analyzed using logistic binomial regression.Placental abruption was more frequent among women of�Asian race, age older than 34 years, women with chronic and�pregnancy-associated hypertension, preeclampsia, preexisting diabetes, previous preterm birth, and interpregnancy interval less than 6�months. First-trimester pregnancy-associated plasma protein-A of the fifth percentile or less, second-trimester alpha fetoprotein of the 95th percentile or greater, unconjugated estriol of the fifth percentile or less, and dimeric inhibin-A of the 95th percentile or greater were associated with placental abruption as well. When logistic models were stratified by the presence or absence of hypertensive disease, only maternal age older than 34 years (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.0-2.0), pregnancy-associated plasma protein-A of the 95th percentile or less (OR, 1.9; 95% CI, 1.2-3.1), and alpha fetoprotein of the 95th percentile or greater (OR, 2.3; 95%�CI, 1.4-3.8) remained statistically significantly associated for abruption.In this large, population-based cohort study, abnormal maternal aneuploidy serum analyte levels were associated with placental abruption, regardless of the presence of hypertensive disease.

View details for DOI 10.1016/j.ajog.2014.03.027

View details for PubMedID 24631707
The society for obstetric anesthesia and perinatology consensus statement on the management of cardiac arrest in pregnancy. Anesthesia and analgesia Lipman, S., Cohen, S., Einav, S., Jeejeebhoy, F., Mhyre, J. M., Morrison, L. J., Katz, V., Tsen, L. C., Daniels, K., Halamek, L. P., Suresh, M. S., Arafeh, J., Gauthier, D., Carvalho, J. C., Druzin, M., Carvalho, B. 2014; 118 (5): 1003-1016
Abstract

This consensus statement was commissioned in 2012 by the Board of Directors of the Society for Obstetric Anesthesia and Perinatology to improve maternal resuscitation by providing health care providers critical information (including point-of-care checklists) and operational strategies relevant to maternal cardiac arrest. The recommendations in this statement were designed to address the challenges of an actual event by emphasizing health care provider education, behavioral/communication strategies, latent systems errors, and periodic testing of performance. This statement also expands on, interprets, and discusses controversial aspects of material covered in the American Heart Association 2010 guidelines.

View details for DOI 10.1213/ANE.0000000000000171

View details for PubMedID 24781570
High rate of preterm birth in pregnancies complicated by rheumatoid arthritis. American journal of perinatology Langen, E. S., Chakravarty, E. F., Liaquat, M., El-Sayed, Y. Y., Druzin, M. L. 2014; 31 (1): 9-14
Abstract

Objective?To describe the outcomes of pregnancies complicated by rheumatoid arthritis (RA) and to estimate potential associations between disease characteristics and pregnancy outcomes.Study Design?We reviewed all pregnancies complicated by RA delivered at our institution from June 2001 through June 2009. Fisher exact tests were used to calculate odds ratios. Univariable regression was performed using STATA 10.1 (StataCorp, College Station, TX). A p value of???0.05 was considered statistically significant.Results?Forty-six pregnancies in 40 women were reviewed. Sixty percent of pregnancies had evidence of disease flare and 28% delivered prior to 37 weeks. We did not identify associations between preterm birth and active disease at conception or during pregnancy. In univariate analysis, discontinuation of medication because of pregnancy was associated with a significantly earlier gestational age at delivery (362/7 versus 383/7 weeks, p?=?0.022).Conclusion?Women with RA may be at higher risk for preterm delivery.

View details for DOI 10.1055/s-0033-1333666

View details for PubMedID 23359233
Response times for emergency cesarean delivery: use of simulation drills to assess and improve obstetric team performance JOURNAL OF PERINATOLOGY Lipman, S. S., Carvalho, B., Cohen, S. E., Druzin, M. L., Daniels, K. 2013; 33 (4): 259-263
Abstract

We documented time to key milestones and determined reasons for transport-related delays during simulated emergency cesarean.Prospective, observational investigation of delivery of care processes by multidisciplinary teams of obstetric providers on the labor and delivery unit at Lucile Packard Children's Hospital, Stanford, CA, USA, during 14 simulated uterine rupture scenarios. The primary outcome measure was the total time from recognition of the emergency (time zero) to that of surgical incision.The median (interquartile range) from time zero until incision was 9?min 27?s (8:55 to 10:27?min:s).In this series of emergency cesarean drills, our teams required approximately nine and a half minutes to move from the labor room to the nearby operating room (OR) and make the surgical incision. Multiple barriers to efficient transport were identified. This study demonstrates the utility of simulation to identify and correct institution-specific barriers that delay transport to the OR and initiation of emergency cesarean delivery.

View details for DOI 10.1038/jp.2012.98

View details for Web of Science ID 000316833300002

View details for PubMedID 22858890
Transdisciplinary translational science and the case of preterm birth JOURNAL OF PERINATOLOGY Stevenson, D. K., Shaw, G. M., Wise, P. H., Norton, M. E., Druzin, M. L., Valantine, H. A., McFarland, D. A. 2013; 33 (4): 251-258
Abstract

Medical researchers have called for new forms of translational science that can solve complex medical problems. Mainstream science has made complementary calls for heterogeneous teams of collaborators who conduct transdisciplinary research so as to solve complex social problems. Is transdisciplinary translational science what the medical community needs? What challenges must the medical community overcome to successfully implement this new form of translational science? This article makes several contributions. First, it clarifies the concept of transdisciplinary research and distinguishes it from other forms of collaboration. Second, it presents an example of a complex medical problem and a concrete effort to solve it through transdisciplinary collaboration: for example, the problem of preterm birth and the March of Dimes effort to form a transdisciplinary research center that synthesizes knowledge on it. The presentation of this example grounds discussion on new medical research models and reveals potential means by which they can be judged and evaluated. Third, this article identifies the challenges to forming transdisciplines and the practices that overcome them. Departments, universities and disciplines tend to form intellectual silos and adopt reductionist approaches. Forming a more integrated (or 'constructionist'), problem-based science reflective of transdisciplinary research requires the adoption of novel practices to overcome these obstacles.

View details for DOI 10.1038/jp.2012.133

View details for PubMedID 23079774
Postpartum hemorrhage treated with a massive transfusion protocol at a tertiary obstetric center: a retrospective study INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Gutierrez, M. C., GOODNOUGH, L. T., Druzin, M., Butwick, A. J. 2012; 21 (3): 230-235
Abstract

A massive transfusion protocol may offer major advantages for management of postpartum hemorrhage. The etiology of postpartum hemorrhage, transfusion outcomes and laboratory indices in obstetric cases requiring the massive transfusion protocol were retrospectively evaluated in a tertiary obstetric center.We reviewed medical records of obstetric patients requiring the massive transfusion protocol over a 31-month period. Demographic, obstetric, transfusion, laboratory data and adverse maternal outcomes were abstracted.Massive transfusion protocol activation occurred in 31 patients (0.26% of deliveries): 19 patients (61%) had cesarean delivery, 10 patients (32%) had vaginal delivery, and 2 patients (7%) had dilation and evacuation. Twenty-six patients (84%) were transfused with blood products from the massive transfusion protocol. The protocol was activated within 2h of delivery for 17 patients (58%). Median [IQR] total estimated blood loss value was 2842 [800-8000]mL. Median [IQR] number of units of red blood cells, plasma and platelets from the massive transfusion protocol were: 3 [1.75-7], 3 [1.5-5.5], and 1 [0-2.5] units, respectively. Mean (SD) post-resuscitation hematologic indices were: hemoglobin 10.3 (2.4)g/dL, platelet count 126 (44)�10(9)/L, and fibrinogen 325 (125)mg/dL. The incidence of intensive care admission and peripartum hysterectomy was 61% and 19%, respectively.Our massive transfusion protocol provides early access to red blood cells, plasma and platelets for patients experiencing unanticipated or severe postpartum hemorrhage. Favorable hematologic indices were observed post resuscitation. Future outcomes-based studies are needed to compare massive transfusion protocol and non-protocol based transfusion strategies for the management of hemorrhage.

View details for DOI 10.1016/j.ijoa.2012.03.005

View details for Web of Science ID 000307685000005

View details for PubMedID 22647592
Obstetric Life Support JOURNAL OF PERINATAL & NEONATAL NURSING Puck, A. L., Oakeson, A. M., Morales-Clark, A., Druzin, M. 2012; 26 (2): 126-135
Abstract

The death of a woman during pregnancy is devastating. Although the incidence of maternal cardiac arrest is increasing, it continues to be a comparatively rare event. Obstetric healthcare providers may go through their entire career without participating in a maternal cardiac resuscitation. Concern has been raised that when an arrest does occur in the obstetric unit, providers who are trained in life support skills at 2-year intervals are ill equipped to provide the best possible care. The quality of resuscitation skills provided during cardiopulmonary arrest of inpatients often may be poor, and knowledge of critical steps to be followed during resuscitation may not be retained after life support training. The Obstetric Life Support (ObLS) training program is a method of obstetric nursing and medical staff training that is relevant, comprehensive, and cost-effective. It takes into consideration both the care needs of the obstetric patient and the adult learning needs of providers. The ObLS program brings obstetric nurses, obstetricians, and anesthesiologists together in multidisciplinary team training that is crucial to developing efficient emergency response.

View details for DOI 10.1097/JPN.0b013e318252ce3e

View details for Web of Science ID 000303605700008

View details for PubMedID 22551860
Diagnositic utility of ultrasound and MRI in women with placenta previa and placental invasion 31st Annual Scientific Meeting of the Society-of-Maternal-Fetal-Medicine (SMFM) Langen, E., El-Sayed, Y., Druzin, M., Park, M., Lee, H. MOSBY-ELSEVIER. 2011: S137?S137
View details for Web of Science ID 000285927500334
High rate of preterm birth in pregnancies complicated by rheumatoid arthritis Chakravarty, E., Langen, E., Druzin, M., Liaqat, M. MOSBY-ELSEVIER. 2011: S316
View details for Web of Science ID 000285927500805
Maternal morbidity in pregnancies complicated by abnormal placentation 31st Annual Scientific Meeting of the Society-of-Maternal-Fetal-Medicine (SMFM) Langen, E., El-Sayed, Y., Druzin, M., Park, M., Lee, H. MOSBY-ELSEVIER. 2011: S57?S57
View details for Web of Science ID 000285927500107
Deficits in the provision of cardiopulmonary resuscitation during simulated obstetric crises AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Lipman, S. S., Daniels, K. I., Carvalho, B., Arafeh, J., Harney, K., Puck, A., Cohen, S. E., Druzin, M. 2010; 203 (2)
Abstract

Previous work suggests the potential for suboptimal cardiopulmonary resuscitation (CPR) in the parturient but did not directly assess actual performance.We evaluated 18 videotaped simulations of maternal amniotic fluid embolus and resultant cardiac arrest. A checklist containing 10 current American Heart Association recommendations for advanced cardiac life support (ACLS) in obstetric patients was utilized. We evaluated which tasks were completed correctly and the time required to perform key actions.Proper compressions were delivered by our teams 56% of the time and ventilations 50% of the time. Critical interventions such as left uterine displacement and placing a firm back support prior to compressions were frequently neglected (in 44% and 22% of cases, respectively). The mean +/- SD overall composite score for the tasks was 45 +/- 12% (range, 20-60%). The neonatal team was called in a median (interquartile range) of 1:42 (0:44-2:18) minutes:seconds; 15 of 18 (83%) teams called only after the patient was completely unresponsive. Fifty percent of teams did not provide basic information to the neonatal teams as required by neonatal resuscitation provider guidelines.Multiple deficits were noted in the provision of CPR to parturients during simulated arrests, despite current ACLS certification for all participants. Current requirements for ACLS certification and training for obstetric staff may require revision.

View details for DOI 10.1016/j.ajog.2010.02.022

View details for Web of Science ID 000280234500037

View details for PubMedID 20417476
Variable expression of soluble fms-like tyrosine kinase 1 in patients at high risk for preeclampsia JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Dwyer, B. K., Krieg, S., Balise, R., Carroll, I. R., Chueh, J., Nayak, N., Druzin, M. 2010; 23 (7): 705-711
Abstract

To explore angiogenic factor differences in preeclamptic patients according to the absence or presence of underlying vascular disease.We prospectively compared serum soluble fms-like tyrosine kinase 1 (sFlt1), soluble endoglin, and placental growth factor (PlGF) from 41 normal-risk and 32 high-risk (preexisting conditions) subjects at serial gestational ages.Median sFlt1 was lower at delivery in preeclamptic patients with underlying chronic hypertension and/or chronic proteinuria (5115 pg/ml) compared with normal risk preeclamptic patients (16375 pg/ml). PlGF was consistently low in patients who developed preeclampsia.Effects of sFlt1 may be contextual, varying according to the health or disease state of vascular endothelium.

View details for DOI 10.3109/14767050903258753

View details for Web of Science ID 000279865300024

View details for PubMedID 19895348
The Effects of Respiratory Failure on Delivery in Pregnant Patients With H1N1 2009 Influenza OBSTETRICS AND GYNECOLOGY Jafari, A., Langen, E. S., Aziz, N., Blumenfeld, Y. J., Mihm, F., Druzin, M. L. 2010; 115 (5): 1033-1035
Abstract

The majority of hospitalizations for H1N1 complications have been in people with high-risk comorbidities, including pregnancy. Here we describe the obstetric and critical care treatment of three patients with confirmed H1N1 influenza virus infection complicated by acute respiratory failure.We describe the clinical and therapeutic courses of three patients with confirmed H1N1 2009 influenza virus infection complicating singleton, twin, and triplet gestations, each of which were complicated by respiratory failure.These three cases illustrate that a high index of suspicion, prompt treatment, timing and mode of delivery considerations, and interdisciplinary treatment are integral to the care of pregnant patients with H1N1 influenza infections complicated by acute respiratory failure.

View details for DOI 10.1097/AOG.0b013e3181da85fc

View details for PubMedID 20410779
Acupuncture for Depression During Pregnancy A Randomized Controlled Trial OBSTETRICS AND GYNECOLOGY Manber, R., Schnyer, R. N., Lyell, D., Chambers, A. S., Caughey, A. B., Druzin, M., Carlyle, E., Celio, C., Gress, J. L., Huang, M. I., Kalista, T., Martin-Okada, R., Allen, J. J. 2010; 115 (3): 511-520
Abstract

To estimate the efficacy of acupuncture for depression during pregnancy in a randomized controlled trial.A total of 150 pregnant women who met Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for major depressive disorder were randomized to receive either acupuncture specific for depression or one of two active controls: control acupuncture or massage. Treatments lasted 8 weeks (12 sessions). Junior acupuncturists, who were not told about treatment assignment, needled participants at points prescribed by senior acupuncturists. All treatments were standardized. The primary outcome was the Hamilton Rating Scale for Depression, administered by masked raters at baseline and after 4 and 8 weeks of treatment. Continuous data were analyzed using mixed effects models and by intent to treat.Fifty-two women were randomized to acupuncture specific for depression, 49 to control acupuncture, and 49 to massage. Women who received acupuncture specific for depression experienced a greater rate of decrease in symptom severity (P<.05) compared with the combined controls (Cohen's d=0.39, 95% confidence interval [CI] 0.01-0.77) or control acupuncture alone (P<.05; Cohen's d=0.46, 95% CI 0.01-0.92). They also had significantly greater response rate (63.0%) than the combined controls (44.3%; P<.05; number needed to treat, 5.3; 95% CI 2.8-75.0) and control acupuncture alone (37.5%; P<.05: number needed to treat, 3.9; 95% CI 2.2-19.8). Symptom reduction and response rates did not differ significantly between controls (control acupuncture, 37.5%; massage, 50.0%).The short acupuncture protocol demonstrated symptom reduction and a response rate comparable to those observed in standard depression treatments of similar length and could be a viable treatment option for depression during pregnancy.Clinicaltrials.gov, www.clinicaltrials.gov, NCT00186654.

View details for DOI 10.1097/AOG.0b013e3181cc0816

View details for Web of Science ID 000275132300006

View details for PubMedID 20177281
Team Training/Simulation CLINICAL OBSTETRICS AND GYNECOLOGY Clark, E. A., Fisher, J., Arafeh, J., Druzin, M. 2010; 53 (1): 265-277
Abstract

Obstetrical emergencies require the rapid formation of a team with clear communication, strong leadership, and appropriate decision-making to ensure a positive patient outcome. Obstetric teams can improve their emergency response capability and efficiency through team and simulation training. Postpartum hemorrhage is an ideal model for team and simulation training, as postpartum hemorrhage requires a multidisciplinary team with the capability to produce a protocol-driven, rapid response. This article provides an overview of team and simulation training and focuses on applications within obstetrics, particularly preparation for postpartum hemorrhage.

View details for DOI 10.1097/GRF.0b013e3181cc4595

View details for Web of Science ID 000275407700025

View details for PubMedID 20142662
Prospective Randomized Trial of Simulation Versus Didactic Teaching for Obstetrical Emergencies Joint Annual Meeting of the Association-of-Professors-of-Gynecology-and-Obstetrics/Council-on-Resident-Education-in-Obstetrics-and-Gynecology Daniels, K., Arafeh, J., Clark, A., Waller, S., Druzin, M., Chueh, J. LIPPINCOTT WILLIAMS & WILKINS. 2010: 40?45
Abstract

The objective of this study was to determine whether simulation was more effective than traditional didactic instruction to train crisis management skills to labor and delivery teams.Participants were nurses and obstetric residents (<5 years experience). Both groups were taught management for shoulder dystocia and eclampsia. The simulation group received 3 hours of training in a simulation laboratory, the didactic group received 3 hours of lectures/video and hands-on demonstration. Subjects completed a multiple-choice questionnaire before training and before testing. After 1 month, all teams underwent performance testing as a labor and delivery drill. All drills were video recorded. Team performances were scored by a blinded reviewer using the video recordings and an expert-developed checklist. The data were analyzed using independent samples Student t test and analysis of variance (one way). P value of < or =0.05 was considered to be statistically significant.There was no statistical difference found between the groups on the pretraining and pretesting multiple-choice questionnaire scores. Performance testing performed as a labor and delivery drill showed statistically significant higher scores for the simulation-trained group for both shoulder dystocia (Sim = 11.75, Did = 6.88, P = 0.002) and eclampsia management (Sim = 13.25, Did = 11.38, P = 0.032).In an academic training program, didactic and simulation-trained groups showed equal results on written test scores. Simulation-trained teams had superior performance scores when tested in a labor and delivery drill. Simulation should be used to enhance obstetrical emergency training in resident education.

View details for DOI 10.1097/SIH.0b013e3181b65f22

View details for Web of Science ID 000276077900009

View details for PubMedID 20383090
Neonatal outcomes following antenatal magnesium sulfate exposure: follow up from a magnesium vs. nifedipine tocolysis RCT Lyell, D., Penn, A., Caughey, A., Kogut, E., McClellan, L., Adams, B., Zarghami, M., Druzin, M., El-Sayed, Y. MOSBY-ELSEVIER. 2009: S180?S181
View details for DOI 10.1016/j.ajog.2009.10.646

View details for Web of Science ID 000279559500476
Acute Liver Failure at 26 Weeks' Gestation in a Patient with Sickle Cell Disease LIVER TRANSPLANTATION Greenberg, M., Daugherty, T. J., Elihu, A., Sharaf, R., Concepcion, W., Druzin, M., Esquivel, C. O. 2009; 15 (10): 1236-1241
Abstract

Orthotopic liver transplantation (OLT) for acute liver failure (ALF) during pregnancy is an uncommon occurrence with variable outcomes. In pregnancy-related liver failure, prompt diagnosis and immediate delivery are essential for a reversal of the underlying process and for maternal and fetal survival. In rare cases, the reason for ALF during pregnancy is either unknown or irreversible, and thus OLT may be necessary. This case demonstrates the development of cryptogenic ALF during the 26th week of pregnancy in a woman with sickle cell disease. She underwent successful cesarean delivery of a healthy male fetus at 27 weeks with concurrent OLT. This report provides a literature review of OLT in pregnancy and examines the common causes of ALF in the pregnant patient. On the basis of the management and outcome of our case and the literature review, we present an algorithm for the suggested management of ALF in pregnancy.

View details for DOI 10.1002/It.21820

View details for Web of Science ID 000270931500014

View details for PubMedID 19790148
Maintenance Nifedipine Tocolysis Compared With Placebo A Randomized Controlled Trial 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Lyell, D. J., Pullen, K. M., Mannan, J., Chitkara, U., Druzin, M. L., Caughey, A. B., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2008: 1221?26
Abstract

To estimate whether maintenance nifedipine tocolysis after arrested preterm labor prolongs pregnancy and improves neonatal outcomes.A prospective, randomized double-blind, multicenter study was conducted. After successful tocolysis, patients were randomly assigned to receive 20 mg nifedipine or an identical-appearing placebo every 4-6 hours until 37 weeks of gestation. The primary outcome was attainment of 37 weeks of gestation. Patients were enrolled between 24 weeks and 34 weeks if they had six or fewer contractions per hour, intact membranes, and less than 4 cm cervical dilation. Exclusion criteria were placental abruption or previa, fetal anomaly incompatible with life, or maternal medical contraindication to tocolysis. Sixty-six patients were required for 80% power to detect a 50% reduction in birth before 37 weeks, with a two-tailed alpha of 0.05. Data were analyzed by intent to treat.Seventy-one patients were randomly assigned. Two patients were excluded after randomization and one was lost to follow-up. Thirty-five patients received placebo, and 33 received nifedipine. There were no maternal demographic differences between groups; the placebo group was significantly more dilated and effaced at study entry. There was no difference in attainment of 37 weeks (39% nifedipine compared with 37% placebo, P>.91), mean delay of delivery (33.5+/-19.9 days nifedipine compared with 32.6+/-21.4 days placebo, P=.81) or delay of delivery for greater than 48 hours or 1, 2, 3, or 4 weeks. Neonatal outcomes were similar between groups.When compared with placebo, maintenance nifedipine tocolysis did not confer a large reduction in preterm birth or improvement in neonatal outcomes.ClinicalTrials.gov, www.clinicaltrials.gov, NCT00185952I.

View details for Web of Science ID 000261316200006

View details for PubMedID 19037029
NST SURVEILLANCE IN A LARGE UNIVERSITY COHORT - RATES OF NONREASSURING TRACINGS BY INDICATION Wong, A., Blumenfeld, Y., El-Sayed, Y., Druzin, M. MOSBY-ELSEVIER. 2008: S235
View details for DOI 10.1016/j.ajog.2008.09.865

View details for Web of Science ID 000262205700827
Use of Simulation Based Team Training for Obstetric Crises in Resident Education SIMULATION IN HEALTHCARE Daniels, K., Lipman, S., Harney, K., Arafeh, J., Druzin, M. 2008; 3 (3): 154-160
Abstract

Obstetric crises are unexpected and random. Traditionally, medical training for these acute events has included lectures combined with arbitrary clinical experiences. This educational paradigm has inherent limitations. During actual crises insufficient time exists for discussion and analysis of patient care. Our objective was to create a simulation program to fill this experiential gap.Ten L&D teams participated in high fidelity simulation training. A team consisted of two or three nurses, one anesthesia resident and one or two obstetric residents. Each team participated in two scenarios; epidural-induced hypotension followed by an amniotic fluid embolism. Each simulation was followed by a facilitated debriefing. All simulations were videotaped. Clinical performances of the obstetric residents were graded by two reviewers using the videotapes and a faculty-developed checklist. Recurrent errors were analyzed and graded using Health Failure Modes Effects Analysis. All team members completed a course evaluation.Performance deficiencies of the obstetric residents were identified by an expert team of reviewers. From this list of errors, the "most valuable lessons" requiring further focused teaching were identified and included 1) Poor communication with the pediatric team, 2) Not assuming a leadership role during the code, 3) Poor distribution of workload, and 4) Lack of proper use of low/outlet forceps. Participants reported the simulation course allowed them to learn new skills needed by teams during a crisis.Simulated obstetric crises training offers the opportunity for educators to identify specific performance deficits of their residents and the subsequent development of teaching modules to address these weaknesses.

View details for DOI 10.1097/SIH.0b013e31818187d9

View details for Web of Science ID 000207536200005

View details for PubMedID 19088659
Urinalysis vs urine protein-creatinine ratio to predict significant proteinuria in pregnancy JOURNAL OF PERINATOLOGY Dwyer, B. K., Gorman, M., Carroll, I. R., Druzin, M. 2008; 28 (7): 461-467
Abstract

To compare the urine protein-creatinine ratio with urinalysis to predict significant proteinuria (>or=300 mg per day).A total of 116 paired spot urine samples and 24-h urine collections were obtained prospectively from women at risk for preeclampsia. Urine protein-creatinine ratio and urinalysis were compared to the 24-h urine collection.The urine protein-creatinine ratio had better discriminatory power than urinalysis: the receiver operating characteristic curve had a greater area under the curve, 0.89 (95% confidence interval (CI) 0.83 to 0.95) vs 0.71 (95% CI 0.64 to 0.77, P<0.001). When matched for clinically relevant specificity, urine protein-creatinine ratio (cutoff >or=0.28) is more sensitive than urinalysis (cutoff >or=1+): 66 vs 41%, P=0.001 (with 95 and 100% specificity, respectively). Furthermore, the urine protein-creatinine ratio predicted the absence or presence of proteinuria in 64% of patients; urinalysis predicted this in only 19%.The urine protein-creatinine ratio is a better screening test. It provides early information for more patients.

View details for DOI 10.1038/jp.2008.4

View details for Web of Science ID 000257271500003

View details for PubMedID 18288120
Editorial summary of symposium on hypertensive disorders of pregnancy CURRENT OPINION IN OBSTETRICS & GYNECOLOGY Druzin, M. L., Charles, B., Johnson, A. L. 2008; 20 (2): 91-91
Abstract

Hypertensive disorders of pregnancy, particularly the preeclampsia/eclampsia syndrome, remain the leading causes of worldwide pregnancy-related maternal and neonatal mortality and morbidity. This group of conditions are a 'riddle wrapped in a mystery inside an enigma' to quote Winston Churchill. We are fortunate to have contributions from leading clinical experts who have devoted many years of their professional careers attempting to solve this conundrum.Dr Jack Moodley has provided us with a perspective on clinical management in underresourced countries. Referral to experts, aggressive treatment of hypertension and use of magnesium sulfate improves care. Dr Shennan focuses on the assessment of risk, close antenatal surveillance and timely delivery. Dr Uzan continues to champion the use of aspirin for prevention of preeclampsia, even though the evidence is contradictory. Dr Sibai addresses the lack of evidence for calcium, vitamin C and E in prevention of preeclampsia. Dr Von Dadelszen is developing a new paradigm for the classification of these disorders and emphasizes the importance of evidence-based intervention.Evidence suggests that treatment of severe hypertension, seizure prophylaxis with magnesium sulfate, and management by experienced healthcare professionals will improve maternal, fetal and neonatal outcomes. Well designed studies will lead to evidence-based improvement in caring for mothers and babies worldwide.

View details for Web of Science ID 000254572900001

View details for PubMedID 18388804
Course of preeclamptic glomerular injury after delivery AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Hladunewich, M. A., Myers, B. D., Derby, G. C., Blouch, K. L., Druzin, M. L., Deen, W. M., Naimark, D. M., Lafayette, R. A. 2008; 294 (3): F614-F620
Abstract

We evaluated the early postpartum recovery of glomerular function over 4 wk in 57 women with preeclampsia. We used physiological techniques to measure glomerular filtration rate (GFR), renal plasma flow, and oncotic pressure (pi(A)) and computed a value for the two-kidney ultrafiltration coefficient (K(f)). Compared with healthy, postpartum controls, GFR was depressed by 40% on postpartum day 1, but by only 19% and 8% in the second and fourth postpartum weeks, respectively. Hypofiltration was attributable solely to depression, at corresponding postpartum times, of K(f) by 55%, 30%, and 18%, respectively. Improvement in glomerular filtration capacity was accompanied by recovery of hypertension to near-normal levels and significant improvement in albuminuria. We conclude that the functional manifestations of the glomerular endothelial injury of preeclampsia largely resolve within the first postpartum month.

View details for DOI 10.1152/ajprenal.00470.2007

View details for Web of Science ID 000253574500019

View details for PubMedID 18199600
Maintenance nifedipine vs. placebo: A prospective, double blind trial Lyell, D., Pullen, K., Mannan, J., Chitkara, U., Druzin, M. L., Caughey, A., El-Sayed, Y. MOSBY-ELSEVIER. 2007: S6
View details for DOI 10.1016/i.ajog.2007.10.012

View details for Web of Science ID 000251708500013
Obstetric risks for women with epilepsy during pregnancy EPILEPSY & BEHAVIOR Kaplan, P. W., Norwitz, E. R., Ben-Menachem, E., Pennell, P. B., Druzin, M., Robinson, J. N., Gordon, J. C. 2007; 11 (3): 283?91
Abstract

Women with epilepsy (WWE) face particular challenges during their pregnancy. Among the several obstetric issues for which there is some concern and the need for further investigation are: the effects of seizures, epilepsy, and antiepileptic drugs on pregnancy outcome and, conversely, the effects of pregnancy and hormonal neurotransmitters on seizure control and antiepileptic drug metabolism. Obstetric concerns include preclampsia/eclampsia, preterm delivery, placental abruption, spontaneous abortion, stillbirth, and small-for-date babies in WWE whether or not they are taking antiepileptic drugs. The role of nutritional health elements, including body mass index, caloric and protein intake, vitamins and iron, and phytoestrogens, warrants further study. During the course of obstetric management, there is a need for a fuller understanding by neurologists of the risk-benefit calculations for various types and frequencies of fetal imaging, including CT, MRI, and ultrasound, as well as for the screening standards of care. As part of the Health Outcomes in Pregnancy and Epilepsy (HOPE) project, this expert panel provides a brief overview of these concerns, offers some approaches to management, and outlines potential areas for further investigation. More detailed information and guidelines are available elsewhere.

View details for DOI 10.1016/j.yebeh.2007.08.012

View details for Web of Science ID 000251067800007

View details for PubMedID 17996636
Randomized comparison of intravenous terbutaline vs nitroglycerin for acute intrapartum fetal resuscitation 27th Annual Meeting of the Society-of-Maternal-Fetal-Medicine Pullen, K. M., Riley, E. T., Waller, S. A., Taylor, L., Caughey, A. B., Druzin, M. L., El-Sayed, Y. Y. MOSBY-ELSEVIER. 2007
Abstract

The purpose of this study was to compare terbutaline and nitroglycerin for acute intrapartum fetal resuscitation.Women between 32-, 42 weeks' gestation were assigned randomly to 250 microg of terbutaline or 400 microg nitroglycerin intravenously for nonreassuring fetal heart rate tracings in labor. The rate of successful acute intrapartum fetal resuscitation and the maternal hemodynamic changes were compared. Assuming a 50% failure rate in the terbutaline arm, we calculated that a total of 110 patients would be required to detect a 50% reduction in failure in the nitroglycerin group (50% to 25%), with an alpha value of .05, a beta value of .20, and a power of 80%.One hundred ten women had nonreassuring fetal heart rate tracings in labor; 57 women received terbutaline, and 53 women received nitroglycerin. Successful acute resuscitation rates were similar (terbutaline 71.9% and nitroglycerin 64.2%; P = .38). Terbutaline resulted in lower median contraction frequency per 10 minutes (2.9 [25-75 percentile, 1.7- 3.3] vs 4 [25-75 percentile, 2.5- 5]; P < .002) and reduced tachysystole (1.8% vs 18.9%; P = .003). Maternal mean arterial pressures decreased with nitroglycerin (81-76 mm Hg; P = .02), but not terbutaline (82-81 mm Hg; P = .73).Although terbutaline provided more effective tocolysis with less impact on maternal blood pressure, no difference was noted between nitroglycerin and terbutaline in successful acute intrapartum fetal resuscitation.

View details for DOI 10.1016/j.ajog.2007.06.063

View details for Web of Science ID 000250097300031

View details for PubMedID 17904983
How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol TRANSFUSION Burtelow, M., Riley, E., Druzin, M., Fontaine, M., Viele, M., Goodnough, L. T. 2007; 47 (9): 1564-1572
Abstract

Management of massive, life-threatening primary postpartum hemorrhage in the labor and delivery service is a challenge for the clinical team and hospital transfusion service. Because severe postpartum obstetrical hemorrhage is uncommon, its occurrence can result in emergent but variable and nonstandard requests for blood products. The implementation of a standardized massive transfusion protocol for the labor and delivery department at our institution after a maternal death caused by amniotic fluid embolism is described. This guideline was modeled on a existing protocol used by the trauma service mandating emergency release of 6 units of group O D- red cells (RBCs), 4 units of fresh frozen or liquid plasma, and 1 apheresis unit of platelets (PLTs). The 6:4:1 fixed ratio of uncrossmatched RBCs, plasma, and PLTs allows the transfusion service to quickly provide blood products during the acute phase of resuscitation and allows the clinical team to anticipate and prevent dilutional coagulopathy. The successful management of three cases of massive primary postpartum hemorrhage after the implementation of our new massive transfusion protocol in the maternal and fetal medicine service is described.

View details for DOI 10.1111/j.1537-2995.2007.01404.x

View details for PubMedID 17725718
Magnesium sulfate compared with nifedipine for acute tocolysis of preterm labor - A randomized controlled trial 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Lyell, D. J., Pullen, K., Campbell, L., Ching, S., Druzin, M. L., Chitkara, U., Burrs, D., Caughey, A. B., El-Sayed, Y. Y. LIPPINCOTT WILLIAMS & WILKINS. 2007: 61?67
Abstract

To compare the efficacy and side effects of intravenous magnesium to oral nifedipine for acute tocolysis of preterm labor.A multicenter randomized trial was performed. Patients in active preterm labor who were at 24 to 33 weeks and 6 days of gestation were randomly assigned to receive magnesium sulfate or nifedipine. The primary outcome was arrest of preterm labor, defined as prevention of delivery for 48 hours with uterine quiescence.One hundred ninety-two patients were enrolled. More patients assigned to magnesium sulfate achieved the primary outcome (87% compared with 72%, P=.01). There were no differences in delivery within 48 hours (7.6% magnesium sulfate compared with 8.0% nifedipine, P=.92), gestational age at delivery (35.8 compared with 36.0 weeks, P=.61), birth before 37 and 32 weeks (57% compared with 57%, P=.97, and 11% compared with 8%, P=.39), and episodes of recurrent preterm labor. Mild and severe maternal adverse effects were significantly more frequent with magnesium sulfate. Birth weight, birth weight less than 2,500 g, and neonatal morbidities were similar between groups, but newborns in the magnesium sulfate group spent longer in the neonatal intensive care unit (8.8+/-17.7 compared with 4.2+/-8.2 days, P=.007).Patients who received magnesium sulfate achieved the primary outcome more frequently. However, delay of delivery, gestational age at delivery, and neonatal outcomes were similar between groups. Nifedipine was associated with fewer maternal adverse effects.

View details for Web of Science ID 000247572700011

View details for PubMedID 17601897
Perinatal outcomes after successful and failed trials of labor after cesarean delivery. American journal of obstetrics and gynecology El-Sayed, Y. Y., Watkins, M. M., Fix, M., Druzin, M. L., Pullen, K. M., Caughey, A. B. 2007; 196 (6): 583 e1-5
Abstract

To compare maternal and neonatal outcomes after successful and failed trials of labor after cesarean in women at term, excluding uterine ruptures, and to examine predictors of successful and failed trials of labor.Matched maternal and neonatal data from 1993-1999 in women with singleton term pregnancies with prior cesarean undergoing trial of labor were reviewed. Women with uterine rupture were excluded. Maternal and neonatal outcomes were analyzed for successful and failed trials. Predictors of success and failure were examined.1284 women and their neonates were available for analysis. 1094 (85.2%) had a vaginal birth and 190 (14.8%) underwent repeat cesarean. Failed trials of labor were associated with higher incidence of choriamnionitis (25.8% vs. 5.5%, P<.001), postpartum hemorrhage (35.8% vs. 15.8%, P<.001), hysterectomy (1% vs. 0%, P=.022), neonatal jaundice (17.4% vs.10.2%, P=.004) and composite major neonatal morbidities (6.3% vs. 2.8%, P=.014).Failed trial of labor in women at term with prior cesarean is associated with increased maternal and neonatal morbidities.

View details for PubMedID 17547905
Alternative techniques in resident education: Simulation team training for obstetric crises 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Daniels, K., Lipman, S., Harney, K., Arafeh, J., Yeager, K., Puck, A., Druzin, M. LIPPINCOTT WILLIAMS & WILKINS. 2007: B26?B26
View details for Web of Science ID 000246032500074
Cesarean delivery on maternal request: Wise use of finite resources? A view from the trenches SEMINARS IN PERINATOLOGY Druzin, M. L., El-Sayed, Y. Y. 2006; 30 (5): 305-308
Abstract

Cesarean section rates are rising in the United States and were at an all time high of 29 percent in 2004. Within this context, the issue of cesarean section on maternal request has been described as being part of a "perfect storm" of medical, legal and personal choice issues, and the lack of an opposing view. An increasing cesarean section rate adds an economic burden on already highly stressed medical systems. There is an incremental cost of cesarean section compared to vaginal delivery. The issue of cost must also be considered more broadly. Rising cesarean section rates are associated with a longer length of stay and a higher occupancy rate. This high occupancy rate leads to the diversion of critical care obstetric transports and has dramatically reduced patient satisfaction. These diversions, and the resultant inability to provide needed care to pregnant women, represent a profound societal cost. These critical care diversions and reduced patient satisfaction also negatively impact a health care institution's financial bottom line and competitiveness. The impact of a rising cesarean section rate on both short and long-term maternal and neonatal complications, and their associated costs, must also be taken into account. The incidence of placenta accreta is increasing in conjunction with the rising cesarean section rate. The added costs associated with this complication (MRI, Interventional Radiology, transfusion, hysterectomy, and intensive care admission) can be prohibitive. It has also been demonstrated that infants born by scheduled cesarean delivery are more likely to require advanced nursery support (with all its associated expense) than infants born to mothers attempting vaginal delivery. The practice of maternal request cesarean section, with limited good data and obvious inherent risk and expense, is increasing in the USA. Patient autonomy and a woman's right to choose her mode of delivery should be respected. However, in our opinion, based on the current evidence regarding cesarean delivery on maternal request, promotion of primary cesarean section on request as a standard of care or as a mandated part of patient counseling for delivery will result in a highly questionable use of finite resources. As of 2004, 46 million Americans did not even have basic health insurance. It is critical that we not allow ourselves to be dragged into the eye of a "perfect storm." This conference is an important step in the rational and objective analysis of this issue.

View details for DOI 10.1053/j.semperi.2006.07.012

View details for Web of Science ID 000241449600013

View details for PubMedID 17011403
Effect of L-arginine therapy on the glomerular injury of preeclampsia: a randomized controlled trial. Obstetrics and gynecology Hladunewich, M. A., Derby, G. C., Lafayette, R. A., Blouch, K. L., Druzin, M. L., Myers, B. D. 2006; 107 (4): 886-895
Abstract

To assess the benefit of l-arginine, the precursor to nitric oxide, on blood pressure and recovery of the glomerular lesion in preeclampsia.Forty-five women with preeclampsia were randomized to receive either l-arginine or placebo until day 10 postpartum. Primary outcome measures including mean arterial pressure, glomerular filtration rate, and proteinuria were assessed on the third and 10th days postpartum by inulin clearance and albumin-to-creatinine ratio. Nitric oxide, cyclic guanosine 3'5' monophosphate, endothelin-1, and asymmetric-dimethyl-arginine and arginine levels were assayed before delivery and on the third and 10th days postpartum. Healthy gravid women provided control values. Assuming a standard deviation of 10 mm Hg, the study was powered to detect a 10-mm Hg difference in mean arterial pressure (alpha .05, beta .20) between the study groups.No significant differences existed between the groups with preeclampsia before randomization. Compared with the gravid control group, women with preeclampsia exhibited significantly increased serum levels of endothelin-1, cyclic guanosine 3'5' monophosphate, and asymmetric-dimethyl-arginine before delivery. Despite a significant increase in postpartum serum arginine levels due to treatment, no differences were found in the corresponding levels of nitric oxide, endothelin-1, cyclic guanosine 3'5' monophosphate, or asymmetric-dimethyl-arginine between the two groups with preeclampsia. Further, there were no significant differences in any of the primary outcome measures with both groups demonstrating similar levels in glomerular filtration rate and equivalent improvements in both blood pressure and proteinuria.Blood pressure and kidney function improve markedly in preeclampsia by the 10th day postpartum. Supplementation with l-arginine does not hasten this recovery.I.

View details for PubMedID 16582128
Outcome of pregnancies complicated by systemic sclerosis and mixed connective tissue disease LUPUS Chung, L., Flyckt, R. L., Colon, I., Shah, A. A., Druzin, M., Chakravarty, E. F. 2006; 15 (9): 595-599
Abstract

Systemic sclerosis (SSc) and mixed connective tissue disease (MCTD) are rare autoimmune diseases which share the common feature of non-inflammatory vasculopathy. Studies evaluating pregnancy outcomes in these patients have yielded conflicting results. We sought to describe the outcomes of pregnancies associated with SSc and MCTD followed at our center utilizing a retrospective review of all pregnant women with SSc and MCTD followed at Stanford University from 1993 to 2003. We identified 20 pregnancies occurring in 13 women with SSc or MCTD. Twelve pregnancies occurred in seven women with SSc and eight pregnancies occurred in six women with MCTD. The overall preterm delivery rate was 39% and small for gestational age infants occurred in 50% and 63% of pregnancies associated with SSc and MCTD, respectively. Fetal loss complicated two pregnancies in women with severe diffuse SSc and the antiphospholipid antibody syndrome. There were no cases of congenital heartblock among infants, and only one case of pre-eclampsia was observed. Maternal flares of disease during pregnancy were generally mild. Most pregnancies in women with SSc and MCTD in this cohort were uncomplicated. The high rates of prematurity and small for gestational age infants underscore the risk for growth restriction consistent with the vasculopathy associated with these diseases.

View details for DOI 10.1177/0961203306071915

View details for Web of Science ID 000241996300007

View details for PubMedID 17080915
Magnesium sulfate versus nifedipine for acute tocolysis of preterm labor Lyell, D., Pullen, K., Campbell, L., Ching, S., Burrs, D., Chitkara, U., Druzin, M. MOSBY, INC. 2005: S18
View details for DOI 10.1016/j.ajog.2005.10.047

View details for Web of Science ID 000233947800044
Factors that predict prematurity and preeclampsia in pregnancies that are complicated by systemic lupus erythematosus 71st Annual Meeting of the Central-Association-of-Obstetricians-and-Gynecologists Chakravarty, E. F., Colon, I., Langen, E. S., Nix, D. A., El-Sayed, Y. Y., Genovese, M. C., Druzin, M. L. MOSBY-ELSEVIER. 2005: 1897?1904
Abstract

The purpose of this study was to describe the outcomes of a 10-year cohort of pregnancies in patients with systemic lupus erythematosus and to evaluate clinical and laboratory markers for adverse outcomes.We reviewed all pregnancies in patients with systemic lupus erythematosus who were seen at Stanford University from 1991 to 2001. Univariate analyses were performed to identify potential risk factors for adverse outcomes.Sixty-three pregnancies in 48 women were identified. Approximately 35% of the pregnancies occurred in women with previous renal disease and 10% in women with previous central nervous system disease. Flares occurred in 68% of the pregnancies, the majority of which were mild to moderate. Preeclampsia complicated 12 pregnancies. Factors that were associated with premature delivery included prednisone use at conception (relative risk, 1.8), the use of antihypertensive medications (relative risk, 1.8), and a severe flare during pregnancy (relative risk, 2.0). Thrombocytopenia was associated with an increased risk of preeclampsia (relative risk, 3.2).Flares, most of which were mild to moderate, occurred most of the pregnancies in our cohort of patients with systemic lupus erythematosus. Thrombocytopenia, hypertension, and prednisone use may be predictive factors for particular adverse outcomes.

View details for DOI 10.1016/j.ajog.2005.02.063

View details for Web of Science ID 000230037600034

View details for PubMedID 15970846
Randomized comparison of intravenous nitroglycerin and subcutaneous terbutaline for external cephalic version under tocolysis AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY El-Sayed, Y. Y., Pullen, K., Riley, E. T., Lyell, D., Druzin, M. L., Cohen, S. E., Chitkara, U. 2004; 191 (6): 2051-2055
Abstract

The purpose of this study was to compare the efficacy and safety of intravenous nitroglycerin with that of subcutaneous terbutaline as a tocolytic agent for external cephalic version at term.We performed a prospective randomized trial. Patients between 37 and 42 weeks of gestation were assigned randomly to receive either 200 microg of intravenous nitroglycerin therapy or 0.25 mg of subcutaneous terbutaline therapy for tocolysis during external cephalic version. The rate of successful external cephalic version and side effects were compared between groups.Of 59 randomly assigned patients, 30 patients received intravenous nitroglycerin, and 29 patients received subcutaneous terbutaline. The overall success rate of external cephalic version in the study was 39%. The rate of successful external cephalic version was significantly higher in the terbutaline group (55% vs 23%; P = .01). The incidence of palpitations was significantly higher in patients who received terbutaline therapy (17.2% vs 0%; P = .02), as was the mean maternal heart rate at multiple time periods.Compared with intravenous nitroglycerin, subcutaneous terbutaline was associated with a significantly higher rate of successful external cephalic version at term.

View details for DOI 10.1016/j.ajog.2004.04.040

View details for Web of Science ID 000225925800030

View details for PubMedID 15592291
Is the urinalysis or the urine protein-creatinine ratio a better predictor for significant 24 hour proteinuria in the third trimester hypertensive patient? 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Dwyer, B., Gorman, M., Druzin, M. MOSBY-ELSEVIER. 2004: S66?S66
View details for Web of Science ID 000225925500207
Prospective randomized clinical trial of inpatient cervical ripening with stepwise oral misoprostol versus vaginal misoprostol 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Colon, I., Clawson, K., Taslimi, M., Druzin, M. MOSBY-ELSEVIER. 2004: S15?S15
View details for Web of Science ID 000225925500035
Vaginal versus ultrasound examination of fetal occiput position during the second stage of labor AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chou, M. R., Kreiser, D., Taslimi, M. M., Druzin, M. L., El-Sayed, Y. Y. 2004; 191 (2): 521-524
Abstract

The purpose of this study was to determine whether ultrasonography is more accurate than vaginal examination in the determination of fetal occiput position in the second stage of labor.Eighty-eight patients in the second stage of labor were evaluated by vaginal examination and by combined transabdominal and transperineal ultrasound examination to determine occiput position. These predictions of position were compared with the actual delivery position at vaginal delivery after spontaneous restitution or at cesarean delivery. Different examiners performed the vaginal examinations and the ultrasound examinations. Each examiner was blinded to the determination of the other examiner.Vaginal examination determined fetal occiput position correctly 71.6% of the time; ultrasound examination determined fetal occiput position correctly 92.0% of the time (P=.018).Ultrasound examination is more accurate than vaginal examination in the diagnosis of fetal occiput position in the second stage of labor.

View details for DOI 10.1016/j.ajog.2004.01.029

View details for Web of Science ID 000203976500020

View details for PubMedID 15343230
Cost-effectiveness of a trial of labor after previous cesarean delivery depends on the a priori chance of success CLINICAL OBSTETRICS AND GYNECOLOGY Macario, A., El-Sayed, Y. Y., Druzin, M. L. 2004; 47 (2): 378-385
View details for Web of Science ID 000231530600009

View details for PubMedID 15166861
Prothrombin gene variants in non-Caucasians with fetal loss and intrauterine growth retardation JOURNAL OF MOLECULAR DIAGNOSTICS Schrijver, I., Lenzi, T. J., Jones, C. D., Lay, M. J., Druzin, M. L., Zehnder, J. L. 2003; 5 (4): 250-253
Abstract

Thrombotic predisposition may affect pregnancy outcome, but in non-Caucasians the contributing genetic factors are poorly characterized. Two recently identified prothrombin gene mutations (20209C>T and 20221C>T) have been observed in non-Caucasian patients with thrombosis. The mutations are located near the commonly identified variant 20210G>A and have not been reported in Caucasian patients. The authors report a novel connection with pregnancy complications. The identification of sequence variants other than 20210G>A in the 3'-untranslated region of the prothrombin gene suggests that additional nucleotide substitutions may contribute to the development of thrombotic events and adverse pregnancy outcomes, especially in less well-characterized populations.

View details for Web of Science ID 000186292700009

View details for PubMedID 14573785
Nitric oxide pathway in pre-eclampsia. Hladunewich, M. A., Lafayette, R. A., Derby, G. C., Blouch, K. L., Bialek, J. W., Druzin, M. L., Myers, B. D. LIPPINCOTT WILLIAMS & WILKINS. 2003: 516A
View details for Web of Science ID 000186219102374
Training and competency assessment in electronic fetal monitoring: A national survey OBSTETRICS AND GYNECOLOGY Murphy, A. A., Halamek, L. P., Lyell, D. J., Druzin, M. L. 2003; 101 (6): 1243-1248
Abstract

To investigate current patterns of training and competency assessment in electronic fetal monitoring (EFM) for obstetrics and gynecology residents and maternal-fetal medicine fellows.A questionnaire was mailed to the directors of all 254 accredited US residencies in obstetrics and gynecology and 61 accredited US fellowships in maternal-fetal medicine. Questions focused on the methods used for teaching and assessing competency in EFM.Two hundred thirty-nine programs (76%) responded to the survey. Clinical experience is used by 219 programs (92%) to teach EFM, both initially and on an ongoing basis. Significantly more residencies than fellowships use written materials and lectures to teach EFM. More than half of all programs require trainees to participate in some type of EFM training at least every 6 months; 23 programs (10%) have no requirement at all. Subjective evaluation is used by 174 programs (73%) to assess competency in EFM. Written or oral examinations, skills checklists, and logbooks are used exclusively by residencies as means of competency assessment. Two thirds of all programs assess EFM skills at least every 6 months; 40 programs (17%), the majority of which are fellowships, have no formal requirement.Most US training programs use supervised clinical experience as both their primary source of teaching EFM and their principal competency assessment tool. Residencies are more likely to have formal instruction and assessment than are fellowships. Few programs are using novel strategies (eg, computers or simulators) in their curriculum.

View details for DOI 10.1016/S0029-7844(03)00351-0

View details for PubMedID 12798531
Abnormal fetal heart rate tracings do not correlate with MRI and neurologic outcome in preterm infants Annual Meeting of the Pediatric-Academic-Societies/Society-for-Pediatric-Research Gupta, S., Mirmiran, M., Ariagno, R. L., Lyell, D., Druzin, M. NATURE PUBLISHING GROUP. 2003: 543A?544A
View details for Web of Science ID 000181897903072
Evaluation of a novel electronic fetal monitor simulator 11th Annual Medicine Meets Virtual Reality Conference Murphy, A. A., Halamek, L. P., Lyell, D. J., Druzin, M. L. I O S PRESS. 2003: 240?244
Abstract

The purpose of this study was to evaluate the content validity and construct validity of a novel electronic fetal monitor (EFM) simulator. Fourteen residents in Gynecology and Obstetrics (OB/GYN) and 7 medical students in their OB/GYN clerkship interpreted 10 fetal heart rate (FHR) tracings and 4 clinical scenarios generated by the EFM simulator. Their responses were scored by experts in maternal-fetal medicine. Construct validity was determined by comparing subjects' scores to their level of experience. Subjects assessed content validity of the EFM simulator by rating the realism of its various elements on a 4-point Likert scale. Residents achieved statistically significant higher mean scores in the description of FHR tracings generated by the simulator than medical students and statistically significant higher mean scores in the correct interpretation of and interventions in 2 of 4 clinical scenarios. Two-thirds of the residents rated the simulator-generated FHR tracings and clinical scenarios as "real" or "very real." The EFM simulator exhibited both content and construct validity, supporting its use in an educational setting.

View details for PubMedID 15455900
Glomerular filtration rate and its determinants in the early puerperium after normal pregnancy. Hladunewich, M. A., Derby, G. C., Blouch, K. L., Deen, W. M., Druzin, M., Myers, B. D., Lafayette, R. A. LIPPINCOTT WILLIAMS & WILKINS. 2002: 450A
View details for Web of Science ID 000177757502200
Central nervous system lupus and pregnancy: 11-year experience at a single center. journal of maternal-fetal & neonatal medicine El-Sayed, Y. Y., Lu, E. J., Genovese, M. C., Lambert, R. E., Chitkara, U., Druzin, M. L. 2002; 12 (2): 99-103
Abstract

To describe the pregnancy outcomes in women with central nervous system (CNS) manifestations of lupus.Between 1991 and 2002, the outcome of five pregnancies in four patients with CNS lupus were retrospectively reviewed. All patients had an established history of systemic lupus erythematosus (SLE), and either a history of CNS lupus or active CNS lupus. Pregnancy outcomes assessed included term and preterm birth, intrauterine growth restriction, abnormal antepartum testing, perinatal mortality, pre-eclampsia and other maternal morbidities.Evidence of active CNS lupus symptoms developed in three of the five pregnancies. Two pregnancies were complicated by early onset pre-eclampsia, abnormal antepartum testing and extreme prematurity, with one subsequent neonatal death. The remaining three pregnancies had good neonatal outcomes, but were complicated by severe maternal post-pregnancy exacerbations, and the eventual death of one patient.CNS lupus in pregnancy represents an especially severe manifestation of SLE, and may involve great maternal and fetal risks.

View details for PubMedID 12420839
A longitudinal analysis of maternal serum insulin-like growth factor I (IGF-I) and total and nonphosphorylated IGF-binding protein-1 in human pregnancies complicated by intrauterine growth restriction IGFBP 2000 Meeting Bhatia, S., Faessen, G. H., Carland, G., Balise, R. L., Gargosky, S. E., Druzin, M., El-Sayed, Y., Wilson, D. M., Giudice, L. C. ENDOCRINE SOC. 2002: 1864?70
Abstract

In cord blood and late gestation maternal serum, IGF-I is positively correlated with birth weight, whereas IGF-binding protein-1 (IGFBP-1) is inversely correlated with birth weight. Our goal was to determine whether maternal serum or amniotic fluid concentrations of IGF-I, IGFBP-1, or nonphosphorylated IGFBP-1 (npIGFBP-1) in early gestation predict later fetal growth abnormalities. Maternal serum was collected prospectively across gestation (5-40 wk) from 749 pregnant subjects. Amniotic fluid was collected after amniocentesis during wk 15-26 from 207 subjects. We compared median serum concentrations of IGF-I, IGFBP-1, and npIGFBP-1 in 38 subjects who delivered growth-restricted infants with the control group of 236 subjects with normal weight infants for each gestational age grouping, wk 5-12, 13-23, and 24-34. In the control group median IGF-I concentrations were 14.8, 11, and 15.6 nmol/liter for wk 5-12, 13-23, and 24-34, respectively, compared with 13.7, 14.3, and 10.6 nmol/liter in the intrauterine growth restriction (IUGR) group. Median IGFBP-1 concentrations were 8.5, 30.4, and 24.4 nmol/liter, respectively, in controls, compared with 11.4, 28.6, and 25.5 nmol/liter in the IUGR group. Median npIGFBP-1 concentrations were 6.9, 22, and 17.4 nmol/liter, respectively, in controls, compared with 5.0, 32.1, and 24.2 nmol/liter in the IUGR group. In the control group the median amniotic fluid IGFBP-1 level was 13,160 nmol/liter, and the median npIGFBP-1 level was 15,970 nmol/liter; in the IUGR group these levels were 13,440 and 18,440 nmol/liter, respectively. No clinically useful differences were found between the IUGR and control groups. Our results do not support the use of maternal serum IGF-I or IGFBP-1 or amniotic fluid IGFBP-1 or npIGFBP-1 early in gestation to predict later fetal growth restriction.

View details for PubMedID 11932331
Screening for complete congenital heart block among fetuses of patients with SSA and SSB antibodies Lyell, D., Rosenthal, D., El-Sayed, Y., Druzin, M. MOSBY, INC. 2001: S188
View details for DOI 10.1016/S0002-9378(01)80425-7

View details for Web of Science ID 000172921000390
Abnormal fetal heart rate tracings and cerebral MRI among newborns under 1500 grams Lyell, D. J., Meinard, J. S., Mirmiran, M., Caughey, A., Ariagno, R. L., Druzin, M. L. MOSBY, INC. 2001: S164
View details for DOI 10.1016/S0002-9378(01)80340-9

View details for Web of Science ID 000172921000306
Decreased amniotic fluid index in low-risk pregnancy JOURNAL OF REPRODUCTIVE MEDICINE Kreiser, D., El-Sayed, Y. Y., Sorem, K. A., Chitkara, U., Holbrook, R. H., Druzin, M. L. 2001; 46 (8): 743-746
Abstract

To evaluate the perinatal outcomes of pregnancies complicated by isolated decreased amniotic fluid volume (AFI) after 30 weeks' gestation (AFI < or = 5 or > 5 cm but < 2.5th percentile).We retrospectively studied 150 low-risk singleton pregnancies > 30 weeks' gestation with decreased AFI. We also compared the outcomes of 57 pregnancies with AFI < or = 5 cm to those of 93 pregnancies with AFI > 5 cm but < 2.5th percentile (borderline AFI). Pregnancy outcome was assessed with respect to antepartum, intrapartum and neonatal measures. Statistical significance (P < .05) between groups was determined by means of the Student t test and chi 2 analysis.There were no statistically significant differences between pregnancies with AFI < or = 5 cm and those with AFI > 5 cm but < 2.5th percentile with respect to labor induction for an abnormal nonstress test (7.0% vs. 7.5%, overall 7.3%), cesarean sections for fetal heart rate abnormalities (7.0% vs. 7.5%, overall 7.3%), presence of meconium (16.1% vs. 15.7%, overall 16%) and Apgar score < 7 at five minutes (0 vs. 1.1%, overall 0.66%). There were no perinatal deaths in either group. Antepartum variable decelerations were more common in pregnancies with AFI < or = 5 cm as compared to those with AFI > 5 cm but < 2.5th percentile (63.1% vs. 45.1%, P = .007; overall 53.3%).With antepartum monitoring, perinatal outcome in low-risk pregnancies with an isolated decreased AFI after 30 weeks' gestation (< or = 5 or > 5 cm but < 2.5th percentile) appears to be good.

View details for Web of Science ID 000170694100009

View details for PubMedID 11547649
Cost-effectiveness of a trial of labor after previous cesarean OBSTETRICS AND GYNECOLOGY Chung, A., Macario, A., El-Sayed, Y. Y., Riley, E. T., Duncan, B., Druzin, M. L. 2001; 97 (6): 932-941
Abstract

To determine the cost-effective method of delivery, from society's perspective, in patients who have had a previous cesarean.We completed an incremental cost-effectiveness analysis of a trial of labor relative to cesarean using a computerized model for a hypothetical 30-year old parturient. The model incorporated data from peer-reviewed studies, actual hospital costs, and utilities to quantify health-related quality of life. A threshold of $50,000 per quality-adjusted life-years was used to define cost-effective.The model was most sensitive to the probability of successful vaginal delivery. If the probability of successful vaginal birth after cesarean (VBAC) was less than 0.65, elective repeat cesarean was both less costly and more effective than a trial of labor. Between 0.65 and 0.74, elective repeat cesarean was cost-effective (the cost-effectiveness ratio was less than $50,000 per quality-adjusted life-years), because, although it cost more than VBAC, it was offset by improved outcomes. Between 0.74 and 0.76, trial of labor was cost-effective. If the probability of successful vaginal delivery exceeded 0.76, trial of labor became less costly and more effective. Costs associated with a moderately morbid neonatal outcome, as well as the probabilities of infant morbidity occurring, heavily impacted our results.The cost-effectiveness of VBAC depends on the likelihood of successful trial of labor. Our modeling suggests that a trial of labor is cost-effective if the probability of successful vaginal delivery is greater than 0.74. Improved algorithms are needed to more precisely estimate the likelihood that a patient with a previous cesarean will have a successful vaginal delivery.

View details for Web of Science ID 000169206300013

View details for PubMedID 11384699
The dynamics of glomerular filtration after caesarean section JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY Lafayette, R. A., Malik, T., Druzin, M., Derby, G., Myers, B. D. 1999; 10 (7): 1561-1565
Abstract

The objective of this study was to determine whether the glomerular hyperfiltration of pregnancy is maintained even after Caesarean section and, if so, to define the responsible hemodynamics. The dynamics of glomerular filtration were evaluated in 12 healthy women who had just completed an uncomplicated pregnancy and were delivered by Caesarean section. Age-matched but non-gravid female volunteers (n = 22) served as control subjects. GFR in postpartum women was elevated above control values by 41%; 149+/-10 versus 106+/-3 ml/min per 1.73 m2, respectively (P < 0.001). In contrast, corresponding renal plasma flow was the same in the two groups, such that the postpartum filtration fraction was significantly elevated by 20%. Computation of glomerular intracapillary oncotic pressure (piGC) from knowledge of plasma oncotic pressure and the filtration fraction revealed this quantity to be significantly reduced in postpartum women, 20.6+/-1.7 versus 26.1+/-2.0 mmHg in control subjects (P < 0.001). A theoretical analysis of glomerular ultrafiltration suggests that depression of piGC, the force opposing the formation of filtrate, is predominantly or uniquely responsible for the observed postpartum hyperfiltration.

View details for Web of Science ID 000081143900017

View details for PubMedID 10405212
Randomized comparison of intravenous nitroglycerin and magnesium sulfate for treatment of preterm labor OBSTETRICS AND GYNECOLOGY El-Sayed, Y. Y., Riley, E. T., Holbrook, R. H., Cohen, S. E., Chitkara, U., Druzin, M. L. 1999; 93 (1): 79-83
Abstract

To compare the safety and efficacy of high-dose intravenous (IV) nitroglycerin with those of IV magnesium sulfate for acute tocolysis of preterm labor.Thirty-one women with preterm labor before 35 weeks' gestation were assigned randomly to IV magnesium sulfate or IV nitroglycerin for tocolysis. Preterm labor was defined as the occurrence of at least two contractions in 10 minutes, with cervical change or ruptured membranes. Acute tocolysis was defined as tocolysis for up to 48 hours. Magnesium sulfate was administered as a 4-g bolus, then at a rate of 2-4 g/h. Nitroglycerin was administered as a 100-microg bolus, then at a rate of 1- to 10-microg/kg/min. The primary outcome measure was achievement of at least 12 hours of successful tocolysis.Thirty patients were available for analysis. There were no significant differences in gestational age, cervical dilation, or incidence of ruptured membranes between groups at the initiation of tocolysis. Successful tocolysis was achieved in six of 16 patients receiving nitroglycerin, compared with 11 of 14 receiving magnesium sulfate (37.5 versus 78.6%, P = .033). Tocolytic failures (nitroglycerin versus magnesium sulfate) were due to persistent contractions with cervical change or rupture of previously intact membranes (five of 16 versus two of 14), persistent hypotension (four of 16 versus none of 14), and other severe side effects (one of 16 versus one of 14). Maternal hemodynamic alterations were more pronounced in patients who received nitroglycerin, and 25% of patients assigned to nitroglycerin treatment had hypotension requiring discontinuation of therapy.Tocolytic failures were more common with nitroglycerin than with magnesium sulfate. The hemodynamic alterations noted in patients receiving nitroglycerin, including a 25% incidence of persistent hypotension, might limit the usefulness of IV nitroglycerin for the acute tocolysis of preterm labor.

View details for Web of Science ID 000077885200017

View details for PubMedID 9916961
A new therapeutic approach to the fetus with congenital complete heart block: Preemptive, targeted therapy with dexamethasone OBSTETRICS AND GYNECOLOGY Rosenthal, D., Druzin, M., Chin, C., Dubin, A. 1998; 92 (4): 689-691
Abstract

Therapy of established congenital complete heart block in the fetus has resulted in improved survival but persistence of heart block. This exposes the infant to the morbidity of heart block, including the risk of sudden death and pacemaker implantation.A 35-year-old gravida 2, para 1, with Sjogren syndrome and a previous pregnancy complicated by congenital complete heart block presented during her second pregnancy. Intensive fetal monitoring with echocardiography was employed. Early evidence of myocardial dysfunction and dysrhythmia was found, dexamethasone therapy was initiated, and the dysfunction and dysrhythmia resolved. The pregnancy went to term without further complication.This represents a new and successful strategy to identify very early signs of myocardial disease in a fetus at high risk of congenital complete heart block, enabling targeted, preemptive therapy.

View details for Web of Science ID 000076159900022

View details for PubMedID 9764666
Nature of glomerular dysfunction in pre-eclampsia KIDNEY INTERNATIONAL Lafayette, R. A., Druzin, M., Sibley, R., Derby, G., Malik, T., Huie, P., Polhemus, C., Deen, W. M., Myers, B. D. 1998; 54 (4): 1240-1249
Abstract

Pre-eclampsia is characterized by hypertension, proteinuria and edema. Simultaneous studies of kidney function and structure have not been reported. We wished to explore the degree and nature of glomerular dysfunction in pre-eclampsia.Physiologic techniques were used to estimate glomerular filtration rate (GFR), renal plasma flow and afferent oncotic pressure immediately after delivery in consecutive patients with pre-eclampsia (PET; N = 13). Healthy mothers completing an uncomplicated pregnancy served as functional controls (N = 12). A morphometric analysis of glomeruli obtained by biopsy and mathematical modeling were used to estimate the glomerular ultrafiltration coefficient (Kf). Glomeruli from healthy female kidney transplant donors served as structural controls (N = 8).The GFR in PET was depressed below the control level, 91 +/- 23 versus 149 +/- 34 ml/min/1.73 m2, respectively (P < 0.0001). In contrast, renal plasma flow and oncotic pressure were similar in the two groups (P = NS). A reduction in the density and size of endothelial fenestrae and subendothelial accumulation of fibrinoid deposits lowered glomerular hydraulic permeability in PET compared to controls, 1.81 versus 2.58 x 10(-9) m/sec/PA. Mesangial cell interposition also curtailed effective filtration surface area. Together, these changes lowered the computed single nephron Kf in PET below control, 4.26 versus 6.78 nl/min x mm Hg, respectively.The proportionate (approximately 40%) depression of Kf for single nephrons and GFR suggests that hypofiltration in PET does not have a hemodynamic basis, but is a consequence of structural changes that lead to impairment of intrinsic glomerular ultrafiltration capacity.

View details for Web of Science ID 000076096900022

View details for PubMedID 9767540
Analysis of prenatal and gestational care given to women with epilepsy NEUROLOGY Seale, C. G., Morrell, M. J., Nelson, L., Druzin, M. L. 1998; 51 (4): 1039-1045
Abstract

To assess past care practices of neurologists and obstetricians to identify areas in which practice patterns differ from currently accepted optimal care.Retrospective chart review of 155 women identified as having a diagnosis of epilepsy (or seizure disorder) who had been pregnant any time between January 1988 and December 1995 and were admitted to Stanford University Hospital for delivery. A total of 161 pregnancies (132 women) were selected for study.An obstetrician was seen at some point during the pregnancy in 99% of the pregnancies, whereas a neurologist was seen at least once in only 64% of the pregnancies. In the 3 months before conception, an obstetrician was seen in 5% of the pregnancies and a neurologist was seen in 15%. Seventy-five percent of the patients taking antiepileptic medication and 65% of the untreated patients had documentation of folate supplementation at any time during pregnancy. Vitamin K supplementation in the final month of pregnancy was documented for only 41% of those receiving antiepileptic drugs. In over one-third of the pregnancies the mother did not have a maternal serum alpha-fetoprotein measure documented and a similar percentage did not receive genetic counseling. Monitoring of the maternal serum concentration of the non-protein-bound fraction of the prescribed antiepileptic drugs was not documented.We identified specific omissions of appropriate vitamin supplementation, genetic counseling, and drug level monitoring. Educational efforts should be targeted to improve the management of pregnancy in women with epilepsy.

View details for Web of Science ID 000076399100024

View details for PubMedID 9781526
Diltiazem for maintenance tocolysis of preterm labor: comparison to nifedipine in a randomized trial. The Journal of maternal-fetal medicine El-Sayed, Y. Y., Holbrook, R. H., Gibson, R., Chitkara, U., Druzin, M. L., Baba, D. 1998; 7 (5): 217-221
Abstract

The objective of this study was to compare the safety and efficacy of maintenance tocolysis with oral diltiazem to oral nifedipine in achieving 37 weeks gestation. After successful intravenous tocolysis with magnesium sulfate, 69 women with preterm labor at <35 weeks gestation were randomly assigned to nifedipine (20 mg orally every 4-6 hr), or diltiazem (30-60 mg orally every 4-6 hr). The primary outcome was the percentage of patients achieving 37 weeks gestation. Maternal cardiovascular alterations and neonatal outcomes were also assessed. Sixty-nine patients were available for final analysis. Less patients on diltiazem as compared to nifedipine achieved 37 weeks (15.1% vs. 41.7%, P = 0.019). Gestational age at delivery was also less for patients receiving diltiazem (35.5 +/- 3.5 weeks vs. 33.4 +/- 3.9 weeks, P = 0.022). There were fewer days gained in utero from randomization to delivery with diltiazem as compared to nifedipine; however, this difference was not statistically significant (22.4 +/- 16.3 days vs. 31.2 +/- 24.4 days, P = 0.084). Maternal blood pressure and pulse during tocolysis did not differ significantly between groups. Despite the theoretical advantages of diltiazem tocolysis, maintenance tocolysis with diltiazem offered no benefit over nifedipine in achieving 37 weeks gestation. The cardiovascular alterations with either drug in normotensive, pregnant patients appear minimal.

View details for PubMedID 9775988
Obstetric complications in pulmonary and critical care medicine CHEST Rizk, N. W., Kalassian, K. G., Gilligan, T., DRUZIN, M. I., Daniel, D. L. 1996; 110 (3): 791-809
View details for Web of Science ID A1996VG59000039

View details for PubMedID 8797428
Systemic lupus erythematosus and pregnancy ANNALES DE MEDECINE INTERNE Druzin, M. L., VANVOLLENHOVEN, R. F. 1996; 147 (4): 265-273
Abstract

SLE is an autoimmune condition primarily affecting females in their reproductive years. Advances in medical management of SLE, improved understanding of pregnancy complications and the improvement in neontal medicine have allowed females with SLE to have successful pregnancies.

View details for Web of Science ID A1996VH51400006

View details for PubMedID 8952746
PREGNANCY COMPLICATED BY PRIMARY ANTIPHOSPHOLIPID ANTIBODY SYNDROME OBSTETRICS AND GYNECOLOGY Hochfeld, M., Druzin, M. L., Maia, D., Wright, J., Lambert, R. E., McGuire, J. 1994; 83 (5): 804-805
Abstract

Primary antiphospholipid antibody syndrome is a clinical entity that may threaten the health of both fetus and mother.We report a fatal case of primary antiphospholipid antibody syndrome in a woman who developed catastrophic disease due to multisystem thrombosis in the postpartum period following a fetal death. Three years before her admission, primary antiphospholipid antibody syndrome was diagnosed on the basis of high titers of immunoglobulin G anticardiolipin antibody, a positive lupus anticoagulant, a false-positive VDRL, and fibrin deposits in the biopsy of a palmar lesion.The physician must recognize the potentially catastrophic complications of pregnancy and the postpartum period in patients with antiphospholipid antibodies, and appropriate patient counseling should be provided.

View details for Web of Science ID A1994NJ17600001

View details for PubMedID 8159355
THE USE OF VIBROACOUSTIC STIMULATION DURING THE ABNORMAL OR EQUIVOCAL BIOPHYSICAL PROFILE OBSTETRICS AND GYNECOLOGY Inglis, S. R., Druzin, M. L., Wagner, W. E., Kogut, E. 1993; 82 (3): 371-374
Abstract

To determine whether vibroacoustic stimulation during the biophysical profile can change the fetal behavioral state and thus improve the score without increasing the false-negative rate of the test.Eighty-one patients whose biophysical profile scores were 6 or lower after 15 minutes of observation had an electronic artificial larynx applied to the maternal abdomen in the region of the fetal head for 3 seconds, followed by continued observation for fetal movement, tone, and breathing for 15 minutes. We compared the obstetric and neonatal outcomes of 41 patients whose biophysical profile scores improved to normal after vibroacoustic stimulation with those of 283 patients whose scores were normal without vibroacoustic stimulation.Vibroacoustic stimulation did improve an abnormal or equivocal biophysical profile score to normal in 67 of 81 cases (82%). No antepartum stillbirths or perinatal deaths occurred. There was no increase in the obstetric and neonatal complication rates of cesarean delivery for fetal distress, meconium staining of the amniotic fluid, and the incidence of small for gestational age infants.Vibroacoustic stimulation improved the biophysical profile scores in most cases, an effect seen throughout the third trimester. Vibroacoustic stimulation did not appear to increase the false-negative rate of the biophysical profile and may reduce the incidence of unnecessary obstetric intervention.

View details for Web of Science ID A1993LU53400011

View details for PubMedID 8355936
SHOULD ALL PREGNANT PATIENTS BE OFFERED PRENATAL-DIAGNOSIS REGARDLESS OF AGE OBSTETRICS AND GYNECOLOGY Druzin, M. L., Chervenak, F., McCullough, L. B., Blatman, R. N., Neidich, J. A. 1993; 81 (4): 615-618
Abstract

To assess the acceptance of prenatal genetic diagnosis by patients younger than 35 years old who are therefore not yet at great risk for non-disjunction trisomies based on maternal age.The patients were counseled regarding the following: 1) the age-related risk of chromosomal abnormalities, 2) the procedure-related risk of fetal loss, 3) clinical implications of chromosomal abnormalities, 4) the need for complete counseling by a certified genetic counselor, and 5) the patient expense of $600-1200 if third-party reimbursement was not available. Patients were recruited from the private practice of the senior author at the New York Hospital--Cornell Medical Center. Five hundred ninety-one patients were offered prenatal genetic diagnosis. The outcome measure was the patient's decision to undergo prenatal diagnosis even though the risk of a non-disjunction trisomy was expected to be low based on maternal age. Amniocentesis was performed in 128 patients and chorionic villus sampling in five.One hundred thirty-three patients (22.5%) chose prenatal diagnosis. Karyotype was obtained in 131 procedures, but two were unsuccessful. One of the 131 karyotypes was abnormal and the patient chose to terminate the pregnancy.The data showed the following: 1) Inappropriate influence of patients by the health provider was not evident; 2) routine offering of genetic diagnosis enhanced the autonomy of pregnant women; 3) the potential increase in the loss of pregnancies that accompanies this practice is ethically justified; and 4) there are no compelling cost-benefit objections to such a practice.

View details for PubMedID 8459978
CONDITION SPECIFIC ANTEPARTUM TESTING - SYSTEMIC LUPUS-ERYTHEMATOSUS AND ASSOCIATED SEROLOGIC ABNORMALITIES INTERNATIONAL CONF ON RHEUMATIC DISEASES IN PREGNANCY Adams, D., Druzin, M. L., Edersheim, T., Bond, A., Kogut, E. MUNKSGAARD INT PUBL LTD. 1992: 159?63
Abstract

Antepartum fetal surveillance is well established in the optimal management of any pregnancy complicated by maternal systemic lupus erythematosus and/or its associated serologic abnormalities. Our experience in antepartum surveillance of the "lupus pregnancy" from 1980 to 1988 is reviewed. An overall perinatal mortality rate of 6.06% compares favorably to the total intrauterine death rate range usually reported for this disease.

View details for Web of Science ID A1992KH72800012

View details for PubMedID 1285869
VENOUS EMBOLI OCCURRING DURING CESAREAN-SECTION - THE EFFECT OF PATIENT POSITION CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE Fong, J., Gadalla, F., Druzin, M. 1991; 38 (2): 191-195
Abstract

The effect of position, horizontal versus 5 degrees reverse Trendelenburg's, on the incidence of venous emboli during Caesarean section was evaluated in 207 patients. Venous emboli were diagnosed using precordial ultrasonic Doppler monitoring. In the horizontal position, 44% (60 of 134) parturients had venous emboli compared with 1% (1 of 73) parturients in the 5 degrees reverse Trendelenburg's position (P less than 0.0001). Epidural anaesthesia was performed in 171 patients, and 36 patients had general anaesthesia. In the epidural group, pulse oximetric haemoglobin oxygen desaturation and complaints of chest pain and/or dyspnoea were associated with the venous emboli. Venous emboli, probably air, occur frequently during Caesarean section with the patient in the horizontal position. This occurrence was minimized by placing the patient in the 5 degrees reverse Trendelenburg's position.

View details for Web of Science ID A1991FA00200010

View details for PubMedID 2021988
LONGITUDINAL-STUDY OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM IN HYPERTENSIVE PREGNANT-WOMEN - DEVIATIONS RELATED TO THE DEVELOPMENT OF SUPERIMPOSED PREECLAMPSIA AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY August, P., Lenz, T., ALES, K. L., Druzin, M. L., Edersheim, T. G., Hutson, J. M., Muller, F. B., Laragh, J. H., Sealey, J. E. 1990; 163 (5): 1612-1621
Abstract

A prospective longitudinal study of 25 pregnant women (30 pregnancies) with chronic hypertension, a group prone to development of preeclampsia, was conducted to explore the relationship between the renin-angiotensin-aldosterone system and the development of superimposed preeclampsia. In women with chronic hypertension in whom preeclampsia did not develop (17 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated, beginning in the first trimester and continuing throughout pregnancy as found previously in normotensive pregnant women (n = 58). Plasma estradiol and progesterone levels also increased progressively. In women with chronic hypertension in whom preeclampsia developed (13 pregnancies), blood pressure decreased and the renin-angiotensin-aldosterone system was stimulated in the first trimester as in the other groups. However, later in pregnancy significant differences were observed. Blood pressure began to rise in the second trimester. Initially the renin-angiotensin-aldosterone system remained stimulated, but in the early third trimester, when preeclampsia was diagnosed, plasma renin activity and urine aldosterone excretion decreased, and atrial natriuretic factor increased. These data provide information that may be useful in the recognition of superimposed preeclampsia, and in the investigation of its pathogenesis.

View details for Web of Science ID A1990EJ61400041

View details for PubMedID 2146881
THE EFFECT OF VIBROACOUSTIC STIMULATION ON THE NONSTRESS TEST AT GESTATIONAL AGES OF 32 WEEKS OR LESS AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Druzin, M. L., Edersheim, T. G., Hutson, J. M., Bond, A. L. 1989; 161 (6): 1476-1478
Abstract

The effect of vibroacoustic stimulation on the nonstress test at gestational ages of less than or equal to 32 weeks was studied in 15 patients who underwent a total of 316 nonstress tests starting at 20 to 25 weeks' gestation. There were 168 nonreactive nonstress tests that were followed by 3 seconds of vibroacoustic stimulation. The incidence of reactive nonstress tests after vibroacoustic stimulation was significantly increased after 26 weeks' gestation. This may have clinical applicability and may be related to functional maturation of the fetal auditory system.

View details for Web of Science ID A1989CG73300008

View details for PubMedID 2603902
UTERINE INCISION AND MATERNAL MORBIDITY AFTER CESAREAN-SECTION FOR DELIVERY OF THE VERY LOW-BIRTH-WEIGHT FETUS SURGERY GYNECOLOGY & OBSTETRICS Druzin, M. L., Hutson, J. M., SanRoman, G. 1989; 169 (2): 131-132
Abstract

The maternal morbidity associated with the type of uterine incision used for the delivery of the very low birthweight (VLBW) fetus was examined. Maternal morbidity factors evaluated included the incidence of infection, bleeding, wound complications, estimated blood loss, blood transfusions, fever and days in hospital. Cesarean section was performed in 115 of 197 VLBW infants, with 31 low transverse and 84 vertical cesarean sections. There were no significant differences in antepartum, intrapartum or postpartum data between these two groups. Short term maternal morbidity was not increased with the use of vertical compared with low transverse cesarean section for the delivery of the VLBW fetus.

View details for Web of Science ID A1989AJ07100007

View details for PubMedID 2756460
ATRIAL NATRIURETIC FACTOR IN NORMAL AND HYPERTENSIVE PREGNANCY AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Bond, A. L., August, P., Druzin, M. L., Atlas, S. A., Sealey, J. E., Laragh, J. H. 1989; 160 (5): 1112-1116
Abstract

Atrial natriuretic factor may play a role in the regulation of blood pressure, renal function, and volume homeostasis in normal and pathologic states. Atrial natriuretic factor and plasma renin activity were measured by radioimmunoassay in pregnant women with normal blood pressure (n = 29), chronic hypertension (n = 17), and preeclampsia (n = 18) during the first, second, and third trimesters and in the postpartum period. Serial data were obtained in 11 patients. Nonpregnant age-matched women were used as controls (n = 14). In normal gestation and in chronic hypertension, atrial natriuretic factor levels were in the same range as that in the control group. Mean atrial natriuretic factor was significantly higher in the antepartum and postpartum periods in severe preeclampsia. There was an inverse relationship between atrial natriuretic factor and plasma renin activity in pregnancies complicated by chronic hypertension or preeclampsia. Although fluctuations in atrial natriuretic factor levels did not predict preeclampsia, atrial natriuretic factor did correlate with the severity of the disease.

View details for Web of Science ID A1989U693200020

View details for PubMedID 2524972
EXPECTANT MANAGEMENT OF ABRUPTIO PLACENTAE BEFORE 35 WEEKS GESTATION AMERICAN JOURNAL OF PERINATOLOGY Bond, A. L., Edersheim, T. G., Curry, L., Druzin, M. L., Hutson, J. M. 1989; 6 (2): 121-123
Abstract

Forty-three patients with abruptio placentae before 35 weeks of pregnancy were managed expectantly with observation or with tocolytic therapy when contractions were present. Mean time to delivery was 12.4 days. Twenty-three patients were delivered within 1 week of admission. In the remaining 20 patients, the mean time to delivery was 26.8 days. There were no intrauterine deaths. In properly selected patients with preterm gestation and low-grade abruptio it is reasonable to defer delivery. These patients must be followed closely with antepartum fetal heart rate monitoring, serial hematologic and coagulation profiles, and serial sonograms when indicated.

View details for Web of Science ID A1989U425900005

View details for PubMedID 2712908
PREDNISONE DOES NOT PREVENT RECURRENT FETAL DEATH IN WOMEN WITH ANTIPHOSPHOLIPID ANTIBODY AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Lockshin, M. D., Druzin, M. L., QAMAR, T. 1989; 160 (2): 439-443
Abstract

Effects of therapy, antibody titer, and pregnancy history on pregnancy outcome were evaluated in pregnancies of women with antiphospholipid antibody. Prior fetal death and a high antiphospholipid antibody titer (greater than 40 IgG phospholipid units) contributed independently, in an additive manner, to current fetal loss. Twenty-one pregnancies occurred in asymptomatic women who had both prior fetal death and a high IgG antiphospholipid antibody titer. In this very high-risk group, 9 of 11 (82%) of pregnancies treated with prednisone, 10 to 60 mg/day, ended in fetal death, compared with 5 of 10 (50%) not treated with prednisone (p approximately 0.01, life-table analysis). Of pregnancies treated with aspirin, 80 mg/day, 9 of 14 (64%) treated and 5 of 7 (71%) not treated with prednisone had a fetal death (difference not significant). Prednisone does not improve, and may worsen, current fetal outcome in asymptomatic pregnant women with a high antiphospholipid antibody titer and prior fetal death.

View details for Web of Science ID A1989T280500043

View details for PubMedID 2916633
2ND-TRIMESTER FETAL MONITORING AND PRETERM DELIVERY IN PREGNANCIES WITH SYSTEMIC LUPUS-ERYTHEMATOSUS AND OR CIRCULATING ANTICOAGULANT AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Druzin, M. L., Lockshin, M., Edersheim, T. G., Hutson, J. M., KRAUSS, A. L., Kogut, E. 1987; 157 (6): 1503-1510
Abstract

Antepartum fetal monitoring was initiated at 19 to 26 weeks' gestation in 15 pregnancies: six (five with systemic lupus erythematosus, one with circulating anticoagulant) with a complicated antepartum course (group 1); three, all systemic lupus erythematosus, with a normal antepartum course (group 2); and six normal control pregnancies (group 3). Group 1 all exhibited nonperiodic fetal heart rate decelerations, without the classical appearance of early, late, or variable decelerations, and four of the six had fetal bradycardia. In three group 1 cases, there was no active intervention because of early gestational age, and fetal death occurred at 23, 27, and 27 weeks, respectively. The other three patients in group 1 received betamethasone and were delivered by cesarean section at 28 to 30 weeks. There were no cases of respiratory distress syndrome or neonatal death. Five of the six infants in group 1 were small for gestational age. The nonperiodic fetal heart rate decelerations were absent in both groups 2 and 3 who all had normal fetal outcomes at term. The abnormal finding of women with nonperiodic fetal heart rate decelerations at 20 to 28 weeks may detect the fetus at risk for intrauterine death in pregnancies complicated by systemic lupus erythematosus or circulating anticoagulant. Continued surveillance, steroid induction of lung maturity, and delivery should be considered in these cases.

View details for Web of Science ID A1987L343100032

View details for PubMedID 3122577
ANTIBODY TO CARDIOLIPIN, LUPUS ANTICOAGULANT, AND FETAL DEATH JOURNAL OF RHEUMATOLOGY Lockshin, M. D., QAMAR, T., Druzin, M. L., Goei, S. 1987; 14 (2): 259-262
Abstract

We compared the concordance and predictive powers of activated partial thromboplastin time (APTT) and of IgG and IgM antibody to cardiolipin (aCL), for predicting fetal death in 50 pregnant women with systemic lupus erythematosus (SLE) and/or lupus anticoagulant. Overall concordance of any abnormal determination of aCL during pregnancy with any abnormal determination of APTT was 76% (0.05 less than p less than 0.10). Fetal death occurred in 6/12 (50%) of patients with high APTT compared to 5/20 (16%) of patients with low APTT; fetal death occurred in 10/13 (77%) of patients with abnormal aCL and in 2/37 (5%) of patients with normal aCL. Sensitivity for predicting fetal death was .55 for APTT and .85 for aCL; specificity was .81 for APTT and .92 for aCL. Abnormalities of APTT and aCL are sufficiently frequently discordant to prevent equation of the 2 assays. ACL is the better assay for predicting fetal death.

View details for Web of Science ID A1987H387700014

View details for PubMedID 3110418
HYPOCALCIURIA IN PREECLAMPSIA NEW ENGLAND JOURNAL OF MEDICINE TAUFIELD, P. A., ALES, K. L., Resnick, L. M., Druzin, M. L., Gertner, J. M., Laragh, J. H. 1987; 316 (12): 715-718
Abstract

We studied 40 women in the third trimester of pregnancy to determine whether alterations in serum calcium levels or in urinary calcium excretion would distinguish patients with preeclampsia from normal pregnant women or women with other forms of gestational hypertension. Our population included 10 normal pregnant women, 5 pregnant women with transient hypertension, 6 with chronic hypertension, 7 with chronic hypertension and superimposed preeclampsia, and 12 with preeclampsia. The serum levels of ionized calcium, phosphate, and 1,25-dihydroxyvitamin D were not different among the various groups. In contrast, the mean (+/- SD) 24-hour urinary calcium excretion in the patients with preeclampsia or hypertension with superimposed preeclampsia was significantly lower (42 +/- 29 and 78 +/- 49 mg) than that in normal pregnant women (313 +/- 140 mg per 24 hours), women with transient hypertension (248 +/- 139 mg per 24 hours), or women with chronic hypertension (223 +/- 41 mg per 24 hours) (P less than 0.0001). The hypocalciuria in the women with preeclampsia was associated with a decreased fractional excretion of calcium. Although the mean creatinine clearance was reduced in the women with preeclampsia, the range of values overlapped with those in the other groups. In contrast, we observed little or no overlap with respect to calcium excretion. We conclude that preeclampsia is associated with hypocalciuria due to increased tubular reabsorption of calcium. Measurement of calcium excretion may be useful in distinguishing preeclampsia from other forms of gestational hypertension.

View details for Web of Science ID A1987G405500004

View details for PubMedID 3821810
RELATIONSHIP OF BASE-LINE FETAL HEART-RATE TO GESTATIONAL-AGE AND FETAL SEX AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Druzin, M. L., Hutson, J. M., Edersheim, T. G. 1986; 154 (5): 1102-1103
Abstract

A study of 37 patients who underwent 365 antepartum fetal heart rate tests showed a significant difference in heart rate between 19 to 24 weeks' and 36 to 40 weeks' gestation. Baseline heart rate remained within the normal range, suggesting that an abnormal heart rate at any gestational age should prompt further fetal assessment. Baseline fetal heart rate was not significantly different between male and female fetuses.

View details for Web of Science ID A1986C380800032

View details for PubMedID 3706438
THE RELATIONSHIP OF THE NONSTRESS TEST TO GESTATIONAL-AGE AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Druzin, M. L., Fox, A., Kogut, E., Carlson, C. 1985; 153 (4): 386-389
Abstract

Five hundred ninety-three nonstress tests were performed on 41 obstetric patients, at gestational ages ranging from 20 to 40 weeks. Diagnoses included 10 cases of prematurity, six cases of diabetes mellitus, five cases of collagen-vascular disease, five cases of poor obstetric history, three cases of cardiac arrhythmia, and one case each of asthma, polyhydramnios, leukemia, nonimmune fetal hydrops; and eight volunteers were without high-risk factors. All neonates had a 5-minute Apgar score greater than 8; 29 neonates weighed greater than or equal to 2500 gm, 12 weighed less than 2500 gm, and four weighed less than 1500 gm. One neonate died of prematurity, and one was small for gestational age. There were no congenital anomalies. There was a significant difference in the number of reactive nonstress tests and nonreactive nonstress tests between the 20- to 24-week, 24- to 28-week, 28- to 32-week, and 32- to 36-week gestational age groups. The increased incidence of nonreactive nonstress tests at earlier gestational ages may have clinical implications.

View details for Web of Science ID A1985ASW4400006

View details for PubMedID 3901768
ANTIBODY TO CARDIOLIPIN AS A PREDICTOR OF FETAL DISTRESS OR DEATH IN PREGNANT PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS NEW ENGLAND JOURNAL OF MEDICINE Lockshin, M. D., Druzin, M. L., Goei, S., QAMAR, T., Magid, M. S., Jovanovic, L., Ferenc, M. 1985; 313 (3): 152-156
Abstract

During a prospective study of pregnancies in women with systemic lupus erythematosus, we examined the relation between antibody to cardiolipin, measured by the enzyme-linked immunosorbent assay, and midpregnancy fetal distress, identified by abnormal results of antepartum fetal heart-rate testing or by fetal death. All of nine patients with lupus and this complication had abnormally high antibody levels (mean, 212.3 +/- 55.3 units), as compared with values in normal nonpregnant women (28.2 +/- 10.1 units). None of 12 pregnant patients with lupus but without this complication had antibody levels above 50 units (mean, 27.5 +/- 3.4 units; P less than 0.005 vs. women with lupus and fetal distress); 4 of 12 pregnant subjects without lupus had antibody levels above 50 units (mean, 42.5 +/- 11.0), and fetal death occurred in the subject with the highest level. The mean antibody level in 12 nonpregnant patients with lupus was 117.4 +/- 35.0 units. Two patients who had lupus anticoagulant but not clinical lupus, both with histories of prior fetal death, also had high antibody levels; fetal death occurred in one, and spontaneous fetal bradycardia in the other. Antibody to cardiolipin was loosely linked to a history, but not the simultaneous presence, of demonstrable lupus anticoagulant or thrombocytopenia, and could be detected as early in pregnancy as either anticoagulant or thrombocytopenia. We conclude that measurement of antibody to cardiolipin is the most sensitive assay to predict fetal distress or death in patients with systemic lupus erythematosus and may be of pathogenetic importance in this syndrome.

View details for Web of Science ID A1985ALZ9700004

View details for PubMedID 3925336
LUPUS PREGNANCY - CASE-CONTROL PROSPECTIVE-STUDY DEMONSTRATING ABSENCE OF LUPUS EXACERBATION DURING OR AFTER PREGNANCY AMERICAN JOURNAL OF MEDICINE Lockshin, M. D., REINITZ, E., Druzin, M. L., MURRMAN, M., Estes, D. 1984; 77 (5): 893-898
Abstract

To assess whether pregnancy is associated with exacerbation of systemic lupus erythematosus (SLE), a variety of clinical markers of disease activity in 28 pregnant patients with SLE (33 pregnancies) were compared with the same markers in age-, race-, organ system-, and disease severity-matched nonpregnant women with SLE. Both groups were followed up for periods of up to one year after delivery. Eight patients elected abortion for nonmedical reasons. In all patient groups, there were no differences between pregnant and nonpregnant patient groups in frequency of any disease activity marker studied including therapy. However, new proteinuria occurred in four pregnant patients compared with one nonpregnant patient, and thrombocytopenia attributable to SLE occurred in five pregnant patients and one nonpregnant patient. Renal disease, when it occurred, more closely resembled pregnancy-induced hypertension than lupus nephritis. It is concluded that pregnancy complications are frequent, but the assertion that pregnancy causes exacerbation of SLE remains unproved.

View details for Web of Science ID A1984TQ95500029

View details for PubMedID 6496544
Outcomes in pregnancies complicated by IUGR before 32 weeks: does the degree of SGA matter? Minor, K., Bianco, K., Sie, L., Druzin, M. L., Lee, H. C., Leonard, S. A. MOSBY-ELSEVIER. 2021: S519
View details for Web of Science ID 000621547401378
Association between paternal health and severe maternal morbidity: analysis of US claims data Murugappan, G., Li, S., Leonard, S. A., Druzin, M. L., Eisenberg, M. L. MOSBY-ELSEVIER. 2021: S117?S118
View details for Web of Science ID 000621547400175
Management of brain tumors presenting in pregnancy: a case series and systematic review Management of brain tumors presenting in pregnancy: a case series and systematic review Rodrigues, A. 2021; 3 (1)
View details for DOI 10.1016/j.ajogmf.2020.100256
Proteomic signatures predict preeclampsia in individual cohorts but not across cohorts - implications for clinical biomarker studies. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians Ghaemi, M. S., Tarca, A. L., Romero, R. n., Stanley, N. n., Fallahzadeh, R. n., Tanada, A. n., Culos, A. n., Ando, K. n., Han, X. n., Blumenfeld, Y. J., Druzin, M. L., El-Sayed, Y. Y., Gibbs, R. S., Winn, V. D., Contrepois, K. n., Ling, X. B., Wong, R. J., Shaw, G. M., Stevenson, D. K., Gaudilliere, B. n., Aghaeepour, N. n., Angst, M. S. 2021: 1?8
Abstract

Early identification of pregnant women at risk for preeclampsia (PE) is important, as it will enable targeted interventions ahead of clinical manifestations. The quantitative analyses of plasma proteins feature prominently among molecular approaches used for risk prediction. However, derivation of protein signatures of sufficient predictive power has been challenging. The recent availability of platforms simultaneously assessing over 1000 plasma proteins offers broad examinations of the plasma proteome, which may enable the extraction of proteomic signatures with improved prognostic performance in prenatal care.The primary aim of this study was to examine the generalizability of proteomic signatures predictive of PE in two cohorts of pregnant women whose plasma proteome was interrogated with the same highly multiplexed platform. Establishing generalizability, or lack thereof, is critical to devise strategies facilitating the development of clinically useful predictive tests. A second aim was to examine the generalizability of protein signatures predictive of gestational age (GA) in uncomplicated pregnancies in the same cohorts to contrast physiological and pathological pregnancy outcomes.Serial blood samples were collected during the first, second, and third trimesters in 18 women who developed PE and 18 women with uncomplicated pregnancies (Stanford cohort). The second cohort (Detroit), used for comparative analysis, consisted of 76 women with PE and 90 women with uncomplicated pregnancies. Multivariate analyses were applied to infer predictive and cohort-specific proteomic models, which were then tested in the alternate cohort. Gene ontology (GO) analysis was performed to identify biological processes that were over-represented among top-ranked proteins associated with PE.The model derived in the Stanford cohort was highly significant (p?=?3.9E-15) and predictive (AUC = 0.96), but failed validation in the Detroit cohort (p?=?9.7E-01, AUC = 0.50). Similarly, the model derived in the Detroit cohort was highly significant (p?=?1.0E-21, AUC = 0.73), but failed validation in the Stanford cohort (p?=?7.3E-02, AUC = 0.60). By contrast, proteomic models predicting GA were readily validated across the Stanford (p?=?1.1E-454, R?=?0.92) and Detroit cohorts (p?=?1.1.E-92, R?=?0.92) indicating that the proteomic assay performed well enough to infer a generalizable model across studied cohorts, which makes it less likely that technical aspects of the assay, including batch effects, accounted for observed differences.Results point to a broader issue relevant for proteomic and other omic discovery studies in patient cohorts suffering from a clinical syndrome, such as PE, driven by heterogeneous pathophysiologies. While novel technologies including highly multiplex proteomic arrays and adapted computational algorithms allow for novel discoveries for a particular study cohort, they may not readily generalize across cohorts. A likely reason is that the prevalence of pathophysiologic processes leading up to the "same" clinical syndrome can be distributed differently in different and smaller-sized cohorts. Signatures derived in individual cohorts may simply capture different facets of the spectrum of pathophysiologic processes driving a syndrome. Our findings have important implications for the design of omic studies of a syndrome like PE. They highlight the need for performing such studies in diverse and well-phenotyped patient populations that are large enough to characterize subsets of patients with shared pathophysiologies to then derive subset-specific signatures of sufficient predictive power.

View details for DOI 10.1080/14767058.2021.1888915

View details for PubMedID 33653202
Towards personalized medicine in maternal and child health: integrating biologic and social determinants. Pediatric research Stevenson, D. K., Wong, R. J., Aghaeepour, N., Maric, I., Angst, M. S., Contrepois, K., Darmstadt, G. L., Druzin, M. L., Eisenberg, M. L., Gaudilliere, B., Gibbs, R. S., Gotlib, I. H., Gould, J. B., Lee, H. C., Ling, X. B., Mayo, J. A., Moufarrej, M. N., Quaintance, C. C., Quake, S. R., Relman, D. A., Sirota, M., Snyder, M. P., Sylvester, K. G., Hao, S., Wise, P. H., Shaw, G. M., Katz, M. 2020
View details for DOI 10.1038/s41390-020-0981-8

View details for PubMedID 32454518
Rate and causes of severe maternal morbidity at readmission: California births in 2008-2012. Journal of perinatology : official journal of the California Perinatal Association Girsen, A. I., Sie, L., Carmichael, S. L., Lee, H. C., Foeller, M. E., Druzin, M. L., Gibbs, R. S. 2019
Abstract

OBJECTIVE: To determine the rate, maternal characteristics, timing, and indicators of severe maternal morbidity (SMM) that occurs at postpartum readmission.STUDY DESIGN: Women with a birth in California during 2008-2012 were included in the analysis. Readmissions up to 42 days after delivery were investigated. SMM was defined as presence of any of the 21 indicators defined by ICD-9 codes.RESULTS: Among 2,413,943 women with a birth, SMM at readmission occurred in 4229 women. Of all SMM, 12.1% occurred at readmission. Over half (53.5%) of the readmissions with SMM occurred within the first week after delivery hospitalization. The most common indicators of SMM were blood transfusion, sepsis, and pulmonary edema/acute heart failure.CONCLUSION: Twelve percent of SMM was identified at readmission with the majority occurring within 1 week after discharge from delivery hospitalization. Because early readmission may reflect lack of discharge readiness, there may be opportunities to improve care.

View details for DOI 10.1038/s41372-019-0481-z

View details for PubMedID 31462721
Maternal Height and Risk of Preeclampsia among Race/Ethnic Groups AMERICAN JOURNAL OF PERINATOLOGY Maric, I., Mayo, J. A., Druzin, M. L., Wong, R. J., Winn, V. D., Stevenson, D. K., Shaw, G. M. 2019; 36 (8): 864?71
View details for DOI 10.1055/s-0038-1675205

View details for Web of Science ID 000474763600013
Fetal antiepileptic drug exposure and learning and memory functioning at 6 years of age: The NEAD prospective observational study EPILEPSY & BEHAVIOR Cohen, M. J., Meador, K. J., May, R., Loblein, H., Conrad, T., Baker, G. A., Bromley, R. L., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W., Labiner, D., Moon, J., Sherman, S., Cantrell, D., Silver, C., Goyal, M., Schoenberg, M. R., Pack, A., Palmese, C., Echo, J., Loring, D., Pennell, P., Drane, D., Moore, E., Denham, M., Epstein, C., Gess, J., Helmers, S., Henry, T., Motamedi, G., Flax, E., Bromfield, E., Boyer, K., Dworetzky, B., Cole, A., Halperin, L., Shavel-Jessop, S., Barkley, G., Moir, B., Harden, C., Tamny-Young, T., Lee, G., Cohen, M., Penovich, P., Minter, D., Moore, L., Murdock, K., Liporace, J., Wilcox, K., Nelson, M. N., Rosenfeld, W., Meyer, M., Mawer, G., Kini, U., Martin, R., Bellman, J., Ficker, D., Baade, L., Liow, K., Baker, G., Booth, A., Bromley, R., Barrie, C., Gummery, A., Shallcross, R., Ramsay, E., Arena, P., Kalayjian, L., Heck, C., Padilla, S., Miller, J., Rosenbaum, G., Wilensky, A., Constantino, T., Smith, J., Adab, N., Veling-Warnke, G., Sam, M., O'Donovan, C., Naylor, C., Nobles, S., Santos, C., Holmes, G. L., Druzin, M., Morrell, M., Nelson, L., Finnell, R., Yerby, M., Adeli, K., Wells, P., Blalock, T., Browning, N., Hendrickson, L., Jolles, B., Kunchai, M., Ogunsola, Y., Renehan, P., Winestone, J., Wolff, M., Zajdowicz, T., NEAD Study Grp 2019; 92: 154?64
View details for DOI 10.1016/j.yebeh.2018.12.031

View details for Web of Science ID 000461905800024
Differential Dynamics of the Maternal Immune System in Healthy Pregnancy and Preeclampsia. Frontiers in immunology Han, X. n., Ghaemi, M. S., Ando, K. n., Peterson, L. S., Ganio, E. A., Tsai, A. S., Gaudilliere, D. K., Stelzer, I. A., Einhaus, J. n., Bertrand, B. n., Stanley, N. n., Culos, A. n., Tanada, A. n., Hedou, J. n., Tsai, E. S., Fallahzadeh, R. n., Wong, R. J., Judy, A. E., Winn, V. D., Druzin, M. L., Blumenfeld, Y. J., Hlatky, M. A., Quaintance, C. C., Gibbs, R. S., Carvalho, B. n., Shaw, G. M., Stevenson, D. K., Angst, M. S., Aghaeepour, N. n., Gaudilliere, B. n. 2019; 10: 1305
Abstract

Preeclampsia is one of the most severe pregnancy complications and a leading cause of maternal death. However, early diagnosis of preeclampsia remains a clinical challenge. Alterations in the normal immune adaptations necessary for the maintenance of a healthy pregnancy are central features of preeclampsia. However, prior analyses primarily focused on the static assessment of select immune cell subsets have provided limited information for the prediction of preeclampsia. Here, we used a high-dimensional mass cytometry immunoassay to characterize the dynamic changes of over 370 immune cell features (including cell distribution and functional responses) in maternal blood during healthy and preeclamptic pregnancies. We found a set of eight cell-specific immune features that accurately identified patients well before the clinical diagnosis of preeclampsia (median area under the curve (AUC) 0.91, interquartile range [0.82-0.92]). Several features recapitulated previously known immune dysfunctions in preeclampsia, such as elevated pro-inflammatory innate immune responses early in pregnancy and impaired regulatory T (Treg) cell signaling. The analysis revealed additional novel immune responses that were strongly associated with, and preceded the onset of preeclampsia, notably abnormal STAT5ab signaling dynamics in CD4+T cell subsets (AUC 0.92, p = 8.0E-5). These results provide a global readout of the dynamics of the maternal immune system early in pregnancy and lay the groundwork for identifying clinically-relevant immune dysfunctions for the prediction and prevention of preeclampsia.

View details for DOI 10.3389/fimmu.2019.01305

View details for PubMedID 31263463

View details for PubMedCentralID PMC6584811
Fetal loss and malformations in the MONEAD study of pregnant women with epilepsy. Neurology Meador, K. J., Pennell, P. B., May, R. C., Van Marter, L. n., McElrath, T. F., Brown, C. n., Gerard, E. n., Kalayjian, L. n., Gedzelman, E. n., Penovich, P. n., Cavitt, J. n., French, J. n., Hwang, S. n., Pack, A. M., Sam, M. n., Birnbaum, A. K., Finnell, R. n. 2019
Abstract

To examine occurrence of severe adverse fetal outcomes (SAO), including fetal loss and major congenital malformations (MCMs), in pregnant women with epilepsy (PWWE) vs healthy pregnant women (HPW).The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is an NIH-funded, prospective, observational, multicenter investigation of pregnancy outcomes for both mother and child, which enrolled women December 2012 through January 2016.The 351 PWWE had 365 conceptions, and 105 HPW had 109 conceptions. SAOs occurred more often in PWWE (7.9%) vs HPW (1.9%) (p = 0.025) with odds ratio (OR) 4.45 (95% confidence intervals [CI] 1.04-19.01). There were no significant differences for fetal loss (2.8% vs 0%, p = 0.126) or MCMs (5.2% vs 1.9%, p = 0.185; OR 2.86, 95% CI 0.65-12.53) individually. No fetal losses in PWWE appeared to be related to acute seizures. Outcomes were not affected by periconceptional folate, unplanned/unwanted pregnancies, prior maternal pregnancy history, or antiepileptic drug (AED) blood levels, except for an AED level effect for fetal loss that appeared to be due to polytherapy. Combined maternal or paternal family history of MCM was marginally associated with increased SAOs (p = 0.046).The findings provide additional information on risks of SAOs in PWWE, assessing effects of both AED levels and periconceptional folate. Group differences in average enrollment gestational age could have affected fetal loss results. Analyses are limited by small sample sizes as the MONEAD study was not powered for these secondary outcomes. The large majority of pregnancies in women with epilepsy do not have SOAs.

View details for DOI 10.1212/WNL.0000000000008687

View details for PubMedID 31806691
Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy BIOINFORMATICS Ghaemi, M., DiGiulio, D. B., Contrepois, K., Callahan, B., Ngo, T. M., Lee-McMullen, B., Lehallier, B., Robaczewska, A., Mcilwain, D., Rosenberg-Hasson, Y., Wong, R. J., Quaintance, C., Culos, A., Stanley, N., Tanada, A., Tsai, A., Gaudilliere, D., Ganio, E., Han, X., Ando, K., McNeil, L., Tingle, M., Wise, P., Maric, I., Sirota, M., Wyss-Coray, T., Winn, V. D., Druzin, M. L., Gibbs, R., Darmstadt, G. L., Lewis, D. B., Nia, V., Agard, B., Tibshirani, R., Nolan, G., Snyder, M. P., Relman, D. A., Quake, S. R., Shaw, G. M., Stevenson, D. K., Angst, M. S., Gaudilliere, B., Aghaeepour, N. 2019; 35 (1): 95?103
View details for DOI 10.1093/bioinformatics/bty537

View details for Web of Science ID 000459313900012
Maternal Height and Risk of Preeclampsia. Maric, I., Mayo, J. A., Druzin, M. L., Wong, R. J., Winn, V. D., Stevenson, D. K., Shaw, G. M. SAGE PUBLICATIONS INC. 2018: 207A?208A
View details for Web of Science ID 000429928200458
An immune clock of human pregnancy SCIENCE IMMUNOLOGY Aghaeepour, N., Ganio, E. A., Mcilwain, D., Tsai, A. S., Tingle, M., Van Gassen, S., Gaudilliere, D. K., Baca, Q., McNeil, L., Okada, R., Ghaemi, M. S., Furman, D., Wong, R. J., Winn, V. D., Druzin, M. L., El-Sayed, Y. Y., Quaintance, C., Gibbs, R., Darmstadt, G. L., Shaw, G. M., Stevenson, D. K., Tibshirani, R., Nolan, G. P., Lewis, D. B., Angst, M. S., Gaudilliere, B. 2017; 2 (15)
View details for DOI 10.1126/sciimmunol.aan2946

View details for Web of Science ID 000434327200004
The use of vibro-acoustic stimulation during the abnormal/equivocal biophysical profile Obstet Gynecol Druzin ML, Inglis SR, Wagner WE, Kogut E.
Acute Fatty Liver of Pregnancy and Risk of Preterm Birth. Foeller, M. E., Mayo, J., Yeaton-Massey, A., Girsen, A., Do, S., Ness, A., Shaw, G., El-Sayed, Y., Druzin, M. SAGE PUBLICATIONS INC. 2017: 246A?247A
View details for Web of Science ID 000399043900621
Pregnancy Complicated by Gorham-Stout Disease and Refractory Chylothorax. AJP reports Hellyer, J., Oliver-Allen, H., Shafiq, M., Tolani, A., Druzin, M., Jeng, M., Rockson, S., Lowsky, R. 2016; 6 (4): e355-e358
Abstract

Introduction?Gorham-Stout Disease (GSD) is a rare disorder of bony destruction due to lymphangiomatosis, and is often triggered by hormones. One complication of GSD is the development of chylothorax, which carries a high mortality rate. Very little experience has been published to guide management in GSD during pregnancy to optimize both fetal and maternal health. Case Study?A 20-year-old woman with known GSD presented with shortness of breath at 18 weeks of pregnancy, due to bilateral chylothoraces which required daily drainage. To minimize chylous fluid formation, she was placed on bowel rest with total parenteral nutrition (limiting lipid intake) and received octreotide to decrease splanchnic blood flow and chylous fluid drainage. Treatment options were limited due to her pregnancy. Twice daily home chest tube drainage of a single lung cavity, total parenteral nutrition, octreotide, and albumin infusions allowed successful delivery of a healthy 37 weeks' gestation infant by cesarean delivery. Discussion?This case illustrates the management of a rare clinical disease of bone resorption and lymphangiomatosis complicated by bilateral, refractory chylothoraces, triggered by pregnancy, in whom treatment options are limited, and the need for a multidisciplinary health care team to ensure successful maternal and fetal outcomes.

View details for PubMedID 27708981
Erratum: Pregnancy Complicated by Gorham-Stout Disease and Refractory Chylothorax. AJP reports Hellyer, J., Oliver-Allen, H., Shafiq, M., Tolani, A., Druzin, M., Jeng, M., Rockson, S., Lowsky, R. 2016; 6 (4)
Abstract

[This corrects the article DOI: 10.1055/s-0036-1593443.].

View details for PubMedID 27822433
Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis. journal of maternal-fetal & neonatal medicine Girsen, A. I., Wallenstein, M. B., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Druzin, M. L., Oshiro, B. T., Blumenfeld, Y. J. 2016; 29 (15): 2500-2504
Abstract

To investigate the association between meconium staining and perinatal and neonatal outcomes in pregnancies with gastroschisis.Retrospective analysis of infants with prenatally diagnosed gastroschisis born in two academic medical centers between 2008 and 2013. Neonatal outcomes of deliveries with and without meconium staining were compared. Primary outcome was defined as any of the following: neonatal sepsis, prolonged mechanical ventilation, bowel atresia or death. Secondary outcomes were preterm delivery, preterm-premature rupture of membranes (PPROM) and prolonged hospital length of stay.One hundred and eight infants with gastroschisis were included of which 56 (52%) had meconium staining at delivery. Infants with meconium staining had a lower gestational age at delivery (36.3 (�1.4) versus 37.0 (�1.2) weeks, p?=?0.007), and a higher rate of PPROM (25% versus 8%, p?=?0.03) than infants without meconium. Meconium staining was not significantly associated with the primary composite outcome or with any of its components. After adjustments, meconium staining remained significantly associated with preterm delivery at?<36 weeks [odds ratio OR?=?4.0, 95% confidence intervals (CI): 1.5-11.4] and PPROM (OR?=?3.8, 95%CI: 1.2-14.5).Among infants with gastroschisis, meconium staining was associated with prematurity and PPROM. No significant increase in other adverse neonatal outcomes was seen among infants with meconium staining, suggesting a limited prognostic value of this finding.

View details for DOI 10.3109/14767058.2015.1090971

View details for PubMedID 26445130
Association between gestational duration in first pregnancies and birth timing in second pregnancies Yang, J., Baer, R. J., Berghella, V., Chambers, C., Chung, P., Coker, T., Currier, R. J., Druzin, M. L., Kuppermann, M., Muglia, L. J., Norton, M. E., Rand, L., Ryckman, K., Shaw, G. M., Stevenson, D., Wise, P., Jelliffe-Pawlowski, L. L. MOSBY-ELSEVIER. 2016: S442
View details for DOI 10.1016/j.ajog.2015.10.898

View details for Web of Science ID 000367092800837
Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Girsen, A. I., Wallenstein, M. B., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Druzin, M. L., Oshiro, B. T., Blumenfeld, Y. J. 2016; 29 (15): 2499-2503
View details for DOI 10.3109/14767058.2015.1090971

View details for Web of Science ID 000374775200021

View details for PubMedID 26445130
Maternal characteristics and mid-pregnancy serum biomarkers as risk factors for subtypes of preterm birth. BJOG : an international journal of obstetrics and gynaecology Jelliffe-Pawlowski, L. L., Baer, R. J., Blumenfeld, Y. J., Ryckman, K. K., O'Brodovich, H. M., Gould, J. B., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Stevenson, D. K., Shaw, G. M., Currier, R. J. 2015; 122 (11): 1484-1493
Abstract

To examine the relationship between maternal characteristics, serum biomarkers and preterm birth (PTB) by spontaneous and medically indicated subtypes.Population-based cohort.California, United States of America.From a total population of 1�004�039 live singleton births in 2009 and 2010, 841�665 pregnancies with linked birth certificate and hospital discharge records were included.Characteristics were compared for term and preterm deliveries by PTB subtype using logistic regression and odds ratios adjusted for maternal characteristics and obstetric factors present in final stepwise models and 95% confidence intervals. First-trimester and second-trimester serum marker levels were analysed in a subset of 125�202 pregnancies with available first-trimester and second-trimester serum biomarker results.PTB by subtype.In fully adjusted models, ten characteristics and three serum biomarkers were associated with increased risk in each PTB subtype (Black race/ethnicity, pre-existing hypertension with and without pre-eclampsia, gestational hypertension with pre-eclampsia, pre-existing diabetes, anaemia, previous PTB, one or two or more previous caesarean section(s), interpregnancy interval ?�60�months, low first-trimester pregnancy-associated plasma protein A, high second-trimester ?-fetoprotein, and high second-trimester dimeric inhibin A). These risks occurred in 51.6-86.2% of all pregnancies ending in PTB depending on subtype. The highest risk observed was for medically indicated PTB <32�weeks in women with pre-existing hypertension and pre-eclampsia (adjusted odds ratio 89.7, 95% CI 27.3-111.2).Our findings suggest a shared aetiology across PTB subtypes. These commonalities point to targets for further study and exploration of risk reduction strategies.Findings suggest a shared aetiology across preterm birth subtypes. Patterns may inform risk reduction efforts.

View details for DOI 10.1111/1471-0528.13495

View details for PubMedID 26111589
Early-Onset Severe Preeclampsia by First Trimester Pregnancy-Associated Plasma Protein A and Total Human Chorionic Gonadotropin AMERICAN JOURNAL OF PERINATOLOGY Jelliffe-Pawlowski, L. L., Baer, R. J., Currier, R. J., Lyell, D. J., Blumenfeld, Y. J., El-Sayed, Y. Y., Shaw, G. M., Druzin, M. L. 2015; 32 (7): 703-711
View details for DOI 10.1055/s-0034-1396697

View details for Web of Science ID 000355418600014

View details for PubMedID 25519199
Extravillous Trophoblasts at the Maternal-Fetal Interface Are the Primary Source of the Increased Production of sFlt1 in Preeclampsia Fan, X., Sung, J. F., Dhal, S., Druzin, M. L., Nayak, N. R. SAGE PUBLICATIONS INC. 2015: 199A
View details for Web of Science ID 000351407202049
Evaluation of a cumulative first trimester characteristic and serum marker risk score for predicting early spontaneous preterm birth Jelliffe-Pawlowski, L. L., Baer, R., Blumenfeld, Y., Chambers, C., Druzin, M., El-Sayed, Y., Kuppermann, M., Lyell, D., Norton, M., O'Brodovich, H., Ryckman, K., Shaw, G., Stevenson, D., Currier, R. MOSBY-ELSEVIER. 2015: S142
View details for DOI 10.1016/j.ajog.2014.10.305

View details for Web of Science ID 000361140900260
TDaP vaccination safety in pregnancy: a comparison of neonatal and obstetric outcomes among women receiving antepartum and postpartum vaccination Judy, A., Singh, A., Lee, H., Gaskari, S., Brodzinsky, L., Vik, J., Druzin, M., El-Sayed, Y., Aziz, N. MOSBY-ELSEVIER. 2015: S300?S301
View details for DOI 10.1016/j.ajog.2014.10.810

View details for Web of Science ID 000361140900599
Opportunities for maternal transport of pregnancies at risk for delivery of VLBW infants - results from the california maternal quality care collaborative Robles, D., Blumenfeld, Y., Lee, H., Gould, J., Main, E., Profit, J., Melsop, K., Druzin, M. MOSBY-ELSEVIER. 2015: S237
View details for DOI 10.1016/j.ajog.2014.10.510

View details for Web of Science ID 000361140900460
Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications JOURNAL OF CLINICAL INVESTIGATION Fan, X., Rai, A., Kambham, N., Sung, J. F., Singh, N., Petitt, M., Dhal, S., Agrawal, R., Sutton, R. E., Druzin, M. L., Gambhir, S. S., Ambati, B. K., Cross, J. C., Nayak, N. R. 2014; 124 (11): 4941-4952
Abstract

There is strong evidence that overproduction of soluble fms-like tyrosine kinase-1 (sFLT1) in the placenta is a major cause of vascular dysfunction in preeclampsia through sFLT1-dependent antagonism of VEGF. However, the cause of placental sFLT1 upregulation is not known. Here we demonstrated that in women with preeclampsia, sFLT1 is upregulated in placental trophoblasts, while VEGF is upregulated in adjacent maternal decidual cells. In response to VEGF, expression of sFlt1 mRNA, but not full-length Flt1 mRNA, increased in cultured murine trophoblast stem cells. We developed a method for transgene expression specifically in mouse endometrium and found that endometrial-specific VEGF overexpression induced placental sFLT1 production and elevated sFLT1 levels in maternal serum. This led to pregnancy losses, placental vascular defects, and preeclampsia-like symptoms, including hypertension, proteinuria, and glomerular endotheliosis in the mother. Knockdown of placental sFlt1 with a trophoblast-specific transgene caused placental vascular changes that were consistent with excess VEGF activity. Moreover, sFlt1 knockdown in VEGF-overexpressing animals enhanced symptoms produced by VEGF overexpression alone. These findings indicate that sFLT1 plays an essential role in maintaining vascular integrity in the placenta by sequestering excess maternal VEGF and suggest that a local increase in VEGF can trigger placental overexpression of sFLT1, potentially contributing to the development of preeclampsia and other pregnancy complications.

View details for DOI 10.1172/JCI76864

View details for Web of Science ID 000344203300029

View details for PubMedCentralID PMC4347223
Endometrial VEGF induces placental sFLT1 and leads to pregnancy complications. journal of clinical investigation Fan, X., Rai, A., Kambham, N., Sung, J. F., Singh, N., Petitt, M., Dhal, S., Agrawal, R., Sutton, R. E., Druzin, M. L., Gambhir, S. S., Ambati, B. K., Cross, J. C., Nayak, N. R. 2014; 124 (11): 4941-4952
Abstract

There is strong evidence that overproduction of soluble fms-like tyrosine kinase-1 (sFLT1) in the placenta is a major cause of vascular dysfunction in preeclampsia through sFLT1-dependent antagonism of VEGF. However, the cause of placental sFLT1 upregulation is not known. Here we demonstrated that in women with preeclampsia, sFLT1 is upregulated in placental trophoblasts, while VEGF is upregulated in adjacent maternal decidual cells. In response to VEGF, expression of sFlt1 mRNA, but not full-length Flt1 mRNA, increased in cultured murine trophoblast stem cells. We developed a method for transgene expression specifically in mouse endometrium and found that endometrial-specific VEGF overexpression induced placental sFLT1 production and elevated sFLT1 levels in maternal serum. This led to pregnancy losses, placental vascular defects, and preeclampsia-like symptoms, including hypertension, proteinuria, and glomerular endotheliosis in the mother. Knockdown of placental sFlt1 with a trophoblast-specific transgene caused placental vascular changes that were consistent with excess VEGF activity. Moreover, sFlt1 knockdown in VEGF-overexpressing animals enhanced symptoms produced by VEGF overexpression alone. These findings indicate that sFLT1 plays an essential role in maintaining vascular integrity in the placenta by sequestering excess maternal VEGF and suggest that a local increase in VEGF can trigger placental overexpression of sFLT1, potentially contributing to the development of preeclampsia and other pregnancy complications.

View details for DOI 10.1172/JCI76864

View details for PubMedID 25329693
Association between maternal characteristics, abnormal serum aneuploidy analytes, and placental abruption. American journal of obstetrics and gynecology Blumenfeld, Y. J., Baer, R. J., Druzin, M. L., El-Sayed, Y. Y., Lyell, D. J., Faucett, A. M., Shaw, G. M., Currier, R. J., Jelliffe-Pawlowski, L. L. 2014; 211 (2): 144 e1-9
View details for DOI 10.1016/j.ajog.2014.03.027

View details for PubMedID 24631707
Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years. JAMA pediatrics Meador, K. J., Baker, G. A., Browning, N., Cohen, M. J., Bromley, R. L., Clayton-Smith, J., Kalayjian, L. A., Kanner, A., Liporace, J. D., Pennell, P. B., Privitera, M., Loring, D. W. 2014; 168 (8): 729-736
Abstract

Breastfeeding is known to have beneficial effects, but concern exists that breastfeeding during maternal antiepileptic drug (AED) therapy may be harmful. We previously noted no adverse effects of breastfeeding associated with AED use on IQ at age 3 years, but IQ at age 6 years is more predictive of school performance and adult abilities.To examine the effects of AED exposure via breastfeeding on cognitive functions at age 6 years.Prospective observational multicenter study of long-term neurodevelopmental effects of AED use. Pregnant women with epilepsy receiving monotherapy (ie, carbamazepine, lamotrigine, phenytoin, or valproate) were enrolled from October 14, 1999, through April 14, 2004, in the United States and the United Kingdom. At age 6 years, 181 children were assessed for whom we had both breastfeeding and IQ data. All mothers in this analysis continued taking the drug after delivery.Differential Ability Scales IQ was the primary outcome. Secondary measures included measures of verbal, nonverbal, memory, and executive functions. For our primary analysis, we used a linear regression model with IQ at age 6 years as the dependent variable, comparing children who breastfed with those who did not. Similar secondary analyses were performed for the other cognitive measures.In total, 42.9% of children were breastfed a mean of 7.2 months. Breastfeeding rates and duration did not differ across drug groups. The IQ at age 6 years was related to drug group (P?
View details for DOI 10.1001/jamapediatrics.2014.118

View details for PubMedID 24934501

View details for PubMedCentralID PMC4122685
On-time scheduled cesarean delivery start time process-improvement initiative. Obstetrics and gynecology Blumenfeld, Y. J., Riley, E., Hilton, G., Lee, H. C., El-Sayed, Y. Y., Druzin, M. L. 2014; 123: 138S-9S
Abstract

Cesarean deliveries comprise approximately 30% of all births, many of which are scheduled. Given the labile nature of labor and delivery units, scheduled cesarean deliveries are often delayed. Our aim was to improve on-time scheduled cesarean delivery start times.A multidisciplinary team (obstetrician-gynecologist, nursing, anesthesia, and hospital administration) met to review scheduled cesarean delivery data, identify logistic barriers to on-time starts, and develop a plan to improve cesarean delivery start times. After identifying possible barriers to on-time starts, the following process was instituted: planned preoperative visit 1-2 days before scheduled cesarean delivery, mandatory submission of History & Physical and consent forms by the time of the preoperative visit, and initial preparation of the first scheduled patient for cesaren delivery by nighttime nursing before morning change of shift. The process launched on March 1, 2013. Data from scheduled cesarean deliveries 6 months before and 3 months after the initiative were reviewed and analyzed.Of 1,298 total cesarean deliveries, 423 were scheduled, defined as cesarean delivery scheduled at least 24 hours in advance (300 before and 123 after the initiative). Sixty-four of 300 scheduled cesarean deliveries (21.3%) were on time before compared with 67 of 123 (54.5%) after the initiative began (P<.001). Among delayed cases, there was no difference in the average delay time between those before and after the initiative (55.7 compared with 54.4 minutes P=.93); however, 50.7% of cases were either on time or delayed by 15 minutes or less before the initiative compared with 69.9% of cases after (P<.001).A multidisciplinary initiative significantly increased scheduled cesarean delivery on-time start times.

View details for DOI 10.1097/01.AOG.0000447113.07157.f3

View details for PubMedID 24770007
Urine culture results and adverse outcomes in women with pyelonephritis. Obstetrics and gynecology Berger, V. K., Yeaton-Massey, A., Kassis, J., Blumenfeld, Y. J., Lee, H. C., Druzin, M. 2014; 123: 138S-?
Abstract

A retrospective cohort study of patients with pyelonephritis in pregnancy and immediately postpartum was conducted. Participants delivered between 2005 and 2009 at a single university center (Lucile Packard Children's Hospital at Stanford) were reviewed. Pyelonephritis was defined by a temperature greater than 38.0�C, flank pain or costovertebral angle tenderness, and bacteruria or pyuria on urinalysis. All patients with pyelonephritis and urine culture results were included. Univariate analyses were performed with the ? test. Means were compared with the Student's t test.One hundred thirteen patients were admitted with pyelonephritis and had a urine culture performed. Of the entire cohort, 70% of patients were Hispanic, 53% were nulliparous, and most were diagnosed in the third trimester. A total of 94 patients (83%) had positive urine cultures. There were no differences in adverse outcomes (preterm birth, anemia, bacteremia, acute respiratory distress syndrome, and hospital stay) between those with positive and negative urine cultures. Among those with positive cultures, there was a statistically significant increase in preterm birth (less than 37 weeks of gestation) between those with resistant uropathogens and those with pan-sensitive pathogens (26.5% compared with 7.6%, P=.01) ().(Table is included in full-text article.): Among women with pyelonephritis, complications did not differ between those with positive and negative urine culture results. Women with resistant bacterial uropathogens are at increased risk for preterm birth compared with those with sensitive pathogens.

View details for DOI 10.1097/01.AOG.0000447112.69038.68

View details for PubMedID 24770006
Pregnancy Stage-Specific Placental VEGF Overexpression in Mice: Placental Vascular Abnormalities and Induction of Preeclampsia-Like Symptoms Fan, X., Dhal, S., Chisholm, K., Kambham, N., Druzin, M., Nayak, N. R. SAGE PUBLICATIONS INC. 2014: 306A
View details for Web of Science ID 000333813003029
Association between Eclampsia, Maternal Characteristics, and Abnormal Levels of First and Second Trimester Serum Biomarkers. Jelliffe-Pawlowski, L., Baer, R., Currier, R., Blumenfeld, Y., El-Sayed, Y., Lyell, D., Shaw, G., Druzin, M. SAGE PUBLICATIONS INC. 2014: 297A
View details for Web of Science ID 000333813002340
Uterine Rupture After Uterine Artery Embolization for Symptomatic Leiomyomas OBSTETRICS AND GYNECOLOGY Yeaton-Massey, A., Loring, M., Chetty, S., Druzin, M. 2014; 123 (2): 418-420
Abstract

There are few data regarding safety of pregnancy after uterine artery embolization. However, numerous women desire future fertility after this procedure. Uterine rupture without a history of cesarean delivery or uterine scarring is an exceedingly rare complication in pregnancy.We report a case of uterine rupture in a primigravid woman after uterine artery embolization. Her pregnancy was also complicated by placenta previa with placenta increta, resulting in a favorable neonatal outcome in an otherwise life-threatening situation for mother and fetus.Uterine artery embolization is a risk factor for abnormal placentation and uterine rupture in subsequent pregnancies.

View details for DOI 10.1097/AOG.0b013e3182a46df9

View details for Web of Science ID 000339069100002

View details for PubMedID 24413250
High Rate of Preterm Birth in Pregnancies Complicated by Rheumatoid Arthritis AMERICAN JOURNAL OF PERINATOLOGY Langen, E. S., Chakravarty, E. F., Liaquat, M., El-Sayed, Y. Y., Druzin, M. L. 2014; 31 (1): 9-13
Abstract

Objective?To describe the outcomes of pregnancies complicated by rheumatoid arthritis (RA) and to estimate potential associations between disease characteristics and pregnancy outcomes.Study Design?We reviewed all pregnancies complicated by RA delivered at our institution from June 2001 through June 2009. Fisher exact tests were used to calculate odds ratios. Univariable regression was performed using STATA 10.1 (StataCorp, College Station, TX). A p value of???0.05 was considered statistically significant.Results?Forty-six pregnancies in 40 women were reviewed. Sixty percent of pregnancies had evidence of disease flare and 28% delivered prior to 37 weeks. We did not identify associations between preterm birth and active disease at conception or during pregnancy. In univariate analysis, discontinuation of medication because of pregnancy was associated with a significantly earlier gestational age at delivery (362/7 versus 383/7 weeks, p?=?0.022).Conclusion?Women with RA may be at higher risk for preterm delivery.

View details for DOI 10.1055/s-0033-1333666

View details for Web of Science ID 000329362900002

View details for PubMedID 23359233
Placental accreta and first and second trimester maternal serum markers and characteristics Lyell, D., Faucett, A., Baer, R., Blumenfeld, Y., Druzin, M., El-Sayed, Y., Shaw, G., Currier, R., Jelliffee-Pawlowski, L. MOSBY-ELSEVIER. 2014: S62
View details for DOI 10.1016/j.ajog.2013.10.129

View details for Web of Science ID 000330322600099
Association between severe early onset preeclampsia (PE) and serum measures of first trimester pregnancy associated plasma protein A (PAPP-A) and human chorionic gonadotrophin (hCG) Jelliffe, L., Druzin, M., Baer, R., Lyell, D., El-Sayed, Y., Blumenfeld, Y., Faucett, A., Shaw, G., Currier, R. MOSBY-ELSEVIER. 2014: S143
View details for DOI 10.1016/j.ajog.2013.10.302

View details for Web of Science ID 000330322600270
Transient, Inducible, Placenta-Specific Gene Expression in Mice ENDOCRINOLOGY Fan, X., Petitt, M., Gamboa, M., Huang, M., Dhal, S., Druzin, M. L., Wu, J. C., Chen-Tsai, Y., Nayak, N. R. 2012; 153 (11): 5637-5644
Abstract

Molecular understanding of placental functions and pregnancy disorders is limited by the absence of methods for placenta-specific gene manipulation. Although persistent placenta-specific gene expression has been achieved by lentivirus-based gene delivery methods, developmentally and physiologically important placental genes have highly stage-specific functions, requiring controllable, transient expression systems for functional analysis. Here, we describe an inducible, placenta-specific gene expression system that enables high-level, transient transgene expression and monitoring of gene expression by live bioluminescence imaging in mouse placenta at different stages of pregnancy. We used the third generation tetracycline-responsive tranactivator protein Tet-On 3G, with 10- to 100-fold increased sensitivity to doxycycline (Dox) compared with previous versions, enabling unusually sensitive on-off control of gene expression in vivo. Transgenic mice expressing Tet-On 3G were created using a new integrase-based, site-specific approach, yielding high-level transgene expression driven by a ubiquitous promoter. Blastocysts from these mice were transduced with the Tet-On 3G-response element promoter-driving firefly luciferase using lentivirus-mediated placenta-specific gene delivery and transferred into wild-type pseudopregnant recipients for placenta-specific, Dox-inducible gene expression. Systemic Dox administration at various time points during pregnancy led to transient, placenta-specific firefly luciferase expression as early as d 5 of pregnancy in a Dox dose-dependent manner. This system enables, for the first time, reliable pregnancy stage-specific induction of gene expression in the placenta and live monitoring of gene expression during pregnancy. It will be widely applicable to studies of both placental development and pregnancy, and the site-specific Tet-On G3 mouse will be valuable for studies in a broad range of tissues.

View details for DOI 10.1210/en.2012-1556

View details for Web of Science ID 000310359300049

View details for PubMedID 23011919

View details for PubMedCentralID PMC3473213
Placental sFlt-1 Production Is Essential for Normal Pregnancy: Relevance to the Mechanisms of Preeclampsia. Nayak, N. R., Ambati, B. K., Dhal, S., Druzin, M. L., Gambhir, S. S., Fan, X. SAGE PUBLICATIONS INC. 2012: 86A
View details for Web of Science ID 000329543601046
Decreased Circulating Soluble Tie2 Levels in Preeclampsia May Result from Inhibition of Vascular Endothelial Growth Factor (VEGF) Signaling JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM Sung, J. F., Fan, X., Dhal, S., Dwyer, B. K., Jafari, A., El-Sayed, Y. Y., Druzin, M. L., Nayak, N. R. 2011; 96 (7): E1148-E1152
Abstract

Recent studies have found dysregulation in circulating levels of a number of angiogenic factors and their soluble receptors in preeclampsia. In this study, we examined the mechanism of production of soluble Tie2 (sTie2) and its potential connection to the failure of vascular remodeling in preeclamptic pregnancies.Serum samples were collected prospectively from 41 pregnant subjects at five different time points throughout pregnancy. Five of these subjects developed preeclampsia. For a second study, serum and placental samples were collected at delivery from preeclamptic and gestational age-matched controls. We examined serum sTie2 levels, and angiopoietin 1, angiopoietin 2, and Tie2 mRNA expression and localization in placental samples from the central basal plate area. We also examined the effects of vascular endothelial growth factor (VEGF) and a matrix metalloproteinase (MMP) inhibitor on proteolytic shedding of Tie2 in uterine microvascular endothelial cells.Serum sTie2 levels were significantly lower in preeclamptic subjects starting at 24-28 wk of gestation and continued to be lower through the time of delivery. In culture experiments, VEGF treatment significantly increased sTie2 levels in conditioned media, whereas the MMP inhibitor completely blocked this increase, suggesting that VEGF-induced Tie2 release is MMP dependent.Our data suggest, for the first time, an interaction between VEGF and Tie2 in uterine endothelial cells and a potential mechanism for the decrease in circulating sTie2 levels in preeclampsia, likely through inhibition of VEGF signaling. Further studies on VEGF-Tie2 interactions during pregnancy should provide new insights into the mechanisms underlying the failure of vascular remodeling in preeclampsia and other pregnancy complications.

View details for DOI 10.1210/jc.2011-0063

View details for Web of Science ID 000292454500015

View details for PubMedID 21525162

View details for PubMedCentralID PMC3135205
A Novel Method of Local Gene Delivery and Noninvasive Imaging of Transgene Expression in the Mouse Endometrium 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) Fan, X., Dhal, S., Wu, J. C., Kuo, C. J., Druzin, M. L., Nayak, N. R. SOC STUDY REPRODUCTION. 2011
View details for Web of Science ID 000310746200585
O1. Dramatic upregulation of HIF-1a in the endovascular and extravillous trophoblasts at the maternal-fetal interface in preeclamptic pregnancies. Pregnancy hypertension Hwang, J., Fan, X., Sung, J. F., Dhal, S., Nayak, N. R., Druzin, M. L. 2011; 1 (3-4): 257-?
View details for DOI 10.1016/j.preghy.2011.08.033

View details for PubMedID 26009063
Serum relaxin levels and kidney function in late pregnancy with or without preeclampsia CLINICAL NEPHROLOGY Lafayette, R. A., Hladunewich, M. A., Derby, G., Blouch, K., Druzin, M. L., Myers, B. D. 2011; 75 (3): 226-232
Abstract

Relaxin, a potent pregnancy-related hormone, has been proposed to be a major mediator of renal physiology in normal pregnancy. We wished to test relaxin levels in pregnancy and preeclampsia.We performed precise physiologic measurements of kidney function in 38 normal peripartum women and 58 women with preeclampsia. We measured serum relaxin levels prior to delivery and over the first 4 postpartum weeks utilizing a modern, validated ELISA. Results were compared to those of 18 normal women of childbearing age.Relaxin levels were substantially elevated in women prior to delivery (364 � 268 vs. 15 � 16 pg/ml) and fell rapidly over the first postpartum week reaching normal non pregnant levels by Week 2 (32 � 64 vs. 15 � 16 pg/ml). No differences were seen between relaxin levels in normal pregnancy as compared to preeclampsia (364 � 268 vs. 376 � 241 pg/ml) despite substantial and persistent abnormalities in GFR (149 � 33 vs. 89 � 25 ml/min), albuminuria (14 vs. 687 mg/g) and mean arterial pressure (80 � 8 vs. 111 � 18). Furthermore no correlation could be established between physiologic measures (GFR, MAP, RBF, RVR) and relaxin levels (p > 0.3), either in the overall population or any of the subgroups.Relaxin is indeed significantly elevated in the serum of women during late pregnancy and the early puerperium. However, serum relaxin does not appear to influence BP, renal vascular resistance, renal blood flow or GFR in late pregnancy or in women with preeclampsia.

View details for DOI 10.5414/CNP75226

View details for Web of Science ID 000288817800007

View details for PubMedID 21329633
Development and Characterization of a Novel Long-Term Human Endometrial Slice Culture System Fan, X., Ootani, A., Dhal, S., Vo, K. C., Giudice, L. C., Druzin, M. L., Kuo, C. J., Nayak, N. R. SAGE PUBLICATIONS INC. 2011: 225A?226A
View details for Web of Science ID 000291721701109
Decreased Circulating sTie2 Levels in Preeclampsia May Involve Inhibition of VEGF Signaling Sung, J. F., Fan, X., Dwyer, B. K., Dhal, S., El-Sayed, Y. Y., Druzin, M. L., Nayak, N. R. SAGE PUBLICATIONS INC. 2011: 79A?79A
View details for Web of Science ID 000291721700029
Noninvasive Monitoring of Placenta-Specific Transgene Expression by Bioluminescence Imaging PLOS ONE Fan, X., Ren, P., Dhal, S., Bejerano, G., Goodman, S. B., Druzin, M. L., Gambhir, S. S., Nayak, N. R. 2011; 6 (1)
Abstract

Placental dysfunction underlies numerous complications of pregnancy. A major obstacle to understanding the roles of potential mediators of placental pathology has been the absence of suitable methods for tissue-specific gene manipulation and sensitive assays for studying gene functions in the placentas of intact animals. We describe a sensitive and noninvasive method of repetitively tracking placenta-specific gene expression throughout pregnancy using lentivirus-mediated transduction of optical reporter genes in mouse blastocysts.Zona-free blastocysts were incubated with lentivirus expressing firefly luciferase (Fluc) and Tomato fluorescent fusion protein for trophectoderm-specific infection and transplanted into day 3 pseudopregnant recipients (GD3). Animals were examined for Fluc expression by live bioluminescence imaging (BLI) at different points during pregnancy, and the placentas were examined for tomato expression in different cell types on GD18. In another set of experiments, blastocysts with maximum photon fluxes in the range of 2.0E+4 to 6.0E+4 p/s/cm(2)/sr were transferred. Fluc expression was detectable in all surrogate dams by day 5 of pregnancy by live imaging, and the signal increased dramatically thereafter each day until GD12, reaching a peak at GD16 and maintaining that level through GD18. All of the placentas, but none of the fetuses, analyzed on GD18 by BLI showed different degrees of Fluc expression. However, only placentas of dams transferred with selected blastocysts showed uniform photon distribution with no significant variability of photon intensity among placentas of the same litter. Tomato expression in the placentas was limited to only trophoblast cell lineages.These results, for the first time, demonstrate the feasibility of selecting lentivirally-transduced blastocysts for uniform gene expression in all placentas of the same litter and early detection and quantitative analysis of gene expression throughout pregnancy by live BLI. This method may be useful for a wide range of applications involving trophoblast-specific gene manipulations in utero.

View details for DOI 10.1371/journal.pone.0016348

View details for PubMedID 21283713
Neonatal morbidity in pregnancies complicated by abnormal placentation Langen, E., El-Sayed, Y., Druzin, M., Park, M., Lee, H. MOSBY-ELSEVIER. 2011: S57
View details for Web of Science ID 000285927500108
Cost-effectiveness of external cephalic version for term breech presentation BMC PREGNANCY AND CHILDBIRTH Tan, J. M., Macario, A., Carvalho, B., Druzin, M. L., El-Sayed, Y. Y. 2010; 10
Abstract

External cephalic version (ECV) is recommended by the American College of Obstetricians and Gynecologists to convert a breech fetus to vertex position and reduce the need for cesarean delivery. The goal of this study was to determine the incremental cost-effectiveness ratio, from society's perspective, of ECV compared to scheduled cesarean for term breech presentation.A computer-based decision model (TreeAge Pro 2008, Tree Age Software, Inc.) was developed for a hypothetical base case parturient presenting with a term singleton breech fetus with no contraindications for vaginal delivery. The model incorporated actual hospital costs (e.g., $8,023 for cesarean and $5,581 for vaginal delivery), utilities to quantify health-related quality of life, and probabilities based on analysis of published literature of successful ECV trial, spontaneous reversion, mode of delivery, and need for unanticipated emergency cesarean delivery. The primary endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted year of life gained. A threshold of $50,000 per quality-adjusted life-years (QALY) was used to determine cost-effectiveness.The incremental cost-effectiveness of ECV, assuming a baseline 58% success rate, equaled $7,900/QALY. If the estimated probability of successful ECV is less than 32%, then ECV costs more to society and has poorer QALYs for the patient. However, as the probability of successful ECV was between 32% and 63%, ECV cost more than cesarean delivery but with greater associated QALY such that the cost-effectiveness ratio was less than $50,000/QALY. If the probability of successful ECV was greater than 63%, the computer modeling indicated that a trial of ECV is less costly and with better QALYs than a scheduled cesarean. The cost-effectiveness of a trial of ECV is most sensitive to its probability of success, and not to the probabilities of a cesarean after ECV, spontaneous reversion to breech, successful second ECV trial, or adverse outcome from emergency cesarean.From society's perspective, ECV trial is cost-effective when compared to a scheduled cesarean for breech presentation provided the probability of successful ECV is > 32%. Improved algorithms are needed to more precisely estimate the likelihood that a patient will have a successful ECV.

View details for DOI 10.1186/1471-2393-10-3

View details for Web of Science ID 000296428000001

View details for PubMedID 20092630

View details for PubMedCentralID PMC2826287
A Novel Method of Monitoring Placenta-Specific Transgene Expression Throughout Pregnancy by Noninvasive Bioluminescence Imaging 43rd Annual Meeting of the Society-for-the-Study-of-Reproduction Fan, X., Ren, P., Dhal, S., Goodman, S. B., Gambhir, S. S., Druzin, M. L., Nayak, N. R. SOC STUDY REPRODUCTION. 2010: 144?145
View details for Web of Science ID 000284381300406
Acupuncture for depression during pregnancy 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine Manber, R., Schnyer, R., Chambers, A., Lyell, D., Caughey, A., Carlyle, E., Druzin, M., Gress, J., Huang, M., Kalista, T., Okada, R., Allen, J. MOSBY-ELSEVIER. 2009: S19?S19
View details for Web of Science ID 000279559500035
Hepatocyte growth factor (HGF) is upregulated at the fetomaternal junction in preeclamptic placentas 30th Annual Clinical Meeting of the Society-for-Maternal-Fetal-Medicine Sung, J., Fan, X., Nguyen, T., Dhal, S., El-Sayed, Y., Druzin, M., Nayak, N. MOSBY-ELSEVIER. 2009: S269?S269
View details for Web of Science ID 000279559500740
Wnt7a Expression Is Limited to the Endometrial Luminal Epithelium: Potential Role in Postmenstrual Endometrial Repair. 57th Annual Meeting of the Pacific-Coast-Reproductive-Society Krieg, S. A., Fan, X., Dahl, S., Westphal, L. W., Druzin, M., Nayak, N. R. ELSEVIER SCIENCE INC. 2009: S5?S5
View details for Web of Science ID 000264143900004
RANDOMIZED CLINICAL TRIAL OF CERVICAL RIPENING AND LABOR INDUCTION USING ORAL MISOPROSTOL WITH OR WITHOUT INTRAVAGINAL ISOSORBIDE MONONITRATE 29th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Collingham, J., Fuh, K., Caughey, A., Pullen, K., Lyell, D., Druzin, M., Kogut, E., El-Sayed, Y. MOSBY-ELSEVIER. 2008: S53?S53
View details for DOI 10.1016/j.ajog.2008.09.172

View details for Web of Science ID 000262205700146
VEGF blockade inhibits angiogenesis and reepithelialization of endometrium FASEB JOURNAL Fan, X., Krieg, S., Kuo, C. J., Wiegand, S. J., Rabinovitch, M., Druzin, M. L., Brenner, R. M., Giudice, L. C., Nayak, N. R. 2008; 22 (10): 3571-3580
Abstract

Despite extensive literature on vascular endothelial growth factor (VEGF) expression and regulation by steroid hormones, the lack of clear understanding of the mechanisms of angiogenesis in the endometrium is a major limitation for use of antiangiogenic therapy targeting endometrial vessels. In the current work, we used the rhesus macaque as a primate model and the decidualized mouse uterus as a murine model to examine angiogenesis during endometrial breakdown and regeneration. We found that blockade of VEGF action with VEGF Trap, a potent VEGF blocker, completely inhibited neovascularization during endometrial regeneration in both models but had no marked effect on preexisting or newly formed vessels, suggesting that VEGF is essential for neoangiogenesis but not survival of mature vessels in this vascular bed. Blockade of VEGF also blocked reepithelialization in both the postmenstrual endometrium and the mouse uterus after decidual breakdown, evidence that VEGF has pleiotropic effects in the endometrium. In vitro studies with a scratch wound assay showed that the migration of luminal epithelial cells during repair involved signaling through VEGF receptor 2-neuropilin 1 (VEGFR2-NP1) receptors on endometrial stromal cells. The leading front of tissue growth during endometrial repair was strongly hypoxic, and this hypoxia was the local stimulus for VEGF expression and angiogenesis in this tissue. In summary, we provide novel experimental data indicating that VEGF is essential for endometrial neoangiogenesis during postmenstrual/postpartum repair.

View details for DOI 10.1096/fj.08-111401

View details for Web of Science ID 000259642600019

View details for PubMedID 18606863

View details for PubMedCentralID PMC2537439
Perinatal outcomes among Asian-white interracial couples 28th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Nystrom, M. J., Caughey, A. B., Lyell, D. J., Druzin, M. L., El-Sayed, Y. Y. MOSBY-ELSEVIER. 2008
Abstract

To investigate whether perinatal outcomes among interracial Asian-white couples are different than among Asian-Asian and white-white couples.This was a retrospective study of Asian, white, and Asian-white couples delivered at the Lucile Packard Children's Hospital from 2000-2005. Asian-white couples were subdivided into white-mother/Asian-father or Asian-mother/white-father. Perinatal outcomes included gestational diabetes, hypertensive disorders of pregnancy, preterm delivery, birth weight >4000 g and <2500 g, and cesarean delivery.In the study population of 868 Asian-white, 3226 Asian, and 5575 white couples there were significant outcome differences. Compared with white couples, Asian-white couples had an increased incidence of gestational diabetes (aOR 2.4 for white-mother/Asian-father and aOR 2.6 for Asian-mother/white-father), though not as high as Asian couples (aOR 4.7). Asian-white couples had larger babies (median 3360 g for Asian-mother/white-father and 3320 g for white-mother/Asian-father vs 3210 g for Asian, P < .001), but only Asian-mother/white-father couples had an increased rate of cesarean delivery (aOR 1.3-2.0).Significant differences in perinatal outcomes exist between Asian, white, and interracial Asian-white couples.

View details for DOI 10.1016/j.ajog.2008.06.065

View details for Web of Science ID 000260045700021

View details for PubMedID 18928981
Perinatal outcomes among Asian, Caucasian, and Asian-Caucasian interracial couples Nystrom, M., Caughey, A., Lyell, D., Druzin, M., El-Sayed, Y. MOSBY-ELSEVIER. 2007: S193
View details for DOI 10.1016/j.ajog.2007.10.702

View details for Web of Science ID 000251708500666
Bacterial flora-typing with targeted, chip-based Pyrosequencing BMC MICROBIOLOGY Sundquist, A., Bigdeli, S., Jalili, R., Druzin, M. L., Waller, S., Pullen, K. M., El-Sayed, Y. Y., Taslimi, M. M., Batzoglou, S., Ronaghi, M. 2007; 7
Abstract

The metagenomic analysis of microbial communities holds the potential to improve our understanding of the role of microbes in clinical conditions. Recent, dramatic improvements in DNA sequencing throughput and cost will enable such analyses on individuals. However, such advances in throughput generally come at the cost of shorter read-lengths, limiting the discriminatory power of each read. In particular, classifying the microbial content of samples by sequencing the < 1,600 bp 16S rRNA gene will be affected by such limitations.We describe a method for identifying the phylogenetic content of bacterial samples using high-throughput Pyrosequencing targeted at the 16S rRNA gene. Our analysis is adapted to the shorter read-lengths of such technology and uses a database of 16S rDNA to determine the most specific phylogenetic classification for reads, resulting in a weighted phylogenetic tree characterizing the content of the sample. We present results for six samples obtained from the human vagina during pregnancy that corroborates previous studies using conventional techniques.Next, we analyze the power of our method to classify reads at each level of the phylogeny using simulation experiments. We assess the impacts of read-length and database completeness on our method, and predict how we do as technology improves and more bacteria are sequenced. Finally, we study the utility of targeting specific 16S variable regions and show that such an approach considerably improves results for certain types of microbial samples. Using simulation, our method can be used to determine the most informative variable region.This study provides positive validation of the effectiveness of targeting 16S metagenomes using short-read sequencing technology. Our methodology allows us to infer the most specific assignment of the sequence reads within the phylogeny, and to identify the most discriminative variable region to target. The analysis of high-throughput Pyrosequencing on human flora samples will accelerate the study of the relationship between the microbial world and ourselves.

View details for DOI 10.1186/1471-2180-7-108

View details for Web of Science ID 000253968300001

View details for PubMedID 18047683

View details for PubMedCentralID PMC2244631
Perinatal outcomes after successful and failed trials of labor after cesarean delivery 73rd Annual Meeting of the Pacific-Coast-Obstetrical-and-Gynecological-Society El-Sayed, Y. Y., Watkins, M. M., Fix, M., Druzin, M. L., Pullen, K. M., Caughey, A. B. MOSBY-ELSEVIER. 2007: 583?85
Abstract

To compare maternal and neonatal outcomes after successful and failed trials of labor after cesarean in women at term, excluding uterine ruptures, and to examine predictors of successful and failed trials of labor.Matched maternal and neonatal data from 1993-1999 in women with singleton term pregnancies with prior cesarean undergoing trial of labor were reviewed. Women with uterine rupture were excluded. Maternal and neonatal outcomes were analyzed for successful and failed trials. Predictors of success and failure were examined.1284 women and their neonates were available for analysis. 1094 (85.2%) had a vaginal birth and 190 (14.8%) underwent repeat cesarean. Failed trials of labor were associated with higher incidence of choriamnionitis (25.8% vs. 5.5%, P<.001), postpartum hemorrhage (35.8% vs. 15.8%, P<.001), hysterectomy (1% vs. 0%, P=.022), neonatal jaundice (17.4% vs.10.2%, P=.004) and composite major neonatal morbidities (6.3% vs. 2.8%, P=.014).Failed trial of labor in women at term with prior cesarean is associated with increased maternal and neonatal morbidities.

View details for DOI 10.1016/j.ajog.2007.03.013

View details for Web of Science ID 000247137600035
Use of a community mobile health van to increase early access to prenatal care MATERNAL AND CHILD HEALTH JOURNAL Edgerley, L. P., El-Sayed, Y. Y., Druzin, M. L., Kiernan, M., Daniels, K. I. 2007; 11 (3): 235-239
Abstract

To examine whether the use of a community mobile health van (the Lucile Packard Childrens Hospital Women's Health Van) in an underserved population allows for earlier access to prenatal care and increased rate of adequate prenatal care, as compared to prenatal care initiated in community clinics.We studied 108 patients who initiated prenatal care on the van and delivered their babies at our University Hospital from September 1999 to July 2004. One hundred and twenty-seven patients who initiated prenatal care in sites other than the Women's Health Van, had the same city of residence and source of payment as the study group, and also delivered their babies at our hospital during the same time period, were selected as the comparison group. Gestational age at which prenatal care was initiated and the adequacy of prenatal care - as defined by Revised Graduated Index of Prenatal Care Utilization (RGINDEX) - were compared between cases and comparisons.Underserved women utilizing the van services for prenatal care initiated care three weeks earlier than women using other services (10.2 +/- 6.9 weeks vs. 13.2 +/- 6.9 weeks, P = 0.001). In addition, the data showed that van patients and non-van patients were equally likely to receive adequate prenatal care as defined by R-GINDEX (P = 0.125).Women who initiated prenatal care on the Women's Health Van achieved earlier access to prenatal care when compared to women initiating care at other community health clinics.

View details for DOI 10.1007/s10995-006-0174-z

View details for Web of Science ID 000246578900005

View details for PubMedID 17243022
Maximized learning in limited time: Using health failure modes effects analysis (HFMEA) in simulated obstetric crisis drills poor communication is the highest ranking team deficiency 39th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology Lipman, S., Daniels, K., Valdez, B., Lopez, D., Druzin, M. LIPPINCOTT WILLIAMS & WILKINS. 2007: B13?B13
View details for Web of Science ID 000246032500049
Terbutaline versus nitroglycerin for acute intrapartum fetal resuscitation Pullen, K., Taylor, L., Waller, S., Langen, E., Druzin, M., Riley, E., Caughey, A., El-Sayed, Y. MOSBY-ELSEVIER. 2006: S30
View details for DOI 10.1016/j.ajog.2006.10.077

View details for Web of Science ID 000242834500067
Postural equilibrium during pregnancy: Decreased stability with an increased reliance on visual cues 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Butler, E. E., Colon, I., Druzin, M. L., Rose, J. MOSBY-ELSEVIER. 2006: 1104?8
Abstract

The purpose of this study was to determine whether there are changes in postural equilibrium during pregnancy and to examine whether the incidence of falls increases during pregnancy.Static postural balance measures were collected from 12 pregnant women at 11 to 14, 19 to 22, and 36 to 39 weeks gestation and at 6 to 8 weeks after delivery and from 12 nulligravid control subjects who were matched for age, height, weight, and body mass index. Subjects were asked to stand quietly on a stable force platform for 30 seconds with eyes open and closed. Path length and average radial displacement were computed on the basis of the average of 3 trials for each condition. The women were asked at each session if they had sustained a fall in the previous 3 months.Postural stability remained relatively stable during the first trimester; however, second and third trimester and postpartum values for path length and average radial displacement with eyes open and closed were increased significantly compared with the control subjects, which indicates diminished postural balance. The difference between the eyes open and closed values of path length increased as pregnancy progressed. Although 25% of pregnant women sustained falls, none of the control subjects had fallen in the past year.These data suggest that postural stability declines during pregnancy and remains diminished at 6 to 8 weeks after delivery. The study also indicates that there is an increased reliance on visual cues to maintain balance during pregnancy.

View details for DOI 10.1016/j.ajog.2006.06.015

View details for Web of Science ID 000241123500034

View details for PubMedID 16846574
Gene expression patterns in human placenta PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Sood, R., Zehnder, J. L., Druzin, M. L., Brown, P. O. 2006; 103 (14): 5478-5483
Abstract

The placenta is the principal metabolic, respiratory, excretory, and endocrine organ for the first 9 months of fetal life. Its role in fetal and maternal physiology is remarkably diverse. Because of the central role that the placenta has in fetal and maternal physiology and development, the possibility that variation in placental gene expression patterns might be linked to important abnormalities in maternal or fetal health, or even variations in later life, warrants investigation. As an initial step, we used DNA microarrays to analyze gene expression patterns in 72 samples of amnion, chorion, umbilical cord, and sections of villus parenchyma from 19 human placentas from successful full-term pregnancies. The umbilical cord, chorion, amnion, and villus parenchyma samples were readily distinguished by differences in their global gene-expression patterns, many of which seemed to be related to physiology and histology. Differentially expressed genes have roles that include placental trophoblast secretion, signal transduction, metabolism, immune regulation, cell adhesion, and structure. We found interindividual differences in expression patterns in villus parenchyma and systematic differences between the maternal, fetal, and intermediate layers. A group of genes that was expressed in both the maternal and fetal villus parenchyma sections of placenta included genes that may be associated with preeclampsia. We identified sets of genes whose expression in placenta was significantly correlated with the sex of the fetus. This study provides a rich and diverse picture of the molecular variation in the placenta from healthy pregnancies.

View details for DOI 10.1073/pnas.0508035103

View details for Web of Science ID 000236636400044

View details for PubMedID 16567644

View details for PubMedCentralID PMC1414632
Effect of L-arginine therapy on the glomerular injury of preeclampsia - A randomized controlled trial OBSTETRICS AND GYNECOLOGY Mladunewich, M. A., Derby, G. C., Lafayette, R. A., Blouch, K. L., Druzin, M. L., Myers, B. D. 2006; 107 (4): 886-895
View details for Web of Science ID 000241296200022
Changes in postural equilibrium during pregnancy 26th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Butler, E., Colon, I., Druzin, M., Rose, J. MOSBY-ELSEVIER. 2005: S168?S168
View details for Web of Science ID 000233947800585
Comparison of rapid intrapartum screening methods for group B streptococcal vaginal colonization JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Aziz, N., Baron, E. J., D'Souza, H., Nourbakhsh, M., Druzin, M. L., Benitz, W. E. 2005; 18 (4): 225-229
Abstract

To compare optical immunoassay (OIA) and rapid polymerase-chain reaction (PCR) with enrichment broth culture for intrapartum detection of vaginal group B streptococcal (GBS) colonization.Paired vaginal swabs from 315 consecutive term pregnant women at the time of presentation for delivery to a university medical center were tested for GBS by OIA, PCR, and culture. Sensitivity, specificity, and positive and negative predictive values were calculated.Vaginal colonization was identified by culture in 56 subjects (17.8%). The sensitivity of OIA (7.1%, 95% confidence interval 5.1-9.5%) was significantly less than that of unenhanced rapid PCR (62.5%, 95% CI 48.5-74.8%).Neither PCR nor OIA is sufficiently sensitive for intrapartum detection of vaginal GBS colonization. Rapid PCR is more sensitive, but further improvements in technique to increase sensitivity will be necessary if PCR is to have a useful role in the management of women at time of presentation for delivery.

View details for DOI 10.1080/14767050500278048

View details for Web of Science ID 000234009900003

View details for PubMedID 16318971
Detection of sonographic markers of fetal aneuploidy depends on maternal and fetal characteristics 10th Congress of the World-Federation-for-Ultrasound-in-Medicine-and-Biology Taslimi, M. M., Acosta, R., Chueh, J., Hudgins, L., Hunter, K., Druzin, M. L., Chitkara, U. AMER INST ULTRASOUND MEDICINE. 2005: 811?15
Abstract

The purpose of this study was to determine factors that influence the detection rate of sonographic markers of fetal aneuploidy (SMFA).We reviewed the sonographic images of 160 consecutive second-trimester trisomic fetuses for the presence of SMFA, either structural anomalies or sonographic soft markers.One hundred forty-nine (93.1%) records were complete and analyzed; 78 cases (52.3%) were identified with 1 or more SMFA. Sonographic markers of fetal aneuploidy were detected in 42.7%, 75.0%, and 90.9% of trisomies 21, 18, and 13, respectively (P<.005). The detection rate of SMFA had a positive linear correlation with gestational age (adjusted R(2)=0.64; P<.002). Sonographic markers of fetal aneuploidy were detected in 43.7% of fetuses of less than 18.0 weeks' gestation and 64.5% of fetuses of 18.0 weeks' gestation or greater (likelihood ratio=6.4; P<.01). Sonographic markers of fetal aneuploidy were detected in 23.5% of patients with suboptimal image quality versus 58.3% of the others (likelihood ratio=7.5; P<.05). The rate of structural malformation was similar between the male and female fetuses, whereas that of soft markers was 49.4% in male and 30.0% in female fetuses (odds ratio=2.3; range, 1.2-4.5; P<.02). Factor analysis showed that some soft markers and some structural anomalies tended to appear together.The type of fetal trisomy, gestational age, sex, and quality of images influence the detection rate of SMFA. The highest detection rate for SMFA in the second trimester is at or above 18 weeks' gestational age. Certain markers are detected in clusters. These findings may explain, in part, the variability in reported rates of detection of SMFA among trisomic fetuses. These findings need to be prospectively tested in the general population of pregnancies for applicability to sonographic risk calculations for fetal trisomies.

View details for Web of Science ID 000229461900009

View details for PubMedID 15914685
Prospective randomized clinical trial of inpatient cervical ripening with stepwise oral misoprostol vs vaginal misoprostot 25th Annual Meeting of the Society-for-Maternal-Fetal-Medicine Colon, I., Clawson, K., Hunter, K., Druzin, M. L., Taslimi, M. M. MOSBY-ELSEVIER. 2005: 747?52
Abstract

The purpose of this study was to compare the efficacy and safety of stepwise oral misoprostol vs vaginal misoprostol for cervical ripening before induction of labor.Two hundred and four women between 32 to 42 weeks of gestation with an unfavorable cervix (Bishop score < or = 6) and an indication for labor induction were randomized to receive oral or vaginal misoprostol every 4 hours up to 4 doses. The oral misoprostol group received 50 microg initially followed by 100 microg in each subsequent dose. The vaginal group received 25 microg in each dose. The primary outcome was the interval from first misoprostol dose to delivery. Patient satisfaction and side effects were assessed by surveys completed after delivery.Ninety-three (45.6%) women received oral misoprostol; 111 (54.4%) received vaginal misoprostol. There was no difference in the average interval from the first dose of misoprostol to delivery in the oral (21.1 + 7.9 hrs) and vaginal (21.5 + 11.0 hrs, P = NS) misoprostol groups. The incidence of hyperstimulation in the oral group was 2.2% vs 5.4% in the vaginal group, P = NS. Eighteen patients in the oral group (19.4%) and 36 (32.4%) in the vaginal group underwent cesarean section (P < .05). This difference was attributed to better tolerance of more doses of misoprostol by the women in the oral group. There was no difference in side effects (nausea, vomiting, diarrhea, shivering) between groups. Fourteen percent of women in the vaginal group versus 7.5% in the oral group were dissatisfied with the use of misoprostol (P = NS).Stepwise oral misoprostol (50 microg followed by 100 microg) appears to be as effective as vaginal misoprostol (25 microg) for cervical ripening with a low incidence of hyperstimulation, no increase in side effects, a high rate of patient satisfaction, and is associated with a lower cesarean section rate.

View details for DOI 10.1016/j.ajog.2004.12.051

View details for Web of Science ID 000227477600014

View details for PubMedID 15746667
Comparison of optical immunoassay and polymerase-chain reaction for Group B streptococcal rapid intrapartum screening Aziz, N., D'Souza, H., Nourbakhsh, M., Baron, E. J., Druzin, M. L., Benitz, W. E. MOSBY, INC. 2004: S59
View details for DOI 10.1016/j.ajog.2004.10.088

View details for Web of Science ID 000225925500185
End-tidal breath carbon monoxide measurements are lower in pregnant women with uterine contractions. Journal of perinatology Hendler, I., Baum, M., Kreiser, D., Schiff, E., Druzin, M., Stevenson, D. K., Seidman, D. S. 2004; 24 (5): 275-278
Abstract

To compare the levels of end-tidal carbon monoxide (ETCOc) among women with and without uterine contractions in term and preterm pregnancies.In all, 55 nonsmoking healthy pregnant women were enrolled. ETCOc levels were compared among women with contractions (10 preterm and 13 term) and 32 women without contractions (34-41 weeks gestation).Maternal age, gravidity and parity were similar among study and control groups. ETCOc levels were significantly lower among women that had uterine contractions (0.99+/-0.38 parts per million (ppm) and 1.15+/-0.34 p.p.m. respectively), compared to women with no contractions (1.70+/-0.52 p.p.m., P<0.002). However, there was no significant difference in the ETCOc levels between women with preterm or term contractions (P=0.48).Low levels of ETCOc are associated with preterm and term uterine contractions.

View details for PubMedID 15042112
End tidal carbon monoxide levels are lower in women with gestational hypertension and pre-eclampsia. Journal of perinatology Kreiser, D., Baum, M., Seidman, D. S., Fanaroff, A., Shah, D., Hendler, I., Stevenson, D. K., Schiff, E., Druzin, M. L. 2004; 24 (4): 213-217
Abstract

The possible role of heme oxygenase and its byproduct carbon monoxide (CO) in the regulation of blood pressure is under investigation. The aim of this study was to compare end tidal breath CO (ETCO) levels in women with gestational hypertension (GH) or pre-eclampsia to the levels in healthy pregnant and nonpregnant women.We prospectively performed ETCO measurements corrected for ambient CO (ETCOc) in two medical centers (Stanford, CA and Cleveland, OH). A Natus CO-Stat End Tidal Breath Analyzer (Natus Medical Inc., San Carlos, CA) was used. The study group included a convenience sample of 31 women with GH/pre-eclampsia (PE). Control groups included 46 nonpregnant healthy women, 44 first-trimester and 48 third-trimester pregnant healthy women.Mean+/-SD ETCOc measurements were significantly lower in the GH/PE group compared to first-trimester (p=0.004) and third-trimester (p=0.001) normotensive pregnant and nonpregnant women (p=0.002) (1.36+/-0.30 vs 1.76+/-0.47, 1.72+/-0.42 and 1.78+/-0.54 ppm, respectively). The ETCOc values were < or =1.6 ppm in 89% of GH/PE women compared with, respectively, only 45, 54, and 46% of nonpregnant, first- and third-trimester normotensive pregnant women (p<0.05). ETCO measurements were not influenced by maternal age, parity, ethnicity, body mass index, gestational age or presence of household smokers. In the two centers, the controls had a similar mean ETCOc and the differences found remained significant when results for each center were analyzed separately.ETCOc levels were found to be significantly lower in women with GH/PE. Further investigation is required to determine if the lower CO levels reflect a deficient compensatory response to the increase in blood pressure or whether these are primary changes of significance to our understanding of the pathogenesis of GH/PE.

View details for PubMedID 15014533
The dynamics of glomerular filtration in the puerperium AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Hladunewich, M. A., Lafayette, R. A., Derby, G. C., Blouch, K. L., Bialek, J. W., Druzin, M. L., Deen, W. M., Myers, B. D. 2004; 286 (3): F496-F503
Abstract

We evaluated the glomerular filtration rate (GFR) during the second postpartum week in 22 healthy women who had completed an uncomplicated pregnancy. We used physiological techniques to measure GFR, renal plasma flow, and oncotic pressure and computed a value for the two-kidney ultrafiltration coefficient (K(f)). We compared these findings with those in pregnant women previously studied on the first postpartum day as well as nongravid women of reproductive age. Healthy female transplant donors of reproductive age permitted the morphometric analysis of glomeruli and computation of the single-nephron K(f). The aforementioned physiological and morphometric measurements were utilized to estimate transcapillary hydraulic pressure (Delta P) from a mathematical model of glomerular ultrafiltration. We conclude that postpartum day 1 is associated with marked glomerular hyperfiltration (+41%). A theoretical analysis of GFR determinants suggests that depression of glomerular capillary oncotic pressure, the force opposing the formation of filtrate, is the predominant determinant of early elevation of postpartum GFR. A reversal of the gestational hypervolemia and hemodilution, still evident on postpartum day 1, eventuates by postpartum week 2. An elevation of oncotic pressure in the plasma that flows axially along the glomerular capillaries to supernormal levels ensues; however, GFR remains modestly elevated (+20%) above nongravid levels. An analysis of filtration dynamics at this time suggests that a significant increase in Delta P by up to 16%, an approximately 50% increase in K(f), or a combination of smaller increments in both must be invoked to account for the persistent hyperfiltration.

View details for DOI 10.1152/ajprenal.00194.2003

View details for Web of Science ID 000188707500009

View details for PubMedID 14612381
Neonatal chest wall rigidity following the use of remifentanil for cesarean delivery in a patient with autoimmune hepatitis and thrombocytopenia INTERNATIONAL JOURNAL OF OBSTETRIC ANESTHESIA Carvalho, B., Mirikitani, E. J., Lyell, D., Evans, D. A., Druzin, A., Riley, E. T. 2004; 13 (1): 53-56
Abstract

Remifentanil is a useful adjunct in general anesthesia for high-risk obstetric patients. It provides effective blunting of the rapid hemodynamic changes that may be associated with airway manipulation and surgical stimulation. There have been no previous reports of opioid-related rigidity in the neonate delivered by a parturient receiving intraoperative remifentanil. We present a case of short-lived neonatal rigidity and respiratory depression following remifentanil administration during cesarean section to a parturient with autoimmune hepatitis complicated by cirrhosis, esophageal varices and thrombocytopenia.

View details for DOI 10.1016/j.ijoa.2003.09.001

View details for Web of Science ID 000188228500013

View details for PubMedID 15321443
Prevalence of maternal and fetal thrombophilias in complicated pregnancies Lenzi, T., Kreiser, D., Zendar, J., Ionel, O., Lay, M., Munro, E., Druzin, M. MOSBY, INC. 2003: S86
View details for DOI 10.1016/j.ajog.2003.10.074

View details for Web of Science ID 000187910500077
Quantitative transcript profiling and the identification of a novel vascular endothelial cell marker, placental endothelial protein-1, by serial analysis of gene expression. 45th Annual Meeting and Exhibition of the American-Society-of-Hematology Chuang, Y. J., Seo, K., Gray, J., Druzin, M., Kuo, C., Leung, L. AMER SOC HEMATOLOGY. 2003: 10A?11A
View details for Web of Science ID 000186536700025
Fetal ear length measurement: a useful predictor of aneuploidy? ULTRASOUND IN OBSTETRICS & GYNECOLOGY Chitkara, U., Lee, L., Oehlert, J. W., Bloch, D. A., Holbrook, R. H., El-Sayed, Y. Y., Druzin, M. L. 2002; 19 (2): 131-135
Abstract

To determine the usefulness of short ear length (EL) measurement in the prenatal detection of fetuses with chromosomal abnormalities.Fetal EL measurements, routine biometry and complete anatomic survey for fetal abnormalities were prospectively performed by antenatal sonography.One thousand eight hundred and forty-eight patients with singleton pregnancies undergoing genetic amniocentesis in the second or third trimester.Complete data for EL, biometry and anatomic survey for major structural abnormalities and minor sonographic markers of chromosomal abnormality were available in 1311 fetuses. Of these, 48 (3.7%) had an abnormal karyotype and 1263 (96.3%) had a normal karyotype. Using an EL measurement of < or = 10th percentile for corresponding gestational age in normal fetuses as abnormal cut-off values, detection rates for chromosomal abnormalities by short EL were determined.Among the 48 abnormal karyotypes, 34 were considered significant, and 11 of these 34 (32.4%) fetuses had short EL. In 14 cases, the karyotypic abnormality was considered non-significant and fetal EL was normal in all cases. Of the 34 fetuses with significant chromosomal abnormalities, six (17.6%) on antenatal sonography had no detectable abnormal findings, other than short EL. An increased biparietal diameter (BPD)/EL ratio of > or = 4.0 was also noted in fetuses with an abnormal karyotype, but the sensitivity and predictive value of increased BPD/EL ratio alone or increased BPD/EL ratio in combination with short EL was no better than the sensitivity and predictive value of short EL alone. A combination of short EL and abnormal ultrasound, however, gave a much higher positive predictive value (46%) for significant chromosomal abnormalities.Our findings suggest that in women at high risk for fetal chromosomal abnormality, a short fetal EL measurement on prenatal ultrasound, either alone or in combination with other sonographically detectable structural abnormalities, may be a useful parameter in predicting fetal aneuploidy.

View details for Web of Science ID 000174123500004

View details for PubMedID 11876803
Mask induction with sevoflurane in a parturient with severe tracheal stenosis ANESTHESIOLOGY Ratner, E. F., Cohen, S. E., El Sayed, Y., Druzin, M. 2001; 95 (2): 553-555
View details for Web of Science ID 000170237800040

View details for PubMedID 11506134
Is a trial of labor in a patient who has had a previous cesarean delivery cost-effective? Chung, A. J., Macario, A., El-Sayed, Y. Y., Riley, E. T., Druzin, M. L. LIPPINCOTT WILLIAMS & WILKINS. 2000: U212?U212
View details for Web of Science ID 000089136800986
Ultrasonographic ear length measurement in normal second-and third-trimester fetuses AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Chitkara, U., Lee, L., El-Sayed, Y. Y., Holbrook, R. H., Bloch, D. K., Oehlert, J. W., Druzin, M. L. 2000; 183 (1): 230-234
Abstract

We sought to develop a nomogram for fetal ear length measurements from a large population of healthy second- and third-trimester fetuses and to investigate the correlation of fetal ear length with other standard fetal biometry measurements, as follows: biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length.Ear length measurement was obtained prospectively in 4240 singleton fetuses between 15 and 40 weeks' gestational age. Either complete data for normal karyotype on amniocentesis or normal infant examination at birth or both were available in 2583 cases. These constituted the final study population.A nomogram was developed by linearly regressing ear length on gestational age (Ear length [in millimeters] = 1.076 x Gestational age [in weeks] - 7. 308). There was a high correlation between ear length and gestational age (r = 0.96; P =.0001).The results of this study provide normative data on growth of fetal ear length from 15 to 40 weeks' gestation. Good correlation was also observed between ear length and other fetal biometric measurements (biparietal diameter, head circumference, abdominal circumference, femur length, and humerus length).

View details for Web of Science ID 000088565500039

View details for PubMedID 10920337
A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Branch, D. W., Peaceman, A. M., Druzin, M., Silver, R. K., El-Sayed, Y., SILVER, R. M., Esplin, M. S., Spinnato, J., Harger, J. 2000; 182 (1): 122-127
Abstract

Treatment with heparin and low-dose aspirin improves fetal survival among women with antiphospholipid syndrome. Despite treatment, however, these pregnancies are frequently complicated by preeclampsia, fetal growth restriction, and placental insufficiency, often with the result of preterm birth. Small case series suggest that intravenous immune globulin may reduce the rates of these obstetric complications, but the efficacy of this treatment remains unproven. This pilot study was undertaken to determine the feasibility of a multicenter trial of intravenous immune globulin and to assess the impact on obstetric and neonatal outcomes among women with antiphospholipid syndrome of the addition of intravenous immune globulin to a heparin and low-dose aspirin regimen.This multicenter, randomized, double-blind pilot study compared treatment with heparin and low-dose aspirin plus intravenous immune globulin with heparin and low-dose aspirin plus placebo in a group of women who met strict criteria for antiphospholipid syndrome. All patients had lupus anticoagulant, medium to high levels of immunoglobulin G anticardiolipin antibodies, or both. Patients with a single live intrauterine fetus at
View details for Web of Science ID 000084987100019

View details for PubMedID 10649166
Risk factors for early-onset group B streptococcal sepsis: Estimation of odds ratios by critical literature review PEDIATRICS Benitz, W. E., Gould, J. B., Druzin, M. L. 1999; 103 (6)
Abstract

To identify and to establish the prevalence of ORs factors associated with increased risk for early-onset group B streptococcal (EOGBS) infection in neonates. streptococcal (EOGBS) infection in neonates.Literature review and reanalysis of published data.Risk factors for EOGBS infection include group B streptococcal (GBS)-positive vaginal culture at delivery (OR: 204), GBS-positive rectovaginal culture at 28 (OR: 9.64) or 36 weeks gestation (OR: 26. 7), vaginal Strep B OIA test positive at delivery (OR: 15.4), birth weight 18 hours (OR: 7.28), intrapartum fever >37.5 degrees C (OR: 4.05), intrapartum fever, PROM, or prematurity (OR: 9.74), intrapartum fever or PROM at term (OR: 11.5), chorioamnionitis (OR: 6.43). Chorioamnionitis is reported in most (88%) cases in which neonatal infection occurred despite intrapartum maternal antibiotic therapy. ORs could not be estimated for maternal GBS bacteriuria during pregnancy, with preterm premature rupture of membranes, or with a sibling or twin with invasive GBS disease, but these findings seem to be associated with a very high risk. Multiple gestation is not an independent risk factor for GBS infection.h Mothers with GBS bacteriuria during pregnancy, with another child with GBS disease, or with chorioamnionitis should receive empirical intrapartum antibiotic treatment. Their infants should have complete diagnostic evaluations and receive empirical treatment until infection is excluded by observation and negative cultures because of their particularly high risk for EOGBS infection. Either screening with cultures at 28 weeks gestation or identification of clinical risk factors, ie, PROM, intrapartum fever, or prematurity, may identify parturients whose infants include 65% of those with EOGBS infection. Intrapartum screening using the Strep B OIA rapid test identifies more at-risk infants (75%) than any other method. These risk identifiers may permit judicious selection of patients for prophylactic interventions.

View details for Web of Science ID 000080613400006

View details for PubMedID 10353974
Preventing early-onset group B streptococcal sepsis: Strategy development using decision analysis PEDIATRICS Benitz, W. E., Gould, J. B., Druzin, M. L. 1999; 103 (6)
Abstract

To evaluate recommended strategies for prevention of early-onset group B streptococcal infections (EOGBS) with reference to strategies optimized using decision analysis.The EOGBS attack rate, prevalence and odds ratios for risk factors, and expected effects of prophylaxis were estimated from published data. Population subgroups were defined by gestational age, presence or absence of intrapartum fever or prolonged rupture of membranes, and presence or absence of maternal group B streptococcus (GBS) colonization. The EOGBS prevalence in each subgroup was estimated using decision analysis. The number of EOGBS cases prevented by an intervention was estimated as the product of the expected reduction in attack rate and the number of expected cases in each group selected for treatment. For each strategy, the number of residual EOGBS cases, cost, and numbers of treated patients were calculated based on the composition of the prophylaxis group. Integrated obstetrical-neonatal strategies for EOGBS prevention were developed by targeting the subgroups expected to benefit most from intervention.Reductions in EOGBS rates predicted by this decision analysis were smaller than those previously estimated for the strategies proposed by the American Academy of Pediatrics in 1992 (32.9% vs 90.7%), the American College of Obstetricians and Gynecologists in 1992 (53.8% vs 88.8%), and the Centers for Disease Control and Prevention in 1996 (75.1% vs 86.0%). Strategies based on screening for GBS colonization with rectovaginal cultures at 36 weeks or on use of a rapid test to screen for GBS colonization on presentation for delivery, combining intrapartum prophylaxis for selected mothers and postpartum prophylaxis for some of their infants, would require treatment of fewer patients and prevent more cases (78.4% or 80.1%, respectively) at lower cost.No strategy can prevent all EOGBS cases, but the attack rate can be reduced at a cost <$12 000 per prevented case. Supplementing intrapartum prophylaxis with postpartum ampicillin in a few infants is more effective and less costly than providing intrapartum prophylaxis for more mothers. Better intrapartum screening tests offer the greatest promise for increasing efficacy. Integrated obstetrical and neonatal regimens appropriate to the population served should be adopted by each obstetrical service. Surveillance of costs, complications, and benefits will be essential to guide continued iterative improvement of these strategies.

View details for Web of Science ID 000080613400005

View details for PubMedID 10353973
Antimicrobial prevention of early-onset group B streptococcal sepsis: Estimates of risk reduction based on a critical literature review PEDIATRICS Benitz, W. E., Gould, J. B., Druzin, M. L. 1999; 103 (6)
Abstract

To identify interventions that reduce the attack rate for early-onset group B streptococcal (GBS) sepsis in neonates.Literature review and reanalysis of published data.The rate of early-onset GBS sepsis in high-risk neonates can be reduced by administration of antibiotics. Treatment during pregnancy (antepartum prophylaxis) fails to reduce maternal GBS colonization at delivery. With the administration of intravenous ampicillin, the risk of early-onset infection in infants born to women with preterm premature rupture of membranes is reduced by 56% and the risk of GBS infection is reduced by 36%; addition of gentamicin may increase the efficacy of ampicillin. Treatment of women with chorioamnionitis with ampicillin and gentamicin during labor reduces the likelihood of neonatal sepsis by 82% and reduces the likelihood of GBS infection by 86%. Universal administration of penicillin to neonates shortly after birth (postpartum prophylaxis) reduces the early-onset GBS attack rate by 68% but is associated with a 40% increase in overall mortality and therefore is contraindicated. Intrapartum prophylaxis, alone or combined with postnatal prophylaxis for the infants, reduces the early-onset GBS attack rate by 80% or 95%, respectively.Women with chorioamnionitis or premature rupture of membranes and their infants should be treated with intravenous ampicillin and gentamicin. Intrapartum antimicrobial prophylaxis may be appropriate for other women whose infants are at increased but less extreme risk, and supplemental postpartum prophylaxis may be indicated for some of their infants. Selection of appropriate candidates and prophylaxis strategies requires careful consideration of costs and benefits for each patient. group B streptococcus, neonatal sepsis, early-onset sepsis, prevention, prophylaxis.

View details for Web of Science ID 000080613400007

View details for PubMedID 10353975
Placental pathology in systemic lupus erythematosus: A prospective study AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Magid, M. S., Kaplan, C., Sammaritano, L. R., Peterson, M., Druzin, M. L., Lockshin, M. D. 1998; 179 (1): 226-234
Abstract

Systemic lupus erythematosus and antiphospholipid antibody, often identified in patients with systemic lupus erythematosus, are associated with poor pregnancy outcome. This study distinguishes between the effect of each of these factors on gestational outcome and placental pathologic conditions in pregnant patients with systemic lupus erythematosus.Thirty-seven pregnancies and 40 placentas from 33 women with systemic lupus erythematosus were studied prospectively.Systemic lupus erythematosus alone, but not systemic lupus erythematosus activity, was associated with increased spontaneous abortions, preterm gestations, and fetal growth restriction. Placental correlates were ischemic-hypoxic change, decidual vasculopathy, decidual and fetal thrombi, chronic villitis, and decreased placental weight. Extensive infarction and fetal death were important antiphospholipid antibody-related findings.Decidual vasculopathy/coagulopathy appears to mediate the antiphospholipid antibody-related and much of the systemic lupus erythematosus-related deleterious effect on the placenta and gestational outcome. The presence of antiphospholipid antibody largely, but not invariably, predicts fetal death. Antiphospholipid antibody-independent chronic villitis may represent a second mechanism of systemic lupus erythematosus-related change.

View details for Web of Science ID 000075199300036

View details for PubMedID 9704792
Prevention of early-onset group B streptococcal disease: Optimizing strategies using risk-allocation decision analysis Benitz, W. E., Gould, J. B., Druzin, M. L. AMER ACAD PEDIATRICS. 1997: 493
View details for Web of Science ID A1997XU27800146
Insulin-like growth factor binding protein-1 at the maternal-fetal interface and insulin-like growth factor-I, insulin-like growth factor-II, and insulin-like growth factor binding protein-1 in the circulation of women with severe preeclampsia 15th Annual Meeting of the American-Gynecological-and-Obstetrical-Society Giudice, L. C., Martina, N. A., CRYSTAL, R. A., Tazuke, S., Druzin, M. MOSBY-YEAR BOOK INC. 1997: 751?57
Abstract

Preeclampsia is characterized by maternal hypertension, proteinuria, edema, and shallow placental invasion. Insulin-like growth factor binding protein-1, abundant in maternal decidua, is believed to play a role in limiting trophoblast invasiveness. In this study we addressed the hypothesis that this binding protein is aberrantly expressed in preeclampsia. We also investigated circulating levels of insulin-like growth factor-I and insulin-like growth factor-II in subjects with severe preeclampsia compared with controls.Insulin-like growth factor binding protein-1 was investigated by immunohistochemistry at the maternal-fetal interface of eight pregnancies complicated by severe preeclampsia and six controls between 21 and 34 weeks of gestation. Cell types were identified with use of cell-specific markers. Circulating levels of insulin-like growth factor binding protein-1, insulin-like growth factor-I, and insulin-like growth factor-II in 16 patients with severe preeclampsia and 29 controls at the same gestational age were determined by an immunoradiometric assay and correlated with clinical parameters. Data were analyzed by t test and Pearson's method.Insulin-like growth factor binding protein-1 was highly expressed on syncytiotrophoblasts, cytotrophoblasts, and decidual cells but not on placental fibroblasts. Immunostaining was greater at the maternal-fetal interface in severe preeclamptic patients compared with controls. Circulating insulin-like growth factor binding protein-1 levels in subjects with severe preeclampsia were 428.3 +/- 85.9 ng/ml compared with 76.6 +/- 11.8 in controls (p = 0.0007). Circulating insulin-like growth factor-I levels were 80.9 +/- 17.2 ng/ml compared with 179.4 +/- 28.2 ng/ml in controls (p = 0.0001). In contrast, insulin-like growth factor-II levels were not significantly different in the two groups. In subjects with severe preeclampsia insulin-like growth factor binding protein-1 levels correlated with diastolic blood pressure (r = 0.498, p 0.049) and aspartate transcarbamylase (0.621, p = 0.010).The abundance of insulin-like growth factor binding protein-1 at the maternal-fetal interface in severely preeclamptic pregnancies suggests that the binding protein may participate in the pathogenesis of the shallow placental invasion observed in this disorder. Low circulating insulin-like growth factor-I and elevated insulin-like growth factor binding protein-1 levels may contribute to restricted placental and therefore fetal growth.

View details for Web of Science ID A1997WV55500007

View details for PubMedID 9125598
Clinical rheumatologic applications of reproductive immunology - Facts, fiction, and fancy ARTHRITIS AND RHEUMATISM Wallace, D. J., Druzin, M. L., Lahita, R. G. 1997; 40 (2): 209?16
View details for DOI 10.1002/art.1780400205

View details for Web of Science ID A1997WH40800004

View details for PubMedID 9041932
Case report: Aa patient with severe CNS lupus during pregnancy ANNALES DE MEDECINE INTERNE KUZIS, C. S., Druzin, M. L., Lambert, R. E. 1996; 147 (4): 274-275
View details for Web of Science ID A1996VH51400007

View details for PubMedID 8952747
ACCURATE INTRAPARTUM ESTIMATION OF FETAL PLATELET COUNT BY FETAL SCALP SAMPLE SMEAR AMERICAN JOURNAL OF PERINATOLOGY Adams, D. M., Bussel, J. B., Druzin, M. L. 1994; 11 (1): 42-45
Abstract

Fetal scalp sampling has been used to determine fetal platelet count in early labor. Because platelet clumping may lead to falsely low platelet counts, this pilot study was carried out to evaluate an improved method of scanning an intrapartum fetal scalp smear for platelet estimation. We report 5 years' experience with the use of scanning of the smear for platelet aggregates instead of direct measurement of platelets. In 22 cases, intrapartum examination of the scalp blood smear at low power revealed the great majority of high-power, dry microscopic fields devoid of platelets, whereas isolated fields contained aggregates of more than 10 platelets. In one case, an adequate number of platelets were evenly distributed. Intrapartum fetal platelet estimation by scanning of the smear (using these platelet aggregates) correctly identified an adequate neonatal platelet count in 23 cases (mean, 264,600 +/- 15,000; range, 133,000 to 396,000). Cesarean section was avoided in 82.6% of these cases. In this pilot study, platelet estimation on fetal scalp sample were reliably performed by scanning of the smear for platelet aggregates. When aggregates were seen, platelet adequacy was found in all cases.

View details for Web of Science ID A1994MV28500013

View details for PubMedID 8155211
IL-1 SECRETION IN PREGNANT-WOMEN WITH SYSTEMIC LUPUS-ERYTHEMATOSUS VS HEALTHY CONTROLS HOCHFELD, M. B., VANVOLLENHOVEN, R. F., Wong, M. J., McGuire, J. L., DRUZIN, M. M., Polan, M. L. WILEY-BLACKWELL. 1993: S111?S111
View details for Web of Science ID A1993MB81600427
PROSPECTIVE EVALUATION OF THE CONTRACTION STRESS AND NONSTRESS TESTS IN THE MANAGEMENT OF POSTTERM PREGNANCY SURGERY GYNECOLOGY & OBSTETRICS Druzin, M. L., KARVER, M. L., Wagner, W., Hutson, J. M., WALTNER, A., Kogut, E. 1992; 174 (6): 507-512
Abstract

Eight hundred and nineteen patients were evaluated at greater than or equal to 280 days' gestation. All patients underwent nonstress test (NST) and breast stimulation to induce contraction stress test (CST), except where contraindicated. If CST was nonqualifying (less than three contractions per ten minutes), Pitocin (oxytocin) was used to complete the CST if there was a nonreactive NST. Delivery was instituted for any abnormal CST, even with a reactive NST, based on the last test within seven days of delivery. There were 747 reactive NST and 72 nonreactive NST. Breast stimulation for CST was done in 655 instances--315 (48 per cent) had nonqualifying CST and 340 (52 per cent) had qualifying CST. There was an increased incidence of induction in the nonqualifying CST group and abnormal CST group. There were no statistically significant differences in perinatal outcomes in the group with reactive NST, irrespective of the CST result. There were no antepartum fetal deaths.

View details for Web of Science ID A1992HX30300010

View details for PubMedID 1595028
ABNORMAL 1,25-DIHYDROXYVITAMIN-D METABOLISM IN PREECLAMPSIA 10TH ANNUAL MEETING OF THE AMERICAN GYNECOLOGICAL AND OBSTETRICAL SOC August, P., MARCACCIO, B., Gertner, J. M., Druzin, M. L., Resnick, L. M., Laragh, J. H. MOSBY-ELSEVIER. 1992: 1295?99
Abstract

We previously reported that preeclampsia is associated with hypocalciuria (N Engl J Med 1987; 316:715). The purpose of this study was to determine whether alterations in calcium regulatory hormones are present in preeclampsia and, if so, whether they are responsible for hypocalciuria. Thirty-two pregnant women were studied in the second and third trimesters of pregnancy (11 women with preeclampsia, nine with chronic hypertension, and 12 normotensive women). 1,25-Dihydroxyvitamin D, C-terminal parathyroid hormone, ionized calcium, and urinary calcium excretion were measured. 1,25-Dihydroxyvitamin D was significantly lower in the women with preeclampsia in the third trimester when the disease developed (37.8 +/- 15 pg/ml) than in women with chronic hypertension (75 +/- 15 pg/ml, p less than 0.05) and normal women (65 +/- 10 pg/ml, p less than 0.05). Parathyroid hormone was higher, but not significantly, in those with preeclampsia. Ionized calcium was not significantly different among the three groups. Urinary calcium excretion was abnormally low for pregnancy (less than 50 mg/24 hr) in all but one women with preeclampsia. We conclude that 1,25-dihydroxyvitamin D is reduced in preeclampsia and may lead to hypocalciuria by causing decreased intestinal absorption of calcium, stimulation of parathyroid hormone, and increased distal renal tubular resorption of calcium. The cause of reduced 1,25-dihydroxyvitamin D in preeclampsia is unknown and may be due to either diminished renal or placental production of the hormone.

View details for Web of Science ID A1992HP86900037

View details for PubMedID 1566788
Condition specific antepartum testing - Sytemic lupus erythematosus and associated serologic abnormaliities Am J Reprod Immun Druzin ML, Adams D, Edersheim T, Bond A, Kogut E. 1992
IMPACT OF ADVANCED MATERNAL AGE ON THE OUTCOME OF PREGNANCY SURGERY GYNECOLOGY & OBSTETRICS ALES, K. L., Druzin, M. L., Santini, D. L. 1990; 171 (3): 209-216
Abstract

We assessed the impact of advanced maternal age on the outcome of pregnancy by studying all 1,328 women who were primarily cared for and delivered at our institution between 14 September 1984 and 12 February 1985. Important peripartum maternal complications were no more frequent in women aged 35 years or more than in women 20 to 34 years old, although operative delivery was significantly more common. Similarly, adverse outcomes of infants were no more frequent. Perinatal mortality tended to be lower. In addition, we noted a trend for fewer infants with congenital anomalies to be born among older women. This trend was related, in part, to the choice to terminate the pregnancy by women with fetuses that had documented chromosomal anomalies. We conclude that advanced maternal age was not associated with an excess of adverse pregnancy outcome and suggest that, with early registration and careful surveillance during pregnancy, women aged 35 years or more can experience excellent pregnancy outcomes.

View details for Web of Science ID A1990DW89800006

View details for PubMedID 2385814
ARE DOPPLER-DETECTED VENOUS EMBOLI DURING CESAREAN-SECTION AIR EMBOLI ANESTHESIA AND ANALGESIA Fong, J., Gadalla, F., Pierri, M. K., Druzin, M. 1990; 71 (3): 254-257
Abstract

The incidence of venous emboli during cesarean section was studied using simultaneous precordial ultrasonic Doppler monitoring and two-dimensional echocardiography. Forty-nine patients receiving either general or continuous epidural anesthesia in the horizontal position were monitored with both Doppler monitoring and echocardiography. There was excellent correlation between the embolic events detected by Doppler monitoring and by echocardiography (kappa value = 1). The incidence of venous emboli was 29% (14/49). The venous emboli detected by Doppler monitoring were indeed air emboli, not amniotic fluid or thromboemboli, as illustrated by their echocardiographic appearance.

View details for Web of Science ID A1990DV42900007

View details for PubMedID 2203279
EPIDURAL-ANESTHESIA FOR LABOR AND CESAREAN-SECTION IN A PARTURIENT WITH A SINGLE VENTRICLE AND TRANSPOSITION OF THE GREAT-ARTERIES CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE Fong, J., Druzin, M., GIMBEL, A. A., Fisher, J. 1990; 37 (6): 680-684
Abstract

We describe a case of a 29-year-old parturient with a single ventricle and transposition of the great arteries who had lumbar epidural analgesia/anaesthesia with a local anaesthetic for labour, emergency Caesarean section and postoperative pain. Her outcome and that of her baby was successful. The anaesthetic techniques used in other parturients with similar congenital cardiac anomalies are reviewed.

View details for Web of Science ID A1990DX76300017

View details for PubMedID 2208543
ESTIMATION OF THE RISK OF THROMBOCYTOPENIA IN THE OFFSPRING OF PREGNANT-WOMEN WITH PRESUMED IMMUNE THROMBOCYTOPENIC PURPURA NEW ENGLAND JOURNAL OF MEDICINE Samuels, P., Bussel, J. B., Braitman, L. E., TOMASKI, A., Druzin, M. L., Mennuti, M. T., Cines, D. B. 1990; 323 (4): 229-235
Abstract

The optimal management of immune thrombocytopenic purpura during pregnancy remains controversial because the risk of severe neonatal thrombocytopenia remains uncertain. We studied the outcome of the index pregnancy in 162 women with a presumptive diagnosis of immune thrombocytopenic purpura to determine the frequency of neonatal thrombocytopenia and to determine whether neonatal risk could be predicted antenatally by history or platelet-antibody testing.Two maternal characteristics were identified as predicting a low risk of severe neonatal thrombocytopenia: the absence of a history of immune thrombocytopenic purpura before pregnancy, and the absence of circulating platelet antibodies in the women who did have a history of the condition. Eighteen of 88 neonates (20 percent; 95 percent confidence interval, 13 to 30 percent) born to women with a history of immune thrombocytopenic purpura had severe thrombocytopenia (platelet count less than 50 x 10(9) per liter at birth), as compared with 0 of 74 (0 percent; 95 percent confidence interval, 0 to 5 percent) born to women first noted to have thrombocytopenia during pregnancy (P less than 0.0001). Among the women with a history of immune thrombocytopenic purpura, 18 of 70 neonates (26 percent; 95 percent confidence interval, 16 to 38 percent) born to those with circulating platelet antibodies had severe thrombocytopenia, as compared with 0 of 18 infants (0 percent; 95 percent confidence interval, 0 to 18.5 percent) born to those without circulating antibodies (P less than 0.02). Thus, the risk of severe neonatal thrombocytopenia in the offspring of women without a history of immune thrombocytopenic purpura before pregnancy and of women with a history of the condition in whom circulating platelet antibodies are not detected was 0 percent (95 percent confidence intervals, 0 to 5 and 0 to 18.5 percent, respectively).The absence of a history of immune thrombocytopenic purpura or the presence of negative results on circulating-antibody testing in pregnant women indicates a minimal risk of severe neonatal thrombocytopenia in their offspring.

View details for Web of Science ID A1990DP59700004

View details for PubMedID 2366833
SIGNIFICANCE OF OBSERVING NO FLUID AT AMNIOTOMY AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Druzin, M. L., Adams, D. M. 1990; 162 (4): 1006-1007
Abstract

Thirty patients with oligohydramnios observed at artificial rupture of membranes were studied to determine the significance of this finding. Fifteen were subsequently found to have meconium-stained amniotic fluid and 21 had abnormal fetal heart rate tracings. This clinical observation warrants close intrapartum surveillance and preparation for delivery.

View details for Web of Science ID A1990DA40000019

View details for PubMedID 2327441
THE CLINICAL-SIGNIFICANCE OF PREDICTIONS BASED ON SCREENING 2ND TRIMESTER MEAN ARTERIAL-PRESSURE - ADVERSE MATERIAL AND INFANT OUTCOMES JOURNAL OF CLINICAL EPIDEMIOLOGY ALES, K. L., Norton, M. E., Druzin, M. L. 1990; 43 (2): 117-124
Abstract

The design of a trial of primary prevention of hypertension in pregnancy rests on both the ability to identify women who are at risk and the definition of a clinically important outcome. The risk of developing antepartum hypertension can now be assessed nonivasively by the midpoint of pregnancy. However, maternal hypertension is not always associated with a clinically important adverse outcome for either mother or infant. The purpose of this study was to prospectively assess whether increasing risk of antepartum hypertension is associated with increasing rates of clinically important maternal and/or infant morbidity. We assembled a prospective cohort of 720 women with singleton pregnancies. The proportion of pregnancies complicated by both antepartum hypertension and maternal and/or infant morbidity increased significantly between low, moderate, and high risk groups (0.2, 6 and 58.8%, respectively, p less than 0.0001). We conclude that a trial of primary prevention of hypertension in pregnancy should include a measure of significant morbidity in mother and infant.

View details for Web of Science ID A1990CQ49200001

View details for PubMedID 2331248
EARLY PREDICTION OF ANTEPARTUM HYPERTENSION OBSTETRICS AND GYNECOLOGY ALES, K. L., Norton, M. E., Druzin, M. L. 1989; 73 (6): 928-933
Abstract

We validated a mid-pregnancy screening mean arterial pressure (MAP2) of 85 mmHg or higher as a significant predictor of hypertension in pregnancy. During the 17-month period from October 1984 through February 1986, 730 women, or 16% of all women cared for and delivered at our institution, were screened at or near 20 weeks of amenorrhea. Of the 139 women with a MAP2 of 85 mmHg or higher, 21.6% developed antepartum hypertension, compared with only 0.7% of the 591 women with a MAP2 below 85 mmHg. The screening MAP2 level of 85 mmHg was the optimal cutoff for MAP2 as a screening test. Controlling for the value of the screening MAP2, the only other important predictors of antepartum hypertension were chronic hypertension and diabetes mellitus. Using these three variables, the probability that an individual pregnant woman will develop antepartum hypertension can be assessed with a high degree of accuracy (84.5%) by 20 weeks of amenorrhea. This assessment is noninvasive and simple to use. Three distinct levels of risk have been defined; the moderate- and high-risk groups warrant careful surveillance during pregnancy and may be reasonable groups in which to test preventive interventions.

View details for Web of Science ID A1989U768600003

View details for PubMedID 2726114
INTRAPARTUM UTERINE RUPTURE OBSTETRICS AND GYNECOLOGY Adams, D. M., Druzin, M. L., CEDERQVIST, L. L. 1989; 73 (3): 471-473
Abstract

The association between diethylstilbestrol (DES) exposure in utero and uterine malformations resulting in poor reproductive performance is well established. A case is presented of uterine rupture in a patient exposed to DES in utero who had no known predisposing factors for uterine rupture.

View details for Web of Science ID A1989T368300010

View details for PubMedID 2915876
PREGNANCY IN SYSTEMIC LUPUS-ERYTHEMATOSUS CLINICAL AND EXPERIMENTAL RHEUMATOLOGY Lockshin, M. D., QAMAR, T., Levy, R. A., Druzin, M. L. 1989; 7: S195-S197
Abstract

Experience with more than 150 pregnancies of women with systemic lupus erythematosus demonstrates that: many conventional measures of lupus activity, including complement, platelet count and urinary protein, are invalid during pregnancy; pregnancy does not cause lupus exacerbation; anti-phospholipid antibody is common and is closely associated with fetal loss, but is not the sole determinant factor of fetal loss; specific characteristics of anti-phospholipid antibody do not identify which antibody-positive women will have poor fetal outcome; prednisone therapy does not improve fetal prognosis; and neonatal lupus, diagnosed by rash and thrombocytopenia, is common but congenital heart block is rare.

View details for Web of Science ID A1989CE25300036

View details for PubMedID 2691157
DONATION OF BLOOD BY THE PREGNANT PATIENT FOR AUTOLOGOUS TRANSFUSION AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Druzin, M. L., Wolf, C. F., Edersheim, T. G., Hutson, J. M., KOGUT, E. A., SALAMON, J. L. 1988; 159 (5): 1023-1027
Abstract

A study was conducted to determine the safety and utility of autologous blood donation in third trimester pregnancy. Thirty-seven obstetric patients, 32 with an obstetric risk factor, donated an average of 485 ml of blood. Twenty-one of the 37 patients were expected to undergo cesarean section. Nonstress testing was performed before and after phlebotomy. Continuous fetal heart rate monitoring was maintained throughout the donation, which lasted an average of 9 minutes. All nonstress test results were normal before and after the phlebotomy except in one case. All fetal heart rates remained stable during phlebotomy and premature labor was not precipitated. All fetal outcomes were normal. One patient delivered on the day of phlebotomy, 6 hours after the procedure. Only one of the autologous units was used, in a patient who had a pelvic infection and moderate anemia. The incidence of primary cesarean section was 35%. Phlebotomy of the mother appears to be safe for the fetus at term. Further investigation is needed to determine the safety of removal of more than 1 unit of blood and blood donation at earlier gestational ages.

View details for Web of Science ID A1988R076700001

View details for PubMedID 3189432
NEONATAL LUPUS RISK TO NEWBORNS OF MOTHERS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS ARTHRITIS AND RHEUMATISM Lockshin, M. D., Bonfa, E., Elkon, K., Druzin, M. L. 1988; 31 (6): 697-701
Abstract

We prospectively studied 91 infants born to women with systemic lupus erythematosus (SLE) or with SLE-like disease. Thirty-eight infants, including 3 sets of twins, were born to women who had anti-Ro, anti-La, or anti-RNP antibodies. Four infants had definite neonatal lupus, and 4 had possible neonatal lupus. No prospectively studied infant had congenital heart block. The presence of neonatal lupus did not correlate with the titer of anti-Ro antibodies. During the same time period, 2 additional babies with neonatal lupus and congenital heart block were born to mothers not previously known to have SLE. Taken together, these findings confirm the association of anti-Ro antibody with neonatal lupus, but indicate that life-threatening neonatal lupus is rare in children born to mothers who are known to have SLE, even when antibodies to Ro, La, or RNP are present. Prophylactic therapy is therefore not indicated for these women. An important proportion of mothers bearing children with neonatal lupus do not have recognized SLE and, currently, cannot be prospectively identified.

View details for Web of Science ID A1988N997500001

View details for PubMedID 3382445
DEVELOPMENT AND VALIDATION OF A MULTIVARIATE PREDICTOR OF MORTALITY IN VERY LOW BIRTH-WEIGHT JOURNAL OF CLINICAL EPIDEMIOLOGY ALES, K. L., FRAYER, W., Hawks, G., AULD, P. M., Druzin, M. L. 1988; 41 (11): 1095-1103
Abstract

Accurate prognosis is critical to the design of all prospective research aimed at improving survival. Predictions based on birth weight, gestational age, or any other single variable, fail to take into account the potentially important contribution of other factors. In order to develop a practical and accurate multivariate model, we studied all singleton pregnancies resulting in viable liveborn infants who weighed less than or equal to 1500 g at birth during 1984 and 1985 at the New York Hospital-Cornell Medical Center. When gestational age, birth weight, and/or crown-heel length were considered, no maternal characteristics were significant predictors of mortality. The model with the maximal predictive accuracy (84.5%) used birth weight and 5-minute Apgar score to calculate a probability of mortality. This prognostic model was then validated in a separate cohort of singletons born in 1986. We conclude that clinical trials should require stratification before randomization, using the calculated probability of mortality, rather than birth weight or gestational age alone. Given the ability of models, such as the one presented here, to generate reasonable estimates of mortality, this information might also be used in the clinical setting to assist parents and physicians in individualized decision-making processes for a given infant.

View details for Web of Science ID A1988R520300008

View details for PubMedID 3060570
FETAL HEART-RATE RESPONSE TO VIBRATORY ACOUSTIC STIMULATION PREDICTS FETAL PH IN LABOR AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Edersheim, T. G., Hutson, J. M., Druzin, M. L., KOGUT, E. A. 1987; 157 (6): 1557-1560
Abstract

Vibratory acoustic stimulation was performed during labor in 188 instances 60 seconds before fetal scalp puncture was done to determine fetal scalp blood pH. The fetal heart rate response was recorded for both vibratory acoustic stimulation and fetal scalp puncture. No instance of fetal acidosis occurred in the presence of an acceleration to either vibratory acoustic stimulation or fetal scalp puncture. Vibratory acoustic stimulation was more likely to elicit an acceleration than fetal scalp puncture in the nonacidotic fetus. Vibratory acoustic stimulation is less invasive and may be used in some instances in which fetal scalp blood puncture for pH determination is technically impossible.

View details for Web of Science ID A1987L343100043

View details for PubMedID 3425661
HAZARDS OF LUPUS PREGNANCY JOURNAL OF RHEUMATOLOGY Lockshin, M. D., QAMAR, T., Druzin, M. L. 1987; 14: 214-217
Abstract

Fetal death occurs in about 1/3 of pregnancies in patients with systemic lupus erythematosus (SLE). It is largely predicted by lupus anticoagulant (estimated by activated partial thromboplastin time) and/or antibody to cardiolipin. These antibodies are not synonymous. Neonatal lupus appears in a minority of infants born to women with antibody to the Ro/La antigens. Hypocomplementemia is common in SLE pregnancies, as in pregnancy induced hypertension. Lupus exacerbation is uncommon either during or after pregnancy. Prematurity and fetal death are the greatest hazards.

View details for Web of Science ID A1987J103600041

View details for PubMedID 3612648
CORRELATION BETWEEN PLASMA-RENIN ACTIVITY AND BIRTH-WEIGHT IN HYPERTENSIVE PREGNANCY JOURNAL OF HYPERTENSION TAUFIELD, P. A., Druzin, M. L., EDERSHEIM, T. E., Sealey, J. E., Laragh, J. H. 1986; 4: S96-S98
Abstract

Plasma renin activity (PRA) was measured in the late third trimester in 26 hypertensive pregnant women and correlated with their infants' birth weights. Seven pre-eclamptics, six chronic hypertensives and 13 chronic hypertensives with superimposed pre-eclampsia were studied. Plasma renin activity was lower in 13 mothers with small for gestational age (SGA) infants (5.2 +/- 0.89 ng/ml per h, compared with 13 mothers with appropriate for gestational age (AGA) infants (16.65 +/- 2.37 ng/ml per h, P less than 0.001. The mean PRA was also lower in mothers with babies weighing less that 2500 g, regardless of gestational age, compared with 11 mothers with babies weighing more than 2500 g, (7.58 +/- 1.61 versus 15.86 +/- 2.73 ng/ml per h, P less than 0.050. Mean PRA was not significantly different in the different hypertensive groups, although women with chronic hypertension appeared to have lower PRA than pre-eclamptics. Our data suggest that in gestational hypertension, low PRA is associated with low infant birth weight, and that late third trimester PRA may therefore identify those at risk for poor fetal outcome.

View details for Web of Science ID A1986G629000031

View details for PubMedID 3553491
ALPHA-2-PLASMIN INHIBITOR - PLASMIN COMPLEXES IN NORMAL AND HYPERTENSIVE PREGNANCY CLINICAL AND EXPERIMENTAL HYPERTENSION PART B-HYPERTENSION IN PREGNANCY ALES, K. L., TAUFIELD, P. A., Harpel, P. C., Druzin, M. L. 1986; 5 (2): 203-215
View details for Web of Science ID A1986D775800004
PLASMA PRORENIN IN 1ST-TRIMESTER PREGNANCY - RELATIONSHIP TO CHANGES IN HUMAN CHORIONIC-GONADOTROPIN AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Sealey, J. E., McCord, D., TAUFIELD, P. A., ALES, K. A., Druzin, M. L., Atlas, S. A., Laragh, J. H. 1985; 153 (5): 514-519
Abstract

Prorenin and human chorionic gonadotropin are both synthesized in chorionic cells. The relationship of changes in maternal plasma prorenin to changes in human chorionic gonadotropin were therefore evaluated during the first trimester. In samples submitted to the routine chemistry laboratory for detection of pregnancy a positive relationship was observed between prorenin and beta human chorionic gonadotropin during the 5 weeks following conception. Subsequently human chorionic gonadotropin continued to rise but prorenin had reached a plateau. Serial studies in one subject demonstrated that prorenin had increased to 65% of maximum by the thirteenth day following conception whereas human chorionic gonadotropin had risen to only 0.2% of maximum. By 3 to 5 days post partum, beta human chorionic gonadotropin had fallen by 98% but prorenin had fallen by only 50%. The early rise in prorenin following conception and the relatively slow fall post partum suggest that pregnancy-related changes in maternal plasma prorenin are of maternal, not fetal, origin.

View details for Web of Science ID A1985AUC1400009

View details for PubMedID 3904454
LUPUS PREGNANCY .2. UNUSUAL PATTERN OF HYPOCOMPLEMENTEMIA AND THROMBOCYTOPENIA IN THE PREGNANT PATIENT ARTHRITIS AND RHEUMATISM Lockshin, M. D., Harpel, P. C., Druzin, M. L., Becker, C. G., Klein, R. F., Watson, R. M., Elkon, K. B., REINITZ, E. 1985; 28 (1): 58-66
Abstract

To explore the causes of complications in pregnant women with systemic lupus erythematosus (SLE), we prospectively evaluated 34 pregnancies in 28 SLE patients, and 2 additional pregnancies in patients with lupus anticoagulant and positive antinuclear antibody, but no other manifestations of SLE. Nineteen pregnancies (55%) were complicated by marked proteinuria, thrombocytopenia, and/or lupus anticoagulant. Hypocomplementemia occurred in 18 pregnancies (52%). Neither thrombocytopenia-anticoagulant nor proteinuria was accompanied by an increase in antibody to double-stranded DNA or by clinical signs of active SLE. Antibody to Ro antigen did not predict fetal death. Both thrombocytopenia and proteinuria appeared abruptly during pregnancy and disappeared quickly after delivery. Fetal death was the result in 7 of 9 (77%) pregnancies in patients with anticoagulant, 6 of 10 (60%) in patients with thrombocytopenia, 6 of 18 (33%) in patients with hypocomplementemia, and 3 of 11 (27%) in patients with proteinuria. Twenty of 29 (68%) children were identified as male. The pathogenesis of hypocomplementemia was evaluated by a new assay, C1s-C1 inhibitor complex, which is thought to measure rate of complement activation by the classical pathway. Most pregnant patients with low CH50 levels and proteinuria had normal levels of C1s-C1 inhibitor complex, whereas nonpregnant patients with equivalent proteinuria and hypocomplementemia had high levels, as did pregnant patients with hypocomplementemia who did not have SLE. Pregnant and nonpregnant hypocomplementemic patients with proteinuria had similar levels of C3 and C4. In pregnant patients with SLE, C1s-C1 inhibitor complex was independent of CH50; in nonpregnant patients a linear relationship between C1s-C1 inhibitor complex and CH50 was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

View details for Web of Science ID A1985AAU1500009

View details for PubMedID 3917671
SPONTANEOUS HYPOGLYCEMIC SEIZURES IN PREGNANCY - A MANIFESTATION OF PANHYPOPITUITARISM ARCHIVES OF INTERNAL MEDICINE NOTTERMAN, R. B., Jovanovic, L., Peterson, R., Solomon, G., Druzin, M., Peterson, C. M. 1984; 144 (1): 189-191
Abstract

A 32-year-old woman had seizures and coma due to severe hypoglycemia (26 mg/dL) in the 32nd week of an otherwise uncomplicated pregnancy. She responded dramatically to the administration of cortisol. Initial endocrine evaluation disclosed prolactin (PRL), corticotropin, and thyrotropin (TSH) deficiencies. The patient recovered completely with cortisol and thyroid hormone therapy and was delivered of a healthy male child at term. Endocrine reevaluations one week and six months postpartum disclosed luteinizing hormone, follicle-stimulating hormone, growth hormone, PRL, corticotropin, and probable TSH deficiencies. The cause of this panhypopituitarism has not been determined. This case suggests that the appropriate initial treatment for spontaneous symptomatic hypoglycemia in pregnancy, while awaiting further endocrine evaluation, is the administration of cortisol.

View details for Web of Science ID A1984RY30500035

View details for PubMedID 6691758
MATERNAL-FETAL IMMUNITY - PRESENCE OF SPECIFIC CELLULAR HYPORESPONSIVENESS AND HUMORAL SUPPRESSOR ACTIVITY IN NORMAL-PREGNANCY AND THEIR ABSENCE IN PRE-ECLAMPSIA CLINICAL AND EXPERIMENTAL HYPERTENSION PART B-HYPERTENSION IN PREGNANCY TAUFIELD, P. A., Suthanthiran, M., ALES, K., Druzin, M., Resnick, L. M., Laragh, J. H., Stenzel, K. H., Rubin, A. L. 1983; 2 (1): 123-131
Abstract

The hypothesis that aberrant maternal-fetal immunity might lead to the development of preeclampsia was examined using mixed lymphocyte culture reactions (MLC) as an in vitro analogue of maternal-fetal immunity. Maternal lymphocytes and serum from five normal pregnant women differed significantly from lymphocytes and serum from five preeclamptics. Maternal cells from normal pregnancy responded appropriately to unrelated control cells, but demonstrated selective hyporesponsiveness to fetal cells in the MLC. Serum from normal pregnancy suppressed MLCs when maternal cells were responder cells (RC) and maternal cells or fetal cells were stimulator cells (SC), and did not inhibit MLCs where maternal cells were RC and control cells were SC. Maternal lymphocytes and serum from preeclamptics did not demonstrate cellular hyporesponsiveness or humoral suppressor activity. Our findings support the notion that specific cellular hyporesponsiveness and humoral suppressor activity is responsible for normal pregnancy; absence of such adaptive immunity might lead to the development of preeclampsia.

View details for Web of Science ID A1983QT81300012

View details for PubMedID 6223727
BIOPHYSICAL TESTS OF FETAL WELL BEING PEDIATRIC ANNALS Fox, A. M., Druzin, M. L. 1983; 12 (2): 120-?
View details for Web of Science ID A1983QC31600003

View details for PubMedID 6835708
EFFECT OF EUGLYCEMIA ON THE OUTCOME OF PREGNANCY IN INSULIN-DEPENDENT DIABETIC WOMEN AS COMPARED WITH NORMAL CONTROL SUBJECTS AMERICAN JOURNAL OF MEDICINE Jovanovic, L., Druzin, M., Peterson, C. M. 1981; 71 (6): 921-927
View details for Web of Science ID A1981MT30100003

View details for PubMedID 7032287

Maurice L. Druzin

Professor of Obstetrics and Gynecology (Maternal Fetal Medicine) and, by courtesy, of Pediatrics at the Stanford University Medical Center

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