Alexis Davis

All Publications

• Umbilical Cord Milking versus Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants. The Journal of pediatrics Kumbhat, N., Eggleston, B., Davis, A. S., DeMauro, S. B., Van Meurs, K. P., Foglia, E. E., Lakshminrusimha, S., Walsh, M. C., Watterberg, K. L., Wyckoff, M. H., Das, A., Handley, S. C. 2021

  Abstract

  To compare in-hospital outcomes after umbilical cord milking versus delayed cord clamping among infants <29 weeks' gestation.Multicenter retrospective study of infants born <29 weeks' gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to UCM or DCC. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in two GA strata, 22-246/7 and 25-286/7 weeks.Among 1,834 infants, 23.6% were exposed to UCM and 76.4% to DCC. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to UCM and 19.1% exposed to DCC, with an adjusted odds ratio that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). UCM exposed infants had higher odds of severe IVH (19.8% UCM vs. 11.8% DCC, aOR 1.70 95% CI 1.20, 2.43), as did the 25-286/7 week stratum (14.8% UCM vs. 7.4% DCC, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups.This analysis of extremely preterm infants suggests that DCC is the preferred practice for placental transfusion, as UCM exposure was associated with an increase in the adverse outcome of severe IVH.

  View details for DOI 10.1016/j.jpeds.2020.12.072

  View details for PubMedID 33417919

• Neonates in the COVID-19 pandemic. Pediatric research Molloy, E. J., Lavizzari, A., Klingenberg, C., Profit, J., Zupancic, J. A., Davis, A. S., Mosca, F., Bearer, C. F., Roehr, C. C., International Neonatal COVID-19 Consortium, Bassler, D., Burn-Murdoch, J., Danhaive, O., Davis, J., Ferri, W. A., Fuchs, H., Ge, H., Gupta, A., Gupta, M., van Kaam, A., Diaz, V. J., Trevino-Perez, R., Mariani, G. L., Naver, L., Patel, A., Shah, P., Szczapa, T., Vento, M., Wellman, S., Zangen, S. 2020

  View details for DOI 10.1038/s41390-020-1096-y

  View details for PubMedID 32746446

• Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Extremely Low Gestational Age Infants. The Journal of pediatrics Shankaran, S., Bajaj, M., Natarajan, G., Saha, S., Pappas, A., Davis, A. S., Hintz, S. R., Adams-Chapman, I., Das, A., Bell, E. F., Stoll, B. J., Walsh, M. C., Laptook, A. R., Carlo, W. A., Van Meurs, K. P., Sanchez, P. J., Ball, M. B., Hale, E. C., Seabrook, R., Higgins, R. D., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network 2020

  Abstract

  OBJECTIVE: To assess outcomes following post-hemorrhagic ventricular dilatation (PHVD) among infants born at ≤26 weeks of gestation.STUDY DESIGN: Observational study of infants born 4/1/11-12/31/15 in the NICHD Neonatal Research Network and categorized into three groups: PHVD, intracranial hemorrhage without ventricular dilatation, or normal head ultrasound. PHVD was treated per center practice. Neurodevelopmental impairment at 18-26 months was defined by cerebral palsy, Bayley III cognitive or motor score <70, blindness or deafness. Multivariable logistic regression examined the association of death or impairment, adjusting for neonatal course, center, maternal education and parenchymal hemorrhage.RESULTS: Of 4216 infants, 815 had PHVD, 769 had hemorrhage without ventricular dilatation, and 2632 had normal head ultrasounds. Progressive dilatation occurred among 119/815 infants; the initial intervention in 66 infants was reservoir placement and 53 had ventriculoperitoneal shunt placement. Death or impairment occurred among 68%, 39%, and 28% of infants with PHVD, hemorrhage without dilatation and normal head ultrasound, respectively; adjusted odds ratios (aOR) 95% CI were 4.6 (3.8-5.7) PHVD vs. normal head ultrasound and 2.98 (2.3-3.8) for PHVD vs hemorrhage without dilatation. Death or impairment was more frequent with intervention for progressive dilatation vs. no intervention [80% vs. 65%; aOR 2.2 (1.38-3.8)]. Death or impairment increased with parenchymal hemorrhage, intervention for PHVD, male sex and surgery for retinopathy; odds decreased with each additional gestational week.CONCLUSIONS: PHVD was associated with high rates of death or impairment among infants with gestational ages ≤26 weeks; risk was further increased among those with progressive ventricular dilation requiring intervention.

  View details for DOI 10.1016/j.jpeds.2020.07.080

  View details for PubMedID 32739261

• International comparison of guidelines for managing neonates at the early phase of the SARS-CoV-2 pandemic. Pediatric research Lavizzari, A., Klingenberg, C., Profit, J., Zupancic, J. A., Davis, A. S., Mosca, F., Molloy, E. J., Roehr, C. C. 2020

  Abstract

  The COVID-19 pandemic threatens global newborn health. We describe the current state of national and local protocols for managing neonates born to SARS-CoV-2-positive mothers.Care providers from neonatal intensive care units on six continents exchanged and compared protocols on the management of neonates born to SARS-CoV-2-positive mothers. Data collection was between March 14 and 21, 2020. We focused on central protocol components, including triaging, hygiene precautions, management at delivery, feeding protocols, and visiting policies.Data from 20 countries were available. Disease burden varied between countries at the time of analysis. In most countries, asymptomatic infants were allowed to stay with the mother and breastfeed with hygiene precautions. We detected discrepancies between national guidance in particular regarding triaging, use of personal protection equipment, viral testing, and visitor policies. Local protocols deviated from national guidance.At the start of the pandemic, lack of evidence-based guidance on the management of neonates born to SARS-CoV-2-positive mothers has led to ad hoc creation of national and local guidance. Compliance between collaborators to share and discuss protocols was excellent and may lead to more consensus on management, but future guidance should be built on high-level evidence, rather than expert consensus.At the rapid onset of the COVID19 pandemic, all countries presented protocols in place for managing infants at risk of COVID19, with a certain degree of variations among regions. A detailed review of ad hoc guidelines is presented, similarities and differences are highlighted. We provide a broad overview of currently applied recommendations highlighting the need for international context-relevant coordination.

  View details for DOI 10.1038/s41390-020-0976-5

  View details for PubMedID 32541844

• Effects of gestational age at delivery and type of labor on neonatal outcomes among infants with gastroschisis. 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 Girsen, A. I., Davis, A. S., Hintz, S. R., Fluharty, E., Sherwin, K., Trepman, P., Desai, A., Mansour, T., Sylvester, K. G., Oshiro, B., Blumenfeld, Y. J. 2019: 1–191

  Abstract

  Objective: To investigate the effect of preterm gestational age on neonatal outcomes of gastroschisis and to compare the neonatal outcomes after spontaneous labor versus iatrogenic delivery both in the preterm and early term gestational periods. Study design: A retrospective study of prenatally-diagnosed gastroschisis cases born at Loma Linda University Medical Center and Lucile Packard Children's Hospital (CA, USA) between January 2009 and October 2016. A total of 194 prenatally diagnosed gastroschisis cases were identified and included in the analysis. We compared infants delivered < 37 0/7 to those ≥ 37 0/7 weeks' gestation. Adverse neonatal outcome was defined as any of: sepsis, short bowel syndrome, prolonged ventilation or death. Prolonged length of stay (LOS) was defined as ≥ 75th percentile value. Outcomes following spontaneous versus iatrogenic delivery were compared. Analyses were performed using chi-squared test or Fisher's exact test for categorical variables, and Student's t-test or Wilcoxon rank-sum test for continuous variables. Results: One hundred six neonates were born < 37weeks and 88 at ≥ 37weeks. Adverse outcome was statistically similar among those born < 37weeks compared to ≥ 37weeks (48 versus 34%, p = 0.07). Prolonged LOS was more frequent among neonates delivered < 37weeks (p = 0.03). Among neonates born < 37weeks, bowel atresia was more frequent in those with spontaneous versus iatrogenic delivery (p = 0.04). There was no significant difference in the adverse neonatal composite outcome between those with spontaneous preterm labor versus planned iatrogenic delivery at < 37weeks (n = 30 (58%) versus n = 21 (39%), p = 0.08). Conclusion: Neonates with gastroschisis delivered < 37weeks had prolonged LOS whereas the rate of adverse neonatal outcomes was similar between those delivered preterm versus term. Neonates born after spontaneous preterm labor had a higher rate of bowel atresia compared to those born after planned iatrogenic preterm delivery.

  View details for DOI 10.1080/14767058.2019.1656191

  View details for PubMedID 31409162

• Prenatally diagnosed omphalocele: characteristics associated with adverse neonatal outcomes. Journal of perinatology : official journal of the California Perinatal Association Chock, V. Y., Davis, A. S., Cho, S., Bax, C., Fluharty, E., Weigel, N., Homeyer, M., Hudgins, L., Jones, R., Rubesova, E., Sylvester, K. G., Blumenfeld, Y. J., Hintz, S. R. 2019

  Abstract

  OBJECTIVE: To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases.STUDY DESIGN: Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed.RESULTS: Out of 63 fetal cases, 33 were live-born, >50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach toomphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3-422), p=0.006).CONCLUSION: Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

  View details for DOI 10.1038/s41372-019-0410-1

  View details for PubMedID 31227786

• IMPACT OF CARDIAC ALGORITHM ON CYTOGENETIC TESTING Floyd, B. J., Hintz, S. R., Suarez, C. J., Cherry, A., Yu, L., Benitz, W., Priest, J. R., Wright, G. E., Bhombal, S., Davis, A., Chock, V. Y., Weigel, N., Kobayashi, D., Fluharty, B., Stevenson, D. BMJ PUBLISHING GROUP. 2019: 207

  View details for DOI 10.1136/jim-2018-000939.327

  View details for Web of Science ID 000457712500337

• Is prophylaxis with early low-dose hydrocortisone in very preterm infants effective in preventing bronchopulmonary dysplasia? Journal of perinatology : official journal of the California Perinatal Association Kumbhat, N., Davis, A. S., Benitz, W. E. 2019

  View details for DOI 10.1038/s41372-019-0485-8

  View details for PubMedID 31471578

• Obstetric and neonatal outcomes in pregnancies complicated by fetal lung masses: does final histology matter? 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 Anderson, J. N., Girsen, A. I., Hintz, S. R., El-Sayed, Y. Y., Davis, A. S., Barth, R. A., Halabi, S., Hazard, F. K., Sylvester, K. G., Bruzoni, M., Blumenfeld, Y. J. 2019: 1–7

  Abstract

  Purpose: Fetal lung masses complicate approximately 1 in 2000 live births. Our aim was to determine whether obstetric and neonatal outcomes differ by final fetal lung mass histology.Materials and methods: A review of all pregnancies complicated by a prenatally diagnosed fetal lung mass between 2009 and 2017 at a single academic center was conducted. All cases included in the final analysis underwent surgical resection and histology diagnosis was determined by a trained pathologist. Clinical data were obtained from review of stored electronic medical records which contained linked maternal and neonatal records. Imaging records included both prenatal ultrasound and magnetic resonance imaging. Fisher's exact test was used for categorical variables and the Kruskal-Wallis test was used for continuous variables. The level of significance was p<.05.Results: Of 61 pregnancies complicated by fetal lung mass during the study period, 45 cases underwent both prenatal care and postnatal resection. Final histology revealed 10 cases of congenital pulmonary airway malformation (CPAM) type 1, nine cases of CPAM type 2, and 16 cases of bronchopulmonary sequestration. There was no difference in initial, maximal, or final CPAM volume ratio between groups, with median final CPAM volume ratio of 0.6 for CPAM type 1, 0.7 for CPAM type 2, and 0.3 for bronchopulmonary sequestration (p = .12). There were no differences in any of the maternal or obstetric outcomes including gestational age at delivery and mode of delivery between the groups. The primary outcome of neonatal respiratory distress was not statistically different between groups (p = .66). Median neonatal length of stay following delivery ranged from 3 to 4 days, and time to postnatal resection was similar as well, with a median of 126 days for CPAM type 1, 122 days for CPAM type 2, and 132 days for bronchopulmonary sequestration (p = .76).Conclusions: In our cohort, there was no significant association between histologic lung mass subtypes and any obstetric or neonatal morbidity including respiratory distress.

  View details for DOI 10.1080/14767058.2019.1689559

  View details for PubMedID 31722592

• Obstetric and neonatal outcomes in pregnancies complicated by fetal lung masses: does final histology matter? Anderson, J. N., Girsen, A. I., Hintz, S. R., El-Sayed, Y. Y., Davis, A. S., Barth, R. A., Halabi, S., Sylvester, K. G., Bruzoni, M., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2019: S151

  View details for DOI 10.1016/j.ajog.2018.11.230

  View details for Web of Science ID 000454249400210

• Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly. Journal of perinatology : official journal of the California Perinatal Association Katz, J. A., Chock, V. Y., Davis, A. S., Blumenfeld, Y. J., Hahn, J. S., Barnes, P., Barth, R. A., Rubesova, E., Hintz, S. R. 2018

  Abstract

  OBJECTIVE: Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM).STUDY DESIGN: Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children's Hospital Stanford 1/1/2009-6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated.RESULTS: A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related.CONCLUSION: Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.

  View details for PubMedID 30158676

• Development of a NeuroNICU with a Broader Focus on All Newborns at Risk of Brain Injury: The First 2 Years. American journal of perinatology Van Meurs, K. P., Yan, E. S., Randall, K. S., Chock, V. Y., Davis, A. S., Glennon, C. S., Clark, C. L., Wusthoff, C. J., Bonifacio, S. L. 2018

  Abstract

  OBJECTIVE: Many critically ill neonates have an existing brain injury or are at risk of neurologic injury. We developed a "NeuroNICU" (neurologic neonatal intensive care unit) to better provide neurologically focused intensive care.STUDY DESIGN: Demographic and clinical variables, services delivered, and patient outcomes were recorded in a prospective database for all neonates admitted to the NeuroNICU between April 23, 2013, and June 25, 2015.RESULTS: In total, 546 neonates were admitted to the NeuroNICU representing 32% of all NICU admissions. The most common admission diagnoses were congenital heart disease (30%), extreme prematurity (18%), seizures (10%), and hypoxic-ischemic encephalopathy (9%). Neuromonitoring was common, with near-infrared spectroscopy used in 69%, amplitude-integrated electroencephalography (EEG) in 45%, and continuous video EEG in 35%. Overall, 43% received neurology or neurosurgery consultation. Death prior to hospital discharge occurred in 11%. Among survivors, 87% were referred for developmental follow-up, and among those with a primary neurologic diagnosis 57% were referred for neurology or neurosurgical follow-up.CONCLUSION: The NeuroNICU-admitted newborns with or at risk of brain injury comprise a high percentage of NICU volume; 38% had primary neurologic diagnoses, whereas 62% had medical diagnoses. We found many opportunities to provide brain focused intensive care, impacting a substantial proportion of newborns in our NICU.

  View details for PubMedID 29702712

• NEONATAL HYPERBILIRUBINEMIA AFTER MECHANICAL CIRCULATORY SUPPORT Bhombal, S., Dasani, R., Davis, A., Axelrod, D. M., Wong, R. J., Bhutani, V. K. BMJ PUBLISHING GROUP. 2018: 164–65

  View details for DOI 10.1136/jim-2017-000663.236

  View details for Web of Science ID 000432007400247

• Outcome and Treatment of Antenatally Diagnosed Nonimmune Hydrops Fetalis FETAL DIAGNOSIS AND THERAPY Nassr, A. A., Ness, A., Hosseinzadeh, P., Salmanian, B., Espinoza, J., Berger, V., Werner, E., Erfani, H., Welty, S., Bateni, Z. H., Shamshirsaz, A. A., Popek, E., Ruano, R., Davis, A. S., Lee, T. C., Keswani, S., Cass, D. L., Olutoye, O. O., Belfort, M. A., Shamshirsaz, A. A. 2018; 43 (2): 123–28

  Abstract

  The objectives of this study were to evaluate the outcome of nonimmune hydrops fetalis in an attempt to identify independent predictors of perinatal mortality.A retrospective cohort study was conducted including all cases of nonimmune hydrops from two tertiary care centers. Perinatal outcome was evaluated after classifying nonimmune hydrops into ten etiological groups. We examined the effect of etiology, site of fluid accumulation, and gestational age at delivery on postnatal survival. Neonatal mortality and hospital discharge survival were compared between the expectant management and fetal intervention groups among those with idiopathic etiology.A total of 142 subjects were available for analysis. Generally, nonimmune hydrops carried 37% risk of neonatal mortality and 50% chance of survival to discharge, which varies markedly based on the underlying etiology. Ascites was an independent predictor of perinatal mortality (p value = 0.003). There was nonsignificant difference in neonatal mortality and hospital discharge survival among idiopathic cases that were managed expectantly versus those in whom fetal intervention was carried out.The outcome of nonimmune hydrops varies largely according to the underlying etiology and the presence of ascites is an independent risk factor for perinatal mortality. In our series, fetal intervention did not offer survival advantage among fetuses with idiopathic nonimmune hydrops.

  View details for PubMedID 28647738

• Relationship of Hospital Staff Coverage and Delivery Room Resuscitation Practices to Birth Asphyxia. American journal of perinatology Tu, J. H., Profit, J., Melsop, K., Brown, T., Davis, A., Main, E., Lee, H. C. 2017; 34 (3): 259-263

  Abstract

  Objective The objective of this study was to assess utilization of specialist coverage and checklists in perinatal settings and to examine utilization by birth asphyxia rates. Design This is a survey study of California maternity hospitals concerning checklist use to prepare for delivery room resuscitation and 24-hour in-house specialist coverage (pediatrician/neonatologist, obstetrician, and obstetric anesthesiologist) and results linked to hospital birth asphyxia rates (preterm and low weight births were excluded). Results Of 253 maternity hospitals, 138 responded (55%); 59 (43%) indicated checklist use, and in-house specialist coverage ranged from 38% (pediatrician/neonatologist) to 54% (anesthesiology). In-house coverage was more common in urban versus rural hospitals for all specialties (p < 0.0001), but checklist use was not significantly different (p = 0.88). Higher birth volume hospitals had more specialist coverage (p < 0.0001), whereas checklist use did not differ (p = 0.3). In-house obstetric coverage was associated with lower asphyxia rates (odds ratio: 0.34; 95% confidence interval [CI]: 0.20, 0.58) in a regression model accounting for other providers. Checklist use was not associated with birth asphyxia (odds ratio: 1.12; 95% CI: 0.75, 1.68). Conclusion Higher birth volume and urban hospitals demonstrated greater in-house specialist coverage, but checklist use was similar across all hospitals. Current data suggest that in-house obstetric coverage has greater impact on asphyxia than other specialist coverage or checklist use.

  View details for DOI 10.1055/s-0036-1586505

  View details for PubMedID 27487231

• Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis. Journal of perinatology Blumenfeld, Y. J., Do, S., Girsen, A. I., DAVIS, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Shamshirsaz, A. A., Lee, H. C. 2017

  Abstract

  To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis.Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations.Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than -2 with the total EFW improved the specificity and PPV but decreased the sensitivity.A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.Journal of Perinatology advance online publication, 26 January 2017; doi:10.1038/jp.2016.275.

  View details for DOI 10.1038/jp.2016.275

  View details for PubMedID 28125100

• Prediction of neonatal respiratory distress in pregnancies complicated by fetal lung masses. Prenatal diagnosis Girsen, A. I., Hintz, S. R., Sammour, R., Naqvi, A., El-Sayed, Y. Y., Sherwin, K., Davis, A. S., Chock, V. Y., Barth, R. A., Rubesova, E., Sylvester, K. G., Chitkara, R., Blumenfeld, Y. J. 2017

  Abstract

  The objective of this article is to evaluate the utility of fetal lung mass imaging for predicting neonatal respiratory distress.Pregnancies with fetal lung masses between 2009 and 2014 at a single center were analyzed. Neonatal respiratory distress was defined as intubation and mechanical ventilation at birth, surgery before discharge, or extracorporeal membrane oxygenation (ECMO). The predictive utility of the initial as well as maximal lung mass volume and congenital pulmonary airway malformation volume ratio by ultrasound (US) and magnetic resonance imaging (MRI) was analyzed.Forty-seven fetal lung mass cases were included; of those, eight (17%) had respiratory distress. The initial US was performed at similar gestational ages in pregnancies with and without respiratory distress (26.4 ± 5.6 vs 22.3 ± 3 weeks, p = 0.09); however, those with respiratory distress had higher congenital volume ratio at that time (1.0 vs 0.3, p = 0.01). The strongest predictors of respiratory distress were maximal volume >24.0 cm(3) by MRI (100% sensitivity, 91% specificity, 60% positive predictive value, and 100% negative predictive value) and maximal volume >34.0 cm(3) by US (100% sensitivity, 85% specificity, 54% positive predictive value, and 100% negative predictive value).Ultrasound and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value. © 2017 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.5002

  View details for PubMedID 28061000

• HDlive imaging of a giant omphalocele. Ultrasound in obstetrics & gynecology Blumenfeld, Y. J., E Milan, K., Rubesova, E., Sylvester, K. G., DAVIS, A. S., Chock, V. Y., Hintz, S. R. 2016; 48 (3): 407-408

  View details for DOI 10.1002/uog.15993

  View details for PubMedID 27299988

• Prenatally Diagnosed Cases of Binder Phenotype Complicated by Respiratory Distress in the Immediate Postnatal Period. Journal of ultrasound in medicine Blumenfeld, Y. J., Davis, A. S., Hintz, S. R., Milan, K., Messner, A. H., Barth, R. A., Hudgins, L., Chueh, J., Homeyer, M., Bernstein, J. A., Enns, G., Atwal, P., Manning, M. 2016; 35 (6): 1353-1358

  Abstract

  Binder phenotype, or maxillonasal dysostosis, is a distinctive pattern of facial development characterized by a short nose with a flat nasal bridge, an acute nasolabial angle, a short columella, a convex upper lip, and class III malocclusion. We report 3 cases of prenatally diagnosed Binder phenotype associated with perinatal respiratory impairment.

  View details for DOI 10.7863/ultra.15.02050

  View details for PubMedID 27162279

• Perinatal Neuroprotection for Extremely Preterm Infants AMERICAN JOURNAL OF PERINATOLOGY Davis, A. S., Berger, V. K., Chock, V. Y. 2016; 33 (3): 290-296

  Abstract

  The preterm brain is vulnerable to injury through multiple mechanisms, from direct cerebral injury through ischemia and hemorrhage, indirect injury through inflammatory processes, and aberrations in growth and development. While prevention of preterm birth is the best neuroprotective strategy, this is not always possible. This article will review various obstetric and neonatal practices that have been shown to confer a neuroprotective effect on the developing brain.

  View details for DOI 10.1055/s-0035-1571148

  View details for Web of Science ID 000370589700010

  View details for PubMedID 26799965

• 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

• Amplitude-integrated electroencephalography: a survey of practices in the United States. American journal of perinatology Shah, N. A., Van Meurs, K. P., Davis, A. S. 2015; 32 (8): 755-760

  Abstract

  Objective Amplitude-integrated electroencephalography (aEEG) is a simplified method for continuous monitoring of brain activity in the neonatal intensive care unit (NICU). Our objective was to describe current aEEG use in the United States. Study Design An online survey was distributed to the American Academy of Pediatrics Section on Perinatal Pediatrics' list serve. Result A total of 654 surveys were received; 55% of respondents reported using aEEG. aEEG was utilized more often in academic and levels III and IV NICUs; hypoxic-ischemic encephalopathy and suspected seizures were the most common indications for use. aEEG was primarily interpreted by neonatologists (87%), with approximately half reporting either self-teaching or hospital-based training for interpretation. For those not using aEEG, uncertain clinical benefit (40%) and cost (17%) were reported as barriers to use. Conclusion More than half of neonatologists utilize aEEG, with practice variation by NICU setting. Barriers to wider adoption include education regarding potential benefit, training, and cost.

  View details for DOI 10.1055/s-0034-1395483

  View details for PubMedID 25519200

• Serial aEEG recordings in a cohort of extremely preterm infants: feasibility and safety JOURNAL OF PERINATOLOGY Davis, A. S., Gantz, M. G., Do, B., Shankaran, S., Hamrick, S. E., Kennedy, K. A., TYSON, J. E., Chalak, L. F., Laptook, A. R., Goldstein, R. F., Hintz, S. R., Das, A., Higgins, R. D., Ball, M. B., HALE, E. C., Van Meurs, K. P. 2015; 35 (5): 373-378

  Abstract

  Objective:Amplitude-integrated electroencephalography (aEEG) monitoring is increasing in the neonatal population, but the safety and feasibility of performing aEEG in extremely preterm infants have not been systematically evaluated.Study Design:Inborn infants 23(0/7) to 28(6/7) weeks gestation or birth weight 401 to 1000 g were eligible. Serial, 6-h aEEG recordings were obtained from first week of life until 36 weeks postmenstrual age. Adverse events were documented, and surveys evaluated the impact of the aEEGs on routine care. Success of performing aEEGs according to protocol and aEEG quality were assessed.Result:A total of 102 infants were enrolled, with 755 recordings performed. 83% of recordings were performed according to schedule, and 96% were without adverse event. Bedside nurses reported no interference with routine care for 89% of recordings. 92% of recordings had acceptable signal quality.Conclusion:Serial aEEG monitoring is safe in preterm infants, with few adverse events and general acceptance by nursing staff.Journal of Perinatology advance online publication, 4 December 2014; doi:10.1038/jp.2014.217.

  View details for DOI 10.1038/jp.2014.217

  View details for PubMedID 25474559

• Peripartum and neonatal outcomes of small- for- gestational- age infants with gastroschisis PRENATAL DIAGNOSIS Girsen, A. I., Do, S., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Blumenfeld, Y. J. 2015; 35 (5): 477-482

  Abstract

  Neonates with gastroschisis are often small-for-gestational-age (SGA) based on population nomograms. Our objective was to evaluate the effect of SGA on perinatal and neonatal outcomes in cases of gastroschisis.Retrospective study of neonates with prenatally diagnosed gastroschisis from two academic centers between 2008-13. Perinatal and neonatal outcomes of neonates with SGA at birth were compared with appropriate for gestational age (AGA) neonates. The primary composite outcome was defined as any of: neonatal sepsis, short bowel syndrome at discharge, prolonged mechanical ventilation (upper quartile for the cohort), bowel atresia, or death.We identified 112 cases of gastroschisis, 25 of whom (22%) were SGA at birth. There were no differences in adverse peripartum outcomes between SGA and AGA infants. No difference was found in the primary composite neonatal outcome (52% vs. 36%, p=0.21), but SGA infants were more likely to have prolonged mechanical ventilation (44% vs. 22%, p=0.04) and prolonged LOS (52% vs. 22%, p=0.007). After adjusting for GA at delivery, SGA remained associated with prolonged LOS (OR=4.3, CI:1.6 - 11.8).Among infants with gastroschisis, SGA at birth is associated with a 4-fold increase in odds for prolonged LOS, independent of GA. © 2015 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.4562

  View details for Web of Science ID 000353987100011

  View details for PubMedID 25613462

• A randomized clinical trial of therapeutic hypothermia mode during transport for neonatal encephalopathy. journal of pediatrics Akula, V. P., Joe, P., Thusu, K., Davis, A. S., Tamaresis, J. S., Kim, S., Shimotake, T. K., Butler, S., Honold, J., Kuzniewicz, M., Desandre, G., Bennett, M., Gould, J., Wallenstein, M. B., Van Meurs, K. 2015; 166 (4): 856-61 e1 2

  Abstract

  To determine if temperature regulation is improved during neonatal transport using a servo-regulated cooling device when compared with standard practice.We performed a multicenter, randomized, nonmasked clinical trial in newborns with neonatal encephalopathy cooled during transport to 9 neonatal intensive care units in California. Newborns who met institutional criteria for therapeutic hypothermia were randomly assigned to receive cooling according to usual center practices vs device servo-regulated cooling. The primary outcome was the percentage of temperatures in target range (33°-34°C) during transport. Secondary outcomes included percentage of newborns reaching target temperature any time during transport, time to target temperature, and percentage of newborns in target range 1 hour after cooling initiation.One hundred newborns were enrolled: 49 to control arm and 51 to device arm. Baseline demographics did not differ with the exception of cord pH. For each subject, the percentage of temperatures in the target range was calculated. Infants cooled using the device had a higher percentage of temperatures in target range compared with control infants (median 73% [IQR 17-88] vs 0% [IQR 0-52], P < .001). More subjects reached target temperature during transport using the servo-regulated device (80% vs 49%, P <.001), and in a shorter time period (44 ± 31 minutes vs 63 ± 37 minutes, P = .04). Device-cooled infants reached target temperature by 1 hour with greater frequency than control infants (71% vs 20%, P < .001).Cooling using a servo-regulated device provides more predictable temperature management during neonatal transport than does usual care for outborn newborns with neonatal encephalopathy.

  View details for DOI 10.1016/j.jpeds.2014.12.061

  View details for PubMedID 25684087

• Fetal centers and the role of the neonatologist in complex fetal care. American journal of perinatology Davis, A. S., Chock, V. Y., Hintz, S. R. 2014; 31 (7): 549-556

  Abstract

  As prenatal imaging and genetic diagnostic techniques developed, clinicians knew earlier and with greater accuracy of the extent and severity of fetal anomalies. This, coupled with an acute awareness of high rates of death or devastating neonatal morbidities in some cases, drove efforts to create innovative fetal interventions. However, with advances in neonatal quaternary care, infants with even the most complex congenital anomalies now have a substantially greater chance of survival. But many still require highly coordinated intensive care from the moment of delivery, have lengthy and complicated hospitalizations, and need ongoing complex care and services. Therefore, a new vision of complex fetal medicine must evolve, actively integrating robust multidisciplinary involvement in collaborative counseling, planning, and management. The clinical arc visualized for complex fetal patients should shift toward a comprehensive continuum of care concept-extending from fetal life, through neonatal intensive care, to childhood. The neonatologist plays a critical role in bridging this trajectory, coordinating complex processes to a smooth delivery and neonatal plan, counseling and preparing expectant mothers, and integrating many components of subspecialty input for families and other fetal team members. Neonatologists' engagement and perspective can substantively inform the clinical and strategic direction for fetal centers.

  View details for DOI 10.1055/s-0034-1371709

  View details for PubMedID 24705973

• Outcomes of extremely preterm infants following severe intracranial hemorrhage. Journal of perinatology DAVIS, A. S., Hintz, S. R., Goldstein, R. F., Ambalavanan, N., Bann, C. M., Stoll, B. J., Bell, E. F., Shankaran, S., Laptook, A. R., Walsh, M. C., HALE, E. C., Newman, N. S., Das, A., Higgins, R. D. 2014; 34 (3): 203-208

  Abstract

  Objective:Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH.Study design:Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI).Result:Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI.Conclusion:Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.

  View details for DOI 10.1038/jp.2013.162

  View details for PubMedID 24370654

• Outcomes of extremely low birthweight infants with acidosis at birth. Archives of disease in childhood. Fetal and neonatal edition Randolph, D. A., Nolen, T. L., Ambalavanan, N., Carlo, W. A., Peralta-Carcelen, M., Das, A., Bell, E. F., Davis, A. S., Laptook, A. R., Stoll, B. J., Shankaran, S., Higgins, R. D. 2014

  Abstract

  To test the hypothesis that acidosis at birth is associated with the combined primary outcome of death or neurodevelopmental impairment (NDI) in extremely low birthweight (ELBW) infants, and to develop a predictive model of death/NDI exploring perinatal acidosis as a predictor variable.The study population consisted of ELBW infants born between 2002 and 2007 at National Institute of Child Health and Development (NICHD) Neonatal Research Network hospitals. Infants with cord blood gas data and documentation of either mortality prior to discharge or 18-22 month neurodevelopmental outcomes were included. Multiple logistic regression analysis was used to determine the contribution of perinatal acidosis, defined as a cord blood gas with a pH<7 or base excess (BE) <-12, to death/NDI in ELBW infants. In addition, a multivariable model predicting death/NDI was developed.3979 patients were identified of whom 249 had a cord gas pH<7 or BE<-12 mEq/L. 2124 patients (53%) had the primary outcome of death/NDI. After adjustment for confounding variables, pH<7 and BE<-12 mEq/L were each significantly associated with death/NDI (OR=2.5 (1.6, 4.2) and OR=1.5 (1.1, 2.0), respectively). However, inclusion of pH or BE did not improve the ability of the multivariable model to predict death/NDI.Perinatal acidosis is significantly associated with death/NDI in ELBW infants. Perinatal acidosis is infrequent in ELBW infants, however, and other factors are more important in predicting death/NDI.

  View details for PubMedID 24554564

• Therapeutic hypothermia during neonatal transport: data from the California Perinatal Quality Care Collaborative (CPQCC) and California Perinatal Transport System (CPeTS) for 2010 JOURNAL OF PERINATOLOGY Akula, V. P., Gould, J. B., DAVIS, A. S., Hackel, A., Oehlert, J., Van Meurs, K. P. 2013; 33 (3): 194-197

  Abstract

  To evaluate cooling practices and neonatal outcomes in the state of California during 2010 using the California Perinatal Quality Care Collaborative and California Perinatal Transport System databases.Database analysis to determine the perinatal and neonatal demographics and outcomes of neonates cooled in transport or after admission to a cooling center.Of the 223 infants receiving therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) in California during 2010, 69% were cooled during transport. Despite the frequent use of cooling in transport, cooling center admission temperature was in the target range (33-34 °C) in only 62 (44%). Among cooled infants, gestational age was <35 weeks in 10 (4.5%). For outborn and transported infants, chronologic age at the time of cooling initiation was >6 h in 20 (11%). When initiated at the birth hospital, cooling was initiated at <6 h of age in 131 (92.9%).More than half of the infants cooled in transport do not achieve target temperature by the time of arrival at the cooling center. The use of cooling devices may improve temperature regulation on transport.

  View details for DOI 10.1038/jp.2012.144

  View details for Web of Science ID 000315664700006

  View details for PubMedID 23223159

• Conservatively Managed Fetal Goiter: An Alternative to in utero Therapy. Fetal diagnosis and therapy Blumenfeld, Y. J., Davis, A., Milan, K., Chueh, J., Hudgins, L., Barth, R. A., Hintz, S. R. 2013; 34 (3): 184-187

  Abstract

  Fetal goiter may arise from a variety of etiologies including iodine deficiency, overtreatment of maternal Graves' disease, inappropriate maternal thyroid replacement and, rarely, congenital hypothyroidism. Fetal goiter is often associated with a retroflexed neck and polyhydramnios, raising concerns regarding airway obstruction in such cases. Prior reports have advocated for cordocentesis and intra-amniotic thyroid hormone therapy in order to confirm the diagnosis of fetal thyroid dysfunction, reduce the size of the fetal goiter, reduce polyhydramnios, aid with the assistance of maternal thyroid hormone therapy and reduce fetal malpresentation. We report two cases of conservatively managed fetal goiter, one resulting in a vaginal delivery, and no evidence of postnatal respiratory distress despite the presence of polyhydramnios and a retroflexed neck on prenatal ultrasound. © 2013 S. Karger AG, Basel.

  View details for DOI 10.1159/000353387

  View details for PubMedID 23920148

• Therapeutic Hypothermia during Neonatal Transport: Current Practices in California AMERICAN JOURNAL OF PERINATOLOGY Akula, V. P., Davis, A. S., Gould, J. B., Van Meurs, K. 2012; 29 (5): 319-326

  Abstract

  Therapeutic hypothermia initiated at <6 hours of age reduces death and disability in newborns ≥ 36 weeks' gestation with moderate to severe hypoxic ischemic encephalopathy. Given the limited therapeutic window, cooling during transport becomes a necessity. Our goal was to describe the current practice of therapeutic hypothermia during transport used in the state of California. All level III neonatal intensive care units (NICUs) were contacted to identify those units providing therapeutic hypothermia. An electronic questionnaire was sent to obtain basic information. Responses were received from 28 (100%) NICUs performing therapeutic hypothermia; 26 NICUs were cooling newborns and two were in the process of program development. Eighteen (64%) centers had cooled a patient in transport, six had not yet cooled in transport, and two do not plan to cool in transport. All 18 centers use passive cooling, except for two that perform both passive and active cooling, and 17 of 18 centers recommend initiation of cooling at the referral hospital. Reported difficulties include overcooling, undercooling, and bradycardia. Cooling on transport is being performed by majority of NICUs providing therapeutic hypothermia. Clinical protocols and devices for cooling in transport are essential to ensure safety and efficacy.

  View details for DOI 10.1055/s-0031-1295661

  View details for Web of Science ID 000302962200001

  View details for PubMedID 22143969

• Association of Antenatal Corticosteroids With Mortality and Neurodevelopmental Outcomes Among Infants Born at 22 to 25 Weeks' Gestation JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Carlo, W. A., McDonald, S. A., Fanaroff, A. A., Vohr, B. R., Stoll, B. J., Ehrenkranz, R. A., Andrews, W. W., Wallace, D., Das, A., Bell, E. F., Walsh, M. C., Laptook, A. R., Shankaran, S., Poindexter, B. B., Hale, E. C., Newman, N. S., Davis, A. S., Schibler, K., Kennedy, K. A., Sanchez, P. J., Van Meurs, K. P., Goldberg, R. N., Watterberg, K. L., Faix, R. G., Frantz, I. D., Higgins, R. D. 2011; 306 (21): 2348-2358

  Abstract

  Current guidelines, initially published in 1995, recommend antenatal corticosteroids for mothers with preterm labor from 24 to 34 weeks' gestational age, but not before 24 weeks due to lack of data. However, many infants born before 24 weeks' gestation are provided intensive care.To determine if use of antenatal corticosteroids is associated with improvement in major outcomes for infants born at 22 and 23 weeks' gestation.Cohort study of data collected prospectively on inborn infants with a birth weight between 401 g and 1000 g (N = 10,541) born at 22 to 25 weeks' gestation between January 1, 1993, and December 31, 2009, at 23 academic perinatal centers in the United States. Certified examiners unaware of exposure to antenatal corticosteroids performed follow-up examinations on 4924 (86.5%) of the infants born between 1993 and 2008 who survived to 18 to 22 months. Logistic regression models generated adjusted odds ratios (AORs), controlling for maternal and neonatal variables.Mortality and neurodevelopmental impairment at 18 to 22 months' corrected age.Death or neurodevelopmental impairment at 18 to 22 months was significantly lower for infants who had been exposed to antenatal corticosteroids and were born at 23 weeks' gestation (83.4% with exposure to antenatal corticosteroids vs 90.5% without exposure; AOR, 0.58 [95% CI, 0.42-0.80]), at 24 weeks' gestation (68.4% with exposure to antenatal corticosteroids vs 80.3% without exposure; AOR, 0.62 [95% CI, 0.49-0.78]), and at 25 weeks' gestation (52.7% with exposure to antenatal corticosteroids vs 67.9% without exposure; AOR, 0.61 [95% CI, 0.50-0.74]) but not in those infants born at 22 weeks' gestation (90.2% with exposure to antenatal corticosteroids vs 93.1% without exposure; AOR, 0.80 [95% CI, 0.29-2.21]). If the mothers had received antenatal corticosteroids, the following events occurred significantly less in infants born at 23, 24, and 25 weeks' gestation: death by 18 to 22 months; hospital death; death, intraventricular hemorrhage, or periventricular leukomalacia; and death or necrotizing enterocolitis. For infants born at 22 weeks' gestation, the only outcome that occurred significantly less was death or necrotizing enterocolitis (73.5% with exposure to antenatal corticosteroids vs 84.5% without exposure; AOR, 0.54 [95% CI, 0.30-0.97]).Among infants born at 23 to 25 weeks' gestation, antenatal exposure to corticosteroids compared with nonexposure was associated with a lower rate of death or neurodevelopmental impairment at 18 to 22 months.

  View details for Web of Science ID 000297680300020

  View details for PubMedID 22147379

• Perspectives of physician parents in the NICU Children's Health Care Batton B, Verhulst S, Batton D, Davis A, Collin A, Walsh M 2011; 40 (4): 326
• Seizures in Extremely Low Birth Weight Infants Are Associated with Adverse Outcome JOURNAL OF PEDIATRICS Davis, A. S., Hintz, S. R., Van Meurs, K. P., Li, L., Das, A., Stoll, B. J., Walsh, M. C., Pappas, A., Bell, E. F., Laptook, A. R., Higgins, R. D. 2010; 157 (5): 720-U47

  Abstract

  To examine risk factors for neonatal clinical seizures and to determine the independent association with death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants.A total of 6499 ELBW infants (401-1000 g) surviving to 36 weeks postmenstrual age (PMA) were included in this retrospective study. Unadjusted comparisons were performed between infants with (n = 414) and without (n = 6085) clinical seizures during the initial hospitalization. Using multivariate logistic regression modeling, we examined the independent association of seizures with late death (after 36 weeks PMA) or NDI after controlling for multiple demographic, perinatal, and neonatal variables.Infants with clinical seizures had a greater proportion of neonatal morbidities associated with poor outcome, including severe intraventricular hemorrhage, sepsis, meningitis, and cystic periventricular leukomalacia (all P < .01). Survivors were more likely to have NDI or moderate-severe cerebral palsy at 18 to 22 months corrected age (both P < .01). After adjusting for multiple confounders, clinical seizures remained significantly associated with late death or NDI (odds ratio, 3.15; 95% CI, 2.37-4.19).ELBW infants with clinical seizures are at increased risk for adverse neurodevelopmental outcome, independent of multiple confounding factors.

  View details for DOI 10.1016/j.jpeds.2010.04.065

  View details for PubMedID 20542294

• Human Neural Stem Cell Grafts Modify Microglial Response and Enhance Axonal Sprouting in Neonatal Hypoxic-Ischemic Brain Injury STROKE Daadi, M. M., Davis, A. S., Arac, A., Li, Z., Maag, A., Bhatnagar, R., Jiang, K., Sun, G., Wu, J. C., Steinberg, G. K. 2010; 41 (3): 516-523

  Abstract

  Hypoxic-ischemic (HI) brain injury in newborn infants represents a major cause of cerebral palsy, development delay, and epilepsy. Stem cell-based therapy has the potential to rescue and replace the ischemic tissue caused by HI and to restore function. However, the mechanisms by which stem cell transplants induce functional recovery are yet to be elucidated. In the present study, we sought to investigate the efficacy of human neural stem cells derived from human embryonic stem cells in a rat model of neonatal HI and the mechanisms enhancing brain repair.The human neural stem cells were genetically engineered for in vivo molecular imaging and for postmortem histological tracking. Twenty-four hours after the induction of HI, animals were grafted with human neural stem cells into the forebrain. Motor behavioral tests were performed the fourth week after transplantation. We used immunocytochemistry and neuroanatomical tracing to analyze neural differentiation, axonal sprouting, and microglia response. Treatment-induced changes in gene expression were investigated by microarray and quantitative polymerase chain reaction.Bioluminescence imaging permitted real time longitudinal tracking of grafted human neural stem cells. HI transplanted animals significantly improved in their use of the contralateral impeded forelimb and in the Rotorod test. The grafts showed good survival, dispersion, and differentiation. We observed an increase of uniformly distributed microglia cells in the grafted side. Anterograde neuroanatomical tracing demonstrated significant contralesional sprouting. Microarray analysis revealed upregulation of genes involved in neurogenesis, gliogenesis, and neurotrophic support.These results suggest that human neural stem cell transplants enhance endogenous brain repair through multiple modalities in response to HI.

  View details for DOI 10.1161/STROKEAHA.109.573691

  View details for Web of Science ID 000274799600019

  View details for PubMedID 20075340

• Bedside cerebral monitoring to predict neurodevelopmental outcomes NeoReviews Chock VY, Davis AS 2009; 10 (3): e121-e129
• Challenges of giant omphalocele: from fetal diagnosis to follow-up NeoReviews Davis AS, Blumenfeld Y, Rubesova E, Abrajano C, El-Sayed YY, Dutta S, Barth RA, Hintz SR 2008; 9 (8): e338-e347
• Gene therapy using SOD1 protects striatal neurons from experimental stroke NEUROSCIENCE LETTERS Davis, A. S., Zhao, H., Sun, G. H., Sapolsky, R. M., Steinberg, G. K. 2007; 411 (1): 32-36

  Abstract

  Reactive oxygen species contribute to neuronal death following cerebral ischemia. Prior studies using transgenic animals have demonstrated the neuroprotective effect of the antioxidant, copper/zinc superoxide dismutase (SOD1). In this study, we investigated whether SOD1 overexpression using gene therapy techniques in non-transgenic animals would increase neuronal survival. A neurotropic, herpes simplex virus-1 (HSV-1) vector containing the SOD1 gene was injected into the striatum either before or after transient focal cerebral ischemia. Striatal neuron survival at 2 days was improved by 52% when vector was delivered 12-15 h prior to ischemia and by 53% when vector delivery was delayed 2 h following ischemia. These data add to the growing literature, which suggests that an antioxidant approach, perhaps by employing gene therapy techniques, may be beneficial in the treatment of stroke.

  View details for DOI 10.1016/j.neulet.2006.08.089

  View details for Web of Science ID 000243153100007

  View details for PubMedID 17110031

  View details for PubMedCentralID PMC1716259