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Prolonged Ductal Patency in Preterm Infants: Does It Matter? The Journal of pediatrics Benitz, W. E., Chock, V. Y. 2020
View details for DOI 10.1016/j.jpeds.2020.10.059

View details for PubMedID 33130156
Theophylline dosing and pharmacokinetics for renal protection in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia. Pediatric research Frymoyer, A., Van Meurs, K. P., Drover, D. R., Klawitter, J., Christians, U., Chock, V. Y. 2020
Abstract

BACKGROUND: Theophylline, a non-selective adenosine receptor antagonist, improves renal perfusion in the setting of hypoxia-ischemia and may offer therapeutic benefit in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing hypothermia. We evaluated the pharmacokinetics and dose-exposure relationships of theophylline in this population to guide dosing strategies.METHODS: A population pharmacokinetic analysis was performed in 22 neonates with HIE undergoing hypothermia who were part of a prospective study or retrospective chart review. Aminophylline (intravenous salt form of theophylline) was given per institutional standard of care for low urine output and/or rising serum creatinine (5mg/kg intravenous (i.v.) load then 1.8mg/kg i.v. q6h). The ability of different dosing regimens to achieve target concentrations (4-10mg/L) associated with clinical response was examined.RESULTS: Birth weight was a significant predictor of theophylline clearance and volume of distribution (p<0.05). The median half-life was 39.5h (range 27.2-50.4). An aminophylline loading dose of 7mg/kg followed by 1.6mg/kg q12h was predicted to achieve target concentrations in 84% of simulated neonates.CONCLUSIONS: In neonates with HIE undergoing hypothermia, theophylline clearance was low with a 50% longer half-life compared to full-term normothermic neonates without HIE. Dosing strategies need to consider the unique pharmacokinetic needs of this population.IMPACT: Theophylline is a potential renal-protective therapy in neonates with HIE undergoing therapeutic hypothermia; however, the pharmacokinetics and dose needs in this population are not known.Theophylline clearance was low in neonates with HIE undergoing therapeutic hypothermia with a 50% longer half-life compared to full-term normothermic neonates without HIE.As theophylline is advanced in clinical development, dosing strategies will need to consider the unique pharmacokinetic needs of neonates with HIE undergoing therapeutic hypothermia.Fig. 1INDIVIDUAL PREDICTED THEOPHYLLINE CONCENTRATIONS IN NEONATES WITH HIE RECEIVING HYPOTHERMIA BASED ON THE FINAL PHARMACOKINETIC MODEL AS COMPARED TO THE OBSERVED MEASURED CONCENTRATIONS.: DBS dried blood samples measured as part of a prospective study, plasma samples measured as part of clinical care.Fig. 2Relationship between the average theophylline concentration over the first 24h of treatment (Cavg,24) and (a) change in urine output (?UOP) 24h after the start of treatment and (b) change in serum creatinine (?SCr) 48h after the start of treatment.Fig. 3Predicted theophylline concentration-time course after aminophylline using (a) dosing strategy used in clinical care during the study time period (loading dose 5mg/kg, followed by 1.8mg/kg every 6h) and (b) optimized dosing strategy (loading dose 7mg/kg, followed by 1.6mg/kg every 12h). Each dosing strategy was simulated in 3000 neonates using the final population pharmacokinetic model. Solid line represents the median and dashed lines represent the 10th and 90th percentile. Shaded area represents targeted concentration range of 4-10mg/L.

View details for DOI 10.1038/s41390-020-01140-8

View details for PubMedID 32919393
Aminophylline for renal protection in neonatal hypoxic-ischemic encephalopathy in the era of therapeutic hypothermia. Pediatric research Chock, V. Y., Cho, S., Frymoyer, A. 2020
Abstract

BACKGROUND: Neonates with hypoxic-ischemic encephalopathy (HIE) frequently develop acute kidney injury (AKI). Aminophylline has been shown to reduce severe renal dysfunction in neonates after perinatal asphyxia. However, the effect of aminophylline on renal function in neonates undergoing hypothermia has not been studied.METHODS: A single-center, retrospective chart review of neonates cooled for moderate/severe HIE who received aminophylline for AKI was conducted to assess changes in urine output (UOP) and serum creatinine (SCr). Comparisons were also made to control neonates matched for hours of life who were cooled but unexposed to aminophylline.RESULTS: Sixteen neonates cooled for HIE received aminophylline starting at 25�14h of life. Within 12h of starting aminophylline, UOP increased by 2.6�1.9mL/kg/h. SCr declined by 0.4�0.2mg/dL in survivors over the first 4 days. When compared to control neonates, UOP increase was greater in the aminophylline group (p<0.001). SCr declined in survivors in both groups, although baseline SCr was higher in the aminophylline group.CONCLUSIONS: Aminophylline use in neonates with HIE undergoing hypothermia was associated with an increase in UOP and a decline in SCr. A randomized trial will be needed to establish a potential renal protective role of aminophylline.IMPACT: The renal protective effect of aminophylline in neonates with HIE has not yet been studied in the context of therapeutic hypothermia.Aminophylline exposure in neonates cooled for HIE was associated with increased UOP and a similar decline in SCr when compared to control infants unexposed to aminophylline.Improved renal function after receiving aminophylline in this observational cohort study suggests the need for future randomized trials to establish the potential benefit of aminophylline in the HIE population undergoing hypothermia.

View details for DOI 10.1038/s41390-020-0999-y

View details for PubMedID 32503030
NIRS improves hemodynamic monitoring and detection of risk for cerebral injury: cases in the neonatal intensive care nursery JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Chock, V. Y., Variane, G. T., Netto, A., Van Meurs, K. P. 2020; 33 (10): 1802?10
View details for DOI 10.1080/14767058.2018.1528223

View details for Web of Science ID 000519294200026
Behavior Profiles at 2Years for Children Born Extremely PretermwithBronchopulmonary Dysplasia. The Journal of pediatrics Brumbaugh, J. E., Bell, E. F., Grey, S. F., DeMauro, S. B., Vohr, B. R., Harmon, H. M., Bann, C. M., Rysavy, M. A., Logan, J. W., Colaizy, T. T., Peralta-Carcelen, M. A., McGowan, E. C., Duncan, A. F., Stoll, B. J., Das, A., Hintz, S. R., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, Caplan, M. S., Polin, R. A., Laptook, A. R., Keszler, M., Hensman, A. M., Vieira, E., Little, E., Burke, R. T., Stephens, B. E., Alksninis, B., Bishop, C., Keszler, M. L., Leach, T. M., Watson, V. E., Knoll, A. M., Walsh, M. C., Fanaroff, A. A., Newman, N. S., Wilson-Costello, D. E., Payne, A., Bhola, M., Yalcinkaya, G., Siner, B. S., Friedman, H. G., Roth, E., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Schibler, K., Poindexter, B. B., Merhar, S., Yolton, K., Gratton, T. L., Grisby, C., Kirker, K., Wuertz, S., Carlton, D. P., Adams-Chapman, I., Hale, E. C., Loggins, Y. C., Bottcher, D. I., Mackie, C., Carter, S. L., LaRossa, M. M., Wineski, L. C., Smikle, G. V., Leon-Hernandez, A., Kendrick-Allwood, S., Cotten, C. M., Goldberg, R. N., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Finkle, J., Fisher, K. A., Grimes, S., Gustafson, K. E., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Warner, D., Wereszczak, J., Kicklighter, S. D., Rhodes-Ryan, G., Higgins, R. D., Wilson Archer, S., Poindexter, B. B., Sokol, G. M., Papile, L. A., Hines, A. C., Herron, D. E., Gunn, S., Smiley, L., Kennedy, K. A., Tyson, J. E., Arldt-McAlister, J., Burson, K., Dempsey, A. G., Evans, P. W., Garcia, C., Jiminez, M., John, J., Jones, P. M., Lillie, M. L., Martin, K., Martin, S. C., McDavid, G. E., Rodgers, S., Siddiki, S. K., Sperry, D., Pierce Tate, P. L., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Wallace, D., Gantz, M. G., Newman, J. E., Auman, J. O., Crawford, M., Gabrio, J., Leblond, D., Petrie Huitema, C. M., Zaterka-Baxter, K. M., Van Meurs, K. P., Chock, V. Y., Stevenson, D. K., Adams, M. M., Ball, M. B., Bentley, B., DeAnda, M. E., Debattista, A. M., Earhart, B., Huffman, L. C., Ismael, M., Krueger, C. E., Palmquist, A. W., Proud, M. S., Reichert, E. N., Sankar, M. N., St John, N. H., Taylor, H. L., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Nylen, E., Furey, A., Sibley, C. E., Brussa, A. K., Carlo, W. A., Ambalavanan, N., Bailey, K. J., Biasini, F. J., Collins, M. V., Cosby, S. S., Phillips, V. A., Rector, R. V., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Rich, W., West, R., Baack, M. L., Ellsbury, D. L., Hogden, L. A., Klein, J. M., Dagle, J. M., Johnson, K. J., Tud, T. L., Elenkiwich, C., Henning, M. M., Broadbent, M., Schmelzel, M. L., Walker, J. R., Goeke, C. A., Baack, M. L., Ellsbury, D. L., Hogden, L. A., Klein, J. M., Dagle, J. M., Johnson, K. J., Tud, T. L., Elenkiwich, C., Henning, M. M., Broadbent, M., Schmelzel, M. L., Walker, J. R., Goeke, C. A., Watterberg, K. L., Ohls, R. K., Backstrom Lacy, C., Brown, S., Fuller, J., Hartenberger, C., Lowe, J. R., Sundquist Beauman, S., Hanson, M. R., Dupont, T., Kuan, E., Schmidt, B., Kirpalani, H., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., D'Angio, C. T., Guillet, R., Myers, G. J., Lakshminrusimha, S., Reynolds, A. M., Hartley-McAndrew, M. E., Wadkins, H. I., Sacilowski, M. G., Reubens, L. J., Jensen, R. L., Merzbach, J., Zorn, W., Farooq, O., Maffett, D., Williams, A., Hunn, J., Guilford, S., Yost, K., Rowan, M., Prinzing, D. M., Wynn, K., Fallone, C., Scorsone, A. M., Wyckoff, M. H., Sanchez, P. J., Brion, L. P., Heyne, R. J., Vasil, D. M., Adams, S. S., Chen, L., De Leon, M. M., Eubanks, F., Guzman, A., Heyne, E. T., Madden, L. A., Miller, N. A., Lee, L. E., Pavageau, L., Sepulveda, P., Boatman, C. T., Faix, R. G., Yoder, B. A., Baserga, M., Osborne, K. A., Baker, S., Bird, K., Burnett, J., Christensen, S., Davis, B., Elmont, J. O., Jensen, J. J., Loertscher, M. C., Marchant, T., Maxson, E., Minton, S. D., Parry, D. M., Rau, C. A., Schaefer, S. T., Sheffield, M. J., Spencer, C., Steffen, M., Weaver-Lewis, K., Winter, S., Woodbury, K. D., Zanetti, K., Shankaran, S., Chawla, S., Sood, B. G., Pappas, A., Natarajan, G., Bajaj, M., Bara, R., Johnson, M. E., Goldston, L., Wiggins, S. A., Christensen, M. K., Carlson, M., Barks, J., White, D. F., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Romano, E. 2020
Abstract

OBJECTIVE: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).STUDY DESIGN: We studied children born at 22-26weeks of gestation and assessed at 22-26months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36weeks of postmenstrual age. CBCL syndrome scales were the primary outcomes. The relationship between BPD grade and behavior was evaluated, adjusting for perinatal confounders. Mediation analysis was performed to evaluate whether cognitive, language, or motor skills mediated the effect of BPD grade on behavior.RESULTS: Of 2310 children, 1208 (52%) had no BPD, 806 (35%) had grade 1 BPD, 177 (8%) had grade 2 BPD, and 119 (5%) had grade 3 BPD. Withdrawn behavior (P<.001) and pervasive developmental problems (P<.001) increased with worsening BPD grade. Sleep problems (P=.008) and aggressive behavior (P=.023) decreased with worsening BPD grade. Children with grade 3 BPD scored 2 points worse for withdrawn behavior and pervasive developmental problems and 2 points better for externalizing problems, sleep problems, and aggressive behavior than children without BPD. Cognitive, language, and motor skills mediated the effect of BPD grade on the attention problems, emotionally reactive, somatic complaints, and withdrawn CBCL syndrome scales (P values<.05).CONCLUSIONS: BPD grade was associated with increased risk of withdrawn behavior and pervasive developmental problems but with decreased risk of sleep problems and aggressive behavior. The relationship between BPD and behavior is complex. Cognitive, language, and motor skills mediate the effects of BPD grade on some problem behaviors.

View details for DOI 10.1016/j.jpeds.2019.12.028

View details for PubMedID 32008764
Simultaneous Near-Infrared Spectroscopy (NIRS) and Amplitude-Integrated Electroencephalography (aEEG): Dual Use of Brain Monitoring Techniques Improves Our Understanding of Physiology FRONTIERS IN PEDIATRICS Variane, G., Chock, V. Y., Netto, A., Pietrobom, R., Van Meurs, K. 2020; 7: 560
Abstract

Continuous brain monitoring tools are increasingly being used in the neonatal intensive care unit (NICU) to assess brain function and cerebral oxygenation in neonates at high risk for brain injury. Near infrared spectroscopy (NIRS) is useful in critically ill neonates as a trend monitor to evaluate the balance between tissue oxygen delivery and consumption, providing cerebral and somatic oximetry values, and allowing earlier identification of abnormalities in hemodynamics and cerebral perfusion. Amplitude-integrated electroencephalography (aEEG) is a method for continuous monitoring of cerebral function at the bedside. Simultaneous use of both monitoring modalities may improve the understanding of alterations in hemodynamics and risk of cerebral injury. Several studies have described correlations between aEEG and NIRS monitoring, especially in infants with hypoxic-ischemic encephalopathy (HIE), but few describe the combined use of both monitoring techniques in a wider range of clinical scenarios. We review the use of NIRS and aEEG in neonates and describe four cases where abnormal NIRS values were immediately followed by changes in brain activity as seen on aEEG allowing the impact of a hemodynamic disturbance on the brain to be correlated with the changes in the aEEG background pattern. These four clinical scenarios demonstrate how simultaneous neuromonitoring with aEEG and NIRS provides important clinical information. We speculate that routine use of these combined monitoring modalities may become the future standard for neonatal neuromonitoring.

View details for DOI 10.3389/fped.2019.00560

View details for Web of Science ID 000510920400001

View details for PubMedID 32039117

View details for PubMedCentralID PMC6985148
Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants. The New England journal of medicine Kirpalani, H., Bell, E. F., Hintz, S. R., Tan, S., Schmidt, B., Chaudhary, A. S., Johnson, K. J., Crawford, M. M., Newman, J. E., Vohr, B. R., Carlo, W. A., D'Angio, C. T., Kennedy, K. A., Ohls, R. K., Poindexter, B. B., Schibler, K., Whyte, R. K., Widness, J. A., Zupancic, J. A., Wyckoff, M. H., Truog, W. E., Walsh, M. C., Chock, V. Y., Laptook, A. R., Sokol, G. M., Yoder, B. A., Patel, R. M., Cotten, C. M., Carmen, M. F., Devaskar, U., Chawla, S., Seabrook, R., Higgins, R. D., Das, A. 2020; 383 (27): 2639?51
Abstract

Limited data suggest that higher hemoglobin thresholds for red-cell transfusions may reduce the risk of cognitive delay among extremely-low-birth-weight infants with anemia.We performed an open, multicenter trial in which infants with a birth weight of 1000 g or less and a gestational age between 22 weeks 0 days and 28 weeks 6 days were randomly assigned within 48 hours after delivery to receive red-cell transfusions at higher or lower hemoglobin thresholds until 36 weeks of postmenstrual age or discharge, whichever occurred first. The primary outcome was a composite of death or neurodevelopmental impairment (cognitive delay, cerebral palsy, or hearing or vision loss) at 22 to 26 months of age, corrected for prematurity.A total of 1824 infants (mean birth weight, 756 g; mean gestational age, 25.9 weeks) underwent randomization. There was a between-group difference of 1.9 g per deciliter (19 g per liter) in the pretransfusion mean hemoglobin levels throughout the treatment period. Primary outcome data were available for 1692 infants (92.8%). Of 845 infants in the higher-threshold group, 423 (50.1%) died or survived with neurodevelopmental impairment, as compared with 422 of 847 infants (49.8%) in the lower-threshold group (relative risk adjusted for birth-weight stratum and center, 1.00; 95% confidence interval [CI], 0.92 to 1.10; P?=?0.93). At 2 years, the higher- and lower-threshold groups had similar incidences of death (16.2% and 15.0%, respectively) and neurodevelopmental impairment (39.6% and 40.3%, respectively). At discharge from the hospital, the incidences of survival without severe complications were 28.5% and 30.9%, respectively. Serious adverse events occurred in 22.7% and 21.7%, respectively.In extremely-low-birth-weight infants, a higher hemoglobin threshold for red-cell transfusion did not improve survival without neurodevelopmental impairment at 22 to 26 months of age, corrected for prematurity. (Funded by the National Heart, Lung, and Blood Institute and others; TOP ClinicalTrials.gov number, NCT01702805.).

View details for DOI 10.1056/NEJMoa2020248

View details for PubMedID 33382931
Cerebral Oxygenation and Autoregulation in Preterm Infants (Early NIRS Study). The Journal of pediatrics Chock, V. Y., Kwon, S. H., Ambalavanan, N., Batton, B., Nelin, L. D., Chalak, L. F., Tian, L., Van Meurs, K. P. 2020
Abstract

To determine if decreased cerebral oxygenation or altered cerebral autoregulation as measured by near-infrared spectroscopy (NIRS) in the first 96 postnatal hours is associated with an increased risk of death or severe neuroradiographic abnormalities in very preterm infants.The Early NIRS prospective, multi-center study enrolled very preterm infants with birth weight <1250 g from 6 tertiary neonatal intensive care units. Mean arterial blood pressure (MAP) and cerebral oxygen saturation (Csat) were continuously monitored using a neonatal sensor until 96 hours of age. Moving window correlations between Csat and MAP determined time periods with altered cerebral autoregulation, and percentiles of correlation were compared between infants with and without the adverse outcome of mortality or severe neuroradiographic abnormalities by early cranial ultrasound.Of 103 subjects with mean gestational age of 26 weeks, 21 (20%) died or had severe neuroradiographic abnormalities. Infants with adverse outcomes had a lower mean Csat (67 � 9%) compared with those without adverse outcomes (72 � 7%, P = .02). Csat <50% was identified as a cut-point for identifying infants with adverse outcome (AUC =0.76). Infants with adverse outcomes were more likely to have significant positive or negative correlations between Csat and MAP, indicating impaired cerebral autoregulation (p=0.006).Early NIRS monitoring may detect periods of lower cerebral oxygenation and altered cerebral autoregulation, identifying preterm infants at risk for mortality or neuroradiographic injury. Improved understanding of the relationship between altered hemodynamics and cerebral oxygenation may inform future strategies to prevent brain injury.

View details for DOI 10.1016/j.jpeds.2020.08.036

View details for PubMedID 32818482
Renal Tissue Oxygenation Monitoring-An Opportunity to Improve Kidney Outcomes in the Vulnerable Neonatal Population. Frontiers in pediatrics Harer, M. W., Chock, V. Y. 2020; 8: 241
Abstract

Adequate oxygenation of the kidney is of critical importance in the neonate. Non-invasive monitoring of renal tissue oxygenation using near-infrared spectroscopy (NIRS) is a promising bedside strategy for early detection of circulatory impairment as well as recognition of specific renal injury. As a diagnostic tool, renal NIRS monitoring may allow for earlier interventions to prevent or reduce injury in various clinical scenarios in the neonatal intensive care unit. Multiple studies utilizing NIRS monitoring in preterm and term infants have provided renal tissue oxygenation values at different time points during neonatal hospitalization, and have correlated measures with ultrasound and Doppler flow data. With the establishment of normal values, studies have utilized renal tissue oxygenation monitoring in preterm neonates to predict a hemodynamically significant patent ductus arteriosus, to assess response to potentially nephrotoxic medications, to identify infants with sepsis, and to describe changes after red blood cell transfusions. Other neonatal populations being investigated with renal NIRS monitoring include growth restricted infants, those requiring delivery room resuscitation, infants with congenital heart disease, and neonates undergoing extracorporeal membrane oxygenation. Furthermore, as the recognition of acute kidney injury (AKI) and its associated morbidity and mortality in neonates has increased over the last decade, alternative methods are being investigated to diagnose AKI before changes in serum creatinine or urine output occur. Studies have utilized renal NIRS monitoring to diagnose AKI in specific populations, including neonates with hypoxic ischemic encephalopathy after birth asphyxia and in infants after cardiac bypass surgery. The use of renal tissue oxygenation monitoring to improve renal outcomes has yet to be established, but results of studies published to date suggest that it holds significant promise to function as a real time, early indicator of poor renal perfusion that may help with development of specific treatment protocols to prevent or decrease the severity of AKI.

View details for DOI 10.3389/fped.2020.00241

View details for PubMedID 32528917

View details for PubMedCentralID PMC7247835
Influence of enteral feeding and anemia on tissue oxygen extraction after red blood cell transfusion in preterm infants. Transfusion Goldstein, G. P., Rao, A., Ling, A. Y., Ding, V. Y., Chang, I. J., Chock, V. Y. 2020
Abstract

Understanding factors that impact tissue oxygen extraction may guide red blood cell (RBC) transfusion decision making in preterm infants. Our objective was to assess the influence of enteral feeding and anemia on cerebral and mesenteric oxygen saturation (Csat and Msat) and fractional tissue oxygen extraction (cFTOE and mFTOE) over the entire time course of RBC transfusion.Preterm, very low-birth-weight infants receiving RBC transfusions at a single center were enrolled. Near-infrared spectroscopy sensors measured Csat and Msat levels from an hour before transfusion to 24?hours after. During this period, changes in Csat, Msat, cFTOE, and mFTOE were described, and their association with enteral feeding status and pretransfusion degree of anemia were assessed using generalized estimating equations.RBC transfusion data from 31 preterm infants were included. Infants receiving enteral feeds exhibited lower pretransfusion Msat. Infants with pretransfusion hematocrit greater than 30% exhibited higher pretransfusion Csat and lower pretransfusion cFTOE. Such differences in baseline measurements persisted through 24?hours after transfusion. However, no statistically significant differences in oxygenation measures over time by enteral feeding or anemia status were identified.Compared to NPO, enteral feeding was associated with lower Msat; anemia (hematocrit ?30%) was associated with lower Csat and higher cFTOE. Over the time course of RBC transfusion, trajectories of Csat, Msat, cFTOE and mFTOE did not differ by enteral feeding or anemia status.

View details for DOI 10.1111/trf.15680

View details for PubMedID 31984520
Intraventricular hemorrhage and white matter injury: is persistent cerebral desaturation a missing link? Pediatric research Chawla, S., Chock, V. Y., Lakshminrusimha, S. 2020
View details for DOI 10.1038/s41390-020-01294-5

View details for PubMedID 33247218
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
Differences in patient characteristics and care practices between two trials of therapeutic hypothermia PEDIATRIC RESEARCH Bonifacio, S. L., McDonald, S. A., Chock, V. Y., Wusthoff, C. J., Hintz, S. R., Laptook, A. R., Shankara, S., Van Meurs, K. P. 2019; 85 (7): 1008?15
View details for DOI 10.1038/s41390-019-0371-2

View details for Web of Science ID 000468524800020
Near-Infrared Spectroscopy in the Diagnostic Evaluation of Mitochondrial Disorders: A Neonatal Intensive Care Unit Case Series JOURNAL OF PEDIATRICS Niemi, A., Chock, V. Y. 2019; 208: 282?86
View details for DOI 10.1016/j.jpeds.2019.01.022

View details for Web of Science ID 000465236700050
Differences in patient characteristics and care practices between two trials of therapeutic hypothermia. Pediatric research Bonifacio, S. L., McDonald, S. A., Chock, V. Y., Wusthoff, C. J., Hintz, S. R., Laptook, A. R., Shankara, S., Van Meurs, K. P. 2019
Abstract

BACKGROUND: The Induced Hypothermia (IH) and Optimizing Cooling (OC) trials for hypoxic-ischemic encephalopathy (HIE) had similar inclusion criteria. The rate of death/moderate-severe disability differed for the subgroups treated with therapeutic hypothermia (TH) at 33.5�C for 72h (44% vs. 29%, unadjusted p=0.03). We aimed to evaluate differences in patient characteristics and care practices between the trials.METHODS: We compared pre/post-randomization characteristics and care practices between IH and OC.RESULTS: There were 208 patients in the IH trial, 102 cooled, and 364 in the OC trial, 95 cooled to 33.5�C for 72h. In OC, neonates were less ill, fewer had severe HIE, and the majority were cooled prior to randomization. Differences between IH and OC were observed in the adjusted difference in the lowest PCO2 (+3.08mmHg, p=0.005) and highest PO2 (-82.7mmHg, p<0.001). In OC, compared to IH, the adjusted relative risk (RR) of exposure to anticonvulsant prior to randomization was decreased (RR 0.58, (0.40-0.85), p=0.005) and there was increased risk of exposure during cooling to sedatives/analgesia (RR 1.86 (1.21-2.86), p=0.005).CONCLUSION: Despite similar inclusion criteria, there were differences in patient characteristics and care practices between trials. Change in care practices over time should be considered when planning future neuroprotective trials.

View details for PubMedID 30862961
Near-Infrared Spectroscopy in the Diagnostic Evaluation of Mitochondrial Disorders: A Neonatal Intensive Care Unit Case Series. The Journal of pediatrics Niemi, A., Chock, V. Y. 2019
Abstract

We assessed the utility of near-infrared spectroscopy to evaluate neonates with mitochondrial disorders. We observed abnormally high cerebral oxygen saturation levels indicating insufficient tissue oxygen utilization. We propose that near-infrared spectroscopy may be an additional tool in the diagnostic evaluation of a suspected mitochondrial disorder.

View details for PubMedID 30853194
Birth Location of Infants with Critical Congenital Heart Disease in California PEDIATRIC CARDIOLOGY Purkey, N. J., Axelrod, D. M., McElhinney, D. B., Rigdon, J., Qin, F., Desai, M., Shin, A. Y., Chock, V. Y., Lee, H. C. 2019; 40 (2): 310?18
View details for DOI 10.1007/s00246-018-2019-0

View details for Web of Science ID 000460553100007
Immediate Postnatal Ventricular Performance Is Associated with Mortality in Hypoplastic Left Heart Syndrome PEDIATRIC CARDIOLOGY Altit, G., Bhombal, S., Chock, V. Y., Tacy, T. A. 2019; 40 (1): 168?76
View details for DOI 10.1007/s00246-018-1974-9

View details for Web of Science ID 000456807300022
Birth Location of Infants with Critical Congenital Heart Disease in California. Pediatric cardiology Purkey, N. J., Axelrod, D. M., McElhinney, D. B., Rigdon, J., Qin, F., Desai, M., Shin, A. Y., Chock, V. Y., Lee, H. C. 2018
Abstract

The American Academy of Pediatrics classifies neonatal intensive care units (NICUs) from level I to IV based on the acuity of care each unit can provide. Birth in a higher level center is associated with lower morbidity and mortality in high-risk populations. Congenital heart disease accounts for 25-50% of infant mortality related to birth defects in the U.S., but recent data are lacking on where infants with critical congenital heart disease (CCHD) are born. We used a linked dataset from the Office of Statewide Health Planning and Development to access ICD-9 diagnosis codes for all infants born in California from 2008 to 2012. We compared infants with CCHD to the general population, identified where infants with CCHD were born based on NICU level of care, and predicted level IV birth among infants with CCHD using logistic regression techniques. From 2008 to 2012, 6325 infants with CCHD were born in California, with 23.7% of infants with CCHD born at a level IV NICU compared to 8.4% of the general population. Level IV birth for infants with CCHD was associated with lower gestational age, higher maternal age and education, the presence of other congenital anomalies, and the diagnosis of a single ventricle lesion. More infants with CCHD are born in a level IV NICU compared to the general population. Future studies are needed to determine if birth in a lower level of care center impacts outcomes for infants with CCHD.

View details for PubMedID 30415381
Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly JOURNAL OF PERINATOLOGY 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; 38 (11): 1444?52
View details for DOI 10.1038/s41372-018-0208-6

View details for Web of Science ID 000449174800002
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; 35 (12): 1197?1205
View details for DOI 10.1055/s-0038-1646954

View details for Web of Science ID 000445491700012
NIRS improves hemodynamic monitoring and detection of risk for cerebral injury: cases in the neonatal intensive care nursery. 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 Chock, V. Y., Variane, G. F., Netto, A., Van Meurs, K. P. 2018: 1?191
Abstract

Near-infrared spectroscopy (NIRS) monitoring provides a noninvasive, bedside measure of cerebral and somatic oxygenation in neonates at risk for hemodynamic instability and brain injury. This technology has been increasingly utilized in the neonatal intensive care unit, however clinicians perceive a lack of evidence for the added value of NIRS monitoring. We present six clinical scenarios illustrating the value of NIRS monitoring for the diagnosis and management of critically ill newborns.

View details for PubMedID 30244630
Immediate Postnatal Ventricular Performance Is Associated with Mortality in Hypoplastic Left Heart Syndrome. Pediatric cardiology Altit, G., Bhombal, S., Chock, V. Y., Tacy, T. A. 2018
Abstract

Right ventricular (RV) function as assessed by deformation has been evaluated prenatally and after palliation in hypoplastic left heart syndrome (HLHS). However, limited data exist about the immediate postnatal cardiac adaptation and RV function in HLHS. We compared echocardiographic measures of cardiac performance in HLHS versus controls in their first week of life. As a secondary objective, we evaluated if markers at the first echocardiogram were associated with mid- and long-term outcomes. Clinical and echocardiographic data of patients with HLHS between 2013 and 2016 were reviewed. The study population was matched with controls whose echocardiograms were obtained due to murmur or rule out coarctation. Speckle-tracking echocardiography was used to assess deformation. Thirty-four patients with HLHS and 28 controls were analyzed. Age at echocardiogram was similar between HLHS and controls. The RV of HLHS was compared to both RV and left ventricle (LV) of controls. HLHS deformation parameters [RV peak global longitudinal strain (GLS), global longitudinal strain rate (GLSR)] and tricuspid annular plane systolic excursion (TAPSE) were decreased compared to RV of controls. The LV-fractional area change, peak GLS, GLSR, circumferential strain, and strain rate of controls were higher than the RV of HLHS. Calculated cardiac output (CO) was higher in the HLHS group (592 vs. 183mL/kg/min, p=0.0001) but similar to the combined LV and RV output of controls. Later mortality or cardiac transplantation was associated with the RV CO and RV stroke distance at initial echocardiogram. Cox proportional hazard regression determined that restriction at atrial septum, decreased initial RV stroke distance and decreased TAPSE had a higher risk of death or cardiac transplantation. TAPSE and RV stroke distance by velocity time integral had adequate inter-reader variability by Bland-Altman plot and Pearson's correlation. Our study found that the HLHS RV deformation is decreased in the early postnatal period when compared to both LV and RV of controls, but deformation was not associated with mid- and long-term outcomes. Later mortality or cardiac transplantation was associated with decreased initial stroke distance and cardiac output. Early evaluation of patients with HLHS should include an assessment of stroke distance and future research should evaluate its implication in management strategies.

View details for PubMedID 30178190
Renal Saturation and Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia JOURNAL OF PEDIATRICS Chock, V. Y., Frymoyer, A., Yeh, C. G., Van Meurs, K. P. 2018; 200: 232-+
View details for DOI 10.1016/j.jpeds.2018.04.076

View details for Web of Science ID 000442390400038
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
Renal Saturation and Acute Kidney Injury in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia. The Journal of pediatrics Chock, V. Y., Frymoyer, A., Yeh, C. G., Van Meurs, K. P. 2018
Abstract

OBJECTIVE: To investigate the range of renal near-infrared spectroscopy (NIRS) measures in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) and to determine the association between renal NIRS measures and the development of acute kidney injury (AKI).STUDY DESIGN: A retrospective chart review was conducted of neonates with moderate to severe HIE who received therapeutic hypothermia at a tertiary care center from 2014 to 2016. Neonates had routine continuous NIRS monitoring of cerebral and renal saturation (Rsat) as part of their clinical care for 72hours of cooling and until 24hours after rewarming. The outcome of AKI was defined by an abnormal rate of decline of serum creatinine over the first 5 days of life. Mixed effects models determined the association between renal NIRS measures and AKI over time.RESULTS: Of 38 neonates with HIE undergoing cooling, 15 (39%) developed AKI. Rsat was lower than cerebral saturation during cooling (P<.01), but Rsat increased over time after rewarming, while renal oxygen extraction levels decreased (P<.0001). Neonates with AKI had higher Rsat levels (P<.01) compared with those without AKI after 24hours of life. Using receiver operating characteristic curves, Rsat >75% by 24-48hours predicted AKI with a sensitivity of 79% and specificity of 82% (area under the receiver operating characteristic curve=0.76).CONCLUSIONS: Throughout cooling, neonates with AKI had higher Rsat measures than those without AKI. These differences may reflect lower oxygen extraction by the injured kidney. NIRS monitoring of Rsat may identify neonates with HIE at risk of developing AKI.

View details for PubMedID 29866591
Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease JOURNAL OF PERINATOLOGY Balasundaram, M., Chock, V. Y., Wu, H., Blumenfeld, Y. J., Hintz, S. R. 2018; 38 (6): 658?64
View details for DOI 10.1038/s41372-018-0093-z

View details for Web of Science ID 000437240700009
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
Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease. Journal of perinatology : official journal of the California Perinatal Association Balasundaram, M., Chock, V. Y., Wu, H. Y., Blumenfeld, Y. J., Hintz, S. R. 2018
Abstract

OBJECTIVE: Multicystic dysplastic kidney (MCDK) is one of the most common anomalies detected by prenatal ultrasound. Our objective was to identify factors associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK STUDY DESIGN: A retrospective review of prenatally diagnosed MCDK (1 January 2009 to 30 December 2014) from a single academic center was conducted. The primary outcome was death or need for dialysis among live-born infants. Associations between prenatal characteristics and outcome were analyzed by Fisher's exact test and Mann-Whitney test.RESULTS: A total of 53 cases of prenatally suspected MCDK were included, of which 46 cases were live-born and confirmed postnatally (38 survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral MCDK, contralateral renal anomalies, and anhydramnios were significantly associated with death or need for dialysis (all p<0.0001).CONCLUSIONS: Prenatally identified findings are associated with adverse neonatal outcome, and can guide counseling and management planning. In the absence of significant associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal course.

View details for PubMedID 29572458
End-Organ Saturation Differences in Early Neonatal Transition for Left-versus Right-Sided Congenital Heart Disease NEONATOLOGY Altit, G., Bhombal, S., Tacy, T. A., Chock, V. Y. 2018; 114 (1): 53?61
Abstract

For neonates with congenital heart disease (CHD), left-sided (LL) and right-sided (RL) single ventricular physiologies (LL, hypoplastic left heart syndrome; RL, tricuspid atresia or pulmonary atresia with intact ventricular septum) may demonstrate distinct changes in tissue saturation in the first 72 h of life. Near-infrared spectroscopy (NIRS) can measure regional cerebral saturation (Csat) and renal saturation (Rsat) to clarify differences between LL and RL over time.Our primary objective was to measure changes in Csat and Rsat in the first 72 h of life using NIRS between CHD infants with LL compared to RL. The secondary objective was to correlate NIRS values to an echocardiographic marker of perfusion.Newborns with hypoplastic left heart syndrome, tricuspid atresia, and pulmonary atresia with intact ventricular septum from 2013 to 2016 underwent routine NIRS monitoring. Csat, Rsat, and systemic saturations (SpO2) in the first 72 h of life were retrospectively analyzed and the echocardiographic descending aorta velocity time integral (VTI) was measured. Mixed effects models compared differences over time between LL and RL.The final cohort included 13 LL, 12 RL, and 4 controls. Csat decreased for RL compared to LL (p = 0.005), while Rsat decreased for both (p = 0.008). Over time, SpO2 increased for LL but decreased for RL (p = 0.046). Compared to the controls, infants with CHD had lower Csat, lower Rsat, and lower SpO2. The descending aorta VTI was correlated with Rsat (R2 = 0.24, p = 0.02).NIRS Csat measures were better preserved in LL compared to RL. Rsat decreased in both groups through time. The correlation between the descending aorta VTI and Rsat suggests an association between NIRS measures of renal saturation and renal perfusion.

View details for PubMedID 29649824
Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy A Randomized Clinical Trial JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Laptook, A. R., Shankaran, S., Tyson, J. E., Munoz, B., Bell, E. F., Goldberg, R. N., Parikh, N. A., Ambalavanan, N., Pedroza, C., Pappas, A., Das, A., Chaudhary, A. S., Ehrenkranz, R. A., Hensman, A. M., Van Meurs, K. P., Chalak, L. F., Hamrick, S. G., Sokol, G. M., Walsh, M. C., Poindexter, B. B., Faix, R. G., Watterberg, K. L., Frantz, I. D., Guillet, R., Devaskar, U., Truog, W. E., Chock, V. Y., Wyckoff, M. H., McGowan, E. C., Carlton, D. P., Harmon, H. M., Brumbaugh, J. E., Cotten, C., Sanchez, P. J., Hibbs, A., Higgins, R. D., Eunice Kennedy Shriver Natl Instit, Human Development Neonatal Res Net 2017; 318 (16): 1550?60
Abstract

Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours.To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy.A randomized clinical trial was conducted between April 2008 and June 2016 among infants at 36 weeks' or later gestation with moderate or severe hypoxic-ischemic encephalopathy enrolled at 6 to 24 hours after birth. Twenty-one US Neonatal Research Network centers participated. Bayesian analyses were prespecified given the anticipated limited sample size.Targeted esophageal temperature was used in 168 infants. Eighty-three hypothermic infants were maintained at 33.5�C (acceptable range, 33�C-34�C) for 96 hours and then rewarmed. Eighty-five noncooled infants were maintained at 37.0�C (acceptable range, 36.5�C-37.3�C).The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization.Hypothermic and noncooled infants were term (mean [SD], 39 [2] and 39 [1] weeks' gestation, respectively), and 47 of 83 (57%) and 55 of 85 (65%) were male, respectively. Both groups were acidemic at birth, predominantly transferred to the treating center with moderate encephalopathy, and were randomized at a mean (SD) of 16 (5) and 15 (5) hours for hypothermic and noncooled groups, respectively. The primary outcome occurred in 19 of 78 hypothermic infants (24.4%) and 22 of 79 noncooled infants (27.9%) (absolute difference, 3.5%; 95% CI, -1% to 17%). Bayesian analysis using a neutral prior indicated a 76% posterior probability of reduced death or disability with hypothermia relative to the noncooled group (adjusted posterior risk ratio, 0.86; 95% credible interval, 0.58-1.29). The probability that death or disability in cooled infants was at least 1%, 2%, or 3% less than noncooled infants was 71%, 64%, and 56%, respectively.Among term infants with hypoxic-ischemic encephalopathy, hypothermia initiated at 6 to 24 hours after birth compared with noncooling resulted in a 76% probability of any reduction in death or disability, and a 64% probability of at least 2% less death or disability at 18 to 22 months. Hypothermia initiated at 6 to 24 hours after birth may have benefit but there is uncertainty in its effectiveness.clinicaltrials.gov Identifier: NCT00614744.

View details for PubMedID 29067428

View details for PubMedCentralID PMC5783566
Changing Management of the Patent Ductus Arteriosus: Effect on Neonatal Outcomes and Resource Utilization. American journal of perinatology Chock, V. Y., Goel, V. V., Palma, J. P., Luh, T. M., Wang, N. A., Gaskari, S., Punn, R., Silverman, N. H., Benitz, W. E. 2017
Abstract

Objective?This historical cohort study investigated how a shift toward a more conservative approach of awaiting spontaneous closure of the patent ductus arteriosus (PDA) in preterm infants has affected neonatal outcomes and resource utilization. Methods?We retrospectively studied very low birth weight infants diagnosed with a PDA by echocardiogram (ECHO) in 2006-2008 (era 1), when medical or surgical PDA management was emphasized, to those born in 2010-2012 (era 2) when conservative PDA management was encouraged. Multiple regression analyses adjusted for gestational age were performed to assess differences in clinical outcomes and resource utilization between eras. Results?More infants in era 2 (35/89, 39%) compared with era 1 (22/120, 18%) had conservative PDA management (p?
View details for DOI 10.1055/s-0037-1601442

View details for PubMedID 28376547
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
Near-infrared spectroscopy for detection of a significant patent ductus arteriosus. Pediatric research Chock, V. Y., Rose, L. A., Mante, J. V., Punn, R. 2016; 80 (5): 675-680
Abstract

Near-infrared spectroscopy (NIRS) may assist with characterization of a hemodynamically significant patent ductus arteriosus (hsPDA) by measuring cerebral and renal saturation (Csat and Rsat) levels. We hypothesized that Csat and Rsat in preterm infants with an hsPDA would be decreased compared to those with no PDA or nonsignificant PDA.This non a-priori designed study retrospectively investigated clinical and ECHO characteristics of preterm infants <29?wk gestation who underwent routine NIRS monitoring. Logistic regression assessed association between NIRS measures and an hsPDA by ECHO.Of 47 infants, 21 had a confirmed hsPDA by ECHO, 14 had a nonsignificant PDA, and 12 had no ECHO performed due to low clinical suspicion for PDA. Logistic regression adjusted for gestational age found that lower Rsat was associated with an hsPDA by ECHO (OR 0.9, 95% CI 0.83-0.98, P = 0.01). Using ROC curves, Rsat < 66% identified an hsPDA with a sensitivity of 81% and specificity of 77%, while Csat was not significant.Low Rsat < 66% was associated with the presence of an hsPDA in the preterm infant. Csat may be preserved if cerebral autoregulation is largely intact. Bedside NIRS monitoring may reasonably increase suspicion for a significant PDA in the preterm infant.

View details for DOI 10.1038/pr.2016.148

View details for PubMedID 27603562
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
Management of the Preterm Infant with Congenital Heart Disease CLINICS IN PERINATOLOGY Axelrod, D. M., Chock, V. Y., Reddy, V. M. 2016; 43 (1): 157-?
Abstract

The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD.

View details for DOI 10.1016/j.clp.2015.11.011

View details for Web of Science ID 000372765500014
Management of the Preterm Infant with Congenital Heart Disease. Clinics in perinatology Axelrod, D. M., Chock, V. Y., Reddy, V. M. 2016; 43 (1): 157-171
Abstract

The premature neonate with congenital heart disease (CHD) represents a challenging population for clinicians and researchers. The interaction between prematurity and CHD is poorly understood; epidemiologic study suggests that premature newborns are more likely to have CHD and that fetuses with CHD are more likely to be born premature. Understanding the key physiologic features of this special patient population is paramount. Clinicians have debated optimal timing for referral for cardiac surgery, and management in the postoperative period has rapidly advanced. This article summarizes the key concepts and literature in the care of the premature neonate with CHD.

View details for DOI 10.1016/j.clp.2015.11.011

View details for PubMedID 26876128
Failed endotracheal intubation and adverse outcomes among extremely low birth weight infants. Journal of perinatology Wallenstein, M. B., Birnie, K. L., Arain, Y. H., Yang, W., Yamada, N. K., Huffman, L. C., Palma, J. P., Chock, V. Y., Shaw, G. M., Stevenson, D. K. 2016; 36 (2): 112-115
Abstract

To quantify the importance of successful endotracheal intubation on the first attempt among extremely low birth weight (ELBW) infants who require resuscitation after delivery.A retrospective chart review was conducted for all ELBW infants ?1000?g born between January 2007 and May 2014 at a level IV neonatal intensive care unit. Infants were included if intubation was attempted during the first 5?min of life or if intubation was attempted during the first 10?min of life with heart rate <100. The primary outcome was death or neurodevelopmental impairment. The association between successful intubation on the first attempt and the primary outcome was assessed using multivariable logistic regression with adjustment for birth weight, gestational age, gender and antenatal steroids.The study sample included 88 ELBW infants. Forty percent were intubated on the first attempt and 60% required multiple intubation attempts. Death or neurodevelopmental impairment occurred in 29% of infants intubated on the first attempt, compared with 53% of infants that required multiple attempts, adjusted odds ratio 0.4 (95% confidence interval 0.1 to 1.0), P<0.05.Successful intubation on the first attempt is associated with improved neurodevelopmental outcomes among ELBW infants. This study confirms the importance of rapid establishment of a stable airway in ELBW infants requiring resuscitation after birth and has implications for personnel selection and role assignment in the delivery room.Journal of Perinatology advance online publication, 5 November 2015; doi:10.1038/jp.2015.158.

View details for DOI 10.1038/jp.2015.158

View details for PubMedID 26540244
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
Prenatal hydrops foetalis associated with infantile free sialic acid storage disease. Journal of obstetrics and gynaecology Chock, V. Y., MILAN, K. E., Folkins, A. K., Hazard, F. K., Bernstein, J. A., Hintz, S. R. 2015; 35 (8): 850-852
View details for DOI 10.3109/01443615.2015.1017558

View details for PubMedID 26076308
Red Blood Cell Transfusion Is Not Associated with Necrotizing Enterocolitis: A Review of Consecutive Transfusions in a Tertiary Neonatal Intensive Care Unit JOURNAL OF PEDIATRICS Wallenstein, M. B., Arain, Y. H., Birnie, K. L., Andrews, J., Palma, J. P., Benitz, W. E., Chock, V. Y. 2014; 165 (4): 678-682
Abstract

To explore the association between red blood cell transfusion and necrotizing enterocolitis (NEC) in a neonatal intensive care unit with liberal transfusion practices.A retrospective cohort study was conducted for all infants weighing <1500�g who received at least 1 packed red blood cell transfusion between January 2008 and June 2013 in a tertiary neonatal intensive care unit. The primary outcome was NEC, defined as Bell stage II or greater. The temporal association of NEC and transfusion was assessed using multivariate Poisson regression.The study sample included 414 very low birth weight infants who received 2889 consecutive red blood cell transfusions. Twenty-four infants (5.8%) developed NEC. Four cases of NEC occurred within 48�hours of a previous transfusion event. Using multivariate Poisson regression, we did not find evidence of a temporal association between NEC and transfusion (P�=�.32).There was no association between NEC and red blood cell transfusion. Our results differ from previous studies and suggest that the association between NEC and transfusion may be contextual.

View details for DOI 10.1016/j.jpeds.2014.06.012

View details for Web of Science ID 000342694200009
Red blood cell transfusion is not associated with necrotizing enterocolitis: a review of consecutive transfusions in a tertiary neonatal intensive care unit. journal of pediatrics Wallenstein, M. B., Arain, Y. H., Birnie, K. L., Andrews, J., Palma, J. P., Benitz, W. E., Chock, V. Y. 2014; 165 (4): 678-682
Abstract

To explore the association between red blood cell transfusion and necrotizing enterocolitis (NEC) in a neonatal intensive care unit with liberal transfusion practices.A retrospective cohort study was conducted for all infants weighing <1500�g who received at least 1 packed red blood cell transfusion between January 2008 and June 2013 in a tertiary neonatal intensive care unit. The primary outcome was NEC, defined as Bell stage II or greater. The temporal association of NEC and transfusion was assessed using multivariate Poisson regression.The study sample included 414 very low birth weight infants who received 2889 consecutive red blood cell transfusions. Twenty-four infants (5.8%) developed NEC. Four cases of NEC occurred within 48�hours of a previous transfusion event. Using multivariate Poisson regression, we did not find evidence of a temporal association between NEC and transfusion (P�=�.32).There was no association between NEC and red blood cell transfusion. Our results differ from previous studies and suggest that the association between NEC and transfusion may be contextual.

View details for DOI 10.1016/j.jpeds.2014.06.012

View details for PubMedID 25039042
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
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): 549-555
View details for DOI 10.1055/s-0034-1371709

View details for Web of Science ID 000337933200002
Predictors of bronchopulmonary dysplasia or death in premature infants with a patent ductus arteriosus. Pediatric research Chock, V. Y., Punn, R., Oza, A., Benitz, W. E., Van Meurs, K. P., Whittemore, A. S., Behzadian, F., Silverman, N. H. 2014; 75 (4): 570-575
Abstract

Background:Preterm infants with a PDA are at risk for death or development of BPD. However, PDA treatment remains controversial. We investigated if PDA treatment and other clinical or echocardiographic (ECHO) factors were associated with the development of death or BPD.Methods:We retrospectively studied clinical and ECHO characteristics of preterm infants with birth weight <1500?g and ECHO diagnosis of a PDA. Logistic regression and classification and regression tree (CART) analyses were performed to assess variables associated with the combined outcome of death or BPD.Results:Of 187 preterm infants with a PDA, 75% were treated with indomethacin or surgery and 25% were managed conservatively. Death or BPD occurred in 80 (43%). Logistic regression found lower gestational age (OR 0.5), earlier year of birth during the study period (OR 0.9), and larger ductal diameter (OR 4.3) were associated with the decision to treat the PDA, while gestational age was the only variable associated with death or BPD (OR 0.6, 95% CI 0.5-0.8).Conclusion:Only lower gestational age and not PDA treatment or ECHO score was associated with the adverse outcome of death or BPD. Further investigation of PDA management strategies and effects on adverse outcomes of prematurity is needed.Pediatric Research (2013); doi:10.1038/pr.2013.253.

View details for DOI 10.1038/pr.2013.253

View details for PubMedID 24378897
NIPT in a Clinical Setting: An analysis of Uptake in the First Months of Clinical Availability. Journal of genetic counseling Taylor, J. B., Chock, V. Y., Hudgins, L. 2014; 23 (1): 72-78
Abstract

The objective of our study was to describe the clinical experience in offering noninvasive prenatal testing (NIPT) for aneuploidy to pregnant patients, highlighting the clinical utility, barriers to acceptance and limitations of this novel test. Data were collected from 961 patients offered NIPT from 3/1/12 to 9/30/12. Univariate and multivariate logistic regression analysis was performed. Twenty-eight percent of patients elected NIPT and 72�% declined. Women continue to elect less sensitive and less specific screening through biochemical markers and nuchal translucency. Women considering all options at average risk for aneuploidy were less likely to accept NIPT testing than women who had a risk adjustment from an ultrasound marker or routine screening test. In our multi-ethnic population, Filipina women were significantly less likely to elect NIPT compared to other ethnicities. Five percent of NIPT ordered failed analysis. Several chromosome abnormalities were detected through CVS or amniocentesis that would not have been detected by NIPT. Even though NIPT offers a non-invasive, highly sensitive and specific analysis for aneuploidy, the majority of women in our study declined this option. NIPT should be offered in the context of genetic counseling so that women understand the limitations of the testing and make an educated decision about the testing option best suited to their situation.

View details for DOI 10.1007/s10897-013-9609-z

View details for PubMedID 23723049
Variables Influencing Pregnancy Termination Following Prenatal Diagnosis of Fetal Chromosome Abnormalities JOURNAL OF GENETIC COUNSELING Hawkins, A., Stenzel, A., Taylor, J., Chock, V. Y., Hudgins, L. 2013; 22 (2): 238-248
Abstract

The objective of this study was to identify variables that may influence the decision to terminate or continue a pregnancy affected by a chromosome abnormality. We performed a retrospective cohort analysis of 286 pregnancies diagnosed with a chromosome abnormality following genetic counseling and prenatal diagnosis. Data obtained included procedure type, chromosome results, ethnicity, maternal age, use of fertility treatments, and uptake of genetic counseling after results, among other factors. Wilcoxon rank sum test, Fisher's exact test, and univariate and multivariate logistic regression models were used for data analysis. The overall termination rate in this study was 82.9�%. A lower likelihood to terminate was found in pregnancies with a diagnosis of a sex chromosome abnormality (OR 0.05, p?
View details for DOI 10.1007/s10897-012-9539-1

View details for Web of Science ID 000316291100008

View details for PubMedID 23001505
Short-term Neurodevelopmental Outcomes in Neonates with Congenital Heart Disease: The Era of Newer Surgical Strategies CONGENITAL HEART DISEASE Chock, V. Y., Chang, I. J., Reddy, V. M. 2012; 7 (6): 544-550
Abstract

The objective of this study was to determine neurodevelopmental outcomes up to 30 months of age in a cohort of neonates requiring surgical intervention without circulatory arrest for congenital heart disease and to correlate these outcomes with characteristics detected prior to hospital discharge.An observational cohort of surviving neonates who underwent surgical intervention without circulatory arrest for congenital heart disease between 2002 and 2003 was studied at a single tertiary care institution.Thirty-five patients were followed from 4 to 6 months of age until 24-30 months of age.Neuromotor abnormalities, use of special services, and degree of developmental delay at set intervals between 4 and 30 months of age were retrospectively obtained from clinical reports. The relationship between these outcomes and clinical characteristics prior to hospital discharge was analyzed.Those with neuromotor abnormalities prior to discharge were likely to have persistent abnormalities in muscle strength, tone, and symmetry until 4-6 months of age, odds ratio 6 (1.3-29). By 24-30 months of age, motor abnormalities or developmental delay occurred in 10 of 20 infants (50%), but were no longer significantly associated with predischarge findings.Infants undergoing surgical intervention for congenital heart disease are at risk for neurodevelopmental abnormalities, which may not become apparent until months after hospital discharge. Early impairment may also resolve over time. Close developmental follow-up in this high-risk cohort of patients is warranted.

View details for DOI 10.1111/j.1747-0803.2012.00678.x

View details for Web of Science ID 000311611000011

View details for PubMedID 22676547

View details for PubMedCentralID PMC3443535
Cerebral Autoregulation in Neonates with a Hemodynamically Significant Patent Ductus Arteriosus JOURNAL OF PEDIATRICS Chock, V. Y., Ramamoorthy, C., Van Meurs, K. P. 2012; 160 (6)
Abstract

Very low birth weight (VLBW) preterm infants are at risk for impaired cerebral autoregulation with pressure passive blood flow. Fluctuations in cerebral perfusion may occur in infants with a hemodynamically significant patent ductus arteriosus (hsPDA), especially during ductal closure. Our goal was to compare cerebral autoregulation using near-infrared spectroscopy in VLBW infants treated for an hsPDA.This prospective observational study enrolled 28 VLBW infants with an hsPDA diagnosed by echocardiography and 12 control VLBW infants without an hsPDA. Near-infrared spectroscopy cerebral monitoring was applied during conservative treatment, indomethacin treatment, or surgical ligation. A cerebral pressure passivity index (PPI) was calculated, and PPI differences were compared using a mixed-effects regression model. Cranial ultrasound and magnetic resonance imaging data were also assessed.Infants with surgically ligated hsPDAs were more likely to have had a greater PPI within 2 hours following ligation than were those treated with conservative management (P=.04) or indomethacin (P=.0007). These differences resolved by 6 hours after treatment.Cerebral autoregulation was better preserved after indomethacin treatment of an hsPDA compared with surgical ligation. Infants requiring surgical hsPDA ligation may be at increased risk for cerebral pressure passivity in the 6 hours following surgery.

View details for DOI 10.1016/j.jpeds.2011.11.054

View details for Web of Science ID 000304377300012

View details for PubMedID 22226574

View details for PubMedCentralID PMC3335982
Cerebral Oxygenation during Different Treatment Strategies for a Patent Ductus Arteriosus NEONATOLOGY Chock, V. Y., Ramamoorthy, C., Van Meurs, K. P. 2011; 100 (3): 233-240
Abstract

Preterm infants with a hemodynamically significant patent ductus arteriosus (hsPDA) are at risk for fluctuations in cerebral blood flow, but it is unclear how different hsPDA treatment strategies may affect cerebral oxygenation.To compare regional cerebral oxygen saturation (rSO(2)) as measured by near-infrared spectroscopy (NIRS) in very low birth weight (VLBW) infants with a hsPDA treated with conservative management, indomethacin, or surgical ligation.This prospective observational study enrolled 33 VLBW infants with a hsPDA diagnosed by echocardiogram and 12 control VLBW infants without a hsPDA. Infants had NIRS cerebral monitoring applied prior to conservative treatment, indomethacin, or surgical ligation. Cranial ultrasound and magnetic resonance imaging data were also collected.Infants undergoing surgical ligation had a greater time period with >20% change in rSO(2) from baseline (30%) compared to those receiving indomethacin (7.4%, p = 0.001) or control infants without a hsPDA (2.6%, p = 0.0004). NIRS measures were not associated with abnormal neuroimaging in this small cohort.These findings suggest that infants requiring surgical ligation for a hsPDA are at high risk for significant changes in cerebral oxygenation, whereas those receiving either indomethacin or conservative management maintain relatively stable cerebral oxygenation levels. Additional research is necessary to determine if NIRS monitoring identifies infants with a hsPDA at highest risk for brain injury.

View details for DOI 10.1159/000325149

View details for Web of Science ID 000295588200004

View details for PubMedID 21701212
Inhaled Nitric Oxide for Preterm Premature Rupture of Membranes, Oligohydramnios, and Pulmonary Hypoplasia AMERICAN JOURNAL OF PERINATOLOGY Chock, V. Y., Van Meurs, K. P., Hintz, S. R., Ehrenkranz, R. A., Lemons, J. A., Kendrick, D. E., Stevenson, D. K. 2009; 26 (4): 317-322
Abstract

We sought to determine if inhaled nitric oxide (iNO) administered to preterm infants with premature rupture of membranes (PPROM), oligohydramnios, and pulmonary hypoplasia improved oxygenation, survival, or other clinical outcomes. Data were analyzed from infants with suspected pulmonary hypoplasia, oligohydramnios, and PPROM enrolled in the National Institute of Child Health and Development Neonatal Research Network Preemie Inhaled Nitric Oxide (PiNO) trial, where patients were randomized to receive placebo (oxygen) or iNO at 5 to 10 ppm. Outcome variables assessed were PaO (2) response, mortality, bronchopulmonary dysplasia (BPD), and severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Twelve of 449 infants in the PiNO trial met criteria. Six infants received iNO and six received placebo. The iNO group had a mean increase in PaO (2) of 39 +/- 50 mm Hg versus a mean decrease of 11 +/- 15 mm Hg in the control group. Mortality was 33% versus 67%, BPD (2/5) 40% versus (2/2) 100%, and severe IVH or PVL (1/5) 20% versus (1/2) 50% in the iNO and control groups, respectively. None of these changes were statistically significant. Review of a limited number of cases from a large multicenter trial suggests that iNO use in the setting of PPROM, oligohydramnios, and suspected pulmonary hypoplasia improves oxygenation and may decrease the rate of BPD and death without increasing severe IVH or PVL. However, the small sample size precludes definitive conclusions. Further studies are required to determine if iNO is of benefit in this specific patient population.

View details for DOI 10.1055/s-0028-1104743

View details for PubMedID 19067285
Inflammation and NF kappa B activation is decreased by hypothermia following global cerebral ischemia NEUROBIOLOGY OF DISEASE Webster, C. M., Kelly, S., Koike, M. A., Chock, V. Y., Giffard, R. G., Yenari, M. A. 2009; 33 (2): 301-312
Abstract

We previously showed that hypothermia attenuates inflammation in focal cerebral ischemia (FCI) by suppressing activating kinases of nuclear factor-kappa B (NFkappaB). Here we characterize the inflammatory response in global cerebral ischemia (GCI), and the influence of mild hypothermia. Rodents were subjected to GCI by bilateral carotid artery occlusion. The inflammatory response was accompanied by microglial activation, but not neutrophil infiltration, or blood brain barrier disruption. Mild hypothermia reduced CA1 damage, decreased microglial activation and decreased nuclear NFkappaB translocation and activation. Similar anti-inflammatory effects of hypothermia were observed in a model of pure brain inflammation that does not cause brain cell death. Primary microglial cultures subjected to oxygen glucose deprivation (OGD) or stimulated with LPS under hypothermic conditions also experienced less activation and less NFkappaB translocation. However, NFkappaB regulatory proteins were not affected by hypothermia. The inflammatory response following GCI and hypothermia's anti-inflammatory mechanism is different from that observed in FCI.

View details for DOI 10.1016/j.nbd.2008.11.001

View details for Web of Science ID 000263120500018

View details for PubMedID 19063968

View details for PubMedCentralID PMC2737398
Neurologic events in neonates treated surgically for congenital heart disease JOURNAL OF PERINATOLOGY Chock, V. Y., Reddy, V. M., Bernstein, D., Madan, A. 2006; 26 (4): 237-242
Abstract

The incidence of acute neurologic events prior to discharge in neonates with congenital heart disease (CHD) was determined and peri-operative characteristics predictive of a neurologic event were identified.A retrospective chart review over 1 year was conducted of infants <1 month of age with a diagnosis of CHD. Outcomes were measured by the occurrence of an acute neurologic event defined as electroencephalogram (EEG)-proven seizure activity, significant hypertonia or hypotonia, or choreoathetosis prior to hospital discharge. Stepwise logistic regression identified variables most likely to be associated with an acute neurologic event.Surgical intervention occurred in 95 infants who were admitted with a diagnosis of CHD. The survival rate was 92%. Of the survivors, 16 (17%) had an acute neurologic event, with 19% of events occurring preoperatively. Factors associated with neurologic events included an elevated nucleated red blood cell (NRBC) count, an abnormal preoperative brain imaging study, and a 5-min Apgar score <7 (P<0.05).Neonates with CHD have a significant risk of neurologic events. Preoperative brain imaging, the 5-min Apgar score, and initial serum NRBC counts may identify infants at highest risk for central nervous system injury.

View details for DOI 10.1038/sj.jp.7211459

View details for Web of Science ID 000241843200006

View details for PubMedID 16496014
Antegrade cerebral perfusion reduces apoptotic neuronal injury in a neonatal piglet model of cardiopulmonary bypass JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Chock, V. Y., Amir, G., DAVIS, C. R., Ramamoorthy, C., Riemer, R. K., Ray, D., Giffard, R. G., Reddy, V. M. 2006; 131 (3): 659-665
Abstract

Neonates with congenital heart disease might require surgical repair with deep hypothermic circulatory arrest, a technique associated with adverse neurodevelopmental outcomes. Antegrade cerebral perfusion is thought to minimize ischemic brain injury, although there are no supporting experimental data. We sought to evaluate and compare the extent of neurologic injury in a neonatal piglet model of deep hypothermic circulatory arrest and antegrade cerebral perfusion.Neonatal piglets undergoing cardiopulmonary bypass were randomized to deep hypothermic circulatory arrest or antegrade cerebral perfusion for 45 minutes. Animals were killed after 6 hours of recovery, and brain tissue was stained for evidence of cellular injury and for the apoptotic markers activated caspase 3 and cytochrome c translocation from mitochondria to cytosol.Piglets from the antegrade cerebral perfusion group exhibited less apoptotic or necrotic injury (4 +/- 3 vs 29 +/- 12 cells per field, P = .03). The piglets undergoing antegrade cerebral perfusion also had less evidence of apoptosis, with fewer cells staining for activated caspase 3 (57 +/- 8 vs 93 +/- 9 cells per field, P = .001) or showing cytochrome c translocation (6 +/- 2 vs 15 +/- 4 cells per field, P = .02).The use of antegrade cerebral perfusion in place of deep hypothermic circulatory arrest reduces evidence of apoptosis and histologic injury in neonatal piglets. Neonates with congenital heart disease might benefit from antegrade cerebral perfusion during complex cardiac surgery to improve their overall neurologic outcome.

View details for DOI 10.1016/j.jtcvs.2005.09.005

View details for Web of Science ID 000235940600024

View details for PubMedID 16515920
Development of neonatal murine microglia in vitro: Changes in response to lipopolysaccharide and ischemia-like injury PEDIATRIC RESEARCH Chock, V. Y., Giffard, R. G. 2005; 57 (4): 475-480
Abstract

Hypoxic/ischemic brain injury in the neonate can activate an inflammatory cascade, which potentiates cellular injury. The role of microglia in this inflammatory response has not been studied extensively. We used an in vitro model of murine microglia to investigate changes in microglial cytokine release and injury during early development. Isolated microglia were subjected to lipopolysaccharide (LPS) activation or injury by glucose deprivation (GD), serum deprivation (SD), or combined oxygen-glucose deprivation (OGD) for varying durations. The extent and the type of cell death were determined by trypan blue, terminal deoxynucleotidyl end-nick labeling, and annexin staining. Early-culture microglia (2-3 d in purified culture) showed significantly more apoptotic cell death after SD, GD, and OGD compared with microglia maintained in culture for 14-17 d. Measurements of tumor necrosis factor-alpha (TNF-alpha) and IL-1beta in culture media demonstrated that OGD induced greater release of both TNF-alpha and IL-1beta than LPS activation, with early-culture microglia producing more TNF-alpha compared with late-culture microglia. Microglia that are cultured for a short time are more sensitive to ischemia-like injury in vitro than those that are cultured for longer durations and may contribute to worsening brain injury by increased release of inflammatory cytokines. Inhibition of microglial activation and decreasing proinflammatory cytokine release may be targets for reduction of neonatal hypoxic/ischemic brain injury.

View details for DOI 10.1203/01.PDR.0000155758.79523.44

View details for Web of Science ID 000227746600003

View details for PubMedID 15718374
Developing microglia are sensitive to injury in an in vitro model of neonatal ischemia Chock, V. Y., Giffard, R. G. KARGER. 2005: 270
View details for Web of Science ID 000230679400062
Susceptibility to apoptosis varies with time in culture for murine neurons and astrocytes: changes in gene expression and activity NEUROLOGICAL RESEARCH Xu, L. J., Chock, V. Y., Yang, E. Y., Giffard, R. G. 2004; 26 (6): 632-643
Abstract

Apoptotic pathways in the brain may differ depending on cell type and developmental stage. To understand these differences, we studied several apoptotic proteins in the murine cortex and primary cultures of neurons and astrocytes of various ages in culture. We then induced apoptosis in our cultures using serum deprivation (SD) and observed changes in these apoptotic proteins. When analyzed by nuclear morphology and TUNEL staining, early cultures showed greater apoptotic injury compared with late cultures, and neuronal cultures showed greater apoptosis than astrocyte cultures. The decrease in apoptosis with development correlated best with a down-regulation of procaspase-3 and bax and decreasing caspase activation. Early culture astrocytes had higher caspase-11 levels compared with neurons. Mitogen-activated protein (MAP) kinases were also differentially expressed with activation of extracellular signal-regulated kinase (ERK) and p38 higher in early culture astrocytes and stress-activated protein kinase/C-jun N-terminal kinase (SAPK/JNK) greater in early culture neurons. However, caspase inhibitors, but not MAP kinase inhibitors reduced cell death. Our findings demonstrate that apoptosis regulatory proteins display cell type and developmentally specific expression and activation.

View details for DOI 10.1179/016164104225017587

View details for Web of Science ID 000223832200005

View details for PubMedID 15327753
Neuroloeic events in neonates with congenital heart disease Chock, Bernstein, D., Reddy, M. V., Madan, A. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2004: 39A
View details for Web of Science ID 000220591100238
REMOVAL OF SIALIC-ACID FROM A GLYCOPROTEIN IN CHO CELL-CULTURE SUPERNATANT BY ACTION OF AN EXTRACELLULAR CHO CELL SIALIDASE BIO-TECHNOLOGY Gramer, M. J., Goochee, C. F., Chock, V. Y., BROUSSEAU, D. T., Sliwkowski, M. B. 1995; 13 (7): 692-698
Abstract

We have directly tested the hypothesis that Chinese hamster ovary (CHO) cell-produced glycoproteins are subject to extracellular degradation by a sialidase endogenous to the CHO cell line. Factors important to understanding the potential for extracellular degradation are addressed including the glycoprotein specificity, subcellular source, mechanism of release, and stability of the sialidase activity. The extracellular CHO cell sialidase apparently originates from the cytosol of the cells, and is released to the cell culture supernatant as a result of damage to the cellular membrane. The extracellular sialidase is active toward a variety of CHO cell-produced glycoproteins, and can hydrolyze sialic acid from the recombinant glycoprotein gp120 in the culture supernatant. While measuring the actual degradation of a glycoprotein by extracellular CHO cell sialidase can be difficult, data presented here suggest that the level of degradation can be estimated indirectly by using a more convenient fluorescent substrate, 4-methylumbelliferyl-alpha-D-N-acetylneuraminic acid, to quantify sialidase activity. Degradation by sialidase is minimized through addition of the sialidase inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid to the culture supernatant. The results in this study suggest additional potential approaches for minimizing degradation by sialidase, including isolation of a sialidase-deficient CHO cell line.

View details for Web of Science ID A1995RG36000023

View details for PubMedID 9634806

Valerie Chock

Associate Professor of Pediatrics (Neonatology) at the Lucile Salter Packard Children's Hospital

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