Publications by authors named "Abhik Das"

227 Publications

Association of High Screen-Time Use With School-age Cognitive, Executive Function, and Behavior Outcomes in Extremely Preterm Children.

JAMA Pediatr 2021 Jul 12. Epub 2021 Jul 12.

Division of Perinatal Neonatal Medicine, Stanford University, Palo Alto, California.

Importance: Both preterm birth and increased screen time are known to be associated with an increase in risk of developmental and behavioral sequelae. The association between high screen time or a television or computer in the bedroom in early school age and adverse cognitive, executive function, language, and behavior outcomes of extremely preterm children (EPT) is not well understood.

Objective: To assess the association of high screen time with cognition, language, executive function, and behavior of EPT children aged 6 to 7 years; a second objective was to examine the association between high screen time and rates of structured physical activity and weight.

Design, Setting, And Participants: This cohort study was a secondary analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial Neuroimaging and Neurodevelopmental Outcomes school-aged cohort and includes 414 EPT children born between February 1, 2005, and February 28, 2009, and evaluated in between 2012 and 2016 at ages 6 years 4 months to 7 years 2 months. The study was conducted from July 7, 2012, and August 15, 2016, and data were analyzed between December 10, 2018, and April 1, 2021.

Exposures: Cohorts included children exposed to low (≤2 hours per day) vs high (>2 hours per day) amounts of screen time and by the presence (no vs yes) of a television/computer in the bedroom.

Main Outcomes And Measures: In addition to growth parameters, assessments included the Wechsler Intelligence Scale for Children-IV, the Behavior Rating Inventory of Executive Function, the Developmental Neuropsychological Assessment, the Conners 3rd Edition-Parent Short-Form, and the Social Communication Questionnaire.

Results: Of the 414 children included in the analysis, 227 (55%) were boys; mean (SD) birth weight was 870.6 (191) g. A total of 238 children (57%) had high screen time and 266 (64%) had a television/computer in their bedroom. In multivariable linear regressions adjusted for center, male sex, gestational age, and social determinants of health, high screen time was independently associated with the following mean (SE) test score changes: lower full-scale IQ (-3.92 [1.64]; P = .02); an increase in association with deficits in executive functions, including metacognition (8.18 [3.01]; P = .007), global executive function (7.49 [2.99]; P = .01), inhibition (-0.79 [0.38]; P = .03), and Conners 3rd Edition-Parent Short-Form inattention (3.32 [1.67]; P = .047). A television/computer in the bedroom was associated with an increase in inhibition (-0.80 [0.39]; P = .04) and hyperactivity/impulsivity (3.50 [1.75]; P = .046) problems.

Conclusions And Relevance: The findings of this study suggest that high screen time contributes to adverse cognitive, executive function, and behavior outcomes at ages 6 to 7 years in children born at less than 28 weeks. These findings support the need for clinicians to have heightened awareness of the risks for EPT children and discuss both the benefits and risks of screen time with families.
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http://dx.doi.org/10.1001/jamapediatrics.2021.2041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276120PMC
July 2021

Growth Rates of Infants Randomized to Continuous Positive Airway Pressure or Intubation After Extremely Preterm Birth.

J Pediatr 2021 Jun 19. Epub 2021 Jun 19.

National Institute of Child Health and Human Development, Bethesda, MD; Department of Global and Community Health, George Mason University, Fairfax, VA.

Objective: To evaluate the effects of early treatment with continuous positive airway pressure (CPAP) on nutritional intake and in-hospital growth rates of extremely preterm (EPT) infants.

Study Design: EPT infants (24-27 weeks of gestation) enrolled in the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) were included. EPT infants who died before 36 weeks of postmenstrual age (PMA) were excluded. The growth rates from birth to 36 weeks of PMA and follow-up outcomes at 18-22 months corrected age of EPT infants randomized at birth to either early CPAP (intervention group) or early intubation for surfactant administration (control group) were analyzed.

Results: Growth data were analyzed for 810 of 1316 infants enrolled in SUPPORT (414 in the intervention group, 396 in the control group). The median gestational age was 26 weeks, and the mean birth weight was 839 g. Baseline characteristics, total nutritional intake, and in-hospital comorbidities were not significantly different between the 2 groups. In a regression model, growth rates between birth and 36 weeks of PMA, as well as growth rates during multiple intervals from birth to day 7, days 7-14, days 14-21, days 21-28, day 28 to 32 weeks PMA, and 32-36 weeks PMA did not differ between treatment groups. Independent of treatment group, higher growth rates from day 21 to day 28 were associated with a lower risk of having a Bayley-III cognitive score <85 at 18-22 months corrected age (P = .002).

Conclusions: EPT infants randomized to early CPAP did not have higher in-hospital growth rates than infants randomized to early intubation.
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http://dx.doi.org/10.1016/j.jpeds.2021.06.026DOI Listing
June 2021

Should Vitamin A Injections to Prevent Bronchopulmonary Dysplasia or Death Be Reserved for High-Risk Infants? Reanalysis of the National Institute of Child Health and Human Development Neonatal Research Network Randomized Trial.

J Pediatr 2021 May 15. Epub 2021 May 15.

Stead Family Department of Pediatrics, University of Iowa, Iowa City, IA.

Objective: To determine whether infants at higher risk of bronchopulmonary dysplasia (BPD) or death benefit more from vitamin A therapy than those at lower risk.

Study Design: We conducted a post hoc reanalysis of a landmark phase III randomized controlled trial conducted from January 1996 to July 1997 at 14 university-affiliated neonatal intensive care units in the US. Data analysis was performed from October 2019 to October 2020. Infants born weighing 401-1000 g and receiving respiratory support at 24 hours of age were assigned to intramuscular vitamin A 5000 IU or sham procedure 3 times weekly for 4 weeks. The primary outcome was BPD, defined as use of supplemental oxygen, or death at 36 weeks postmenstrual age. An externally validated model for predicting BPD or death was used to estimate the risk of these outcomes for each infant.

Results: As previously reported, 222 of 405 infants (54.8%) assigned vitamin A therapy and 248 of 402 infants (61.7%) in the control group developed BPD or died (relative risk [RR], 0.89 [95% CI, 0.80-0.99]; risk difference [RD], -6.9% [95% CI, -13.0 to -0.7]). The predicted individual risks of BPD or death ranged from 7.1% to 98.6% (median, 61.5%; mean, 60.9%). The effect of vitamin A therapy on BPD or death depended on infants' risk of the primary outcome (P = .03 for interaction): for example, a RR of 0.73 (RD, -14.5%) for infants with a 25% predicted risk and a RR of 0.96 (RD, -1.0%) for infants with a 75% risk. There was no difference in the decrease in vitamin A deficiency across risk groups.

Conclusions: Contrary to expectations, the effect of vitamin A therapy on BPD or death was greater for lower risk than higher risk infants.

Trial Registration: ClinicalTrials.gov NCT01203488.
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http://dx.doi.org/10.1016/j.jpeds.2021.05.022DOI Listing
May 2021

Early Determination of Prognosis in Neonatal Moderate or Severe Hypoxic-Ischemic Encephalopathy.

Pediatrics 2021 Jun 13;147(6). Epub 2021 May 13.

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.

Background And Objectives: Early determination of prognosis is important in neonates with hypoxic-ischemic encephalopathy (HIE). Our objective was to test scoring systems developed earlier (original scoring system) and develop new prognostic models.

Methods: Secondary analysis of data from the multicenter randomized controlled trial of longer, deeper, or usual care cooling in neonatal HIE (NCT01192776) that enrolled 364 neonates diagnosed with moderate or severe HIE. The primary outcome was death or moderate or severe disability at 18 to 22 months, and secondary outcome was death during initial hospitalization. Testing of early neurologic clinical examination (<6 hours of age) and the original scoring system for prognostic ability was done, followed by development of new scoring systems and classification and regression tree (CART) models by using early clinical variables (<6 hours of age).

Results: For death or disability, the original scoring system correctly classified 75% (95% confidence interval: 69%-81%), whereas the new scoring system correctly classified 78% (73%-82%), and the CART model correctly classified 76% (72%-81%). Early neurologic clinical examination also had a correct classification rate of 76% (71%-80%). Depth and duration of cooling did not affect prediction. Only a few components of the early neurologic examination were associated with poor outcome. For death, the original scoring system correctly classified 72% (66%-77%), the new scoring system 68% (63%-72%), the new CART model 87% (83%-90%), and early neurologic evaluation 81% (77%-85%).

Conclusions: The 3 models (scoring system, CART, and early neurologic evaluation) were comparable in predicting death or disability. For in-hospital death, CART models were superior to scoring systems and early neurologic examination.
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http://dx.doi.org/10.1542/peds.2020-048678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168606PMC
June 2021

Neurodevelopmental outcome of preterm infants enrolled in myo-inositol randomized controlled trial.

J Perinatol 2021 Mar 23. Epub 2021 Mar 23.

Department of Ophthalmology and Visual Science, McGovern Medical School at The University of Texas Health Science Center at Houston, Houston, TX, USA.

Objective: This study evaluates the 24-month follow-up for the NICHD Neonatal Research Network (NRN) Inositol for Retinopathy Trial.

Study Design: Bayley Scales of Infants Development-III and a standardized neurosensory examination were performed in infants enrolled in the main trial. Moderate/severe NDI was defined as BSID-III Cognitive or Motor composite score <85, moderate or severe cerebral palsy, blindness, or hearing loss that prevents communication despite amplification were assessed.

Results: Primary outcome was determined for 605/638 (95%). The mean gestational age was 25.8 ± 1.3 weeks and mean birthweight was 805 ± 192 g. Treatment group did not affect the risk for the composite outcome of death or survival with moderate/severe NDI (60% vs 56%, p = 0.40).

Conclusions: Treatment group did not affect the risk of death or survival with moderate/severe NDI. Despite early termination, this study represents the largest RCT of extremely preterm infants treated with myo-inositol with neurodevelopmental outcome data.
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http://dx.doi.org/10.1038/s41372-021-01018-5DOI Listing
March 2021

Phenobarbital and Clonidine as Secondary Medications for Neonatal Opioid Withdrawal Syndrome.

Pediatrics 2021 03;147(3)

Environmental Influences on Child Health Outcomes Program, Office of the Director, National Institutes of Health, Rockville, Maryland.

Background And Objectives: Despite the neonatal opioid withdrawal syndrome (NOWS) epidemic in the United States, evidence is limited for pharmacologic management when first-line opioid medications fail to control symptoms. The objective with this study was to evaluate outcomes of infants receiving secondary therapy with phenobarbital compared with clonidine, in combination with morphine, for the treatment of NOWS.

Methods: We performed a retrospective cohort study of infants with NOWS from 30 hospitals. The primary outcome measures were the length of hospital stay, duration of opioid treatment, and peak morphine dose. Outcomes were compared by group by using analysis of variance and multivariable linear regression controlling for relevant confounders.

Results: Of 563 infants with NOWS treated with morphine, 32% ( = 180) also received a secondary medication. Seventy-two received phenobarbital and 108 received clonidine. After adjustment for covariates, length of hospital stay was 10 days shorter, and, in some models, duration of morphine treatment was 7.5 days shorter in infants receiving phenobarbital compared with those receiving clonidine, with no difference in peak morphine dose. Infants were more likely to be discharged from the hospital on phenobarbital than clonidine (78% vs 29%, < .0001).

Conclusions: Among infants with NOWS receiving morphine and secondary therapy, those treated with phenobarbital had shorter length of hospital stay and shorter morphine treatment duration than clonidine-treated infants but were discharged from the hospital more often on secondary medication. Further investigation is warranted to determine if the benefits of shorter hospital stay and shorter duration of morphine therapy justify the possible neurodevelopmental consequences of phenobarbital use in infants with NOWS.
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http://dx.doi.org/10.1542/peds.2020-017830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919109PMC
March 2021

Umbilical Cord Milking vs Delayed Cord Clamping and Associations with In-Hospital Outcomes among Extremely Premature Infants.

J Pediatr 2021 May 5;232:87-94.e4. Epub 2021 Jan 5.

Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA; Leonard Davis Institute of Health Economics, The University of Pennsylvania, Philadelphia, PA. Electronic address:

Objective: To compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation.

Study Design: Multicenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of 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 2 gestational age strata, 22-24 and 25-28 weeks.

Results: Among 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-28 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups.

Conclusions: This analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH.

Trial Registration: ClinicalTrials.gov: NCT00063063.
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http://dx.doi.org/10.1016/j.jpeds.2020.12.072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084979PMC
May 2021

Outcomes of infants with hypoxic ischemic encephalopathy and persistent pulmonary hypertension of the newborn: results from three NICHD studies.

J Perinatol 2021 Mar 6;41(3):502-511. Epub 2021 Jan 6.

Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, CA, USA.

Objective: To determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia.

Methods: We compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, "usual care" arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18-22 months adjusted for severity of HIE, center, and RCT.

Results: Among 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86-3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92-4.53), respectively.

Conclusions: PPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.
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http://dx.doi.org/10.1038/s41372-020-00905-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954876PMC
March 2021

Site-Level Variation in the Characteristics and Care of Infants With Neonatal Opioid Withdrawal.

Pediatrics 2021 01 21;147(1). Epub 2020 Dec 21.

Department of Pediatrics, School of Medicine, University of Louisville, Louisville, Kentucky.

Background And Objectives: Variation in pediatric medical care is common and contributes to differences in patient outcomes. Site-to-site variation in the characteristics and care of infants with neonatal opioid withdrawal syndrome (NOWS) has yet to be quantified. Our objective was to describe site-to-site variation in maternal-infant characteristics, infant management, and outcomes for infants with NOWS.

Methods: Cross-sectional study of 1377 infants born between July 1, 2016, and June 30, 2017, who were ≥36 weeks' gestation, with NOWS (evidence of opioid exposure and NOWS scoring within the first 120 hours of life) born at or transferred to 1 of 30 participating hospitals nationwide. Site-to-site variation for each parameter within the 3 domains was measured as the range of individual site-level means, medians, or proportions.

Results: Sites varied widely in the proportion of infants whose mothers received adequate prenatal care (31.3%-100%), medication-assisted treatment (5.9%-100%), and prenatal counseling (1.9%-75.5%). Sites varied in the proportion of infants with toxicology screening (50%-100%) and proportion of infants receiving pharmacologic therapy (6.7%-100%), secondary medications (1.1%-69.2%), and nonpharmacologic interventions including fortified feeds (2.9%-90%) and maternal breast milk (22.2%-83.3%). The mean length of stay varied across sites (2-28.8 days), as did the proportion of infants discharged with their parents (33.3%-91.1%).

Conclusions: Considerable site-to-site variation exists in all 3 domains. The magnitude of the observed variation makes it unlikely that all infants are receiving efficient and effective care for NOWS. This variation should be considered in future clinical trial development, practice implementation, and policy development.
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http://dx.doi.org/10.1542/peds.2020-008839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780957PMC
January 2021

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.

N Engl J Med 2020 12;383(27):2639-2651

From the Department of Pediatrics, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia (H.K., B.S., A.S.C.); the Department of Pediatrics, University of Iowa, Iowa City (E.F.B., K.J.J., J.A.W.); the Department of Pediatrics, Division of Neonatal and Developmental Medicine, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto (S.R.H., V.Y.C.), and the Department of Pediatrics, University of California, Los Angeles, Los Angeles (U.D.) - both in California; the Biostatistics and Epidemiology Division, RTI International, Research Triangle Park (S.T., M.M.C.), and the Department of Pediatrics, Duke University School of Medicine, Durham (C.M.C.) - both in North Carolina; the Biostatistics and Epidemiology Division, RTI International, Rockville (J.E.N., A.D.), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda (R.D.H.) - both in Maryland; the Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, RI (B.R.V., A.R.L.); the Division of Neonatology, University of Alabama at Birmingham, Birmingham (W.A.C.); the University of Rochester School of Medicine and Dentistry, Rochester, NY (C.T.D., M.F.C.); the Department of Pediatrics, McGovern Medical School at the University of Texas Health Science Center at Houston, Houston (K.A.K.), and the Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas (M.H.W.); the University of New Mexico Health Sciences Center, Albuquerque (R.K.O.); the Department of Pediatrics, Division of Neonatology, University of Utah School of Medicine, Salt Lake City (R.K.O., B.A.Y.); the Department of Pediatrics, Indiana University School of Medicine, Indianapolis (B.B.P., G.M.S.); Cincinnati Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati (B.B.P., K.S.), the Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland (M.C.W.), and Nationwide Children's Hospital and the Department of Pediatrics, Ohio State University College of Medicine, Columbus (R.S.); the Department of Pediatrics, Dalhousie University, Halifax, NS, Canada (R.K.W.); the Department of Neonatology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston (J.A.F.Z.); the Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO (W.E.T.); Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta (R.M.P.); the Department of Pediatrics, Wayne State University, Detroit (S.C.); and the College of Health and Human Services, George Mason University, Fairfax, VA (R.D.H.).

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.).
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http://dx.doi.org/10.1056/NEJMoa2020248DOI Listing
December 2020

Limitations of Conventional Magnetic Resonance Imaging as a Predictor of Death or Disability Following Neonatal Hypoxic-Ischemic Encephalopathy in the Late Hypothermia Trial.

J Pediatr 2021 03 13;230:106-111.e6. Epub 2020 Nov 13.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Pregnancy and Perinatology Branch, Bethesda, MD; George Mason University, Fairfax, VA.

Objective: To investigate if magnetic resonance imaging (MRI) is an accurate predictor for death or moderate-severe disability at 18-22 months of age among infants with neonatal encephalopathy in a trial of cooling initiated at 6-24 hours.

Study Design: Subgroup analysis of infants ≥36 weeks of gestation with moderate-severe neonatal encephalopathy randomized at 6-24 postnatal hours to hypothermia or usual care in a multicenter trial of late hypothermia. MRI scans were performed per each center's practice and interpreted by 2 central readers using the Eunice Kennedy Shriver National Institute of Child Health and Human Development injury score (6 levels, normal to hemispheric devastation). Neurodevelopmental outcomes were assessed at 18-22 months of age.

Results: Of 168 enrollees, 128 had an interpretable MRI and were seen in follow-up (n = 119) or died (n = 9). MRI findings were predominantly acute injury and did not differ by cooling treatment. At 18-22 months, death or severe disability occurred in 20.3%. No infant had moderate disability. Agreement between central readers was moderate (weighted kappa 0.56, 95% CI 0.45-0.67). The adjusted odds of death or severe disability increased 3.7-fold (95% CI 1.8-7.9) for each increment of injury score. The area under the curve for severe MRI patterns to predict death or severe disability was 0.77 and the positive and negative predictive values were 36% and 100%, respectively.

Conclusions: MRI injury scores were associated with neurodevelopmental outcome at 18-22 months among infants in the Late Hypothermia Trial. However, the results suggest caution when using qualitative interpretations of MRI images to provide prognostic information to families following perinatal hypoxia-ischemia.

Trial Registration: Clinicaltrials.gov: NCT00614744.
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http://dx.doi.org/10.1016/j.jpeds.2020.11.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914162PMC
March 2021

Withholding or withdrawing life-sustaining treatment in extremely low gestational age neonates.

Arch Dis Child Fetal Neonatal Ed 2021 May 20;106(3):238-243. Epub 2020 Oct 20.

Dean's Office, University of Texas Health Science Center at Houston, Houston, Texas, USA.

Objective: To identify sociodemographic and clinical factors associated with withholding or withdrawing life-sustaining treatment (WWLST) for extremely low gestational age neonates.

Design: Observational study of prospectively collected registry data from 19 National Institute of Child Health and Human Development Neonatal Research Network centres on neonates born at 22-28 weeks gestation who died >12 hours through 120 days of age during 2011-2016. Sociodemographic and clinical factors were compared between infants who died following WWLST and without WWLST.

Results: Of 1168 deaths, 67.1% occurred following WWLST. Withdrawal of assisted ventilation (97.4%) was the primary modality. WWLST rates were inversely proportional to gestational age. Life-sustaining treatment was withheld or withdrawn more often for non-Hispanic white infants than for non-Hispanic black infants (72.7% vs 60.4%; 95% CI 1.00 to 1.92) or Hispanic infants (72.7% vs 67.2%; 95% CI 1.32 to 3.72). WWLST rates varied across centres (38.6-92.6%; p<0.001). The centre with the highest rate had adjusted odds 4.89 times greater than the average (95% CI 1.18 to 20.18). The adjusted odds of WWLST were higher for infants with necrotiing enterocolitis (OR 1.77, 95% CI 1.21 to 2.59) and severe brain injury (OR 1.98, 95% CI 1.44 to 2.74).

Conclusions: Among infants who died, WWLST rates varied widely across centres and were associated with gestational age, race, ethnicity, necrotiing enterocolitis, and severe brain injury. Further exploration is needed into how race, centre, and approaches to care of infants with necrotiing enterocolitis and severe brain injury influence WWLST.
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http://dx.doi.org/10.1136/archdischild-2020-318855DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055718PMC
May 2021

Blood Biomarkers and 6- to 7-Year Childhood Outcomes Following Neonatal Encephalopathy.

Am J Perinatol 2020 Oct 10. Epub 2020 Oct 10.

Department of Global and Community Health, George Mason University, Fairfax, Virginia.

Objective:  This study aimed to profile the cytokine/chemokine response from day 0 to 7 in infants (≥36 weeks of gestational age) with neonatal encephalopathy (NE) and to explore the association with long-term outcomes.

Study Design:  This was a secondary study of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network randomized controlled trial of whole body hypothermia for NE. Eligible infants with moderate-severe NE were randomized to cooling or normothermia. Blood spots were collected on days 0 to 1, 2 to 4, and 6 to 7. Twenty-four cytokines/chemokines were measured using a multiplex platform. Surviving infants underwent neurodevelopmental assessment at 6 to 7 years. Primary outcome was death or moderate-severe impairment defined by any of the following: intelligence quotient <70, moderate-severe cerebral palsy (CP), blindness, hearing impairment, or epilepsy.

Results:  Cytokine blood spots were collected from 109 participants. In total 99 of 109 (91%) were assessed at 6 to 7 years; 54 of 99 (55%) developed death/impairment. Neonates who died or were impaired had lower early regulated upon activation normal T cell expressed and secreted (RANTES) and higher day 7 monocyte chemotactic protein (MCP)-1 levels than neonates who survived without impairment. Though TNF-α levels had no association with death/impairment, higher day 0 to 1 levels were observed among neonates who died/developed CP. On multiple regression analysis adjusted for center, treatment group, sex, race, and level of hypoxic ischemic encephalopathy, higher RANTES was inversely associated with death/impairment (odds ratio (OR): 0.31, 95% confidence interval [CI]: 0.13-0.74), while day seven MCP-1 level was directly associated with death/impairment (OR: 3.70, 95% CI: 1.42-9.61). Targeted cytokine/chemokine levels demonstrated little variation with hypothermia treatment.

Conclusion:  RANTES and MCP-1 levels in the first week of life may provide potential targets for future therapies among neonates with encephalopathy.

Key Points: · Elevation of specific cytokines and chemokines in neonates with encephalopathy has been noted along with increased risk of neurodevelopmental impairment in infancy.. · Cytokine/chemokines at <7 days were assessed among neonates in a trial of hypothermia for HIE.. · Neonates who died or were impaired at 6 to 7 years following hypoxic-ischemic encephalopathy had lower RANTES and higher MCP-1 levels than those who survived without impairment..
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http://dx.doi.org/10.1055/s-0040-1717072DOI Listing
October 2020

In-hospital mortality and morbidity among extremely preterm infants in relation to maternal body mass index.

J Perinatol 2021 May 6;41(5):1014-1024. Epub 2020 Oct 6.

Department of Pediatrics, Wayne State University, Detroit, MI, USA.

Objective: The objective of this paper is to compare in-hospital survival and survival without major morbidities in extremely preterm infants in relation to maternal body mass index (BMI).

Methods: This retrospective cohort study included extremely preterm infants (gestational age 22-28 weeks). This study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites. Primary outcome was survival without any major morbidity.

Results: Maternal BMI data were available for 2415 infants. Survival without any major morbidity was not different between groups: 30.8% in the underweight/normal, 28.1% in the overweight, and 28.5% in the obese (P = 0.65). However, survival was lower in the obese group (76.5%) compared with overweight group (83.2%) (P = 0.02). Each unit increase in maternal BMI was associated with decreased odds of infant survival (P < 0.01).

Conclusions: Survival without any major morbidity was not associated with maternal obesity. An increase in maternal prepregnancy BMI was associated with decreased odds of infant survival.
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http://dx.doi.org/10.1038/s41372-020-00847-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021608PMC
May 2021

Genetic predictors of severe intraventricular hemorrhage in extremely low-birthweight infants.

J Perinatol 2021 Feb 25;41(2):286-294. Epub 2020 Sep 25.

Department of Pediatrics, Duke University, Durham, NC, USA.

Objective: To test associations between grades 3 or 4 (severe) intraventricular hemorrhage (IVH) and single nucleotide polymorphisms (SNPs) associated with coagulation, inflammation, angiogenesis, and organ development in an exploratory study.

Study Design: Extremely low-birthweight (ELBW) infants enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's (NRN) Cytokines Study were included if they had cranial ultrasound (CUS) and genotyping data available in the NRN Anonymized DNA Repository and Database. Associations between SNPs and IVH severity were tested with multivariable logistic regression analysis.

Result: One hundred thirty-nine infants with severe IVH and 687 infants with grade 1 or 0 IVH were included. One thousand two hundred seventy-nine SNPs were genotyped. Thirteen were preliminarily associated with severe IVH including five related to central nervous system (CNS) neuronal and neurovascular development.

Conclusion: Genetic variants for CNS neuronal and neurovascular development may be associated with severe IVH in premature infants.
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http://dx.doi.org/10.1038/s41372-020-00821-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889697PMC
February 2021

Growth from Birth Through Six Months for Infants of Mothers in the "Women First" Preconception Maternal Nutrition Trial.

J Pediatr 2021 02 18;229:199-206.e4. Epub 2020 Sep 18.

RTI International, Durham, NC.

Objective: To evaluate whether the fetal linear growth effects of maternal nutrition supplementation would be maintained through 6 months postnatal age.

Study Design: The Women First trial was a multicountry, individually randomized clinical trial that compared the impact of maternal nutrition supplementation initiated preconception (Arm 1) vs at ∼11 weeks of gestation (Arm 2), vs no supplement (Arm 3); the intervention was discontinued at delivery. Trial sites were in Democratic Republic of Congo, Guatemala, India, and Pakistan. Analysis includes 2421 infants born to 2408 randomized women. Primary outcome was the trajectory of length-for-age z scores (LAZ) by arm, based on assessments at birth and 1, 3, and 6 months. We fitted longitudinal models on growth from birth to 6 months using generalized estimating equations; maternal intervention effects were evaluated, adjusting for site and baseline maternal covariates.

Results: Linear growth for Arms 1 and 2 was statistically greater than for Arm 3 in 3 of the 4 countries, with average pairwise mean differences in LAZ of 0.25 (95% CI 0.15-0.35; P < .001) and 0.19 (95% CI 0.09-0.28; P < .001), respectively. Compared with Arm 3, average overall adjusted relative risks (95% CI) for stunting (LAZ <-2) were lower for Arms 1 and 2: 0.76 (0.66-0.87; P < .001) and 0.77 (0.67-0.88; P < .001), respectively.

Conclusions: Improved linear growth in early infancy observed for the 2 intervention arms supports the critical importance of maternal nutrition before conception and in the early phase of gestation.

Trial Registration: ClinicalTrials.gov: NCT01883193.
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http://dx.doi.org/10.1016/j.jpeds.2020.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855785PMC
February 2021

Early Hypoxic Respiratory Failure in Extreme Prematurity: Mortality and Neurodevelopmental Outcomes.

Pediatrics 2020 10 17;146(4). Epub 2020 Sep 17.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland; and.

Objectives: To evaluate the survival and neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants at 18 to 26 months with early hypoxemic respiratory failure (HRF). We also assessed whether African American infants with early HRF had improved outcomes after exposure to inhaled nitric oxide (iNO).

Methods: ELBW infants ≤1000 g and gestational age ≤26 weeks with maximal oxygen ≥60% on either day 1 or day 3 were labeled as "early HRF" and born between 2007 and 2015 in the Neonatal Research Network were included. Using a propensity score regression model, we analyzed outcomes and effects of exposure to iNO overall and separately by race.

Results: Among 7639 ELBW infants born ≤26 weeks, 22.7% had early HRF. Early HRF was associated with a mortality of 51.3%. The incidence of moderate-severe NDI among survivors was 41.2% at 18 to 26 months. Mortality among infants treated with iNO was 59.4%. Female sex (adjusted odds ratio [aOR]: 2.4, 95% confidence interval [CI]: 1.8-3.3), birth weight ≥720 g (aOR: 2.3, 95% CI: 1.7-3.1) and complete course of antenatal steroids (aOR: 1.6, 95% CI: 1.1-2.2) were associated with intact survival. African American infants had a similar incidence of early HRF (21.7% vs 23.3%) but lower exposure to iNO (16.4% vs 21.6%). Among infants with HRF exposed to iNO, intact survival (no death or NDI) was not significantly different between African American and other races (aOR: 1.5, 95% CI: 0.6-3.6).

Conclusions: Early HRF in infants ≤26 weeks' gestation is associated with high mortality and NDI at 18 to 26 months. Use of iNO did not decrease mortality or NDI. Outcomes following iNO exposure were not different in African American infants.
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http://dx.doi.org/10.1542/peds.2019-3318DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546092PMC
October 2020

Blood myo-inositol concentrations in preterm and term infants.

J Perinatol 2021 Feb 15;41(2):247-254. Epub 2020 Sep 15.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.

Objective: To describe relationship between cord blood (representing fetal) myo-inositol concentrations and gestational age (GA) and to determine trends of blood concentrations in enterally and parenterally fed infants from birth to 70 days of age.

Design/methods: Samples were collected in 281 fed or unfed infants born in 2005 and 2006. Myo-inositol concentrations were displayed in scatter plots and analyzed with linear regression models of natural log-transformed values.

Results: In 441 samples obtained from 281 infants, myo-inositol concentrations varied from nondetectable to 1494 μmol/L. Cord myo-inositol concentrations decreased an estimated 11.9% per week increase in GA. Postnatal myo-inositol concentrations decreased an estimated 14.3% per week increase in postmenstrual age (PMA) and were higher for enterally fed infants compared to unfed infants (51% increase for fed vs. unfed infants).

Conclusions: Fetal myo-inositol concentrations decreased with increasing GA. Postnatal concentrations decreased with increasing PMA and were higher among enterally fed than unfed infants.
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http://dx.doi.org/10.1038/s41372-020-00799-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889639PMC
February 2021

Outcomes Following Post-Hemorrhagic Ventricular Dilatation among Infants of Extremely Low Gestational Age.

J Pediatr 2020 Jul 30. Epub 2020 Jul 30.

College of Health and Human Services, George Mason University, Fairfax, VA.

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 April 1, 2011, to December 31, 2015, in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network and categorized into 3 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 Scales of Infant and Toddler Development, 3rd edition, 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 of 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; aOR (95% CI) were 4.6 (3.8-5.7) PHVD vs normal head ultrasound scan 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.
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http://dx.doi.org/10.1016/j.jpeds.2020.07.080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855243PMC
July 2020

Placental transfusion and short-term outcomes among extremely preterm infants.

Arch Dis Child Fetal Neonatal Ed 2021 Jan 30;106(1):62-68. Epub 2020 Jul 30.

Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Objective: To compare short-term outcomes after placental transfusion (delayed cord clamping (DCC) or umbilical cord milking (UCM)) versus immediate cord clamping among extremely preterm infants.

Design: Retrospective study.

Setting: The National Institute of Child Health and Human Development Neonatal Research Network registry.

Patients: Infants born <29 weeks' gestation in 2016 or 2017 without congenital anomalies who received active treatment after delivery.

Intervention/exposure: DCC or UCM.

Main Outcome Measures: Primary outcomes: (1) composite of mortality or major morbidity by 36 weeks' postmenstrual age (PMA); (2) mortality by 36 weeks PMA and (3) composite of major morbidities by 36 weeks' PMA. Secondary composite outcomes: (1) any grade intraventricular haemorrhage or mortality by 36 weeks' PMA and (2) hypotension treatment in the first 24 postnatal hours or mortality in the first 12 postnatal hours. Outcomes were assessed using multivariable regression, adjusting for mortality risk factors identified a priori, significant confounders and centre as a random effect.

Results: Among 3116 infants, 40% were exposed to placental transfusion, which was not associated with the primary composite outcome of mortality or major morbidity by 36 weeks' PMA (adjusted OR (aOR) 1.26, 95% CI 0.95 to 1.66). However, exposure was associated with decreased mortality by 36 weeks' PMA (aOR 0.71, 95% CI 0.55 to 0.92) and decreased hypotension treatment in first 24 postnatal hours (aOR 0.66, 95% CI 0.53 to 0.82).

Conclusion: In this extremely preterm infant cohort, exposure to placental transfusion was not associated with the composite outcome of mortality or major morbidity, though there was a reduction in mortality by 36 weeks' PMA.

Trial Registration Number: NCT00063063.
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http://dx.doi.org/10.1136/archdischild-2019-318710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736256PMC
January 2021

Racial/Ethnic Disparities Among Extremely Preterm Infants in the United States From 2002 to 2016.

JAMA Netw Open 2020 06 1;3(6):e206757. Epub 2020 Jun 1.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.

Importance: Racial/ethnic disparities in quality of care among extremely preterm infants are associated with adverse outcomes.

Objective: To assess whether racial/ethnic disparities in major outcomes and key care practices were changing over time among extremely preterm infants.

Design, Setting, And Participants: This observational cohort study used prospectively collected data from 25 US academic medical centers. Participants included 20 092 infants of 22 to 27 weeks' gestation with a birth weight of 401 to 1500 g born at centers participating in the National Institute of Child Health and Human Development Neonatal Research Network from 2002 to 2016. Of these infants, 9316 born from 2006 to 2014 were eligible for follow-up at 18 to 26 months' postmenstrual age (excluding 5871 infants born before 2006, 2594 infants born after 2014, and 2311 ineligible infants including 64 with birth weight >1000 g and 2247 infants with gestational age >26 6/7 weeks), of whom 745 (8.0%) did not have known follow-up outcomes at 18 to 26 months.

Main Outcomes And Measures: Rates of mortality, major morbidities, and care practice use over time were evaluated using models adjusted for baseline characteristics, center, and birth year. Data analyses were conducted from 2018 to 2019.

Results: In total, 20 092 infants with a mean (SD) gestational age of 25.1 (1.5) weeks met the inclusion criteria and were available for the primary outcome: 8331 (41.5%) black infants, 3701 (18.4%) Hispanic infants, and 8060 (40.1%) white infants. Hospital mortality decreased over time in all groups. The rate of improvement in hospital mortality over time did not differ among black and Hispanic infants compared with white infants (black infants went from 35% to 24%, Hispanic infants went from 32% to 27%, and white infants went from 30% to 22%; P = .59 for race × year interaction). The rates of late-onset sepsis among black infants (went from 37% to 24%) and Hispanic infants (went from 45% to 23%) were initially higher than for white infants (went from 36% to 25%) but decreased more rapidly and converged during the most recent years (P = .02 for race × year interaction). Changes in rates of other major morbidities did not differ by race/ethnicity. Death before follow-up decreased over time (from 2006 to 2014: black infants, 14%; Hispanic infants, 39%, white infants, 15%), but moderate-severe neurodevelopmental impairment increased over time in all racial/ethnic groups (increase from 2006 to 2014: black infants, 70%; Hispanic infants, 123%; white infants, 130%). Rates of antenatal corticosteroid exposure (black infants went from 72% to 90%, Hispanic infants went from 73% to 83%, and white infants went from 86% to 90%; P = .01 for race × year interaction) and of cesarean delivery (black infants went from 45% to 59%, Hispanic infants went from 49% to 59%, and white infants went from 62% to 63%; P = .03 for race × year interaction) were initially lower among black and Hispanic infants compared with white infants, but these differences decreased over time.

Conclusions And Relevance: Among extremely preterm infants, improvements in adjusted rates of mortality and most major morbidities did not differ by race/ethnicity, but rates of neurodevelopmental impairment increased in all groups. There were narrowing racial/ethnic disparities in important care practices, including the use of antenatal corticosteroids and cesarean delivery.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.6757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287569PMC
June 2020

Early working memory is a significant predictor of verbal and processing skills at 6-7 years in children born extremely preterm.

Early Hum Dev 2020 08 23;147:105083. Epub 2020 May 23.

University of New Mexico Health Sciences Center, Albuquerque, NM, USA.

Objective: The study was designed to investigate whether attainment of object permanence, a measure of early working memory used at 18-22 months corrected age, was associated with executive function at 6-7 years in a cohort of children born extremely preterm.

Study Design: Children enrolled in the Neuroimaging and Neurodevelopmental Outcome (NEURO) study, a secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) of the NICHD NRN, were eligible for this longitudinal study. Testing completed at 18 to 22 months corrected age was compared to testing at school age with a specific focus on measures of executive function.

Results: Children who had achieved object permanence mastery at a corrected age of 18-22 months had higher mean scores on the WISC-IV tests of verbal comprehension and processing speed at age 6-7 years. Regression models indicated that object permanence scores were significant predictors of both verbal comprehension and processing speeds scores, after controlling for other factors. When analyzed by subgroup for sex, these results were significant for girls but not for boys.

Conclusions: This study found that an early mastery of object permanence was associated with higher scores in areas of verbal comprehension and processing speed in girls. These results have implications for potentially identifying young children born preterm that are at greater risk for difficulties with cognitive and working memory skills at school age.
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http://dx.doi.org/10.1016/j.earlhumdev.2020.105083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384388PMC
August 2020

Early-Onset Neonatal Sepsis 2015 to 2017, the Rise of Escherichia coli, and the Need for Novel Prevention Strategies.

JAMA Pediatr 2020 07 6;174(7):e200593. Epub 2020 Jul 6.

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland.

Importance: Early-onset sepsis (EOS) remains a potentially fatal newborn condition. Ongoing surveillance is critical to optimize prevention and treatment strategies.

Objective: To describe the current incidence, microbiology, morbidity, and mortality of EOS among a cohort of term and preterm infants.

Design, Setting, And Participants: This prospective surveillance study included a cohort of infants born at a gestational age (GA) of at least 22 weeks and birth weight of greater than 400 g from 18 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from April 1, 2015, to March 31, 2017. Data were analyzed from June 14, 2019, to January 28, 2020.

Main Outcomes And Measures: Early-onset sepsis defined by isolation of pathogenic species from blood or cerebrospinal fluid culture within 72 hours of birth and antibiotic treatment for at least 5 days or until death.

Results: A total of 235 EOS cases (127 male [54.0%]) were identified among 217 480 newborns (1.08 [95% CI, 0.95-1.23] cases per 1000 live births). Incidence varied significantly by GA and was highest among infants with a GA of 22 to 28 weeks (18.47 [95% CI, 14.57-23.38] cases per 1000). No significant differences in EOS incidence were observed by sex, race, or ethnicity. The most frequent pathogens were Escherichia coli (86 [36.6%]) and group B streptococcus (GBS; 71 [30.2%]). E coli disease primarily occurred among preterm infants (68 of 131 [51.9%]); GBS disease primarily occurred among term infants (54 of 104 [51.9%]), with 24 of 45 GBS cases (53.3%) seen in infants born to mothers with negative GBS screening test results. Intrapartum antibiotics were administered to 162 mothers (68.9%; 110 of 131 [84.0%] preterm and 52 of 104 [50.0%] term), most commonly for suspected chorioamnionitis. Neonatal empirical antibiotic treatment most frequently included ampicillin and gentamicin. All GBS isolates were tested, but only 18 of 81 (22.2%) E coli isolates tested were susceptible to ampicillin; 6 of 77 E coli isolates (7.8%) were resistant to both ampicillin and gentamicin. Nearly all newborns with EOS (220 of 235 [93.6%]) displayed signs of illness within 72 hours of birth. Death occurred in 38 of 131 infected infants with GA of less than 37 weeks (29.0%); no term infants died. Compared with earlier surveillance (2006-2009), the rate of E coli infection increased among very low-birth-weight (401-1500 g) infants (8.68 [95% CI, 6.50-11.60] vs 5.07 [95% CI, 3.93-6.53] per 1000 live births; P = .008).

Conclusions And Relevance: In this study, EOS incidence and associated mortality disproportionately occurred in preterm infants. Contemporary cases have demonstrated the limitations of current GBS prevention strategies. The increase in E coli infections among very low-birth-weight infants warrants continued study. Ampicillin and gentamicin remained effective antibiotics in most cases, but ongoing surveillance should monitor antibiotic susceptibilities of EOS pathogens.
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http://dx.doi.org/10.1001/jamapediatrics.2020.0593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199167PMC
July 2020

Authors' Response.

Pediatrics 2020 Mar 31. Epub 2020 Mar 31.

Neonatologist, Wayne State University.

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http://dx.doi.org/10.1542/peds.2020-0056BDOI Listing
March 2020

Assessment of an Updated Neonatal Research Network Extremely Preterm Birth Outcome Model in the Vermont Oxford Network.

JAMA Pediatr 2020 05 4;174(5):e196294. Epub 2020 May 4.

Office of Research, George Mason University College of Health and Human Services, Fairfax, Virginia.

Importance: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals.

Objective: To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States.

Design, Setting, And Participants: This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks' 0 days' to 25 weeks' 6 days' gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019.

Exposures: Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids.

Main Outcomes And Measures: The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months' corrected age and measures of hospital resource use (days of hospitalization and ventilator use).

Results: Among 4176 actively treated infants in the NRN cohort (48% female; mean [SD] gestational age, 24.2 [0.8] weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean [SD] gestational age, 24.2 [0.8] weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean [SD] gestational age, 24.1 [0.8] weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean [SD] gestational age, 24.1 [0.8] weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age-only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%).

Conclusions And Relevance: An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.
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http://dx.doi.org/10.1001/jamapediatrics.2019.6294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052789PMC
May 2020

Neonatal oxygen saturations and blood pressure at school-age in children born extremely preterm: a cohort study.

J Perinatol 2020 06 28;40(6):902-908. Epub 2020 Feb 28.

Department of Pediatrics, University of New Mexico, Albuquerque, NM, USA.

Objective: To explore the relationship between neonatal oxygen saturation and BP at age 6-7 years in a cohort of infants born extremely preterm.

Study Design: Infants <28 weeks gestation were assigned to a higher or lower oxygen saturation target. Oximeter data were monitored throughout the neonatal period. A subset of survivors was seen at age 6. BP was measured and compared by group assignment, achieved saturations, and time spent in hypoxemia (saturations <80%).

Results: There was no difference in systolic or diastolic BP between assigned groups. Median achieved weekly oxygen saturation was not associated with BP. Longer duration of hypoxemia during the first week of age was associated with higher systolic BP.

Conclusions: Neither target nor actual median oxygen saturations in this study was associated with BP at school age. Increased duration of hypoxemia in the first postnatal week was associated with higher systolic BP at 6-7 years of age.
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http://dx.doi.org/10.1038/s41372-020-0619-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260090PMC
June 2020

Behavior Profiles at 2 Years for Children Born Extremely Preterm with Bronchopulmonary Dysplasia.

J Pediatr 2020 04 31;219:152-159.e5. Epub 2020 Jan 31.

Department of Pediatrics, Stanford University, Palo Alto, CA.

Objective: To characterize behavior of 2-year-old children based on the severity of bronchopulmonary dysplasia (BPD).

Study Design: We studied children born at 22-26 weeks of gestation and assessed at 22-26 months of corrected age with the Child Behavior Checklist (CBCL). BPD was classified by the level of respiratory support at 36 weeks 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.
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http://dx.doi.org/10.1016/j.jpeds.2019.12.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096270PMC
April 2020

Preconception nutrition intervention improved birth length and reduced stunting and wasting in newborns in South Asia: The Women First Randomized Controlled Trial.

PLoS One 2020 29;15(1):e0218960. Epub 2020 Jan 29.

Pediatric Nutrition, University of Colorado School of Medicine, Aurora, Colorado, United States of America.

South Asia has >50% of the global burden of low birth weight (LBW). The objective was to determine the extent to which maternal nutrition interventions commenced before conception or in the 1st trimester improved fetal growth in this region. This was a secondary analysis of combined newborn anthropometric data for the South Asian sites (India and Pakistan) in the Women First Preconception Maternal Nutrition Trial. Participants were 972 newborn of mothers who were poor, rural, unselected on basis of nutritional status, and had been randomized to receive a daily lipid-based micronutrient supplement commencing ≥3 months prior to conception (Arm 1), in the 1st trimester (Arm 2), or not at all (Arm 3). An additional protein-energy supplement was provided if BMI <20 kg/m2 or gestational weight gain was less than guidelines. Gestational age was established in the 1st trimester and newborn anthropometry obtained <48-hours post-delivery. Mean differences at birth between Arm 1 vs. 3 were length +5.3mm and weight +89g. Effect sizes (ES) and relative risks (RR) with 95% CI for Arm 1 vs. 3 were: length-for-age Z-score (LAZ) +0.29 (0.11-0.46, p = 0.0011); weight-for-age Z-score (WAZ) +0.22 (0.07-0.37, p = 0.0043); weight-to-length-ratio-for-age Z-score (WLRAZ) +0.27 (0.06-0.48, p = 0.0133); LAZ<-2, 0.56 (0.38-0.82, p = 0.0032); WAZ <-2, 0.68 (0.53-0.88, p = 0.0028); WLRAZ <-2, 0.76 (0.64-0.89, p = 0.0011); small-for-gestational-age (SGA), 0.74 (0.66-0.83, p<0.0001); low birth weight 0.81 (0.66-1.00, p = 0.0461). For Arm 2 vs. 3, LAZ, 0.21 (0.04-0.38); WAZ <-2, 0.70 (0.53-0.92); and SGA, 0.88 (0.79-0.97) were only marginally different. ES or RR did not differ for preterm birth for either Arm 1 vs. 3 or 2 vs. 3. In conclusion, point estimates for both continuous and binary anthropometric outcomes were consistently more favorable when maternal nutrition supplements were commenced ≥3 months prior to conception indicating benefits to fetal growth of improving women's nutrition in this population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0218960PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988936PMC
March 2020

Is routine evaluation of gastric residuals for premature infants safe or effective?

J Perinatol 2020 03 7;40(3):540-543. Epub 2020 Jan 7.

Biostatistics and Epidemiology Division, RTI International, Rockville, MD, USA.

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http://dx.doi.org/10.1038/s41372-019-0582-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127870PMC
March 2020
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