Timing of postnatal steroids for bronchopulmonary dysplasia: association with pulmonary and neurodevelopmental outcomes

Objective: To determine the associations between age at first postnatal corticosteroids (PNS) exposure and risk for severe bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). Study Design: Cohort study of 951 infants born <27 weeks gestational age at NICHD Neonatal Research Network sites who received PNS between 8 days of life (DOL) and 36 weeks’ postmenstrual age was used to produce adjusted odds ratios (aOR). Results: Compared to infants in the reference group (22–28 DOL-lowest rate), aOR for severe BPD was similar for children given PNS between DOL 8–49 but higher among infants treated at DOL 50–63 (aOR 1.77, 95% CI 1.03–3.06), and at DOL ≥64 (aOR 3.06, 95% CI 1.44–6.48). The aOR for NDI did not vary significantly by age of PNS exposure. Conclusion: For infants at high risk of BPD, initial PNS should be considered prior to 50 DOL for the lowest associated odds of severe BPD

Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial

Importance: 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. Objective: 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. Design, Setting, and Participants: 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. Interventions: 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). Main Outcomes and Measures: The composite of death or disability (moderate or severe) at 18 to 22 months adjusted for level of encephalopathy and age at randomization. Results: 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. Conclusions and Relevance: 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

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

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

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Immediate and delayed cord clamping in infants born between 24 and 32 weeks: A pilot randomized controlled trial

Objective: This pilot study\u27s aim was establish feasibility of a protocol for delayed cord clamping (DCC) versus immediate cord clamping (ICC) at preterm birth and to examine its effects on initial blood pressure and other outcomes. Study design: A randomized controlled trial recruited 32 infants between 24 and 32 weeks. Immediately before delivery, mothers were randomized to ICC (cord clamped at 5 to 10 seconds) or DCC (30- to 45-second delay in cord clamping) groups. Results: Intention-to-treat analyses revealed that the DCC group were more likely to have higher initial mean blood pressures (adjusted OR 3.4) and less likely to be discharged on oxygen (adjusted OR 8.6). DCC group infants had higher initial glucose levels (ICC = 36 mg/dl, DCC = 73.1 mg/dl; p = 0.02). Conclusion: The research design is feasible. The immediate benefit of improved blood pressure was confirmed and other findings deserve consideration for further study

Determinants of Neonatal Readmission in Healthy Term Infants: Results from a Nested Case-Control Study

Objective The aim of this study was to estimate the incidence and identify the factors associated with neonatal readmission among healthy term infants. Study Design A nested case-control study with matching was conducted at a large level III perinatal hospital with approximately 8,700 deliveries each year. Each case infant (n = 130) was matched to two control infants (n = 260) on the case infant\u27s date of birth (±7 days) and the mother\u27s maternal age (\u3c20 years, 20-29, 30-39, and \u3e39 years). All infants were selected from a cohort of eligible term, healthy, in-state infants admitted to the newborn unit postdelivery from January 1, 2016 to May 8, 2017. Data were analyzed using hierarchical conditional logistic regression. Results The incidence of neonatal readmission was 2.2%, and all readmissions occurred within 8.6 days of birth. Earlier gestational age (37 weeks; odds ratio [OR]: 4.11, 95% confidence interval [CI]: 1.79-9.45; 38 weeks OR: 1.29, CI 0.60-2.75; [ref] 39 weeks), jaundice on day two of life (OR: 2.45; CI: 1.40-4.30), maternal group B streptococcus chemoprophylaxis (OR: 2.55; CI: 1.23-5.28 [Ref N/A]) were associated with readmission. Delivery by cesarean section (OR: 0.31, CI: 0.12-0.79) and each milliliter of formula [first three days] (OR: 0.96; CI: 0.993-0.999) were protective. Conclusion Neonatal readmission in healthy term infants may potentially be reduced with identification of modifiable determinants of readmission prior to discharge. Policies to capture the true incidence of neonatal readmissions should include admissions to hospitals other than the birth hospital

The effects of betamethasone on the amplitude integrated EEG of infants born at 34- or 35-weeks gestation

OBJECTIVE: Assess if maternal betamethasone administration at 34-35 weeks accelerated neonatal amplitude integrated EEG (aEEG) maturation. STUDY DESIGN: Nested, observational cohort in 7 centers participating in the Antenatal Late Preterm Steroid randomized trial. Up to 2 aEEGs were obtained in neonates born from 34-35 weeks gestation before 72 h (aEEG 1) and at 5-7 days (aEEG 2) if hospitalized. Personnel and aEEG central readers were masked to the intervention. The primary outcome was maturation reflected by cycle frequency; secondary outcomes were border voltage, span, and discontinuity. RESULTS: 58 neonates were enrolled (betamethasone, 28, placebo, 30). On aEEG 1, cycle frequency did not differ, but betamethasone exposed infants had a greater lower border voltage and a broader span. On aEEG 2, both groups displayed increases in lower border voltage. CONCLUSIONS: Betamethasone associated changes in lower border voltage support accelerated electrical activity. Further investigation is needed to understand the broader span

Blood Myo-Inositol Concentrations in Preterm and Term Infants

© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. 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

Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm

© 2018 Elsevier Inc. Objective: To investigate associations in toddlers born extremely preterm (\u3c28 weeks) between neonatal neuroimaging and 18- to 22-month developmental and behavioral outcomes. Study design: Cohort analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely preterm. Subjects underwent cranial ultrasonography and near-term magnetic resonance imaging (MRI). At 18-22 months of corrected age, the assessment included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem and Competence Scale scores and the Bayley Scales of Infant Development, Third Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the Competence Scale assesses social-emotional competence. We examined associations of Problem and Competence scores and positive screen rates with cranial ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were compared using ANOVA and positive screen rates with the χ 2 test. We computed correlations between BITSEA and Bayley-III scores. Results: Of the 397 children, positive BITSEA screens were found in 34% for the Problem score and 26% for the Competence score. Presence of lesions on near-term MRI that included cerebellar lesions were significantly associated with lower BITSEA Competence but not with Problem scores; Competence scores were inversely related to the presence/significance of lesions. Positive screens on Competence scores and on both Competence and Problem scores were significantly associated with Bayley-III cognitive and language scores \u3c85 (P \u3c.001). Conclusions: Social–emotional competence contributes to deficits in cognitive and language development. Presence of injury on near-term MRI that includes cerebellar lesions is associated with later social–emotional competence and may be a useful predictor to guide early assessment and intervention. Trial registration: ClinicalTrials.gov: NCT00063063 and NCT00233324