QuestionWhat are the early school-age functional outcomes of preterm-born children who were treated with hydrocortisone vs placebo for prevention of bronchopulmonary dysplasia (BPD)?FindingsIn this follow-up study of a randomized clinical trial, neonatal hydrocortisone treatment for prevention of BPD did not improve functional outcomes (functional impairment in 71.3% who received hydrocortisone vs 73.3% who received placebo) or any of the individual components of this composite outcome, including cognitive delay, motor delay, academic delay, or exercise capacity at corrected age 5 to 7 years.MeaningNeonatal hydrocortisone treatment of preterm infants with high risk for BPD did not provide benefit or evident harm at early school age. ImportanceBronchopulmonary dysplasia (BPD) is the most common in-hospital morbidity of prematurity, associated with significant long-term medical and neurodevelopmental sequelae and health resource utilization. The Neonatal Research Network (NRN) Hydrocortisone for BPD Trial evaluated the efficacy and safety of hydrocortisone to prevent BPD in high-risk very preterm infants; the impact of hydrocortisone on school-age outcomes in this trial cohort is previously unreported.ObjectiveTo evaluate the impact of neonatal hydrocortisone treatment on early school-age functional motor, cognitive, academic, and pulmonary outcomes among children who participated in the Hydrocortisone for BPD Trial.Design, Setting, and ParticipantsThis prospective long-term cohort study is a follow-up of a randomized clinical trial, the Hydrocortisone for BPD Trial, conducted at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development NRN. Participants, enrolled from August 2011 to February 2018, included intubated infants who had been born before 30 weeks' gestational age and had been mechanically ventilated for at least 7 days by postnatal day 14 to 28. They were eligible for a single, in-person, early school-age visit between corrected age 5 years 0 months and 7 years 11 months, conducted from September 2017 to July 2024. Data analysis was performed from July 2024 to September 2025.InterventionParticipants were randomized to a 10-day tapering course of hydrocortisone or placebo beginning at 14 to 28 postnatal days.Main Outcomes and MeasuresEarly school-age study visits were performed by certified, masked assessors. The primary outcome of functional impairment was defined as any of the following: cognitive delay, motor delay, academic delay, or poor functional exercise capacity.ResultsThe primary outcome was available for 545 of 674 eligible children (80.9%), including 272 children in the hydrocortisone group (152 [55.9%] female; mean [SD] gestational age, 24.9 [1.5] weeks; mean [SD] age at visit, 5.3 [0.6] years) and 273 in the placebo group (108 [39.6%] female; mean [SD] gestational age, 24.8 [1.5] weeks; mean [SD] age at visit, 5.4 [0.6] years). There was no difference in the rate of functional impairment between the hydrocortisone group (194 of 272 children [71.3%]) and the placebo group (200 of 273 children [73.3%]) (adjusted relative risk, 0.99; 95% CI, 0.89-1.10), nor were there differences in the rates of the individual components. Motor delay was the most common impairment (308 of 510 children [60.4%]), followed by poor functional exercise capacity (175 of 484 children [36.2%]).Conclusions and RelevanceIn this study, neonatal hydrocortisone treatment of preterm infants with high risk for BPD did not impact functional impairment or its components; nearly three-quarters of the children demonstrated functional impairment at school age.Trial RegistrationClinicalTrials.gov Identifier: NCT01353313 This follow-up cohort study of a randomized clinical trial evaluates whether neonatal hydrocortisone treatment is associated with functional motor, cognitive, academic, and pulmonary outcomes at early school age.

BACKGROUND:Infants with congenital diaphragmatic hernia (CDH) remain at high risk for ECMO and mortality. We previously reported improved outcomes after implementing new CDH care guidelines. This study reassesses ECMO rates, survival, and guideline adherence to determine if improvements persisted. METHODS:Retrospective review of all neonatal CDH cases at a single center during pre-guideline (2003-2015, n = 229) and post-guideline (2016-2024, n = 160) periods, with post-guideline subdivided into two epochs: post-1 (2016-2019, n = 70) and post-2 (2020-2024, n = 90). RESULTS:Survival without ECMO improved (pre-53%; post-1 74%; post-2 82%; p < 0.001), as did overall survival (72% vs. 83% vs. 86%; p = 0.006). ECMO use decreased (31% vs. 14% vs. 6%; p < 0.001). Inhaled nitric oxide use remained low, and vasoactive medication use dropped significantly in post-2. CONCLUSION:Sustained survival improvement and reduced ECMO use followed guideline changes emphasizing minimal stimulation, gentle ventilation, delayed transfer, pre-ductal saturation monitoring, and limited vasoactive therapy.

Congenital diaphragmatic hernia (CDH) is a complex neonatal condition characterized by pulmonary hypoplasia and pulmonary hypertension, requiring specialized ventilatory management from birth through postoperative care. This article synthesizes the current evidences and evolving strategies for optimizing respiratory support in CDH, emphasizing the importance of gentle ventilation to minimize lung injury and improve outcomes. We discuss delivery room resuscitation protocols, initial ventilator settings, and the comparative roles of conventional mechanical ventilation and high-frequency ventilation. Despite advances, significant variability persists in practice, underscoring the need for high-quality clinical trials to refine evidence-based guidelines and reduce morbidity and mortality in this vulnerable population.

Importance:Bronchopulmonary dysplasia (BPD) is the most common in-hospital morbidity of prematurity, associated with significant long-term medical and neurodevelopmental sequelae and health resource utilization. The Neonatal Research Network (NRN) Hydrocortisone for BPD Trial evaluated the efficacy and safety of hydrocortisone to prevent BPD in high-risk very preterm infants; the impact of hydrocortisone on school-age outcomes in this trial cohort is previously unreported. Objective:To evaluate the impact of neonatal hydrocortisone treatment on early school-age functional motor, cognitive, academic, and pulmonary outcomes among children who participated in the Hydrocortisone for BPD Trial. Design, Setting, and Participants:This prospective long-term cohort study is a follow-up of a randomized clinical trial, the Hydrocortisone for BPD Trial, conducted at 19 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development NRN. Participants, enrolled from August 2011 to February 2018, included intubated infants who had been born before 30 weeks' gestational age and had been mechanically ventilated for at least 7 days by postnatal day 14 to 28. They were eligible for a single, in-person, early school-age visit between corrected age 5 years 0 months and 7 years 11 months, conducted from September 2017 to July 2024. Data analysis was performed from July 2024 to September 2025. Intervention:Participants were randomized to a 10-day tapering course of hydrocortisone or placebo beginning at 14 to 28 postnatal days. Main Outcomes and Measures:Early school-age study visits were performed by certified, masked assessors. The primary outcome of functional impairment was defined as any of the following: cognitive delay, motor delay, academic delay, or poor functional exercise capacity. Results:The primary outcome was available for 545 of 674 eligible children (80.9%), including 272 children in the hydrocortisone group (152 [55.9%] female; mean [SD] gestational age, 24.9 [1.5] weeks; mean [SD] age at visit, 5.3 [0.6] years) and 273 in the placebo group (108 [39.6%] female; mean [SD] gestational age, 24.8 [1.5] weeks; mean [SD] age at visit, 5.4 [0.6] years). There was no difference in the rate of functional impairment between the hydrocortisone group (194 of 272 children [71.3%]) and the placebo group (200 of 273 children [73.3%]) (adjusted relative risk, 0.99; 95% CI, 0.89-1.10), nor were there differences in the rates of the individual components. Motor delay was the most common impairment (308 of 510 children [60.4%]), followed by poor functional exercise capacity (175 of 484 children [36.2%]). Conclusions and Relevance:In this study, neonatal hydrocortisone treatment of preterm infants with high risk for BPD did not impact functional impairment or its components; nearly three-quarters of the children demonstrated functional impairment at school age. Trial Registration:ClinicalTrials.gov Identifier: NCT01353313.

Objective To assess accuracy of prediction of oxygenation index (OI=mean airway pressure*FiO2*100÷PaO2) with a non-invasive alternative, oxygen saturation index (OSI= FiO2*100÷SpO2) in a prospectively collected multicenter cohort of children with congenital diaphragmatic hernia (CDH) with substantial degree of hypoxemia (OI≥10 or OSI≥5). Study design This secondary analysis of the Milrinone in CDH Trial studied 61 subjects with OI≥10 or OSI≥5 at randomization. Prospectively collected arterial blood gas (ABG) data with PaO2 and preductal and postductal SpO2 were used to compare all OI and preductal OSI, all OI and postductal OSI, preductal OI/OSI only and postductal OI/OSI, by simple linear and quadratic regression modelling. Results Indwelling arterial lines were present in 61 of 66 randomized subjects (51 as umbilical arterial lines). There were 572 matched pairs of PaO2-SpO2 data. Repeated measures correlation (95% CI) between all OI and preductal OSI by linear regression was 0.82 (0.79,0.85; n=61 patients, 572 samples), and between OI and OSI with SpO2 matched from the same preductal or postductal sites as the ABG were 0.97 (9.91,0.89) and 0.86 (0.84,0.89) respectively. The relationship between preductal OI and OSI was described best by the quadratic equation, OI=0.3*OSI+0.1*OSI2+2.4 (4 patients, 22 samples) and postductal OI and OSI by OI=0.6*OSI +0.08*OSI2+2.6 (54 patients, 477 samples). There was no difference in quasi-likelihood under the independence model information criterion (QlCu) between linear and quadratic models (461 vs 462 respectively). Use of site-specific (preductal vs postductal) quadratic equations captured the non-linear relationship but did not improve QlCu. Conclusion Non-invasive OSI values correlate well with OI. The use of OSI based on preductal SpO2 may be a suitable alternate strategy for clinical trials even if post-ductal arterial access is available.

Importance:Extremely preterm infants are at high risk for bronchopulmonary dysplasia (BPD) and death. Multiple small randomized clinical trials showed that a combination of budesonide with surfactant compared with surfactant alone reduced BPD or death. Objective:To determine if early intratracheal administration of a combination of budesonide (0.25 mg/kg) mixed with surfactant, compared with surfactant alone, reduces physiologic BPD or death by 36 weeks' postmenstrual age in extremely preterm infants. Design, Setting, and Participants:This double-masked randomized clinical trial was conducted from April 2021 to June 2024 in the 17 centers of the United States Neonatal Research Network. Infants 22 to 28 weeks' gestation or 401 to 1000 g birth weight were enrolled after clinical decision to give surfactant, with the first dose of surfactant being study drug (prior surfactant was an exclusion criterion). Interventions:Infants were randomly allocated 1:1 to receive 1 to 2 doses of budesonide + surfactant (poractant alfa) or surfactant alone via endotracheal tube within 50 hours of birth. Main Outcomes and Measures:The primary outcome was physiologic BPD or death by 36 weeks' postmenstrual age. There were 5 prespecified secondary outcomes and multiple prespecified exploratory and safety outcomes. Results:The trial was stopped with 641 infants enrolled (55.3% of 1160 planned; mean birth weight, 810 g [SD, 256 g]; gestational age, 25.9 weeks [SD, 1.9 weeks]), because interim analysis at 50% enrollment reached the prespecified futility threshold. The incidence of BPD or death was 68.5% in the budesonide + surfactant group and 67.9% in the surfactant-alone group (adjusted relative risk [RR], 1.00 [95% CI, 0.90-1.11]). No differences were noted in mortality (15.3% vs 13.2%; adjusted RR, 1.13 [95% CI, 0.78-1.64]) or BPD among survivors to 36 weeks' postmenstrual age (62.9% vs 63.0%; adjusted RR, 0.99 [95% CI, 0.87-1.12]). More infants who received budesonide + surfactant compared with surfactant alone had hyperglycemia (66.7% vs 49.8%; adjusted RR, 1.33 [95% CI, 1.17-1.51]). Conclusions and Relevance:In this large multicenter trial, the combination of budesonide with surfactant did not reduce the risk of BPD or death at 36 weeks' postmenstrual age in extremely preterm infants. Trial Registration:ClinicalTrials.gov Identifier: NCT04545866.

Importance Hypothermia begun less than 6 hours after birth reduces death or disability in infants with encephalopathy due to hypoxia-ischemia at 36 or more weeks' gestation. Trials of hypothermia for infants younger than 36 weeks' gestation are lacking. Objective To assess the probability that hypothermia at less than 6 hours after birth decreases death or disability in infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy. Design, Setting, and Participants This randomized clinical trial was conducted between July 2015 and December 2022 for infants 33 to 35 weeks' gestation with moderate or severe hypoxic-ischemic encephalopathy at less than 6 hours after birth. Bayesian and intention-to-treat analyses were prespecified. The setting included 19 US Neonatal Research Network centers. Data were analyzed from March 2023 to November 2024. Interventions Infants received unblinded targeted esophageal temperature management. Infants with hypothermia were maintained at 33.5 degrees C (acceptable 33-34 degrees C) for 72 hours and then rewarmed. Infants with normothermia were to be maintained at 37 degrees C (acceptable 36.5-37.3 degrees C). Main Outcomes and Measures Composite of death or disability (moderate or severe) at 18 to 22 months' corrected age adjusted for level of encephalopathy and center. Results A total of 168 infants with hypothermia and normothermia were preterm (mean [SD] age, 34.0 [0.8] weeks' gestation and 34.1 [0.8] weeks' gestation, respectively), while 46 of 88 (52%) and 45 of 80 (56%) were male, respectively. Randomization occurred at mean (SD) 4.5 (1.2) hours and 4.5 (1.3) hours for the groups with hypothermia and normothermia, respectively. The primary outcome occurred in 29 of 83 infants (35%) with hypothermia and 20 of 69 infants (29%) with normothermia (adjusted relative risk [hypothermic/normothermic], 1.11; 95% credibility interval, 0.74-2.00), and death occurred in 18 of 88 infants (20%) with hypothermia and 9 of 78 infants (12%) with normothermia (adjusted relative risk, 1.38; 95% credibility interval, 0.79-2.85). Bayesian analysis with neutral prior indicated 74% probability of increased death or disability and 87% probability of increased death with hypothermia. Conclusions and Relevance Among infants 33 to 35 weeks' gestation with hypoxic-ischemic encephalopathy, hypothermia at less than 6 hours' age did not reduce death or disability at 18 to 22 months' corrected age. Trial Registration ClinicalTrials.gov Identifier: NCT01793129

Background Mortality in congenital diaphragmatic hernia (CDH) approximates 30 %. Both severe lung hypoplasia and other anomalies contribute to demise regardless of repair and/or extracorporeal membrane oxygenation (ECMO). We report clinical and physiological parameters for CDH infants not offered repair or ECMO (NoR/ECMO). Methods A single center retrospective analysis of 364 CDH infants managed from 01/2003 - 12/2024. We analyzed reasonings to not offer repair or ECMO in 49 infants (13 %) across two time epochs. We compared the outcomes of infants that did or did not meet 3 possible lethal lung hypoplasia criteria based on maximum SpO2 and minimum paCO2 in the first 24 h of life. Results Concurrent anomalies (n = 27, 55 %), prematurity <34 weeks gestation (n = 17, 35 %), and/or severe lung hypoplasia (n = 15, 30 %) were the most common reasons for NoR/ECMO; multiple reasons occurred in 19 (39 %). There were no differences between epochs for NoR/ECMO. We assessed 3 combinations of highest SpO2 and lowest paCO2 in the first 24 h of life on outcomes. Only 9/364 (2.5 %) patients had both highest SpO2 < 85 % and lowest paCO2 > 75 mmHg; none were offered ECMO or repair. Another 15 infants met one or the other criteria; 4 were offered ECMO and repair with no survivors. Conclusion In our center, severe concurrent anomalies, prematurity, and severe lung hypoplasia accounted for 90 % of all CDH infants not offered repair or ECMO. Failure to achieve either SpO2 ≥ 85 % and/or paCO2 ≤ 75 mmHg within the first 24 h of life despite optimal medical management was uncommon but consistent with lethal lung hypoplasia.

In their recently online-published Review Article, El-Dib included multiple critiques of our Randomized Controlled Trial (RCT) of Whole Body Hypothermia in Preterm Infants 33–35 Wks Gestation. We agree that more data from larger studies may help to further assess safety and efficacy of therapeutic hypothermia (TH) for infants 35 wks GA or less, provided that such studies are rigorously designed, implemented and reported. Given the results of our trial, the efficacy and safety of hypothermia in this population has not been established. Responses to many of the issues they raise about our trial are included. For now, the results of our RCT remain the best available data regarding therapeutic hypothermia in this population.

Previous studies suggest that administration of erythropoiesis-stimulating agents darbepoetin or erythropoietin to preterm infants results in fewer transfusions, fewer donor exposures, and improved neurodevelopmental outcome. To determine if, compared with placebo, preterm infants randomized to weekly darbepoetin would have greater red cell mass during hospitalization and better neurocognitive outcome at 22 to 26 months’ corrected age. This randomized clinical trial was conducted between September 2017 and November 2019 for infants 23 0/7 to 28 6/7 weeks’ gestation in 19 US Neonatal Research Network centers comprising 33 neonatal intensive care units. Follow-up occurred through January 2023. Infants were randomized by 36 hours after birth to weekly placebo or darbepoetin (10 μg/kg) through 35 weeks’ postmenstrual age. Iron administration and transfusions were administered by protocol. Study data were analyzed from June to October 2023. The primary outcome was the mean cognitive composite score on the Bayley Scales of Infant Development, third edition (Bayley-III) at 22 to 26 months’ corrected age. The lowest possible score (54) was assigned to infants who died. A total of 650 infants (322 darbepoetin; 328 placebo; mean [SD] gestational age, 26.2 [1.7] weeks; 328 female [50.5%]) were enrolled. Five hundred eighty-three infants (291 darbepoetin; 292 placebo) had the primary outcome determined (90% of those enrolled). Mean (SD) cognitive scores were similar between groups: 80.7 (19.5) darbepoetin vs 80.1 (18.7) placebo, adjusted mean difference, −0.23 (95% CI, −3.09 to 2.64). Compared with infants receiving placebo, more infants in the darbepoetin group were transfusion free (40% [127 of 319] vs 21% [70 of 327]; adjusted relative risk [RR], 1.3; 95% CI, 1.2-1.5), received fewer transfusions (mean [SD], 2.3 [3.1] vs 3.3 [3.5]), were exposed to fewer donors (mean [SD], 1.6 [2.3] vs 2.2 [2.3]), had higher red cell mass by week 2 of age (adjusted mean difference, 3.2; 95% CI, 1.7-4.7), and higher mean hematocrit by week 2 of age (adjusted mean difference, 2.8; 95% CI, 2.1-3.6), and were less likely to have bronchopulmonary dysplasia greater than grade 1 (35% [91 of 261] vs 46% [128 of 277]; RR, 0.78; 95% CI, 0.64-0.96). The incidence of retinopathy of prematurity stage greater than 2 was similar between groups, 13% (35 of 273) in the darbepoetin group vs 16% (45 of 279) in the placebo group. There were no differences in adverse effects between groups. Results of this randomized clinical trial reveal that this dose and dosing schedule of darbepoetin did not improve cognitive scores of preterm infants at 22 to 26 months’ corrected age. Darbepoetin significantly increased red cell mass resulting in higher hematocrit values, fewer transfusions, and fewer donor exposures. ClinicalTrials.gov Identifier: NCT03169881

Introduction: The aim of this study was to correlate oxygenation index (OI) and oxygen saturation index (OSI) in congenital diaphragmatic hernia (CDH) and determine the impact of guideline changes from two different epochs. Methods: Retrospective analysis of 390 CDH neonates managed at University of Utah/Primary Children's Hospitals from 2003 to 2024. We performed regression analysis for paired OI and OSI values over the first week of life (2,604 pairs), comparing pre- (2003-2015) and post- (2016-2024) epoch effects of a 2016 CDH guideline. We analyzed predictive abilities for OI and OSI within and between epochs for extracorporeal membrane oxygenation (ECMO) and/or death. Results: OI and OSI showed higher correlation in the post- (R-2 = 0.755) vs. pre-epoch (R-2 = 0.650). Between epochs analysis demonstrated lower inspired oxygen, mean airway pressure, arterial oxygen pressure, OI, and OSI in the post-epoch. ECMO use was lower in post-epoch (9.8% vs. 33%), but pre-ECMO OI and OSI were similar between epochs. Classification of severe lung dysfunction by OI >25 or OSI >12 showed similar abilities to predict ECMO and/or death. Discussion: OI and OSI were highly correlated in CDH but affected by variation in CDH management. OSI classified severity of cardiopulmonary dysfunction as effectively as OI.

Hospitalization of moderately preterm infants may be prolonged while waiting for apnea of prematurity to resolve after discontinuing caffeine. To evaluate whether extending caffeine treatment reduces the duration of hospitalization. From February 2019 to December 2022, this randomized clinical trial in 29 US hospitals enrolled infants born at 29 to 33 weeks’ gestation who at 33 to 35 weeks’ postmenstrual age were receiving caffeine treatment with plans to discontinue it plus receiving full feeds (≥120 mL/kg/d). Follow-up was completed on March 20, 2023. Infants were randomized to oral caffeine citrate (10 mg/kg/d) or placebo until 28 days after discharge. The primary outcome was days to discharge after randomization. Secondary outcomes included days to physiological maturity (apnea free for 5 consecutive days, receiving full oral feeds, and out of the incubator for at least 48 hours), postmenstrual age at discharge, all-cause hospital readmissions, all-cause sick and emergency department visits, safety outcomes, and death. A total of 827 infants (median gestational age, 31 weeks; 414 female [51%]) were randomized (416, caffeine; 411, placebo) out of the 878 planned before reaching the prespecified futility threshold. Days of hospitalization after randomization did not differ between groups (18.0 days [IQR, 10 to 30 days] for caffeine vs 16.5 [IQR, 10 to 27 days] for placebo; adjusted median difference, 0 days [95% CI, −1.7 to 1.7 days]), nor did days to physiological maturity differ (14.0 vs 15.0 days, adjusted median difference, −1 day [95% CI, −2.4 to 0.4 days]). Infants receiving caffeine were apnea free sooner (6.0 vs 10.0 days; adjusted median difference, −2.7 days [95% CI, −3.4 to −2.0 days ]) but had similar days to full oral feeding (7.5 vs 6.0 days, adjusted median difference, 0 days [95% CI, −0.1 to 0.1]). Rates of readmissions and sick visits did not differ between groups. There was no statistically significant difference in adverse events between the 2 groups. In moderately preterm infants, continuation of caffeine treatment compared with placebo did not shorten hospitalization. ClinicalTrials.gov Identifier: NCT03340727

PURPOSE:Infants with large congenital diaphragmatic hernia (CDH) defects pose a clinical challenge. Despite evidence that muscle flap repair (MFR) has lower recurrence rates than patch repair (PR), MFR remains uncommon and understudied. This study evaluated long-term outcomes in CDH patients who underwent MFR compared to PR at a single institution. We hypothesized that patients who underwent MFR have lower recurrence rates than patients who underwent PR. METHODS:Using an internal institutional registry, we identified all CDH patients who underwent repair between 1998 and 2024. Patients were stratified based on repair type, excluding primarily and non-repaired patients. Long-term follow-up was obtained through our institutional pulmonary hypoplasia clinic and retrospective chart review, with supplementary phone calls made to patients who were lost to follow-up. Our primary outcome was CDH recurrence and secondarily wound infection, small bowel obstruction (SBO), abdominal wall hernia, scoliosis and pectus excavatum. Analysis was done using bivariate comparisons. RESULTS:A retrospective cohort of 456 patients with CDH from 1998 to 2024 was identified. 71 patients were not repaired, and 246 underwent primary repair. The remaining 139 patients underwent complex repair: 108 MFR and 31 PR. 32 did not survive after repair to discharge from NICU (19 MFR and 13 PR). 12 patients were lost to follow-up and we have reliable long-term follow-up in 95 patients. Of these, there are 80 MFR and 15 PR. The median follow-up time was 5 years [IQR 3-11]. Demographics were similar across cohorts. In the MFR group, 5/80 (6.3 %) had a recurrence compared to 7/15 (46.7 %) in the patch group (p=<0.001). PR had a significantly higher rate of infection than MFR. SBO and hernia rates were similar across groups. Scoliosis and chest wall deformity rates were similar, with five patients requiring operative intervention for scoliosis and one requiring minimally invasive repair of pectus excavatum. CONCLUSION:MFR is a viable treatment option for large CDH defects and has a lower recurrence rate than PR. In this long-term follow-up study, MFR did not result in a higher rate of infection, bowel obstruction, hernia, chest wall deformity, or scoliosis. LEVEL OF EVIDENCE:IV.

(Abstracted from JAMA Network Open 2024;7:e2416870) Delaying umbilical cord clamping at least 30 to 60 seconds at birth has been shown to improve neurodevelopmental outcomes in full-term infants and survival in preterm infants. However, in nonvigorous infants who may need resuscitation, the optimal umbilical cord management is unclear.

Objective To determine if timing of first postnatal echocardiogram (ECHO), early vs delayed, affects the use of extracorporeal membrane oxygenation (ECMO) and survival to discharge in neonates with congenital diaphragmatic hernia (CDH). Study design We retrospectively reviewed 306 neonates with CDH managed between January 2007 through December 2023. We excluded 21 neonates diagnosed at >24 hours age and 14 outborn neonates transferred at >12 hours age. Based on initial ECHO guideline recommendation changes, we compared 2 ECHO cohorts: early (<24 hours, 2007-2015) vs delayed (>24 hours, 2016-2023). Outcomes of interest included ECMO use, survival, rates of cardiopulmonary therapies, and key ECHO parameters. Results The median age for first preoperative ECHO was 7 hours (IQR, 4-13 hours) in the early epoch vs 40 hours (IQR, 19-62 hours) in the delayed epoch (P < .001). Despite similar demographics including gestation, birth weight, defect size, and intrathoracic liver, ECMO use (31% vs 9%) and survival (70% vs 82%) were improved significantly in association with delayed timing of first ECHO (P < .05). Measures of pulmonary hypertension, ventricular size, and ventricular function were similar, but significantly less inhaled nitrous oxide and vasoactive drugs were used in the delayed ECHO epoch. Conclusions A delay in the timing of the initial postnatal ECHO for critically ill neonates with CDH, as part of a broader series of guideline changes, was associated with less ECMO, improved survival, and lower use of inhaled nitrous oxide and vasoactive drugs despite similar ECHO measures of pulmonary hypertension, ventricular size, and ventricular function. Randomized studies are needed to define better the optimal timing and interventions related to the initial ECHO for CDH.

Importance Hypothermia begun less than 6 hours after birth reduces death or disability in infants with encephalopathy due to hypoxia-ischemia at 36 or more weeks’ gestation. Trials of hypothermia for infants younger than 36 weeks’ gestation are lacking. Objective To assess the probability that hypothermia at less than 6 hours after birth decreases death or disability in infants 33 to 35 weeks’ gestation with moderate or severe hypoxic-ischemic encephalopathy. Design, Setting, and Participants This randomized clinical trial was conducted between July 2015 and December 2022 for infants 33 to 35 weeks’ gestation with moderate or severe hypoxic-ischemic encephalopathy at less than 6 hours after birth. Bayesian and intention-to-treat analyses were prespecified. The setting included 19 US Neonatal Research Network centers. Data were analyzed from March 2023 to November 2024. Interventions Infants received unblinded targeted esophageal temperature management. Infants with hypothermia were maintained at 33.5 °C (acceptable 33-34 °C) for 72 hours and then rewarmed. Infants with normothermia were to be maintained at 37 °C (acceptable 36.5-37.3 °C). Main Outcomes and Measures Composite of death or disability (moderate or severe) at 18 to 22 months’ corrected age adjusted for level of encephalopathy and center. Results A total of 168 infants with hypothermia and normothermia were preterm (mean [SD] age, 34.0 [0.8] weeks’ gestation and 34.1 [0.8] weeks’ gestation, respectively), while 46 of 88 (52%) and 45 of 80 (56%) were male, respectively. Randomization occurred at mean (SD) 4.5 (1.2) hours and 4.5 (1.3) hours for the groups with hypothermia and normothermia, respectively. The primary outcome occurred in 29 of 83 infants (35%) with hypothermia and 20 of 69 infants (29%) with normothermia (adjusted relative risk [hypothermic/normothermic], 1.11; 95% credibility interval, 0.74-2.00), and death occurred in 18 of 88 infants (20%) with hypothermia and 9 of 78 infants (12%) with normothermia (adjusted relative risk, 1.38; 95% credibility interval, 0.79-2.85). Bayesian analysis with neutral prior indicated 74% probability of increased death or disability and 87% probability of increased death with hypothermia. Conclusions and Relevance Among infants 33 to 35 weeks’ gestation with hypoxic-ischemic encephalopathy, hypothermia at less than 6 hours’ age did not reduce death or disability at 18 to 22 months’ corrected age. Trial Registration ClinicalTrials.gov Identifier: NCT01793129

Extremely preterm infants are at high risk for bronchopulmonary dysplasia (BPD) and death. Multiple small randomized clinical trials showed that a combination of budesonide with surfactant compared with surfactant alone reduced BPD or death. To determine if early intratracheal administration of a combination of budesonide (0.25 mg/kg) mixed with surfactant, compared with surfactant alone, reduces physiologic BPD or death by 36 weeks’ postmenstrual age in extremely preterm infants. This double-masked randomized clinical trial was conducted from April 2021 to June 2024 in the 17 centers of the United States Neonatal Research Network. Infants 22 to 28 weeks’ gestation or 401 to 1000 g birth weight were enrolled after clinical decision to give surfactant, with the first dose of surfactant being study drug (prior surfactant was an exclusion criterion). Infants were randomly allocated 1:1 to receive 1 to 2 doses of budesonide + surfactant (poractant alfa) or surfactant alone via endotracheal tube within 50 hours of birth. The primary outcome was physiologic BPD or death by 36 weeks’ postmenstrual age. There were 5 prespecified secondary outcomes and multiple prespecified exploratory and safety outcomes. The trial was stopped with 641 infants enrolled (55.3% of 1160 planned; mean birth weight, 810 g [SD, 256 g]; gestational age, 25.9 weeks [SD, 1.9 weeks]), because interim analysis at 50% enrollment reached the prespecified futility threshold. The incidence of BPD or death was 68.5% in the budesonide + surfactant group and 67.9% in the surfactant-alone group (adjusted relative risk [RR], 1.00 [95% CI, 0.90-1.11]). No differences were noted in mortality (15.3% vs 13.2%; adjusted RR, 1.13 [95% CI, 0.78-1.64]) or BPD among survivors to 36 weeks’ postmenstrual age (62.9% vs 63.0%; adjusted RR, 0.99 [95% CI, 0.87-1.12]). More infants who received budesonide + surfactant compared with surfactant alone had hyperglycemia (66.7% vs 49.8%; adjusted RR, 1.33 [95% CI, 1.17-1.51]). In this large multicenter trial, the combination of budesonide with surfactant did not reduce the risk of BPD or death at 36 weeks’ postmenstrual age in extremely preterm infants. ClinicalTrials.gov Identifier: NCT04545866

Congenital diaphragmatic hernia (CDH) is associated with high neonatal morbidity and mortality, often due to complex cardiovascular physiology and ventricular dysfunction. Echocardiography is a critical tool for assessing cardiac anatomy, ventricular performance, pulmonary hypertension, and shunt dynamics in both the prenatal and postnatal periods. Early echocardiographic evaluation can identify high-risk physiologic phenotypes and guide targeted interventions, yet optimal timing and frequency remain uncertain. This review outlines the role of fetal and neonatal echocardiography in CDH, highlights view-specific imaging strategies, and discusses key physiologic patterns. While early imaging may inform management, it must be interpreted in context to avoid unnecessary interventions. A targeted, phenotype-driven approach to echocardiography can support individualized care. Further research is needed to establish standardized protocols and determine the impact of echocardiographic timing on outcomes in this vulnerable population.

OBJECTIVE:To evaluate a composite metric incorporating the DIGIROP-Birth (DRB) and Neonatal Research Network Bronchopulmonary Dysplasia Outcome Estimator (NRN-BPD) for predicting severe retinopathy of prematurity requiring treatment (TR-ROP). STUDY DESIGN:This was a retrospective cohort study of 990 infants born prematurely undergoing dilated eye examinations between January 2010 and August 2023. We performed a chart review to assess a primary outcome of TR-ROP and secondary outcome of stage 2 or greater ROP. DRB and 14-day NRN-BPD scores were quantified for each infant, and optimal thresholds for predicting TR-ROP were analyzed using receiver operator characteristic curves. Sensitivity and specificity for TR-ROP were assessed. RESULTS:Of the 990 infants, 364 (36.8%) had stage 2 or greater ROP and 68 (6.9%) had TR-ROP. Receiver operator characteristic analysis with (95% CI) showed areas under the curve of 0.867 (0.829-0.906) for DRB and 0.845 (0.809-0.881) for NRN-BPD. Optimal cutoff scores were 1.7 for DRB and 40% for NRN-BPD with respective sensitivities of 97% and 96%. Composite screening for babies meeting either cutoff allowed 100% sensitivity for predicting TR-ROP while decreasing number of infants qualifying for screening from 990 to 562 (43% reduction). CONCLUSIONS:A composite metric using DigiROP-Birth and NRN-BPD Outcome Estimator scores may allow an early, simple approach to predict TR-ROP with 100% sensitivity yet allow significant reduction in the number of infants requiring screening eye examinations. Additional large validation studies are needed.

PURPOSE:Infants with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia leading to cardiopulmonary derangements such as pulmonary hypertension. Extracorporeal membranous oxygenation (ECMO) can be necessary for survival in some patients. Our institution implemented a change in the NICU critical care management guideline for neonates with CDH in 2016. Indications for ECMO remained the same in the revised guideline. This study evaluated survival and surgical outcomes in CDH patients who underwent repair before and after this guideline change. METHODS:Using an internal institutional registry, we identified a retrospective cohort of all CDH patients treated at our institution between January 2003 and December 2024. Patients were stratified based on year of birth before 2016 or 2016 and after. A retrospective chart review was conducted to extract primary and secondary outcome variables, which were analyzed using bivariate comparisons. RESULTS:A retrospective cohort of 389 patients with CDH was identified. Two hundred twenty-nine patients were treated before 2016, and 160 during or after 2016. ECMO was performed on 71 (31.0 %) patients prior to 2016 and 15 (9.4 %) patients during or after 2016 (p < 0.001). ECMO runs and repairs on ECMO significantly decreased for patients with the most severe defect sizes (C, D). Survival was not significantly different for A, B, or C defects and was significantly improved in the most severe defects (D) (90.9 % vs 42.9 %, p < 0.001) after the guideline change. Complications from ECMO, massive bleeding events, and thrombosis were not statistically different between time points. CONCLUSION:Changes in clinical management guideline, but not indications for ECMO, resulted in fewer ECMO runs and fewer CDH repairs on ECMO. Overall survival improved, including a significant improvement in survival for the most severe defect subgroup (D). ECMO complications, bleeding, and clotting were not different between groups, indicating that the risks of ECMO were not affected by the guideline changes. LEVEL OF EVIDENCE:IV.