Eat, Sleep, Console Approach or Usual Care for Neonatal Opioid Withdrawal.

BACKGROUND: Although clinicians have traditionally used the Finnegan Neonatal Abstinence Scoring Tool to assess the severity of neonatal opioid withdrawal, a newer function-based approach - the Eat, Sleep, Console care approach - is increasing in use. Whether the new approach can safely reduce the time until infants are medically ready for discharge when it is applied broadly across diverse sites is unknown. METHODS: In this cluster-randomized, controlled trial at 26 U.S. hospitals, we enrolled infants with neonatal opioid withdrawal syndrome who had been born at 36 weeks' gestation or more. At a randomly assigned time, hospitals transitioned from usual care that used the Finnegan tool to the Eat, Sleep, Console approach. During a 3-month transition period, staff members at each hospital were trained to use the new approach. The primary outcome was the time from birth until medical readiness for discharge as defined by the trial. Composite safety outcomes that were assessed during the first 3 months of postnatal age included in-hospital safety, unscheduled health care visits, and nonaccidental trauma or death. RESULTS: A total of 1305 infants were enrolled. In an intention-to-treat analysis that included 837 infants who met the trial definition for medical readiness for discharge, the number of days from birth until readiness for hospital discharge was 8.2 in the Eat, Sleep, Console group and 14.9 in the usual-care group (adjusted mean difference, 6.7 days; 95% confidence interval [CI], 4.7 to 8.8), for a rate ratio of 0.55 (95% CI, 0.46 to 0.65; P<0.001). The incidence of adverse outcomes was similar in the two groups. CONCLUSIONS: As compared with usual care, use of the Eat, Sleep, Console care approach significantly decreased the number of days until infants with neonatal opioid withdrawal syndrome were medically ready for discharge, without increasing specified adverse outcomes. (Funded by the Helping End Addiction Long-term (HEAL) Initiative of the National Institutes of Health; ESC-NOW ClinicalTrials.gov number, NCT04057820.).

Hydrocortisone to Improve Survival without Bronchopulmonary Dysplasia.

BACKGROUND: Bronchopulmonary dysplasia is a prevalent complication after extremely preterm birth. Inflammation with mechanical ventilation may contribute to its development. Whether hydrocortisone treatment after the second postnatal week can improve survival without bronchopulmonary dysplasia and without adverse neurodevelopmental effects is unknown. METHODS: We conducted a trial involving infants who had a gestational age of less than 30 weeks and who had been intubated for at least 7 days at 14 to 28 days. Infants were randomly assigned to receive either hydrocortisone (4 mg per kilogram of body weight per day tapered over a period of 10 days) or placebo. Mandatory extubation thresholds were specified. The primary efficacy outcome was survival without moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age, and the primary safety outcome was survival without moderate or severe neurodevelopmental impairment at 22 to 26 months of corrected age. RESULTS: We enrolled 800 infants (mean [±SD] birth weight, 715±167 g; mean gestational age, 24.9±1.5 weeks). Survival without moderate or severe bronchopulmonary dysplasia at 36 weeks occurred in 66 of 398 infants (16.6%) in the hydrocortisone group and in 53 of 402 (13.2%) in the placebo group (adjusted rate ratio, 1.27; 95% confidence interval [CI], 0.93 to 1.74). Two-year outcomes were known for 91.0% of the infants. Survival without moderate or severe neurodevelopmental impairment occurred in 132 of 358 infants (36.9%) in the hydrocortisone group and in 134 of 359 (37.3%) in the placebo group (adjusted rate ratio, 0.98; 95% CI, 0.81 to 1.18). Hypertension that was treated with medication occurred more frequently with hydrocortisone than with placebo (4.3% vs. 1.0%). Other adverse events were similar in the two groups. CONCLUSIONS: In this trial involving preterm infants, hydrocortisone treatment starting on postnatal day 14 to 28 did not result in substantially higher survival without moderate or severe bronchopulmonary dysplasia than placebo. Survival without moderate or severe neurodevelopmental impairment did not differ substantially between the two groups. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01353313.).

Psychological distress among postpartum women who took opioids during pregnancy: the role of perceived stigma in healthcare settings.

This study examined the relationship between perceived stigma in healthcare settings during pregnancy and psychological distress and well-being in the postpartum period among individuals who took opioids while pregnant. Analyses included 134 birth mothers of opioid-exposed infants. At 0-1 months postpartum, perceived stigma and psychological distress were measured using the Prenatal Opioid use Perceived Stigma scale and measures from the Patient-Reported Outcome Measurement Information System (PROMIS). Food insecurity, housing instability, and Adverse Childhood Experiences (ACEs) were also assessed. Linear and generalized linear mixed-effect models were conducted to compare PROMIS scale scores and unmet needs by stigma, adjusting for site/location, age, race/ethnicity, marital status, education, public insurance, and parity. More than half of participants (54%) perceived stigma in healthcare settings. Individuals reporting stigma had higher depression, anxiety, and anger scores (p < 0.001) indicating greater psychological distress in the postpartum period compared to those reporting no stigma, after controlling for demographic characteristics. In addition, they scored significantly lower on the PROMIS meaning and purpose scale, an indicator of well-being (p = 0.002). Those reporting stigma were more likely to have food insecurity (p = 0.003), three or more ACEs (p = 0.040), verbal or physical abuse during pregnancy (p < 0.001), and less emotional support (p = 0.006) than those who did not. An association was observed between perceived stigma in the prenatal period and psychological distress in the postpartum period, providing support for stigma reduction interventions and education for healthcare providers on trauma-informed care.

Utilization of Transport Data to Decrease Unnecessarily Repeated Laboratory Tests.

OBJECTIVES: In pediatric patients being transported for management of diabetic ketoacidosis, laboratory tests will frequently be trended throughout transportation and subsequently immediately repeated upon arrival to a particular institution. These laboratory tests may not add value to a patient's care trajectory and therefore may be unnecessary. This study examines differences between pH, sodium, potassium, chloride, bicarbonate, and glucose levels drawn during transportation and those drawn at our home institution immediately upon arrival to determine if repeating those laboratory tests upon arrival to the emergency department serves any purpose in adding to patient care. METHODS: This study compares pH, sodium, potassium, chloride, bicarbonate, and glucose levels drawn during transport and at our home institution. Box and whisker plots between transport and institution laboratory values were constructed. A Wilcoxon signed rank test was performed to determine differences between pH, sodium, potassium, bicarbonate, and glucose levels, as these value sets were not normally distributed. A paired t test was performed to determine differences between transport and institution chloride values given that these value sets were normally distributed. Savings were then calculated based on charges to the patient to determine overall cost savings by not immediately repeating these laboratory tests upon presentation. RESULTS: Box and whisker plots showed marked similarity between laboratory tests drawn in transport and those immediately upon arrival to our ED. Paired t test did not demonstrate a statistical difference between transport and ED chloride levels ( P = 0.5699); therefore, we failed to reject the null hypothesis. Wilcoxon signed rank test did not demonstrate a statistical difference between transport and ED pH ( P = 0.1294) and potassium ( P = 0.4523) values; therefore, we failed to reject the null hypothesis. However, Wilcoxon signed rank test did demonstrate a statistically significant difference between uncorrected sodium ( P = 0.0006), corrected sodium ( P = 0.0075), bicarbonate ( P = <0.0001), and glucose levels ( P = 0.0086). CONCLUSIONS: Although there were some statistically significant differences between the laboratory value sets, it is arguable whether there are any clinically significant differences between them.Based on our failure to show a clinically significant difference between laboratory values drawn during transportation and those drawn immediately upon presentation to the institution, repeating laboratory draws after transportation do not add value to a patient's care trajectory. We should therefore rely on the laboratory values that were drawn from our transportation teams as part of the continuum of patient care.

Neurodevelopmental Outcomes of Extremely Preterm Infants Fed Donor Milk or Preterm Infant Formula: A Randomized Clinical Trial.

Importance: Maternal milk feeding of extremely preterm infants during the birth hospitalization has been associated with better neurodevelopmental outcomes compared with preterm formula. For infants receiving no or minimal maternal milk, it is unknown whether donor human milk conveys similar neurodevelopmental advantages vs preterm formula. Objective: To determine if nutrient-fortified, pasteurized donor human milk improves neurodevelopmental outcomes at 22 to 26 months' corrected age compared with preterm infant formula among extremely preterm infants who received minimal maternal milk. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 15 US academic medical centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants younger than 29 weeks 0 days' gestation or with a birth weight of less than 1000 g were enrolled between September 2012 and March 2019. Intervention: Preterm formula or donor human milk feeding from randomization to 120 days of age, death, or hospital discharge. Main Outcomes and Measures: The primary outcome was the Bayley Scales of Infant and Toddler Development (BSID) cognitive score measured at 22 to 26 months' corrected age; a score of 54 (score range, 54-155; a score of ≥85 indicates no neurodevelopmental delay) was assigned to infants who died between randomization and 22 to 26 months' corrected age. The 24 secondary outcomes included BSID language and motor scores, in-hospital growth, necrotizing enterocolitis, and death. Results: Of 1965 eligible infants, 483 were randomized (239 in the donor milk group and 244 in the preterm formula group); the median gestational age was 26 weeks (IQR, 25-27 weeks), the median birth weight was 840 g (IQR, 676-986 g), and 52% were female. The birthing parent's race was self-reported as Black for 52% (247/478), White for 43% (206/478), and other for 5% (25/478). There were 54 infants who died prior to follow-up; 88% (376/429) of survivors were assessed at 22 to 26 months' corrected age. The adjusted mean BSID cognitive score was 80.7 (SD, 17.4) for the donor milk group vs 81.1 (SD, 16.7) for the preterm formula group (adjusted mean difference, -0.77 [95% CI, -3.93 to 2.39], which was not significant); the adjusted mean BSID language and motor scores also did not differ. Mortality (death prior to follow-up) was 13% (29/231) in the donor milk group vs 11% (25/233) in the preterm formula group (adjusted risk difference, -1% [95% CI, -4% to 2%]). Necrotizing enterocolitis occurred in 4.2% of infants (10/239) in the donor milk group vs 9.0% of infants (22/244) in the preterm formula group (adjusted risk difference, -5% [95% CI, -9% to -2%]). Weight gain was slower in the donor milk group (22.3 g/kg/d [95% CI, 21.3 to 23.3 g/kg/d]) compared with the preterm formula group (24.6 g/kg/d [95% CI, 23.6 to 25.6 g/kg/d]). Conclusions and Relevance: Among extremely preterm neonates fed minimal maternal milk, neurodevelopmental outcomes at 22 to 26 months' corrected age did not differ between infants fed donor milk or preterm formula. Trial Registration: ClinicalTrials.gov Identifier: NCT01534481.

Higher or Lower Hemoglobin Transfusion Thresholds for Preterm Infants.

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.).

Outcomes of Babies with Opioid Exposure (OBOE): protocol of a prospective longitudinal cohort study.

BACKGROUND: While the health, social, and economic impacts of opioid addiction on adults and their communities are well known, the impact of maternal opioid use on the fetus exposed in utero is less well understood. METHODS: This paper presents the protocol of the ACT NOW Outcomes of Babies with Opioid Exposure (OBOE) Study, a multi-site prospective longitudinal cohort study of infants with antenatal opioid exposure and unexposed controls. Study objectives are to determine the impact of antenatal opioid exposure on brain development and neurodevelopmental outcomes over the first 2 years of life and explore whether family, home, and community factors modify developmental trajectories during this critical time period. RESULTS: Primary outcomes related to brain development include cortical volumes, deep cerebral gray matter volumes, resting-state functional connectivity measures, and structural connectivity measures using diffusion tensor imaging. Primary neurodevelopmental outcomes include visual abnormalities, cognitive, language, and motor skills measured using the Bayley Scales of Infant Development and social-emotional and behavioral problems and competence measured by the Brief Infant-Toddler Social and Emotional Assessment. CONCLUSIONS: The OBOE study has been designed to overcome challenges of previous studies and will help further understanding of the effects of antenatal opioid exposure on early infant development. IMPACT: This study will integrate MRI findings and comprehensive neurodevelopmental assessments to provide early insights into the functional topography of the brain in this high-risk population and assess MRI as a potential biomarker. Rather than conducting neuroimaging at a single time point, the study will include serial MRI assessments from birth to 2 years, allowing for the examination of trajectories throughout this period of rapid brain development. While previous studies often have had limited information on exposures, this study will use umbilical cord assays to accurately measure amounts of opioids and other substances from 20 weeks of gestation to birth.

Early brain and abdominal oxygenation in extremely low birth weight infants.

BACKGROUND: Extremely low birth weight (ELBW) infants are at risk for end-organ hypoxia and ischemia. Regional tissue oxygenation of the brain and gut as monitored with near-infrared spectroscopy (NIRS) may change with postnatal age, but normal ranges are not well defined. METHODS: A prospective study of ELBW preterm infants utilized NIRS monitoring to assess changes in cerebral and mesenteric saturation (Csat and Msat) over the first week after birth. This secondary study of a multicenter trial comparing hemoglobin transfusion thresholds assessed cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE) and relationships with perinatal variables. RESULTS: In 124 infants, both Csat and Msat declined over the first week, with a corresponding increase in oxygen extraction. With lower gestational age, lower birth weight, and 5-min Apgar score ≤5, there was a greater increase in oxygen extraction in the brain compared to the gut. Infants managed with a lower hemoglobin transfusion threshold receiving ≥2 transfusions in the first week had the lowest Csat and highest cFTOE (p < 0.001). CONCLUSION: Brain oxygen extraction preferentially increased in more immature and anemic preterm infants. NIRS monitoring may enhance understanding of cerebral and mesenteric oxygenation patterns and inform future protective strategies in the preterm ELBW population. IMPACT: Simultaneous monitoring of cerebral and mesenteric tissue saturation demonstrates the balance of oxygenation between preterm brain and gut and may inform protective strategies. Over the first week, oxygen saturation of the brain and gut declines as oxygen extraction increases. A low hemoglobin transfusion threshold is associated with lower cerebral saturation and higher cerebral oxygen extraction compared to a high hemoglobin transfusion threshold, although this did not translate into clinically relevant differences in the TOP trial primary outcome. Greater oxygen extraction by the brain compared to the gut occurs with lower gestational age, lower birth weight, and 5-min Apgar score ≤5.

Outcomes of Moderately Preterm Infants of Insulin-Dependent Diabetic Mothers.

OBJECTIVE: Little is known about the hospital outcomes of moderately preterm (MPT; 29 0/7-33 6/7 weeks gestational age) infants born to insulin-dependent diabetic mothers (IDDMs). We evaluated characteristics and outcomes of MPT infants born to IDDMs compared with those without IDDM (non-IDDM). STUDY DESIGN: Cohort study of infants from 18 centers included in the MPT infant database from 2012 to 2013. We compared characteristics and outcomes of infants born to IDDMs and non-IDDMs. RESULTS: Of 7,036 infants, 527 (7.5%) were born to IDDMs. Infants of IDDMs were larger at birth, more often received continuous positive pressure ventilation in the delivery room, and had higher risk of patent ductus arteriosus (adjusted relative risk or aRR: 1.49, 95% confidence interval [CI]: 1.20-1.85) and continued hospitalization at 40 weeks postmenstrual age (aRR: 1.55, 95% CI: 1.18-2.05). CONCLUSION: MPT infants of IDDM received more respiratory support and prolonged hospitalizations, providing further evidence of the important neonatal health consequences of maternal diabetes. KEY POINTS: · Little data are available on moderate preterm infants of IDDMs.. · MPT infants of IDDMs need more respiratory support.. · Longer neonatal intensive care unit stays among MPT infants of IDDMs..

Mortality, In-Hospital Morbidity, Care Practices, and 2-Year Outcomes for Extremely Preterm Infants in the US, 2013-2018.

IMPORTANCE: Despite improvement during recent decades, extremely preterm infants continue to contribute disproportionately to neonatal mortality and childhood morbidity. OBJECTIVE: To review survival, in-hospital morbidities, care practices, and neurodevelopmental and functional outcomes at 22-26 months' corrected age for extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS: Prospective registry for extremely preterm infants born at 19 US academic centers that are part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. The study included 10 877 infants born at 22-28 weeks' gestational age between January 1, 2013, and December 31, 2018, including 2566 infants born before 27 weeks between January 1, 2013, and December 31, 2016, who completed follow-up assessments at 22-26 months' corrected age. The last assessment was completed on August 13, 2019. Outcomes were compared with a similar cohort of infants born in 2008-2012 adjusting for gestational age. EXPOSURES: Extremely preterm birth. MAIN OUTCOMES AND MEASURES: Survival and 12 in-hospital morbidities were assessed, including necrotizing enterocolitis, infection, intracranial hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia. Infants were assessed at 22-26 months' corrected age for 12 health and functional outcomes, including neurodevelopment, cerebral palsy, vision, hearing, rehospitalizations, and need for assistive devices. RESULTS: The 10 877 infants were 49.0% female and 51.0% male; 78.3% (8495/10848) survived to discharge, an increase from 76.0% in 2008-2012 (adjusted difference, 2.0%; 95% CI, 1.0%-2.9%). Survival to discharge was 10.9% (60/549) for live-born infants at 22 weeks and 94.0% (2267/2412) at 28 weeks. Survival among actively treated infants was 30.0% (60/200) at 22 weeks and 55.8% (535/958) at 23 weeks. All in-hospital morbidities were more likely among infants born at earlier gestational ages. Overall, 8.9% (890/9956) of infants had necrotizing enterocolitis, 2.4% (238/9957) had early-onset infection, 19.9% (1911/9610) had late-onset infection, 14.3% (1386/9705) had severe intracranial hemorrhage, 12.8% (1099/8585) had severe retinopathy of prematurity, and 8.0% (666/8305) had severe bronchopulmonary dysplasia. Among 2930 surviving infants with gestational ages of 22-26 weeks eligible for follow-up, 2566 (87.6%) were examined. By 2-year follow-up, 8.4% (214/2555) of children had moderate to severe cerebral palsy, 1.5% (38/2555) had bilateral blindness, 2.5% (64/2527) required hearing aids or cochlear implants, 49.9% (1277/2561) had been rehospitalized, and 15.4% (393/2560) required mobility aids or other supportive devices. Among 2458 fully evaluated infants, 48.7% (1198/2458) had no or mild neurodevelopmental impairment at follow-up, 29.3% (709/2419) had moderate neurodevelopmental impairment, and 21.2% (512/2419) had severe neurodevelopmental impairment. CONCLUSIONS AND RELEVANCE: Among extremely preterm infants born in 2013-2018 and treated at 19 US academic medical centers, 78.3% survived to discharge, a significantly higher rate than for infants born in 2008-2012. Among infants born at less than 27 weeks' gestational age, rehospitalization and neurodevelopmental impairment were common at 2 years of age.

Initial Laparotomy Versus Peritoneal Drainage in Extremely Low Birthweight Infants With Surgical Necrotizing Enterocolitis or Isolated Intestinal Perforation: A Multicenter Randomized Clinical Trial.

OBJECTIVE: The aim of this study was to determine which initial surgical treatment results in the lowest rate of death or neurodevelopmental impairment (NDI) in premature infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP). SUMMARY BACKGROUND DATA: The impact of initial laparotomy versus peritoneal drainage for NEC or IP on the rate of death or NDI in extremely low birth weight infants is unknown. METHODS: We conducted the largest feasible randomized trial in 20 US centers, comparing initial laparotomy versus peritoneal drainage. The primary outcome was a composite of death or NDI at 18 to 22 months corrected age, analyzed using prespecified frequentist and Bayesian approaches. RESULTS: Of 992 eligible infants, 310 were randomized and 96% had primary outcome assessed. Death or NDI occurred in 69% of infants in the laparotomy group versus 70% with drainage [adjusted relative risk (aRR) 1.0; 95% confidence interval (CI): 0.87-1.14]. A preplanned analysis identified an interaction between preoperative diagnosis and treatment group (P = 0.03). With a preoperative diagnosis of NEC, death or NDI occurred in 69% after laparotomy versus 85% with drainage (aRR 0.81; 95% CI: 0.64-1.04). The Bayesian posterior probability that laparotomy was beneficial (risk difference <0) for a preoperative diagnosis of NEC was 97%. For preoperative diagnosis of IP, death or NDI occurred in 69% after laparotomy versus 63% with drainage (aRR, 1.11; 95% CI: 0.95-1.31); Bayesian probability of benefit with laparotomy = 18%. CONCLUSIONS: There was no overall difference in death or NDI rates at 18 to 22 months corrected age between initial laparotomy versus drainage. However, the preoperative diagnosis of NEC or IP modified the impact of initial treatment.

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

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, 22-246/7 and 25-286/7 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 25-286/7 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.

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

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.

Association between Policy Changes for Oxygen Saturation Alarm Settings and Neonatal Morbidity and Mortality in Infants Born Very Preterm.

OBJECTIVE: To determine the impact of policy changes for pulse oximetry oxygen saturation (SpO2) alarm limits on neonatal mortality and morbidity among infants born very preterm. STUDY DESIGN: This was a retrospective cohort study of infants born very preterm in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants were classified based on treatment at a hospital with an SpO2 alarm policy change and study epoch (before vs after policy change). We used a generalized linear mixed model to determine the effect of hospital group and epoch on the primary outcomes of mortality and severe retinopathy of prematurity (ROP) and secondary outcomes of necrotizing enterocolitis, bronchopulmonary dysplasia, and any ROP. RESULTS: There were 3809 infants in 10 hospitals with an SpO2 alarm policy change and 3685 infants in 9 hospitals without a policy change. The nature of most policy changes was to narrow the SpO2 alarm settings. Mortality was lower in hospitals without a policy change (aOR 0.63; 95% CI 0.50-0.80) but did not differ between epochs in policy change hospitals. The odds of bronchopulmonary dysplasia were greater for hospitals with a policy change (aOR 1.65; 95% CI 1.36-2.00) but did not differ for hospitals without a policy change. Severe ROP and necrotizing enterocolitis did not differ between epochs for either group. The adjusted odds of any ROP were lower in recent years in both hospital groups. CONCLUSIONS: Changing SpO2 alarm policies was not associated with reduced mortality or increased severe ROP among infants born very preterm.

Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth.

OBJECTIVE: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment. STUDY DESIGN: A multicenter cohort study of 4858 infants 22-26 weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22 months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24 weeks of gestation to rates observed at 25-26 weeks of gestation. RESULTS: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24 weeks (rate ratio [95% CI] at 22 weeks: 1.7 [1.3-2.2]; 23 weeks: 2.6 [2.2-3.2]; 24 weeks: 1.0 [0.8-1.2]) when compared with 25-26 weeks. Among infants resuscitated at 23 weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26 weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22 weeks, where few (n = 22) resuscitated infants received antenatal corticosteroids. CONCLUSIONS: Infants born at 23 weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment. TRIAL REGISTRATION: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).

Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial.

OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02160002.

Causes and timing of death in extremely premature infants from 2000 through 2011.

BACKGROUND: Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. METHODS: We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences. RESULTS: The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days. CONCLUSIONS: We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).

Between-hospital variation in treatment and outcomes in extremely preterm infants.

BACKGROUND: Between-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth. METHODS: We studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%). RESULTS: Overall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and survival without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to 6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR, 78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26 weeks of gestation. Hospital rates of active treatment accounted for 78% and 75% of the between-hospital variation in survival and survival without severe impairment, respectively, among children born at 22 or 23 weeks of gestation, and accounted for 22% and 16%, respectively, among those born at 24 weeks of gestation, but the rates did not account for any of the variation in outcomes among those born at 25 or 26 weeks of gestation. CONCLUSIONS: Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients. (Funded by the National Institutes of Health.).

Admission Temperature and Associated Mortality and Morbidity among Moderately and Extremely Preterm Infants.

OBJECTIVE: To evaluate the temperature distribution among moderately preterm (MPT, 29-33 weeks) and extremely preterm (EPT, <29 weeks) infants upon neonatal intensive care unit (NICU) admission in 2012-2013, the change in admission temperature distribution for EPT infants between 2002-2003 and 2012-2013, and associations between admission temperature and mortality and morbidity for both MPT and EPT infants. STUDY DESIGN: Prospectively collected data from 18 centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network were used to examine NICU admission temperature of inborn MPT and EPT infants. Associations between admission temperature and mortality and morbidity were determined by multivariable logistic regression. EPT infants from 2002-2003 and 2012-2013 were compared. RESULTS: MPT and EPT cohorts consisted of 5818 and 3213 infants, respectively. The distribution of admission temperatures differed between the MPT vs EPT (P < .01), including the percentage <36.5°C (38.6% vs 40.9%), 36.5°C-37.5°C (57.3% vs 52.9%), and >37.5°C (4.2% vs 6.2%). For EPT infants in 2012-2013 compared with 2002-2003, the percentage of temperatures between 36.5°C and 37.5°C more than doubled and the percentage of temperatures >37.5°C more than tripled. Admission temperature was inversely associated with in-hospital mortality. CONCLUSIONS: Low and high admission temperatures are more frequent among EPT than MPT infants. Compared with a decade earlier, fewer EPT infants experience low admission temperatures but more have elevated temperatures. In spite of a change in distribution of NICU admission temperature, an inverse association between temperature and mortality risk persists.