Late-Onset Sepsis Among Extremely Preterm Infants During the COVID-19 Pandemic.

Objectives: To compare incidence of late-onset sepsis (LOS) among extremely preterm infants before and during the COVID-19 pandemic.

Methods: Multicenter cohort study of infants with birthweight 401 to 1000 g or gestational age 22 to 28 weeks. LOS was defined as a bacterial or fungal pathogen isolated from blood or cerebrospinal fluid culture obtained after 72 hours of age.

Prediction of site-specific pharmacologic therapy among newborns with neonatal opioid withdrawal syndrome.

Objective: To predict pharmacotherapy for NOWS based on factors available shortly after birth.

Study Design: A multi-center, retrospective study of 1377 opioid exposed newborns between 2016 and 2017 dichotomized based on pharmacologic treatment (N = 665 treated, N = 712 not treated) was conducted. A multilevel mixed-effect logistic regression model that considered cluster effect from sites determined significant maternal and newborn factors associated with pharmacotherapy, which were combined in a nomogram to predict probability of treatment for infants at each participating site.

Hypothermia for Hypoxic-ischemic Encephalopathy: Second-generation Trials to Address Gaps in Knowledge.

Multiple randomized controlled trials of hypothermia for moderate or severe neonatal hypoxic-ischemic encephalopathy (HIE) have uniformly demonstrated a reduction in death or disability at early childhood evaluation. These initial trials along with other smaller studies established hypothermia as a standard of care in the neonatal community for moderate or severe HIE. The results of the initial trials have identified gaps in knowledge.

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.

Association of maternal pre-pregnancy or first trimester body mass index with neurodevelopmental impairment or death in extremely low gestational age neonates.

Objective: To compare the rates of death or survival with severe neurodevelopmental impairment (sNDI) at 2 years among extremely preterm infants in relation to pre-pregnancy or first-trimester maternal body mass index (BMI).

Methods: This retrospective cohort study included extremely preterm infants (gestational age 22-26 weeks). The study was conducted at National Institute of Child Health and Human Development Neonatal Research Network sites.

Neonatal Hypoxic-Ischemic Encephalopathy and Hypothermia Treatment.

Neonatal hypoxic-ischemic encephalopathy (HIE) is an important clinical entity because it is associated with death and long-term disability, including cognitive impairment, cerebral palsy, seizures, and neurosensory deficits. Over the past 40 years, there has been an intensive search to identify therapies to improve the prognosis of neonates with HIE. Hypothermia treatment represents the culmination of laboratory investigations including small and large animal studies, followed by pilot human studies, and, finally, randomized controlled trials to establish efficacy and safety.

Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants: A Secondary Near-Infrared Spectroscopy Study of the Transfusion of Prematures Randomized Clinical Trial (TOP NIRS).

Importance: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes.

Objective: To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age.

Design, Setting, And Participants: This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.

Serum ferritin values in neonates <29 weeks' gestation are highly variable and do not correlate with reticulocyte hemoglobin content.

Objectives: To compare serum ferritin and RET-He values among extremely low gestational age neonates ELGANs with other markers of iron-deficient erythropoiesis.

Study Design: This is a secondary analysis of the NICHD Darbepoetin Trial. Study data from placebo recipients who had a serum ferritin, a RET-He, and a mean corpuscular volume (MCV) measurement within a 24-hour period were analyzed for correlation.

Use of term reference infants in assessing the developmental outcome of extremely preterm infants: lessons learned in a multicenter study.

Objective: Extremely preterm (EP) impairment rates are likely underestimated using the Bayley III norm-based thresholds scores and may be better assessed relative to concurrent healthy term reference (TR) infants born in the same hospital.

Study Design: Blinded, certified examiners in the Neonatal Research Network (NRN) evaluated EP survivors and a sample of healthy TR infants recruited near the 2-year assessment age.

Results: We assessed 1452 EP infants and 183 TR infants.

Pragmatic, randomized, blinded trial to shorten pharmacologic treatment of newborns with neonatal opioid withdrawal syndrome (NOWS).

Background: The incidence of maternal opioid use in the USA has increased substantially since 2000. As a consequence of opioid use during pregnancy, the incidence of neonatal opioid withdrawal syndrome (NOWS) has increased fivefold between 2002 and 2012. Pharmacological therapy is indicated when signs of NOWS cannot be controlled, and the objective of pharmacological therapy is to control NOWS signs.

Antenatal Steroids, Prophylactic Indomethacin, and the Risk of Spontaneous Intestinal Perforation.

Objective: To estimate if the odds of spontaneous intestinal perforation (SIP) are increased when antenatal steroids (ANS) given close to delivery are combined with indomethacin on day 1 after birth (Indo-D1).

Study Design: A retrospective cohort study using the Neonatal Research Network (NRN) database of inborn infants, gestational age 22-28 weeks or birth weight of 401-1000 g, born between January 1, 2016 and December 31, 2019, and surviving >12 hours. The primary outcome was SIP through 14 days.

Evaluation of heterogeneity in effect of therapeutic hypothermia by sex among infants with neonatal encephalopathy.

Background: Our objective was to examine heterogeneity in the effect of therapeutic hypothermia by sex in infants with moderate or severe neonatal encephalopathy.

Methods: We conducted a post hoc analysis of the Induced Hypothermia trial, which included infants born at gestational ages ≥36 weeks, admitted at ≤6 postnatal hours with evidence of severe acidosis or perinatal complications and moderate or severe neonatal encephalopathy. Multivariate modified Poisson regression models were used to compare the treatment effect of whole-body hypothermia versus control, with an evaluation of interaction by sex, on the primary outcome of death or moderate or severe disability at 18-22 months of corrected age.

Maternal hypertensive disorders and survival without major morbidities among extremely low gestation newborns.

Objective: Evaluate if odds of survival without major morbidity are higher among extremely low gestation neonates (ELGANs) born to mothers with chronic hypertension (cHTN) or hypertensive disorders of pregnancy (HDP) compared to ELGANs born to mothers without hypertension (HTN).

Study Design: Retrospective study of prospectively collected data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Included children had a birthweight of 401-1000 g and/or gestational age of 22 to 28 wks.

Antiseizure medication at discharge in infants with hypoxic-ischaemic encephalopathy: an observational study.

Objectives: To assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic encephalopathy (HIE) and seizures.

Design: Retrospective study of infants enrolled in three National Institute of Child Health and Human Development Neonatal Research Network Trials of therapeutic hypothermia.

Setting: 22 US centres.

Neuroprotective therapies in the NICU in term infants: present and future.

Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While TH for NE in term and near-term infants has proven beneficial, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. There is therefore a critical need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children.

Association of Antenatal Steroid Exposure at 21 to 22 Weeks of Gestation With Neonatal Survival and Survival Without Morbidities.

Importance: The provision of antenatal corticosteroids to pregnant patients at gestational age (GA) 22 6/7 weeks or less remains controversial and lacks support from randomized clinical trials.

Objective: To compare rates of survival and survival without major morbidities among infants born at GA 22 0/7 to 23 6/7 weeks after exposure to antenatal steroids at 22 6/7 weeks' gestation or less vs no exposure to antenatal steroids.

Design, Setting, And Participants: This cohort study enrolled infants born at GA 22 0/7 to 23 6/7 weeks between January 1, 2016, and December 31, 2019, at centers in the National Institute of Child Health and Human Development Neonatal Research Network.

Neuroprotection for hypoxic-ischemic encephalopathy: Contributions from the neonatal research network.

Therapeutic hypothermia (TH) is now well established as the standard of care treatment for moderate to severe neonatal encephalopathy secondary to perinatal hypoxic ischemic encephalopathy (HIE) in infants ≥36 weeks gestation in high income countries. The Neonatal Research Network (NRN) contributed greatly to the study of TH as a neuroprotectant with three trials now completed in infants ≥36 weeks gestation and the only large randomized-controlled trial of TH in preterm infants now in the follow-up phase. Data from the first NRN TH trial combined with data from other large trials of TH affirm the safety and neuroprotective qualities of TH and highlight the importance of providing TH to all infants who qualify.

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.

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.

Model for severe intracranial hemorrhage and role of early indomethacin in extreme preterm infants.

Background: To develop a model for prediction of severe intracranial hemorrhage (ICH) or death based on variables from the first 12 h of age and to compare mortality and morbidities with and without exposure to early indomethacin.

Methods: This retrospective cohort study included extreme preterm (22-26 weeks) infants born at National Institute of Child Health and Human Development Neonatal Research Network sites. Primary outcome was a composite of severe ICH and/or death.

Predictive Ability of 10-Minute Apgar Scores for Mortality and Neurodevelopmental Disability.

Objective: To test the hypothesis that an Apgar score at 10 minutes is independently predictive for death or moderate or severe disability.

Methods: A secondary analysis of the Optimizing Cooling Trial (NCT01192776) including 347 infants with ≥36 weeks' gestational age at birth and hypoxic-ischemic encephalopathy and 18- to 22-month outcomes from 18 US centers in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome was the composite of death or moderate/severe disability at 18 to 22 months of age.

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.

Blanket temperature during therapeutic hypothermia and outcomes in hypoxic ischemic encephalopathy.

Objective: Determine whether blanket temperatures during therapeutic hypothermia (TH) are associated with 18-22 month outcomes for infants with hypoxic ischemic encephalopathy (HIE).

Study Design: Retrospective cohort study of 181 infants with HIE who received TH in two randomized trials within the Neonatal Research Network. We defined summative blanket temperature constructs and evaluated for association with a primary composite outcome of death or moderate/ severe disability at 18-22 months.