Outcomes of Extremely Preterm Infants Exposed to Prolonged Prelabor Rupture of Membranes before 24 Weeks of Gestation.

Background: Preterm prelabor rupture of membranes (PPROM) before or around the limit of fetal viability is associated with serious maternal and neonatal complications including chorioamnionitis, extremely preterm birth, and pulmonary hypoplasia.

Objectives: To describe contemporary outcomes of extremely preterm infants born after prolonged periviable PPROM, and to identify perinatal factors associated with survival and survival without severe neurodevelopmental impairment (NDI).

Study Design: Among actively treated infants born alive at <27 weeks' gestational age (GA) in centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network from 2012 to 2018, the outcomes of survival and survival without severe NDI at 22-26 months' corrected age were compared between infants exposed to prolonged (≥120 hours) periviable (<24 weeks' GA) PPROM and unexposed infants born after rupture of membranes ≤18 hours before delivery or at delivery, adjusting for birth GA, sex, multiple gestation, antenatal steroids, small for gestational age (SGA), insurance, and center.

Cerebrospinal Fluid Composition of Infants with Ischemic Stroke.

Objective: To characterize the cerebrospinal fluid (CSF) of infants with stroke and compare those findings to the CSF of infants with bacterial meningitis and neither condition in the first 14 postnatal days.

Study Design: Cohort study of 30,092 infants who received a lumbar puncture in the first 14 postnatal days discharged from >300 neonatal intensive care units from 1997-2020. CSF parameters were compared between infants with stroke and bacterial meningitis using non-parametric hypothesis testing and quantile regression.

Cerebral injury and retinopathy as risk factors for blindness in extremely preterm infants.

Objective: This study investigates whether and to what extent cerebral injury is associated with bilateral blindness in extremely preterm infants, which has been attributed mainly to retinopathy of prematurity (ROP).

Design: Multicentre analysis of children born from 1994 to 2021 at gestational age 22 0/7 to 28 6/7 weeks with follow-up at 18-26 months. Logistic regression examined the adjusted association of bilateral blindness with severe ROP and/or cerebral injury among extremely preterm infants.

Use and utility of C-reactive protein (CRP) in neonatal early-onset sepsis: a secondary analysis of a prospective surveillance study.

Objective: Characterize C-reactive protein (CRP) within 72 postnatal hours in early-onset sepsis (EOS).

Study Design: Secondary analysis of a prospective surveillance study of neonates with EOS 2015-2017. We examined CRP use by center and neonatal characteristics, and CRP levels by time, neonatal characteristics, clinical signs, and pathogen.

The association of the room air challenge with long-term outcomes in extremely preterm infants.

Objective: Evaluate the association between results of the room air (RA) challenge and death, respiratory morbidity, and neurodevelopmental impairment (NDI) at 2 years' corrected age.

Study Design: Cohort study of infants born <27 weeks' gestational age who underwent a RA challenge to determine BPD diagnosis at 36 weeks postmenstrual age.

Results: Of 1022 infants eligible for the RA challenge, 554 underwent testing and 223 passed.

Decreasing Blood Transfusions in Premature Infants Through Quality Improvement.

Background And Objectives: Packed red blood cell transfusions (pRBCT) in preterm infants have been associated with significant morbidity. Although infants <26 weeks' gestational age typically require several pRBCT, preterm infants born between 26 and 34 weeks' gestational age may also require pRBCT during their hospitalization that are potentially preventable. We aimed to reduce pRBCT in this population by 20%.

Genomic Differences between Spontaneous versus Indicated Extreme Preterm Birth.

Objective:  Extremely preterm infants are at high risk of neonatal mortality and morbidity. Extreme preterm birth (PTB) may result from spontaneous preterm labor or preterm premature rupture of membranes or may be indicated due to preeclampsia, eclampsia, hypertension, or other causes. Our objective was to identify single nucleotide polymorphisms (SNPs) and biological pathways associated with spontaneous versus indicated extreme PTB using the neonatal genome.

Effect of Early vs Late Inguinal Hernia Repair on Serious Adverse Event Rates in Preterm Infants: A Randomized Clinical Trial.

Importance: Inguinal hernia repair in preterm infants is common and is associated with considerable morbidity. Whether the inguinal hernia should be repaired prior to or after discharge from the neonatal intensive care unit is controversial.

Objective: To evaluate the safety of early vs late surgical repair for preterm infants with an inguinal hernia.

Social distancing and extremely preterm births in the initial COVID-19 pandemic period.

Hypothesis: Increased social distancing was associated with a lower incidence of extremely preterm live births (EPLB) during the initial COVID-19 pandemic period.

Study Design: Prospective study at the NICHD Neonatal Research Network sites comparing EPLB (22-28 weeks) and extremely preterm intrapartum stillbirths (EPIS) rates during the pandemic period (March-July, weeks 9-30 of 2020) with the reference period (same weeks in 2018 and 2019), correlating with state-specific social distancing index (SDI).

Results: EPLB and EPIS percentages did not significantly decrease (1.

Late-Onset Sepsis Evaluation and Empiric Therapy in Extremely Low Gestational Age Newborns.

Background: Little is known about late-onset sepsis (LOS) evaluations in extremely low gestational age newborns (ELGANs). We describe frequencies of LOS evaluation in ELGANs, infant characteristics, and empiric therapy choices during evaluations.

Methods: Cohort study of infants 22-28 weeks gestational age (GA) discharged from 243 centers from 2009 to 2018, excluding infants with congenital anomalies, discharged or deceased prior to postnatal day (PND) 2, or admitted after PND 2.

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.

Genetic Predisposition to Adverse Neurodevelopmental Outcome of Extremely Low Birth Weight Infants.

Objective: This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants.

Study Design: We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication.

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.

The effect of sex on retinopathy of prematurity severity among premature mixed-sex multiple gestation infants.

This retrospective study of 68 premature infants examined whether there was a difference between male and female mixed-sex multiple gestation infants with regard to stage of retinopathy of prematurity (ROP) developed or need for ROP treatment. We found that among mixed-sex twin infants there was no statistically significant difference between sexes in most severe ROP stage developed or need for ROP treatment, but males were treated at an earlier postmenstrual age (PMA) than females, despite females having a lower mean birthweight and slower mean growth velocity compared to males.

Association of patent ductus arteriosus with extubation failure among preterm infants.

Background: Mechanical ventilation is associated with mortality/morbidities in preterm infants. Nearly a third of these infants fail extubation, and this may increase morbidities.

Objective: To evaluate the association of moderate to large symptomatic patent ductus arteriosus (PDA) with failure of extubation among preterm infants.

Early pumping frequency and coming to volume for mother's own milk feeding in hospitalized infants.

Objective: To identify daily pumping frequencies associated with coming to volume (CTV: producing > 500 milliliters of milk per day by postnatal day 14) for mothers of infants in the neonatal intensive care unit (NICU).

Study Design: We compared demographics and daily pumping frequencies for mothers who did and did not experience CTV.

Results: Of 427 mothers who produced milk, 201 (50.

Rapid Whole Genome Sequencing in Critically Ill Neonates Enables Precision Medicine Pipeline.

Rapid genome sequencing in critically ill infants is increasingly identified as a crucial test for providing targeted and informed patient care. We report the outcomes of a pilot study wherein eight critically ill neonates received rapid whole genome sequencing with parental samples in an effort to establish a prompt diagnosis. Our pilot study resulted in a 37.

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.

Indomethacin Prophylaxis in Preterm Infants: Changes over Time.

Objective:  Our objective was to examine changes in the use of indomethacin prophylaxis in the neonatal intensive care unit (NICU) between 2008 and 2018.

Study Design:  The design of the study included cohort of 19,715 infants born between 22 and 26 weeks' gestation from 213 NICUs. A nonparametric trend test evaluated indomethacin prophylaxis and the percentage of sites using any prophylaxis over time.

Contributions of the NICHD neonatal research network to the diagnosis, prevention, and treatment of bronchopulmonary dysplasia.

Despite improvements in the care and outcomes of infants born extremely preterm, bronchopulmonary dysplasia (BPD) remains a common and frustrating complication of prematurity. This review summarizes the BPD-focused research conducted by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN). To improve disease classification and outcome prediction, the NRN developed new data-driven diagnostic criteria for BPD and web-based tools that allow clinicians and investigators to reliably estimate BPD risk in preterm infants.

Indomethacin Prophylaxis in Preterm Infants: Changes over Time.

Objective: Our objective was to examine changes in the use of indomethacin prophylaxis in the neonatal intensive care unit (NICU) between 2008 and 2018.

Study Design: The design of the study included cohort of 19,715 infants born between 22 and 26 weeks' gestation from 213 NICUs. A nonparametric trend test evaluated indomethacin prophylaxis and the percentage of sites using any prophylaxis over time.

Overview of the neonatal research network: History, contributions, challenges, and future.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network (NRN) has been a leader in neonatal research since 1986. In this chapter we review its history and achievements in (1) continuing observation of populations, treatments, short and longer-term outcomes, and trends over time; (2) "negative studies" (trials with non-significant primary outcomes) and trials stopped for futility or adverse events, which have influenced practice and subsequent trial design; and, (3) landmark trials that have changed neonatal care. Its consistent framework has enabled the NRN to be a pioneer in conducting longer-term, school-age follow-up.

Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease.

Background: Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991.

Aims: Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs).

Study Design: We obtained demographic information and acyclovir dosing via medical records.

Online clinical tool to estimate risk of bronchopulmonary dysplasia in extremely preterm infants.

Objective: Develop an online estimator that accurately predicts bronchopulmonary dysplasia (BPD) severity or death using readily-available demographic and clinical data.

Design: Retrospective analysis of data entered into a prospective registry.

Setting: Infants cared for at centres of the United States Neonatal Research Network between 2011 and 2017.