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.

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.

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.

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.

A Pilot Phase I Trial of Allogeneic Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells in Neonates With Hypoxic-Ischemic Encephalopathy.

Hypoxic ischemic encephalopathy (HIE) in neonates causes increased mortality and long-term morbidity in surviving babies. Hypothermia (HT) has improved outcomes, however, mortality remains high with ~half of surviving babies developing neurological impairment in their first years. We previously explored the use of autologous cord blood (CB) to determine if CB cells could lessen long-term damage to the brain.

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.

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.

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.

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.

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.

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.