Thermoregulation-Focused Implementation of Delayed Cord Clamping among <34 Weeks' Gestational Age Neonates.

Objective: Delayed cord clamping (DCC) is recommended for all neonates; however, adapting such practice can be slow or unsustainable, especially among preterm neonates. During DCC neonates are exposed to a cool environment, raising concerns for neonatal hypothermia. Moderate hypothermia may induce morbidities that counteract the potential benefits of DCC.

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.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

Background: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking.

Methods: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care.

Prevalence and Risk Factors for Kidney Disease and Elevated BP in 2-Year-Old Children Born Extremely Premature.

Background And Objectives: Extremely low gestational age neonates born <28 weeks gestation are at risk for chronic disease. We sought to describe the prevalence of kidney outcomes by gestational age and determine risk factors for their development.

Design, Setting, Participants, & Measurements: The Recombinant Erythropoietin for Protection of Infant Renal Disease (REPAIReD) study examined kidney outcomes of extremely low gestational age neonates enrolled in the Preterm Epo NeuroProtection Trial (PENUT) study.

Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

Background: Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.

Methods: In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia.

Implications of an Elevated Nucleated Red Blood Cell Count in Neonates with Moderate to Severe Hypoxic-Ischemic Encephalopathy.

Objectives: To investigate associations between nucleated red blood cell (NRBC) count in neonates with hypoxic-ischemic encephalopathy (HIE), acute perinatal sentinel events, and neurodevelopmental outcomes and to examine the mechanism(s) causing elevated counts.

Study Design: We included newborn infants with HIE treated with therapeutic hypothermia with ≥3 NRBC counts during their neonatal intensive care unit hospitalization and neurodevelopmental evaluations at a mean of 24 ± 6 months.

Results: Ninety-five of 152 infants who met our study criteria (63%) had a normal NRBC count after birth, defined as ≤95th percentile of the upper reference interval, and the other 57 (37%) had an elevated count.

Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial): A Randomized Controlled Trial: Background, Aims and Study Protocol.

Neonatal hypoxia-ischemia encephalopathy (HIE) is the leading cause of neonatal death and poor neurodevelopmental outcomes worldwide. Therapeutic hypothermia (TH), while beneficial, still leaves many HIE treated infants with lifelong disabilities. Furthermore, infants undergoing TH often require treatment for pain and agitation which may lead to further brain injury.

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.

Extremely Preterm Infant Admissions Within the SafeBoosC-III Consortium During the COVID-19 Lockdown.

To evaluate if the number of admitted extremely preterm (EP) infants (born before 28 weeks of gestational age) differed in the neonatal intensive care units (NICUs) of the SafeBoosC-III consortium during the global lockdown when compared to the corresponding time period in 2019. This is a retrospective, observational study. Forty-six out of 79 NICUs (58%) from 17 countries participated.

Darbepoetin as a neuroprotective agent in mild neonatal encephalopathy: a randomized, placebo-controlled, feasibility trial.

Objective: To assess the feasibility and safety of one dose of Darbepoetin alpha (Darbe) administered to neonates ≥34 weeks with mild neonatal encephalopathy (NE).

Methods: Randomized, masked, placebo-controlled study including neonates ≥34 weeks gestation with mild NE. Neonates were randomized to receive one dose of Darbe (10 μg/kg IV) or placebo.

Challenges in Implementing Exclusive Human Milk Diet to Extremely Low-Birth-Weight Infants in a Level III Neonatal Intensive Care Unit.

Problem: Extremely low-birth-weight (ELBW) infants require fortification of human milk (HM) to prevent growth failure. Bovine milk-based fortifiers (BOV-f) may be associated with feeding intolerance and necrotizing enterocolitis. Evidence suggests that an exclusive HM diet (EHMD) using HM-based fortifier (HM-f) may improve these outcomes.

Abnormal Splanchnic Regional Saturations in a Preterm Infant That Developed Necrotizing Enterocolitis Following a Red Blood Cell Transfusion.

Background: Necrotizing enterocolitis (NEC) has been associated with red blood cell (RBC) transfusions in preterm infants. Near-infrared spectroscopy (NIRS) can be used to noninvasively monitor regional oxygen saturations (rSO2).

Clinical Findings: This former 28-week female premature infant, 29 days old, received an RBC transfusion due to increased apneic spells and a hematocrit of 27%.

Effect of High-Dose Erythropoietin on Blood Transfusions in Extremely Low Gestational Age Neonates: Post Hoc Analysis of a Randomized Clinical Trial.

Importance: Extremely preterm infants are among the populations receiving the highest levels of transfusions. Erythropoietin has not been recommended for premature infants because most studies have not demonstrated a decrease in donor exposure.

Objectives: To determine whether high-dose erythropoietin given within 24 hours of birth through postmenstrual age of 32 completed weeks will decrease the need for blood transfusions.

A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants.

Background: High-dose erythropoietin has been shown to have a neuroprotective effect in preclinical models of neonatal brain injury, and phase 2 trials have suggested possible efficacy; however, the benefits and safety of this therapy in extremely preterm infants have not been established.

Methods: In this multicenter, randomized, double-blind trial of high-dose erythropoietin, we assigned 941 infants who were born at 24 weeks 0 days to 27 weeks 6 days of gestation to receive erythropoietin or placebo within 24 hours after birth. Erythropoietin was administered intravenously at a dose of 1000 U per kilogram of body weight every 48 hours for a total of six doses, followed by a maintenance dose of 400 U per kilogram three times per week by subcutaneous injection through 32 completed weeks of postmenstrual age.

Splanchnic-Cerebral Oxygenation Ratio Decreases during Enteral Feedings in Anemic Preterm Infants: Observations under Near-Infrared Spectroscopy.

Background: Anemia is common in premature infants. Due to risks with red blood cell transfusions, many anemic infants are not transfused. The implications of this pathophysiologic status, especially at times of increased metabolic demand (enteral feedings), is not well understood.

Darbepoetin administration to neonates undergoing cooling for encephalopathy: a safety and pharmacokinetic trial.

Background: Despite therapeutic hypothermia, neonates with encephalopathy (NE) have high rates of death or disability. Darbepoetin alfa (Darbe) has comparable biological activity to erythropoietin, but has extended circulating half-life (t(1/2)). Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia.

Population Pharmacokinetics of Darbepoetin Alfa in Conjunction with Hypothermia for the Treatment of Neonatal Hypoxic-Ischemic Encephalopathy.

Aim: The aim of this study was to determine the population pharmacokinetics of darbepoetin alfa in hypothermic neonates with hypoxic-ischemic encephalopathy treated with hypothermia.

Methods: Neonates ≥36 weeks gestation and <12 h postpartum with moderate to severe hypoxic-ischemic encephalopathy who were undergoing hypothermia treatment were recruited in this randomized, multicenter, investigational, new drug pharmacokinetic study. Two intravenous darbepoetin alfa treatment groups were evaluated: 2 and 10 µg/kg.

Organ-specific defects in insulin-like growth factor and insulin receptor signaling in late gestational asymmetric intrauterine growth restriction in Cited1 mutant mice.

Late gestational placental insufficiency resulting in asymmetric intrauterine organ growth restriction (IUGR) is associated with an increased incidence of diabetes, cardiovascular and renal disease in adults. The molecular mechanisms mediating these defects are poorly understood. To explore this, we investigated the mechanisms leading to IUGR in Cited1 knockout mice, a genetic model of late gestational placental insufficiency.

Fetal growth restriction alters transcription factor binding and epigenetic mechanisms of renal 11beta-hydroxysteroid dehydrogenase type 2 in a sex-specific manner.

Intrauterine growth restriction (IUGR) increases the risk of serious adult morbidities such as hypertension. In an IUGR rat model of hypertension, we reported a persistent decrease in kidney 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) mRNA and protein levels from birth through postnatal (P) day 21. This enzyme deficiency can lead to hypertension by limiting renal glucocorticoid deactivation.

Uteroplacental insufficiency affects kidney VEGF expression in a model of IUGR with compensatory glomerular hypertrophy and hypertension.

Low nephron endowment secondary to intrauterine growth restriction (IUGR) results in compensatory hypertrophy of the remaining glomeruli, which in turn is associated with hypertension. However, gender differences exist in the response of the kidney to injury, and IUGR female offspring seems protected from an unfavorable outcome. We previously reported differences in gender-specific gene expression in the IUGR kidney as well as increased circulating corticosterone levels following uteroplacental insufficiency (UPI).