Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

Background: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system.

Objective: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes.

Accuracy of preterm infant weight gain velocity calculations vary depending on method used and infant age at time of measurement.

Background: We examined preterm infants' weight gain velocity (WGV) to determine how much calculation methods influences actual WGV during the first 28 days of life.

Methods: WGV methods (Average 2-point, Exponential 2-point, Early 1-point, and Daily) were calculated weekly and for various start times (birth, nadir, regain, day 3 and day 7) to 28 days of age for 103 preterm < 1500 gram infants, with daily weights.

Results: Range of WGV estimates decreased 10-22 g/kg/day to 15.

Genetic variants associated with patent ductus arteriosus in extremely preterm infants.

Objective: Patent ductus arteriosus (PDA) is a commonly observed condition in preterm infants. Prior studies have suggested a role for genetics in determining spontaneous ductal closure. Using samples from a large neonatal cohort we tested the hypothesis that common genetic variations are associated with PDA in extremely preterm infants.

An Attempt to Standardize the Calculation of Growth Velocity of Preterm Infants-Evaluation of Practical Bedside Methods.

Objective: To examine how well growth velocity recommendations for preterm infants fit with current growth references: Fenton 2013, Olsen 2010, INTERGROWTH 2015, and the World Health Organization Growth Standard 2006.

Study Design: The Average (2-point), Exponential (2-point), Early (1-point) method weight-gains were calculated for 1,4,8,12, and 16-week time-periods. Growth references' weekly velocities (g/kg/d, gram/day and cm/week) were illustrated graphically with frequently-quoted 15 g/kg/d, 10-30 grams/day and 1 cm/week rates superimposed.

Effect of Therapeutic Hypothermia Initiated After 6 Hours of Age on Death or Disability Among Newborns With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial.

Importance: Hypothermia initiated at less than 6 hours after birth reduces death or disability for infants with hypoxic-ischemic encephalopathy at 36 weeks' or later gestation. To our knowledge, hypothermia trials have not been performed in infants presenting after 6 hours.

Objective: To estimate the probability that hypothermia initiated at 6 to 24 hours after birth reduces the risk of death or disability at 18 months among infants with hypoxic-ischemic encephalopathy.

Late (> 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Background: Many preterm infants who survive go on to develop bronchopulmonary dysplasia, probably as the result of persistent inflammation in the lungs. Corticosteroids have powerful anti-inflammatory effects and have been used to treat individuals with established bronchopulmonary dysplasia. However, it is unclear whether any beneficial effects outweigh the adverse effects of these drugs.

Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

Background: Bronchopulmonary dysplasia remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to prevent or treat bronchopulmonary dysplasia because of their potent anti-inflammatory effects.

Effect of Depth and Duration of Cooling on Death or Disability at Age 18 Months Among Neonates With Hypoxic-Ischemic Encephalopathy: A Randomized Clinical Trial.

Importance: Hypothermia for 72 hours at 33.5°C for neonatal hypoxic-ischemic encephalopathy reduces death or disability, but rates continue to be high.

Objective: To determine if cooling for 120 hours or to a temperature of 32.

Preterm Infant Growth Velocity Calculations: A Systematic Review.

Context: Clinicians assess the growth of preterm infants and compare growth velocity using a variety of methods.

Objective: We determined the numerical methods used to describe weight, length, and head circumference growth velocity in preterm infants; these methods include grams/kilogram/day (g/kg/d), grams/day (g/d), centimeters/week (cm/week), and change in scores.

Data Sources: A search was conducted in April 2015 of the Medline database by using PubMed for studies that measured growth as a main outcome in preterm neonates between birth and hospital discharge and/or 40 weeks' postmenstrual age.

Neurodevelopmental outcomes and nutritional strategies in very low birth weight infants.

The developing brain of the very low birth weight (VLBW) infant is highly sensitive to effects of the nutritional milieu during the neonatal hospitalization and after discharge. Strategies to optimize nutritional care play an important role in reducing long-term neurodevelopmental morbidities in this population. Currently available interventions to ensure that the unique nutrient requirements of the VLBW infant are met include various dietary fortification strategies and parenteral nutrition.

Early Elevation in Interleukin-6 is Associated with Reduced Growth in Extremely Low Birth Weight Infants.

 To determine whether reduced growth velocity (GV) in extremely low birth weight infants is preceded by elevated inflammatory cytokines.  GV was determined at 36 weeks' postmenstrual age (PMA) in 768 infants 401 to 1,000 g birth weight (BW). Association between blood cytokines measured through day of life 21 and GV was explored using linear regression models that adjusted for late-onset sepsis (LOS), BW, small for gestational age (SGA), gender, race, energy intake, and center.

Growth Outcomes of Preterm Infants Exposed to Different Oxygen Saturation Target Ranges from Birth.

Objective: To test whether infants randomized to a lower oxygen saturation (peripheral capillary oxygen saturation [SpO2]) target range while on supplemental oxygen from birth will have better growth velocity from birth to 36 weeks postmenstrual age (PMA) and less growth failure at 36 weeks PMA and 18-22 months corrected age.

Study Design: We evaluated a subgroup of 810 preterm infants from the Surfactant, Positive Pressure, and Oxygenation Randomized Trial, randomized at birth to lower (85%-89%, n = 402, PMA 26 ± 1 weeks, birth weight 839 ± 186 g) or higher (91%-95%, n = 408, PMA 26 ± 1 weeks, birth weight 840 ± 191 g) SpO2 target ranges. Anthropometric measures were obtained at birth, postnatal days 7, 14, 21, and 28; then at 32 and 36 weeks PMA; and 18-22 months corrected age.

Blood Cytokine Profiles Associated with Distinct Patterns of Bronchopulmonary Dysplasia among Extremely Low Birth Weight Infants.

Objective: To explore differences in blood cytokine profiles among distinct bronchopulmonary dysplasia (BPD) patterns.

Study Design: We evaluated blood spots collected from 943 infants born at ≤1000 g and surviving to 28 days on postnatal days 1, 3, 7, 14, and 21 for 25 cytokines. Infants were assigned to the following lung disease patterns: (1) no lung disease (NLD); (2) respiratory distress syndrome without BPD; (3) classic BPD (persistent exposure to supplemental oxygen until 28 days of age); or (4) atypical BPD (period without supplemental oxygen before 28 days).

Safety and pharmacokinetics of multiple dose myo-inositol in preterm infants.

Background: Preterm infants with respiratory distress syndrome (RDS) given inositol had reduced bronchopulmonary dysplasia (BPD), death and severe retinopathy of prematurity (ROP). We assessed the safety and pharmacokinetics of daily inositol to select a dose providing serum levels previously associated with benefit, and to learn if accumulation occurred when administered throughout the normal period of retinal vascularization.

Methods: Infants ≤ 29 wk GA (n = 122, 14 centers) were randomized and treated with placebo or inositol at 10, 40, or 80 mg/kg/d.

Biochemical Screening for Pulmonary Hypertension in Preterm Infants with Bronchopulmonary Dysplasia.

Background: Pulmonary hypertension (PH) in infants with bronchopulmonary dysplasia (BPD) is associated with increased morbidity and mortality. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and decreased levels of amino acid precursors of nitric oxide (NO) have been associated with PH, but have not been studied in infants with PH secondary to BPD.

Objective: The aim of this study was to identify a biochemical marker for PH in infants with BPD.

The Rising Burden of Preeclampsia in the United States Impacts Both Maternal and Child Health.

Objective: Preeclampsia is one of the top six causes of maternal mortality in the United States (US) and is associated with considerable perinatal morbidity and mortality. Evidence suggests the US incidence of preeclampsia has increased dramatically over the past two decades. This study aims to compile, summarize, and critique the literature on the health and economic burden of preeclampsia and early-onset preeclampsia.

Weight Status in the First 2 Years of Life and Neurodevelopmental Impairment in Extremely Low Gestational Age Newborns.

Objective: To examine the extent to which weight gain and weight status in the first 2 years of life relate to the risk of neurodevelopmental impairment in extremely preterm infants.

Study Design: In a cohort of 1070 infants born between 23 and 27 weeks' gestation, we examined weight gain from 7-28 days of life (in quartiles) and weight z-score at 12 and 24 months corrected age (in 4 categories: <-2; ≥-2, <-1; ≥1, <1; and ≥1) in relation to these adverse neurodevelopmental outcomes: Bayley-II mental development index <55, Bayley-II psychomotor development index <55, cerebral palsy, Gross Motor Function Classification System ≥1 (cannot walk without assistance), microcephaly. We adjusted for confounders in logistic regression, stratified by sex, and performed separate analyses including the entire sample, and excluding children unable to walk without assistance (motor impairment).

Impaired Activity of Blood Coagulant Factor XIII in Patients with Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is the most common gastrointestinal (GI) medical/surgical emergency of the newborn and a leading cause of preterm neonate morbidity and mortality. NEC is a challenge to diagnose since it often shares similar clinical features with neonatal sepsis. In the present study, plasma protein profiling was compared among NEC, sepsis and control cohorts using gel electrophoresis, immunoblot and mass spectrometry.

Identifying Barriers to Initiating Minimal Enteral Feedings in Very Low-Birth-Weight Infants: A Mixed Methods Approach.

Objective: This study aims to elicit physician and nursing perceptions about initiation of minimal enteral feedings (MEF) in very low-birth-weight (VLBW) infants.

Study Design: A three-phase, mixed methods study including a quantitative chart review of 37 VLBW infants, followed by 26 qualitative observations of morning rounds, 26 interviews of neonatal intensive care unit (NICU) medical team members, tailored interventions based on the identified barriers to MEF, and finally a postintervention chart audit of 50 VLBW infants.

Results: The main barriers to initiation of MEF were failure to appreciate the differences between the goals of MEF versus nutritive feedings, inconsistent definition of "sick" infant, indomethacin for intraventricular hemorrhage prophylaxis, awaiting mother's own milk, complicated feeding protocols/algorithms for feeding intolerance, and lack of buy-in from nurses/nurse practitioners.

Weight Growth Velocity and Postnatal Growth Failure in Infants 501 to 1500 Grams: 2000-2013.

Background: Very low birth weight infants often gain weight poorly and demonstrate growth failure during the initial hospitalization. Although many of the major morbidities experienced by these infants during their initial NICU stays have decreased in recent years, it is unclear whether growth has improved.

Methods: We studied 362 833 infants weighing 501 to 1500 g without major birth defects born from 2000 to 2013 and who were hospitalized for 15 to 175 days at 736 North American hospitals in the Vermont Oxford Network.

Neonatal sepsis 2004-2013: the rise and fall of coagulase-negative staphylococci.

Objectives: To evaluate data for the period 2004-2013 to identify changes in demographics, pathogens, and outcomes in a single, level IV neonatal intensive care unit.

Study Design: Sepsis episodes were identified prospectively and additional information obtained retrospectively from infants with sepsis while in the neonatal intensive care unit from 2004 to 2013. Demographics, hospital course, and outcome data were collected and analyzed.

Definitions of cardiovascular insufficiency and relation to outcomes in critically ill newborn infants.

Background: We previously reported on the overall incidence, management, and outcomes in infants with cardiovascular insufficiency (CVI). However, there are limited data on the relationship of the specific different definitions of CVI to short-term outcomes in term and late preterm newborn infants.

Objective: This study aims to evaluate how four definitions of CVI relate to short-term outcomes and death.

Cognitive outcomes after neonatal encephalopathy.

Objectives: To describe the spectrum of cognitive outcomes of children with and without cerebral palsy (CP) after neonatal encephalopathy, evaluate the prognostic value of early developmental testing and report on school services and additional therapies.

Methods: The participants of this study are the school-aged survivors of the National Institute of Child Health and Human Development Neonatal Research Network randomized controlled trial of whole-body hypothermia. Children underwent neurologic examinations and neurodevelopmental and cognitive testing with the Bayley Scales of Infant Development-II at 18 to 22 months and the Wechsler intelligence scales and the Neuropsychological Assessment-Developmental Neuropsychological Assessment at 6 to 7 years.

Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial.

Importance: Hypothermia at 33.5°C for 72 hours for neonatal hypoxic ischemic encephalopathy reduces death or disability to 44% to 55%; longer cooling and deeper cooling are neuroprotective in animal models.

Objective: To determine if longer duration cooling (120 hours), deeper cooling (32.

An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk of bronchopulmonary dysplasia.

Infants at higher risk of bronchopulmonary dysplasia had increased rates of survival free of cerebral palsy after postnatal corticosteroid treatment in a previous metaregression of data from 14 randomized controlled trials. The relationship persists and is stronger in an updated analysis with data from 20 randomized controlled trials.