The HYdrocortisone for Bronchopulmonary Dysplasia Respiratory and Developmental (HYBRiD) outcomes study: protocol for a longitudinal cohort study.

Background: Bronchopulmonary dysplasia (BPD) affects up to half of extremely preterm infants, and is associated with adverse long-term respiratory, neurodevelopmental, and educational sequelae and costly health service and family economic outcomes. The NICHD Neonatal Research Network Hydrocortisone for Bronchopulmonary Dysplasia (BPD) Trial evaluated the efficacy and safety of hydrocortisone treatment to prevent BPD in high-risk infants. The trial enrolled 800 very preterm infants with respiratory failure and followed the participants until 2 years corrected age to assess safety of the trial intervention.

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.

Longitudinal Assessment of Preterm Infants Treated with Erythropoiesis Stimulating Agents.

Objective: We previously reported improved neurodevelopment at 2 and 4 years among preterm infants treated with erythropoietin or darbepoetin, known as erythropoiesis-stimulating agents (ESAs). We now characterize longitudinal outcomes through 6 years.

Methods: Children randomized to ESAs or placebo were evaluated at 6 years.

Early developmental trajectory of children with prenatal alcohol and opioid exposure.

Background: With significant increases in opioid use/misuse and persistent high prevalence of prenatal alcohol exposure (PAE), identifying infants at risk for long-term developmental sequelae due to these exposures remains an urgent need. This study reports on developmental outcomes in young children from a prospective cohort, ENRICH-1, which recruited pregnant women and followed up maternal-infant pairs.

Methods: Subjects were assigned to four study groups based on prenatal use of medications for opioid use disorder (MOUD), PAE, MOUD+PAE, and unexposed controls (UC).

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.

Preliminary longitudinal evidence for stability of maternal behavior and infant stress regulation among infants born preterm at 4 and 9 months during the Still Face paradigm.

Stress regulation begins to develop in the first year of life through interactions with caregivers, particularly in the presence of stressors. High quality caregiving, characterized by maternal sensitivity and responsiveness to the infant's emotional cues, is particularly important in the development of infant stress regulation. The purpose of this study was to assess the longitudinal stability of, and associations between, maternal interactive behavior and infant stress regulation (indexed by positive infant affect and cortisol reactivity) in response to the Still Face paradigm (SF) in a cohort of infants born preterm (< 32 weeks gestation, N = 22) at four months and nine months (adjusted age).

Cortisol awakening response and developmental outcomes at 6-7 years in children born extremely preterm.

Background: Extremely preterm (EPT) birth has been related to dysregulation of stress responses and behavioral/learning problems at school age. Early adverse experiences can blunt HPA axis reactivity. We hypothesized that an attenuated cortisol awakening response would be associated with developmental and behavioral problems at school age in EPT children.

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.

Relationships between retinopathy of prematurity without ophthalmologic intervention and neurodevelopment and vision at 2 years.

Background: Severe retinopathy of prematurity (ROP) is associated with adverse outcomes. Relationships between milder ROP and outcomes have not been defined. We hypothesized that children with ROP stage ≤3 who did not receive ophthalmologic intervention would have worse motor, cognitive, and language skills and more vision abnormalities than children without ROP.

The role of maternal interactive behavior and gestational age in predicting infant affect during the Still-Face Paradigm.

Background: Emotion regulation develops through bidirectional affective communication.

Aim: To investigate the role of maternal interactive behavior in predicting infant affect among preterm versus full-term infants.

Study Design: The association between maternal interactive behavior (contingent, attention seeking, watching) and infant affect during a modified Still Face (SF) paradigm in a sample of 22 preterm and 28 full term infants (3 ½ - 4 ½ months old) was investigated.

Maternal verbal scaffolding: association with higher language skills for 20-month-old children with prenatal polysubstance exposure.

Background: The number of children with prenatal polysubstance exposure is increasing. Supportive mother-child interaction is a protective factor, which can ameliorate adverse effects of prenatal polysubstance exposure on developmental outcomes.

Aim: To examine the role of maternal verbal scaffolding on cognitive and language development in children with prenatal polysubstance exposure.

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.

DNA methylation in former extremely low birth weight newborns: association with cardiovascular and endocrine function.

Background: There is increased risk of cardiovascular, metabolic, and hypertensive disorders in later life in the preterm population. We studied school-age children who had been born extremely premature who had undergone endocrine, cardiovascular, and anthropometric evaluations.

Methods: School age measurements of salivary cortisol, adrenal androgens, blood pressure, and anthropometric markers were correlated with DNA methylation of 11-betahydroxysteroid dehydrogenase type 2 (11BHSD2), leptin, and the LINE1 repetitive DNA element.

Effect of blood transfusions on cognitive development in very low birth weight infants.

Objective: Preterm infants frequently receive red cell transfusions; however, the effect of transfusions on cognition is unclear. We evaluated the relationship between transfusions and cognitive outcomes in preterm infants enrolled in a randomized trial of erythropoiesis stimulating agents (ESAs).

Study Design: Preterm infants were randomized to ESAs or placebo during initial hospitalization, and transfusions recorded.

The association of infant temperament and maternal sensitivity in preterm and full-term infants.

Infants who experience sensitive caregiving are at lower risk for numerous adverse outcomes. This is especially true for infants born preterm, leading them to be more susceptible to risks associated with poorer quality caregiving. Some research suggests that preterm and full-term infants differ on temperament, which may contribute to these findings.

Self-regulation and emotional reactivity in infants with prenatal exposure to opioids and alcohol.

Background: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.

Methods: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.

Early working memory is a significant predictor of verbal and processing skills at 6-7 years in children born extremely preterm.

Objective: The study was designed to investigate whether attainment of object permanence, a measure of early working memory used at 18-22 months corrected age, was associated with executive function at 6-7 years in a cohort of children born extremely preterm.

Study Design: Children enrolled in the Neuroimaging and Neurodevelopmental Outcome (NEURO) study, a secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Trial (SUPPORT) of the NICHD NRN, were eligible for this longitudinal study. Testing completed at 18 to 22 months corrected age was compared to testing at school age with a specific focus on measures of executive function.

Neural and visceral manipulation in infants with congenital muscular torticollis: a feasibility study.

[Purpose] As an alternative to manual stretching, the aim of this study was to investigate the feasibility of using neural/visceral manipulation as a safe and effective intervention to increase neck range of motion of infants with congenital muscular torticollis. [Participants and Methods] Ten 4-month old infants with congenital muscular torticollis received eight sessions of neural/visceral manipulation administered for 30-50 minutes without observed pain. Specific palpation techniques addressed restricted tissue areas of neck, head, trunk and extremities.

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.

Developmental Outcomes of Extremely Preterm Infants with a Need for Child Protective Services Supervision.

Objective: To evaluate neurodevelopmental outcomes of preterm infants with need for Child Protective Services (CPS) supervision at hospital discharge compared with those discharged without CPS supervision.

Study Design: For infants born at <27 weeks of gestation between 2006 and 2013, prospectively collected maternal and neonatal characteristics and 18- to 26-month corrected age follow-up data were analyzed. Bayley-III cognitive and language scores of infants with discharge CPS supervision were compared with infants without CPS supervision using regression analysis while adjusting for potentially confounding variables, including entering CPS after discharge from the hospital.

The association between maternal interaction and infant cortisol stress reactivity among preterm and full term infants at 4 months adjusted age.

The purpose of this study was to assess the association between maternal interactive behavior and infant cortisol stress reactivity in response to the Still Face paradigm (SF) in a cohort of four-month old infants (adjusted age) born preterm (<32 weeks gestation, N = 22) compared with infants born full term (>37 weeks gestation, N = 28). Infant cortisol reactivity was calculated as area under the curve (AUC) from baseline to the third cortisol sample (30 min post-SF) using the trapezoidal rule, while the percent of time mothers spent using a contingent interaction style was measured (0-100%) during episodes 1 (Play; baseline), 3 (Reunion#1), and 5 (Reunion#2) while mother-infant dyads participated in the SF paradigm. We hypothesized that because infants born preterm are at increased risk for dysregulation, they would show, compared to full-term infants, a blunted stress response, involving under-responsiveness.

Postnatal diagnosis of de novo complex der(8) in a boy with prenatal diagnosis of recombinant chromosome 8 syndrome.

Recombinant chromosome 8 syndrome is caused by duplication of 8q and deletion of 8p. A fetus with anomalies was misdiagnosed with this syndrome based on an amniocyte karyotype. Postnatal chromosomal microarray and other studies identified a de novo derivative chromosome 8.

Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm.

Background: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children.

Methods: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol.

Association between prenatal opioid exposure, neonatal opioid withdrawal syndrome, and neurodevelopmental and behavioral outcomes at 5-8 months of age.

Background: While use of prescription opioids and medication assisted therapy (MAT) for opioid use disorder in pregnancy, as well as the incidence of neonatal opioid withdrawal syndrome (NOWS) continue to rise, little is known about outcomes for children with NOWS beyond the newborn period.

Methods: We examined 1) prenatal MAT exposure vs. unexposed healthy controls [HC]; and 2) treatment for NOWS and NOWS severity on infant neurodevelopmental and behavioral outcomes at 5-8 months of age in 78 maternal-infant pairs from the ENRICH prospective cohort study.