Randomized Trial of Enteral Vitamin D Supplementation in Infants < 28 Weeks Gestational Age or <1000 Grams Birth Weight

Randomized Trial of Enteral Vitamin D Supplementation in Infants < 28 Weeks Gestational Age or <1000 Grams Birth Weight

Randomized Trial of Enteral Vitamin D Supplementation in Infants < 28 Weeks Gestational Age or <1000 Grams Birth Weight

The objective of the study is to compare supplementation with vitamin D at 800 IU/day to usual care for the first 28 days after birth with respect to 25 (OH) vitamin D levels and indicators of likely or plausible effects of vitamin D supplementation on the function or structure of the lung, bones, immune system, and brain in extremely premature (EP) infants who are <28 weeks gestational age (GA) or <1000 grams of birth weight (BW). The study results will be analyzed as intention to treat Bayesian analyses (Frequentist analyses will also be performed).

Infants will receive placebo (normal saline) in the first 28 days after birth. Co-interventions will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices.

Infants will receive cholecalciferol 800 IU/day in the first 28 days after birth, given enterally four times per day (0.5mL per dose = 200 IU) until the infant is provided 400 IU/day. At that point the study cholecalciferol will be reduced to 400 IU/day for a total supplementation of 800 IU/day.

Placebo is normal saline, given in the first 28 days after birth, prepared to have the same volume and appearance as vitamin D, which is a clear odorless solution.

800 IU/day Vitamin D supplementation until 400 IU/ day are provided as part of usual care. At that point the intervention becomes a supplement of 400 IU/day above that given with usual care. In this way all infants in the intervention group receive 800 IU/day of vitamin D total supplementation in the first 28 days after birth with feedings.

Co-interventions will be unaffected and provided based on the judgment of the attending neonatal faculty and NICU policies and routine practices

Data will be reported categorically as: Number of participants who survive without respiratory support Number of participants who survive with nasal cannula at ≤ 2 liters (L)/minute Number of participants who survive with nasal cannula >2 L/minute or noninvasive positive airway pressure Number of participants who survive with invasive mechanical ventilation Number of participants who die

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Z-scores range from -4 standard deviations to +4 standard deviations. A higher Z-score indicates a better outcome.

Neurodevelopment as assessed by the Bayley-IV Scale of Infant and Toddler Development (Cognitive composite score)

Neurodevelopment as assessed by the Bayley-IV Scale of Infant and Toddler Development (Language composite score)

Neurodevelopment as assessed by the Bayley-IV Scale of Infant and Toddler Development (Motor composite score)

Morbidities include retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), bronchopulmonary dysplasia (BPD), neurodevelopmental impairment (NDI), necrotizing enterocolitis (NEC), and patent ductus arteriosus (PDA).

Vitamin D status as indicated by serum concentration of 24,25(OH)2D3 as assessed by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS)

Inclusion Criteria: Infants born at < 28 weeks gestational age (GA) or <1000 grams birth weight (BW) Inborn Informed written consent in an Institutional Review Board (IRB)-approved manner Exclusion Criteria: GA >32 weeks regardless of birth weight (BW) Any major congenital anomaly An known congenital nonbacterial infection Prenatal diagnosis of disorders that affect vitamin D absorption (e.g, cystic fibrosis) Such severe illness or immaturity that the attending neonatologist judges intensive care to be unjustified.