Vitamin D Supplementation for Extremely Preterm Infants

After informed consent obtained, infants will be randomized using computer-generated
stratified randomization codes by the pharmacy. Clinicians, researcher, and primary
caregivers will be masked. Subjects will be randomly assigned to one of the treatment arms
or to a placebo concurrent control.

Early vitamin D supplementation/placebo will be initiated within the first 7 days after
birth. Premature infants will be randomized to receive one of the 3 fixed doses of vitamin
D: either placebo (zero dose), 200 IU/day, or 800 IU/day. The supplementation will be
started within 72 hours of enteral feeds being initiated and will continue until postnatal
day 28. After this period of supplementation, routine supplementation will be conducted in
all groups.

Remnant cord blood samples will be analyzed for vitamin D levels (serum hydroxyvitamin D
[25(OH)D]. Two circulating vitamin D concentrations (25(OH)D concentrations) will be
measured on postnatal days 14 and 28. Urine samples will be collected weekly, to determine
calcium excretion if high serum calcium concentrations are found.

Supplementation will be discontinued and infant will exit the study if surgical necrotizing
enterocolitis/bowel perforation is diagnosed, if 25 (OH)D concentrations >60ng/mL
(>150nmol/L; potentially toxic) are detected or, if infant NPO for greater than 24 hours. If
infant made briefly NPO (<24h) for feeding intolerance, suspected sepsis,
hypotension,hemodynamically significant PDA, or respiratory difficulties, enteral vitamin D
will not be discontinued.

All infants will be followed to discharge for primary, secondary outcomes as well as adverse
events.

Inclusion Criteria:

- Infants admitted to the Regional Newborn ICU of the University of Alabama with
gestational age between 23-27 completed weeks

Exclusion Criteria:

- Major congenital/chromosomal anomalies

- Moribund infant with low likelihood of survival, in opinion of the clinical team