Vitamin D supplementation during pregnancy: Double‐blind, randomized clinical trial of safety and effectiveness

Double-blind randomized clinical trial in pregnant women with singleton pregnancies enrolled at the Medical University of South Carolina in Charleston, South Carolina, at 12 to 16 weeks' gestation. Participants were randomized to 400 IU/day (n=166), 2000 IU/day (n=167), or 4000 IU/day (n=169) vitamin D supplementation and followed through delivery.

Pregnant participants received a daily prenatal multivitamin containing 400 IU vitamin D plus an additional vitamin D3 (cholecalciferol) supplement of 0 IU, 1600 IU, or 3600 IU, for total vitamin D intakes of 400 IU/day, 2000 IU/day, or 4000 IU/day. Supplementation began between 12 and 16 weeks' gestation and continued until delivery; route was not stated.

Vitamin D3 supplementation was effective, and 4000 IU/day was the most effective dose for achieving maternal and neonatal vitamin D sufficiency without identified safety concerns. Mean circulating 25(OH)D was highest in the 4000 IU group at second trimester (98.6 nmol/L) and one month prior to delivery (114.2 nmol/L), both with p < 0.0001 versus lower-dose groups. Neonatal 25(OH)D also increased with dose: 45.5 nmol/L, 57.0 nmol/L, and 66.3 nmol/L, with sufficiency by IOM criteria in 39.7%, 58.2%, and 78.6% of infants for the 400 IU, 2000 IU, and 4000 IU groups, respectively (p < 0.0001). No adverse events were attributed to vitamin D supplementation, and gestational age at delivery, birth weight, and neonatal care level did not differ across groups.

The trial was conducted at a single center in Charleston, South Carolina, in women with singleton pregnancies, which limits generalizability. The main benefits were shown on biochemical vitamin D outcomes rather than hard maternal or neonatal clinical endpoints, and the study was not designed to detect rare safety events or modest differences in delivery outcomes.