Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency.

Double-blind randomized controlled trial in pregnant Arab women in Al Ain, United Arab Emirates, with singleton pregnancies and very high baseline vitamin D deficiency. A total of 192 women were randomized to 400 IU/day, 2000 IU/day, or 4000 IU/day, and 162 were followed to delivery.

Pregnant participants were randomized to daily oral vitamin D3 tablets plus standard prenatal vitamins, for a total vitamin D3 intake of either 400 IU/day, 2000 IU/day, or 4000 IU/day. Supplementation began at 12-16 weeks of gestation and continued until delivery.

Vitamin D3 at 4000 IU/day was the most effective dose and was reported as safe, with 2000 IU/day also improving vitamin D status versus 400 IU/day. Mean serum 25(OH)D concentrations at delivery and in cord blood were significantly higher in the 2000 and 4000 IU/day groups than in the 400 IU/day group (p<0.001), and the 4000 IU/day group produced the highest levels. At delivery, 65% of mothers on 4000 IU/day were vitamin D sufficient compared with less than 10% on 400 IU/day; if a 25(OH)D threshold of >20 ng/ml was used, 91% of mothers on 4000 IU/day achieved it, and their infants were four times more likely to achieve >20 ng/ml than infants of mothers on 400 IU/day. No adverse events related to vitamin D supplementation were observed.

The trial was relatively small, single-region, and had attrition, with 30 participants discontinuing and only 126 mothers having serum 25(OH)D available at delivery. Confidence intervals were not reported for the main effect estimates, and the study was not designed to determine effects on fetal growth or nonskeletal clinical outcomes.