Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial.

This was a multicentre, double-blind, randomized placebo-controlled trial in pregnant women in the United Kingdom at three NHS sites. The active cholecalciferol arm included 565 randomized participants with singleton pregnancies enrolled in early gestation and baseline vitamin D status within the trial's prespecified range.

Cholecalciferol 1000 IU/day was given orally as a single capsule from 14 weeks' gestation until delivery, or as soon as possible before 17 weeks' gestation if recruitment occurred later, compared with placebo.

Overall, maternal vitamin D supplementation did not increase neonatal whole-body bone mineral content at birth, although it safely maintained maternal vitamin D repletion. In the cholecalciferol group, neonatal whole-body BMC was 61.6 g [95% CI 60.3-62.8] versus 60.5 g [59.3-61.7] with placebo (p=0.21), and neonatal BMD was identical at 0.203 g/cm2 in both groups (p=0.96). Birthweight also did not differ materially: 3481 g [3432-3530] versus 3518 g [3472-3564] with placebo (p=0.28). A prespecified seasonal analysis suggested a benefit among winter births, with a BMC mean difference of 5.5 g [95% CI 1.8-9.1] (p=0.004), but this finding needs replication.

The primary endpoint was null, and the apparent winter-birth benefit came from a subgroup analysis that requires replication. Outcome availability was incomplete, with usable neonatal DXA scans for only about 65% of participants and full protocol completion in 55%, which raises the possibility of attrition bias. Generalizability is limited by the UK setting and the specific baseline vitamin D eligibility range.