High-Dose Monthly Maternal Cholecalciferol Supplementation during Breastfeeding Affects Maternal and Infant Vitamin D Status at 5 Months Postpartum: A Randomized Controlled Trial.

Randomized, double-blind, placebo-controlled trial in healthy women in New Zealand who planned to exclusively breastfeed, and their healthy exclusively breastfed infants. For the 50,000 IU/month group, 30 participants were randomized and 28 completed; for the 100,000 IU/month group, 30 were randomized and 30 completed.

Monthly oral cholecalciferol tablets were self-administered from 4 weeks postpartum to 16 weeks postpartum, with a last dose at 16 weeks. Active doses were 50,000 IU/month and 100,000 IU/month, compared with placebo.

Maternal vitamin D status improved with both cholecalciferol doses, and the 100,000 IU/month regimen also improved infant vitamin D status by 20 weeks postpartum. Maternal 25(OH)D increased from 4 weeks to 20 weeks postpartum by 10.8 nmol/L with 50,000 IU/month (P = 0.041, adjusted) and 20.7 nmol/L with 100,000 IU/month (P < 0.001, adjusted). In infants, the adjusted change in 25(OH)D from cord blood to 20 weeks was 5.0 nmol/L with 50,000 IU/month (P = 0.54) and 19.1 nmol/L with 100,000 IU/month (P = 0.025). At study end, infant 25(OH)D <50 nmol/L was 29% with 50,000 IU/month and 19% with 100,000 IU/month versus 27% with placebo, while no hypercalcemia or hypocalcemia occurred. The authors concluded that monthly maternal cholecalciferol, especially 100,000 IU/month, may help prevent infant vitamin D deficiency and appeared safe.

The active-arm sample sizes were small, and the trial was conducted in healthy, predominantly New Zealand European mothers in one New Zealand center, which limits generalizability. Follow-up was short and the lower dose did not show a clear infant benefit, so the optimal maternal dose and dosing schedule remain uncertain. Infant outcomes were modest and some analyses were not statistically significant, despite favorable trends at the higher dose.