Prenatal high-dose vitamin D supplementation and offspring bone mineral content and density at age 13 years: a secondary analysis of a randomised clinical trial.

Background: We previously demonstrated effect of maternal high-dose vitamin D supplementation on offspring bone health in preschool-age children. However, it is unknown whether this effect is long-lasting. Methods: We investigated the effect of 2800 (high-dose) vs. 400 (placebo + standard-dose) IU/day of gestational vitamin D supplementation on the prespecified secondary outcomes (bone mineral content and density (BMC and BMD)) at age 13 years and longitudinally (age 3, 6 and 13 years) in a double-blinded, randomized clinical trial (RCT) (NCT00856947) of 584 children in COPSAC Findings: In 416 children (71%) with a DXA scan at age 13 years, there were no differences in a linear regression model in total body BMC (6.7 (-28.3:41.6), p = 0.71) or total body BMD (-0.003 (-0.017:0.011), p = 0.68) among children in the high-dose (n = 212) vs. standard-dose vitamin D group (n = 204). In sensitivity analyses stratified by sex, birth season or maternal pre-interventional vitamin D levels there were no differences between the intervention groups. A mixed effects model of DXA scans from age 3, 6 and 13 years combined also showed no effects and there was no effect on fracture risk until age 13 years in a Cox (time to first) or Quasi-Poisson (incidence) regression model. Interpretation: This 13-year follow-up of a prespecified secondary outcome of the COPSAC Funding: The study received funding from the Thrasher Research Fund Award and Kong Christian IX and Dronning Louises Jubilæumslegat.