Pregnancy vitamin D supplementation and childhood bone mass at age 4 years: Findings from the MAVIDOS Randomised Controlled Trial

In the MAVIDOS randomised trial, vitamin D supplementation in pregnancy did not lead to greater neonatal bone mass across the trial as a whole, but, in a prespecified secondary analysis by season of birth, led to greater neonatal bone mass amongst winter-born babies. Demonstrating persistence of this effect into childhood would increase confidence in a long-term benefit of this intervention. We investigated whether antenatal vitamin D supplementation increases offspring bone mineralisation in early childhood in a prespecified, single-centre follow-up of a double-blinded, multicentre, randomised controlled clinical trial based in the UK (MAVIDOS).1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25-100 nmol/l from three research centres (2008-2014) were randomised to 1000 IU/day cholecalciferol or matched placebo from 14 weeks' gestation to delivery. Offspring born at the Southampton, UK research centre were assessed at age 4 years (2013-2018). Anthropometry and dual-energy x-ray absorptiometry (DXA) were performed [yielding whole body less head (WBLH) bone mineral content (BMC), areal bone mineral density (aBMD), bone area (BA) and body composition].564/723 (78.0%) children attended the 4-year visit, of whom 452 had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo [mean (95%CI): supplemented group: 0.477 (0.472, 0.481)g/cm2; placebo group: 0.470 (0.466, 0.475)g/cm2, p=0.048]. Associations were consistent for BMC and lean mass, and in age and sex adjusted models. Effects were observed across the whole cohort irrespective of season of birth. Maternal-child interactions were observed, with a greater effect size amongst children with low milk intake and low levels of physical activity. Child weight, height and BMI were similar by maternal randomisation group.These findings suggest a sustained beneficial effect of maternal vitamin D supplementation in pregnancy on offspring aBMD at age 4 years but will require replication in other trials