Pregnancy Vitamin D Supplementation and Childhood Bone Mass at Age 4 Years: Findings From the Maternal Vitamin D Osteoporosis Study (MAVIDOS) Randomized Controlled Trial

Abstract

In the Maternal Vitamin D Osteoporosis Study (MAVIDOS) randomized 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 among 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 mineralization in early childhood in a prespecified, single-center follow-up of a double-blinded, multicenter, randomized controlled clinical trial based in the UK (MAVIDOS). A total of 1123 women in early pregnancy with a baseline 25-hydroxyvitamin D level 25-100 nmol/L from three research centers (2008)(2009)(2010)(2011)(2012)(2013)(2014) were randomized to 1000 IU/d cholecalciferol or matched placebo from 14 weeks of gestation to delivery. Offspring born at the Southampton, UK research center were assessed at age 4 years (2013)(2014)(2015)(2016)(2017)(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). Of 723 children, 564 (78.0%) children attended the 4-year visit, 452 of whom had a useable DXA. Maternal vitamin D supplementation led to greater WBLH aBMD in the children compared with placebo (mean [95% confidence interval {CI}]: supplemented group: 0.477 (95% CI, 0.472-0.481) g/cm 2 ; placebo group: 0.470 (95% CI, 0.466-0.475) g/cm 2 , 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 among children with low milk intake and low levels of physical activity. Child weight, height, and body massThis is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Maternal B-vitamin and vitamin D status before, during, and after pregnancy and the influence of supplementation preconception and during pregnancy: Prespecified secondary analysis of the NiPPeR double-blind randomized controlled trial

“…The dose of vitamin D recommended for routine use in pregnancy varies internationally, with some advocating 100 μg daily or higher [ 50 ], while the World Health Organization/Food and Agriculture Organization of the United Nations recommends 5 μg daily [ 51 ]; in the UK, it is recommended that pregnant women should consider taking a supplement containing 10 μg between September and March [ 4 ]. In the MAVIDOS randomized trial supplementation, 25 μg of vitamin D daily from 14 weeks gestation until delivery lowered the incidence of infantile atopic eczema [ 5 ] and increased childhood areal bone mineral density in the offspring [ 6 ]. Vitamin D is stored in adipose tissue, and our trial suggests that low dose (10 μg) supplementation over a long period starting preconception can support improved gestational vitamin D status.…”

“…The principal exception relates to preconception and early pregnancy folic acid supplementation and fortification programs, underpinned by the landmark Medical Research Council trial [ 2 ]. Vitamin D supplementation is also generally recommended, in part based on the recent Maternal Vitamin D Osteoporosis Study (MAVIDOS) trial [ 3 ]; MAVIDOS used a higher dose of vitamin D than is recommended in many settings (25 μg of cholecalciferol daily from early pregnancy until delivery versus 10 μg daily recommended in countries such as the United Kingdom [ 4 ]), which reduced the incidence of infantile atopic eczema in the offspring [ 5 ] and improved measures of bone health in the children at age 4 years [ 6 ].…”

Does antenatal cholecalciferol supplementation affect the mode or timing of delivery? Post hoc analyses of the MAVIDOS randomized controlled trial

“…This, however, would be offset against the reduction in maternal and neonatal morbidity, and thus could be a relatively cheap intervention and warrants further investigation. If these findings and the other identified benefits of higher dose antenatal vitamin D supplementation such as increased offspring bone mass 66 are replicated in further high quality randomized controlled trials without increased risk of harm, consideration should be given to increasing the recommended pregnancy supplementation guidance to 1000 IU/day in the UK. In the interim, promotion of the current guidelines recommending 400 IU/day vitamin D in pregnancy is appropriate to increase the current low uptake of supplementation.…”

Early Life Programming of Skeletal Health

“…Our own metaanalysis of these studies suggested a small positive effect on birth weight and neonatal serum calcium. There are, however, fewer studies that have examined the effect of pregnancy vitamin D supplementation on offspring musculoskeletal parameters; to date, there are 2 published trials assessing neonatal BMD [91,92] and four trials with assessment of BMD in early childhood [93][94][95][96]. The largest published RCT is the MAVIDOS study, which was conducted in three centres in the UK and randomised women with a baseline 25(OH)D of 25-100 nmol/l to either 1000 IU/day cholecalciferol or placebo from 14 to 17 weeks' gestation until delivery [97].…”