Maternal high-dose vitamin D supplementation tied to better bone health in offspring

High-dose vitamin D supplementation (2,800 IU/day) during pregnancy may improve bone mineralization, specifically bone mineral content (BMC) and bone mineral density (BMD), in offspring during the first 6 years of life, according to a prespecified secondary analysis of a study from Denmark.

“This trial suggests that an increased vitamin D intake [of 2,800 IU/day] during pregnancy has the potential to promote greater bone health in the offspring, which could have a protective effect on risk of fractures,” said the researchers.

Participants were 623 pregnant women and their 584 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. The women were randomized to receive either vitamin D₃ at 2,400 IU/day or placebo* from 24 weeks of gestation to 1 week after birth, in addition to the recommended intake of 400 IU/day. DXA** scans were used to assess bone mineralization in offspring until 6 years of age. [JAMA Pediatr 2020;doi:10.1001/jamapediatrics.2019.6083]

After adjusting for age, sex, height, and weight, children born to mothers who received high-dose vitamin D had a significantly higher total BMC compared with those whose mothers received placebo (adjusted estimate, 11.5 g; p=0.01). They also had greater total-body-less-head BMC (adjusted estimate, 7.5 g; p=0.01) and head BMD (adjusted estimate, 0.023 g/cm²; p=0.03) for combined results of ages 3 and 6 years.

Among mothers with insufficient 25(OH)D levels (<75 nmol/L) pre-intervention, children born to mothers in the high-dose vitamin D group had significantly higher total BMD (0.72 vs 0.71 g/cm²; p=0.04), total BMC (834.0 vs 817.3 g; p=0.02), and head BMD (1.43 vs 1.40 g/cm²; p=0.01) vs those whose mothers received placebo.

A lower incidence of fracture was observed among children of mothers on high-dose vitamin D than those on placebo, though this was not significant (7 percent vs 11 percent; incidence rate ratio, 0.62; p=0.08). There was also no significant difference in anthropometric outcomes at 6 years between the high-dose vitamin D and placebo groups.

“[Previous studies have shown that] vitamin D is an essential hormone for bone mineralization that begins in utero and continues throughout childhood until early adulthood,” said the researchers.

“[S]upplementation of 2,800 IU/day of vitamin D from gestational week 24 resulted in an overall higher mineralization status in the offspring compared with standard dose, with the most pronounced effects among children born to mothers with insufficient [pre-intervention] 25(OH)D levels,” they said.

However, previous research has pointed to negative effects of high maternal vitamin D supplementation in offspring. [J Bone Miner Res 2014;5:1088-1095] “[B]efore recommending sevenfold supplementation of vitamin D to pregnant women to improve offspring bone health, more research is required … [and the] possible long-term adverse effects of high-dose vitamin D supplementation have to be investigated carefully,” wrote Dr Sture Andersson and colleagues from Children’s Hospital, Pediatric Research Center at University of Helsinki and Helsinki University Hospital, Helsinki, Finland, in an editorial. [JAMA Pediatr 2020;doi:10.1001/jamapediatrics.2019.6102]

*As advised by the Danish Health Authority, women were recommended to continue taking vitamin D at a dose of 400 IU/day. As such, the study compares a high dose (2,800 IU/day) vs a standard dose (400 IU/day) of vitamin D intake