Vitamin D supplementation during pregnancy is associated with higher bone mineral content in the offspring, even up to 6 years after birth, research suggests.
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“The well-established tracking of bone mineralization from early life throughout childhood and early adulthood is a key factor for the final peak bone mass gained and the subsequent risk of fractures and osteoporosis later in life,” wrote Nicklas Brustad, MD, of the Herlev and Gentofte Hospital at the University of Copenhagen, and coauthors. Their report is in JAMA Pediatrics.This was a secondary analysis of a prospective, double-blind, randomized controlled trial of high versus standard dose vitamin D supplementation in 623 pregnant Danish women and the outcomes in their 584 children. The women were randomized either to a daily dose of 2,400 IU vitamin D3 (cholecalciferol) or matching placebo capsules from 24 weeks’ gestation until 1 week after birth. All women were advised to maintain a daily intake of 400 IU of vitamin D3.
The children underwent anthropometric growth assessments regularly up to age 6 years, and underwent whole-body dual-energy radiograph absorptiometry (DXA) scanning at 3 years and 6 years.
At 3 years, children of mothers who received the vitamin D supplements showed significantly higher mean total-body-less-head (TBLH) bone mineral content (BMC) compared with those who received placebo (294 g vs. 289 g) and total-body BMC (526 g vs. 514 g), respectively, after adjustment for age, sex, height, and weight.
The difference in total-body BMC was particularly evident in children of mothers who had insufficient vitamin D levels at baseline, compared with those with sufficient vitamin D levels (538 g vs. 514 g). The study also saw higher head bone mineral density (BMD) in children of mothers with insufficient vitamin D at baseline who received supplementation.
At 6 years, there still were significant differences in BMC between the supplementation and placebo groups. Children in the vitamin D group had an 8-g greater TBLH BMC compared with those in the placebo group, and a 14-g higher total BMC.
Among the children of mothers with insufficient preintervention vitamin D, there was an 18-g higher mean total BMC and 0.0125 g/cm2 greater total BMD, compared with those with sufficient vitamin D at baseline.
Overall, the children of mothers who received high-dose vitamin D supplementation had a mean 8-g higher TBLH BMC, a mean 0.023 g/cm2 higher head BMD, and a mean 12-g higher total BMC.
Dr. Brustad and associates noted that the head could represent the most sensitive compartment for intervention, because 80% of bone mineralization of the skull occurs by the age of 3 years.
The study also showed a seasonal effect, such that mothers who gave birth in winter showed the greatest effects of vitamin D supplementation on head BMC.
There was a nonsignificant trend toward a lower fracture rate among children in the supplementation group, compared with the placebo group.
“We speculate that these intervention effects could be of importance for bone health and osteoporosis risk in adult life, which is supported by our likely underpowered post hoc analysis on fracture risk, suggesting an almost 40% reduced incidence of fractures of the larger bones in the high-dose vitamin D group,” the authors wrote.
Vitamin D supplementation did not appear to affect the children’s growth. At 6 years, there were no significant differences between the two groups in body mass index, height, weight, or waist, head, and thorax circumference.
Neonatologist Carol Wagner, MD, said in an interview that the study provided an absolute reason for vitamin D supplementation during pregnancy.
“At the very least, a study like this argues for much more than is recommended by the European nutrition group or the U.S. group,” said Dr. Wagner, professor of pediatrics at the Medical University of South Carolina, Charleston. “Here you have a therapy that costs literally pennies a day, and no one should be deficient.”
She also pointed out that the study was able to show significant effects on BMC despite the fact that there would have been considerable variation in postnatal vitamin D intake from breast milk or formula.
Cristina Palacios, PhD, an associate professor in the department of dietetics and nutrition at Florida International University, Miami, said that vitamin D deficiency is increasingly prevalent worldwide, and is associated with a return of rickets – the skeletal disorder caused by vitamin D deficiency – in children.
“If women are deficient during pregnancy, providing vitamin D supplementation in pregnancy may promote bone health in their offspring,” Dr. Palacios said in an interview. “Because vitamin D is such an important component of bone metabolism, this could prevent future rickets in these children.”
Dr. Palacios coauthored a recent Cochrane review that examined the safety of high-dose vitamin D supplementation in pregnancy, and said the analysis found no evidence of safety concerns.
The study was supported by The Lundbeck Foundation, the Ministry of Health, Danish Council for Strategic Research, and the Capital Region Research Foundation. The authors declared no conflicts of interest.
SOURCE: Brustad N et al. JAMA Pediatrics 2020 Feb 24. doi: 10.1001/jamapediatrics.2019.6083.