Vitamin D supplements taken during pregnancy do not improve bone mass in babies compared with placebo overall; however, those born in winter months did gain significant bone benefits from maternal vitamin D supplementation, show results of the Maternal Vitamin D Osteoporosis Study (MAVIDOS) study, published online March 1 in Lancet Diabetes and Endocrinology.
MAVIDOS is the first randomized controlled trial investigating the effects of pregnant women taking vitamin D on offspring bone mass, and initial results were reported at the American Society for Bone and Mineral Research meeting last October.
The data support the current recommendation in the United Kingdom, which is for pregnant women to take 400 IU vitamin D per day aimed at reducing the risk of infant rickets and neonatal hypocalcemia, second author Nicholas Harvey, MD, PhD, professor of rheumatology and clinical epidemiology at the MRC Lifecourse Epidemiology Unit, University of Southampton, United Kingdom, told Medscape Medical News.
However, he added, "The results also suggest that those women due to deliver in the winter months may consider taking a higher dose, at 1000 IU per day."
"MAVIDOS has given us the first evidence that supplementing mothers with vitamin D during pregnancy counteracts the seasonal drop in maternal vitamin D levels and may help to ensure good bone development in these winter births," he emphasized.
Vitamin D is considered important for regulating calcium levels, and maternal vitamin D deficiency has been associated with poor bone formation in the developing fetus and a risk of diseases such as rickets and osteoporosis in later life.
But previous observational studies have provided conflicting evidence regarding associations between a mother's vitamin D status and bone development in the uterus.
Experts now say that these new MAVIDOS findings likely indicate that targeted supplementation of vitamin D is needed, so that only women with very low levels should receive supplementation while the majority with normal levels will probably not require it.Testing the Hypothesis
The aim of MAVIDOS was to test the hypothesis that babies born to mothers who received vitamin D supplements during pregnancy would have greater whole-body bone mineral content (BMC) at birth than those of mothers who did not receive supplementation. The researchers further hypothesized that there would be an interaction between season of birth and treatment effect.
The multicenter, double-blind randomized controlled trial recruited over 1000 women with singleton pregnancies and a serum 25[OH]D concentration of 25 to 100 nmol/L at 10 to 17 weeks' gestation.
They were randomly assigned to either cholecalciferol (vitamin D3) 1000 IU/day — which is two and a half times the dose routinely recommended for pregnant women to take in the United Kingdom —or matched placebo, taken orally, most from 14 weeks' gestation until delivery.
The primary outcome was neonatal whole-body bone mineral content (BMC), assessed within 2 weeks of birth by dual-energy X-ray absorptiometry (DXA), alongside several other safety outcomes.Vitamin D in Late Pregnancy Important for Bone Strength
Around 65% of the babies in the study had a usable DXA scan, and overall, there was no significant difference between the BMC of those born to mothers who took vitamin D during pregnancy compared with those born to mothers who took placebo (61.6 g vs 60.5 g).
But among babies born in the winter, a prespecified secondary outcome, these figures were significantly different, 63.0 g vs 57.5 g, respectively (P = .004).
Dr Harvey explained the results show that supplementation with vitamin D3 1000 IU/day is highly effective at increasing vitamin D levels in pregnant mothers.
"More than 80% of women who had received the supplement had satisfactory levels of vitamin D when measured in late pregnancy, which is the point at which most calcium bone mineral is transferred from mother to baby to increase bone strength," he explained; this compared with around 35% of the placebo group who had satisfactory vitamin D levels at the same point in pregnancy.
And in mothers who gave birth in the winter, he continued, vitamin D concentrations fell from 14 to 34 weeks' gestation in the placebo group but rose in the treatment group.
"These findings suggest that vitamin D supplementation may counteract the drop in the body's normal levels of vitamin D caused by lack of sunlight when late pregnancy occurs in the winter months and therefore the tendency for these babies to have lower bone density than those born during the summer," he said.Toward Targeted Supplementation?
Commenting on the MAVIDOS findings, Daghni Rajasingam, MD, a spokesperson for the United Kingdom's Royal College of Obstetricians and Gynaecologists (RCOG), said that pregnant women in the United Kingdom are advised to take vitamin D supplements when pregnant and breastfeeding because "it can be difficult to get enough vitamin D from food alone and also because the amount of time you need in the sun to make enough vitamin D is different for every person."
Canada, like the United Kingdom, recommends supplementation for all pregnant women, but in the United States, the American College of Obstetrics and Gynecology (ACOG) has said vitamin D shouldn't be given routinely in pregnancy, other than in the form of a prenatal vitamin, until the results of ongoing randomized trials report. (ACOG has yet to issue any response to the newly published MAVIDOS findings.)
Dr Rajasingam highlighted that women at most risk of vitamin D deficiency include those of south Asian, black African, black Caribbean, or Middle Eastern origin, women who have limited exposure to sunlight, obese women, and those who eat a diet low in vitamin D. "It is particularly important these women get their required dose."
However, in light of these new study findings, he noted that "further research on the effectiveness of vitamin D supplementation on women at low risk of deficiency would be beneficial."
In a comment accompanying the MAVIDOS results, Prof Ian R Reid, of University of Auckland, New Zealand, agrees.
"To the purist, MAVIDOS shows no benefit from vitamin D supplementation in pregnancy. However, the subgroup analysis provides data that might help to address the vexed issue of what constitutes vitamin D deficiency. The findings suggest that when 25(OH)D concentration is lower than 30 nmol/L, neonatal fat and bone mass could be affected by maternal supplementation," says Dr Reid, adding, "For births occurring in winter, vitamin D supplementation increased neonatal BMC by almost 10%."
"In pregnancy and other contexts, we should be moving to targeted supplementation with vitamin D in individuals likely to have concentrations of lower than 25 to 30 nmol/L and away from mass medication, which is without proved benefit," he advises.Ongoing Study Will Try to Replicate Findings
Dr Harvey said an ongoing study in Southampton is attempting to replicate the seasonal findings of MAVIDOS and will provide further data on this issue.
"In addition, it will be really important to demonstrate whether the effects we observed at birth are sustained into late childhood. The follow-up of the MAVIDOS children over the next few years should provide invaluable information here."
Dr Harvey reports personal fees, consultancy, lecture fees, and honoraria from the Alliance for Better Bone Health, Amgen, MSD, Eli Lilly, Servier, Shire, Consilient Healthcare, and Internis Pharma, outside the submitted work. Disclosures for the coauthors are listed in the article.