Vitamin D in Pregnancy: Winter Babies Benefit, High Doses Harm

SEATTLE — Early results from the Maternal Vitamin D Osteoporosis Study (MAVIDOS) in England suggest that taking vitamin D supplements during pregnancy may stop the decline in bone mass in women from December through February and may increase the bone mass of babies born then.

In contrast, a related study in Denmark found that taking vitamin D supplements did not improve bone health in pregnant women or their infants, and moreover, high-dose vitamin D supplements weakened the femoral bones in the mothers.

The findings from these two randomized controlled trials were presented at the recent American Society for Bone and Mineral Research (ASBMR) 2015 Annual Meeting.

Co–first author of the English study, Nicholas C Harvey, MB, PhD, from the University of Southampton, United Kingdom, toldMedscape Medical News that, in MAVIDOS, more than 1000 women were randomized at week 12 of pregnancy to receive placebo or 1000-IU (25-µg) cholecalciferol (vitamin D3) daily.

The findings "[support] policies in the UK and elsewhere for [prenatal vitamin D] supplementation," according to Dr Harvey.

During his presentation, he added that "the [seasonal] interaction…was significant." In infants born in seasons with more sunlight, there was no difference in whole-body bone-mineral content assessed by dual-energy X-ray absorptiometry (DEXA) within 2 weeks of birth.

In another oral session, Gitte Bloch Rasmussen, MD, PhD, from Aarhus University Hospital, Denmark, told the audience that in their trial, 193 women who had low levels of vitamin D and were planning to become pregnant were randomized to receive 70 µg (2800 IU) or 35 µg (1400 IU) cholecalciferol daily or placebo.

The women who received the high-dose supplements had decreased bone-mineral density at the femoral neck compared with women who received placebo. "Overall, our findings call for caution in recommending the use of high-dose vitamin D supplementation during pregnancy," Dr Rasmussen said.

Does Boosting Mom's Vitamin D Strengthen Progeny's Bones?

"Several, but not all, studies in this area have demonstrated positive associations between maternal [serum] 25-hydroxyvitamin D [25(OH)D] concentrations and pregnancy offspring bone development," Dr Harvey told Medscape Medical News.

MAVIDOS aimed to determine whether giving pregnant women vitamin D supplements would increase the bone mass in offspring relative to placebo. In a secondary prespecified analysis, they also looked at whether there was an interaction between vitamin D supplements and the season of birth of the offspring.

The trial recruited 1149 women in Southampton, Sheffield, and Oxford at the 12-week pregnancy checkup. Women with a 25 OH(D) concentration between 25 and 100 nmol/L were randomized to receive 1000-IU cholecalciferol or placebo daily.

At 34 weeks of pregnancy, 83% of women in the treatment group vs 37% of women in the placebo group had sufficient vitamin D levels (> 50 nmol/L; P = .004).

A total of 327 infants born to mothers in the placebo group and 328 infants born to mothers in the treatment group had whole-body DEXA scans. The bone-mineral content of the offspring was similar for infants born to mothers who received vitamin D supplements and mothers who received placebo (61.6 g vs 60.5 g, P = .21). Thus, the primary outcome was negative.

However, infants born in winter months to mothers who received cholecalciferol had a greater whole-body bone-mineral content than infants whose mothers received placebo (63.0 g vs 57.5 g; P = .004).

"These findings may have implications for public-health policy" for antenatal vitamin D supplementation, said Dr Harvey.

Should Pregnant Women Take High- or Low-Dose Vitamin D Pills?

In a prior Danish study, one-third of fertile and postpartum women had insufficient vitamin D levels (< 50 nmol/L), and up to 90% of childbearing women of certain ethnicities may be deficient in this vitamin, said Dr Rasmussen.

A Danish prospective study reported that pregnant women had bone loss in the lumbar spine, total hip, forearm, and whole body that was reversed about a year after breastfeeding had ceased, she added.

The current study aimed to see if bone loss during pregnancy could be mitigated.

They randomized 193 healthy women planning to become pregnant who had insufficient vitamin D (< 50 nmol/L) to receive high or low levels of vitamin D or a placebo.

A total of 90 women gave birth. At the time of delivery, the serum vitamin D levels were 118 nmol/L, 98 nmol/L, and 60 nmol/L in the women who had received high-dose, low-dose, and no vitamin D supplements, respectively.

At the femoral neck, the bone-mineral density decreased 4.8% more in women who received high-dose vitamin D supplements than in women who received placebo (P = .03). In contrast, at the mid-distal forearm, bone-mineral density increased 0.6% more in the group treated with high-dose vitamin D supplements than in women who received placebo (P = .03).

"We haven't [yet determined the reason] for these differences," Dr Rasmussen said.

There were no significant improvements in bone markers in infants born to mothers who had been taking vitamin D supplements.

In reply to a question, Dr Rasmussen agreed that they would expect to see increases in parathyroid hormone (PTH) in response to vitamin D supplements, but they did not see this.

The researchers plan to follow this cohort to see if there are any long-term effects on the development of chronic conditions, such as asthma or diabetes, in children whose mothers took vitamin D supplements during pregnancy.

American Society for Bone and Mineral Research 2015 Annual Meeting; Seattle, Washington. Abstract FR0052, presented October 9, 2015; Abstract 1089, presented October 10, 2015.