Miriam E. Tucker
February 26, 2020
Maternal supplementation with high-dose vitamin D during pregnancy might improve bone health in offspring compared with the standard recommended dose, new research suggests. But some experts express caution about introducing such high doses.
The findings, from a prespecified secondary analysis of the double-blinded, randomized Copenhagen Prospective Studies on Asthma in Childhood, were published online February 24 in JAMA Pediatrics.
Compared to a standard dose of 400 IU/day, maternal supplementation with 2800 IU/day from week 24 of pregnancy through week 1 post partum resulted in overall improved bone mineralization in the offspring through age 6 years.
The strongest effect was seen among mothers who had baseline vitamin D insufficiency and among children born during the winter months, note Nicklas Brustad, MD, of the University of Copenhagen, Denmark, and colleagues.
«There is evidence to suggest the need for higher doses of vitamin D during pregnancy,» coauthor Hans Bisgaard, MD, also of the University of Copenhagen, told Medscape Medical News. «The studies show multiorgan effects, which substantiates that this is not a chance finding; [effects included] reduced risk of early asthmatic symptoms, enamel defects in the teeth reduced by half, and improved bone mineralization.»
In an accompanying editorial, Elisa Holmlund-Suila, MD, PhD, of Children’s Hospital, Pediatric Research Center, University of Helsinki, and colleagues write, «The study by Brustad et al adds to our knowledge on the effects of maternal vitamin D supplementation on bone parameters in children… Still, future studies are needed to define the optimal timing and duration of intervention.»
The editorialists urge caution regarding the safety of high doses. «[P]revious observations of potential disadvantageous effects of high maternal vitamin D on offspring health outcomes are concerning. Thus, before recommending 7-fold supplementation of vitamin D to pregnant women to improve offspring bone health, more research is required. Also, possible long-term adverse effects of high-dose vitamin D supplementation have to be investigated carefully.»
Asked to comment on that, Bisgaard said, «The precautionary principle is important and ‘further studies are needed’ appropriate. Still, waiting for decades for such studies is not without cost. Meanwhile, generations may [miss] the benefits. At some point, decision makers should count the evidence and make an informed choice.»
Upping the Dose Has Significant Impact
The current analysis was part of a larger prospective randomized trial to study the effect of high-dose vitamin D supplementation on persistent wheezing in offspring through the first 3 years of life. The study sample included 623 pregnant women and their 584 children. The mothers were randomly assigned to receive either 2800 IU or 400 IU daily from week 24 of pregnancy through week 1 after birth.
Longitudinal anthropometry assessments were conducted with dual-energy radiography absorptiometry scans at age 3 years and 6 years.
There were no significant differences between the two treatment groups in gestational age; size for gestational age; prevalence of being small for gestational age; birth weight; or birth length. By 6 years, there were no differences in body mass index, height, weight, head circumference, or thorax circumference.
At age 3 years, 244 of the children underwent technically approved DXA scanning. Those in the high-dose vitamin D group had significantly higher bone mineral content for total body, not including the head (mean, 293.8 g vs 288.8 g; P = .05) and total body bone mineral content (526.2 g vs 513.5 g; P = .04).
The greatest difference was among children born to mothers with insufficient (<30 ng/mL) vs sufficient (≥30 ng/mL) levels of 25(OH)D levels at baseline (537.5 g vs 513.6 g; P = .03).
At age 6 years, among the 383 children who had undergone DXA scanning, those in the high-dose vitamin D group had significantly higher total body (not including the head) bone mineral content (adjusted mean difference [aMD], 7.8 g; P = .03), head bone mineral density (aMD, 0.033 g/cm2; P = .01), head bone mineral content (aMD, 6.1 g; P = .03), total bone mineral density (aMD, 0.009 g/cm2; P = .04), and total bone mineral content (aMD, 13.9 g; P = .01).
Again, the effect was greatest among children born to mothers with insufficient baseline 25(OH)D levels (total bone mineral content, 834.0 g vs 817.3 g; P = .02) and total bone mineral density (aMD, 0.0125 g/cm2; P = .04).
Birth during winter (December–February) was associated with the greatest effect on head bone mineral content. When stratified by baseline 25(OH)D level, there was a significant effect of high-dose supplementation on head bone mineral content and total bone mineral content for birth during the period November 8 to May 7 but not during the period May 8 to November 7.
There were a total of 59 fractures among the 584 children, 23 born to mothers in the high-dose group and 36 born to mothers in the standard-dose group, which was not a statistically significant difference. Fracture rates did not differ by maternal baseline 25(OH)D levels.
Holmlund-Suila and colleagues note several caveats to the study, including low numbers of children for whom high-quality scans were avilable and lack of accounting for the children’s dietary vitamin D intake, especially after the study was unblinded at 3 years.
«Prenatal and early-life intervention is a tempting tool to examine programming and probable epigenetic effects,» they write. «Here, the intervention was timed from the late second trimester onwards. One could speculate that intervention at an earlier stage of fetal development could result in different outcomes. Thus, optimal timing for vitamin D intervention needs to be explored in future studies.»
Neither the study authors nor the editorial writers have disclosed any relevant financial relationships.