Effect of High-Dose vs Standard-Dose Vitamin D Supplementation in Pregnancy on Bone Mineralization in Offspring Until Age 6 Years

Abstract

IMPORTANCE Studies suggest an association between maternal vitamin D status during pregnancy and offspring anthropometry and bone mineralization, but investigations are few and with mixed results.OBJECTIVE To investigate the effect of a high dose vs standard dose of vitamin D supplementation in pregnancy on anthropometric and bone outcomes until age 6 years in the offspring. DESIGN, SETTING, AND PARTICIPANTSA prespecified analysis of a double-blinded, randomized clinical trial in the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort that included 623 pregnant mothers and their 584 children. Data were analyzed between January 2019 and September 2019.INTERVENTIONS Vitamin D supplementation of 2800 IU/d (high-dose) vs 400 IU/d (standard-dose) from pregnancy week 24 until 1 week after birth. MAIN OUTCOMES AND MEASURESLongitudinal anthropometry assessments including length/height, weight, and body mass index until age 6 years and bone mineral content (BMC) and bone mineral density (BMD) at age 3 years and 6 years from dual-energy radiography absorptiometry scans.RESULTS At age 6 years, 517 children (89%) completed the clinical follow-up. All participants were Danish and white; 261 were boys and 256 were girls. A mixed-effects model analysis of dual-energy radiography absorptiometry scan outcomes from ages 3 years and 6 years showed that children in the vitamin D vs placebo group had higher whole-body BMC: mean difference adjusted (aMD) for age, sex, height, and weight was 11.5 g (95% CI, 2.3-20.7; P = .01); higher whole-body-less-head BMC aMD was 7.5 g (95% CI, 1.5-13.5; P = .01); and higher head BMD aMD was 0.023 g/cm 2 (95% CI, 0.003-0.004; P = .03). The largest effect was in children from vitamin D-insufficient mothers (<30 ng/mL; to convert to nanomoles per liter, multiply by 2.496) and among winter births. In a post hoc analysis, we found borderline lower incidence of fractures in the vitamin D group (n = 23 vs n = 36; incidence rate ratio, 0.62 [95% CI, 0.37-1.05]; P = .08), but no differences in any anthropometric outcomes. Adjustment for a concomitant ω-3 polyunsaturated fatty acids intervention did not change the results.CONCLUSIONS AND RELEVANCE High-dose vitamin D supplementation in pregnancy improved offspring bone mineralization through age 6 years compared with the standard dose, suggesting an increased recommended gestational intake, which may influence peak bone mass, fracture risk, and risk of osteoporosis later in life. We found no supplementation effect on anthropometric outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00856947

Vitamin D Update

“…Together with calcium, vitamin D helps protect This article is part of the Topical Collection on Photodermatology older adults from osteoporosis. There is strong, consistent evidence supporting the role of vitamin D in childhood bone health, although most studies have been done in a limited range of skin types, as exemplified in a very recent report showing that high-dose vitamin D supplementation during pregnancy improved bone health in children [4]. In this case, all participants were white and Danish.…”

Effect of Vitamin D Supplementation in Early Life on Children’s Growth and Body Composition: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Twelve RCTs [3,26,27,[30][31][32][33][34][35][36][37][38][39][40] involving a total of 4583 participants were included in this systematic review. Nine trials conducted vitamin D supplementation during pregnancy [3,26,27,30,31,33,34,36,40], and three trials performed vitamin D supplementation during infancy [30,34,38]. One study involved a subgroup of vitamin D supplementation in lactation [37].…”

“…One study [32] followed up children at 1 (Hazell 2014) [33] and 3 (Hazell 2017) [34] years of age. Six studies [3,26,[36][37][38][39] were placebo-controlled; four [27,30,34,40] were comparisons between higher vs. lower doses of vitamin D, and the lowest-dose group (400 IU/day) (this low dose is part of the standard care) served as the control; and two [33,36] involved control groups without supplements. All intervention groups were supplemented with cholecalciferol, except two studies [31,39] that used ergocalciferol supplementation.…”

Variation in plasma 25-hydroxyvitamin D2 and D3 in normal pregnancy with gestational age, sampling season, and complications: A longitudinal cohort study

“…A review on the long-term effects of low maternal 25(OH)D levels on extra-skeletal health in offspring found some associations with disease, although evidence was conflicting and sparse [36]. However, a recent randomized trial showed effect of high dose vitamin D supplementation in the third trimester judged by improved bone mineralization in offspring up age six [37].…”