Vitamin D supplementation during pregnancy: Double‐blind, randomized clinical trial of safety and effectiveness
What this study found
Vitamin D3 supplementation was effective, and 4000 IU/day was the most effective dose for achieving maternal and neonatal vitamin D sufficiency without identified safety concerns. Mean circulating 25(OH)D was highest in the 4000 IU group at second trimester (98.6 nmol/L) and one month prior to delivery (114.2 nmol/L), both with p < 0.0001 versus lower-dose groups. Neonatal 25(OH)D also increased with dose: 45.5 nmol/L, 57.0 nmol/L, and 66.3 nmol/L, with sufficiency by IOM criteria in 39.7%, 58.2%, and 78.6% of infants for the 400 IU, 2000 IU, and 4000 IU groups, respectively (p < 0.0001). No…
- Study & population
- Double-blind randomized clinical trial in pregnant women with singleton pregnancies enrolled at the Medical University of South Carolina in Charleston, South Carolina, at 12 to 16 weeks' gestation.
- Intervention
- Pregnant participants received a daily prenatal multivitamin containing 400 IU vitamin D plus an additional vitamin D3 (cholecalciferol) supplement of 0 IU, 1600 IU, or 3600 IU, for total vitamin D intakes of 400 IU/day, 2000 IU/day, or 4000 IU/day.
- Key limitation
- The trial was conducted at a single center in Charleston, South Carolina, in women with singleton pregnancies, which limits generalizability.
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Open PDFOriginal abstract
The need, safety, and effectiveness of vitamin D supplementation during pregnancy remain controversial. In this randomized, controlled trial, women with a singleton pregnancy at 12 to 16 weeks' gestation received 400, 2000, or 4000 IU of vitamin D3 per day until delivery. The primary outcome was maternal/neonatal circulating 25‐hydroxyvitamin D [25(OH)D] concentration at delivery, with secondary outcomes of a 25(OH)D concentration of 80 nmol/L or greater achieved and the 25(OH)D concentration required to achieve maximal 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] production. Of the 494 women enrolled, 350 women continued until delivery: Mean 25(OH)D concentrations by group at delivery and 1 month before delivery were significantly different (p < 0.0001), and the percent who achieved sufficiency was significantly different by group, greatest in 4000‐IU group (p < 0.0001). The relative risk (RR) for achieving a concentration of 80 nmol/L or greater within 1 month of delivery was significantly different between the 2000‐ and the 400‐IU groups (RR = 1.52, 95% CI 1.24–1.86), the 4000‐ and the 400‐IU groups (RR = 1.60, 95% CI 1.32–1.95) but not between the 4000‐ and. 2000‐IU groups (RR = 1.06, 95% CI 0.93–1.19). Circulating 25(OH)D had a direct influence on circulating 1,25(OH)2D3 concentrations throughout pregnancy (p < 0.0001), with maximal production of 1,25(OH)2D3 in all strata in the 4000‐IU group. There were no differences between groups on any safety measure. Not a single adverse event was attributed to vitamin D supplementation or circulating 25(OH)D levels. It is concluded that vitamin D supplementation of 4000 IU/d for pregnant women is safe and most effective in achieving sufficiency in all women and their neonates regardless of race, whereas the current estimated average requirement is comparatively ineffective at achieving adequate circulating 25(OH)D concentrations, especially in African Americans. © 2011 American Society for Bone and Mineral Research