Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness

Authors

  • Bruce W Hollis,

    Corresponding author
    1. Division of Neonatology and Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA
    • Medical University of South Carolina, 173 Ashley Avenue, MSC 513, Charleston, SC 29425, USA.
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  • Donna Johnson,

    1. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA
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  • Thomas C Hulsey,

    1. Division of Epidemiology, Department of Pediatrics, and Medical University of South Carolina, Charleston, SC, USA
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  • Myla Ebeling,

    1. Division of Epidemiology, Department of Pediatrics, and Medical University of South Carolina, Charleston, SC, USA
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  • Carol L Wagner

    1. Division of Neonatology and Department of Obstetrics and Gynecology, Medical University of South Carolina, Charleston, SC, USA
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Errata

This article is corrected by:

  1. Errata: Erratum: Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness Volume 26, Issue 12, 3001, Article first published online: 21 November 2011

  • For a Commentary on this article, please see Abrams (J Bone Miner Res. 2011;26:2338-2340. DOI: 10.1002/jbmr.498).

  • Presented in part at the 14th Vitamin D Workshop, Brugge, Belgium, October 2009, and the Pediatric Academic Societies Meeting, Vancouver, British Columbia, Canada, May 2010.

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

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