Randomized trial of three doses of vitamin D to reduce deficiency in pregnant Mongolian women

EBioMedicine. 2019 Jan:39:510-519. doi: 10.1016/j.ebiom.2018.11.060. Epub 2018 Dec 11.

Abstract

Background: In winter in Mongolia, 80% of adults have 25-hydroxyvitamin D (25(OH)D) concentrations <25 nmol/l (<10 ng/ml) and 99% have <50 nmol/l (<20 ng/ml). The vitamin D dose to avert deficiency during pregnancy in this population is unknown.

Methods: We conducted a randomized, controlled, double-blind trial of daily 600, 2000, or 4000 IU vitamin D3 for pregnant women in Mongolia (Clinicaltrials.gov #NCT02395081). We examined 25(OH)D concentrations at baseline (12-16 weeks' gestation), 36-40 weeks' gestation and in umbilical cord blood, using enzyme linked fluorescent assay. Sample size was determined to detect 0.4 standard deviation differences in 25(OH)D concentrations with 80% power.

Findings: 119 pregnant women were assigned 600 IU, 121 assigned 2000 IU and 120 assigned 4000 IU from February 2015 through December 2016. Eighty-eight percent of participants took ≥80% of assigned supplements. At baseline, 25(OH)D concentrations were similar across arms; overall mean ± standard deviation concentration was 19 ± 22 nmol/l; 91% were < 50 nmol/l. At 36-40 weeks, 25(OH)D concentrations increased to 46 ± 21, 70 ± 23, and 81 ± 29 nmol/l for women assigned 600, 2000, and 4000 IU, respectively (p < 0.0001 across arms; p = 0.002 for 2000 vs. 4000 IU). Mean umbilical cord 25(OH)D concentrations differed by study arm (p < 0.0001 across arms; p < 0.0001 for 2000 vs. 4000 IU) and were proportional to maternal concentrations. There were no adverse events, including hypercalcemia, attributable to vitamin D supplementation.

Interpretation: Daily supplementation of 4000 IU during pregnancy is safe and achieved higher maternal and neonatal 25(OH)D concentrations than 2000 IU. Daily 600 IU supplements are insufficient to prevent vitamin D deficiency in Mongolia. FUND: Anonymous foundation and Brigham and Women's Hospital.

Keywords: Dosing; Pregnancy; Trial; Vitamin D deficiency.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fetal Blood / chemistry*
  • Humans
  • Pregnancy
  • Pregnancy Trimester, First / blood
  • Pregnancy Trimester, Third / blood
  • Pregnancy Trimesters / blood*
  • Treatment Outcome
  • Vitamin D / administration & dosage
  • Vitamin D / analogs & derivatives*
  • Vitamin D / therapeutic use
  • Vitamin D Deficiency / drug therapy*
  • Young Adult

Substances

  • Vitamin D
  • 25-hydroxyvitamin D

Associated data

  • ClinicalTrials.gov/NCT02395081