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

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.

Fig. 1

‘From Healthy Mother, Healthy Baby’ Trial profile.

Fig. 2

Mean (standard error) 25(OH)D concentrations at baseline and end of follow-up by trial arm. The blue line at 50 nmol/l (20 ng/ml) indicates the threshold for Vitamin D deficiency [1]. Means are estimated using a Tobit model to account for left censoring of samples below the assay limit of detection (20 nmol/l). Sample sizes were 119, 121, and 120 at baseline, and 112, 116, and 116 at end of follow-up, respectively, for the 600 IU, 2000 IU and 4000 IU arms.

Fig. 3

Mean (standard error) 25(OH)D concentrations in umbilical cord blood at end of follow-up by trial arm. The blue line at 50 nmol/l (20 ng/ml) indicates the threshold for Vitamin D deficiency [1]. Sample sizes were 109, 111, and 113 at baseline, for the 600 IU, 2000 IU and 4000 IU arms. Means are estimated using a Tobit model to account for left censoring of samples below the assay limit of detection (20 nmol/l).