RESUMO
BACKGROUND: In winter in Mongolia, 80% of adults have 25-hydroxyvitamin D (25(OH)D) concentrations <25â¯nmol/l (<10â¯ng/ml) and 99% have <50â¯nmol/l (<20â¯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 4000â¯IU vitamin D3 for pregnant women in Mongolia (Clinicaltrials.gov #NCT02395081). We examined 25(OH)D concentrations at baseline (12-16â¯weeks' gestation), 36-40â¯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 600â¯IU, 121 assigned 2000â¯IU and 120 assigned 4000â¯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⯱â¯standard deviation concentration was 19⯱â¯22â¯nmol/l; 91% wereâ¯<â¯50â¯nmol/l. At 36-40â¯weeks, 25(OH)D concentrations increased to 46⯱â¯21, 70⯱â¯23, and 81⯱â¯29â¯nmol/l for women assigned 600, 2000, and 4000â¯IU, respectively (pâ¯<â¯0.0001 across arms; pâ¯=â¯0.002 for 2000 vs. 4000â¯IU). Mean umbilical cord 25(OH)D concentrations differed by study arm (pâ¯<â¯0.0001 across arms; pâ¯<â¯0.0001 for 2000 vs. 4000â¯IU) and were proportional to maternal concentrations. There were no adverse events, including hypercalcemia, attributable to vitamin D supplementation. INTERPRETATION: Daily supplementation of 4000â¯IU during pregnancy is safe and achieved higher maternal and neonatal 25(OH)D concentrations than 2000â¯IU. Daily 600â¯IU supplements are insufficient to prevent vitamin D deficiency in Mongolia. FUND: Anonymous foundation and Brigham and Women's Hospital.