Periconceptional multiple-micronutrient supplementation and placental function in rural Gambian women: a double-blind, randomized, placebo-controlled trial

Double-blind, randomized, placebo-controlled trial in rural Gambian women of reproductive age who were menstruating and not pregnant at enrollment. The active UNIMMAP arm included 567 randomized participants from the Kiang West region, with follow-up through conception and delivery.

The active intervention was UNIMMAP, a coated multiple-micronutrient tablet containing 15 vitamins and trace elements. Women were instructed to take 1 tablet daily from preconception until their first antenatal checkup, or for up to 1 year if they did not conceive; when pregnancy was confirmed, the study supplement was stopped and replaced with antenatal iron and folic acid.

Periconceptional UNIMMAP produced a modest improvement in uterine-artery vascular indices, but most placental function measures and birth outcomes were unchanged, so the clinical importance remains uncertain. At 18-22 weeks, uterine artery PI was lower with UNIMMAP than placebo (1.12 vs 1.20; difference -0.08, 95% CI -0.16 to -0.01; P = 0.025) and uterine artery RI was also slightly lower (0.61 vs 0.63; P = 0.050). Longitudinally, UNIMMAP reduced UtARI by 0.02 units over 18-32 weeks (95% CI -0.03 to -0.00; P = 0.040), but there was no effect on PAI-1, PAI-2, PAI-1:PAI-2 ratio, hCG, hPL, or measles antibody transfer ratio at delivery. Preterm birth was lower in the UNIMMAP arm (10 of 177, 5.6%) than placebo (23 of 190, 12.1%; OR 0.43, 95% CI 0.20 to 0.94; P = 0.035), while birth weight, length, head circumference, and placental weight were not different.

The key biological effects were small, and several analyses used reduced sample sizes, which limits precision. Many outcomes were null despite the primary mechanistic hypothesis, and the clinical significance of the observed Doppler changes is unclear. Generalizability is limited to rural Gambian women in a setting of likely micronutrient inadequacy, and some outcomes were incompletely captured or not reported in detail.