Effect of Maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: The JiVitA-3 randomized trial

IMPORTANCE: Maternal micronutrient deficienciesmay adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia.

OBJECTIVE: To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes.

DESIGN, SETTING, AND PARTICIPANTS: Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11,2008.Six-month infant follow-up ended August 30, 2012. Surveillance included 127 282 women; 44 567 became pregnant and were included in the analysis and delivered 28 516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12).

INTERVENTIONS: Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum.

TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00860470.

MAIN OUTCOMES AND MEASURES: The primary outcomewas all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α =.05, a Bonferroni-corrected α =.01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5).

RESULTS: Among the 22 405 pregnancies in the multiple micronutrient group and the 22 162 pregnancies in the iron-folic acid group, there were 14 374 and 14 142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95%CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95%CI, 0.81-0.99; P =.02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95%CI, 0.80-0.91; P <.001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95%CI, 0.85-0.91; P <.001).

CONCLUSIONS AND RELEVANCE: In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight.