Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries: meta-analysis and meta-regression

Objective To systematically review randomized controlled trials comparing the effect of supplementation with multiple micronutrients versus iron and folic acid on pregnancy outcomes in developing countries. Methods MEDLINE and EMBASE were searched. Outcomes of interest were birth weight, low birth weight, small size for gestational age, perinatal mortality and neonatal mortality. Pooled relative risks (RRs) were estimated by random effects models. Sources of heterogeneity were explored through subgroup meta-analyses and meta-regression. Findings Multiple micronutrient supplementation was more effective than iron and folic acid supplementation at reducing the risk of low birth weight (RR: 0.86, 95% confidence interval, CI: 0.79-0.93) and of small size for gestational age (RR: 0.85; 95% CI: 0.78 0.93). Micronutrient supplementation had no overall effect on perinatal mortality (RR: 1.05; 95% CI: 0.90-1.22), although substantial heterogeneity was evident (P = 58%; P for heterogeneity = 0.008). Subgroup and meta-regression analyses suggested that micronutrient supplementation was associated with a lower risk of perinatal mortality in trials in which >50% of mothers had formal education (RR:0.93; 95% CI: 0.82-1.06) or in which supplementation was initiated after a mean of 20 weeks of gestation (RR: 0.88; 95% CI: 0.80-0.97). Conclusion Maternal education or gestational age at initiation of supplementation may have contributed to the observed heterogeneous effects on perinatal mortality. The safety, efficacy and effective delivery of maternal micronutrient supplementation require further research.