Modifiers of the effect of maternal multiple micronutrient supplementation on stillbirth, birth outcomes, and infant mortality: a meta-analysis of individual patient data from 17 randomised trials in low-income and middle-income countries

Abstract

Abstract Objective To identify individual-level effect modifiers of the effect of multiple micronutrient supplementation (MMS) containing iron and folic acid (IFA) during pregnancy, compared to IFA alone, on the risk of stillbirth, infant mortality, and birth outcomes. Methods We performed an individual patient data meta-analysis. Study-specific estimates were generated, and we pooled subgroup estimates using fixed effects models. Findings We included 17 randomized controlled trials (including 112,953 pregnancies). MMS resulted in greater reductions in low birthweight (RR 0.81; 95% CI: 0.74–0.89), small-for-gestational age births (RR 0.91; 95% CI: 0.87–0.96), and six-month mortality (RR: 0.71; 95% CI: 0.60–0.86) among anemic (hemoglobin <110g/L) as compared with non-anemic pregnant women. MMS had a greater impact on preterm birth among underweight pregnant women (body mass index <18.5kg/m2) (RR: 0.84; 95% CI: 0.78–0.90) compared to those with BMI ≥18.5 (RR: 0.94; 95% CI 0.90–0.98) (p value heterogeneity 0.01). MMS provided significantly greater reductions in infant mortality for female (RR: 0.87; 95% CI: 0.77–0.99) as compared to male infants (RR: 1.05; 95% CI: 0.93–1.18) (p value heterogeneity 0.04). In general, the survival and birth outcome effects of MMS were greater with high adherence (≥95%) to supplementation. Conclusion MMS produced greater birth outcome benefits for pregnant women with indicators of nutritional deficiency and improved survival for female infants.