Effects of Prenatal Multiple Micronutrient Supplementation on Miscarriage in Developing Countries: A Meta-analysis of Randomized Controlled Trials.

ABSTRACT

Objectives: The potential adverse impact of prenatal multiple micronutrient supplementation (MMN) versus iron-folic acid (IFA) on perinatal mortality is concerned. It has been speculated that MMN might survive frail fetuses to late pregnancy or early infancy, resulting in an increase in perinatal death. If the speculation holds true, MMN would prevent miscarriages. We aimed to assess the speculation. Methods: Pubmed, Embase, Web of Knowledge, and Cochrane Library were searched. Primary outcome was miscarriages. Secondary outcomes were stillbirths, perinatal deaths, and infant deaths; death events combined with miscarriages. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were estimated with fixed- or random-effect model, depending on heterogeneity tests. Pre-specified stratified and sensitivity analyses were planned to assess whether results varied by maternal baseline or trial characteristics. Results: In total, 15 trials were identified. MMN versus IFA significantly reduced miscarriage risk (RR 0.91, 95% CI 0.83-1.00). MMN significantly reduced infant death risk within 90 days (RR 0.86, 95% CI 0.78-0.95); this reduction remained when miscarriage and stillbirth were included (RR 0.88, 95% CI 0.82-0.94). MMN insignificantly increased perinatal death risk (RR 1.08, 95% CI 0.93-1.25), but the increased risk vanished when miscarriages were included (RR 0.99, 95% CI 0.89-1.10). No difference for other death events between groups was observed, irrespective of whether miscarriages were accounted for. Conclusions: MMN versus IFA supplementation prevented miscarriages and infant deaths within 90 days. The modestly increased perinatal mortality risk is a fallacy due to the survival bias resulting from protective effect on miscarriages.