Evidence for multiple micronutrient effects based on randomized controlled trials and meta-analyses in developing countries.

Providing multiple micronutrients via supplements, powders, or fortified ready-to-use foods is increasingly becoming a strategy for simultaneously addressing multiple nutrient deficiencies in developing countries. The pros and cons of the "gold standard" randomized controlled trial (RCT) design and meta-analyses of trials for establishing efficacy of nutritional interventions are discussed. Over the past decade, numerous RCT have been undertaken to test the efficacy of multiple micronutrient supplementation in both pregnant women and young children. Outcomes of interest have ranged from birth weight to child growth, and infant morbidity and mortality to nutrient status and cognitive function. These RCT have also been submitted to meta-analyses for estimating pooled effect sizes for various outcomes. Meta-analyses of antenatal multiple micronutrient supplementation reveal a modest but significant increase in birth weight of 22.4 g (95% CI: 8.3, 36.4 g) and an 11% (95% CI: 3, 19) reduction in low birth weight but no impact on preterm birth or perinatal mortality. In children, small effect sizes of 0.13 (95% CI: 0.06, 0.21) for length/height and 0.14 (95% CI: 0.03, 0.25) for weight have been shown with 3 or more micronutrients compared to fewer micronutrients, but there is limited evidence for an impact on outcomes such as morbidity and cognitive function. Gaps in research and future challenges for programmatic application of this strategy for both pregnant women and young children are discussed.