Effect of Multiple Micronutrient Supplementation on Pregnancy and Infant Outcomes: A Systematic Review

Authors

  • Usha Ramakrishnan,

    Corresponding author
    1. Hubert Department of Global Health, Rollins School of Public Health, Emory University
    2. Nutrition & Health Sciences Program, Graduate Division of Biological & Biomedical Sciences, Emory University, Atlanta, GA, USA
      Usha Ramakrishnan, Hubert Department of Global Health, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Room 7009, Atlanta, GA 30322, USA. Email: uramakr@sph.emory.edu
    Search for more papers by this author
  • Frederick Kobina Grant,

    1. Hubert Department of Global Health, Rollins School of Public Health, Emory University
    2. Nutrition & Health Sciences Program, Graduate Division of Biological & Biomedical Sciences, Emory University, Atlanta, GA, USA
    Search for more papers by this author
  • Tamar Goldenberg,

    1. Hubert Department of Global Health, Rollins School of Public Health, Emory University
    Search for more papers by this author
  • Vinh Bui,

    1. Nutrition & Health Sciences Program, Graduate Division of Biological & Biomedical Sciences, Emory University, Atlanta, GA, USA
    Search for more papers by this author
  • Aamer Imdad,

    1. Division of Women & Child Health, The Aga Khan University, Karachi, Pakistan
    Search for more papers by this author
  • Zulfiqar Ahmed Bhutta

    1. Division of Women & Child Health, The Aga Khan University, Karachi, Pakistan
    Search for more papers by this author

Usha Ramakrishnan, Hubert Department of Global Health, Rollins School of Public Health, Emory University, 1518 Clifton Road NE, Room 7009, Atlanta, GA 30322, USA. Email: uramakr@sph.emory.edu

Abstract

Supplementation with multiple micronutrients (MM) during pregnancy may result in improved pregnancy and infant outcomes. We conducted meta-analyses of randomised controlled trials that evaluated the effects of prenatal supplementation with MM (defined as containing at least five micronutrients and typically included iron or iron and folic acid). The outcomes of interest were low birthweight (<2500 g), birthweight, small-for-gestational age (SGA), gestational age, preterm birth (<37 weeks' gestation), stillbirth and neonatal death, maternal morbidity and mortality. We identified eligible studies through PubMed and EMBASE database searches. Meta-analyses were performed by pooling results for outcomes that were reported from more than one trial and sub-analyses were conducted to evaluate the effect of timing of intervention and amount of iron. We included published results from 16 trials in this review. Compared with control supplementation that was usually iron plus folic acid in most studies, MM supplementation resulted in a significant reduction in the incidence of low birthweight [pooled risk ratio (RR) 0.86; 95% confidence interval (CI) 0.81, 0.91] and SGA (pooled RR 0.83 [95% CI 0.73, 0.95]) and an increase in mean birthweight (weighted mean difference (WMD) 52.6 g [95% CI 43.2 g, 62.0 g]). There was no significant difference in the overall risk of preterm birth, stillbirth, and maternal or neonatal mortality, but we found an increased risk of neonatal death for the MM group compared with iron–folate in the subgroup of five trials that began the intervention after the first trimester (RR 1.38 [95% CI 1.05, 1.81]). None of the studies evaluated maternal morbidity. Compared with iron plus folic acid supplementation alone, prenatal maternal supplementation with MM resulted in a reduction in the incidence of low birthweight and SGA but increased risk of neonatal death in the subgroup of studies that began the intervention after the first trimester.

Ancillary