title: Maternal multiple micronutrient supplementation and pregnancy outcomes in developing countries: meta-analysis and meta-regression.
abstract: 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.
  
  
  RESULTS
  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 (I(2) = 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).
  
  
  CONCLUSIONS
  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.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kawai
authors.forename: Donna
authors.initials: D
authors.lastname: Spiegelman
authors.forename: Anuraj H
authors.initials: AH
authors.lastname: Shankar
authors.forename: Wafaie W
authors.initials: WW
authors.lastname: Fawzi
mesh_terms: D016001:Confidence Intervals; D003906:Developing Countries; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D019266:Iron, Dietary / Q000627:therapeutic use; D018977:Micronutrients / Q000502:physiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D039401:Prenatal Nutritional Physiological Phenomena; D012044:Regression Analysis; D012306:Risk; D013223:Statistics as Topic; D014803:Vitamin B Complex / Q000627:therapeutic use
chemical_list: D019266:Iron, Dietary; D018977:Micronutrients; D014803:Vitamin B Complex; D005492:Folic Acid