title: Effect of multiple micronutrient supplementation during pregnancy on maternal and birth outcomes.
abstract: OBJECTIVE
  Given the widespread prevalence of micronutrient deficiencies in developing countries, supplementation with multiple micronutrients rather than iron-folate alone, could be of potential benefit to the mother and the fetus. These benefits could relate to prevention of maternal complications and reduction in other adverse pregnancy outcomes such as small-for-gestational age (SGA) births, low birth weight, stillbirths, perinatal and neonatal mortality. This review evaluates the evidence of the impact of multiple micronutrient supplements during pregnancy, in comparison with standard iron-folate supplements, on specific maternal and pregnancy outcomes of relevance to the Lives Saved Tool (LiST). DATA SOURCES/REVIEW METHODS: A systematic review of randomized controlled trials was conducted. Search engines used were PubMed, the Cochrane Library, the WHO regional databases and hand search of bibliographies. A standardized data abstraction and Child Health Epidemiology Reference (CHERG) adaptation of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) technique were used for data abstraction and overall quality of evidence. Meta-analyses were performed to calculate summary estimates of utility to the LiST model for the specified outcome of incidence of SGA births. We also evaluated the potential impact of multiple micronutrients on neonatal mortality according to the proportion of deliveries occurring in facilities (using a threshold of 60% to indicate functionality of health systems for skilled births).
  
  
  RESULTS
  We included 17 studies for detailed data abstraction. There was no significant benefit of multiple micronutrients as compared to iron folate on maternal anemia in third trimester [Relative risk (RR) = 1.03; 95% confidence interval (CI): 0.87 - 1.22 (random model)]. Our analysis, however, showed a significant reduction in SGA by 9% [RR = 0.91; 95% CI: 0.86 - 0.96 (fixed model)]. In the fixed model, the SGA outcome remained significant only in women with mean body mass index (BMI) ≥ 22 kg/m2. There was an increased risk of neonatal mortality in studies with majority of births at home [RR = 1.47, 95% CI: 1.13-1.92]; such an effect was not evident where ≥ 60% of births occurred in facility settings [RR = 0.94, 95% CI: 0.81-1.09]. Overall there was no increase in the risk of neonatal mortality [RR = 1.05, 95% CI: 0.92 - 1.19 (fixed model)].
  
  
  CONCLUSIONS
  This review provides evidence of a significant benefit of MMN supplementation during pregnancy on reducing SGA births as compared to iron-folate, with no significant increase in the risk of neonatal mortality in populations where skilled birth care is available and majority of births take place in facilities. Given comparability of impacts on maternal anemia, the decision to replace iron-folate with multiple micronutrients during pregnancy may be taken in the context of available services in health systems and birth outcomes monitored.
authors.affiliation: Division of Women & Child Health, The Aga Khan University, Karachi, Pakistan.
authors.forename: Batool Azra
authors.initials: BA
authors.lastname: Haider
authors.forename: Mohammad Yawar
authors.initials: MY
authors.lastname: Yakoob
authors.forename: Zulfiqar A
authors.initials: ZA
authors.lastname: Bhutta
mesh_terms: D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D058085:Iron Compounds / Q000008:administration & dosage; D019266:Iron, Dietary / Q000008:administration & dosage*; D018977:Micronutrients / Q000008:administration & dosage*; D011247:Pregnancy; D011256:Pregnancy Outcome; D039401:Prenatal Nutritional Physiological Phenomena; D016032:Randomized Controlled Trials as Topic; D014803:Vitamin B Complex / Q000008:administration & dosage*
chemical_list: D058085:Iron Compounds; D019266:Iron, Dietary; D018977:Micronutrients; D014803:Vitamin B Complex; D005492:Folic Acid