title: Effect of maternal multiple micronutrient supplementation on fetal loss and infant death in Indonesia: a double-blind cluster-randomised trial.
abstract: BACKGROUND
  Maternal nutrient supplementation in developing countries is generally restricted to provision of iron and folic acid (IFA). Change in practice toward supplementation with multiple micronutrients (MMN) has been hindered by little evidence of the effects of MMN on fetal loss and infant death. We assessed the effect of maternal supplementation with MMN, compared with IFA, on fetal loss and infant death in the setting of routine prenatal care services.
  
  
  METHODS
  In a double-blind cluster-randomised trial in Lombok, Indonesia, we randomly assigned 262 midwives to distribute IFA (n=15 ,86) or MMN (n=15,804) supplements to 31 290 pregnant women through government prenatal care services that were strengthened by training and community-based advocacy. Women obtained supplements, to be taken daily, every month from enrolment to 90 days post partum. The primary outcome was early infant mortality (deaths until 90 days post partum). Secondary outcomes were neonatal mortality, fetal loss (abortions and stillbirths), and low birthweight. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN34151616.
  
  
  RESULTS
  Infants of women consuming MMN supplements had an 18% reduction in early infant mortality compared with those of women given IFA (35.5 deaths per 1000 livebirths vs 43 per 1000; relative risk [RR] 0.82, 95% CI 0.70-0.95, p=0.010). Infants whose mothers were undernourished (mid upper arm circumference <23.5 cm) or anaemic (haemoglobin <110 g/L) at enrolment had a reduction in early infant mortality of 25% (RR 0.75, 0.62-0.90, p=0.0021) and 38% (RR 0.62, 0.49-0.78, p<0.0001), respectively. Combined fetal loss and neonatal deaths were reduced by 11% (RR 0.89, 0.81-1.00, p=0.045), with significant effects in undernourished (RR 0.85, 0.73-0.98, p=0.022) or anaemic (RR 0.71, 0.58-0.87, p=0.0010) women. A cohort of 11 101 infants weighed within 1 h of birth showed a 14% (RR 0.86, 0.73-1.01, p=0.060) decreased risk of low birthweight for those in the MMN group, with a 33% (RR 0.67, 0.51-0.89, p=0.0062) decrease for infants of women anaemic at enrolment.
  
  
  CONCLUSIONS
  Maternal MMN supplementation, as compared with IFA, can reduce early infant mortality, especially in undernourished and anaemic women. Maternal MMN supplementation might therefore be an important part of overall strengthening of prenatal-care programmes.
authors.affiliation: Helen Keller International, Jakarta, Indonesia; Johns Hopkins University, Baltimore, MD, USA.
authors.forename: A H
authors.initials: AH
authors.lastname: Shankar
authors.forename: A B
authors.initials: AB
authors.lastname: Jahari
authors.forename: S K
authors.initials: SK
authors.lastname: Sebayang
authors.lastname: Aditiawarman
authors.forename: M
authors.initials: M
authors.lastname: Apriatni
authors.forename: B
authors.initials: B
authors.lastname: Harefa
authors.forename: H
authors.initials: H
authors.lastname: Muadz
authors.forename: S D A
authors.initials: SD
authors.lastname: Soesbandoro
authors.forename: R
authors.initials: R
authors.lastname: Tjiong
authors.forename: A
authors.initials: A
authors.lastname: Fachry
authors.forename: A V
authors.initials: AV
authors.lastname: Shankar
authors.lastname: Atmarita
authors.forename: S
authors.initials: S
authors.lastname: Prihatini
authors.forename: G
authors.initials: G
authors.lastname: Sofia
mesh_terms: D000328:Adult; D001724:Birth Weight / Q000187:drug effects; D015331:Cohort Studies; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005313:Fetal Death / Q000517:prevention & control*; D005492:Folic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007214:Indonesia; D007226:Infant Mortality; D007231:Infant, Newborn; D007501:Iron / Q000008:administration & dosage / Q000627:therapeutic use*; D008428:Maternal Mortality; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods*; D012923:Social Class; D014131:Trace Elements / Q000008:administration & dosage / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D014131:Trace Elements; D014803:Vitamin B Complex; D005492:Folic Acid; D007501:Iron