title: Effect of maternal multiple micronutrient vs iron-folic acid supplementation on infant mortality and adverse birth outcomes in rural Bangladesh: the JiVitA-3 randomized trial.
abstract: OBJECTIVE
  Maternal micronutrient deficiencies may adversely affect fetal and infant health, yet there is insufficient evidence of effects on these outcomes to guide antenatal micronutrient supplementation in South Asia.
  
  
  OBJECTIVE
  To assess effects of antenatal multiple micronutrient vs iron-folic acid supplementation on 6-month infant mortality and adverse birth outcomes.
  
  
  METHODS
  Cluster randomized, double-masked trial in Bangladesh, with pregnancy surveillance starting December 4, 2007, and recruitment on January 11, 2008. Six-month infant follow-up ended August 30, 2012. Surveillance included 127,282 women; 44,567 became pregnant and were included in the analysis and delivered 28,516 live-born infants. Median gestation at enrollment was 9 weeks (interquartile range, 7-12).
  
  
  METHODS
  Women were provided supplements containing 15 micronutrients or iron-folic acid alone, taken daily from early pregnancy to 12 weeks postpartum.
  
  
  METHODS
  The primary outcome was all-cause infant mortality through 6 months (180 days). Prespecified secondary outcomes in this analysis included stillbirth, preterm birth (<37 weeks), and low birth weight (<2500 g). To maintain overall significance of α = .05, a Bonferroni-corrected α = .01 was calculated to evaluate statistical significance of primary and 4 secondary risk outcomes (.05/5).
  
  
  RESULTS
  Among the 22,405 pregnancies in the multiple micronutrient group and the 22,162 pregnancies in the iron-folic acid group, there were 14,374 and 14,142 live-born infants, respectively, included in the analysis. At 6 months, multiple micronutrients did not significantly reduce infant mortality; there were 764 deaths (54.0 per 1000 live births) in the iron-folic acid group and 741 deaths (51.6 per 1000 live births) in the multiple micronutrient group (relative risk [RR], 0.95; 95% CI, 0.86-1.06). Multiple micronutrient supplementation resulted in a non-statistically significant reduction in stillbirths (43.1 vs 48.2 per 1000 births; RR, 0.89; 95% CI, 0.81-0.99; P = .02) and significant reductions in preterm births (18.6 vs 21.8 per 100 live births; RR, 0.85; 95% CI, 0.80-0.91; P < .001) and low birth weight (40.2 vs 45.7 per 100 live births; RR, 0.88; 95% CI, 0.85-0.91; P < .001).
  
  
  CONCLUSIONS
  In Bangladesh, antenatal multiple micronutrient compared with iron-folic acid supplementation did not reduce all-cause infant mortality to age 6 months but resulted in a non-statistically significant reduction in stillbirths and significant reductions in preterm births and low birth weight.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00860470.
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Keith P
authors.initials: KP
authors.lastname: West
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland2The JiVitA Project, Gaibandha, Bangladesh.
authors.forename: Abu Ahmed
authors.initials: AA
authors.lastname: Shamim
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Sucheta
authors.initials: S
authors.lastname: Mehra
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Alain B
authors.initials: AB
authors.lastname: Labrique
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland2The JiVitA Project, Gaibandha, Bangladesh.
authors.forename: Hasmot
authors.initials: H
authors.lastname: Ali
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland2The JiVitA Project, Gaibandha, Bangladesh.
authors.forename: Saijuddin
authors.initials: S
authors.lastname: Shaikh
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Rolf D W
authors.initials: RD
authors.lastname: Klemm
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Lee S-F
authors.initials: LS
authors.lastname: Wu
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Maithilee
authors.initials: M
authors.lastname: Mitra
authors.affiliation: The JiVitA Project, Gaibandha, Bangladesh.
authors.forename: Rezwanul
authors.initials: R
authors.lastname: Haque
authors.affiliation: The JiVitA Project, Gaibandha, Bangladesh.
authors.forename: Abu A M
authors.initials: AA
authors.lastname: Hanif
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland3Department of Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland.
authors.forename: Allan B
authors.initials: AB
authors.lastname: Massie
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Rebecca Day
authors.initials: RD
authors.lastname: Merrill
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Schulze
authors.affiliation: Center for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001459:Bangladesh; D003677:Deficiency Diseases / Q000150:complications / Q000188:drug therapy*; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007501:Iron; D018977:Micronutrients / Q000627:therapeutic use*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D047928:Premature Birth; D011295:Prenatal Care; D012424:Rural Population; D050497:Stillbirth; D055815:Young Adult
chemical_list: D018977:Micronutrients; D005492:Folic Acid; D007501:Iron