title: A cluster-randomized, placebo-controlled, maternal vitamin A or beta-carotene supplementation trial in Bangladesh: design and methods.
abstract: BACKGROUND
  We present the design, methods and population characteristics of a large community trial that assessed the efficacy of a weekly supplement containing vitamin A or beta-carotene, at recommended dietary levels, in reducing maternal mortality from early gestation through 12 weeks postpartum. We identify challenges faced and report solutions in implementing an intervention trial under low-resource, rural conditions, including the importance of population choice in promoting generalizability, maintaining rigorous data quality control to reduce inter- and intra- worker variation, and optimizing efficiencies in information and resources flow from and to the field.
  
  
  METHODS
  This trial was a double-masked, cluster-randomized, dual intervention, placebo-controlled trial in a contiguous rural area of ~435 sq km with a population of ~650,000 in Gaibandha and Rangpur Districts of Northwestern Bangladesh. Approximately 120,000 married women of reproductive age underwent 5-weekly home surveillance, of whom ~60,000 were detected as pregnant, enrolled into the trial and gave birth to ~44,000 live-born infants. Upon enrollment, at ~ 9 weeks' gestation, pregnant women received a weekly oral supplement containing vitamin A (7000 ug retinol equivalents (RE)), beta-carotene (42 mg, or ~7000 ug RE) or a placebo through 12 weeks postpartum, according to prior randomized allocation of their cluster of residence. Systems described include enlistment and 5-weekly home surveillance for pregnancy based on menstrual history and urine testing, weekly supervised supplementation, periodic risk factor interviews, maternal and infant vital outcome monitoring, birth defect surveillance and clinical/biochemical substudies.
  
  
  RESULTS
  The primary outcome was pregnancy-related mortality assessed for 3 months following parturition. Secondary outcomes included fetal loss due to miscarriage or stillbirth, infant mortality under three months of age, maternal obstetric and infectious morbidity, infant infectious morbidity, maternal and infant micronutrient status, fetal and infant growth and prematurity, external birth defects and postnatal infant growth to 3 months of age.
  
  
  CONCLUSIONS
  Aspects of study site selection and its "resonance" with national and rural qualities of Bangladesh, the trial's design, methods and allocation group comparability achieved by randomization, field procedures and innovative approaches to solving challenges in trial conduct are described and discussed. This trial is registered with http://Clinicaltrials.gov as protocol NCT00198822.
authors.affiliation: Center for Human Nutrition, Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA. alabriqu@jhsph.edu
authors.forename: Alain B
authors.initials: AB
authors.lastname: Labrique
authors.forename: Parul
authors.initials: P
authors.lastname: Christian
authors.forename: Rolf D W
authors.initials: RD
authors.lastname: Klemm
authors.forename: Mahbubur
authors.initials: M
authors.lastname: Rashid
authors.forename: Abu Ahmed
authors.initials: AA
authors.lastname: Shamim
authors.forename: Allan
authors.initials: A
authors.lastname: Massie
authors.forename: Kerry
authors.initials: K
authors.lastname: Schulze
authors.forename: Andre
authors.initials: A
authors.lastname: Hackman
authors.forename: Keith P
authors.initials: KP
authors.lastname: West
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001459:Bangladesh / Q000453:epidemiology; D016000:Cluster Analysis; D003906:Developing Countries; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005865:Gestational Age; D006801:Humans; D008428:Maternal Mortality; D008875:Middle Aged; D015990:Placebo Effect; D049590:Postpartum Period; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D011295:Prenatal Care; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014801:Vitamin A / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage*; D055815:Young Adult; D019207:beta Carotene / Q000008:administration & dosage*
chemical_list: D014815:Vitamins; D019207:beta Carotene; D014801:Vitamin A