title: Maternal vitamin D supplementation during pregnancy and lactation to promote infant growth in Dhaka, Bangladesh (MDIG trial): study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Vitamin D regulates bone mineral metabolism and skeletal development. Some observational studies have suggested that prenatal vitamin D deficiency increases the risk of adverse pregnancy and/or birth outcomes; however, there is scant evidence from controlled trials, leading the World Health Organization to advise against routine vitamin D supplementation in pregnancy. Importantly, little is known about the effect of maternal vitamin D status on infant linear growth in communities in South Asia where stunting is highly prevalent and maternal-infant vitamin D status is commonly suboptimal.
  
  
  METHODS
  The Maternal Vitamin D for Infant Growth study is a randomized, placebo-controlled, dose-ranging trial of maternal vitamin D supplementation during pregnancy and lactation in Dhaka, Bangladesh. The primary aims are to estimate (1) the effect of maternal prenatal oral vitamin D3 supplementation (4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk, administered as weekly doses) versus placebo on infant length at 1 year of age and (2) the effect of maternal postpartum oral vitamin D3 supplementation (28,000 IU/wk) versus placebo on length at 1 year of age among infants born to women who received vitamin D 28,000 IU/wk during pregnancy. Generally healthy pregnant women (n = 1300) in the second trimester (17-24 weeks of gestation) are randomized to one of five parallel arms: placebo 4200 IU/wk, 16,800 IU/wk, or 28,000 IU/wk in the prenatal period and placebo in the postpartum period or 28,000 IU/wk in the prenatal period and 28,000 IU/wk in the postpartum period. Household- and clinic-based follow-up of mother-infant pairs is conducted weekly by trained personnel until 26 weeks postpartum and every 3 months thereafter. The primary trial outcome measure is length for age z-score at 1 year of age. Anthropometric measurements, clinical information, and biological specimens collected at scheduled intervals will enable the assessment of a range of maternal, perinatal, and infant outcomes.
  
  
  CONCLUSIONS
  The role of vitamin D in maternal and infant health remains unresolved. This trial is expected to contribute unique insights into the effects of improving maternal-infant vitamin D status in a low-income setting where stunting and adverse perinatal outcomes represent significant public health burdens.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier: NCT01924013. Registered on 13 August 2013.
authors.affiliation: Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. daniel.roth@sickkids.ca.|Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. daniel.roth@sickkids.ca.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Roth
authors.affiliation: Department of Nutritional Sciences, Penn State University, 110 Chandlee Laboratory, University Park, PA, USA. adg14@psu.edu.
authors.forename: Alison D
authors.initials: AD
authors.lastname: Gernand
authors.affiliation: Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. shaun.morris@sickkids.ca.|Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. shaun.morris@sickkids.ca.
authors.forename: Shaun K
authors.initials: SK
authors.lastname: Morris
authors.affiliation: Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. bpezzack@gmail.com.|Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. bpezzack@gmail.com.
authors.forename: Brendon
authors.initials: B
authors.lastname: Pezzack
authors.affiliation: Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. mislam@icddrb.org.
authors.forename: M Munirul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. michelle.dimitris@sickkids.ca.|Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. michelle.dimitris@sickkids.ca.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Dimitris
authors.affiliation: Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. shaila.sharmeen@icddrb.org.
authors.forename: Shaila S
authors.initials: SS
authors.lastname: Shanta
authors.affiliation: Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. stanley.zlotkin@sickkids.ca.|Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. stanley.zlotkin@sickkids.ca.
authors.forename: Stanley H
authors.initials: SH
authors.lastname: Zlotkin
authors.affiliation: Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. andy@andywillan.com.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Willan
authors.affiliation: Centre for Nutrition and Food Security, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. tahmeed@icddrb.org.
authors.forename: Tahmeed
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. pshah@mtsinai.on.ca.|Division of Neonatology, Mt. Sinai Hospital, 600 University Avenue, Toronto, ON, Canada. pshah@mtsinai.on.ca.
authors.forename: Prakesh S
authors.initials: PS
authors.lastname: Shah
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto and Mt. Sinai Hospital, 600 University Avenue, Toronto, ON, Canada. kmurphy@mtsinai.on.ca.
authors.forename: Kellie E
authors.initials: KE
authors.lastname: Murphy
authors.affiliation: Department of Paediatrics, University of Toronto and the Centre for Global Child Health, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. rweksb@sickkids.ca.|Genetics and Genome Biology, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. rweksb@sickkids.ca.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Weksberg
authors.affiliation: Genetics and Genome Biology, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada. sanaa.choufani@sickkids.ca.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Choufani
authors.affiliation: Department of Health and Nutrition, Save the Children USA, 2000 L Street NW, Suite 500, Washington, DC, USA. mshah@savechildren.org.
authors.forename: Rashed
authors.initials: R
authors.lastname: Shah
authors.affiliation: Centre for Child and Adolescent Health, International Centre for Diarrhoeal Disease Research (ICDDR,B), 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh. mahmud@icddrb.org.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Al Mahmud
mesh_terms: D000284:Administration, Oral; D000367:Age Factors; D001459:Bangladesh / Q000453:epidemiology; D001827:Body Height; D002657:Child Development; D002675:Child, Preschool; D002762:Cholecalciferol / Q000008:administration & dosage*; D002985:Clinical Protocols; D003906:Developing Countries; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006130:Growth Disorders / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009752:Nutritional Status; D011247:Pregnancy; D015995:Prevalence; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002762:Cholecalciferol