title: Maternal vitamin D supplementation during pregnancy and lactation to prevent acute respiratory infections in infancy in Dhaka, Bangladesh (MDARI trial): protocol for a prospective cohort study nested within a randomized controlled trial.
abstract: Early infancy is a high-risk period for severe acute respiratory infection (ARI), particularly in low-income countries with resource-limited health systems. Lower respiratory tract infection (LRTI) is commonly preceded by upper respiratory infection (URTI), and often caused by respiratory syncytial virus (RSV), influenza and other common community-acquired viral pathogens. Vitamin D status is a candidate modifiable early-life determinant of the host antiviral immune response and thus may influence the risk of ARI-associated morbidity in high-risk populations.
  
  
  
  In the Maternal Vitamin D for Infant Growth (MDIG) study in Dhaka, Bangladesh (NCT01924013), 1300 pregnant women are randomized to one of five groups: placebo, 4200 IU/week, 16,800 IU/week, or 28,000 IU/week from 2ndtrimester to delivery plus placebo from 0-6 months postpartum; or, 28,000 IU/week prenatal and until 6-months postpartum. In the Maternal Vitamin D for ARI in Infancy (MDARI) sub-study nested within the MDIG trial, trained personnel conduct weekly postnatal home visits to inquire about ARI symptoms and conduct a standardized clinical assessment. Supplementary home visits between surveillance visits are conducted when caregivers make phone notifications of new infant symptoms. Mid-turbinate nasal swab samples are obtained from infants who meet standardized clinical ARI criteria. Specimens are tested by polymerase chain reaction (PCR) for 8 viruses (influenza A/B, parainfluenza 1/2/3, RSV, adenovirus, and human metapneumovirus), and nasal carriage density of Streptococcus pneumoniae. The primary outcome is the incidence rate of microbiologically-positive viral ARI, using incidence rate ratios to estimate between-group differences. We hypothesize that among infants 0-6 months of age, the incidence of microbiologically-confirmed viral ARI will be significantly lower in infants whose mothers received high-dose prenatal/postpartum vitamin D supplements versus placebo. Secondary outcomes include incidence of ARI associated with specific pathogens (influenza A or B, RSV), clinical ARI, and density of pneumococcal carriage.
  
  
  
  If shown to reduce the risk of viral ARI in infancy, integration of maternal prenatal/postpartum vitamin D supplementation into antenatal care programs in South Asia may be a feasible primary preventive strategy to reduce the burden of ARI-associated morbidity and mortality in young infants.
  
  
  
  NCT02388516 , registered March 9, 2015.
authors.affiliation: Department of Paediatrics, University of Toronto and the Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada. shaun.morris@sickkids.ca.|Centre for Global Child Health, SickKids Research Institute, 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.|Division of Infectious Diseases, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada. shaun.morris@sickkids.ca.
authors.forename: Shaun K
authors.initials: SK
authors.lastname: Morris
authors.affiliation: Centre for Global Child Health, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Pell
authors.affiliation: Zoonotic Diseases Research Group, Centre for Communicable Diseases, icddr,b, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Mohammed Ziaur
authors.initials: MZ
authors.lastname: Rahman
authors.affiliation: Centre for Global Child Health, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Dimitris
authors.affiliation: Centre for Child and Adolescent Health, icddr,b, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Mahmud
authors.affiliation: Centre for Nutrition and Food Security, icddr,b, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: M Munirul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Centre for Nutrition and Food Security, icddr,b, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Tahmeed
authors.initials: T
authors.lastname: Ahmed
authors.affiliation: Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Pullenayegum
authors.affiliation: Centre for Nutrition and Food Security, icddr,b, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Tahmid
authors.initials: T
authors.lastname: Kashem
authors.affiliation: Centre for Nutrition and Food Security, icddr,b, 68 Shaheed Tajuddin Ahmed Sarani, Mohakhali, Dhaka, 1212, Bangladesh.
authors.forename: Shaila S
authors.initials: SS
authors.lastname: Shanta
authors.affiliation: Department of Paediatrics, University of Toronto and the Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada.|Public Health Ontario, 661 University Ave., Toronto, ON, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Gubbay
authors.affiliation: Centre for Global Child Health, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.
authors.forename: Eszter
authors.initials: E
authors.lastname: Papp
authors.affiliation: Department of Paediatrics, University of Toronto and the Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada.|Division of Infectious Diseases, Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G1X8, Canada.
authors.forename: Michelle
authors.initials: M
authors.lastname: Science
authors.affiliation: Department of Paediatrics, University of Toronto and the Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada.|Centre for Global Child Health, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.|Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.
authors.forename: Stanley
authors.initials: S
authors.lastname: Zlotkin
authors.affiliation: Department of Paediatrics, University of Toronto and the Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada.|Centre for Global Child Health, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.|Child Health Evaluative Sciences, SickKids Research Institute, Hospital for Sick Children, 686 Bay Street, Toronto, ON, Canada.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Roth
mesh_terms: D000208:Acute Disease; D000328:Adult; D001459:Bangladesh; D001942:Breast Feeding; D002985:Clinical Protocols; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000517:prevention & control* / Q000821:virology; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods*; D011446:Prospective Studies; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control / Q000821:virology; D012141:Respiratory Tract Infections / Q000517:prevention & control* / Q000821:virology; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D014815:Vitamins; D014807:Vitamin D
keywords: Acute respiratory infection; Bangladesh; Infant; Influenza; Pneumonia; Pregnancy; Respiratory syncytial virus; Streptococcus pneumoniae; Vitamin D