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

BMC Pregnancy Childbirth. 2016 Oct 13;16(1):309. doi: 10.1186/s12884-016-1103-9.


Background: 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.

Methods/design: 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 2nd trimester 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.

Discussion: 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.

Trial registration: NCT02388516 , registered March 9, 2015.

Keywords: Acute respiratory infection; Bangladesh; Infant; Influenza; Pneumonia; Pregnancy; Respiratory syncytial virus; Streptococcus pneumoniae; Vitamin D.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Bangladesh
  • Breast Feeding
  • Clinical Protocols
  • Dietary Supplements*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Newborn, Diseases / prevention & control*
  • Infant, Newborn, Diseases / virology
  • Lactation*
  • Male
  • Maternal Nutritional Physiological Phenomena
  • Pregnancy
  • Prenatal Care / methods*
  • Prospective Studies
  • Respiratory Syncytial Virus Infections / prevention & control
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Tract Infections / prevention & control*
  • Respiratory Tract Infections / virology
  • Treatment Outcome
  • Vitamin D / administration & dosage*
  • Vitamins / administration & dosage*


  • Vitamins
  • Vitamin D

Associated data