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

BackgroundEarly 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/DesignIn 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.DiscussionIf 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.

Genetic characterization of human metapneumovirus identified through community and facility‐based surveillance of infants in Dhaka, Bangladesh

“…hMPV samples were obtained from mid‐turbinate swabs collected from infants between 0 and 6 months of age in Dhaka, Bangladesh as part of the Maternal Vitamin D Supplementation During Pregnancy and Lactation to Prevent Acute Respiratory Infections in Infancy study (MDARI, Clinicaltrials.gov identifier NCT02388516) study . The MDARI study is a nested substudy within the Maternal Vitamin D Supplementation During Pregnancy and Lactation to Promote Infant Growth (MDIG, Clinicaltrials.gov identifier NCT01924013) trial .…”

“…Between December 2014 and August 2016, 3810 mid‐turbinate nasal swab specimens were collected from infants who met standardized clinical criteria for ARI. Full details regarding the study setting and population, surveillance systems, and clinical criteria for ARI have been published elsewhere …”

“…During Pregnancy and Lactation to Prevent Acute Respiratory Infections in Infancy study (MDARI, Clinicaltrials.gov identifier NCT02388516) study. 18 The MDARI study is a nested substudy within the Maternal Vitamin D Supplementation During Pregnancy and Lactation to Promote Infant Growth (MDIG, Clinicaltrials.gov identifier NCT01924013) trial. 19 Between December 2014 and August 2016, 3810 mid-turbinate nasal swab specimens were collected from infants who met standardized clinical criteria for ARI.…”

“…Full details regarding the study setting and population, surveillance systems, and clinical criteria for ARI have been published elsewhere. 18,19…”

Vitamin D in pediatric age: consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Federation of Pediatricians

“…Thus, the results of this study do not support the routine use of high-dose vitamin D supplementation in children for the prevention of viral upper respiratory tract infections [ 271 ]. Finally, limited data are available on vitamin D supplementation in pregnancy and the risk of respiratory infections in the offspring [ 272 , 273 ].…”