Effects of Maternal Vitamin D Supplementation During Pregnancy and Lactation on Infant Acute Respiratory Infections: Follow-up of a Randomized Trial in Bangladesh

Abstract

Background We examined the effect of maternal vitamin D supplementation during pregnancy and lactation on risk of acute respiratory infection (ARI) in infants up to 6 months of age in Bangladesh. Methods This study was nested in a randomized, double-blind, placebo-controlled, 5-arm dose-ranging trial of prenatal and postpartum vitamin D supplementation. One group of women received 0 IU vitamin D per week during pregnancy and for 26 weeks post delivery (“placebo” group), one group received high-dose prenatal vitamin D supplementation of 28 000 IU per week and 26 weeks post delivery, and there were 3 additional dose-ranging groups receiving vitamin D supplementation during pregnancy only (4200, 16 800, and 28 000 IU per week, respectively). Episodes of ARI were identified by active and passive surveillance. The primary outcome was microbiologically confirmed ARI, and the primary analysis compared the high-dose prenatal plus postpartum vitamin D vs placebo groups. Results In total, 1174 mother-infant pairs were included. Among infants born to mothers in the placebo group, 98% had a venous umbilical cord 25(OH)D level below 30 nmol/L compared with none in the high-dose prenatal plus postdelivery vitamin D group. Incidence of microbiologically confirmed ARI in the high-dose prenatal plus postpartum vitamin D (1.21 episodes per 6 person-months; N = 235) and placebo groups (1.07 episodes per 6 person-months; N = 234) was not significantly different (hazard ratio of 1.12 [95% confidence intervals: 0.90-1.40]). There were no differences in the incidence of microbiologically confirmed or clinical ARI, upper, lower, or hospitalized lower respiratory tract infection between high-dose prenatal plus postpartum vitamin D and placebo groups. Conclusions Despite a high prevalence of maternal baseline vitamin D deficiency and significant effects of maternal vitamin D supplementation on infant vitamin D status, the intervention did not reduce the risk of microbiologically confirmed ARI in infants up to 6 months of age.

Effect of maternal vitamin D supplementation on nasal pneumococcal acquisition, carriage dynamics and carriage density in infants in Dhaka, Bangladesh

“…Written informed consent was obtained from all women for participation in the MDIG and MDARI studies, including consent for storage and use of biological specimens. Detailed methods and primary results of the MDIG trial and MDARI study were previously described [ 33 , 35 , 36 ]. The MDARI study was approved by research ethics committees at the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) (ERC protocol PR-14079), and as a MDIG sub-study at the Hospital for Sick Children in Toronto (REB 100039072).…”

“…Infant ARI episodes were monitored by active and passive surveillance from birth to 6 months, as described previously [ 33 , 35 , 36 ]. Infants with signs of ARI or other illness detected during routine home visits were referred to study physicians for further assessment.…”

“…Sensitivity analyses tested the robustness of all primary analyses including variations of model fit and model variation including a sensitivity analysis where all infants were assumed carriage-negative at day 7 since infants were not considered at-risk of ARI during the first postnatal week in the MDARI study [ 33 ]. To test the robustness of the parametric interval-censored modelling, a Cox Proportional Hazard Model sensitivity test was completed.…”

“…Observational studies in children found VD insufficiency and deficiency associated with longer recovery times from pneumonia, increased pneumonia severity and increased risk of acute respiratory infections (ARI) [ 26 – 29 ]. Yet, results from randomized controlled trials of VD supplementation as a prevention or treatment method for ARI in children are mixed [ 30 – 33 ]. No studies directly addressed whether VD affects pneumococcal carriage in young children.…”

“…Bangladesh is a LMIC with a high burden of IPD [ 34 ] and a high prevalence of maternal and neonatal VD deficiency [ 35 ]. In this sub-study of a randomized controlled trial and nested cohort study in Bangladesh [ 33 , 35 ], we aimed to estimate the dose-dependent effect of maternal VD supplementation during pregnancy and lactation on the risk of nasal pneumococcal acquisition, carriage dynamics (cycling between negative and positive carriage) and nasal pneumococcal carriage density (copies/mL) in infants from birth to 6 months of age.…”