ABSTRACT
Neonatal rotavirus infections are predominantly asymptomatic. While an association with gastrointestinal symptoms has been described in some settings, factors influencing differences in clinical presentation are not well understood. Using multidisciplinary approaches, we show that a complex interplay between human milk oligosaccharides (HMOs), milk microbiome, and infant gut microbiome impacts neonatal rotavirus infections. Validating in vitro studies where HMOs are not decoy receptors for neonatal strain G10P[11], population studies show significantly higher levels of Lacto-N-tetraose (LNT), 2'-fucosyllactose (2'FL), and 6'-siallylactose (6'SL) in milk from mothers of rotavirus-positive neonates with gastrointestinal symptoms. Further, these HMOs correlate with abundance of Enterobacter/Klebsiella in maternal milk and infant stool. Specific HMOs also improve the infectivity of a neonatal strain-derived rotavirus vaccine. This study provides molecular and translational insight into host factors influencing neonatal rotavirus infections and identifies maternal components that could promote the performance of live, attenuated rotavirus vaccines.
Subject(s)
Gastrointestinal Microbiome , Milk, Human/chemistry , Milk, Human/microbiology , Oligosaccharides/metabolism , Rotavirus Infections/microbiology , Feces/microbiology , Humans , Infant, Newborn , Rotavirus/pathogenicity , Rotavirus Infections/immunology , Rotavirus Vaccines/immunologyABSTRACT
OBJECTIVE: The aim of this study was to assess vitamin D status of preterm babies at birth and adequacy of daily supplementation with vitamin D. METHODS: This prospective cohort study recruited 111 preterm babies, 25 to 32 weeks' gestation from a tertiary care perinatal center in south India. Cord blood was assayed for serum calcium, phosphate, alkaline phosphatase, and 25-hydroxyvitamin D (25(OH)D). All of the babies were fed unfortified breast-milk and supplemented daily with calcium, phosphate, and 400 IU of vitamin D. At 6 weeks serum calcium, phosphate, alkaline phosphatase, parathyroid hormone, and 25(OH)D levels were estimated. RESULTS: Of 111 preterm babies recruited, a total of 90 (81%) of the preterm babies were followed up until 6 weeks. The median (interquartile range) vitamin D level in the preterm group was 34.7 (25.6-50.1) and 19.3 (13.9-27.1) ng/mL at birth and 6 weeks, respectively. Using a cutoff value of <20 ng/mL to determine vitamin D insufficiency (VDI), it was observed that 12.6% of the babies were vitamin D insufficient at birth. This increased to 52.2% at 6 weeks despite the recommended supplementation with vitamin D (P < 0.001). CONCLUSIONS: The prevalence of VDI was not high at birth; however, a large proportion of preterm babies were vitamin D insufficient at 6 weeks despite being supplemented with vitamin D 400 IU/day. The recommended vitamin D supplementation of 400 IU appears to be inadequate to prevent VDI, and hence randomized controlled trials looking at higher doses of vitamin D supplementation are needed.