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Background Invasive pneumococcal disease is a major cause of infant morbidity and death worldwide. Vitamin D promotes anti-pneumococcal immune responses in vitro, but whether improvements in infant vitamin D status modify risks of nasal pneumococcal acquisition in early life is not known. Methods This is a secondary analysis of data collected in a trial cohort in Dhaka, Bangladesh. Acute respiratory infection (ARI) surveillance was conducted from 0 to 6 months of age among 1060 infants of women randomized to one of four pre/post-partum vitamin D dose combinations or placebo. Nasal swab samples were collected based on standardized ARI criteria, and pneumococcal DNA quantified by qPCR. Hazards ratios of pneumococcal acquisition and carriage dynamics were estimated using interval-censored survival and multi-state modelling. Results Pneumococcal carriage was detected at least once in 90% of infants by 6 months of age; overall, 69% of swabs were positive (2616/3792). There were no differences between any vitamin D group and placebo in the hazards of pneumococcal acquisition, carriage dynamics, or carriage density (p > 0.05 for all comparisons). Conclusion Despite in vitro data suggesting that vitamin D promoted immune responses against pneumococcus, improvements in postnatal vitamin D status did not reduce the rate, alter age of onset, or change dynamics of nasal pneumococcal colonization in early infancy. Trial registration Registered in ClinicalTrials.gov with the registration number of NCT02388516 and first posted on March 17, 2015.

Additional file 5: Table S5. Effects of maternal vitamin D supplementation of varying doses on infant nasal pneumococcal carriage dynamics using a multi-state model with day 7 start.

Additional file 1: Table S1. MDARI definitions for acute respiratory infections.

Additional file 7: Figure S1. Probability of change to positive state from a negative state start aggregated across all treatment groups over trial period based on predicted multi-state model probabilities from day 0 to day 189 (N = 3792 swabs).

Additional file 6: Method S1. Determination of intervals used in interval-censored model.

Additional file 6: Method S1. Determination of intervals used in interval-censored model.

Additional file 7: Figure S1. Probability of change to positive state from a negative state start aggregated across all treatment groups over trial period based on predicted multi-state model probabilities from day 0 to day 189 (N = 3792 swabs).

Additional file 4: Table S4. Effects of maternal vitamin D supplementation of varying doses on the risk of pneumococcal acquisition using a Cox proportional hazard model with day 7 start.

Additional file 2: Table S2. Effect of maternal vitamin D supplementation on risk of pneumococcal acquisition in infants in Bangladesh using an interval-censored model with a day 7 start.

Additional file 3: Table S3. Effects of maternal vitamin D supplementation of varying doses on the risk of pneumococcal acquisition using a Cox proportional hazard model with day 0 start.

Additional file 1. HBB Prompt Phase 1a Focus Group Guide Plan and Standard Operating Procedures. Focus group guide with operational details, questions and prompts used to conduct focus group discussions during Phase 1a.

Additional file 2. HBB Prompt Phase 1b Focus Group Guide Plan and Standard Operating Procedures. Focus group guide with operational details, questions and prompts used to conduct focus group discussions during Phase 1b.

Additional file 1.

ObjectiveTo evaluate the cost-effectiveness of distribution of the integrated neonatal care kit (iNCK) by community health workers from the healthcare payer perspective in Rahimyar Khan, Pakistan.SettingRahimyar Khan, Pakistan.ParticipantsN/A.InterventionCost-utility analysis using a Markov model based on cluster randomised controlled trial (cRCT: NCT 02130856) data and a literature review. We compared distribution of the iNCK to pregnant mothers to local standard of care and followed infants over a lifetime horizon.Primary and secondary outcome measuresThe primary outcome was incremental net monetary benefit (INMB, at a cost-effectiveness threshold of US$15.50), discounted at 3%. Secondary outcomes were life years, disability-adjusted life years (DALYs) and costs.ResultsAt a cost-effectiveness threshold of US$15.50, distribution of the iNCK resulted in lower expected DALYs (28.7 vs 29.6 years) at lower expected cost (US$52.50 vs 55.20), translating to an INMB of US$10.22 per iNCK distributed. These results were sensitive to the baseline risk of infection, cost of the iNCK and the estimated effect of the iNCK on the relative risk of infection. At relative risks of infection below 0.79 and iNCK costs below US$25.90, the iNCK remained cost-effective compared with current local standard of care.ConclusionThe distribution of the iNCK dominated the current local standard of care (ie, the iNCK is less costly and more effective than current care standards). Most of the cost-effectiveness of the iNCK was attributable to a reduction in neonatal infection.