Statistical analyses
episodes/child/12, breast milk 25OHD, pneumonia, ARI, bronchiolitis
REGRESSION, PNEUMONIA, SENSITIVITY, BRONCHIOLITIS
The RCT is being conducted and reported according to CONSORT (Consolidated Standards of Reporting Trials) guidelines.The primary ‘intention-to-treat’ analysis will compare the incidence of infant ARI (episodes/child/12 months) between active and placebo groups using a negative binomial regression model and producing an estimate of the incidence rate ratio (IRR) with 95%CIs. The model will include terms to account for repeat mothers and twins. There will be no imputation for missing data. Supplementation efficacy will be defined as (1−IRR)×100.Secondary analyses (clinical) will include between group comparisons of (1) the proportion of children having any ARI episode <12 months (using a generalised linear model with effects presented as risk ratios), (2) time to first ARI presentation (using Cox regression with effects presented as HRs) and (3) the incidence of ARI subgroup outcomes (pneumonia, bronchiolitis and OM using negative binomial regression with effects presented as IRRs). Sensitivity analyses will include those (1) with hospitalised outcomes and (2) clinical outcomes requiring antibiotics. A per-protocol analysis (excluding those who missed >3 consecutive doses) will also be conducted for all clinical outcomes.Secondary analyses (biological) will compare between-group differences in (1) circulating vitamin D levels: mean plasma 25OHD at each visit and breast milk 25OHD at birth (Student’s t-test), (2) microbiological outcomes: proportions of nasal swabs positive for For all analyses, p values <0.05 will be considered statistically significant. No adjustments will be made for multiple comparisons.