Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood: long‐term follow‐up of a randomized controlled trial

Background Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood. Methods In Guinea–Bissau, low‐birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG . A subgroup was also randomly assigned vitamin A supplementation or placebo in a two‐by‐two factorial design. Participants were followed up at age 3–9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy. Results Two hundred eighty‐one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups ( OR , 0.71; 95% CI , 0.34–1.47). Atopy was significantly reduced in children who had responded to BCG with a scar ( OR , 0.42; 0.19–0.94). Vitamin A supplementation was associated with increased atopy ( OR , 2.88; 1.26–6.58), especially in those who received simultaneous BCG (5.99; 1.99–18.1, P  =   0.09 for interaction between vitamin A supplementation and BCG ). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months ( OR , 2.45; 1.20–4.96). Conclusions There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy. Study Registration Clinicaltrials.gov NCT 01420705.