The Effect of Neonatal Vitamin A Supplementation on the Risk of Atopy; Long-term Follow-up on a Randomized Controlled Trial in Guinea-Bissau
Sofie Aage *
Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau and Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institute, Copenhagen, Denmark.
Nick Kiraly
Murdoch Childrens Research Institute, Parkville, Australia.
Kassarai Da Costa
Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau.
Stine Byberg
Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau and Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institute, Copenhagen, Denmark.
Morten Bjerregaard-Andersen
Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau and Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institute, Copenhagen, Denmark.
Ane Bærent Fisker
Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau and Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institute, Copenhagen, Denmark.
Peter Aaby
Bandim Health Project, Indepth Network, Bissau, Guinea-Bissau and Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institute, Copenhagen, Denmark.
Christine Stabell Benn
Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Institute, Copenhagen, Denmark and OPEN University, Clinical Institute, University of Southern Denmark/Odense University Hospital, Odense, Denmark.
*Author to whom correspondence should be addressed.
Abstract
Objectives: Neonatal vitamin A (NVAS) is currently being considered as policy in low income countries at risk of deficiency. We conducted NVAS trials in Guinea-Bissau and found sex-differential effects of NVAS on mortality, the effect being negative for females. We examined the effect of NVAS on atopy in long term follow-up of trial participants.
Methods: In 2002-2004 we randomised 4345 normal birth weight neonates to NVAS (50,000 IU) or placebo together with their Bacille Calmette Guérin-vaccination. In 2013, we visited the 1692 (39%) children who were still living in the study area, and 1478 (87%) were found at home. Provided consent, a skin prick test was performed, and history of allergic symptoms was recorded. Associations of NVAS and atopy (defined as a skin prick test reaction of >3 mm) were analysed using binomial regression, overall and stratified by sex.
Results: Of the 1430 children with a valid skin prick test, 228 were positive (16%; boys 20%, girls 12%). NVAS did not increase the overall risk of atopy (RR 1.10; 95% CI=0.87-1.40). However, NVAS was associated with significantly increased risk for females (1.78; 1.17-2.72) but not for males (0.86; 0.64-1.15), resulting in a significant interaction between NVAS and sex (p=0.01). Furthermore NVAS tended to increase the risk of wheezing for girls (RR 1.73; 0.99-3.03).
Conclusions: NVAS increased the risk of atopy and tended to increase the risk of wheezing among females. Further studies on NVAS and atopy are warranted. These findings might have implications for future policy decisions.