Vitamin A supplementation at birth might prime the response to subsequent vitamin A supplements in girls. Three year follow-up of a randomized trial

Abstract

Objectives: Within a randomised trial of neonatal vitamin A supplementation (VAS) in Guinea-Bissau, neonatal VAS did not affect overall infant mortality. We conducted a post-hoc analysis to test the hypothesis that neonatal VAS primes the response to subsequent vitamin A.

Methods: All trial children were offered VAS after follow-up ended at 1 year of age (FU-VAS). We compared mortality between 1 and 3 years of age according to initial randomization to neonatal VAS or placebo in Cox-regression models; we expected that children randomized to neonatal VAS compared with those randomized to placebo would have lower mortality after reception of FU-VAS.

Results: Of 4345 infants enrolled in the original trial, 3646 lived in the study area at 1 year of age and 2958 received FU-VAS. Between 1 and 3 years of age, 112 children died. After FU-VAS, neonatal VAS was associated with lower mortality than placebo: Mortality Rate Ratio (MRR) = 0.54 (95%CI: 0.31-0.94). The effect was more pronounced in girls (MRR = 0.37 (0.16-0.89)) than boys (MRR = 0.73 (0.35-1.51)). The beneficial effect of neonatal VAS may have been particularly strong for girls who received both VAS in a campaign and FU-VAS (MRR = 0.15 (0.03-0.67)). Among children who had not received FU-VAS, mortality in the second and third year of life did not differ according to reception of neonatal VAS or placebo. Hence, in the second and third year of life the effect of neonatal VAS versus placebo was different in girls who had or had not received FU-VAS (p for homogeneity = 0.01).

Conclusions: The present results suggest that neonatal VAS primes the response in girls such that they get a beneficial effect after a subsequent dose of VAS.

Trial registration: Clinicaltrials.gov NCT00168597.

Figure 1. Trial profile.

# Note: children in “A” contribute survival time in group C between age 12 months and date of reception of FU-VAS. ¤ Note: children in “B” contribute survival time in group D between age 12 months and date of reception of FU-VAS. * Among absent and travelling children 11 deaths occurred before 3 years of age (Vitamin A: 6; placebo: 5), bringing the total number of deaths up to 112.

Figure 2. Cumulative mortality in the second and third year of life.

Cumulative mortality depending on whether the children had received neonatal vitamin A (50,000 IU) or placebo and vitamin A (100,000 IU) at follow-up after 1 year of age (FU-VAS). Graphs by sex.