ABSTRACT
Objectives: A previous follow-up study of a neonatal vitamin A supplementation (NVAS) trial in Guinea-Bissau indicated that NVAS primed for a beneficial response to subsequent VAS in girls. We aimed to test this hypothesis in another study population. Methods: In 2004-2007 we conducted a NVAS trial in Guinea-Bissau randomising newborns 2:1 to VAS (50,000 IU or 25,000 IU) or placebo. We followed the children to 24 months and registered reception of subsequent VAS provided in campaigns or by our assistants. Mortality according to NVAS and subsequent VAS between 6 months (the earliest age of subsequent VAS) and 24 months was compared in Cox proportional-hazards models. Results: Among 6048 children enrolled in the NVAS-trial, 5507 children (91%) remained in the study area after 6 months of age. Between 6 months and the first VAS opportunity, 33 non-accident deaths occurred (28 NVAS, 5 placebo). NVAS was associated with a mortality rate ratio (MRR) of 2.71 (1.04-7.04). After reception of VAS, 12 children died (7 NVAS, 5 placebo) and the MRR was 0.69 (0.22-2.18), p=0.07 for different effect of NVAS before and after subsequent VAS. The effect was similar in boys and girls. Conclusions: The effect of NVAS tended to differ by reception of a subsequent VAS, but we could not confirm that the effect differed for girls only. More studies are needed to identify in which situations VAS is beneficial and in which it is not, in order to define a vitamin A policy which optimises the impact on child survival.
ABSTRACT
Objectives: Though VAS at vaccination contacts has been recommended for many years, the policy has never been evaluated for its effect on overall mortality in randomised controlled trials. We evaluated the effect of the WHO recommendation of vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age. Methods: We conducted a randomised controlled trial of VAS. Children aged 6-23 months were randomised 1:1 to VAS (100,000 IU if aged 6-11 months, 200,000 IU if aged 12-23 months) or placebo at vaccination contacts in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards models overall, and by sex and vaccine. Results: Between August 2007 and November 2010, 7587 children were enrolled. Within 6 months of follow-up there were 81 non-accident deaths (VAS: 39; placebo: 42). The mortality rate ratio (MRR) comparing VAS versus placebo recipients was 0.93 (95% CI: 0.60-1.44) and differed significantly between boys (MRR=1.92 (0.98-3.75)) and girls (MRR=0.49 (0.26-0.92)) (p=0.004 for interaction between VAS and sex). At enrolment 42% (3161/7587) received live measles vaccine, 29% (2154/7587) received inactivated diphtheria-tetanus-pertussis-containing vaccines and 21% (1610/7587) received both live and inactivated vaccines. The effect of VAS did not differ by vaccine group. Conclusions: This is the first randomised trial of the effect of VAS at routine vaccination contacts on mortality. VAS had no overall effect, but the effect differed significantly by sex. More trials to ensure an optimal evidence-based vitamin A policy are warranted.
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.
ABSTRACT
A number of trials on maternal multi-micronutrient supplementation (MMS) have found a benefical effect on birth weight, but few have demonstrated a beneficial effect on infant survival. We examined the effect of two different preparations of antenatal MMS on fetal loss and under-2-years child mortality, as compared with iron-folic acid supplementation among 2,100 pregnant women in Guinea-Bissau. Women receiving a 1xRDA MMS preparation (consisting of 14 vitamins and minerals) had a marginally reduced risk of fetal loss (Relative risk (RR) 0.65, 95% CI 0.40; 1.05), and women receiving a 2xRDA MMS preparation had a similar effect (RR 0.67, 95% CI 0.42; 1.08), the pooled effect being 0.66 (95% CI 0.44; 0.99). None of the supplements reduced under-2-years mortality or the combination of fetal loss and under-2-years mortality. There was a marginally negative effect of both the 1xRDA (RR 2.10, 95% CI 0.99; 4.46) and the 2xRDA (RR 2.02, 95% CI 0.95; 4.32) MMS preparation on mortality specifically between 92365 days of age. (Afr. J. Reprod. Health 2010; 14[2]:17-26)