To assess the effect of vitamin A supplementation in women of reproductive age in Ghana on cause- and age-specific infant mortality. In addition, because of recently published studies from Guinea Bissau, effects on infant mortality by sex and season were assessed.
Double-blind, cluster-randomised, placebo-controlled trial.
7 contiguous districts in the Brong Ahafo region of Ghana.
All women of reproductive age (15–45 years) resident in the study area randomised by cluster of residence. All live born infants from 1 June 2003 to 30 September 2008 followed up through 4-weekly home visits.
Weekly low-dose (25 000 IU) vitamin A.
Main outcome measures
Early infant mortality (1–5 months); late infant mortality (6–11 months); infection-specific infant mortality (0–11 months).
1086 clusters, 62 662 live births, 52 574 infant-years and 3268 deaths yielded HRs (95% CIs) comparing weekly vitamin A with placebo: 1.04 (0.88 to 1.05) early infant mortality; 0.99 (0.84 to 1.18) late infant mortality; 1.03 (0.92 to 1.16) infection-specific infant mortality. There was no evidence of modification of the effect of vitamin A supplementation on infant mortality by sex (Wald statistic =0.07, p=0.80) or season (Wald statistic =0.03, p=0.86).
This is the largest analysis of cause of infant deaths from Africa to date. Weekly vitamin A supplementation in women of reproductive age has no beneficial or deleterious effect on the causes of infant death to age 6 or 12 months in rural Ghana.
Trial registration number
This paper reports the results of planned (a priori) analyses of the effect of vitamin A supplementation in women of reproductive age on cause- and age-specific infant mortality in the ObaapaVitA trial.
In addition, because of the recent interest in potential differential effects, we also assessed effects by sex and season.
The analyses from this trial indicate that weekly vitamin A supplementation in women of reproductive age has no beneficial or deleterious effect on the causes of death in their babies of age 6 or 12 months, no effect on infection-specific infant mortality and no role for inclusion in child survival programs in Asia and Africa.
We also failed to demonstrate any benefit or harm from vitamin A supplementation in women of reproductive age and in infant males or females in our study population. There was also no modification of the effect of vitamin A supplementation and mortality by season.
Strengths and limitations of this study
There were some limitations to our trial. There was no direct observation of capsule taking; however, adherence was supported by an extensive Information, Education and Communication strategy, and we estimated that on average 75% of women both received and took all four capsules every month.
We also used verbal postmortems (VPMs) and physician coders to assign cause of death, and it was not possible to use health facility records or postmortem examinations to verify the cause of death. Misclassification is common in VPM studies, but this can be minimised when broad categories such as ‘infection’, ‘prematurity’ and ‘asphyxia’ are used. Our VPM tools were also validated in similar study populations, and acceptable sensitivity and specificity were reported in comparison to a gold standard.
Strengths included the fact that our study was large (62 000 infants) prospective and population-based. All resident women in the trial districts and their babies were enrolled, and loss to follow-up was low, even in women with babies who had died.