Effect of vitamin A supplementation in women of reproductive age on maternal survival in Ghana (ObaapaVitA): a cluster-randomised, placebo-controlled trial

Abstract

A previous trial in Nepal showed that supplementation with vitamin A or its precursor (betacarotene) in women of reproductive age reduced pregnancy-related mortality by 44% (95% CI 16-63). We assessed the effect of vitamin A supplementation in women in Ghana. ObaapaVitA was a cluster-randomised, double-blind, placebo-controlled trial undertaken in seven districts in Brong Ahafo Region in Ghana. The trial area was divided into 1086 small geographical clusters of compounds with fieldwork areas consisting of four contiguous clusters. All women of reproductive age (15-45 years) who gave informed consent and who planned to remain in the area for at least 3 months were recruited. Participants were randomly assigned by cluster of residence to receive a vitamin A supplement (25 000 IU retinol equivalents) or placebo capsule orally once every week. Randomisation was blocked and based on an independent, computer-generated list of numbers, with two clusters in each fieldwork area allocated to vitamin A supplementation and two to placebo. Capsules were distributed during home visits undertaken every 4 weeks, when data were gathered on pregnancies, births, and deaths. Primary outcomes were pregnancy-related mortality and all-cause female mortality. Cause of death was established by verbal post mortems. Analysis was by intention to treat (ITT) with random-effects regression to account for the cluster-randomised design. Adverse events were synonymous with the trial outcomes. This trial is registered with ClinicalTrials.gov, number NCT00211341. 544 clusters (104 484 women) were randomly assigned to vitamin A supplementation and 542 clusters (103 297 women) were assigned to placebo. The main reason for participant drop out was migration out of the study area. In the ITT analysis, there were 39 601 pregnancies and 138 pregnancy-related deaths in the vitamin A supplementation group (348 deaths per 100 000 pregnancies) compared with 39 234 pregnancies and 148 pregnancy-related deaths in the placebo group (377 per 100 000 pregnancies); adjusted odds ratio 0.92, 95% CI 0.73-1.17; p=0.51. 1326 women died in 292 560 woman-years in the vitamin A supplementation group (453 deaths per 100 000 years) compared with 1298 deaths in 289 310 woman-years in the placebo group (449 per 100 000 years); adjusted rate ratio 1.01, 0.93-1.09; p=0.85. The body of evidence, although limited, does not support inclusion of vitamin A supplementation for women in either safe motherhood or child survival strategies. UK Department for International Development, and USAID.