A trial in Ghana has shown that vitamin A supplementation does not reduce maternal mortality—contradicting previous findings from a trial in Nepal which showed a 44% decrease. The new study (ObaapaVitA) is reported in an Article Online First and in an upcoming edition of The Lancet—written by Professor Betty R Kirkwood, Department of Nutrition and Public Health Intervention Research, London School of Hygiene and Tropical Medicine, UK, and colleagues.
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 clusters. All women of reproductive age (15 years) who gave informed consent and who planned to remain in the area for at least 3 months were recruited. Participants were randomly allocated either a vitamin A supplement or placebo capsule orally once every week. Two clusters in each fieldwork area were 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 mortem.
A total 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 final analysis, there was no statistically significant difference between the intervention and control groups—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). 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).
The authors say: "Our results suggest that vitamin A supplementation once a week in women of reproductive age has no beneficial effect on their survival or on the survival of their babies in rural Ghana. The absence of an effect on stillbirth rate, neonatal survival, or infant survival accords with the findings of trials undertaken in Nepal and Bangladesh. However, the absence of an effect of vitamin A supplementation on pregnancy-related mortality contrasts with the substantial reduction in mortality reported in the Nepal trial, the only other trial in which all women of reproductive age were given supplements."
They conclude: "Further trials to assess the effect of vitamin A supplementation on maternal mortality are unlikely to be undertaken because of their size and cost. The body of evidence, although limited, does not support inclusion of low-dose vitamin A supplementation for women in either safe motherhood or child survival strategies."
In an accompanying Comment, Professor Anthony Costello and Dr David Osrin UCL Institute for Global Health, University College London, UK, discuss the possible reasons behind the difference between the Nepal and Ghana trial results, including possible varying patterns of vitamin A deficiency between population.
They conclude: "Evaluation of new interventions to reduce maternal mortality is a high priority in view of the lack of progress towards Millennium Development Goal 5. The ObaapaVitA Trial Team are to be congratulated for their commitment to its measurement as a primary outcome. We need more of these trials across a range of interventions, but they have to be large. Maternal deaths, even in high-mortality settings, are fairly rare events and trial groups might need to include 100 000 pregnancies or more. If we are to provide policy makers with new options, how can we design trials that can be completed within a reasonable timeframe? It took 10 years to confirm that vitamin A supplementation in childhood improved survival, and it has taken more than 15 years to resolve the question of its effects on maternal mortality. To get results within 3 years will require multisite trials, simple surveillance procedures to measure maternal deaths in communities, and donors willing to put up millions of pounds for studies that cover large and poor populations. There have been few trials of interventions to reduce maternal mortality ratios, and we need new evidence of effectiveness at scale if we are to reduce the unacceptable toll of maternal mortality."
For Professor Betty R Kirkwood, Nutrition and Public Health Intervention Research Unit, London School of Hygiene and Tropical Medicine, UK, please contact Sally Hall, Media Manager onT) +44 (0) 20 7927 2073, out of hours +44 (0)7790 992 797 E) sally.hall@lshtm.ac.uk / betty.kirkwood@lshtm.ac.uk
For Professor Anthony Costello and Dr David Osrin, UCL Institute for Global Health, University College London, UK, please contact Ruth Howells, UCL Media Relations Manager on T) +44 (0)20 7679 9739, M) +44 (0)7990 675 947, out of hours +44 (0)7917 271 364, E) ruth.howells@ucl.ac.uk / a.costello@ich.ucl.ac.uk
For full Article and Comment, see: http://press.thelancet.com/vita.pdf
Journal
The Lancet