Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial
Awasthi, S.; Peto, R.; Read, S.; Clark, S.; Pande, V.; Bundy, D.; Ayyar, L.; Chandra, A.; Joshi, V.Chandra.; Narang, N.; Rehman, H.; Saxena, N.; Prakash, N.; Sharma, A.; Sharma, M.; Tripathi, M.; Upreti, D.Kumar.; Das, R.; Lal, A.; Rastogi, T.; Mani, S.S.; Chitransh, D.; Pandey, L.; Tandon, A.; Bajpai, D.; Chandra, U.; Dwivedi, A.; Pant, P.K.; Shukla, V.; Ahmad, A.; Ahmad, H.; Bahadur, J.; Chandra, H.; Chandra, R.; Chaturvedi, A.; Dwivedi, S.; Kumar, A.; Kumar, D.; Kumar, M.; Kumar, N.; Kumar, R
Lancet 381(9876): 1469-1477
2013
ISSN/ISBN: 0140-6736 PMID: 23498849 DOI: 10.1016/s0140-6736(12)62125-4Document Number: 572598
In north India, vitamin A deficiency (retinol <0·70 μmol/L) is common in pre-school children and 2-3% die at ages 1·0-6·0 years. We aimed to assess whether periodic vitamin A supplementation could reduce this mortality. Participants in this cluster-randomised trial were pre-school children in the defined catchment areas of 8338 state-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks (clusters) were cluster-randomly allocated in Oxford, UK, between 6-monthly vitamin A (retinol capsule of 200,000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of retinol effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6-72 months. Annually, one centre per block was randomly selected and visited by a study team 1-5 months after any trial vitamin A to sample blood (for retinol assay, technically reliable only after mid-study), examine eyes, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100,000 visits, 25,000 deaths at ages 1·0-6·0 years , mortality ratio 0·96, 95% CI 0·89-1·03, p=0·22), suggesting absolute risks of death between ages 1·0 and 6·0 years of approximately 2·5% retinol versus 2·6% control. No specific cause of death was significantly affected. DEVTA contradicts the expectation from other trials that vitamin A supplementation would reduce child mortality by 20-30%, but cannot rule out some more modest effect. Meta-analysis of DEVTA plus eight previous randomised trials of supplementation (in various different populations) yielded a weighted average mortality reduction of 11% (95% CI 5-16, p=0·00015), reliably contradicting the hypothesis of no effect. UK Medical Research Council, USAID, World Bank (vitamin A donated by Roche).