vitamin A supplements in neonates

Andrew Prentice in the BMJ 20th March 2010 comments on a linked randomised controlled trial, where Benn and colleagues ( BMJ 20th March 2010 ) assess the effect of giving high dose vitamin A supplements to low birth weight neonates in Guinea-Bissau. They found no effect on infant mortality, although boys tended to benefit but a significantly harmful effect was seen on girls’ survival.
In 1983 it was reported that young Indonesian children with mild xerophthalmia, Bitot’s spots, and night blind¬ness, ie vitamin A deficiency had a higher mortality rate . A subsequent randomised controlled trial of vitamin A supplementation showed an impressive benefit on mortality. A meta-analysis of large scale trials in Asia and Africa showed that this cheap and simple intervention reduces child mortality by 30% in countries with evidence of at least marginal vitamin A deficiency. The World Health Organization recommended universal vitamin A supplementation of children aged six to 60 months, which is government policy in more than 60 countries. .
The question was than asked if it was better to give vitamin A to newborn babies or later to infants or children . Infant mortality is greatest in the first six months of life. Clinical trials of supplementing breast feeding mothers postpartum gave varying results and some infant complications eg acute bulging fontanelles after dosing. More trials were conducted and a meta-analysis found a mixed picture , no survival benefit, but evidence of benefit from Asian trials and evidence of no effect (or even harm) in two African trials eg previous one by Benn and colleagues in Guinea-Bissau.
Yet vitamin A supplementation has saved many thousands of lives. Benn has indicated no benefit and even harmful effect of vitamin A at birth that seemed to be confined to girls. Benn has shown repeated examples of how vaccines, micronutrients, and exposure to infections can strongly affect all cause mortality in regions with a high burden of infection. Sex differences in susceptibility to certain infections and in responses to vaccination have been recognised for decades,
WHO has commissioned three large trials in an attempt to resolve the possibility that neonatal vitamin A supplementation may be beneficial in Asia but not in Africa. These trials will assess mortality up to six months of age.
Prentice 2010 Vitamin A supplements and survival in children BMJ vol 340 pp 607-8
Benn et al 2010 Vitamin A supplementation and BCG vaccination at birth in two low birthweight neonates: two by two factorial randomised trial BMJ vol 340 p 636

Martin Eastwood

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