The study, published in The Lancet (Vol. 367, pp. 133-143), claims that giving all young children iron and folic acid supplements in areas endemic with malaria leads to higher rates of severe illness and death.
Iron deficiency and associated anaemia have been associated with delayed cognitive and motor development, and slower growth amongst children. The WHO currently recommends daily iron and folic acid supplements for children if more than 40 per cent of young children in a population are anaemic.
Anaemia is the most common nutritional problem in the world, with three quarters of East Africa's under-fives reported to be anaemic.
The scientists supplemented the normal diet of 8000 children on the island of Pumba, Zanzibar, with folic acid (50 micrograms) and iron (12.5 milligrams). Another 8000 children received iron, folic acid and zinc supplements, and a further 8000 children received a placebo.
Lead author Sunil Sazawal from John Hopkins University, reported: "Those who received iron and folic acid with or without zinc were 12 per cent more likely to die or need hospital treatment for an adverse event; there were also 15 per cent more deaths in these groups."
It is proposed that the iron/folic acid supplements were interacting with the local malarial treatment method of sulfodoxine and pyrimethamine. Previous studies have shown that the mix of supplements and treatment leads to a biologically and statistically significant delay in parasite clearance and cure.
Sazawal and colleagues concluded: "In the presence of an active programme to detect and treat malaria, iron-deficient and anaemic children can benefit from supplements. However, supplementation of those who are not iron deficient may be harmful."
"As such, current guidelines for universal supplementation with iron and folic acid should be revised," they said.
In a parallel study in Nepal, researchers reported that iron and folic acid supplements with or without zinc had no effect on child mortality.
Also published in The Lancet (Vol. 367, pp. 144-152), the study reported that although the supplements had no effect on mortality, they did observe a decrease in severe and moderate anaemia.
"Limitations in iron status are not the only nutritional deficiency affecting responses to infectious morbidity and mortality in this setting," said lead author James Tielsch.
The two studies garnered praise in an accompanying editorial by Mike English and Robert Snow from the Wellcome Trust Collaborative in Kenya.
"Such studies are rare and the study teams are to be applauded," they wrote. "Both papers are far superior to any previous examination of the survival benefits and risks of supplementation with iron and folate an might never be superceded."
However, in response to calls for a change to WHO guidelines, English and Snow commented: "The current trials, while a significant advance, represent data from two ends of the spectrum of malaria ecologies and do not yet provide adequate evidence for global policy."