Researchers at the Johns Hopkins Bloomberg School of Public Health, working with the Ministry of Health of Zanzibar, found that iron supplementation improved motor and language development in rural African preschoolers, while an anti-helminth (worm) treatment had a slight but non-significant positive effect on both motor and language development.
The study, which appeared in the December 15, 2001, issue of the British Medical Journal (BMJ), was the first published investigation of the effects of geohelminth infections on the development of preschool children, and the first study of iron and early child development in Africa.
Iron deficiency anemia is associated with developmental delays that lead to poor performance on scales of mental and motor development among infants and toddlers, as well as on tests of intelligence and cognitive function among preschool and school-age children. The study was carried out in a population exposed to numerous health risks, including widespread malnutrition and infection by Plasmodium falciparum (the cause of the most serious form of malaria) and by geohelminths (worms). In addition, the anemia suffered by the children in the study was more severe than that of children in any other similar published study.
"Our results highlight the presence of severely anemic children in malaria-endemic African communities who are not detected by the current health care system, and who appear to be at significant developmental risk," said lead author Rebecca Stoltzfus, PhD, an associate professor of international health at the Johns Hopkins Bloomberg School of Public Health. "Nearly one third of apparently healthy toddlers in this community were severely anemic. Before intervention, children with severe anemia showed distinct delays in both gross motor and language milestones for their age, and daily oral iron syrup helped to correct those deficits."
In this double-blind, placebo-controlled, randomized trial, 614 children in Pemba Island, Zanzibar, were randomly assigned to receive over a 12-month period either a daily oral iron supplement or a placebo. During the same year, these children also received quarterly doses of either an anti-worm medication, mebendazole, or a placebo. Motor and language development were assessed at baseline and at the end of the experiment by using parents' reports of whether a child had reached certain age-appropriate gross motor and language milestones.
At the study's beginning and one year later, blood was collected to determine levels of hemoglobin, iron, and erythrocyte protoporphyrin (a precursor of hemoglobin), as well as the numbers of malaria parasites. Before and after the intervention, the numbers of helminth eggs were determined from the children's fecal samples.
Iron supplementation. Younger children benefitted most from iron. Iron supplementation significantly improved iron status in the children but the supplement's effect on hemoglobin levels was small in all but the most severely anemic children. Iron improved motor and language development, although iron's effect on motor development was limited to the most anemic children with very low baseline hemoglobin.
Language scores at baseline were strongly related to both hemoglobin and erythrocyte protoporphyrin, and iron supplementation improved language development significantly across a wide range of baseline hemoglobin concentrations. These findings suggest that iron supplementation has important benefits for children even if other important causes of anemia, such as malaria, are not corrected.
Mebendazole therapy. Before intervention, infections by worms were common but moderate. At baseline these infections were not associated with baseline motor or language scores. Those children who received mebendazole for one year had slightly better developmental scores for both motor skills and language, but these effects were small and did not approach statistical significance. This could mean that worms don't affect children's development. But it may also be true that the developmental assessments used were not sufficiently sensitive, or that mebendazole did not completely treat all the worms. As expected, mebendazole significantly reduced infections by Ascaris lumbricoides (roundworm) and Trichuris trichiura (whipworm) infections but not of hookworms.
The authors emphasized that determining the optimal treatment and follow-regimen for severely anemic children is a high priority for future research. "Although the best dose and duration remains to be clarified, long-term treatment with oral iron may be an important component in the optimal treatment and follow-up of severely anemic children, " said Stoltzfus.
Support for this study was provided by the Thrasher Research Fund, the U.S. Agency for International Development, and AL Pharma, Inc.
Co-authors of this report: Jane D. Kvalsvig, PhD, director, Child Development Programme, University of Natal, Durban, South Africa; Hababu M. Chwaya, MD, PhD, director of preventive services, Ministry of Health, Zanzibar, Tanzania; Antonio Montresor, MD, medical officer, Parasitic Diseases and Vector Control, World Health Organization, Geneva, Switzerland; Marco Albonico, MD, scientific secretary, Ivo de Carneri Foundation, Milan, Italy; James M. Tielsch, PhD, professor, International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Md., USA; Lorenzo Savioli, MD, coordinator, Parasitic Diseases and Vector Control, World Health Organization, Geneva, Switzerland; Ernesto Pollitt, PhD, professor, Human Development and Behavior Research, Department of Pediatrics, School of Medicine, University of California at Davis, USA.