Primary school children with anemia have better cognitive and physical health when given daily iron supplements, according to a systematic review and meta-analysis published online October 15 in the Canadian Medical Association Journal.
A team of Australian investigators analyzed data from 32 randomized trials almost exclusively conducted in low- and middle-income countries. The trials had a total of 7089 children aged 5 to 12 years, the majority of whom were anemic.
The results show that iron supplementation improved both global cognitive scores, by a third of a point, and intelligence quotient, by about 5 points, in children who were anemic at baseline.
Supplementation was also associated with better age-adjusted height among all children and age-adjusted weight among the anemic subset. Furthermore, it cut the risk for anemia by half and the risk for iron deficiency by more than three fourths.
Although supplementation appeared generally safe and well-tolerated, the analysis was underpowered to definitively assess adverse effects.
"[R]outine daily iron supplementation is likely to benefit cognitive performance in primary-school–aged children in developing settings where anemia is prevalent and testing hemoglobin before iron supplementation may not be feasible," write Michael Low, MBBS, from the Department of Clinical Haematology, Alfred Hospital, Prahran, Australia, and colleagues. "In developed settings, our data support ensuring that anemia is detected and treated.... Daily iron supplementation could benefit educational attainment and economic potential at the individual level and, in settings where anemia is prevalent, population level," they conclude.
In an accompanying commentary, Katherine Gray-Donald, PhD, from the School of Dietetics and Human Nutrition, McGill University, Montreal, Quebec, Canada, writes that the meta-analysis "is important in that it quantifies the robust effects of iron supplementation on cognitive performance among anemic children who are iron deficient. The next challenge is to determine how to safely, economically and sustainably provide better iron nutrition to children in many poor settings of the world. Clearly anemic children will benefit, but the risks of iron for all remain to be elucidated," she maintains.
The best approaches to addressing iron deficiency anemia will require an understanding of the specific causes in a given setting and may include reducing infections, providing nutrient supplements, and using strategies such as fortification to improve nutrient intake, according to Dr. Gray-Donald.
The findings of the meta-analysis have unclear relevance for children in Canada and other higher-income countries, the iron status of which tends to be much better, she notes. "Because so few children in Canada are anemic, population-level interventions are obviously not advised for primary-school–aged children."
High Rate of Anemia in Trials
For the meta-analysis, the investigators identified trials that randomly assigned primary school–aged children to daily (≥5 days/week) oral iron supplementation or control. More than half of the children each had anemia and iron deficiency.
The rate of adherence with iron supplementation ranged from 50% to 90%, according to reported data.
Compared with control peers, children in the iron supplementation group had better global cognitive scores, with a standardized mean difference of 0.50 points. However, in subgroup analyses, the difference was significant only among anemic children, with a standardized mean difference of 0.29 points.
Age-adjusted IQ did not differ between groups overall, but in the anemic subgroup, children given iron supplements had mean IQs that were a significant 4.55 points higher.
Supplementation was also associated with significantly better attention and concentration, as assessed with the maze test (mean difference, 1.30) and clerical task scores (standardized mean difference, 0.44). No benefit was seen in terms of digit span, visual memory score, math scores, and language test scores.
Absolute height did not differ between groups, but children given iron supplements were taller for their age, as assessed with z score (mean difference, 0.09). The groups did not differ with respect to absolute weight or weight for age, as also assessed with z score. In a single study, iron supplementation was associated with a significantly better weight for age among children with iron deficiency anemia (mean difference, 0.13).
Only 6 of the trials reported safety outcomes. The iron supplementation and control groups were statistically indistinguishable in terms of rates of malaria infection and gastrointestinal adverse effects. Any effect on respiratory tract infection was unclear.
A single trial calculated overall morbidity scores, finding that children given iron supplements had lower scores than control peers (mean difference, −2.73). None of the trials reported mortality or hospitalizations. Any effect of supplementation on exercise performance was also unclear.
Relative to their counterparts in the control group, children in the iron supplementation group had a significantly lower prevalence of anemia (risk ratio, 0.50) and iron deficiency (risk ratio, 0.21).
Dr. Low has received travel expenses from Gilead Sciences, and 1 coauthor is coinvestigator on an unrestricted research grant from Vifor Pharma. The other authors and Dr. Gray-Donald have disclosed no relevant financial relationships.
CMAJ. Published online October 15, 2013. Full text
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