Systematic Review and Meta-Analysis of Randomized Controlled Trials
M Low, A Farrell, BA Biggs, SR Pasricha
CMAJ 2013 Oct 15;[EPub Ahead of Print]
TAKE-HOME MESSAGE
- What are the benefits of daily iron supplementation in primary school–aged children?
- A literature review was conducted of randomized controlled trials on iron supplementation in children aged 5 through 12 years. Out of 16,501, 32 studies were retained, which included 7089 children.
- Iron supplementation improved global cognitive scores, intelligence quotient among anemic children, and measures of attention and concentration, as well as age-adjusted height among all children and age-adjusted weight among anemic children.
Commentary By: Oscar W Brown, MD, FAAP
The authors of this article, after a comprehensive literature review and meta-analysis of many studies, reached the conclusion that iron supplementation safely improves hematologic and nonhematologic outcomes among primary school–aged children in low- and moderate-income settings, with very few ill effects. This conclusion should be understood in light of the data reviewed and the source of the various study group participants. The vast majority of these studies were conducted in developing countries with noted rates of IDA in excess of 25% of school-aged children (Mali, Thailand, Indonesia, Ethiopia, India, Zambia, and Bolivia were some). None was conducted in European (except one from France), Australian, or North American areas. The IDA is reported to be 3% to 10% in Europe and European populations. Therefore, this study addresses a very different population from the group that most practitioners in the “developed” world manage. There are, of course, certain groups within so-called developed nations that reflect some of the issues noted in this study, even though the base populations are from different geographic regions.
With the nature of the various studies reviewed for inclusion in the final meta-analysis understood, it can be said that the analysis contains some significant findings applicable to all regions.
- Children with anemia at baseline showed significant improvement in IQ after iron supplementation compared with controls.
- Other cognitive tests were less dramatically affected, if at all. Digit span, visual memory score, math scores, and language tests scores were not significantly impacted when pre- and post-supplementation results were assessed.
- Iron supplementation not associated with a difference in absolute height, although a small benefit was noted in height for age.
- No difference in weight was noted between iron supplementation and control subjects.
- In children infected with malaria parasitemia, findings were similar in the iron and control groups. In children with respiratory tract infections, data were conflicting.
- No differences were noted in GI upset, constipation, vomiting, or diarrhea in children who received iron vs control.
- Iron supplementation improved hemoglobin and ferritin levels, and corrected anemia and iron-deficiency anemia.
- No effects were noted relative to other micronutrients, such as copper, zinc, and lead.
- Findings associated with exercise performance were conflicting between control and iron-supplemented subjects, with little clear-cut difference noted.
- Iron supplementation conferred a positive benefit on cognitive performance among primary school–aged children when expressed in terms of IQ performance. Daily supplementation decreased the risk of anemia by 50% and subsequently reduced risk of iron-deficiency anemia by 79%. Iron supplements appeared to be well-tolerated, and no significant safety issues were noted with their use.
The take-away message is that evaluation of diet and dietary intake of iron is important and evaluation of at-risk age-groups in all populations is important. It is important because there is more benefit to be had than simply correcting nutritional anemia. It is also important to understand that this study was limited to supplementation and did not address the use of therapeutic dosing of iron in anemic children. That is food for another study.
ABSTRACT
Background: Anemia is an important public health and clinical problem. Observational studies have linked iron deficiency and anemia in children with many poor outcomes, including impaired cognitive development; however, iron supplementation, a widely used preventive and therapeutic strategy, is associated with adverse effects. Primary-school–aged children are at a critical stage in intellectual development, and optimization of their cognitive performance could have long-lasting individual and population benefits. In this study, we summarize the evidence for the benefits and safety of daily iron supplementation in primary-school–aged children.
Methods: We searched electronic databases (including MEDLINE and Embase) and other sources (July 2013) for randomized and quasi-randomized controlled trials involving daily iron supplementation in children aged 5–12 years. We combined the data using random effects meta-analysis.
Results: We identified 16 501 studies; of these, we evaluated 76 full-text papers and included 32 studies including 7089 children. Of the included studies, 31 were conducted in low- or middle-income settings. Iron supplementation improved global cognitive scores (standardized mean difference 0.50, 95% confidence interval [CI] 0.11 to 0.90, p = 0.01), intelligence quotient among anemic children (mean difference 4.55, 95% CI 0.16 to 8.94, p = 0.04) and measures of attention and concentration. Iron supplementation also improved age-adjusted height among all children and age-adjusted weight among anemic children. Iron supplementation reduced the risk of anemia by 50% and the risk of iron deficiency by 79%. Adherence in the trial settings was generally high. Safety data were limited.
Interpretation: Our analysis suggests that iron supplementation safely improves hematologic and nonhematologic outcomes among primary-school–aged children in low- or middle-income settings and is well-tolerated.
Journal Abstract: http://dx.doi.org/10.1503/cmaj.130628