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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

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The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis

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Review published: .

CRD summary

This review found some evidence that iron supplementation improved attention and concentration in women and adolescents and intelligence in women and children who were anaemic at baseline. No effects on other cognitive outcomes were found. Further longer term trials were needed to confirm the findings. The review was well conducted and the conclusions appear suitably conservative.

Authors' objectives

To assess the effects of iron supplementation on cognition in people aged six years or older.

Searching

MEDLINE, EMBASE, PsycINFO and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to November 2008. The search terms were given. No language restrictions were applied. Reference lists of included studies and relevant reviews were checked.

Study selection

Two authors independently assessed papers for inclusion; disagreements were resolved through team discussion. Where necessary, authors were contacted for queries related to inclusion criteria.

Randomised controlled trials (RCTs) that assessed the effects of iron supplementation (as fortified food or supplement) compared to placebo or no intervention in people aged six years or older and that reported on some objective measure of cognitive performance were eligible for inclusion. Duration of treatment had to be at least four weeks. Primary outcomes were measures of intelligence, memory, concentration, psychomotor skills and scholastic achievement.

Most participants in the included studies were children aged six to 18 (male and female). Others participants were pregnant women, women with infants and/or premenopausal women. No studies assessed men or older women. Half of the studies were carried out in developing countries and half were in developed countries. Most people were anaemic or iron deficient; some were iron replete (see paper for definitions and details). Iron was given in the form of oral supplements (ferrous sulphate, ferrous carbonate, ferrous fumarate). All studies used placebo as a control. A variety of cognitive tests were used (see paper for details).

Assessment of study quality

Quality assessment was performed by two reviewers independently. Disagreements were resolved by team discussion.

Quality was assessed on items such as description of randomisation, allocation concealment, masking of participants, researchers and outcome assessors, whether change in iron status was described, completeness of follow-up and potential funding bias.

Data extraction

Where studies provided several different tests for any outcome data, that used in other included studies was extracted. For scholastic skills, outcomes that tested mathematical skills were extracted in preference. Where studies had more than one iron treatment group (dosage or timing) these were combined and compared with the control group. Where participants did not have anaemia and serum ferritin was not described they were classified as "iron deficient and/or replete".

Mean change and standard deviation from baseline to follow-up were calculated; if these data were unavailable, absolute measures at end of treatment were extracted.

Change in iron status was taken as positive if there was a statistical difference in haemoglobin (Hb) or serum ferritin between treatment and control group or, if unavailable, the intervention duration was at least 12 weeks.

Data were extracted by two reviewers independently. Disagreements were resolved by team discussion. Where necessary, authors were contacted for missing data.

Methods of synthesis

Where pooling was possible, standardised mean differences (SMD) and 95% confidence intervals (CI) were calculated using a random-effects model. Heterogeneity was assessed using the I2 statistic. Sensitivity analyses were performed with removal of studies where it was not clear that iron status had been altered during the study. Subgroup analyses were performed based on baseline iron status and by age group.

Where it was not possible to pool data (because of a lack of appropriate data) results were discussed in the narrative.

Publication bias was assessed using a funnel plot.

Results of the review

Fourteen RCTs (3,645 participants) were included. Ten studies (3,344 participants) were on children and four (301 participants) on premenopausal women. Nine RCTs ( 2,274 participants) provided data for meta-analyses. Results from five studies (1,070 participants) were discussed in narrative. Study duration ranged from four to 29 weeks.

The method of randomisation was described in five trials, partially described in three and not described in six. Allocation concealment was reported in one trial and was unclear in others. Full details of all quality assessment was reported.

Iron supplementation was associated with a benefit in attention or concentration (SMD 0.59, 95% CI 0.29 to 0.90, I2=0%; 179 participants). This could be interpreted as a moderate effect. In subgroup analysis the improvement remained apparent for children (132 participants), but showed no effect for premenopausal women (47 participants). The effect was weakened but remained statistically significant when one study that did not clearly report an improvement in iron status was removed.

Five trials met the inclusion criteria, but were not able to be included in the meta-analysis. One trial on children reported a beneficial effect on attention or concentration and four (one in premenopausal women and three in children) reported no statistically significant effect.

The overall pooling showed no evidence of an effect on intelligence, although there was evidence of heterogeneity (I2=81%). Subgroup analyses showed a benefit for those who were anaemic at baseline (SMD 0.54, 95% CI 0.26 to 0.81, I2=0%; 209 participants). Age group results suggested no effect in children (2,289 participants) and a positive effect in premenopausal women (72 participants). Three trials not included in the meta-analyses found no statistical difference in intelligence between iron and placebo groups.

Pooled results showed there was no evidence of any effect on memory (255 participants) or psychomotor function (255 participants) either in overall analysis or in subgroups by age. One of four studies not included in the meta-analysis reported a beneficial effect on memory; one trial reported on psychomotor function and found no effect.

Results for scholastic achievement were heterogeneous. Two studies found improvement and two found impairment; overall pooling showed no effect (heterogeneity 12=96%, 1,824 participants). Subgroup analyses appeared to show that iron supplementation was deleterious in those who were iron deficient. In the one study where participants were anaemic at baseline and the effect on iron status was clear, results suggested a harmful effect of iron (100 participants). One of three studies not included in the meta-analysis found an improvement with iron and two found no difference.

Adverse effects were not well reported; where reported there was no statistical difference in risk of dropping out with iron compared to placebo.

A funnel plot for the outcome of intelligence (the most commonly reported outcome), showed some indication of publication bias.

Authors' conclusions

There was some evidence that iron supplementation improved attention and concentration in adolescents and women regardless of baseline iron status. Iron supplementation also improved intelligence in women and children who were anaemic at baseline, but had no effect on other groups or on other cognitive outcomes.

CRD commentary

The aims of this review were clearly stated in terms of participants, study design and treatment. The search covered a number of relevant sources and no language restrictions were applied; these were likely to have reduced risks of language and publication biases, although the authors' tests showed that publication bias was a possibility. The review methods aimed at reducing reviewer error or bias. Study quality was assessed. Methods of synthesis and investigations of heterogeneity appeared appropriate. Where data from studies could not be used in the pooled analyses, the authors usefully included results in a narrative form. The methods of the review and information from the included studies were clearly reported in detail. Overall this was a well-conducted review and the conclusions were suitably conservative given the available data.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that further well-powered, blinded and independently funded trials of at least one year duration in children, adolescents, adults and older people were needed. These should use well validated tests for cognition and look at people with varying levels of baseline iron status.

Funding

University of East Anglia; University of Leeds.

Bibliographic details

Falkingham M, Abdelhamid A, Curtis P, Fairweather-Tait S, Dye L, Hooper L. The effects of oral iron supplementation on cognition in older children and adults: a systematic review and meta-analysis. Nutrition Journal 2010; 9:4. [PMC free article: PMC2831810] [PubMed: 20100340]

Indexing Status

Subject indexing assigned by NLM

MeSH

Administration, Oral; Adolescent; Adult; Anemia /drug therapy; Child; Cognition /drug effects; Dietary Supplements /statistics & numerical data; Educational Status; Female; Humans; Intelligence /drug effects; Intelligence Tests /statistics & numerical data; Iron, Dietary /administration & dosage /pharmacology /therapeutic use; Male; Memory /drug effects; Psychomotor Performance /drug effects; Randomized Controlled Trials as Topic; Young Adult

AccessionNumber

12010003457

Database entry date

29/09/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

Copyright © 2014 University of York.
Bookshelf ID: NBK80340

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