Iron therapy for improving physical and intellectual development in children under the age of three who are anaemic due to a lack of iron

It has been suggested that a lack of iron in young children negatively affects their physical and intellectual development and therefore those who are anaemic should be treated. To assess the effects of iron therapy on psychomotor development and cognitive function in very young iron deficient anaemic children, we searched eight electronic databases in April 2013 for relevant studies. We looked for studies where children less than three years of age with iron deficiency anaemia were randomly assigned either to receive iron or iron plus vitamin C versus a placebo ('dummy pill') or vitamin C alone, and their developmental status or cognitive function was independently assessed by someone who did not know if they had received any iron. To make sure we had not missed any studies, we also searched reference lists, ran citation searches and contacted key experts in this area.

Two review authors independently read through all the titles and abstracts retrieved from the searches to see if the studies were relevant. Where necessary, we looked at the full-text version of the paper to check if it matched the inclusion criteria for our review. The same review authors independently extracted data from the studies for analysis and assessed the risk of bias in each of the studies. We analysed the data separately depending on whether assessments were performed within one month of beginning iron therapy or after one month.

We found eight studies to include in the review. Six studies (involving 225 children) looked at the effects of iron therapy within 30 days of starting it and we were able to combine the results of five of them. Iron therapy did not appear to improve scores on either the Bayley Scale Psychomotor Development Index (PDI) or the Bayley Scale Mental Development Index (MDI). Two studies (160 children) considered the effects of iron therapy more than 30 days after starting it. One study found no benefit of iron therapy on the acquistion of skills as measured by the Denver Developmental Screening Test. The other study, however, found that scores on the Bayley scales PDI and MDI were significantly higher for the group receiving iron therapy.

This review concludes that there is no convincing evidence that iron given by mouth or by injection will improve physical or intellectual development in young children who are anaemic because of a lack of iron within one month after start of treatment. It is unclear whether longer-term treatment is beneficial for physical and intellectual development in these children. Large randomised controlled trials with long-term follow-up are needed in the future.

Authors' conclusions: 

There is no convincing evidence that iron treatment of young children with IDA has an effect on psychomotor development or cognitive function within 30 days after commencement of therapy. The effect of longer-term treatment remains unclear. There is an urgent need for further large randomised controlled trials with long-term follow-up.

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Background: 

Iron deficiency and iron deficiency anaemia (IDA) are common in young children. It has been suggested that the lack of iron may have deleterious effects on children's psychomotor development and cognitive function. To evaluate the benefits of iron therapy on psychomotor development and cognitive function in children with IDA, a Cochrane review was carried out in 2001. This is an update of that review.

Objectives: 

To determine the effects of iron therapy on psychomotor development and cognitive function in iron deficient anaemic children less than three years of age.

Search strategy: 

We searched the following databases in April 2013: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, LILACS, ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform (ICTRP). We also searched the reference lists of review articles and reports, and ran citation searches in the Science Citation Index for relevant studies identified by the primary search. We also contacted key authors.

Selection criteria: 

Studies were included if children less than three years of age with evidence of IDA were randomly allocated to iron or iron plus vitamin C versus a placebo or vitamin C alone, and assessment of developmental status or cognitive function was carried out using standardised tests by observers blind to treatment allocation.

Data collection and analysis: 

Two review authors independently screened titles and abstracts retrieved from the searches and assessed full-text copies of all potentially relevant studies against the inclusion criteria. The same review authors independently extracted data and assessed the risk of bias of the eligible studies. Data were analysed separately depending on whether assessments were performed within one month of beginning iron therapy or after one month.

Main results: 

We identified one eligible study in the update search that had not been included in the original review. In total, we included eight trials.

Six trials, including 225 children with IDA, examined the effects of iron therapy on measures of psychomotor development and cognitive function within 30 days of commencement of therapy. We could pool data from five trials. The pooled difference in pre- to post-treatment change in Bayley Scale Psychomotor Development Index (PDI) between iron and placebo groups was -1.25 (95% confidence interval (CI) -4.56 to 2.06, P value = 0.65; I2 = 33% for heterogeneity, random-effects meta-analysis; low quality evidence) and in Bayley Scale Mental Development Index (MDI) was 1.04 (95% CI -1.30 to 3.39, P value = 0.79; I2 = 31% for heterogeneity, random-effects meta-analysis; low quality evidence).

Two studies, including 160 randomised children with IDA, examined the effects of iron therapy on measures of psychomotor development and cognitive function more than 30 days after commencement of therapy. One of the studies reported the mean number of skills gained after two months of iron therapy using the Denver Developmental Screening Test. The intervention group gained 0.8 (95% CI -0.18 to 1.78, P value = 0.11, moderate quality of evidence) more skills on average than the control group. The other study reported that the difference in pre- to post-treatment change in Bayley Scale PDI between iron-treated and placebo groups after four months was 18.40 (95% CI 10.16 to 26.64, P value < 0.0001; moderate quality evidence) and in Bayley Scale MDI was 18.80 (95% CI 10.17 to 27.43, P value < 0.0001; moderate quality evidence).

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