Enteral iron supplementation in preterm and low birth weight infants

This review examined whether providing iron supplementation is beneficial for preterm and low birth weight infants. The potential benefits included improvements in the level of red blood cells and stored iron in their blood. In the longer term, it was thought that iron supplementation might improve the babies' growth and development. We identified 25 randomised controlled trials (RCTs) which were relevant to this topic. We concluded that the long term benefits of iron supplementation for preterm and low birth weight babies remain uncertain. Regarding red blood cell and iron levels, it was found that in the first year of life, after two months of age, iron supplementation may result in slightly higher iron stores and red blood cell levels, and lower rates of iron deficiency anaemia. However, there was a lot of variability between different studies. More RCTs are needed, using well defined patient groups.

Authors' conclusions: 

The available data suggest that infants who receive iron supplementation have a slightly higher haemoglobin level, improved iron stores and a lower risk of developing iron deficiency anaemia when compared with those who are unsupplemented. However, it is unclear whether iron supplementation in preterm and low birth weight infants has long term benefits in terms of neurodevelopmental outcome and growth. The optimum timing and duration of iron supplementation remains unclear.

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Background: 

Preterm infants are at risk of exhausting their body iron stores much earlier than healthy term newborns. It is widespread practice to give enteral iron supplementation to preterm and low birth weight infants to prevent iron deficiency anaemia. However, it is unclear whether supplementing preterm and low birth weight infants with iron improves growth and neurodevelopment. It is suspected that excess exogenous iron can contribute to oxidative injury in preterm babies, causing or exacerbating conditions such as necrotising enterocolitis and retinopathy of prematurity. Additionally, the optimal dose and timing of commencement and cessation of iron supplementation are uncertain.

Objectives: 

To evaluate the effect of prophylactic enteral iron supplementation on growth and neurodevelopmental outcomes in preterm and low birth weight infants. The secondary objectives were to determine whether iron supplementation results in improved haematological parameters and prevents other causes of morbidity and mortality.

Search strategy: 

We used the standard search strategy of the Cochrane Neonatal Review Group. We searched Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 8), MEDLINE (1951 to August 2011), CINAHL (1982 to August 2011) and conference proceedings and previous reviews.

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-randomised trials that compared enteral iron supplementation with no iron supplementation, or different regimens of enteral iron supplementation in preterm or low birth weight infants or both.

Data collection and analysis: 

We extracted data using the standard methods of the Cochrane Neonatal Review Group. Both review authors separately evaluated trial quality and data extraction. We synthesised data using risk ratios (RRs), risk differences (RDs) and weighted mean differences (WMDs). Where data about the methodology and results or both were lacking, we made an attempt to contact the study authors for further information.

Main results: 

We included twenty-six studies (2726 infants) in the analysis. The heterogeneity of participants, methods and results precluded an extensive quantitative synthesis. Of the 21 studies comparing iron supplementation with controls, none evaluated neurodevelopmental status as an outcome. Of thirteen studies reporting at least one growth parameter as an outcome, only one study of poor quality found a significant benefit of iron supplementation. Regarding haematological outcomes, no benefit for iron supplementation was demonstrated within the first 8.5 weeks of postnatal life (16 trials), except by two poor quality studies. After this age, most studies reported a higher mean haemoglobin in iron-supplemented infants. We were only able to include a limited number of studies in a quantitative meta-analysis, which suggested the haemoglobin concentration in iron-supplemented infants was higher by about 6 g/L at six to nine months. One study comparing high dose and low dose iron supplementation monitored neurodevelopmental outcome for one year, without finding any significant difference between the groups. One study comparing early versus late commencement of iron supplementation found no difference in cognitive outcome, but an increased rate of abnormal neurological examination in the late iron group at five years of age. The studies comparing high and low doses of iron indicated that there was no discernible haematological benefit in exceeding 'standard' doses of iron (i.e. 2 mg/kg/day to 3 mg/kg/day).

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