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Iron supplementation in preterm and low-birth-weight infants: a systematic review of intervention studies
Elaine K McCarthy1,2, Eugene M Dempsey1,3, Mairead E Kiely1,2
1INFANT Research Centre, University College Cork, Cork, Republic of Ireland.
Insights
Enteral iron supplementation improves iron status and reduces anemia in preterm infants. However, more research is needed on long-term effects and optimal dosing for infant health.
Area of Science:
- Neonatal nutrition and development
- Pediatric hematology
- Evidence-based medicine
Background:
- Current enteral iron supplementation guidelines for preterm infants (born <37 weeks' gestation) and low-birth-weight (LBW, <2500g) infants are outdated (2010) and based on limited evidence.
- Optimizing iron intake is crucial for growth and development while avoiding iron overload in vulnerable infants.
Purpose of the Study:
- To systematically review the effects of enteral iron supplementation on iron status, growth, neurological development, and clinical outcomes in preterm and LBW infants.
- To identify gaps in the evidence and inform future research directions.
Main Methods:
- A systematic review of randomized controlled trials (RCTs) and nonrandomized interventions was conducted.
- Searches of PubMed/Medline and Cochrane Library databases were performed up to October 31, 2018.
- Study quality was assessed using Cochrane Collaboration's criteria.
Main Results:
- Supplementation for ≥8 weeks improved hemoglobin and ferritin levels, reducing iron deficiency and anemia.
- No studies reported on iron overload.
- Growth parameters were unaffected; one RCT suggested a positive effect on behavior at 3.5 and 7 years.
- No significant associations were found with adverse clinical outcomes.
Conclusions:
- Long-term enteral iron supplementation benefits iron status in preterm and LBW infants.
- High-quality evidence on long-term functional health outcomes and iron overload is lacking.
- Well-designed, dose-response RCTs are needed to determine optimal iron provision strategies.
Context:
Enteral iron supplementation in preterm infants is recommended to supply sufficient iron for growth and development without increasing the risk of iron overload. However, the current recommendations date from 2010 and are based on limited evidence.
Objective:
This systematic review aimed to investigate the effects of enteral iron supplementation on iron status, growth, neurological development, and adverse clinical outcomes in preterm (<37 weeks' gestation) and low-birth-weight (LBW, <2500 g) infants.
Data Sources:
The PubMed/Medline and Cochrane Library databases were searched to 31 October 2018.
Data Extraction:
Of the 684 records identified, 27 articles, describing 18 randomized controlled trials (RCTs) plus 4 nonrandomized interventions, were included. Using the Cochrane Collaboration's criteria, study quality was found to be poor to fair overall.
Results:
Most articles (23/27) reported iron status indices; supplementation for ≥8 weeks resulted in increased hemoglobin and ferritin concentrations and a reduction in iron deficiency and anemia. No article reported on iron overload. Growth-related parameters reported in 12 articles were not affected by supplementation. Among the 7 articles on neurological development, a positive effect on behavior at 3.5 and 7 years was observed in one Swedish RCT. No association was found between supplementation and adverse clinical outcomes in the 9 articles reporting on studies in which such data was collected.
Conclusions:
Long-term iron supplementation appears to result in improved iron status and a reduction in iron deficiency and anemia in preterm and LBW infants. However, high-quality evidence regarding the long-term effects of supplementation on functional health outcomes is lacking. Iron overload has largely been ignored. Well-designed, long-term, dose-response RCTs are required to ascertain the optimal dose and delivery method for the provision of dietary iron in preterm infants, with consideration of short- and long-term health effects.
Systematic Review Registration:
PROSPERO registration no. CRD42018085214.
