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Enteral Iron Supplementation in Infants Born Extremely Preterm and its Positive Correlation with Neurodevelopment;
Kendell R German1, Phuong T Vu2, Bryan A Comstock2
1Department of Pediatrics, University of Washington, Seattle, WA.
Insights
Increased iron supplementation in preterm infants shows positive neurodevelopmental effects, particularly on cognitive scores. Higher iron doses may enhance outcomes, especially for infants receiving erythropoietin (Epo).
Area of Science:
- Neonatalogy
- Neurodevelopmental Pediatrics
- Pediatric Nutrition
Background:
- Premature infants are at high risk for iron deficiency, impacting neurodevelopment.
- Early iron supplementation is crucial for optimal growth and cognitive function in vulnerable infants.
- The Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT) investigated interventions for preterm infants.
Purpose of the Study:
- To determine if increased enteral iron dose is associated with improved neurodevelopmental outcomes in preterm infants.
- To analyze the relationship between iron supplementation and scores on the Bayley Scales of Infant Development, third edition (BSID-III).
- To explore potential synergistic effects of iron and erythropoietin (Epo) on neurodevelopment.
Main Methods:
- Post hoc analysis of the randomized PENUT trial, including infants born at 24-28 weeks gestation assessed at 2 years.
- Generalized estimating equations models were used to assess associations between enteral iron dose (at 60 and 90 days) and BSID-III scores.
- Analyses were adjusted for potential confounding factors to ensure robust findings.
Main Results:
- A significant positive association was observed between iron dose at 60 days and BSID-III cognitive scores (0.77 points per 50 mg/kg increase, P=.03).
- Higher iron doses showed trends towards improved motor and language scores, though not statistically significant.
- Infants treated with erythropoietin (Epo) demonstrated a consistently greater effect size regarding iron supplementation and neurodevelopmental outcomes.
Conclusions:
- Increased iron supplementation at 60 days is associated with enhanced cognitive outcomes in preterm infants.
- The findings suggest potential neuroprotective benefits of higher iron doses in this population.
- Erythropoietin (Epo) treatment may potentiate the positive neurodevelopmental effects of iron supplementation in preterm infants.
Objectives:
To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development, third edition (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT).
Study Design:
This is a post hoc analysis of a randomized trial that enrolled infants born at 24-28 completed weeks of gestation. All infants in PENUT who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders.
Results:
In total, 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged from 0 to 14.7 mg/kg/d (IQR 2.1-5.8 mg/kg/d) at day 60, with a mean of 3.6 mg/kg/d in infants treated with placebo and 4.8 mg/kg/d in infants treated with Epo. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Greater iron doses were associated with greater motor and language scores but did not reach statistical significance. Results at 90 days were not significant. The effect size in the infants treated with Epo compared with placebo was consistently greater.
Conclusions:
A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in infants born preterm, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo.
Trial Registration:
Clinicaltrials.gov: NCT01378273.
