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Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns

Abstract

Background

The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD).

Methods

A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks’ gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization.

Results

Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks’ 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD.

Conclusions

We find no support for an increased risk of BPD with iron supplementation.

Trial registration number

NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273

Impact

  • Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants.

  • For 24–27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.

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Fig. 1: The relationship between iron exposure in the first 28 days and diagnosis of bronchopulmonary dysplasia (BPD) at 36 weeks’.
Fig. 2: Variation in enteral iron exposure in the first 28 days by recruitment site.

Data availability

The datasets analyzed for this study are available through the NINDS Archived Clinical Research Datasets at https://www.ninds.nih.gov/Current-Research/Research-Funded-NINDS/Clinical-Research/Archived-Clinical-Research-Datasets.

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Funding

This work was funded by NINDS U01NS077955 and U01NS077953.

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Contributions

M.R.G. contributed to study conception and design, interpretation of data, drafting the article, revising it critically for important intellectual content, and final approval of the version to be published. B.A.C. substantially contributed to study design, acquisition of data, analysis of data, interpretation of data, revising the article critically for important intellectual content, and final approval of the version to be published. R.M.P., V.N.T., and C.D.J. substantially contributed to study conception and design, interpretation of data, revising the article critically for important intellectual content, and final approval of the version to be published. M.K.G., R.R., and S.E.J. substantially contributed to study conception and design, acquisition of data, interpretation of data, revising the article critically for important intellectual content, and final approval of the version to be published. S.E.M. substantially contributed to study design, analysis and interpretation of data, revising the article critically for important intellectual content, and final approval of the version to be published. K.A.A. substantially contributed to study conception and design, acquisition of data, interpretation of data, drafting the article, revising the article critically for important intellectual content, and final approval of the version to be published.

Corresponding author

Correspondence to Kaashif A. Ahmad.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Added individual patient consent was not required for this study, which utilized deidentified patient data. All patient families consented for enrollment in the PENUT Trial. Patient consent was obtained for the original PENUT Trial enrollment but was not required for this secondary study.

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Garcia, M.R., Comstock, B.A., Patel, R.M. et al. Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns. Pediatr Res (2022). https://doi.org/10.1038/s41390-022-02160-2

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