Abstract
Background
Intestinal iron is a nutritional compound, which is essential for enteric microbiota. We evaluated the hypothesis that polymorphisms, which are known modifiers of intestinal iron uptake in adults, are associated with necrotizing enterocolitis (NEC) in preterm infants.
Methods
Preterm infants (birth weight below 1,500 g) were studied. Single-nucleotide polymorphisms with known effects on serum iron levels (rs1800562, rs1799945, and rs855791) were determined using PCR. The effects of polymorphisms on NEC surgery were tested by Mendelian randomization. Outcome data were compared with χ2-test, Fisher’s exact test, t-test, and Cochran–Armitage test for trend and multiple logistic regression analysis.
Results
Complete genotyping data were available for 11,166 infants. High serum iron levels due to rs855791 genotype were associated with a significantly reduced risk of NEC surgery (odds ratio (OR) 0.265; 95% confidence interval (CI) 0.11–0.65; adjusted P=0.011). Carriers of the rs855791 A-allele not receiving prophylactic probiotics had a higher risk of NEC surgery (OR 1.12, 95% CI 1.08–1.70, nominal P=0.002). Prophylactic treatment with probiotics was associated with a reduced risk of NEC surgery in carriers of the rs855791 A-Allele. No differences were found with regard to other short- or long-term outcome data.
Conclusion
Polymorphisms inducing lower intestinal iron uptake like the rs855791 A-allele might be an underestimated risk factor for NEC.
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Acknowledgements
We thank all infants and their parents who participated. We also thank each neonatal unit and its staff for helping us with the study. We are grateful to Greco M. for providing the code for the Mendelian randomization analysis that they used in their own analysis.
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This study was funded by the German Federal Ministry of Education and Research (BMBF 01ER0805 and BMBF 01ER1501). A.Z. acknowledges funding from the German Research Foundation (Research Unit ProtectMove, FOR 2488).
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Orlikowsky T. (Aachen); Wieg C. (Aschaffenburg); Rossi R. (Berlin); Weller U. (Bielefeld); Teig N. (Bochum); Hepping N. (Bonn); Körner T. (Bremen); Gerleve H. (Coesfeld); Roll C. (Datteln); Brune T. (Detmold); Heitmann F. (Dortmund); Rüdiger M. (Dresden); Höhn T. (Düsseldorf); Andree Berghäuser M. (Düsseldorf); Felderhoff-Müser U. (Essen); Reese J. (Eutin); Dördelmann M. (Flensburg); Ehlers S. (Frankfurt); Hentschel R. (Freiburg); Küster H. (Göttingen); Linnemann K. (Greifswald); Haase R. (Halle-Saale); v.d.Wense Axel (Hamburg); Schmidkte S. (Hamburg); Guthmann F. (Hannover); Jensen R. (Heide); Gortner L. (Homburg); Hillebrand G. (Itzehoe); Dawczynski K. (Jena); Müller D. (Kassel); Bendiks M. (Kiel); Kribs A. (Köln); Böckenholt K. (Köln); Gebauer C. (Leipzig); Eichhorn J.G. (Leverkusen); Böttger R. (Magdeburg); Schaible T. (Mannheim); Wintgens J. (Mönchengladbach); Hörnig-Franz I. (Münster); Urlichs F. (Münster); Seeliger S. (Neuburg/Donau); Schäfer S. (Nürnberg); Segerer H. (Regensburg); Olbertz D. (Rostock); Möller J. (Saarbrücken); Kannt O. (Schwerin); Hubert M. (Siegen); Vochem M. (Stuttgart); Heldmann M. (Wuppertal).
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Göpel, W., Drese, J., Rausch, T. et al. Necrotizing enterocolitis and high intestinal iron uptake due to genetic variants. Pediatr Res 83, 57–62 (2018). https://doi.org/10.1038/pr.2017.195
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DOI: https://doi.org/10.1038/pr.2017.195
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