Necrotizing enterocolitis and high intestinal iron uptake due to genetic variants

Pediatr Res. 2018 Jan;83(1-1):57-62. doi: 10.1038/pr.2017.195. Epub 2017 Sep 13.


BackgroundIntestinal 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.MethodsPreterm 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.ResultsComplete 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.ConclusionPolymorphisms inducing lower intestinal iron uptake like the rs855791 A-allele might be an underestimated risk factor for NEC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Enterocolitis, Necrotizing / genetics*
  • Enterocolitis, Necrotizing / metabolism*
  • Follow-Up Studies
  • Genetic Variation
  • Genotype
  • Germany / epidemiology
  • Hemochromatosis Protein / genetics
  • Humans
  • Infant, Newborn
  • Infant, Premature
  • Intestinal Perforation / epidemiology
  • Iron / blood
  • Iron / metabolism*
  • Iron / pharmacokinetics*
  • Membrane Proteins / genetics
  • Mendelian Randomization Analysis
  • Microbiota
  • Polymorphism, Single Nucleotide
  • Regression Analysis
  • Risk Factors
  • Serine Endopeptidases / genetics


  • HFE protein, human
  • Hemochromatosis Protein
  • Membrane Proteins
  • Iron
  • Serine Endopeptidases
  • TMPRSS6 protein, human