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. 2025 Nov 10.
doi: 10.1038/s41390-025-04536-6. Online ahead of print.

Genetic susceptibility to necrotizing enterocolitis in very preterm infants: evidence from twin data

Ruimiao Bai #  1   2 , Xiang Chen #  3 , Siyuan Jiang  1   4 , Yan Mo  5 , Aimin Qian  6 , Yun Cao  1   4 , Lizhong Du  7   8 , Shoo Kim Lee  9   10 , LiYuan Hu  1 , Jie Yang  4 , Yajun Li  2 , Xiaoping Lei  11 , Lijuan Luo  12 , Wenhao Zhou  13 ; Chinese Neonatal Network
Collaborators, Affiliations

Genetic susceptibility to necrotizing enterocolitis in very preterm infants: evidence from twin data

Ruimiao Bai et al. Pediatr Res. .

Abstract

Background: Necrotising enterocolitis (NEC) is a significant complication for very preterm infants (VPIs). The role of genetic predisposition in the development of NEC among VPIs has not been firmly established. This study aimed to explore the heritability factors in NEC among VPIs.

Methods: A retrospective cohort study was conducted on 4138 infants from 2069 twin pairs. Twins were categorised based on chorionicity.Chi-square analyses were conducted to compare the incidence of NEC between monochorionic and dichorionic twin pairs. The Pearson chi-square test and ACE modelling appropriate for analysing twin cohorts were utilised. Stratified analyses were conducted for early-onset and late-onset NEC, surgical NEC, and NEC in different gestational age groups.

Results: The overall incidence of NEC was 5%. No significant difference was observed between monochorionic and dichorionic twins. ACE modelling revealed no contribution of heritability to NEC risk (% A = 0.00%, 95% CI [0.00%, 0.07%]). Stratified analyses for early-onset and late-onset NEC, surgical NEC, and NEC in different gestational age groups (GA < 28 weeks and 28+0-31+6 weeks) also revealed no significant heritability.

Conclusion: Our findings suggest that, under the current conditions of medical practice, heritability does not play a major role in the development of NEC.

Impact: NEC is a significant and potentially life-threatening complication in very preterm infants (VPIs). Previous studies have suggested a potential genetic susceptibility to NEC, although the evidence has been inconsistent. Genetic heritability does not play a major role in the development of NEC. Stratified analyses for early-onset and late-onset NEC, surgical NEC, and different gestational age groups also confirmed the lack of significant genetic influence. Our findings suggest that attention should be given to the risk factors contributing to the occurrence of NEC and that efforts should be made to improve the level of clinical treatment.

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Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

    1. Battersby, C., Longford, N., Mandalia, S., Costeloe, K. & Modi, N. Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012-13: a whole-population surveillance study. Lancet Gastroenterol. Hepatol. 2, 43–51 (2017). - DOI - PubMed
    1. Zhu, Z. et al. Mortality and morbidity of infants born extremely preterm at tertiary medical centers in China from 2010 to 2019. JAMA Netw. Open 4, e219382 (2021). - DOI - PubMed - PMC
    1. Cao, Y. et al. Assessment of neonatal intensive care unit practices, morbidity, and mortality among very preterm infants in China. JAMA Netw. Open 4, e2118904 (2021). - DOI - PubMed - PMC
    1. Cao, X. et al. Epidemiology of necrotizing enterocolitis in preterm infants in China: a multicenter cohort study from 2015 to 2018. J. Pediatr. Surg. 57, 382–386 (2022). - DOI - PubMed
    1. Bell, E. F. et al. Mortality, in-hospital morbidity, care practices, and 2-year outcomes for extremely preterm infants in the US, 2013-2018. JAMA 327, 248–263 (2022). - DOI - PubMed

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