Callaghan, W. M., MacDorman, M. F., Rasmussen, S. A., Qin, C. & Lackritz, E. M. The contribution of preterm birth to infant mortality rates in the United States. Pediatrics 118, 1566–1573 (2006).

Article  PubMed  Google Scholar 

Bell, M. J. et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann. Surg. 187, 1–7 (1978).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jones, I. H. & Hall, N. J. Contemporary outcomes for infants with necrotizing enterocolitis — a systematic review. J. Pediatr. 220, 86–92.e3 (2020).

Article  PubMed  Google Scholar 

Battersby, C., Santhalingam, T., Costeloe, K. & Modi, N. Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review. Arch. Dis. Child. Fetal Neonatal Ed. 103, F182–F189 (2018). This paper is a systematic review of NEC incidence in high-income countries, including 14 studies from 12 countries in the final analysis, which found a difference in the reported rate of NEC ranging from 2% to 7% among babies born before 32 weeks’ gestation and from 5% to 22% in those with a birth weight below 1,000 g.

Article  PubMed  Google Scholar 

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).

Article  PubMed  Google Scholar 

Alsaied, A., Islam, N. & Thalib, L. Global incidence of necrotizing enterocolitis: a systematic review and meta-analysis. BMC Pediatr. 20, 344 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Tsigkos, S. et al. Establishing rarity in the context of orphan medicinal product designation in the European Union. Drug Discov. Today 23, 681–686 (2018).

Article  PubMed  Google Scholar 

Ahle, M., Drott, P. & Andersson, R. E. Epidemiology and trends of necrotizing enterocolitis in Sweden: 1987–2009. Pediatrics 132, e443–e451 (2013).

Article  PubMed  Google Scholar 

Scheese, D. et al. Cytomegalovirus worsens necrotizing enterocolitis severity in mice via increased Toll-like receptor 4 signaling. Cell Mol. Gastroenterol. Hepatol. 19, 101473 (2025).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mani, S. et al. Viral infections and neonatal necrotizing enterocolitis: a meta-analysis. Pediatrics 152, e2022060876 (2023).

Article  PubMed  Google Scholar 

Garg, P. M. et al. Incomplete resection of necrotic bowel may increase mortality in infants with necrotizing enterocolitis. Pediatr. Res. 89, 163–170 (2021).

Article  PubMed  Google Scholar 

Garg, P. M., Hitt, M. M., Blackshear, C. & Maheshwari, A. Clinical determinants of postoperative outcomes in surgical necrotizing enterocolitis. J. Perinatol. 40, 1671–1678 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Remon, J. et al. Acute drop in blood monocyte count differentiates NEC from other causes of feeding intolerance. J. Perinatol. 34, 549–554 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Remon, J. I. et al. Depth of bacterial invasion in resected intestinal tissue predicts mortality in surgical necrotizing enterocolitis. J. Perinatol. 35, 755–762 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Patel, R. M. et al. Causes and timing of death in extremely premature infants from 2000 through 2011. N. Engl. J. Med. 372, 331–340 (2015).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bernstein, I. M., Horbar, J. D., Badger, G. J., Ohlsson, A. & Golan, A. Morbidity and mortality among very-low-birth-weight neonates with intrauterine growth restriction. Am. J. Obstet. Gynecol. 182, 198–206 (2000).

Article  CAS  PubMed  Google Scholar 

Rose, A. T. & Patel, R. M. A critical analysis of risk factors for necrotizing enterocolitis. Semin. Fetal Neonatal Med. 23, 374–379 (2018). This paper reveals that among a number of associations, growth restriction is the most consistent endogenous infant factor reported to affect NEC incidence; that antenatal glucocorticoids, progesterone, postnatal erythropoietin, lactoferrin, fluid restriction, arginine, human milk and probiotics may reduce risk; and that lower oxygen saturation targets and sepsis, and formula may increase risk.

Article  PubMed  PubMed Central  Google Scholar 

McGoldrick, E., Stewart, F., Parker, R. & Dalziel, S. R. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst. Rev. https://doi.org/10.1002/14651858.CD004454.pub4 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Jammeh, M. L. et al. Racial/ethnic differences in necrotizing enterocolitis incidence and outcomes in premature very low birth weight infants. J. Perinatol. 38, 1386–1390 (2018). This paper reveals differences in NEC incidence and severity between racial groups, and identifies a higher incidence in infants of Black African ancestry.

Article  PubMed  Google Scholar 

Seeman, S. M., Mehal, J. M., Haberling, D. L., Holman, R. C. & Stoll, B. J. Infant and maternal risk factors related to necrotising enterocolitis-associated infant death in the United States. Acta Paediatr. 105, e240–e246 (2016).

Article  PubMed  Google Scholar 

Filias, A. et al. Phagocytic ability of neutrophils and monocytes in neonates. BMC Pediatr. 11, 29 (2011).

Article  PubMed  PubMed Central  Google Scholar 

Melvan, J. N., Bagby, G. J., Welsh, D. A., Nelson, S. & Zhang, P. Neonatal sepsis and neutrophil insufficiencies. Int. Rev. Immunol. 29, 315–348 (2010).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Nowicki, P. T. Ischemia and necrotizing enterocolitis: where, when, and how. Semin. Pediatr. Surg. 14, 152–158 (2005).

Article  PubMed  Google Scholar 

Nankervis, C. A., Giannone, P. J. & Reber, K. M. The neonatal intestinal vasculature: contributing factors to necrotizing enterocolitis. Semin. Perinatol. 32, 83–91 (2008).

Article  PubMed  Google Scholar 

Harris, M. C. et al. Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis. J. Pediatr. 124, 105–111 (1994).

Article  CAS  PubMed  Google Scholar 

Kovler, M. L., Sodhi, C. P. & Hackam, D. J. Precision-based modeling approaches for necrotizing enterocolitis. Dis. Model. Mech. 13, dmm044388 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Elgin, T. G., Kern, S. L. & McElroy, S. J. Development of the neonatal intestinal microbiome and its association with necrotizing enterocolitis. Clin. Ther. 38, 706–715 (2016).

Article  CAS  PubMed  Google Scholar 

Sampah, M. E. S. & Hackam, D. J. Prenatal immunity and influences on necrotizing enterocolitis and associated neonatal disorders. Front. Immunol. 12, 650709 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lu, P. et al. Animal models of gastrointestinal and liver diseases. Animal models of necrotizing enterocolitis: pathophysiology, translational relevance, and challenges. Am. J. Physiol. Gastrointest. Liver Physiol. 306, G917–G928 (2014).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Warner, B. B. et al. Gut bacteria dysbiosis and necrotising enterocolitis in very low birthweight infants: a prospective case-control study. Lancet 387, 1928–1936 (2016).

Article  PubMed  PubMed Central  Google Scholar 

Pammi, M. et al. Intestinal dysbiosis in preterm infants preceding necrotizing enterocolitis: a systematic review and meta-analysis. Microbiome 5, 31 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Wala, S. J. et al. Superior performance of biofilm versus planktonic Limosilact