Risk Factors for 30-day Mortality in Patients with Surgically Treated Necrotizing Enterocolitis: A Multicenter Retrospective Cohort Study

Abstract

Purpose

Necrotizing enterocolitis (NEC) is a leading cause of death in very preterm born infants. The most severe variant is NEC totalis (NEC-T), where necrosis of the small intestines is so extensive that curative care is often withdrawn. Mortality and NEC-T are difficult to predict before surgery, complicating counseling and decision-making. This study's aim was to identify preoperative risk factors for overall 30-day mortality and NEC-T in preterm born infants with surgical NEC.

Methods

This multicenter retrospective cohort study included preterm born infants (<35 weeks) surgically treated for NEC between 2008 and 2022. NEC-T was defined as necrosis of the majority of small intestine, leading to a surgical open-close procedure without curative treatment. Preoperative risk factors for 30-day postoperative mortality, NEC-T, and mortality without NEC-T were assessed using multivariable logistic regression analyses.

Results

Among the 401 patients included, the 30-day mortality rate was 34.2% (137/401), of which 18.7% (75/401) involved NEC-T. Significant risk factors for mortality were male sex (odds ratio [OR]: 2.53; 95% confidence interval [CI]: 1.54–4.16), lower birthweight (OR: 0.91; 95% CI: 0.86–0.96/100 g), portal venous gas (PVG) on abdominal radiograph (OR: 1.89; 95% CI: 1.11–3.20), need for cardiovascular support between NEC diagnosis and surgery (OR: 3.26; 95% CI: 2.02–5.24), and shorter time between diagnosis and surgery (OR: 0.74; 95% CI: 0.65–0.84). Similar risk factors were found for NEC-T. In patients without NEC-T, the need for cardiovascular support (OR: 2.33; 95% CI: 1.33–4.09) and time between diagnosis and surgery (OR: 0.77; 95% CI: 0.64–0.91) were significant.

Conclusion

Male sex, lower birthweight, PVG, cardiovascular support, and a short interval between NEC diagnosis and surgery are preoperative risk factors for 30-day mortality and NEC-T. Preoperative cardiovascular support and a shorter time interval between diagnosis and surgery are also risk factors for mortality without NEC-T.

Level of evidence

II

Keywords

NEC totalis - portal venous gas - neonates - cardiovascular support

^* These authors contributed equally.

Publikationsverlauf

Eingereicht: 05. September 2024

Angenommen: 09. Februar 2025

Artikel online veröffentlicht:
21. März 2025

• References

• 1 Alsaied A, Islam N, Thalib L. Global incidence of necrotizing enterocolitis: a systematic review and meta-analysis. BMC Pediatr 2020; 20 (01) 344
• 2 Jones IH, Hall NJ. Contemporary outcomes for infants with necrotizing enterocolitis-a systematic review. J Pediatr 2020; 220: 86-92.e3
• 3 Zozaya C, García González I, Avila-Alvarez A. et al. Incidence, treatment, and outcome trends of necrotizing enterocolitis in preterm infants: a multicenter cohort study. Front Pediatr 2020; 8: 188
• 4 Murthy K, Yanowitz TD, DiGeronimo R. et al. Short-term outcomes for preterm infants with surgical necrotizing enterocolitis. J Perinatol 2014; 34 (10) 736-740
• 5 Golubkova A, Hunter CJ. Updates and recommendations on the surgical management of NEC. Semin Perinatol 2023; 47 (01) 151698
• 6 Shi B, Shen L, Huang W. et al. A nomogram for predicting surgical timing in neonates with necrotizing enterocolitis. J Clin Med 2023; 12 (09) 3062
• 7 Samuels N, van de Graaf RA, de Jonge RCJ, Reiss IKM, Vermeulen MJ. Risk factors for necrotizing enterocolitis in neonates: a systematic review of prognostic studies. BMC Pediatr 2017; 17 (01) 105
• 8 Hull MA, Fisher JG, Gutierrez IM. et al. Mortality and management of surgical necrotizing enterocolitis in very low birth weight neonates: a prospective cohort study. J Am Coll Surg 2014; 218 (06) 1148-1155
• 9 Holman RC, Stoll BJ, Clarke MJ, Glass RI. The epidemiology of necrotizing enterocolitis infant mortality in the United States. Am J Public Health 1997; 87 (12) 2026-2031
• 10 Bhatt D, Travers C, Patel RM. et al. Predicting mortality or intestinal failure in infants with surgical necrotizing enterocolitis. J Pediatr 2017; 191: 22-27.e3
• 11 Olthuis AJ, Jaarsma CVHAS. Necrotiserende enterocolitis; 2014. Accessed at: https://www.neonatology.eu/sites/default/files/nec.pdf
• 12 Fenton TR, Kim JH. A systematic review and meta-analysis to revise the Fenton growth chart for preterm infants. BMC Pediatr 2013; 13: 59
• 13 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92 (04) 529-534
• 14 Walsh MC, Kliegman RM. Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin North Am 1986; 33 (01) 179-201
• 15 Pumberger W, Mayr M, Kohlhauser C, Weninger M. Spontaneous localized intestinal perforation in very-low-birth-weight infants: a distinct clinical entity different from necrotizing enterocolitis. J Am Coll Surg 2002; 195 (06) 796-803
• 16 Rose AT, Zaniletti I, Santore MT, Piazza AJ. Characteristics and outcomes of a multi-institution cohort of infants with necrotizing enterocolitis totalis. J Perinatol 2022; 42 (04) 440-445
• 17 Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39 (12) 1890-1900
• 18 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. Crit Care Med 1992; 20 (06) 864-874
• 19 Tennant PWG, Murray EJ, Arnold KF. et al. Use of directed acyclic graphs (DAGs) to identify confounders in applied health research: review and recommendations. Int J Epidemiol 2021; 50 (02) 620-632
• 20 Guthrie SO, Gordon PV, Thomas V, Thorp JA, Peabody J, Clark RH. Necrotizing enterocolitis among neonates in the United States. J Perinatol 2003; 23 (04) 278-285
• 21 Thyoka M, de Coppi P, Eaton S. et al. Advanced necrotizing enterocolitis part 1: mortality. Eur J Pediatr Surg 2012; 22 (01) 8-12
• 22 Calvert W, Sampat K, Jones M, Baillie C, Lamont G, Losty PD. Necrotising enterocolitis-A 15-year outcome report from a UK specialist centre. Acta Paediatr 2021; 110 (02) 495-502
• 23 Carter BM, Holditch-Davis D. Risk factors for necrotizing enterocolitis in preterm infants: how race, gender, and health status contribute. Adv Neonatal Care 2008; 8 (05) 285-290
• 24 Llanos AR, Moss ME, Pinzòn MC, Dye T, Sinkin RA, Kendig JW. Epidemiology of neonatal necrotising enterocolitis: a population-based study. Paediatr Perinat Epidemiol 2002; 16 (04) 342-349
• 25 Guner YS, Friedlich P, Wee CP, Dorey F, Camerini V, Upperman JS. State-based analysis of necrotizing enterocolitis outcomes. J Surg Res 2009; 157 (01) 21-29
• 26 Boghossian NS, Geraci M, Edwards EM, Horbar JD. Sex differences in mortality and morbidity of infants born at less than 30 weeks' gestation. Pediatrics 2018; 142 (06) e20182352
• 27 van Westering-Kroon E, Huizing MJ, Villamor-Martínez E, Villamor E. Male disadvantage in oxidative stress-associated complications of prematurity: a systematic review, meta-analysis and meta-regression. Antioxidants 2021; 10 (09) 1490
• 28 Chen S, Hu Y, Liu Q, Li X, Wang H, Wang K. Comparison of abdominal radiographs and sonography in prognostic prediction of infants with necrotizing enterocolitis. Pediatr Surg Int 2018; 34 (05) 535-541
• 29 Cuna AC, Reddy N, Robinson AL, Chan SS. Bowel ultrasound for predicting surgical management of necrotizing enterocolitis: a systematic review and meta-analysis. Pediatr Radiol 2018; 48 (05) 658-666
• 30 Bohnhorst B. Usefulness of abdominal ultrasound in diagnosing necrotising enterocolitis. Arch Dis Child Fetal Neonatal Ed 2013; 98 (05) F445-F450
• 31 Sharma R, Tepas III JJ, Hudak ML. et al. Portal venous gas and surgical outcome of neonatal necrotizing enterocolitis. J Pediatr Surg 2005; 40 (02) 371-376
• 32 Bonasso PC, Dassinger MS, Ryan ML, Gowen MS, Burford JM, Smith SD. 24-hour and 30-day perioperative mortality in pediatric surgery. J Pediatr Surg 2019; 54 (04) 628-630
• 33 Thompson A, Bizzarro M, Yu S, Diefenbach K, Simpson BJ, Moss RL. Risk factors for necrotizing enterocolitis totalis: a case-control study. J Perinatol 2011; 31 (11) 730-738
• 34 Dukleska K, Devin CL, Martin AE. et al. Necrotizing enterocolitis totalis: high mortality in the absence of an aggressive surgical approach. Surgery 2019; 165 (06) 1176-1181
• 35 Voss M, Moore SW, van der Merwe I, Pieper C. Fulminating necrotising enterocolitis: outcome and prognostic factors. Pediatr Surg Int 1998; 13 (08) 576-580
• 36 Belza C, Wales PW. Impact of multidisciplinary teams for management of intestinal failure in children. Curr Opin Pediatr 2017; 29 (03) 334-339
• 37 Lacaille F, Boluda ER, Gupte G. et al. Indications and successes of intestinal transplantation in children in the 21st century: a retrospective cohort study. Clin Nutr ESPEN 2024; 62: 247-252
• 38 Imren C, Vlug LE, de Koning BAE. et al. Necrotizing enterocolitis in a Dutch cohort of very preterm infants: prevalence, mortality, and long-term outcomes. Eur J Pediatr Surg 2022; 32 (01) 111-119