Experimental studies on risk factors of necrotizing enterocolitis

Cover Page


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Introduction. Necrotizing enterocolitis (NEC) is one of the most life-threatening conditions in the neonatal period. This disease is considered to be polyethiological one; however, the pattern of NEC pathogenesis is not clear yet. The aim of the present research is to study in details NEC risk factors and pathogenetic mechanisms in experiment.
Material and methods. NEC was induced in 28 rat pups (breed: Wistar). Newborn animals (21-day gestation age) were labored from three female rats aged 9-12 months. In the research, the experimental animals were induced: hypoxia, inadequate formula feeding and bacterial contamination. The observation period lasted for 96 hours; the obtained results were assessed by the following criteria: clinical symptoms, mortality, intraoperative findings, histological findings and microbiological spectrum.
Results. NEC clinical signs were seen both in subgroup 1A (animals had hypoxia and inadequate formula feeding) and in subgroup 1B (additionally, animals had microbial contamination). Clinical and morphological findings were more pronounced in subgroup 1B. Mortality in subgroup 1B was 50%. The histological picture in subgroup 1A corresponded to that of NEC stage 1A-2A and in subgroup 1B – to NEC stage 2B–3B (by Walsh and Kliegmann). In subgroup 1B, there was a massive intestinal colonization in the intestinal lumen.
Conclusion. Hypoxia and inadequate formula feeding are, as such, risk factors of necrotizing enterocolitis. Additionally, bacterial aggression significantly worsens the course of necrotizing enterocolitis and its prognosis. However, the lack of bacterial component does not rule out NEC onset in newborns.

About the authors

T. A. Zebrova

Samara State Medical University

Author for correspondence.
Email: zebryonok5292@yandex.ru
ORCID iD: 0000-0001-8028-8945

Tatiana A. Zebrova, assistant of the chair of pediatric surgery

443099, Samara

Россия

M. A. Barskaya

Samara State Medical University

Email: fake@neicon.ru
ORCID iD: 0000-0002-7069-7267

443099, Samara

Россия

I. I. Kozin

Samara State Medical University

Email: fake@neicon.ru
ORCID iD: 0000-0001-9583-4013

443099, Samara

Россия

S. V. Poletayeva

Samara State Medical University

Email: fake@neicon.ru
ORCID iD: 0000-0001-8433-9068

443099, Samara

Россия

A. V. Lyamin

Samara State Medical University

Email: fake@neicon.ru
ORCID iD: 0000-0002-5905-1895

443099, Samara

Россия

T. K. Ustinova

Samara State Medical University

Email: fake@neicon.ru
ORCID iD: 0000-0001-8400-7151

443099, Samara

Россия

References

  1. Uauy R.D., Fanaroff A.A., Korones S.B., Elizabeth A., Philips J.B., Wright L.L. Necrotizing enterocolitis in very low birth weightinfants: Biodemographic and clinical correlates. J Pediatr. 1991; 119(4): 630–8.
  2. Hack M., Wright L.L., Shankaran S., Tyson J.E., Horbar J.D., Bauer C.R., et al. of Child Health and Human Development Neonatal. Am J Obs Gynecol. 1995; 172(2): 457–64.
  3. Sankaran K., Puckett B., Lee D.S.C., Seshia M., Boulton J., Qiu Z., et al. Variations in Incidence of Necrotizing Enterocolitis in Canadian Neonatal Intensive Care Units. J Pediatr Gastroenterol Nutr. 2004; 39(4): 366–72.
  4. Lin P.W., Stoll B.J. Necrotising enterocolitis. Lancet. 2006; 368(7): 1271–83.
  5. Schnabl K.L., Van Aerde J.E., Thomson A.B.R., Clandinin M.T. Necrotizing enterocolitis: A multifactorial disease with no cure. World J Gastroenterol. 2008; 14(14): 2142–61.
  6. Ou J., Courtney C.M., Steinberger A.E., Tecos M.E., Warner B.W. Nutrition in necrotizing enterocolitis and following intestinal resection. Nutrients. 2020; 520(12): 1–16.
  7. Lloyd J.R. The etiology of gastrointestinal perforations in the newborn. J Pediatr Surg. 1969; 4(1): 77–84.
  8. Caplan M.S., Jilling T. New concepts in necrotizing enterocolitis Early diagnosis. Curr Opin Pediatr. 2001; 13(2):111–5.
  9. Подкаменев В.В., Протопопова Н.В., Подкаменев А.В. Факторы риска язвенно-некротического энтероколита у новорождённых. Вопросы диагностики в педиатрии. 2009; 1(6): 53–8. https://www.elibrary.ru/item.asp?id=14628381
  10. Papillon S., Castle S.L., Gayer C.P., Ford H.R. Necrotizing enterocolitis: Contemporary management and outcomes. Adv Pediatr [Internet]. 2013; 60(1): 263–79. https://doi.org/10.1016/j.yapd.2013.04.011
  11. Miller M.J.S., Adams J., Gu X., Zhang X.J., Clark D.A. Hemodynamic and permeability characteristics of acute experimental necrotizing enterocolitis. Dig Dis Sci. 1990; 35(10): 1257–64.
  12. Neu J. The “myth” of asphyxia and hypoxia-ischemia as primary causes of necrotizing enterocolitis. Biol Neonate. 2005; 87(2): 97–8.
  13. Meister A.L., Doheny K.K., Travagli R.A. Necrotizing enterocolitis: It’s not all in the gut. Exp Biol Med. 2020; 245(2): 85–95.
  14. Fu X., Li S., Jiang Y., Hu X., Wu H. Necrotizing Enterocolitis and Intestinal Microbiota: The Timing of Disease and Combined Effects of Multiple Species. Front Pediatr. 2021; 9(May): 1–10.
  15. Nino D.F., Sodhi C.P., Hackam D.J. Necrotizing enterocolitis: new insights into pathogenesis and mechanisms. Nat Rev Gastroenterol Hepatol. 2016; 13(10): 590–600.
  16. Behrman R.E., Stoll B.J., Kanto W.P., Glass R.I., Nahmias A.J., Brann A.W. Epidemiology of necrotizing enterocolitis: A case control study. J Pediatr. 1980; 96(3, Part 1): 447–51.
  17. Stoll B.J. Epidemiology of Necrotizing Enterocolitis. Clin Perinatol. 1994; 21(2): 205–18.
  18. Llanos A.R., Moss M.E., Pinzòn M.C., Dye T., Sinkin R.A., Kendig J.W. Epidemiology of neonatal necrotising enterocolitis: A population-based study. Paediatr Perinat Epidemiol. 2002; 16(4): 342–9.
  19. Guthrie S.O., Gordon P. V., Thomas V., Thorp J.A., Peabody J., Clark R.H. Necrotizing enterocolitis among neonates in the United States. J Perinatol. 2003; 23: 278–85.
  20. Hsueh W., Caplan M.S., Qu X.W., Tan X. Di, De Plaen I.G., GonzalezCrussi F. Neonatal necrotizing enterocolitis: Clinical considerations and pathogenetic concepts. Pediatr Dev Pathol. 2003; 6: 6–23.
  21. Luig M., Lui K. Epidemiology of necrotizing enterocolitis – Part II: Risks and susceptibility of premature infants during the surfactant era: A regional study. J Paediatr Child Health. 2005; 41: 174–9.
  22. Boston V.E. Necrotising enterocolitis and localised intestinal perforation: different diseases or ends of a spectrum of pathology. Pediatr Surg Int. 2006; 22: 477–84.
  23. Козлов Ю.А., Новожилов В.А., Ковальков К.А., Чубко Д.М., Барадиева П.Ж., Тимофеев А.Д. и соавт. Некротизирующий энтероколит у новорождённых. Новые взгляды и тенденции. 2016; 20(4): 188–93.
  24. Козлов Ю.А., Новожилов В.А., Ковальков К.А., Чубко Д.М., Распутин А.А., Вебер И.Н. и соавт. Хирургическое лечение некротизирующего энтероколита у недоношенных детей – результаты многоуровневого сравнения. Педиатрия. Хирургические аспекты педиатрии. 2017; 97(1): 88–95.
  25. McGuire W., Anthony M.Y. Donor human milk versus formula for preventing necrotising enterocolitis in preterm infants: Systematic review. Arch Dis Child Fetal Neonatal Ed. 2003;88(1):11–4.
  26. Ghoneim N., Bauchart-Thevret C., Oosterloo B., Stoll B., Kulkarni M., De Pipaon M.S., et al. Delayed initiation but not gradual advancement of enteral formula feeding reduces the incidence of necrotizing enterocolitis (NEC) in preterm pigs. PLoS One. 2014; 9(9): 1–12.
  27. Карпова И.Ю. Некротизирующий энтероколит у новорождённых. Автореф. дис. … д-ра мед. наук. Нижний Новгород, 2016.
  28. Samuels N., van de Graaf R.A., de Jonge R.C.J., Reiss I.K.M., Vermeulen M.J. Risk factors for necrotizing enterocolitis in neonates: A systematic review of prognostic studies. BMC Pediatr. 2017; 17(105): 1–9.
  29. Rose A.T., Patel R.M. A Critical Analysis of Risk Factors for NEC. Semin Fetal Neonatal Med. 2018; 23(6): 374–9.
  30. Карпова И.Ю., Молчанова Д.В., Ладыгина Т.М. Экспериментальное моделирование некротизирующего энтероколита: патогенез, преликторы заболевания, профилактика. Вестник экспериментальной и клинической хирургии. 2020; 13(3): 293–300.
  31. Barlow B., Santuli T. V., Heird W.C., Pitt J., Blanc W.A., Schullinger J.N. An Exparimental Study of Acute Neonatl Enterocolitis – The Importance of Breast Milk. J Pediatr Surg. 1974; IX(5): 587–95.
  32. Mendez Y.S., Khan F.A., Perrier G. Van, Radulescu A. Animal models of necrotizing enterocolitis. World J Pediatr Surg. 2020; 3(1): e000109.
  33. Bührer C., Fischer H.S., Wellmann S. Nutritional interventions to reduce rates of infection, necrotizing enterocolitis and mortality in very preterm infants. Pediatr Res [Internet]. 2020; 87: 371–7. https://dx.doi.org/10.1038/s41390-019-0630-2
  34. Neu J. Necrotizing Enterocolitis: A Multi-omic Approach and the Role of the Microbiome. Dig Dis Sci [Internet]. 2020; 65(3): 789–96. https://doi.org/10.1007/s10620-020-06104-w

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2021

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies