nogrЭкспериментальная и клиническая гастроэнтерологияExperimental and Clinical Gastroenterology1682-8658«Global Media Technologies»10.31146/1682-8658-ecg-202-6-56-60nogr-2094Research ArticleКЛИНИЧЕСКАЯ ГАСТРОЭНТЕРОЛОГИЯCLINICAL GASTROENTEROLOGYФакторы пренатального риска неонатального некротизирующего энтероколитаPrenatal risk factors for neonatal necrotizing enterocolitishttps://orcid.org/0000-0002-6896-7563ЧерненковЮрий ВалентиновичChernenkovYu. V.noemail@neicon.ruhttps://orcid.org/0000-0002-4634-3696БочковаЛариса ГеннадьевнаBochkovaL. G.lu_lg@mail.ruhttps://orcid.org/0000-0003-3387-4321ПанинаОльга СергеевнаPaninaO. S.noemail@neicon.ruhttps://orcid.org/0000-0003-0773-0682НечаевВладимир НиколаевичNechaevV. N.noemail@neicon.ruФГБОУ ВО «Саратовский ГМУ им. В. И. Разумовского» Минздрава РоссииРоссияSaratov State Medical University named after V. I. RazumovskyyRussian Federation202221112022065660Copyright © Черненков Ю.В., Бочкова Л.Г., Панина О.С., Нечаев В.Н., 20222022Черненков Ю.В., Бочкова Л.Г., Панина О.С., Нечаев В.Н.Chernenkov Y.V., Bochkova L.G., Panina O.S., Nechaev V.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.nogr.org/jour/article/view/2094

Целью исследования явилось определение наличия взаимосвязи между пренатальным влиянием потенциальных факторов риска и развитием некротизирующего энтероколита (НЭК) у недоношенных новорожденных. Материалы и методы: исследованы клинические данные 99 пар «мать - новорожденный с диагнозом НЭК IIA стадии по Беллу» и сопоставимой группы сравнения. Клинические характеристики основной группы с НЭК сравнивались с группой контроля с помощью t-критерия Стьюдента. Для оценки выраженности воздействия потенциальных факторов риска использовался метод Кохрана - Мантеля-Хензеля с построением модели логистической регрессии. Результаты. Определена статистически значимая связь между назначением матерям ампициллина во время беременности и возникновением НЭК у новорожденных. Скорректированное отношение шансов (OШ) при пренатальном воздействия ампициллина было значительно больше для младенцев с НЭК (OШ 2.3, 95% ДИ 1,1, 4,8, P = 0,003), чем для детей из группы сравнения. Установлены потенциальные факторы влияния (гипертензия, хориоамнионит, искусственное вскармливание и мужской гендер), оказывающие воздействие на развитие НЭК у новорожденных на фоне проводимой дородовой антибиотикотерапии.

The study aimed to determine the presence of a relationship between prenatal exposure to potential risk factors and the development of necrotizing enterocolitis (NEC) in premature infants. Materials and Methods: The clinical data of 99 mother-newborn couples diagnosed with Bell’s stage IIA NEC and a comparable comparison group were studied. The clinical characteristics of the main group with NEC were compared with the control group using the Student’s t-test. To assess the severity of the impact of potential risk factors, the Cochran - Mantel - Hensel method was used with the construction of a logistic regression model. Results. A statistically significant relationship was established between ampicillin prescribed to pregnant women and the occurrence of NEC in newborns. The adjusted odds ratio (OR) of prenatal ampicillin exposure was significantly greater for infants with NEC (OR 2.3, 95% CI 1.1, 4.8, P = 0.003) than for infants in the comparison group. Potential influencing factors (arterial hypertension, chorioamnionitis, artificial feeding and male sex) which also contribute to the development of NEC in newborns during prenatal antibiotic therapy, have been identified.

факторы рисканекротизирующий энтероколитнедоношенные новорожденныеантибиотикотерапияrisk factorsnecrotizing enterocolitispremature infantsantibiotic therapyReferencesHenry M.C., Moss R. L. Neonatal necrotizing enterocolitis. Semin Pediatr Surg. 2008 May;17(2):98-109. doi: 10.1053/j.sempedsurg.2008.02.005.Henry M.C., Moss R. L. Neonatal necrotizing enterocolitis. Semin Pediatr Surg. 2008 May;17(2):98-109. doi: 10.1053/j.sempedsurg.2008.02.005.Luig M., Lui K.; NSW & ACT NICUS Group. Epidemiology of necrotizing enterocolitis - Part II: Risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005 Apr;41(4):174-9. doi: 10.1111/j.1440-1754.2005.00583.x.Luig M., Lui K.; NSW & ACT NICUS Group. Epidemiology of necrotizing enterocolitis - Part II: Risks and susceptibility of premature infants during the surfactant era: a regional study. J Paediatr Child Health. 2005 Apr;41(4):174-9. doi: 10.1111/j.1440-1754.2005.00583.x.Kucherov Yu.I., Zhirkova Yu.V., Shishkina T. N., Mikhalev I. A., Arsa A. V., Chebotaeva L. I. Necrotizing enterocolitis in premature infants: Diagnosis and treatment. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2014;59(6):18-24. (In Russ.) @@Кучеров Ю. И., Жиркова Ю. В., Шишкина Т. Н., Михалев И. А., Арса А. В., Чеботаева Л. И. Диагностика и лечение некротического энтероколита у недоношенных. Российский вестник перинатологии и педиатрии. 2014;59(6):18-24.Kucherov Yu.I., Zhirkova Yu.V., Shishkina T. N., Mikhalev I. A., Arsa A. V., Chebotaeva L. I. Necrotizing enterocolitis in premature infants: Diagnosis and treatment. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2014;59(6):18-24. (In Russ.) @@Кучеров Ю. И., Жиркова Ю. В., Шишкина Т. Н., Михалев И. А., Арса А. В., Чеботаева Л. И. Диагностика и лечение некротического энтероколита у недоношенных. Российский вестник перинатологии и педиатрии. 2014;59(6):18-24.Lin PW, Nasr TR, Stoll BJ. Necrotizing enterocolitis: recent scientific advances in pathophysiology and prevention. Semin Perinatol. 2008 Apr;32(2):70-82. doi: 10.1053/j.semperi.2008.01.004.Lin PW, Nasr TR, Stoll BJ. Necrotizing enterocolitis: recent scientific advances in pathophysiology and prevention. Semin Perinatol. 2008 Apr;32(2):70-82. doi: 10.1053/j.semperi.2008.01.004.Lin P.W., Stoll B. J. Necrotising enterocolitis. Lancet. 2006 Oct 7;368(9543):1271-83. doi: 10.1016/S0140-6736(06)69525-1.Lin P.W., Stoll B. J. Necrotising enterocolitis. Lancet. 2006 Oct 7;368(9543):1271-83. doi: 10.1016/S0140-6736(06)69525-1.Anand R.J., Leaphart C. L., Mollen K. P., Hackam D. J. The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis. Shock. 2007 Feb;27(2):124-33. doi: 10.1097/01.shk.0000239774.02904.65.Anand R.J., Leaphart C. L., Mollen K. P., Hackam D. J. The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis. Shock. 2007 Feb;27(2):124-33. doi: 10.1097/01.shk.0000239774.02904.65.Hunter C.J., Upperman J. S., Ford H. R., Camerini V. Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC). Pediatr Res. 2008 Feb;63(2):117-23. doi: 10.1203/PDR.0b013e31815ed64c.Hunter C.J., Upperman J. S., Ford H. R., Camerini V. Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC). Pediatr Res. 2008 Feb;63(2):117-23. doi: 10.1203/PDR.0b013e31815ed64c.Petrosyan M., Guner Y. S., Williams M., Grishin A., Ford H. R. Current concepts regarding the pathogenesis of necrotizing enterocolitis. Pediatr Surg Int. 2009 Apr;25(4):309-18. doi: 10.1007/s00383-009-2344-8.Petrosyan M., Guner Y. S., Williams M., Grishin A., Ford H. R. Current concepts regarding the pathogenesis of necrotizing enterocolitis. Pediatr Surg Int. 2009 Apr;25(4):309-18. doi: 10.1007/s00383-009-2344-8.Claud E.C., Walker W. A. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J. 2001 Jun;15(8):1398-403. doi: 10.1096/fj.00-0833hyp.Claud E.C., Walker W. A. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J. 2001 Jun;15(8):1398-403. doi: 10.1096/fj.00-0833hyp.Emami C.N., Petrosyan M., Giuliani S., Williams M., Hunter C., Prasadarao N. V., Ford H. R. Role of the host defense system and intestinal microbial flora in the pathogenesis of necrotizing enterocolitis. Surg Infect (Larchmt). 2009 Oct;10(5):407-17. doi: 10.1089/sur.2009.054.Emami C.N., Petrosyan M., Giuliani S., Williams M., Hunter C., Prasadarao N. V., Ford H. R. Role of the host defense system and intestinal microbial flora in the pathogenesis of necrotizing enterocolitis. Surg Infect (Larchmt). 2009 Oct;10(5):407-17. doi: 10.1089/sur.2009.054.Harmsen H.J.M., Wildeboer-Veloo A.C.M., Raangs G. C., et al. Analysis of intestinal flora development in breast-fed and formula-fed infants using molecular identification and detection methods. J Pediatr Gastroenterol Nutr. 2000 Jan;30(1):61-7. doi: 10.1097/00005176-200001000-00019.Harmsen H.J.M., Wildeboer-Veloo A.C.M., Raangs G. C., et al. Analysis of intestinal flora development in breast-fed and formula-fed infants using molecular identification and detection methods. J Pediatr Gastroenterol Nutr. 2000 Jan;30(1):61-7. doi: 10.1097/00005176-200001000-00019.Grönlund M.M., Lehtonen O. P., Eerola E., Kero P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr. 1999 Jan;28(1):19-25. doi: 10.1097/00005176-199901000-00007.Grönlund M.M., Lehtonen O. P., Eerola E., Kero P. Fecal microflora in healthy infants born by different methods of delivery: permanent changes in intestinal flora after cesarean delivery. J Pediatr Gastroenterol Nutr. 1999 Jan;28(1):19-25. doi: 10.1097/00005176-199901000-00007.Bonnemaison E., Lanotte P. H., Cantagrel S., Thionois S., Quentin R., Chamboux C. et al.Comparison of fecal flora following administration of two antibiotic protocols for suspected maternofetal infection. Biol Neonate. 2003;84(4):304-10. doi: 10.1159/000073639.Bonnemaison E., Lanotte P. H., Cantagrel S., Thionois S., Quentin R., Chamboux C. et al.Comparison of fecal flora following administration of two antibiotic protocols for suspected maternofetal infection. Biol Neonate. 2003;84(4):304-10. doi: 10.1159/000073639.Tanaka S., Kobayasi T., Songjinda P., et al. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunol Med Microbiol. 2009 Jun;56(1):80-7. doi: 10.1111/j.1574-695X.2009.00553.x.Tanaka S., Kobayasi T., Songjinda P., et al. Influence of antibiotic exposure in the early postnatal period on the development of intestinal microbiota. FEMS Immunol Med Microbiol. 2009 Jun;56(1):80-7. doi: 10.1111/j.1574-695X.2009.00553.x.Hallstrom M., Eerola E., Vuento R., Janas M., Tammela O. Effects of mode of delivery and necrotizing enterocolitis on the intestinal microflora in preterm infants. Eur J Clin Microbiol Infect Dis. 2004 Jun;23(6):463-70. doi: 10.1007/s10096-004-1146-0.Hallstrom M., Eerola E., Vuento R., Janas M., Tammela O. Effects of mode of delivery and necrotizing enterocolitis on the intestinal microflora in preterm infants. Eur J Clin Microbiol Infect Dis. 2004 Jun;23(6):463-70. doi: 10.1007/s10096-004-1146-0.Duan M., Han Z., Huang N. Changes of intestinal microflora in neonatal necrotizing enterocolitis: a single-center study. J Int Med Res. 2020 Sep;48(9):300060520957804. doi: 10.1177/0300060520957804.Duan M., Han Z., Huang N. Changes of intestinal microflora in neonatal necrotizing enterocolitis: a single-center study. J Int Med Res. 2020 Sep;48(9):300060520957804. doi: 10.1177/0300060520957804.Jacquot A., Neveu D., Aujoulat F., et al. Dynamics and clinical evolution of bacterial gut microflora in extremely premature patients. J Pediatr. 2011 Mar;158(3):390-6. doi: 10.1016/j.jpeds.2010.09.007.Jacquot A., Neveu D., Aujoulat F., et al. Dynamics and clinical evolution of bacterial gut microflora in extremely premature patients. J Pediatr. 2011 Mar;158(3):390-6. doi: 10.1016/j.jpeds.2010.09.007.Schrag S., Gorwitz R., Fultz-Butts K., Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep. 2002 Aug 16;51(RR-11):1-22. PMID: 12211284.Schrag S., Gorwitz R., Fultz-Butts K., Schuchat A. Prevention of perinatal group B streptococcal disease. Revised guidelines from CDC. MMWR Recomm Rep. 2002 Aug 16;51(RR-11):1-22. PMID: 12211284.Mercer B.M., Miodovnik M., Thurnau G. R., et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA. 1997 Sep 24;278(12):989-95. PMID: 9307346.Mercer B.M., Miodovnik M., Thurnau G. R., et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA. 1997 Sep 24;278(12):989-95. PMID: 9307346.Edwards R. K. Chorioamnionitis and labor. Obstet Gynecol Clin North Am. 2005 Jun;32(2):287-96, x. doi: 10.1016/j.ogc.2004.12.002.Edwards R. K. Chorioamnionitis and labor. Obstet Gynecol Clin North Am. 2005 Jun;32(2):287-96, x. doi: 10.1016/j.ogc.2004.12.002.Kenyon S.L., Taylor D. J., Tarnow-Mordi W.; ORACLE Collaborative Group. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet. 2001 Mar 31;357(9261):979-88. doi: 10.1016/s0140-6736(00)04233-1. Erratum in: Lancet 2001 Jul 14;358(9276):156. PMID: 11293640.Kenyon S.L., Taylor D. J., Tarnow-Mordi W.; ORACLE Collaborative Group. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. ORACLE Collaborative Group. Lancet. 2001 Mar 31;357(9261):979-88. doi: 10.1016/s0140-6736(00)04233-1. Erratum in: Lancet 2001 Jul 14;358(9276):156. PMID: 11293640.Al-Sabbagh A., Moss S., Subhedar N. Neonatal necrotising enterocolitis and perinatal exposure to co-amoxyclav. Arch Dis Child Fetal Neonatal Ed. 2004 Mar;89(2): F187. doi: 10.1136/adc.2002.022731.Al-Sabbagh A., Moss S., Subhedar N. Neonatal necrotising enterocolitis and perinatal exposure to co-amoxyclav. Arch Dis Child Fetal Neonatal Ed. 2004 Mar;89(2): F187. doi: 10.1136/adc.2002.022731.Ehsanipoor R.M., Chung J. H., Clock C. A., McNulty J.A., Wing D. A. A retrospective review of ampicillin-sulbactam and amoxicillin + clavulanate vs cefazolin/cephalexin and erythromycin in the setting of preterm premature rupture of membranes: maternal and neonatal outcomes. Am J Obstet Gynecol. 2008 May;198(5): e54-6. doi: 10.1016/j.ajog.2007.12.022.Ehsanipoor R.M., Chung J. H., Clock C. A., McNulty J.A., Wing D. A. A retrospective review of ampicillin-sulbactam and amoxicillin + clavulanate vs cefazolin/cephalexin and erythromycin in the setting of preterm premature rupture of membranes: maternal and neonatal outcomes. Am J Obstet Gynecol. 2008 May;198(5): e54-6. doi: 10.1016/j.ajog.2007.12.022.Yahamanyam P.K., Rasiah S. V., Ewer A. K. Necrotizing enterocolitis: current perspectives. Research and Reports in Neonatology. 2014; 4: 31-42. doi: 10.2147/RRN.S36576.Yahamanyam P.K., Rasiah S. V., Ewer A. K. Necrotizing enterocolitis: current perspectives. Research and Reports in Neonatology. 2014; 4: 31-42. doi: 10.2147/RRN.S36576.Kobrinsky B.A., Molodchenkov A. I., Blagosklonov N. A., Lukin A. V. Applying meta-analysis methods in liver failure diagnosis and treatment. 2017; 30(4):745-753. (in Russ.) doi: 10.15827/0236-235X.120.745-753. @@Кобринский Б. А., Молодченков А. И., Благосклонов Н. А., Лукин А. В. Применение методов метаанализа в диагностике и лечении пациентов с печеночной недостаточностью. Программные продукты и системы. 2017; 30(4):745-753. doi: 10.15827/0236-235X.120.745-753.Kobrinsky B.A., Molodchenkov A. I., Blagosklonov N. A., Lukin A. V. Applying meta-analysis methods in liver failure diagnosis and treatment. 2017; 30(4):745-753. (in Russ.) doi: 10.15827/0236-235X.120.745-753. @@Кобринский Б. А., Молодченков А. И., Благосклонов Н. А., Лукин А. В. Применение методов метаанализа в диагностике и лечении пациентов с печеночной недостаточностью. Программные продукты и системы. 2017; 30(4):745-753. doi: 10.15827/0236-235X.120.745-753.Mercer B. M. Preterm premature rupture of the membranes. Obstet Gynecol. 2003 Jan;101(1):178-93. doi: 10.1016/s0029-7844(02)02366-9.Mercer B. M. Preterm premature rupture of the membranes. Obstet Gynecol. 2003 Jan;101(1):178-93. doi: 10.1016/s0029-7844(02)02366-9.

The authors declare that there are no conflicts of interest present.