mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-CMO-3446mimmun-3446Research ArticleОБЗОРЫREVIEWSЦитокины – маркеры ранних неонатальных инфекцийCytokines – markers of the early neonatal infectionshttps://orcid.org/0009-0000-9423-0840ИвановаН. В.IvanovaN. V.

Иванова Надежда Владимировна – врач – анестезиолог-реаниматолог СПб ГБУЗ «Детская городская больница № 17 Святителя Николая Чудотворца»; младший научный сотрудник ФБУН «Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени Пастера» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека

190121, Санкт-Петербург, ул. Декабристов, 40, лит. А

Nadezhda V. Ivanova - Anaestesiologist-Reanimatologist, Children’s City Hospital No. 17 of St. Nicholas the Wonderworker; Junior Researcher

40A Dekabristov St St. Petersburg 190121 

7901895@gmail.comhttps://orcid.org/0000-0003-2490-308XАрсентьеваН. А.ArsentievaN. A.

К.б.н., старший научный сотрудник

Санкт-Петербург

PhD (Biology), Senior Researcher

St. Petersburg

arsentieva_n.a@bk.ruШатиллоИ. М.ShatilloI. M.

К.м.н., доцент кафедры педиатрии и неонатологии 

Санкт-Петербург

PhD (Medicine), Associate Professor, Department of Pediatrics and Neonatology

St. Petersburg

irina.Shatillo@szgmu.ruРоманюкФ. П.RomanyukF. P.

Д.м.н., профессор, заведующий кафедрой педиатрии и неонатологии 

Санкт-Петербург

PhD, MD (Medicine), Professor, Head, Department of Pediatrics and Neonatology

St. Petersburg

pitspb2004@mail.ruСПб ГБУЗ «Детская городская больница № 17 Святителя Николая Чудотворца»; ФБУН «Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени Пастера» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаРоссияChildren’s City Hospital No. 17 of St. Nicholas the Wonderworker; Saint Petersburg Pasteur InstituteRussian FederationФБУН «Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени Пастера» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаРоссияSaint Petersburg Pasteur InstituteRussian FederationФГБОУ ВО «Северо-Западный государственный медицинский университет имени И.И. Мечникова» Министерства здравоохранения РФРоссияI. Mechnikov North-Western State Medical UniversityRussian Federation202620062026282309320Copyright © Иванова Н.В., Арсентьева Н.А., Шатилло И.М., Романюк Ф.П., 20262026Иванова Н.В., Арсентьева Н.А., Шатилло И.М., Романюк Ф.П.Ivanova N.V., Arsentieva N.A., Shatillo I.M., Romanyuk F.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/3446

Неонатальный период – это время, когда дети особенного уязвимы и подвергаются наибольшему риску летального исхода от инфекций, которые могли бы быть предотвращены при ранней диагностике и надлежащем лечении. Сложности ранней клинической диагностики определяют необходимость поиска маркера, который позволил бы отличить новорожденного с инфекцией от новорожденных с перинатальными симптомами, имитирующими инфекцию. Микробиологическое исследование крови часто чревато ложноотрицательными результатами, при этом доказана низкая чувствительность посевов крови у новорожденных. Молекулярные методы ПЦР обладают умеренной диагностической точностью и не могут заменить бактериологическое исследование крови в качестве эталонного стандарта. То же относится к определению уровней СРБ и ПКТ. Уровень идеального маркера должен быстро повышаться после контакта с патогеном до появления клинических признаков и столь же быстро снижаться после излечения инфекции, обладая высокой чувствительностью и специфичностью. Одними из маркеров начала развития инфекционного процесса служат цитокины, которые первыми синтезируются при распознавании бактерий паттерн-распознающими рецепторами. Их концентрация в плазме крови существенно увеличивается в первые часы после начала противоинфекционного иммунного ответа. Поэтому оценка уровней цитокинов при развитии ранних неонатальных инфекций может внести существенный вклад в их диагностику и правильный выбор алгоритма лечения. В обзоре приведены данные по изучению уровней ряда цитокинов у новорожденных с неонатальными инфекциями и сепсисом, продемонстрирована их значимость в диагностике данных состояний. В целом исследования уровней цитокинов у новорожденных очень немногочисленны, и референсные уровни цитокинов для диагностики ранних неонатальных инфекций изучены недостаточно. Семейство цитокинов насчитывает несколько сотен медиаторов, и многие из них имеют важное значение в развитии воспалительной реакции и сепсиса, однако далеко не все они исследованы в плане изменения синтеза при развитии тяжелых инфекций, в т. ч. в неонатальном периоде. Видимо, одновременный анализ уровней нескольких цитокинов и соотношения их синтеза могут дать новые информативные данные для диагностики ранней неонатальной инфекции.

Neonatalperiodisthetimewhenchildrenareextremelyvulnerableandsusceptibletolethalinfectious complications that could be prevented due to early diagnostic procedures and adequate therapy. Problems with early clinical diagnostics determine the need for searching a marker which could help to differentiate newborn with infection from the newborn with perinatal symptoms resembling infection. Blood microbiological testing frequently gives false negative results, and newborn blood culture tests have low sensitivity. Molecular methods, especially PCR, have also moderate diagnostic accuracy, and can not replace bacteriological blood testing as a reference standard. The same problems exist with C-reactive protein and procalcitonin determination. Ideal marker’s level must quickly rise after contact with pathogen prior to clinical symptoms onset and also quickly decrease after infection healing having high sensitivity and specificity. Cytokines are one of the markers for the infectious process beginning. These molecules are among first to be synthesized after bacterial recognition by pattern-recognition receptors. Their blood plasma concentrations significantly increase during first hours after antiinfectious immune response beginning. That is why cytokines levels determination during neonatal infections may serve as significant tool for early diagnostics and adequate choice for treatment strategy. In this review we tried to summarize existing data on cytokine levels in newborns with neonatal infections and sepsis, and data on its significance in diagnostic approaches. Studies on cytokine levels in newborns are few in number, and reference concentrations are not yet determined. Cytokine family consists of hundreds of molecules, most of them are important mediators of inflammation and sepsis. However not all of them are studied for blood level changes during severe infections in neonatal period. Probably simultaneous studies of several cytokine levels and their synthesis ratio could give new informative data for early neonatal infection diagnostics improvement.

цитокиныхемокиныбиомаркерыиммунодиагностикановорожденныеранние неонатальные инфекцииcytokineschemokinesbiomarkersimmunodiagnosticsnewbornearly neonatal infectionReferencesКоробова З.Р., Арсентьева Н.А., Тотолян А.А. IL-27 как эффекторное звено иммунного ответа при вирусных инфекция // Инфекция и иммунитет, 2025. Т. 15, № 5. С. 837-845. doi: 10.15789/2220-7619-IAE-17947.Korobova Z.R., Arsentieva N.A., Totolian A.A. IL-27 as effector molecule in viral infections and immunity. Infection and immunity. - 2025. – Vol 15, № 5 pp. 837–845. DOI: 10.15789/2220-7619-IAE-17947Сепсис новорожденных: клинические рекомендации Министерства здравоохранения Российской Федерации [Электронный ресурс]. М., 2025. 98 с. Режим доступа: https://cr.minzdrav.gov.ru/view-cr/912_1 (дата обращения: 29.01.2026).Neonatal sepsis: ICD 10: P36.0, P36.1, P36.2, P36.3, P36.4, P36.5, P36.8, P36.9: clinical recommendations / Ministry of Health of the Russian Federation, Russian public organization for the promotion of neonatology development "Russian Society of Neonatologists". Moscow, 2025. - 98 p. - Text: electronic / Rubricator of clinical recommendations of the Ministry of Health of the Russian Federation.Bakhuizen S.E., de Haan T.R., Teune M.J., van Wassenaer-Leemhuis A.G., van der Heyden J.L., van der Ham D.P., Mol B.W. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr., 2014, Vol. 103, no. 12, pp. 1211-1218.Bakhuizen S., de Haan T., Teune M., van Wassenaer-Leemhuis A., van der Heyden J., van der Ham D., Mol B. Meta-analysis shows that infants who have suffered neonatal sepsis face an increased risk of mortality and severe complications. Acta Paediatr., 2014, Vol. 103, no. 12, pp. 1211-1218. doi: 10.1111/apa.12764.Boscarino G., Migliorino R., Carbone G., Davino G., Dell’Orto V., Perrone S., Principi N., Esposito S. Biomarkers of Neonatal Sepsis: Where We Are and Where We Are Going. Antibiotics (Basel), 2023, Vol. 12, no. 8, 1233. doi: 10.3390/antibiotics12081233.Boscarino G., Migliorino R., Carbone G., Davino G., Dell'Orto V., Perrone S., Principi N., Esposito S. Biomarkers of Neonatal Sepsis: Where We Are and Where We Are Going. Antibiotics (Basel), 2023. - Vol. 12, no. 8.- P. 1233. doi: 10.3390/antibiotics12081233.Boskabadi H., Maamouri G., Tavakol Afshari J., Mafinejad S., Hosseini G., Mostafavi-Toroghi H., Saber H., Ghayour-Mobarhan M., Ferns G. Evaluation of serum interleukins-6, 8 and 10 levels as diagnostic markers of neonatal infection and possibility of mortality. Iran J. Basic Med. Sci., 2013, Vol. 16, no. 12, pp. 1232-1237.Boskabadi H., Maamouri G., Tavakol Afshari J., Mafinejad S., Hosseini G., Mostafavi-Toroghi H., Saber H., Ghayour-Mobarhan M., Ferns G. Evaluation of serum interleukins-6, 8 and 10 levels as diagnostic markers of neonatal infection and possibility of mortality. Iran J Basic Med Sci., 2013. – Vol.16, no. 12. – P. 1232-1237. PMID: 24570828Camargo J., Caldas J., Marba S. Early neonatal sepsis: prevalence, complications and outcomes in newborns with 35 weeks of gestational age or more. Rev. Paul. Pediatr., 2021, Vol. 4, no. 40, e2020388. doi: 10.1590/1984-0462/2022/40/2020388.Camargo J., Caldas J., Marba S. Early neonatal sepsis: prevalence, complications and outcomes in newborns with 35 weeks of gestational age or more. Rev Paul Pediatr. 2021. – Vol. 4, no. 40. – P. e2020388. doi: 10.1590/1984-0462/2022/40/2020388Celik I., Demirel G., Uras N., Oguz E.S., Erdeve O., Dilmen U. The role of serum interleukin-6 and C-reactive protein levels for differentiating aetiology of neonatal sepsis. Arch. Argent. Pediatr., 2015, Vol. 113, pp. 534-537.Celik I., Demirel G., Uras N., Oguz E.S., Erdeve O., Dilmen U. The role of serum interleukin-6 and C-reactive protein levels for differentiating aetiology of neonatal sepsis. Arch. Argent. Pediatr., 2015. – Vol. 113. – P. 534–537. doi: 10.5546/aap.2015.eng.534.Celik I.H., Hanna M., Canpolat F., Mohan Pammi. Diagnosis of neonatal sepsis: the past, present and future. Pediatr. Res., 2022, Vol. 91, no. 2, pp. 337-350.Celik I., Hanna M., Canpolat F., Mohan Pammi. Diagnosis of neonatal sepsis: the past, present and future. Pediatr Res., 2022. – Vol. 91, no. 2. – P.337-350. doi: 10.1038/s41390-021-01696-z.Chavez B., Kiaris H. Insights on the role of the chemokine CCL8 in pathology. Cell Signal., 2025, Vol. 134, 111951. doi: 10.1016/j.cellsig.2025.111951.Chavez B., Kiaris H. Insights on the role of the chemokine CCL8 in pathology. Cell Signal., 2025. – Vol. 134. – P. 111951. doi: 10.1016/j.cellsig.2025.111951.Chen Q., Chen J., Zhong R. Diagnostic utility of combined serum procalcitonin and C-Reactive Proteins In Neonatal Sepsis. Br. J. Hosp. Med. (Lond.), 2025, Vol. 86, no. 12, pp. 1-18.Chen Q., Chen J., Zhong R. Diagnostic Utility of Combined Serum Procalcitonin and C-Reactive Proteins in Neonatal Sepsis. Br J Hosp Med (Lond)., 2025. – Vol. 86, no. 12. – P. 1-18. doi: 10.12968/hmed.2025.0745.Chen S., Kuang M., Qu Y., Huang S., Gong B., Lin S., Wang H., Wang G., Tao H., Yu J., Yang Z., Jiang M., Xie Q. Expression of Serum Cytokines Profile in Neonatal Sepsis. Infect. Drug Resist., 2022, Vol. 15, pp. 3437-3445.Chen S., Kuang M., Qu Y., Huang S., Gong B., Lin S., Wang H., Wang G., Tao H., Yu J., Yang Z., Jiang M., Xie Q. Expression of Serum Cytokines Profile in Neonatal Sepsis. Infect Drug Resist., 2022. – Vol. 15. – P. 3437-3445. doi: 10.2147/IDR.S368772.Cicchinelli S., Pignataro G., Gemma S., Piccioni A., Picozzi D., Ojetti V., Franceschi F., Candelli M. PAMPs and DAMPs in Sepsis: A review of their molecular features and potential clinical implications. Int. J. Mol. Sci., 2024, Vol. 25, no. 2, 962. doi: 10.3390/ijms25020962Cicchinelli S., Pignataro G., Gemma S., Piccioni A., Picozzi D., Ojetti V., Franceschi F., Candelli M. PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications. Int J Mol Sci., 2024. – Vol. 25, no. 2. – P. 962. doi: 10.3390/ijms25020962.De Rose D., Ronchetti M., Martini L., Rechichi J., Iannetta M., Dotta A., Auriti C. Diagnosis and management of neonatal bacterial sepsis: current challenges and future perspectives. Trop. Med. Infect. Dis., 2024, Vol. 9, no. 9, 199. doi: 10.3390/tropicalmed9090199.De Rose D., Ronchetti M., Martini L., Rechichi J., Iannetta M., Dotta A., Auriti C. Diagnosis and Management of Neonatal Bacterial Sepsis: Current Challenges and Future Perspectives. Trop Med Infect Dis., 2024. – Vol. 9, no. 9. – P. 199. doi: 10.3390/tropicalmed9090199Eichberger J., Resch B. Reliability of interleukin-6 alone and in combination for diagnosis of early onset neonatal sepsis: systematic review. Front. Pediatr., 2022, Vol. 10, 840778. doi: 10.3389/fped.2022.840778.Eichberger J., Resch B. Reliability of Interleukin-6 Alone and in Combination for Diagnosis of Early Onset Neonatal Sepsis: Systematic Review. Front Pediatr., 2022. – Vol. 10. – P. 840778. doi: 10.3389/fped.2022.840778.Fleischmann-Struzek C., Goldfarb D., Schlattmann P., Schlapbach L., Reinhart K., Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir. Med., 2018, Vol. 6, no. 3, pp. 223-230.Fleischmann-Struzek C., Goldfarb D., Schlattmann P., Schlapbach L., Reinhart K., Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med., 2018. – Vol. 6, no. 3. – P. 223-230. doi: 10.1016/S2213-2600(18)30063-8.Glaser M.A., Hughes L.M., Jnah A., Newberry D., Harris-Haman P.A. Neonatal Sepsis: A review of pathophysiology and current management strategies. Adv. Neonatal Care, 2021, Vol. 21, pp. 49-60.Glaser M.A., Hughes L.M., Jnah A., Newberry D., Harris-Haman P.A. Neonatal Sepsis: A Review of Pathophysiology and Current Management Strategies. Adv. Neonatal Care., 2021. – Vol. 21. – P. 49–60. doi: 10.1097/ANC.0000000000000769Go H., Nagano N., Katayama D., Akimoto T., Imaizumi T., Aoki R., Hijikata M., Seimiya A., Kato R., Okahashi A., Morioka I. Diagnostics (Basel)., 2022, Vol. 12, no. 10, 2277. doi: 10.3390/diagnostics12102277.Go H., Nagano N., Katayama D., Akimoto T., Imaizumi T., Aoki R., Hijikata M., Seimiya A., Kato R., Okahashi A., Morioka I. Diagnostics (Basel)., 2022. – Vol. 12, no. 10. – P. 2277. doi: 10.3390/diagnostics12102277.Green E., Garrick S., Peterson B., Berger P., Galinsky R., Hunt R., Cho S., Bourke J., Nold M., Nold-Petry C. The role of the interleukin-1 family in complications of prematurity. Int. J. Mol. Sci., 2023, Vol. 24, no. 3, 2795. doi: 10.3390/ijms24032795.Green E., Garrick S., Peterson B., Berger P., Galinsky R., Hunt R., Cho S., Bourke J., Nold M., Nold-Petry C. The Role of the Interleukin-1 Family in Complications of Prematurity. Int J Mol Sci., 2023. – Vol. 24, no. 3. – P. 2795. doi: 10.3390/ijms24032795.Gude S., Peddi N., Vuppalapati S., Venu Gopal S., Marasandra Ramesh H., Gude S. Biomarkers of neonatal sepsis: from being mere numbers to becoming guiding diagnostics. Cureus, 2022, Vol. 14, no. 3, e23215. doi: 10.7759/cureus.23215.Gude S., Peddi N., Vuppalapati S., Venu Gopal S., Marasandra Ramesh H., Gude S. Biomarkers of Neonatal Sepsis: From Being Mere Numbers to Becoming Guiding Diagnostics. Cureus, 2022. – Vol. 14, no. 3. – P. e23215. doi: 10.7759/cureus.23215.Halil H., Tayman C., Buyuktiryaki M., Okur N., Cakır U., Serkant U. Serum interleukin-33 as a biomarker in predicting neonatal sepsis in premature infants. Comb. Chem. High Throughput Screen., 2018, Vol. 21, pp. 510-515.Halil H., Tayman C., Buyuktiryaki M., Okur N., Cakır U., Serkant U. Serum Interleukin-33 as a Biomarker in Predicting Neonatal Sepsis in Premature Infants. Comb. Chem. High Throughput Screen., 2018. – Vol. 21. – P. 510–515. doi: 10.2174/1386207321666180911090656.Jiang K., Zhang Z., Huang X., Hao C., Huang H., Liu W., Fan L., Lu W. Global, regional, and national incidence and mortality of neonatal sepsis and other neonatal infections, 1990-2021 and predictions to 2050. BMC Pediatr., 2025, Vol. 25, 711. doi: 10.1186/s12887-025-06044-2.Jiang K., Zhang Z., Huang X., Hao C., Huang H., Liu W., Fan L., Lu W. Global, regional, and national incidence and mortality of neonatal sepsis and other neonatal infections, 1990-2021 and predictions to 2050. BMC Pediatr., 2025. – Vol. 25, no. 1. – P. 711. doi: 10.1186/s12887-025-06044-2.Kilpatrick R., Greenberg R., Hansen N., Shankaran S., Carlo W., Cotten C., Stoll B. Use and utility of C-reactive protein (CRP) in neonatal early-onset sepsis: a secondary analysis of a prospective surveillance study. J. Perinatol., 2024, Vol. 45, no. 1, pp. 139-145.Kilpatrick R., Greenberg R., Hansen N., Shankaran S., Carlo W., Cotten C., Stoll B.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Use and utility of C-reactive protein (CRP) in neonatal early-onset sepsis: a secondary analysis of a prospective surveillance study. J Perinatol., 2024. – Vol. 45, no. 1. – P. 139–145. doi: 10.1038/s41372-024-02064-5Klingenberg C., Kornelisse R., Buonocore G., Maier R., Stocker M. Culture-Negative Early-Onset Neonatal Sepsis – At The Crossroad Between Efficient Sepsis Care And Antimicrobial Stewardship. Front. Pediatr., 2018, Vol. 6, 285. doi: 10.3389/fped.2018.00285.Klingenberg C., Kornelisse R., Buonocore G., Maier R., Stocker M. Culture-Negative Early-Onset Neonatal Sepsis — At the Crossroad Between Efficient Sepsis Care and Antimicrobial Stewardship. Front Pediatr., 2018. – Vol. 6. – P. 285. doi: 10.3389/fped.2018.00285Kurt A., Aygun A., Godekmerdan A., Kurt A., Dogan Y., Yilmaz E. Serum IL-1beta, IL-6, IL-8, and TNFalpha levels in early diagnosis and management of neonatal sepsis. Mediat. Inflamm., 2007, Vol. 2007, 31397. doi: 10.1155/2007/31397.Kurt A., Aygun A., Godekmerdan A., Kurt A., Dogan Y., Yilmaz E. Serum IL-1beta, IL-6, IL-8, and TNF-alpha levels in early diagnosis and management of neonatal sepsis. Mediat. Inflamm., 2007. – Vol. 2007. – P. 31397. doi: 10.1155/2007/31397.Kuster H., Weiss M., Willeitner A., Detlefsen S., Jeremias I., Zbojan J., Geiger R., Lipowsky G., Simbruner G. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet, 1998, Vol. 352, no. 9136, pp. 1271-1277.Kuster H., Weiss M., Willeitner A., Detlefsen S., Jeremias I., Zbojan J., Geiger R., Lipowsky G., Simbruner G. Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation. Lancet, 1998. – Vol. 352, no. 9136. – P. 1271–1277. doi: 10.1016/S0140-6736(98)08148-3.Leal Y., Álvarez-Nemegyei J., Lavadores-May A., Girón-Carrillo J., Cedillo-Rivera R., Velazquez J. Cytokine profile as diagnostic and prognostic factor in neonatal sepsis. J. Matern. Fetal Neonatal Med., 2019, Vol. 32, no. 17, pp. 2830-2836.Leal Y., Álvarez-Nemegyei J., Lavadores-May A., Girón-Carrillo J., Cedillo-Rivera R., Velazquez J. Cytokine profile as diagnostic and prognostic factor in neonatal sepsis. J Matern Fetal Neonatal Med., 2019. – Vol.32, no. 17. – P. 2830-2836. doi: 10.1080/14767058.2018.1449828.Leonardi L., Pennetta V., Laitano R., Carsetti R., Duse M., Fiore M., Natale F., Tarani L., Spalice A., Förster-Waldl E. Inflammatory signatures and immunomodulation in neonates: a pilot study. Clin. Ter., 2025, Vol. 176, no. 3, pp. 350-357.Leonardi L., Pennetta V., Laitano R., Carsetti R., Duse M., Fiore M., Natale F., Tarani L., Spalice A., Förster-Waldl E. Inflammatory signatures and immunomodulation in neonates: a pilot study. Clin Ter., 2025. – Vol. 176, no. 3. – P. 350-357. doi: 10.7417/CT.2025.5233.Liang J., Su Y., Wang N., Wang X., Hao L., Ren C. A meta-analysis of the association between inflammatory cytokine polymorphism and neonatal sepsis. PLoS ONE, 2024, Vol. 19, no. 6, e0301859. doi: 10.1371/journal.pone.0301859.Liang J., Su Y., Wang N., Wang X., Hao L., Ren C. A meta-analysis of the association between inflammatory cytokine polymorphism and neonatal sepsis. PLoS One, 2024. – Vol. 19, no. 6. – P. e0301859. doi: 10.1371/journal.pone.0301859.Medzhitov R, Janeway CA Jr. Innate immunity: the virtues of a nonclonal system of recognition. Cell, 1997, Vol. 91, no. 3, pp. 295-298.Medzhitov R, Janeway CA Jr. Innate immunity: the virtues of a nonclonal system of recognition. Cell, 1997.- Vol. 91, no. 3. – P. 295-298. doi: 10.1016/s0092-8674(00)80412-2.Mwesigye P., Rizwan F., Alassaf N., Khan R. The role and validity of diagnostic biomarkers in late-onset neonatal sepsis. Cureus, 2021, Vol. 13, no. 8, e17065. doi: 10.7759/cureus.17065.Mwesigye P., Rizwan F., Alassaf N., Khan R. The role and validity of diagnostic biomarkers in late-onset neonatal sepsis. Cureus, 2021. – 13, no. 8. – P. e17065. doi: 10.7759/cureus.17065.Neonatal infection: antibiotics for prevention and treatment (NICE guideline NG195). Available at: https://www.nice.org.uk/guidance/ng195.Neonatal infection: antibiotics for prevention and treatment (NICE guideline NG195) [ Aug; 2025]. 2024. https://www.nice.org.uk/guidance/ng195Odabasi I., Bulbul A. Neonatal Sepsis. Sisli Etfal Hastan. Tip Bul., 2020, Vol. 54, no. 2, pp. 142-158.Odabasi I., Bulbul A. Neonatal Sepsis. Sisli Etfal Hastan Tip Bul., 2020. – Vol. 54, no. 2. – P. 142-158. doi: 10.14744/SEMB.2020.00236.Paucard L., Varga B., Kermorvant-Duchemin E., Huynh B., Watier L. Hospital admissions after early-onset neonatal bacterial infection management guidelines in France. JAMA Netw. Open, 2025, Vol. 8, no. 11, e2545436. doi: 10.1001/jamanetworkopen.2025.45436.Paucard L., Varga B., Kermorvant-Duchemin E., Huynh B., Watier L. Hospital Admissions After Early-Onset Neonatal Bacterial Infection Management Guidelines in France. JAMA Netw Open, 2025. – Vol. 8, no. 11. – P. e2545436. doi: 10.1001/jamanetworkopen.2025.45436.Pickler R., Brown L., McGrath J., Lyon D., Rattican D., Cheng C., Howland L., Jallo N. Integrated review of cytokines in maternal, cord, and newborn blood: part II – associations with early infection and increased risk of neurologic damage in preterm infants. Biol. Res. Nurs., 2010, Vol. 11, no. 4, pp. 377-386.Pickler R., Brown L., McGrath J., Lyon D., Rattican D., Cheng C., Howland L., Jallo N. Integrated review of cytokines in maternal, cord, and newborn blood: part II — associations with early infection and increased risk of neurologic damage in preterm infants. Biol Res Nurs, 2010. – Vol. 11, no. 4. – P. 377–386. doi: 10.1177/1099800409344619Rautela A., Garg J., Agarwal J., Raj N., Das A., Sen M. Evaluation of a novel serum marker, interleukin 27, in comparison to procalcitonin and C-reactive protein in the diagnosis of early-onset neonatal sepsis in a tertiary care center in north India. Int. J. Crit. Illn. Inj. Sci., 2024, Vol. 14, no. 4, pp. 181-187.Rautela A., Garg J., Agarwal J., Raj N., Das A., Sen M. Evaluation of a novel serum marker, interleukin 27, in comparison to procalcitonin and C-reactive protein in the diagnosis of early-onset neonatal sepsis in a tertiary care center in north India. Int J Crit Illn Inj Sci., 2024. – Vol. 14, no. 4. – P. 181-187. doi: 10.4103/ijciis.ijciisSantana C., Guindeo M., González G., García-Muñoz F., Saavedra P., Doménech E. Cord blood levels of cytokines as predictors of early neonatal sepsis. Acta Paediatr., 2001, Vol. 90, no. 10, pp. 1176-1181.Santana C., Guindeo M., González G., García-Muñoz F., Saavedra P., Doménech E. Cord blood levels of cytokines as predictors of early neonatal sepsis. Acta Paediatr., 2001. – Vol. 90, no. 10. – P. 1176-1181. doi: 10.1080/080352501317061602. PMID: 11697431.Schleier M., Lubig J., Kehl S., Hébert S., Woelfle J., van der Donk A., Bär A., Reutter H., Hepp T., Morhart P. Diagnostic Utility of interleukin-6 in early-onset sepsis among term newborns: impact of maternal risk factors and CRP evaluation. Children (Basel), 2023, Vol. 11, no. 1, 53. doi: 10.3390/children11010053.Schleier M., Lubig J., Kehl S., Hébert S., Woelfle J., van der Donk A., Bär A., Reutter H., Hepp T., Morhart P. Diagnostic Utility of Interleukin-6 in Early-Onset Sepsis among Term Newborns: Impact of Maternal Risk Factors and CRP Evaluation. Children (Basel), 2023. – Vol. 11, no. 1. – P. 53. doi: 10.3390/children11010053Shankar-Hari M., Phillips G., Levy M., Seymour C., Liu V., Deutschman C., Angus D., Rubenfeld G., Singer M. Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA, 2016, Vol. 315, no. 8, pp. 775-787.Shankar-Hari M., Phillips G., Levy M., Seymour C., Liu V., Deutschman C., Angus D., Rubenfeld G., Singer M.; Sepsis Definitions Task Force. Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016. – Vol. 315, no. 8. - P. 775-87. doi: 10.1001/jama.2016.0289.Sharma D., Farahbakhsh N., Shastri S., Sharma P. Biomarkers for diagnosis of neonatal sepsis: A literature review. J. Matern. Fetal Neonatal Med., 2018, Vol. 31, no. 12, pp. 1646-1659.Sharma D., Farahbakhsh N., Shastri S., Sharma P. Biomarkers for diagnosis of neonatal sepsis: A literature review. J. Matern. Fetal Neonatal Med., 2018. – Vol. 31, no. 12. – P. 1646–1659. doi: 10.1080/14767058.2017.1322060.Sikora J., Chlebna-Sokol D., Krzyzanska-Oberbek A. Proinflammatory cytokines (IL-6, IL-8), cytokine inhibitors (IL-6sR, sTNFRII) and anti-inflammatory cytokines (IL-10, IL-13) in the pathogenesis of sepsis in newborns and infants. Arch. Immunol. Ther. Exp. (Warsz.), 2001, Vol. 49, no. 5, pp. 399-404.Sikora J., Chlebna-Sokol D., Krzyzanska-Oberbek A. Proinflammatory cytokines (IL-6, IL-8), cytokine inhibitors (IL-6sR, sTNFRII) and anti-inflammatory cytokines (IL-10, IL-13) in the pathogenesis of sepsis in newborns and infants. Arch Immunol Ther Exp (Warsz), 2001. – Vol. 49, no. 5. – P. 399–404. PMID: 11798138.Silveira R., Procianoy R. Evaluation of interleukin-6, tumour necrosis factor-alpha and interleukin-1beta for early diagnosis of neonatal sepsis. Acta Paediatr., 1999, Vol. 88, no. 6, pp. 647-650.Silveira R., Procianoy R. Evaluation of interleukin-6, tumour necrosis factor-alpha and interleukin-1beta for early diagnosis of neonatal sepsis. Acta Paediatr., 1999. – Vol. 88, no. 6. – P. 647-650. doi: 10.1080/08035259950169314.Simonsen K., Anderson-Berry A., Delair S., Dele Davies H. Early-onset neonatal sepsis. Clin. Microbiol. Rev., 2014, Vol. 27, no. 1, pp. 21-47.Simonsen K., Anderson-Berry A., Delair S., Dele Davies H. Early-onset neonatal sepsis. Clinical Microbiology Reviews, 2014. – Vol.27, no. 1. – P. 21–47. doi: 10.1128/CMR.00031-13Thomas-Rüddel D., Giamarellos-Bourboulis E., Neumann C., Briegel J., Roquilly A., Annane D., Wetzker R., Bauer M.; iRECORDS study group. IFNγ in human sepsis: a scoping review. Ann. Intensive Care, 2025, Vol. 15, 112. doi: 10.1186/s13613-025-01534-z.Thomas-Rüddel D., Giamarellos-Bourboulis E., Neumann C., Briegel J., Roquilly A., Annane D., Wetzker R., Bauer M.; iRECORDS study group. IFNγ in human sepsis: a scoping review. Ann Intensive Care, 2025. – Vol. 15, no. 1. – P. 112. doi: 10.1186/s13613-025-01534-z.van Leeuwen L., Fourie E., van den Brink G., Bekker V., van Houten M. Diagnostic value of maternal, cord blood and neonatal biomarkers for early-onset sepsis: a systematic review and meta-analysis. Clin. Microbiol. Infect., 2024, Vol. 30, no. 7, pp. 850-857.van Leeuwen L., Fourie E., van den Brink G., Bekker V., van Houten M. Diagnostic value of maternal, cord blood and neonatal biomarkers for early-onset sepsis: a systematic review and meta-analysis. Clin Microbiol Infect., 2024. – Vol. 30, no. 7. – P. 850-857. doi: 10.1016/j.cmi.2024.03.005.Vasilescu D., Dan A., Stefan L., Vasilescu S., Dima V., Cîrstoiu M. Assessment of culture-negative neonatal early-onset sepsis: risk factors and utility of currently used serum biomarkers. Children (Basel), 2025, Vol. 12, no. 3, 355. doi: 10.3390/children12030355.Vasilescu D., Dan A., Stefan L., Vasilescu S., Dima V., Cîrstoiu M. Assessment of Culture-Negative Neonatal Early-Onset Sepsis: Risk Factors and Utility of Currently Used Serum Biomarkers. Children (Basel), 2025. – Vol. 12, no. 3. – P. 355. doi: 10.3390/children12030355Vucic J., Vucic M., Stankovic T., Stamenkovic H., Stankovic S., Zlatanovic D. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates. Open Med. (Wars.), 2021, Vol. 16, no. 1, pp. 139-145.Vucic J., Vucic M., Stankovic T., Stamenkovic H., Stankovic S., Zlatanovic D. Potential role of IFN-γ and IL-5 in sepsis prediction of preterm neonates. Open Med (Wars), 2021. – Vol. 16, no. 1. - P. 139-145. doi: 10.1515/med-2021-0206.Wen S., Ezure Y., Rolley L., Spurling G., Lau C., Riaz S., Paterson D., Irwin A. Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis. PLoS Med., 2021, Vol. 18, no. 9, e1003787. doi: 10.1371/journal.pmed.1003787.Wen S., Ezure Y., Rolley L., Spurling G., Lau C., Riaz S., Paterson D., Irwin A. Gram-negative neonatal sepsis in low- and lower-middle-income countries and WHO empirical antibiotic recommendations: A systematic review and meta-analysis. PLoS Med., 2021. – Vol. 18, no. 9. – P. e1003787. doi: 10.1371/journal.pmed.1003787.Wiersinga W., Leopold S., Cranendonk D., van der Poll T. Host innate immune responses to sepsis. Virulence, 2014, Vol. 5, no. 1, pp. 36-44.Wiersinga W., Leopold S., Cranendonk D., van der Poll T. Host innate immune responses to sepsis. Virulence, 2014. – Vol. 5, no. 1. – P. 36-44. doi: 10.4161/viru.25436.World Health Organization. WHO recommendations for management of serious bacterial infections in infants aged 0-59 days. Available at: https://www.who.int/publications/i/item/9789240102903.WHO recommendations for management of serious bacterial infections in infants aged 0-59 days. [Aug; 2025]. 2024. https://www.who.int/publications/i/item/9789240102903World Health Organization. WHO releases new target product profile for diagnostic tests to detect serious bacterial infections in young infants. Available at: https://www.who.int/news/item/06-08-2025-who-releases-newtpp-for-diagnostic-tests-to-detect-serious-bacterial-infections-in-young-infants.World Health Organization. WHO releases new target product profile for diagnostic tests to detect serious bacterial infections in young infants https://www.who.int/news/item/06-08-2025-who-releases-new-tpp-for-diagnostic-tests-to-detect-serious-bacterial-infections-in-young-infantsWynn J., Polin R. Progress in the management of neonatal sepsis: The importance of a consensus definition. Pediatr. Res., 2018, Vol. 83, no. 1-1, pp. 13-15.Wynn J., Polin R. Progress in the management of neonatal sepsis: The importance of a consensus definition. Pediatr. Res., 2018. – Vol. 83, no. 1-1. – P. 13–15. doi: 10.1038/pr.2017.224.Yang K., He Y., Xiao S., Ai Q., Yu J. Identification of progranulin as a novel diagnostic biomarker for earlyonset sepsis in neonates. Clin. Microbiol. Infect. Dis., 2020, Vol. 39, no. 12, pp. 2405-2414.Yang K., He Y., Xiao S., Ai Q., Yu J. Identification of progranulin as a novel diagnostic biomarker for early-onset sepsis in neonates. Clin Microbiol Infect Dis., 2020. – Vol. 39, no. 12. - P. 2405-2414. doi: 10.1007/s10096-020-03981-x.Ye Q., Du L., Shao W., Shang S. Utility of cytokines to predict neonatal sepsis. Pediatr. Res., 2017, Vol. 81, no. 4, pp. 616-621.Ye Q., Du L., Shao W., Shang S. Utility of cytokines to predict neonatal sepsis. Pediatr Res., 2017. – Vol. 81, no. 4. – P. 616-621. doi: 10.1038/pr.2016.267.

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