nodgoРоссийский журнал детской гематологии и онкологии (РЖДГиО)Russian Journal of Pediatric Hematology and Oncology2311-12672413-5496LTD “Graphica”10.17650/2311-1267-2018-5-2-25-31nodgo-380Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESДискуссионные вопросы и новые стратегии применения препаратов иммуноглобулинов для внутривенного введения в неонатологической практикеDiscussion issues and new strategies of intravenous immunoglobulins treatment in neonatal practiceПанкратьеваЛ. Л.PankratievaL. L.fdoc@yandex.ruМухинВ. Е.MukhinV. E.МилеваО. И.MilevaO. I.РумянцевА. Г.RumyantseA. G.ВолодинН. Н.VolodinN. N.ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России; Филиал ГБУЗ «Городская клиническая больница № 24 Департамента здравоохранения города Москвы» – «Перинатальный центр»РоссияDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of Russia; City Clinical Hospital № 24 of the Moscow City Health Department – Perinatal CenterRussian FederationФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава РоссииРоссияDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Health of RussiaRussian FederationФилиал ГБУЗ «Городская клиническая больница № 24 Департамента здравоохранения города Москвы» – «Перинатальный центр»РоссияCity Clinical Hospital № 24 of the Moscow City Health Department – Perinatal CenterRussian Federation201823042018522531Copyright © Панкратьева Л.Л., Мухин В.Е., Милева О.И., Румянцев А.Г., Володин Н.Н., 20182018Панкратьева Л.Л., Мухин В.Е., Милева О.И., Румянцев А.Г., Володин Н.Н.Pankratieva L.L., Mukhin V.E., Mileva O.I., Rumyantse A.G., Volodin N.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nodgo.org/jour/article/view/380

Риск развития генерализованных бактериальных инфекций у глубоко недоношенных детей значительно выше по сравнению с более зрелыми по сроку гестации новорожденными. В неонатологической практике препараты иммуноглобулинов для внутривенного введения (ИГВВ) применяются как в качестве стратегии профилактики, так и адъювантной терапии при реализации раннего и позднего неонатального сепсиса. В то же время незрелость иммунной системы у детей с очень низкой и экстремально низкой массой тела является основной причиной, определяющей неэффективность применения препаратов ИГВВ у недоношенных детей. Чрезвычайную актуальность приобретают выявление факторов, ограничивающих терапевтическую эффективность препаратов ИГВВ у недоношенных детей, и определение стратегии оптимизации эффективности ИГВВ у недоношенных новорожденных с внутриутробной и нозокомиальной инфекциями.

The risk of developing generalized bacterial infections in deeply premature infants is significantly higher than compared with the more mature newborns in terms of gestational age. In the neonatological practice, immunoglobulin preparations for intravenous administration (IVIg) are used both as a strategy for prevention and adjuvant therapy for the implementation of early and late neonatal sepsis. At the same time, the immaturity of the immune system in children with underweight and extremely low body weight is the main cause determining the ineffectiveness of IVIg medications in premature infants. Extremely actuality is the identification of factors limiting the therapeutic effectiveness of IVIg medications in premature infants, and the definition of a strategy for optimizing the effectiveness of IVIg in preterm infants with intrauterine and nosocomial infections.

недоношенностьиммуноглобулины для внутривенного введенияфагоцитознеонатальный сепсисиммуномодулирующая терапияprematurityimmunoglobulins for intravenous administrationphagocytosisneonatal sepsisimmunomodulatory therapyReferencesДегтярева М.В., Бирюкова Т.В., Володин Н.Н. и др. Клиниколабораторные особенности раннего неонатального сепсиса у детей различного гестационного возраста и оценка эффективности иммунозаместительной терапии Пентаглобином. Педиатрия. Журнал им. Г.Н. Сперанского 2008;87(1):32–40. [Degtyareva M.V., Biryukova T.V., Volodin N.N. et al. Clinical and laboratory peculiarities of early neonatal sepsis in children with different gestation age and estimation of efficacy of immunosubstitutive therapy by Pentaglobin. Pediatriya. Zhurnal im. G.N. Speranskogo = Pediatria. Journal named after G.N. Speransky 2008;87(1):32– 40. (In Russ.)].Дегтярева М.В., Бирюкова Т.В., Володин Н.Н. и др. Клиниколабораторные особенности раннего неонатального сепсиса у детей различного гестационного возраста и оценка эффективности иммунозаместительной терапии Пентаглобином. Педиатрия. Журнал им. Г.Н. Сперанского 2008;87(1):32–40. [Degtyareva M.V., Biryukova T.V., Volodin N.N. et al. Clinical and laboratory peculiarities of early neonatal sepsis in children with different gestation age and estimation of efficacy of immunosubstitutive therapy by Pentaglobin. Pediatriya. Zhurnal im. G.N. Speranskogo = Pediatria. Journal named after G.N. Speransky 2008;87(1):32– 40. (In Russ.)].Fanaroff A.A., Korones S.B., Wright L.L. et al. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute Of Child Health And Human Development Neonatal Research Network. N Engl J Med 1994;330(16):1107–13. doi: 10.1056/NEJM199404213301602.Fanaroff A.A., Korones S.B., Wright L.L. et al. A controlled trial of intravenous immune globulin to reduce nosocomial infections in very-low-birth-weight infants. National Institute Of Child Health And Human Development Neonatal Research Network. N Engl J Med 1994;330(16):1107–13. doi: 10.1056/NEJM199404213301602.Christensen R.D., Hardman T., Thornton J., Hill H.R. A randomized, double-blind, placebo-controlled investigation of the safety of intravenous immune globulin administration to preterm neonates. J Perinatol 1989;9(2):126–30. PMID: 2738720.Christensen R.D., Hardman T., Thornton J., Hill H.R. A randomized, double-blind, placebo-controlled investigation of the safety of intravenous immune globulin administration to preterm neonates. J Perinatol 1989;9(2):126–30. PMID: 2738720.Kempf C., Stucki M., Boschetti N. Pathogen inactivation and removal procedures used in the production of intravenous immunoglobulins. Biologicals 2007;35(1):35–42. doi: 10.1016/j.biologicals.2006.01.002.Kempf C., Stucki M., Boschetti N. Pathogen inactivation and removal procedures used in the production of intravenous immunoglobulins. Biologicals 2007;35(1):35–42. doi: 10.1016/j.biologicals.2006.01.002.Stoll B.J., Hansen N. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin Perinatol 2003;27(4):293–301. PMID: 14510320.Stoll B.J., Hansen N. Infections in VLBW infants: studies from the NICHD Neonatal Research Network. Semin Perinatol 2003;27(4):293–301. PMID: 14510320.Adams-Chapman I., Stoll B.J. Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis 2006;19(3):290–7. doi: 10.1097/01.qco.0000224825.57976.87.Adams-Chapman I., Stoll B.J. Neonatal infection and long-term neurodevelopmental outcome in the preterm infant. Curr Opin Infect Dis 2006;19(3):290–7. doi: 10.1097/01.qco.0000224825.57976.87.Wilson-Costello D., Friedman H., Minich N. et al. Improved neurodevelopmental outcomes for extremely low birth weight infants in 2000–2002. Pediatrics 2007;119(1):37–45. doi: 10.1542/peds.2006-1416Wilson-Costello D., Friedman H., Minich N. et al. Improved neurodevelopmental outcomes for extremely low birth weight infants in 2000–2002. Pediatrics 2007;119(1):37–45. doi: 10.1542/peds.2006-1416Ohlsson A., Lacy J.B. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2004. Issue no. 1. Article no. CD001239.Ohlsson A., Lacy J.B. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2004. Issue no. 1. Article no. CD001239.Ohlsson A., Lacy J.B. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2013. Issue no. 7. Article no.Ohlsson A., Lacy J.B. Intravenous immunoglobulin for suspected or subsequently proven infection in neonates. Cochrane Database Syst Rev 2013. Issue no. 7. Article no.CD001239.CD001239.INIS Study Collaborative Group. The INIS Study. International neonatal immunotherapy study: non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis – an international, placebo controlled, multicentre randomised trial. BMC Pregnancy Childbirth 2008;8:52. doi: 10.1186/1471-2393-8-52.INIS Study Collaborative Group. The INIS Study. International neonatal immunotherapy study: non-specific intravenous immunoglobulin therapy for suspected or proven neonatal sepsis – an international, placebo controlled, multicentre randomised trial. BMC Pregnancy Childbirth 2008;8:52. doi: 10.1186/1471-2393-8-52.Ohlsson A., Lacy J.B. Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants. Cochrane Database Syst Rev 2004. Issue no. 1.Ohlsson A., Lacy J.B. Intravenous immunoglobulin for preventing infection in preterm and/or low-birth-weight infants. Cochrane Database Syst Rev 2004. Issue no. 1.Article no. CD000361.Article no. CD000361.Negi V.S., Elluru S., Sibéril S. et al. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol 2007;27(3):233–45. doi: 10.1007/ s10875-007-9088-9.Negi V.S., Elluru S., Sibéril S. et al. Intravenous immunoglobulin: an update on the clinical use and mechanisms of action. J Clin Immunol 2007;27(3):233–45. doi: 10.1007/ s10875-007-9088-9.Mussi-Pinhata M.M., Rego M.A. Immunological peculiarities of extremely preterm infants: a challenge for the prevention of nosocomial sepsis. J Pediatr (Rio J) 2005; 81(1 Suppl):S59–68. PMID: 15809699.Mussi-Pinhata M.M., Rego M.A. Immunological peculiarities of extremely preterm infants: a challenge for the prevention of nosocomial sepsis. J Pediatr (Rio J) 2005; 81(1 Suppl):S59–68. PMID: 15809699.Källman J., Schollin J., Schalèn C., Erlandsson A., Kihlström E. Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates. Arch Dis Child Fetal Neonatal Ed 1998;78(1):F46–50. PMID: 9536841.Källman J., Schollin J., Schalèn C., Erlandsson A., Kihlström E. Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates. Arch Dis Child Fetal Neonatal Ed 1998;78(1):F46–50. PMID: 9536841.Wolach B., Dolfin T., Regev R., Gilboa S., Schlesinger M. The development of the complement system after 28 weeks’ gestation. Acta Paediatr 1997;86(5):523–7. PMID: 9183493.Wolach B., Dolfin T., Regev R., Gilboa S., Schlesinger M. The development of the complement system after 28 weeks’ gestation. Acta Paediatr 1997;86(5):523–7. PMID: 9183493.Cates K.L., Goetz C., Rosenberg N. et al. Longitudinal development of specific and functional antibody in very low birth weight premature infants. Pediatr Res 1988;23(1):14–22. doi: 10.1203/00006450198801000-00005.Cates K.L., Goetz C., Rosenberg N. et al. Longitudinal development of specific and functional antibody in very low birth weight premature infants. Pediatr Res 1988;23(1):14–22. doi: 10.1203/00006450198801000-00005.Lewis D., Wilson C. Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In: Remington, Klein, Wilson and Baker (eds.) Infectious diseases of the fetus and newborn infant, 6th ed. Elsevier Saunders: Philadelphia, 2006.Lewis D., Wilson C. Developmental immunology and role of host defenses in fetal and neonatal susceptibility to infection. In: Remington, Klein, Wilson and Baker (eds.) Infectious diseases of the fetus and newborn infant, 6th ed. Elsevier Saunders: Philadelphia, 2006.Baley J.E. Neonatal sepsis: the potential for immunotherapy. Clin Perinatol 1988;15(4):755–71. PMID: 3061698.Baley J.E. Neonatal sepsis: the potential for immunotherapy. Clin Perinatol 1988;15(4):755–71. PMID: 3061698.Shaw C.K., Thapalial A., Shaw P., Malla K. Intravenous immunoglobulins and haematopoietic growth factors in the prevention and treatment of neonatal sepsis: ground reality or glorified myths? Int J Clin Pract 2007;61(3):482–7. doi: 10.1111/j.1742-1241.2006.01162.x.Shaw C.K., Thapalial A., Shaw P., Malla K. Intravenous immunoglobulins and haematopoietic growth factors in the prevention and treatment of neonatal sepsis: ground reality or glorified myths? Int J Clin Pract 2007;61(3):482–7. doi: 10.1111/j.1742-1241.2006.01162.x.Maeda M., van Schie R.C., Yüksel B. et al. Differential expression of Fc receptors for IgG by monocytes and granulocytes from neonates and adults. Clin Exp Immunol 1996;103(2):343–7. PMID: 8565322.Maeda M., van Schie R.C., Yüksel B. et al. Differential expression of Fc receptors for IgG by monocytes and granulocytes from neonates and adults. Clin Exp Immunol 1996;103(2):343–7. PMID: 8565322.Nagelkerke S., Kuijpers T. Immunomodulation by IVIg and the Role of Fc-Gamma Receptors: Classic Mechanisms of Action after all? Front Immunol 2015;5:674. doi: 10.3389/fimmu.2014.00674.Nagelkerke S., Kuijpers T. Immunomodulation by IVIg and the Role of Fc-Gamma Receptors: Classic Mechanisms of Action after all? Front Immunol 2015;5:674. doi: 10.3389/fimmu.2014.00674.Haridan U., Mokhtar U., Machado L. A comparison of assays for accurate copy number measurement of the low-affinity Fc gamma receptor genes FCGR3A and FCGR3B. PLoS One 2015;10(1):e0116791. doi: 10.1371/journal.pone.0116791.Haridan U., Mokhtar U., Machado L. A comparison of assays for accurate copy number measurement of the low-affinity Fc gamma receptor genes FCGR3A and FCGR3B. PLoS One 2015;10(1):e0116791. doi: 10.1371/journal.pone.0116791.Calhoun D., Lunøe M., Du Y. et al. Granulocyte colony-stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor. Pediatrics 2000;105(2):392–7. PMID: 10654961.Calhoun D., Lunøe M., Du Y. et al. Granulocyte colony-stimulating factor serum and urine concentrations in neutropenic neonates before and after intravenous administration of recombinant granulocyte colony-stimulating factor. Pediatrics 2000;105(2):392–7. PMID: 10654961.

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