mvjrМедицинский вестник Юга РоссииMedical Herald of the South of Russia2219-80752618-7876The Rostov State Medical University10.21886/2219-8075-2024-15-3-77-82mvjr-1952Research ArticleПЕДИАТРИЯPAEDIATRICSПредикторы неблагоприятных неврологических исходов у недоношенных детей: современный взгляд на проблемуPredictors of unfavorable neurological outcomes in premature children: a modern view on the problemПавлиноваЕ. Б.PavlinovaE. B.

Павлинова Елена Борисовна, д.м.н., доцент, заведующая кафедрой госпитальной педиатрии с курсом ДПО, проректор по учебной работе

Омск

Elena B. Pavlinova, Dr. Sci. (Med.), Associate Professor, Head of the Department of Hospital Pediatrics with Postgraduate Course, Vice-Rector for Academic Affairs

Omsk

elena@mail.ruhttps://orcid.org/0000-0003-2035-5653СавченкоО. А.SavchenkoO. A.

Савченко Ольга Анатольевна, к.м.н., доцент кафедры госпитальной педиатрии с курсом ДПО

Омск

Olga A. Savchenko, Cand. Sci. (Med.), Associate Professor, Hospital Pediatrics with Postgraduate Course

Omsk

olgasav1978@mail.ruОмский государственный медицинский университетOmsk State Medical University2024120720241537782Copyright © Павлинова Е.Б., Савченко О.А., 20242024Павлинова Е.Б., Савченко О.А.Pavlinova E.B., Savchenko O.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medicalherald.ru/jour/article/view/1952

Цель: оценить прогностическую значимость антител к NR2-субъединице N-метил-D-аспартат (NMDA) рецептора глутамата и мозгового натрийуретического пропептида (NTproBNP) как предикторов неблагоприятных неврологических исходов у недоношенных детей.Материалы и методы: в проспективное когортное сплошное исследование включён 151 недоношенный ребенок с гестационным возрастом (ГВ) 26–32 недели и массой тела 590–1990 г. Детям проводилось количественное определение уровня NTproBNP в пуповинной крови и уровень антител к NR2- субъединице NMDA рецептора глутамата в сыворотке крови на 21-е сутки жизни. Распределение детей по группам проводилось на основании оценки неврологических исходов в контрольных точках исследования: 1-я контрольная точка — момент выписки из стационара, 2-я контрольная точка — скоррегированный возраст (СКВ) 1 год жизни, 3-я контрольная точка — 4 года жизни.Результаты: установлено «каскадное» увеличение когорты детей с неблагоприятными неврологическими исходами с 36,4% на момент выписки из стационара до 70% к 4-летнему возрасту. Установлены высокие значения уровня NT-proBNP в пуповинной крови и антител к NR2-субъединице NMDA рецептора глутамата на 21-е сутки постнатальной жизни у детей как с макроструктурными поражениями головного мозга в неонатальном периоде, так имеющих неблагоприятный неврологический исход в 1 год СКВ и в 4 года жизни.Заключение: современные нейрохимические маркеры поражения ЦНС NT-proBNP и антитела к NR2-субъединице NMDA рецептора глутамата открывают возможности ранней диагностики повреждения головного мозга на клеточном уровне и начала нейропротективной терапии с целью снижения неврологической инвалидизации.

Objective: to assess the prognostic significance of antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor and brain natriuretic propeptide (NTproBNP) as predictors of unfavorable neurological outcomes in premature children.Materials and methods: A prospective cohort continuous study included 151 premature children, with a gestational age (GA) of 26–32 weeks and a body weight of 590–1990 gr. The children were measured the quantitation of NTproBNP level in the cord blood and level of antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor in the blood serum on the 21st day of life. The division of children into groups was carried out in accordance with the assessment of neurological outcomes at control points of the research: 1 control point — at the time of discharge from the hospital, 2 control point — at the age of 1 year of corrected age (CA), 3 control point — 4 years of life.Results: in the course of the study, it was found a “cascade” increase in the cohort of children with unfavorable neurological outcomes from 36.4% at the time of discharge from the hospital to 70% by the age of 4 years. High values of NT-proBNP level in cord blood and antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor were established on 21st day of postnatal life in children with both macrostructural brain damages in the neonatal period and having an unfavorable neurological outcome at the age of 1 year of corrected age (CA) and at 4 years of life.Conclusion: modern neurochemical markers of CNS damages N-proBNP and antibodies to the NR2 subunit of the N-methyl-D-aspartate (NMDA) glutamate receptor open up the possibilities of early diagnosis of brain damages at the cellular level and the start of neuroprotective therapy to reduce neurological disability.

недоношенностьневрологический исходпредикторыэксайтотоксичностьмозговой натрийуретический пропептидprematurityneurological outcomepredictorsexcitotoxicitybrain natriuretic propeptideReferencesFinch-Edmondson M, Morgan C, Hunt RW, Novak I. Emergent Prophylactic, Reparative and Restorative Brain Interventions for Infants Born Preterm With Cerebral Palsy. Front Physiol. 2019;10:15. https://doi.org/10.3389/fphys.2019.00015Finch-Edmondson M, Morgan C, Hunt RW, Novak I. Emergent Prophylactic, Reparative and Restorative Brain Interventions for Infants Born Preterm With Cerebral Palsy. Front Physiol. 2019;10:15. https://doi.org/10.3389/fphys.2019.00015Penn AA, Gressens P, Fleiss B, Back SA, Gallo V. Controversies in preterm brain injury. Neurobiol Dis. 2016;92(Pt A):90-101. https://doi.org/10.1016/j.nbd.2015.10.01Penn AA, Gressens P, Fleiss B, Back SA, Gallo V. Controversies in preterm brain injury. Neurobiol Dis. 2016;92(Pt A):90-101. https://doi.org/10.1016/j.nbd.2015.10.01Malik S, Vinukonda G, Vose LR, Diamond D, Bhimavarapu BB, et al. Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. J Neurosci. 2013;33(2):411-423. https://doi.org/10.1523/JNEUROSCI.4445-12.2013Malik S, Vinukonda G, Vose LR, Diamond D, Bhimavarapu BB, et al. Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. J Neurosci. 2013;33(2):411-423. https://doi.org/10.1523/JNEUROSCI.4445-12.2013Oltman SP, Rogers EE, Baer RJ, Jasper EA, Anderson JG, et al. Newborn metabolic vulnerability profile identifies preterm infants at risk for mortality and morbidity. Pediatr Res. 2021;89(6):1405-1413. https://doi.org/10.1038/s41390-020-01148-0Oltman SP, Rogers EE, Baer RJ, Jasper EA, Anderson JG, et al. Newborn metabolic vulnerability profile identifies preterm infants at risk for mortality and morbidity. Pediatr Res. 2021;89(6):1405-1413. https://doi.org/10.1038/s41390-020-01148-0Weider S, Lærum AMW, Evensen KAI, Reitan SK, Lydersen S, et al. Neurocognitive function and associations with mental health in adults born preterm with very low birthweight or small for gestational age at term. Front Psychol. 2023;13:1078232. https://doi.org/10.3389/fpsyg.2022.1078232Weider S, Lærum AMW, Evensen KAI, Reitan SK, Lydersen S, et al. Neurocognitive function and associations with mental health in adults born preterm with very low birthweight or small for gestational age at term. Front Psychol. 2023;13:1078232. https://doi.org/10.3389/fpsyg.2022.1078232Vo Van P, Alison M, Morel B, Beck J, Bednarek N, et al. Advanced Brain Imaging in Preterm Infants: A Narrative Review of Microstructural and Connectomic Disruption. Children (Basel). 2022;9(3):356. https://doi.org/10.3390/children9030356Vo Van P, Alison M, Morel B, Beck J, Bednarek N, et al. Advanced Brain Imaging in Preterm Infants: A Narrative Review of Microstructural and Connectomic Disruption. Children (Basel). 2022;9(3):356. https://doi.org/10.3390/children9030356Ma Q, Wang H, Rolls ET, Xiang S, Li J, et al. Lower gestational age is associated with lower cortical volume and cognitive and educational performance in adolescence. BMC Med. 2022;20(1):424. https://doi.org/10.1186/s12916-022-02627-3Ma Q, Wang H, Rolls ET, Xiang S, Li J, et al. Lower gestational age is associated with lower cortical volume and cognitive and educational performance in adolescence. BMC Med. 2022;20(1):424. https://doi.org/10.1186/s12916-022-02627-3Miyoshi T, Hosoda H, Minamino N. Significance of Atrial and Brain Natriuretic Peptide Measurements in Fetuses With Heart Failure. Front Physiol. 2021;12:654356. https://doi.org/10.3389/fphys.2021.654356Miyoshi T, Hosoda H, Minamino N. Significance of Atrial and Brain Natriuretic Peptide Measurements in Fetuses With Heart Failure. Front Physiol. 2021;12:654356. https://doi.org/10.3389/fphys.2021.654356Abdelalim EM, Takada T, Torii R, Tooyama I. Molecular cloning of BNP from heart and its immunohistochemical localization in the hypothalamus of monkey. Peptides. 2006;27(7):1886-1893. https://doi.org/10.1016/j.peptides.2006.01.001Abdelalim EM, Takada T, Torii R, Tooyama I. Molecular cloning of BNP from heart and its immunohistochemical localization in the hypothalamus of monkey. Peptides. 2006;27(7):1886-1893. https://doi.org/10.1016/j.peptides.2006.01.001Gallo G, Bianchi F, Cotugno M, Volpe M, Rubattu S. Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension. J Clin Med. 2020;9(7):2265. https://doi.org/10.3390/jcm9072265Gallo G, Bianchi F, Cotugno M, Volpe M, Rubattu S. Natriuretic Peptides, Cognitive Impairment and Dementia: An Intriguing Pathogenic Link with Implications in Hypertension. J Clin Med. 2020;9(7):2265. https://doi.org/10.3390/jcm9072265Zonneveld HI, Ikram MA, Hofman A, Niessen WJ, van der Lugt A, et al. N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population. Radiology. 2017;283(1):205-214. https://doi.org/10.1148/radiol.2016160548Zonneveld HI, Ikram MA, Hofman A, Niessen WJ, van der Lugt A, et al. N-Terminal Pro-B-Type Natriuretic Peptide and Subclinical Brain Damage in the General Population. Radiology. 2017;283(1):205-214. https://doi.org/10.1148/radiol.2016160548Савченко О.А., Павлинова Е.Б. Отдаленные неврологические исходы у недоношенных детей при эксайтотоксическом повреждении головного мозга. Журнал неврологии и психиатрии им. С.С. Корсакова. Спецвыпуски. 2022;122(9-2):37-41. https://doi.org/10.17116/jnevro202212209237Savchenko O.A., Pavlinova E.B. Long-term neurological outcomes in premature children with excitotoxic brain damage. S.S. Korsakov Journal of Neurology and Psychiatry. 2022;122(9-2):37-41. (In Russ.) https://doi.org/10.17116/jnevro202212209237

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