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Abstract
Тhere is active research into the concept of placental influence on programming neurological and neuropyschological disorders in fetuses and newborns caused by release of pro-inflammatory substances and deficiency of regulatory neuroendocrine placenta functions.
The aim of this study was to establish a relationship between maternal levels of extracellular interaction mediators and the development of neurological disorders in neonates as well as determine cytokine profiles in children with neurological deficits.
Materials and methods. We examined 50 full-term infants discharged from maternity hospital in satisfactory condition. Levels of C-reactive protein, key pro-inflammatory (IL-1β, IFN-γ, IL-8, IL-6, TNF-α) and anti-inflammatory (IL-10, IL-4) cytokines were analyzed in umbilical cord blood at birth, at age three days, and at three months old. At three months of age, depending on presence or absence of motor impairments, children were divided into groups. Statistical hypotheses testing utilized Mann-Whitney U test and Student's t-test. Standardized values based on mean concentration were used for statistical data transformation.
Results. In mothers whose children developed neurological disorders, statistically significant elevation of IL-1β level was observed. These children showed increased activity of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, IL-8) at birth, at day three (IL-8, TNF-α), and at three months (IL-8, IL-10). This corresponds to a chronic inflammatory reaction pattern. Insufficient production of anti-inflammatory cytokines (IL-10, IL-4) noted in umbilical cord blood and at three months resulted in immune process imbalance impeding recovery of brain tissue structural and functional properties.
Conclusion. In healthy children, balance of pro- and anti-inflammatory cytokines exhibits bidirectional dynamics by three months. Children developing neurological pathologies show similar patterns across all studied cytokines reflecting severity of clinical conditions.
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Ramirez BY, Novoa GM. Estudio neuropsicologico en ninos de anos con antecedente de hipoxia perinatal. Arch Neurocien. 2008; 13(3): 162-169
Feldman R. The development of regulatory functions from birth to 5 years: insights from premature infants. Child Dev. 2009; 80(2): 544-561. doi: 10.1111/j.1467-8624.2009.01278.x
Medina A, Kahn I, Munoz H, Leyva J, Moreno J, Vega SM. Child neurodevelopment: normal characteristics and warning signs in children under five years. Rev Peru Med Exp Salud Publica. 2015; 32(3): 565-573
Manganaro L, Bernardo S, La Barbera L, Noia G, Masini L, Tomei A, et al. Role of foetal MRI in the evaluation of ischaemic-haemorrhagic lesions of the foetal brain. J Perinat Med. 2012; 40(4): 419-26. doi: 10.1515/jpm-2011-0182
Jarvis D, Mooney C, Cohen J, Papaioannou D, Bradburn M, Sutton A, Griffiths PD. A systematic review and meta-analysis to determine the contribution of mr imaging to the diagnosis of foetal brain abnormalities In Utero. Eur Radiol. 2017; 27(6): 2367-2380. doi: 10.1007/s00330-016-4563-4
Roberts JA, Iyer KK, Finnigan S, Vanhatalo S, Breakspear M. Scale-free bursting in human cortex following hypoxia at birth. J Neurosci. 2014; 34(19): 6557-6572. doi: 10.1523/JNEUROSCI.4701-13.2014
Kratimenos P, Penn AA. Placental programming of neuropsychiatric disease. Pediatr Res. 2019; 86: 157-164. doi: 10.1038/s41390-019-0405-9
Robillard S, Mercier C, Breton V, Paquin-Veillette J, Guay A, Lizotte F, Geraldes P. Ablation of angiotensin type 2 receptor prevents endothelial nitric oxide synthase glutathionylation and nitration in ischaemic abductor muscle of diabetic mice. Diab Vasc Dis Res. 2020; 17(1): 1-10. doi: 10.1177/1479164119883978
Dommergues MA, Plaisant F, Vemey C. Early microglial activation following neonatal excitotoxic brain damage in mice: a potential target for neuroprotection. Neuroscience. 2003; 121(3): 619-628. doi: 10.1016/s0306-4522(03)00558-x
Anderson P, Klenman CS, Lister G. Cardiovascular function during development and the response to hypoxia. Fetal and neonat physiology. 3rd ed. Philadelphia: Saunders. 2004; 456-487
Miller S, Weiss J, Barnwell A, Ferriero DM, Latal-Hajnal B, Ferrer-Rogers A, et al. Seizure-associated brain injury in term newborns with perinatal asphyxia. Neurology. 2002; 58(4): 542-548. doi: 10.1212/wnl.58.4.542
Santana C, Guindeo MC, Gonzakz G, García-Muñoz F, Saavedra P, Doménech E. Cord blood levels of cytokines as predictors of early neonatal sepsis. Acta Pediatr. 2001; 90(10): 1176-1181. doi: 10.1080/08035250131706160
Sidorova IS, Nikitina NA, Hunanyan AL, Ageev MB. Fetal brain development and the influence of prenatal damaging factors on the main stages of neurogenesis. Russian Bulletin of the obstetrician-gynecologist. 2022; 22(1): 35-44. Russian (Сидорова И.С., Никитина Н.А., Унанян А.Л., Агеев М.Б. Развитие головного мозга плода и влияние пренатальных повреждающих факторов на основные этапы нейрогенеза //Российский вестник акушера-гинеколога. 2022. Т. 22, № 1. С. 35-44.) doi:10.17116/rosakush20222201135
Sugimoto MA, Sousa LP, Pinho V, Perretti M, Teixeira MM. Resolution of inflammation: what controls its onset? Front Immunol. 2016; 7: 160. doi: 10.3389/fimmu.2016.00160 15
Schett G, Neurath MF. Resolution of chronic inflammatory disease: universal and tissue-specific concepts. Nat Commun. 2018; 9(1): 3261. doi: 10.1038/s41467- 018-05800-6 16
del Pilar Medina Alva M, Kahn IC, Huerta PM, Sánchez JL, Calixto JM, Sánchez SMV. Child neurodevelopment: normal characteristics and warning signs in children under five years. Rev Peru Med Exp Salud Publica. 2015; 32(3): 565-573. doi: 10.17843/rpmesp.2015.323.1693 17
Cutfield WS, Hofman PL, Mitchell M, Morison IM. Could epigenetics play a role in the developmental origins of health and disease? Pediatr Res. 2007; 61(5 Pt 2): 68-75. doi: 10.1203/pdr.0b013e318045764c
Clark SM, Notarangelo FM, Li X, Chen S, Schwarcz R, Tonelli LH. Maternal immune activation in rats blunts brain cytokine and kynurenine pathway responses to a second immune challenge in early adulthood. Prog Neuropsychopharmacol Biol Psychiatry. 2019; 89: 286-294. doi: 10.1016/j.pnpbp.2018.09.011
Duggan PJ, Maalouf EF, Watts TL, Sullivan MH, Counsell SJ, Allsop J, et al. Intrauterine T-cell activation and increased proinflammatory cytokine concentrations in preterm infants with cerebral lesions. Lancet. 2001; 358(9294): 1699-1700. doi: 10.1016/S0140-6736(01)06723-x
Coomey R, Stowell R, Majewska A, Tropea D. The role of microglia in neurodevelopmental disorders and their therapeutics. Curr Top Med Chem. 2020; 20(4): 272-276. doi: 10.2174/1568026620666200221172619
Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008; 61(4): 344-349. doi: 10.1016/j.jclinepi.2007.11.008
Higuchi M, Takeuchi S. Studies on neurobehavioral response (Scanlon test) in newborns after epidural anesthesia with various anesthetic agents for cesarean section. Nippon Sanka Fujinka Gakkai Zasshi. 1982; 34:(12): 2143-2148
Mammadbeyli AK. Peculiarities of central nervous system' damage at newborns with intranatal infections. Biomedicine. 2008; 2: 14-17. Russian (Мамедбейли А.К. Особенности поражения центральной нервной системы у новорожденных детей при внутриутробных инфекциях //Биомедицина. 2008. № 2. С. 14-17)
Nikitina IV, Zhukova AS, Vanko LV, Vtorushina VV, Matveeva NK, Krechetova LV, et al. Cytokine status of preterm newborns with infectious and noninfectious diseases. Neonatology: News, Opinions, Training. 2018; 6(4): 16-23. Russian (Никитина И.В., Жукова А.С., Ванько Л.В., Вторушина В.В., Матвеева Н.К., Кречетова Л.В. и др. Особенности цитокинового статуса у недоношенных новорожденных с заболеваниями легких инфекционного и неинфекционного генеза //Неонатология: новости, мнения, обучение. 2018. Т. 6, № 4. С. 16-23.) doi: 10.24411/2308-2402-2018-14002