Etiology, pathomorphologic changes and perinatal CNS lesions in intrauterine encephalitis in fetuses and newborns

I n t r o d u c t i o n . Among perinatal infections, the significance of intrauterine encephalitis (IUE) is determined by the high mortality rate in fetuses and newborns and the development of disabilities in subsequent periods of life, including cerebral palsy, schizophrenic, and autistic disorders. The morphological picture of IUE is characterized by significant polymorphism, which is due to both the multietiological nature of encephalitis and different types of neuron response under pathological conditions.

A i m . Studying the etiology and morphological features of IUE and its outcomes.

M a t e r i a l s a n d m e t h o d s . The brains of 37 fetuses and newborns at a gestation period of 24–27 were examined, in which the signs of IUE were detected morphologically. Light microscopy and immunohistochemical examination were used. By immunohistochemical typing, the markers of the following pathogens were determined: herpes simplex virus types 1 and 2, cytomegalovirus, Toxoplasma gondii, Epstein-Barr virus.

R e s u l t s . IUE was at most a manifestation of systemic intrauterine infection – 86,48% of cases. The morphological picture in IUE was characterized by two main manifestations: productive encephalitis, including granulomatous one, and exudative and productive encephalitis, which probably reflects its etiological features. Etiology of IUE: viral (66,7%), bacterial and fungal (33,3%) pathogens predominated. IUE was complicated by hemorrhagic syndrome with the development of fatal forms: in 21,68% (8 cases) – by subependymal hemorrhages, in 16,2% (6 cases) – by intraventricular hemorrhages.

C o n c l u s i o n . The IUE development in fetuses and newborns is a severe form of systemic intrauterine infection associated primarily with the pathogens of the TORCH complex, the complications of which are fatal subependymal and intraventricular hemorrhages.

1. Deng Y., Wang R., Zhou X. et al. Fetal, neonatal, and infant death in central China (Hubei): A 16-year retrospective study of forensic autopsy cases. Medicine (Baltimore). 2019;98(23):e15788. DOI: 10.1097/ MD.0000000000015788.

2. Bezie M.M., Asebe H.A., Asnake A.A. et al. Factors associated with perinatal mortality in sub-Saharan Africa: A multilevel analysis. PLoS One. 2024;19(11):e0314096. DOI: 10.1371/journal.pone.031409.

3. Gautam Bhattarai S.K., Ghimire R., Duwadi S. et al. Perinatal mortality among all deliveries in a tertiary care center: a descriptive cross-sectional study. JNMA J. Nepal Med. Assoc. 2021;59(243):1075-1080. DOI: 10.31729/jnma.6691.

4. Baloga O., Korchynska O., Zhultakova S. et al. Modern aspects of intrauterine infection. Wiad. Lek. 2022;75(5pt2):1395-1402. DOI: 10.36740/ WLek202205229.

5. Tsinzerling V.A., Melnikova V.F. (2002). Perinatal Infections. Issues of Pathogenesis, Morphological Diagnosis and Clinical and Morphological Comparisons: Practice Guidelines. St. Petersburg. Elbi-SPb. 352 p. (In Russ.)

6. Nadeev A.P., Shkurupiy V.A., Marinkin I.O. (2014). Liver and Placenta in Peri- and Postnatal Periods under Pathological Conditions: Clinical and Experimental Study. Novosibirsk: Nauka. 244 p. (In Russ.)

7. Afroza S. Neonatal sepsis-- a global problem: an overview. Mymensingh Med. J. 2006;15(1):108-114. DOI: 10.3329/mmj.v15i1.2.

8. Daripa M., Caldas H.M., Flores L.P. et al. Perinatal asphyxia associated with early neonatal mortality: populational study of avoidable deaths. Rev. Paul. Pediatr. 2013;31(1):37-45. DOI: 10.1590/s0103-0582201300010000.

9. Yanai T., Yoshida S., Kawakami K.J. The association between children’s autism spectrum disorders and central nervous system infections: using a nationwide claims database. J. Autism Dev. Disord. 2024. DOI: 10.1007/s10803-024-06327-0.

10. Ostrander B., Bale J.F. Congenital and perinatal infections. Handb. Clin. Neurol. 2019;162:133-153. DOI: 10.1016/B978-0-444-64029-1.00006-0.

11. Kosenchuk V.V., Rybalkina T.N., Boshyan R.E. et al. The role of opportunistic pathogens as etiological agents of intrauterine infections. Children’s Infections. 2019;3(68):17-24. DOI: 10.22627/2072-8107-2019-18-3-17-24. (In Russ.)

12. Skripchenko N.V., Lobzin Y.V., Ivanova G.P. et al. Neuroinfectious diseases in children. Children’ Infections. 2014;13(1):8-18. DOI: 10.22627/2072-8107-2014-13-1-8-18. (In Russ.)

13. Tsinzerling V.A., Chukhovina M.L. (2005). An Infectious Lesion of the Nervous System. Issues of Etiology, Pathogenesis, and Diagnosis. St. Petersburg. ELBISPb. 448 p. (In Russ.)

14. Auriti C., De Rose D.U., Santisi A. et al. Pregnancy and viral infections: Mechanisms of fetal damage, diagnosis and prevention of neonatal adverse outcomes from cytomegalovirus to SARS-CoV-2 and Zika virus. Biochim. Biophys. Acta Mol. Basis Dis. 2021;1867(10):166198. DOI: 10.1016/j.bbadis.2021.166198.

15. Vlasyuk V.V. (2009). Birth Trauma and Perinatal Disorders of Cerebral Circulation. St. Petersburg. NestorIstoriya. 252 p. (In Russ.) 16. Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr. Res. 2010;67(1):1-8. DOI: 10.1203/PDR.0b013e3181c1b176.

16. De Rose D.U., Bompard S., Maddaloni C. et al. Neonatal herpes simplex virus infection: From the maternal infection to the child outcome. J. Med. Virol. 2023;95(8):e29024. DOI: 10.1002/jmv.29024.

17. Leavy A., Jimenez Mateos E.M. Perinatal brain injury and inflammation: lessons from experimental murine models. Cells. 2020;9(12):2640. DOI: 10.3390/cells9122640.

18. Xu H., Zhang L., Xuan X.Y.et al. Intrauterine cytomegalovirus infection: a possible risk for cerebral palsy and related to its clinical features, neuroimaging findings: a retrospective study. BMC Pediatr. 2020;20(1):555. DOI: 10.1186/s12887-020-02449-3.

19. Afzal B., Roychaudhuri S., El-Dib M., Erdei C. Early neonatal presentation and neuroimaging of parechovirus meningoencephalitis in a preterm baby: a case report. Pediatr. Infect. Dis. J. 2024;43(5):463-466. DOI: 10.1097/INF.0000000000004275.