Modern Pediatrics. Ukraine. (2024). 3(139): 93-100. doi: 10.15574/SP.2024.139.93
Khaitovych M. V., Zhdanovych R. I.
Bogomolets National Medical University, Kyiv, Ukraine

For citation: Khaitovych MV, Zhdanovych RI. (2024). Neuroprotection in intrauterine herpesvirus infection. Modern Pediatrics. Ukraine. 3(139): 93-100. doi: 10.15574/SP.2024.139.93.
Article received: Feb 08, 2024. Accepted for publication: Apr 09, 2024.

The aim of the study is to assess the effectiveness of the neuroprotection complex in intrauterine herpesvirus infection.
Materials and methods. To test the effectiveness of the developed neuroprotection complex (erythropoietin, early use of sensory integration techniques), 60 children with intrauterine herpesvirus infection, who were classified as high-risk for significant central nervous system disorders, were examined from birth to 1 year of age: the main group was 30 newborns who were additionally treated with a new complex of neuroprotection, and the comparison group – 30 children, whose medical support was carried out in accordance with the protocols of the Ministry of Health of Ukraine. The obtained data were processed by the methods of variational statistics accepted in medicine, using the Student's t-test for numerical indicators and Fisher's angular transformation for indicators represented by frequencies, with a critical significance level of p<0.05.
The results. According to the static and motor development of children at the age of 12 months by the Denver scale, the vast majority of children (70.0%) of the comparison group were delayed in development by 2-4 months, while in the main group only 6 (20.0%) remained slight delay of 1-2 months. Accordingly, the assessment of psychomotor development according to the Griffiths scale was significantly reduced relative to the main group (112.7±7.6 points vs. 156.4±7.1 points, respectively). There were no cases of infant death in the examined children. Perinatal disorders of the central nervous system led to the disability of 2 (6.7%) children of the comparison group. Side effects or complications of the proposed therapy were not observed.
Conclusion. The use of a complex of therapeutic and preventive measures aimed at neuroprotection in newborns with intrauterine infection with herpesviruses (prediction of the risk of central nervous system disorders at birth, in children at high risk – early neuroprotective treatment with low doses of recombinant erythropoietin and early use of sensory-motor integration) allows to improve neurocognitive and psychomotor abilities of children up to 1 year of age. The effectiveness of the neuroprotective complex was 80.0%.
The research was carried out in accordance with the principles of the Declaration of Helsinki. The research protocol was approved by the Local Ethics Committee of the specified institution. Informed consent of the children's parents was obtained for the research.
The authors declare no conflict of interest.
Keywords: newborn, herpesvirus infection, central nervous system disorders neuroprotection, erythropoietin, sensory integration.
REFERENCES

1. Al-Haddad BJS, Oler E, Armistead B, et al. (2019). The fetal origins of mental illness. Am J Obstet Gynecol. 221(6): 549-562. https://doi.org/10.1016/j.ajog.2019.06.013; PMid:31207234 PMCid:PMC6889013

2. Apaydın U, Yıldız R, Yıldız A, Acar ŞS, Gücüyener K, Elbasan B. (2023). Short-term effects of SAFE early intervention approach in infants born preterm: A randomized controlled single-blinded study. Brain Behav. 13(10): e3199. https://doi.org/10.1002/brb3.3199; PMid:37534617 PMCid:PMC10570479

3. Cemali M, Pekçetin S, Akı E. (2022). The Effectiveness of Sensory Integration Interventions on Motor and Sensory Functions in Infants with Cortical Vision Impairment and Cerebral Palsy: A Single Blind Randomized Controlled Trial. Children. 9: 1123. https://doi.org/10.3390/children9081123; PMid:36010014 PMCid:PMC9406788

4. Frankenburg WK, Dobbs JB. (1967). The Denver developmental screening test. J. Pediatr. 71(2): 181-191. https://doi.org/10.1016/S0022-3476(67)80070-2; PMid:6029467

5. Gonzalez FF, Larpthaveesarp A, McQuillen P et al. (2013). Erythropoietin increases neurogenesis and oligodendrogliosis of subventricular zone precursor cells after neonatal stroke. Stroke. 44(3): 753-758. https://doi.org/10.1161/STROKEAHA.111.000104; PMid:23391775 PMCid:PMC3689426

6. Griffiths R. (1996) Manual: The Griffiths mental development scales from birth to 2 years. UK: Association for Research in Infant and Child Development; Revision. https://doi.org/10.1037/t03301-000

7. James C, Harfouche M, Welton NJ et al. (2020). Herpes simplex virus: global infection prevalence and incidence estimates, 2016. Bull World Health Organ. 98(5): 315-329. https://doi.org/10.2471/BLT.19.237149; PMid:32514197 PMCid:PMC7265941

8. Lane SJ, Mailloux Z, Schoen S et al. (2019). Neural Foundations of Ayres Sensory Integration®. Brain Sci. 9(7): 153. https://doi.org/10.3390/brainsci9070153; PMid:31261689 PMCid:PMC6680650

9. Leeper C, Lutzkanin A. (2018). Infections During Pregnancy. Prim Care. 45(3): 567-586. https://doi.org/10.1016/j.pop.2018.05.013; PMid:30115342

10. Malla RR, Asimi R, Teli MA, Shaheen F, Bhat MA. (2017). Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial. J Perinatol. 37(5): 596-601. https://doi.org/10.1038/jp.2017.17; PMid:28277490

11. Molloy EJ, El-Dib M, Juul SE et al. (2023). Neuroprotective therapies in the NICU in term infants: present and future. Pediatr Res. 93(7): 1819-1827. https://doi.org/10.1038/s41390-022-02295-2; PMid:36195634 PMCid:PMC10070589

12. Morozova A. (2023). Sensory integration as one of the methods of effective functioning of the early intervention program. International Science Journal of Education & Linguistics. 2(3): 1-6. https://doi.org/10.46299/j.isjel.20230203.01

13. Oliveira V, Kumutha JR, E N, Somanna J, Benkappa N, Bandya P et al. (2018). Hypothermia for encephalopathy in low-income and middle-income countries: feasibility of whole-body cooling using a low-cost servo-controlled device. BMJ Paediatr Open. 2(1): e000245. https://doi.org/10.1136/bmjpo-2017-000245; PMid:29637198 PMCid:PMC5887762

14. Peng CC, Chang JH, Lin HY, Cheng PJ, Su BH. (2018). Intrauterine inflammation, infection, or both (Triple I): A new concept for chorioamnionitis. Pediatr Neonatol. 59(3): 231-237. https://doi.org/10.1016/j.pedneo.2017.09.001; PMid:29066072

15. Perrone S, Lembo C, Gironi F. (2022). Erythropoietin as a Neuroprotective Drug for Newborn Infants: Ten Years after the First Use. Antioxidants (Basel). 11(4): 652. https://doi.org/10.3390/antiox11040652; PMid:35453337 PMCid:PMC9031072

16. Schepanski S, Buss C, Hanganu-Opatz IL, Arck PC. (2018). Prenatal Immune and Endocrine Modulators of Offspring's Brain Development and Cognitive Functions Later in Life. Front Immunol. 9: 2186. https://doi.org/10.3389/fimmu.2018.02186; PMid:30319639 PMCid:PMC6168638

17. Wood S, Crawford S, Hicks M, Mohammad K. (2021). Hospital-related, maternal, and fetal risk factors for neonatal asphyxia and moderate or severe hypoxic-ischemic encephalopathy: a retrospective cohort study. J Matern Fetal Neonatal Med. 34(9): 1448-1453. https://doi.org/10.1080/14767058.2019.1638901; PMid:31331211

18. Wu YW, Mathur AM, Chang T et al. (2016). High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. Pediatrics. 137(6): e20160191. https://doi.org/10.1542/peds.2016-0191; PMid:27244862

19. Yates N, Gunn AJ, Bennet L, Dhillon SK, Davidson JO. (2021). Preventing Brain Injury in the Preterm Infant-Current Controversies and Potential Therapies. Int J Mol Sci. 22(4): 1671. https://doi.org/10.3390/ijms22041671; PMid:33562339 PMCid:PMC7915709

20. Zhu S, Viejo-Borbolla A. (2021). Pathogenesis and virulence of herpes simplex virus. Virulence. 12(1): 2670-2702. https://doi.org/10.1080/21505594.2021.1982373; PMid:34676800 PMCid:PMC8923070