UDC: 616.9:614-051.1.3
THE ROLE OF CYTOMEGALOVIRUS INFECTION IN THE INBORN MALFORMATION IN CHILDREN
Sh.A Agzamova1, G.M. Khasanova2
National Children's Medical Center, Ministry of healthcare, Uzbekistan Tashkent Pediatric Medical Institute Tashkent, Uzbekistan
To date, the problem of infections caused by herpes viruses is very relevant, considering their implication in the development of congenital malformations of various organs and systems.
Aim ofthe study. To establish the frequency and clinical characteristics of congenital cytomegalovirus infection in children.
Materials and methods. Follow-up observation of 116 children aged from the neonatal period to 4 years. CMVI infection in parturient women was determined by detecting the pathogen genome in venous blood and urine by PCR and real-time PCR immediately after delivery. To detect intrauterine infection of newborns on the 1st-2nd and 15-28th days of life and the persistence of infection at the age of 3-6,12-22 months, samples of umbilical and venous blood, urine, scraping of the epithelium from the nasopharynx were used.
Conclusions. Congenital cytomegalovirus infection can manifest itself before the age of 4 years as an occult cytomegalovirus syndrome. Children with congenital malformations of the kidneys, heart, central nervous system, eyes, liver damage, thyroid gland should be examined for cytomegalovirus and, if necessary, antiviral therapy should be prescribed in a timely manner.
Keywords: дети, цитомегаловирусная инфекция, врожденные пороки развития.
РОЛЬ ЦИТОМЕГАЛОВИРУСНОЙ ИНФЕКЦИИ В ФОРМИРОВАНИИ ВРОЖДЕННЫХ ПОРОКОВ РАЗВИТИЯ У ДЕТЕЙ
Ш. А. Агзамова 1 Г. М. Хасанова 2
Национальный детский медицинский центр,Ташкент, Узбекистан Ташкентский педиатрический медицинский институт, Ташкент, Узбекистан
На сегодняшний день проблема инфекций, вызванных герпес вирусами является весьма актуальной, в виду возможности их участия в развитии прогностически неблагоприятных последствий для здоровья ребенка, в частности, развитием врожденных пороков развития различных органов и систем.
Цель исследования. Установить особенности клиники и частоты врожденной цитомегаловирусной инфекции у
детей.
Материалыиметоды. Катамнестическое наблюдения 116 детей в возрасте от периода новорожденности до 4 лет. Инфекцию ЦМВИ у рожениц определяли путем выявления генома возбудителя в венозной крови и моче методами ПЦР и ПЦР в реальном времени сразу после родов. Для выявления внутриутробного инфицирования новорожденных на 12-е и 15-28-е сутки жизни и персистенции инфекции в возрасте 3-6,12-22 мес использовали образцы пуповинной и венозной крови, мочи, соскоб эпителия из носоглотки.
Выводы. Врожденная цитомегаловирусная инфекция может носитьхарактер «скрытого» цитомегаловирусного синдрома и проявляться в возрасте до 4 лет. Детей с врожденными пороками развития почек, сердца, ЦНС, глаз, поражением печени, щитовидной железы необходимо обследовать на цитомегаловирус и при необходимости своевременно назначать противовирусную терапию.
Кпючевыеспова: дети, цитомегаловирусная инфекция, врожденные пороки развития.
СТАТЬИ
To date, the problem of infections caused by herpes viruses is very relevant, considering their implication in the development of prognostically unfavorable consequences for the health ofthe child [2]. According to the literature, the frequen-
cy of primary cytomegalovirus infection of the fetus during pregnancy does not exceed 1%, and intrauterine infection occurs in 30-50% during delivery. While 5-18% of children develop clinical signs of the congenital cytomegalovirus infection,
which is characterized by a severe course and often causes death. Currently, the possibility of superinfection due to the presence of different strains of the virus is not excluded. In these cases, fetal damage can also occur when an occult infection is reactivated in a pregnant woman or when she is infected with a new strain of cytomegalovirus [6]. Risk factors for the development of intrauterine cytomegalovirus infection, include previous abortions, miscarriages, stillbirths, early infant mortality, young age of the mother, the presence of chronic pathology, complicated current pregnancy [7]. It is known that cytomegalovirus is capable of long-term persistence in the body, has predominantly neurotropic, epitheli-otropic, hepatotropic and cardiotropic manifestations. The ability of the virus to persist for a long time in the central nervous system leads to the development of specific encephalitis in the fetus, which often results in neurological defects in the form of mental retardation, epilepsy, and sensory-neural deafness [5]. It has now been proven that in the case of the development of CMVI in a seropositive lactating woman, natural feeding should not be stopped, since in this case the child receives anti-CMV antibodies with mother's milk. Passive specific immunization of a newborn prevents active replication of the virus and contributes to the development of an asymptomatic form of the disease [4]. Cytomegalovirus infection occurs in 30-50% of cases with infection during childbirth or in the postnatal period. It can have various clinical manifestations: from fever, sialadenitis, mononucleosis-like syndrome, gastrointestinal tract lesions to the development of generalized forms with consistent involvement of all organs and systems [1].
With cytomegaly, there is a high risk of: - abortion; - spontaneous miscarriage; - non-developing pregnancy; - antenatal fetal death; - developmental anomalies; - polyhydramnios. Ultrasound markers of fetal infection: microcephaly, calcifications in the brain, ventriculomegaly, intestinal hyper-echogenicity, heart defects, renal agenesis [3]. Aim of the study
To identify the clinical features and frequency of congenital cytomegalovirus infection in children. Material and methods
A total of 116 children aged from the neonatal period to 4 years were under followup. CMVI infection in parturient women was determined by detection of the pathogen genome in venous blood and urine by PCR and real-time PCR immediately after delivery. Specimens of umbilical and venous blood, urine, and epithelial swabs of the nasopharynx were tested on the lst-2nd and l5-28th days of life to detect possible intrauterine infection of newborns and at the age of 3-6, 12-22 months to detect the persistence of the infection. PCR diagnostics was carried out in the laboratory of the Scientific and Diagnostic Center "IMMUNOGEN TEST" of the Institute of Immunology of the Academy of Sciences of the Republic of Uzbekistan. Follow-up observation of newborns (n=H6) was carried out at 6, 9-12 months of life, at 1-2, 3-4 years of age by means of a routine clinical and neurological examination, laboratory and instrumental examination with an assessment of
psychomotor and physical development. All observed children were examined by specialists: a neurologist, an oculist, an endocrinologist, a cardiologist and a nephrologist at the City Medical Children's Consultative and Diagnostic Center in Tashkent.
Results and discussion
During the follow-up examination, congenital cytomegalovirus infection was diagnosed in 41 children, of which in 15 (36.6%) patients in the first year of life, in 14 (34.1%) - in the second year, at the age of 3-4 years - in 12 (29.2%) people. While the remaining 75 children had an acquired cytomegalovirus infection, occurring in the form of infectious mononucleosis. In 10 (28.6%) children, a "hidden" cytomegalovirus syndrome was established, in which: there were no clinical manifestations of infection both at birth and over the next two years, the children grew and developed according to age and belonged to the group of conditionally healthy. And only at the age of 2-4 years, during a dispensary examination by specialists, malformations of the internal organs were revealed in them.
mations in the examined children
In 10 (28.6%) children with congenital cytomegalovirus infection, kidney pathology was established: hydronephrosis, congenital vascular anomalies, kidney hypoplasia. 20 (57.1%) children had eye lesions in the form of focal chorioretinitis. In 16 (45.7%) patients, malformations of the heart were detected: minor anomalies, aortic stenosis, atrial septal defect. 11 patients had comorbidities. Only 2 children were diagnosed with congenital generalized cytomegalovirus infection in the maternity hospital. They developed clinical symptoms from the first day of life, many organs and systems were involved in the process. Respiratory and cardiac disorders were noted, jaundice was detected, which had a wave-like character, hemorrhagic syndrome associated with thrombocytopenia, and the development of cytomegalovirus encephalitis was observed. In one child aged 7 months, an endocrinologist revealed hypoplasia of the thyroid gland, which was combined with congenital heart disease - aortic stenosis and ventricular septal defect against the background of Williams syndrome. 40% of children had chronic liver pathology. Fig. 1. Conclusion
Thus, cytomegalovirus infection is an actual problem of childhood, the clinical manifestations of which are very diverse, which is the reason for their late diagnosis. Congenital infec-
tion may have the character of a "hidden" cytomegalovirus syndrome and manifest itself before the age of 4 years. Therefore, children with congenital malformations of the kidneys, heart, central nervous system, eyes, damage to the liver, thy-
roid gland should be examined for cytomegalovirus and, if necessary, antiviral therapy should be prescribed in a timely manner.
REFERENCES
1. Bardanzellu F., Fanos V., Reali A. Human breast milk-acquired cytomegalovirus infection: certainties, doubts and perspectives. Current pediatric reviews. 2019;15(1):30-41. https://doi.org/l0.2174/l573396315666181126105812
2. Hansell P., Palm F. A role for the extracellular matrix component hyaluronan in kidney dysfunction during ACE-inhibitor fetopathy. ActaPhysiologica. 2015; 213(4):795-804. https://doi.org/l0.111l/apha.12456
3. Paladini D., Volpe P. Ultrasound of congenital fetal anomalies: differential diagnosis and prognostic indicators. CRC press. 2018. https://doi.org/l0.4324/9780429462450
4. Permar S. R., Schleiss M. R., Plotkin S. A. Advancing our understanding of protective maternal immunity as a guide for development of vaccines to reduce congenital cytomegalovirus infections. Journal of virology.2018; 92(7):e00030-18. https://doi.org/l0.1128/JVI.00030-18
5. Sittivarakul W, Benjhawaleemas T, Aui-Aree N, Jirarattana-sopaP,Liabsuetrakul T. Incidence rate and risk factors for con-tralateraleye involvement among patients with AIDS and cy-tomegalovirusretinitis treated with local therapy. Ocular Immunology and Inflammation. 2016;24:530-536. doi.org/10.3109/09273948.2015.1032307
6. Zhang X. Y., Fang F. Congenital human cytomegalovirus infection and neurologic diseases in newborns. Chinese Medical Journal. 2019;132(17):2109-2118. D0l:10.1097/CM9.0000000000000404
7. Zinserling V. Brain Lesions in Perinatal Infections //Infectious Lesions of the Central Nervous System. Springer, Cham. 2022; 251-270. https://doi.org/l0.1007/978-3-030-96260-9_16
Corresponding author:
Agzamova Shoira Abdusalamovna - Doctor of Medical Sciences - Professor head of the Science Department of the National Children's Medical Center of Uzbekistan. E-mail: [email protected]