VOLUME LXXIII, ISSUE 10, OCTOBER 2020 Since 1928 ALUNA Publishing House Memory of dr Władysław BiegańskiOfficial journal of the Polish Medical Association Wiadomości Lekarskie monthly journal You can order the subscription for the journal from Wydawnictwo Aluna by: prenumerata@wydawnictwo-aluna.pl Wydawnictwo Aluna Z.M. Przesmyckiego 29 05-510 Konstancin-Jeziorna Poland Place a written order first. If you need, ask for an invoice. Payment should be done to the following account of the Publisher: account number for Polish customers (PLN): 82 1940 1076 3010 7407 0000 0000 Credit Agricole Bank Polska S. A., SWIFT: AGRIPLPR account number for foreign customers (EURO): 57 2490 0005 0000 4600 7604 3035 Alior Bank S. A.: SWIFT: ALBPPLPW Subscription of twelve consecutive issues (1-12): Customers in Poland: 360 PLN/year Customers from other countries: 320 EURO/year Wiadomości Lekarskie is abstracted and indexed in: PUBMED/MEDLINE, SCOPUS, EMBASE, INDEX COPERNICUS, POLISH MINISTRY OF SCIENCE AND HIGHER EDUCATION, POLISH MEDICAL BIBLIOGRAPHY Copyright: © ALUNA Publishing House. Articles published on-line and available in open access are published under Creative Com- mon Attribution-Non Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) allowing to download articles and share them with others as long as they credit the authors and the pu- blisher, but without permission to change them in any way or use them commercially. © Aluna Wiadomości Lekarskie 2016, tom LXIX, nr 4 605 Pediatria Prof. dr hab. med. Ewa Małecka-Tendera (SUM Katowice) Dr hab. med. Tomasz Szczepański (SUM Katowice) Położnictwo i ginekologia Prof. dr hab. med. Jan Kotarski (UM Lublin) Prof. dr hab. med. Andrzej Witek (SUM Katowice) Stomatologia Prof. dr hab. Maria Kleinrok (UM Lublin) Polskie Towarzystwo Lekarskie Prof. dr hab. med. Waldemar Kostewicz (Prezes ZG PTL) Prof. dr hab. med. Jerzy Woy-Wojciechowski (Prezes Honorowy PTL) Prof. emerytowany dr hab. med. Tadeusz Petelenz (O. Katowicki PTL) Koordynator projektu Agnieszka Rosa tel. 694 778 068 amarosa@wp.pl Redakcja zagraniczna dr n. med. Lesia Rudenko l.rudenko@wydawnictwo-aluna.pl Wydawca Wydawnictwo Aluna ul. Przesmyckiego 29 05-510 Konstancin-Jeziorna www.aluna.waw.pl Prenumerata prenumerata@wydawnictwo-aluna.pl www.wiadomoscilekarskie.pl/prenumerata Opracowanie graficzne Piotr Dobrzyński (www.poligrafia.nets.pl) Nakład do 6 tys. egz © Copyright by Aluna Publishing Wydanie czasopisma Wiadomości Lekarskie w formie papierowej jest wersją pierwotną (referencyjną). Redakcja wdraża procedurę zabezpieczającą oryginalność prac naukowych oraz przestrzega zasad recenzowania zgodnie z wytycznymi Ministerstwa Nauki i Szkolnictwa Wyższego. Czasopismo indeksowane w: PubMed/Medline, EBSCO, MNISW (11 pkt), Index Copernicus, PBL, Scopus Redaktor naczelny Prof. dr hab. med. Władysław Pierzchała (SUM Katowice) Zastępca redaktora naczelnego Prof. zw. dr hab. med. Aleksander Sieroń (SUM Katowice) Redaktor wydania prof. dr hab. Maria Majdan prof. dr hab. Mirosław Jabłoński Redaktor statystyczny dr n. med. Lesia Rudenko Rada naukowa Redaktorzy tematyczni: Chirurgia Prof. dr hab. med. Krzysztof Bielecki (CMKP Warszawa) Prof. dr hab. med. Stanislav Czudek (Onkologickié Centrum J.G. Mendla Czechy) Prof. dr hab. med. Marek Rudnicki (University of Illinois USA) Choroby wewnętrzne Prof. dr hab. med. Ryszarda Chazan, pneumonologia i alergologia (UM Warszawa) Prof. dr hab. med. Jacek Dubiel, kardiologia (CM UJ Kraków) Prof. dr hab. med. Zbigniew Gąsior, kardiologia (SUM Katowice) Prof. dr hab. med. Marek Hartleb, gastroenterologia (SUM Katowice) Prof. dr hab. med. Jerzy Korewicki, kardiologia (Instytut Kardiologii Warszawa) Dr hab. med. Krzysztof Łabuzek, farmakologia kliniczna, diabetologia (SUM Katowice) Prof. dr hab. med. Tadeusz Płusa, pneumonologia i alergologia (WIM Warszawa) Dr hab. med. Antoni Wystrychowski, nefrologia (SUM Katowice) Choroby zakaźne Prof. dr hab. med. Andrzej Gładysz (UM Wrocław) Epidemiologia Prof. dr hab. med. Jan Zejda (SUM Katowice) Neurologia i neurochirurgia Prof. dr hab. med. Henryk Majchrzak, neurochirurgia (SUM Katowice) Prof. dr hab. med. Krystyna Pierzchała, neurologia (SUM Katowice) Redaktor naczelny Prof. dr hab. med. Władysław Pierzchała (SUM Katowice) Zastępca redaktora naczelnego Prof. zw. dr hab. n. med. Aleksander Sieroń (SUM Katowice) Sekretarz redakcji Joanna Grocholska Redaktor statystyczny Ewa Guterman Rada naukowa Redaktorzy tematyczni: Chirurgia Prof. dr hab. med. Krzysztof Bielecki (CMKP Warszawa) Prof. dr hab. med. Stanislav Czudek (Onkologickié Centrum J.G. Mendla Czechy) Prof. dr hab. med. Marek Rudnicki (University of Illinois USA) Choroby wewnętrzne Prof. dr hab. med. Marek Hartleb, gastroenterologia (SUM Katowice) Prof. dr hab. med. Jacek Dubiel, kardiologia (CM UJ Kraków) Prof. dr hab. med. Zbigniew Gąsior, kardiologia (SUM Katowice) Prof. dr hab. med. Jerzy Korewicki, kardiologia (Instytut Kardiologii Warszawa) Dr hab. med. Antoni Wystrychowski, nefrologia (SUM Katowice) Prof. dr hab. med. Ryszarda Chazan, pneumonologia i alergologia (UM Warszawa) Prof. dr hab. med. Tadeusz Płusa, pneumonologia i alergologia (WIM Warszawa) Choroby zakaźne Prof. dr hab. med. Andrzej Gładysz (UM Wrocław) Epidemiologia Prof. dr hab. med. Jan Zejda (SUM Katowice) Neurologia i neurochirurgia Prof. dr hab. med. Krystyna Pierzchała, neurologia (SUM Katowice) Prof. dr hab. med. Henryk Majchrzak, neurochirurgia (SUM Katowice) Pediatria Prof. dr hab. med. Ewa Małecka-Tendera (SUM Katowice) Dr hab. med. Tomasz Szczepański (SUM Katowice) Położnictwo i ginekologia Prof. dr hab. med. Jan Kotarski (UM Lublin) Prof. dr hab. med. Andrzej Witek (SUM Katowice) Stomatologia Prof. dr hab. Maria Kleinrok (UM Lublin) Polskie Towarzystwo Lekarskie Prof. dr hab. med. Jerzy Woy-Wojciechowski (Prezes PTL) Prof. emerytowany dr hab. med. Tadeusz Petelenz (O. Katowicki PTL) Kontakt z redakcją i wydawnictwem Joanna Grocholska e-mail: j.grocholska@blue-sparks.pl Wydawca Blue Sparks Publishing Group Sp. z o.o. ul. Obornicka 15/4, 02-948 Warszawa tel. (22) 858-92-53 Zarząd: dr Anna Łuczyńska − prezes Reklama i marketing: Agnieszka Rosa tel. 662-116-020 e-mail: a.rosa@blue-sparks.pl Zamówienia na prenumeratę: e-mail: prenumerata@blue-sparks.pl lub tel. (22) 858-92-53 Projekt okładki: Dorota Cybulska Opracowanie gra� czne: Tomasz Białkowski Nakład: do 6000 egz. © Copyright by Blue-Sparks Publishing Group Wydanie czasopisma Wiadomości Lekarskie w formie papierowej jest wersją pierwotną (referencyjną). Redakcja wdraża procedurę zabezpieczającą ory- ginalność publikacji naukowych oraz przestrzega zasad recenzowania prac zgodnie z wytycznymi Ministerstwa Nauki i Szkolnictwa Wyższego. Czasopismo indeksowane w: Medline, EBSCO, MNiSW (6 pkt), Index Copernicus, PBL. Czasopismo Polskiego Towarzystwa Lekarskiego Pamięci dra Władysława Biegańskiego Wiadomości Lekarskie WL_1_2013.indb 1 27.03.2013 12:23 Editor in-Chief: Prof. Władysław Pierzchała Deputy Editor in-Chief: Prof. Aleksander Sieroń Statistical Editor: Dr Lesia Rudenko Managing Editor: Agnieszka Rosa – amarosa@wp.pl International Editorial Office: Lesia Rudenko (editor) – l.rudenko@wydawnictwo-aluna.pl Nina Radchenko (editor's assistant) – n.radchenko@wydawnictwo-aluna.pl Polish Medical Association (Polskie Towarzystwo Lekarskie): Prof. Waldemar Kostewicz – President PTL Prof. Jerzy Woy-Wojciechowski – Honorary President PTL Prof. Tadeusz Petelenz Kris Bankiewicz San Francisco, USA Christopher Bara Hannover, Germany Krzysztof Bielecki Warsaw, Poland Zana Bumbuliene Vilnius, Lithuania Ryszarda Chazan Warsaw, Poland Stanislav Czudek Ostrava, Czech Republic Jacek Dubiel Cracow, Poland Zbigniew Gasior Katowice, Poland Andrzej Gładysz Wroclaw, Poland Nataliya Gutorova Kharkiv, Ukraine Marek Hartleb Katowice, Poland Roman Jaeschke Hamilton, Canada Andrzej Jakubowiak Chicago, USA Oleksandr Katrushov Poltava, Ukraine Peter Konturek Saalfeld, Germany Jerzy Korewicki Warsaw, Poland Jan Kotarski Lublin, Poland George Krol New York, USA Krzysztof Łabuzek Katowice, Poland Henryk Majchrzak Katowice, Poland Ewa Małecka-Tendera Katowice, Poland Stella Nowicki Memphis, USA Alfred Patyk Gottingen, Germany Palmira Petrova Yakutsk, Russia Krystyna Pierzchała Katowice, Poland Tadeusz Płusa Warsaw, Poland Waldemar Priebe Houston, USA Maria Siemionow Chicago, USA Vladyslav Smiianov Sumy, Ukraine Tomasz Szczepański Katowice, Poland Andrzej Witek Katowice, Poland Zbigniew Wszolek Jacksonville, USA Vyacheslav Zhdan Poltava, Ukraine Jan Zejda Katowice, Poland Distribution and Subscriptions: Bartosz Guterman prenumerata@wydawnictwo-aluna.pl Graphic design / production: Grzegorz Sztank www.red-studio.eu Publisher: ALUNA Publishing House ul. Przesmyckiego 29, 05-510 Konstancin – Jeziorna www.wydawnictwo-aluna.pl www.wiadomoscilekarskie.pl www.wiadlek.pl International Editorial Board – in-Chief: Marek Rudnicki Chicago, USA International Editorial Board – Members: 2107 Wiadomości Lekarskie, VOLUME LXXIII, ISSUE 10, OCTOBER 2020© Aluna Publishing CONTENTS ORIGINAL ARTICLES Olena V. Markovska, Olena L. Tovazhnyanska, Mykhailo S. Myroshnychenko, Anton S. Shapkin, Nataliya O. Nekrasova, Hanna P. Samoilova, Iryna O. Lapshyna FEATURES OF LOCAL IMMUNE REACTIONS IN SKIN WITH UNDERLYING SOFT TISSUES IN PATIENTS WITH MULTIPLE SCLEROSIS 2109 Оlga G. Kmet, Nаtaliia D. Filipets, Taras I. Kmet, Yurii M. Vepriuk, Kateryna V. Vlasova BIOCHEMICAL AND MORPHOLOGICAL MARKERS OF EXPERIMENTAL SCOPOLAMINE-INDUCED NEURODEGENERATION AND THE EFFECT OF ENALAPRIL ON THEM 2114 Paulina Kiebuła, Katarzyna Tomczyk, Joanna Furman, Beata Łabuz-Roszak ASSOCIATION BETWEEN EATING HABITS AND PHYSICAL ACTIVITY IN PRIMARY SCHOOL STUDENTS 2120 Ivan V. Yavtushenko, Svitlana M. Nazarenko, Oleksandr V. Katrushov, Vitalii O. Kostenko QUERCETIN LIMITS THE PROGRESSION OF OXIDATIVE AND NITROSATIVE STRESS IN THE RATS’ TISSUES AFTER EXPERIMENTAL TRAUMATIC BRAIN INJURY 2127 Dariia I. Voroniak, Oleg S. Godik, Larysa Ya. Fedoniuk, Olena М. Shapoval, Viktoriia V. Piliponova ROLE OF STAGE ENDOSCOPIC VARICEAL BAND LIGATION IN TREATMENT OF CHILDREN WITH PORTAL HYPERTENSION 2133 Igor V. Yanishen, Olena L. Fedotova, Nataliia L. Khlystun, Olena O. Berezhna, Roman V. Kuznetsov QUALITY OF ORTHOPEDIC REHABILITATION OF PATIENTS WITH POST-TRAUMATIC DEFECTS OF THE UPPER JAW BY CHARACTERISTICS OF BIOCENOSIS OF THE ORAL CAVITY 2138 Valentyn A. Rohozynskyi, Anatolii F. Levytskyi, Mykola M. Dolianytskyi, Irina M. Benzar TREATMENT OF SEVERE SPINAL DEFORMATIONS IN CHILDREN WITH IDIOPATHIC SCOLIOSIS USING HALO-GRAVITY TRACTION 2144 Igor D. Duzhiy, Andrii S. Nikolaienko, Vasyl M. Popadynets, Oleksandr V. Kravets, Igor Y. Hresko, Stanislav O. Holubnichyi, Vladyslav V. Sikora, Mykola S. Lуndіn, Anatolii M. Romaniuk REPARATIVE PROCESSES FEATURES IN TROPHIC ULCERS CAUSED BY DIABETES MELLITUS WITH THE USE OF PLATELET-RICH PLASMA 2150 Alexandr N. Zinchuk, Olga A. Golubovska, Borys A. Herasun, Andrii M. Zadorozhnyi, Oleksandr B. Herasun INTENSIFICATION OF ANTIVIRAL THERAPY OF CHRONIC HEPATITIS B BY MEANS OF INTRADERMAL IMMUNIZATION WITH AUTOLEUKOCYTES 2156 Andrey B.Gryazov, Yulia V. Medvedovska, Andrey A. Gryazov DIFFERENTIAL DIAGNOSTICS OF A RADIONECROSIS AND LOCAL TUMORAL RECURRENCE ACCORDING TO ARTERIAL SPIN LABELLING AFTER RADIOSURGERY TREATMENT OF MALIGNANT GLIOMAS OF A BRAIN 2160 Ekaterina Yu. Lipakova, Oleksandr V. Bilchenko, Tetiana A. Rudenko, Maksym O. Holianishchev, Olena V. Vysotska, Liubov M. Rysovana MORPHOLOGICAL AND STRUCTURAL CHANGES IN MYOCARDIUM, LIPID AND CORBOHYDRATE METABOLISM DURING DIFFERENT OUTCOMES OF CHRONIC HEART FAILURE IN PATIENTS WITH ISCHEMIC HEART DISEASE AND DIABETES MELLITUS TYPE II 2165 Oleksii M. Korzh EVALUATION OF DIABETES SELF-MANAGEMENT EDUCATION IN PATIENTS WITH CONCOMITANT CHRONIC KIDNEY DISEASE 2170 Anna V. Blagaia, Mykola V. Kondratiuk, Sergii T. Omelchuk, Ihor M. Pelo, Natalia D. Kozak COMPARATIVE HYGIENIC ASSESSMENT OF PESTICIDES BEHAVIOR IN SOIL IN INTENSIVE GRAIN FARMING TECHNOLOGIES 2175 Vladyslav A. Smiianov, Tetyana A. Vasilyeva, Olena Y. Chygryn, Pavlo M. Rubanov, Tetyana M. Mayboroda SOCIO-ECONOMIC PATTERNS OF LABOR MARKET FUNCTIONING IN THE PUBLIC HEALTH: CHALLENGES CONNECTED WITH COVID-19 2181 Vasyl V. Kruchanytsia, Vasyl V. Skryp, Ivan S. Myroniuk, Hennady O. Slabkiy ON THE ISSUES OF PROVISION OF DRUG AID AT THE PRIMARY LEVEL OF MEDICAL ASSISTANCE 2188 Oleksandr P. Volosovets, Tetyana O. Kryuchko, Viktor L. Veselsky, Sergii P. Kryvopustov, Tetiana M. Volosovets, Viktor Y. Shatilo, Veronyka M. Dudnik CONGENITAL ANOMALIES IN CHILDREN OF UKRAINE: 25-YEAR MONITORING OF MORBIDITY AND PREVALENCE 2193 Yelyzaveta S. Sirchak, Vasilij I. Griga, Oksana I. Petrichko CORRECTION OF AUTONOMIC AND COGNITIVE DISTURBANCES IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE 2198 Ivan Yu. Lobanov THE TESTOSTERON-CORTISOL MODEL AS A WAY TO UNDERSTAND THE MECHANISM OF ALCOHOL DEPENDENCE WHICH STARTED IN PUBERTY 2204 Svetlana N. Chuhray, Viktoria E. Lavrynenko, Rostyslav F. Kaminsky, Larysa B. Shobat, Oleksandr I. Kovalchuk, Yurii B. Chaikovsky, Liudmyla M. Sokurenko CARDIO-VASCULAR SYSTEM OF THE MATURE RATS WITH CONGENITAL HYPOTHYROIDISM AND ARTERIAL HYPERTENSION 2209 Nataliia S. Alekseyenko, Vitalii M. Andriychuk, Ruslan V. Radoha, Lyudmila V. Fomina, Larysa Ya. Fedoniuk COMPARATIVE CHARACTERISTICS OF THE PARAMETERS’ CHANGES OF SKIN AND FAT FLEXURES THICKNESS OF EXTREMETIES AT YOUTH UNDER THE CONDITION OF HIGHER EDUCATION 2214 Valeriy Pokhylko, Yuliia Cherniavska, Nataliia Adamchuk,Svitlana Tsvirenko, Yuliia Klimchuk CLINICAL PREDICTION OF EARLY ONSET SEPSIS IN PRETERM NEONATES 2219 Оlexander М. Yakymchuk, Іvan М. Klishch, Alla V. Boychuk, Juliia В. Yakymchuk ACTIVATION OF ENDOGENOUS INTOXICATION UNDER THE INFLUENCE OF ANESTHETICS IN EXPERIMENTAL HYPERTHYROIDISM 2224 Tetiana S. Gruzieva, Nataliia V. Stuchynska, Hanna V. Inshakova RESEARCH ON THE EFFECTIVENESS OF TEACHING BIOSTATISTICS OF FUTURE PHYSICIANS 2227 Volodymyr S. Lychko DIAGNOSTIC FEATURES OF DYSFUNCTION IN CYTOKINE AND SYMPATHOADRENAL SYSTEMS WITH ISCHEMIC STROKE 2233 Liliya S. Babinets, Iryna M. Halabitska, Iryna O. Borovyk, Olena V. Redkva, Halyna M. Sasyk THE INFLUENCE OF EXOCRINE PANCREATIC INSUFFICIENCY IN THE FORMATION OF OSTEOPENIA IN PATIENTS WITH PRIMARY OSTEOARTHRITIS 2238 Roman Ozhohan, Mykola M. Rozhko, Zinoviy R. Ozhogan, Roman M. Khopta, Lidiia Miziuk MODERN METHODS OF PATIENTS TREATMENT WITH DENTITION DEFECTS COMBINED WITH FUNCTIONAL DISORDERS OF THE TEMPOROMANDIBULAR JOINT 2241 Galyna V. Yeryomenko, Tetiana V. Bezditko, Olena V. Vysotska, Liubov M. Rysovana, Anna I. Pecherska PECULIARITIES OF METABOLIC CHANGES IN ASTHMA 2246 Oksana O. Kopchak, Natalia Yu. Bachinskaya, Oleksandr R. Pulyk VASCULAR RISK FACTORS AND COGNITIVE FUNCTIONS IN THE PATIENTS WITH CEREBROVASCULAR DISEASE 2250 Tetiana O. Kriuchko, Liudmyla M. Bubyr, Inna M. Nesina, Olha Y. Tkachenko, Olha V. Izmailova, Olha A. Poda, Viktoriia V. Shcherbak WAYS OF OPTIMIZING THE DIAGNOSTICS OF FOOD ALLERGIES IN CHILDREN BASED ON THE CLINICAL AND IMMUNOLOGICAL CRITERIA 2255 REVIEW ARTICLES Tatiana V. Peresypkina WAYS TO IMPROVE THE SYSTEM OF MEDICAL PROVIDING OF PUPILS IN UKRAINE 2261 Oleksandr M. Naumenko, Yurii M. Skaletsky, Viacheslav L. Didkovskyy, Mykhailo M. Rigan, Oksana O. Maluk SAFETY OF PATIENTS AND MEDICAL STAFF IN CURRICULA AND TRAINING PROGRAMS FOR MEDICAL PROFESSIONALS IN UKRAINE 2265 Liudmyla A. Vygivska, Lesia A. Rudenko, Violeta B. Kalnytska, Olena Yu. Litvinenko FEATURES OF THE COURSE OF PERINATAL INFECTIONS AT THE PRESENT STAGE 2269 Kamila Fuczyło, Magdalena Piegza, Robert Pudlo SEXUAL DISORDERS AFTER HEART TRANSPLANT 2277 Pashkov Vitalii, Harkusha Andrii, Harkusha Yevheniia STAND-ALONE SOFTWARE AS A MEDICAL DEVICE: QUALIFICATION AND LIABILITY ISSUES 2282 Tetіana A. Pavlenko, Tetіana Ye. Dunaieva, Marina Yu. Valuiska PROSPECTS OF EUTHANASIA LEGAL REGULATION IN UKRAINE 2289 Halyna Yu. Morokhovets, Olena M. Bieliaieva, Yuliia V. Lysanets THE RESULTS OF MONITORING THE SYCHOLOGICAL READINESS FOR PROFESSIONAL ACTIVITIES IN MEDICAL STUDENTS 2295 Katarzyna Karina Pawlik, Anna Bohdziewicz, Magdalena Chrabąszcz, Anna Stochmal, Mariusz Sikora, Rosanna Alda-Malicka, Joanna Czuwara, Lidia Rudnicka BIOMARKERS OF DISEASE ACTIVITY IN SYSTEMIC SCLEROSIS 2300 CASE STUDIES Volodymyr B. Dobrorodniy, Anatoliy D. Bedenyuk, Viktoria G. Khoperiia, Andriy V. Dobrorodniy PAPILLARY CARCINOMA, A METASTASIS OF THE BRAIN AND BONE: A RARE CASE 2306 Aleksandra Bełz, Violetta Rosiek, Joanna Głogowska- Szeląg, Katarzyna Stęplewska, Beata Kos-Kudła LUNG NODULE 25 YEARS AFTER LOBECTOMY – RECURRENCE OF BRONCHIAL CARCINOID 2309 Grzegorz K. Jakubiak, Józefina Ochab-Jakubiak, Anna Król-Zybura, Grzegorz Cieślar, Agata Stanek DYSPNOEA AS THE FIRST SYMPTOM OF COLON CANCER 2313 SHORT COMMUNICATION Paweł Żebrowski, Jacek Zawierucha, Wojciech Marcinkowski, Tomasz Prystacki, Inga Chomicka, Jolanta Malyszko HOME DIALYSIS DURING COVID-19 OUTBREAK – IT IS WORTH TO CONSIDER 2316 2269 Wiadomości Lekarskie, VOLUME LXXIII, ISSUE 10, OCTOBER 2020© Aluna Publishing INTRODUCTION Perinatal infections often play a leading role in the causes of such adverse effects of pregnancy as stillbirth, early infant death and morbidity, which makes it important to study this issue comprehensively. Infections cause the termination of every fifth pregnancy. The term “perinatal infection” usually refers to infections transmitted from the mother to the infant during prenatal development (prenatal or congenital infections), during childbirth (perinatal or intranatal infections), as well as immediately after birth (postnatal infections). Currently, perinatal infections include sexually transmitted infections, vaginal dysbiosis and TORCH syndrome infections. In addition, there are new infections that were not previously known to mankind, a disease caused by parvovirus B19, herpes virus type 6, etc. [1-2]. The number of children born with signs of intrauterine infection from pregnant women with infectious-inflamma- tory diseases does not tend to decrease, but on the contrary, increases, ranging from 10 to 58% [3]. Mаnagement of perinatal infections is a difficult task because of the absence of apparent specific symptoms inherent to a particular pathology, as well as the correlation between the severity of infectious pathology of the pregnant woman and the involvement of the fetus [4]. Newborns with clinical manifes- tations of infection require costly therapy and further rehabili- tation, which does not completely exclude the development of the pathological process into chronic form and even complete disability of the child. Both mother and fetus often have mixed forms of viral-bacterial infections, which dictates the need for therapeutic measures aimed at increasing nonspecific resistance of the body and correction of metabolic changes [5]. Today, thanks to vaccination, it is possible to control such infections as viral hepatitis B, rubella, measles, mumps. Bacterial and sexually transmitted infections are also controlled through the use of effective antibacterial agents. A large number of perinatal infections can now also be controlled using certain chemotherapeutic agents. Some women have such infections as cytomegaly or toxoplasmosis in childhood, and by the re- productive period they acquire natural immunity [6]. However, it should be noted that, despite vaccination, such infections as genital herpes, papillomavirus infection, and par- vovirus B19 infection are not sufficiently controlled. The solution to the problem of perinatal infections is their prevention during pregravid preparation by vaccination, elimi- nation of pathogens and stabilization of chronic diseases such as herpes simplex virus. This approach requires the collaboration of specialist physicians (obstetrician, gynecologist, infectious disease specialist) to adequately assess the risks to the mother and child and to prescribe therapy. THE AIM To characterize the course of the most common perinatal infections on the basis of assessment of the literature data. FEATURES OF THE COURSE OF PERINATAL INFECTIONS AT THE PRESENT STAGE 10.36740/WLek202010132 Liudmyla A. Vygivska¹, Lesia A. Rudenko², Violeta B. Kalnytska¹, Olena Yu. Litvinenko¹ 1KHARKIV NATIONAL MEDICAL UNIVERSITY, KHARKIV, UKRAINE 2ALUNA PUBLISHING HOUSE, KONSTANCIN-JEZIORNA, POLAND ABSTRACT The aim: To characterize the course of the most common perinatal infections on the basis of assessment of the literature data. Materials and methods: This article provides an assessment of 125 literature sources submitted to PubMed, Medline, Cochrane Library, CyberLeninka, Google Scholar and V.I. Vernadsky National Library of Ukraine. The description of the most common viral, bacterial and parasitic perinatal infections, transmission methods, clinical manifestations, methods of diagnosis and treatment, their clinical consequences are described. Perinatal infections are the leading cause of severe congenital pathology, a serious worldwide medical and social problem that needs to be addressed. Conclusions: Perinatal infections are a serious issue of today, requiring a multidisciplinary approach and the collaboration of doctors of different specialties. Their prevalence among the population, high rates of perinatal mortality, concealment under the mask of other disorders, and the absence of specific clinical symptoms in pregnant and newborns require careful consideration of this problem. Improving the quality of diagnosis and treatment of this pathological condition will help to minimize the risk of transmission of infection, as well as to avoid a number of abnormaalities in the neonatal period and the development of congenital infection. KEY WORDS: perinatal infections, routes of transmission, diagnosis, treatment, prevention Wiad Lek. 2020;73(10):2269-2276 REVIEW ARTICLE Liudmyla A. Vygivska et al. 2270 MATERIALS AND METHODS This article provides assessment of 125 literary sources. Particular attention is paid to sources over the last 5 years (2014-2019), but some earlier publications that have not lost their relevance are also included in the review. The sources were taken from scientific metric databases PubMed, Medline, databases of electronic libraries Cochrane Library, CyberLeninka, search engine Google Scholar and the portal of scientific periodicals of V.I. Vernadsky National Library of Ukraine. The description of the most common viral, bacterial and parasitic perinatal infections, transmission methods, clinical manifestations, methods of diagnosis and treatment, their clinical consequences are presented. Perinatal infections are a leading cause of severe congenital pathology, a serious worldwide medical and social problem that needs to be addressed [7-8]. REVIEW AND DISCUSSION Perinatal infections are a topical issue today because: in the structure of perinatal mortality, the proportion of in- trauterine infection ranges from 2 to 65.6%; the structure of infectious morbidity of pregnant women, the fetus and the newborn has changed; the role of pathogens of sexu- ally transmitted diseases has increased dramatically; the problem of diagnosis of this disorder (often hidden by such diagnoses as intrauterine hypoxia, asphyxia, birth trauma) remains extremely important and complicated [9]. Up to 2500 different infections are known in modern medical science. Proven pathogens for intrauterine infec- tions are over 27 species of bacteria, viruses, parasites, 6 species of fungi, 4 types of protozoa and rickettsia. There is no relationship between the severity of the infectious process in the mother and the fetus. Current perinatal care guidelines developed by the American Academy of Pediatricians and the American College of Obstetricians and Gynecologists suggest that only some infections occurring during the pre- and in- tranatal period can significantly affect the fetus and the newborn [10]. VIRAL INFECTIONS Cytomegalovirus infection (CMV) is one of the most common perinatal infections. 1% of newborns are infect- ed with CMV pre-natally, and the virus is released after birth. Signs of infection are observed from birth in 10% of newborns with congenital CMV infection [11-12]. Thus, intrauterine growth retardation, jaundice, purpura, hepa- tosplenomegaly, microcephaly, intracerebral calcifications, retinitis, and neurosensory hearing loss are detected in one third of all cases [13]. CMV is the main non-genetic cause of neurosensory hearing loss [14]. Ways of transmission: transplacental, contact with infected mother’s secretions, swallowing of infected breast milk, blood transfusions from seropositive donors. Infection occurs from mothers with primary CMV infection, primarily from those infected in the first and second trimesters [15]. The benefit of routine serological screening of women or newborns has not yet been proven [16]. Testing is carried out only to pregnant women and newborns with suspected CMV. Isolation of the virus or detection of the CMV genome by polymerase chain reaction (PCR) from amniotic fluid is the most sensitive test for the detection of fetal infection. In addition, cord blood obtained by cordocentesis can be tested for CMV-specific immunoglobulin M (IgM), but this test is less sensitive than the release of culture or PCR of amniotic fluid [17]. Today, the treatment of CMV infection in clinically healthy people is not carried out. Antiviral treatment is provided to patients whose condition is life-threatening. The use of hyperimmune globulin in pregnant women with primary CMV infection may reduce the risk of congenital CMV [18]. However, insufficient data have yet been collected on its effectiveness, which makes it difficult to recommend for widespread use. Enteroviruses. They include a group of viruses: poliovirus- es, Coxsackie viruses, echoviruses and other enteroviruses. The widespread use of the vaccine has helped to eliminate poliovirus infection. Enterovirus infection is spread by fecal-oral route and through the air. Enteroviruses are common and pregnant women are often exposed to them, especially in the summer and autumn months. Most of the enterovirus infections during pregnancy are mild or asymptomatic. However, in the third trimester, infection can be the cause of the onset of labor [19]. Enteroviruses penetrate the placenta and cause disease in the fetus and antenatal death. Vertical transmission of enteroviruses can occur at birth under the influence of a virus contained in maternal blood or vaginal secretions. Signs of enterovirus infection in newborns are usually observed 3-7 days after birth. In newborns, manifestation may include pneumonia, rash, aseptic meningitis, encephalitis, paralysis, hepatitis, conjunctivitis, myocarditis, and pericarditis [20]. The diagnosis is confirmed by isolation of the virus from smears from the throat or rectum and samples of feces, cerebrospinal fluid or blood. Herpes simplex virus. Herpes simplex virus (HSV) is a DNA virus. Types 1, 2 and 6 are relevant in obstetrics [21]. Most sexually transmitted infections with HSV are caused by HSV-2. However, HSV-1 is increasingly the cause of genital herpes infection [22]. In 60% of cases the course is asymptomatic, in 20% atyp- ical, and 20% have typical clinical signs of the disease [23]. There are primary infection and relapses. Primary infection occurs in women without evidence of previous herpetic infection (i.e. seronegative for both HSV-1 and HSV-2) or primary infection of HSV-2 in women with prior HSV-1 infection or vice versa [24]. In relapses, infections occur in women with clinical or serological data from previous genital herpes (the same serotype) [25]. The fact that HSV-2 infection is confirmed serologically but not clinically diagnosed in most women is indicative of the asymptomatic course of most primary infections [26]. FEATURES OF THE COURSE OF PERINATAL INFECTIONS AT THE PRESENT STAGE 2271 Women with primary HSV infection which develop at late stages of pregnancy (symptomatic or asymptomatic) who give birth vaginally are at high risk (30-50%) of trans- mitting the virus to their children. The risk of transmission during vaginal birth is much lower in recurrent infection (less than 2-5%). Although routine HSV screening is not recommended, all suspected herpes virus infections should be evaluated and confirmed using methods of virus detection (viral culture or viral PCR detection of the antigen) or a test for a specific serological antibody [27]. In Ukraine, according to the order No. 906 “Perinatal infections” as of 27.12.2006, treatment with antiviral drugs is not carried out, except in cases when it is urgently indi- cated to the mother. Foreign scientists have shown that the use of acyclovir in pregnant women reduces the risk of clinical recurrence of HSV. Acyclovir can be given orally to pregnant women with a first episode of genital herpes or severe recurrence of herpes infection. Intravenous administration is indicated in severe genital HSV infection or with disseminated herpetic infection [28]. Pre-natal infection is extremely rare. Most children who develop HSV infection acquire it during the passage through the infected maternal lower genital tract or premature rupture of the fetal membranes when the ascending infection occurs [29]. Signs of infection appear within 48 hours of birth [30]. Human papillomavirus. Human papillomavirus (HPV) infections are common. There are more than 100 types of HPVs, more than 40 of which can infect the genital area. HPV-6 and HPV-11 are the cause of respiratory pap- illomatosis, HPV-16 and HPV-18 contribute to genital carcinoma [31]. Most cervical HPV infections are sexually transmitted and have an asymptomatic course. Genital HPV infections can be exacerbated during pregnancy. Imiquimod, sinecatechins, podophyllin, and podofilox drugs should not be used during pregnancy because they have a toxic effect on the fetus. Cryotherapy, laser therapy and trichloroacetic acid can be safely used in the treatment of HPV during pregnancy [32]. FDA-approved vaccines have no adverse effect on pregnancy. However, if a woman becomes aware that she is pregnant at the time of vacci- nation, it must be postponed until delivery. Vaccination is not contraindicated when breast-feeding [33]. There is a risk of transmission of HPV from mother to child. The risk of transmission of recurrent respiratory papillomatosis is very low. Aspiration of infectious secretions can occur during the passage through the birth canal. In large condylomas caesarean section is recommended as they contribute to the deterioration of vaginal stretching during childbirth, and can also cause large vulvovaginal ruptures. Human parvovirus. Parvovirus B19 is a DNA virus that causes exanthema in children. Transmission is most often through air and by contact routes, that is, through the airways and from hand to mouth. In 33% of cases the infection is asymptomatic [34]. Most people carry the infection in a mild form and completely recover. Perinatal transmission. Parvovirus B19 affects fetal erythrocytes and causes anemia, which can lead to non-immune dropsy, isolated pleural and pericardial effusions, fetal developmental de- lay and death syndrome. Future parents should be aware that, although the rate of intrauterine transmission is high (approximately 50%), the risk of fetal death is between 2% and 6% [35]. Most reported perinatal infections caused by parvovirus lead to fetal death when infection occurs between the 10th and 20th weeks of pregnancy, fetal death or miscarriage usually occurs 4–6 weeks after infection [36]. Congenital abnormalities caused by parvovirus are extremely rare. The teratogenic effect of parvovirus has not been proven [37]. Due to the prevalence of asymptomatic parvovirus infection in adults and children, all pregnant women are at some risk of infection. If a pregnant woman becomes aware that she has been in contact with a patient, the potential risk to the fetus should be assessed and a serological test (ELISA and Western blot tests) should be carried out. If the test is negative, it should be repeated in 3-4 weeks to determine seropositivity [38]. When seroconversion occurs, the fetus should be mon- itored for 10 weeks by serial ultrasound to assess the pres- ence of non-immune fetal hydrops, placenta and growth disorders [39]. In the development of fetal hydrops, it is recommended to perform umbilical cord blood sampling with determination of hematocrit, leukocytes and platelets, as well as viral DNA to choose strategy for pregnancy man- agement and subsequent treatment of the newborn [40]. Rubella. Rubella during pregnancy can lead to miscar- riage, fetal death, or congenital rubella syndrome. The most common manifestations associated with congenital rubella syndrome are ophthalmic (cataracts, pigmented retinopathy, microphthalmus and congenital glaucoma), cardiac (open arterial duct, pulmonary artery stenosis), auditory (neuro- sensory disorders of hearing) and neurological (behavioral disorders, meningoencephalitis and mental retardation). Mild forms of congenital rubella syndrome may be associ- ated with minor clinical manifestations at birth [41]. At the preconception stage, it is desirable to undergo serological screening for immunity to rubella [42]. Sero- negative women should be vaccinated. Vaccination against rubella is carried out by live attenuated cultures, is very effective and has few side effects. However, vaccination against rubella is not recommended during pregnancy. Breastfeeding is not a contraindication for vaccination. After vaccination within 1 month, conception is not rec- ommended. However, if a woman becomes pregnant within 1 month of vaccination against rubella, or is accidentally vaccinated early in pregnancy, she should be informed of the potential teratogenic risk to the fetus [43]. If a pregnant woman is diagnosed with rubella, she should be advised of the risk of infecting the fetus and decide whether it is necessary to terminate the pregnancy. Structural anomalies can be caused by infection during em- bryogenesis [44]. If the infection occurs after the 20th week of pregnancy, birth defects rarely develop. All newborns Liudmyla A. Vygivska et al. 2272 with signs of congenital rubella or those born to women who had rubella during pregnancy should be isolated for further examination and treatment [45]. Varicella zoster virus. Varicella zoster virus (VZV) is a highly contagious DNA herpesvirus that is transmitted through the air and by contact route. Varicella in pregnant women can lead to the transmission of a fetal virus or newborn. It can cause congenital varicella syndrome, which is manifested by low birth weight, skin scars, limb hypoplasia, microcephaly, chorioretinitis and cataracts, neurological disorders [46]. It is observed in 1.5% of children born to women who had the disease before 28 weeks of gestation. If the infection occurred on the eve of childbirth (5 to 2 days), newborns develop a severe form of varicella, which has a high mortality rate [47-48]. VZV in the mother is usually diagnosed on the basis of clini- cal data and laboratory testing is not required. Pregnant women with severe varicella should be hospitalized with administration of acyclovir [49-50]. BACTERIAL INFECTIONS Chlamydial infection. Chlamydia trachomatis is the most common sexually transmitted infection. It is especially widespread among sexually active adolescents and young people (15-24 years old) [51]. Infected women have few symptoms, but C. trachomatis can cause urethritis and mucous-purulent (non-cancerous) cervicitis. Chlamydial infection is also associated with postpartum endometritis and infertility. The infection can be transmitted to the newborn during the passage through the birth canal. Clinical manifestations in fetuses/newborns: low birth weight, conjunctivitis, pneumonia [52-53]. Pre-conceptual counseling should include testing for chlamydial infection. High-risk women should be re-examined in the third tri- mester. The diagnosis of C. trachomatis infection is based on enzyme-linked immunosorbent assay and PCR. Treatment is carried out both to the woman and to the sexual partner according to specially developed schemes (josamycinum 500 mg orally 3 times a day for 7 days or 1 g of azithromycin orally in a single dose or amoxicillin 500 mg orally three times a day for 7 days) [54]. Gonorrhea. It is also one of the most common sexually transmitted infections. Women as young as 25 are at high- est risk of contracting gonorrhea. New or multiple sexual partners, misuse of condoms, commercial sex work, and illicit drug use are among causes of infection [55]. Gonococcal genital tract infections in women are often asymptomatic. Common clinical syndromes are vaginitis, urethritis, endocervicitis and salpingitis. Asymptomatic infection in women can develop into a more severe disease involving pelvic organs, such as inflammation of the pelvis with obstruction of the fallopian tubes, resulting in ectopic pregnancy or infertility [56]. Women at risk should be screened for gonorrhea. It is characterized by premature discharge of amniotic fluid, premature delivery. It may cause preterm death of fetus, gonoblenorrhea and sepsis in newborns [57]. Endo- cervical or vaginal smears as well as urinalysis are used for diagnosis. PCR diagnosis is a highly sensitive and specific method for detecting gonorrhea [58-59]. Group B streptococci. Group B (GBS) streptococci, also known as Streptococcus agalactiae, have been a major cause of perinatal morbidity and mortality since the 1970s, despite the fact that streptococci are a pathogen [60]. Vag- inal or rectal colonization with Streptococcus agalactiae is observed in 10–40% of pregnant women [61]. Group B streptococci can cause maternal urinary tract infection, amnionitis, endometritis, sepsis, and less commonly, meningitis. Vertical transmission of infection during childbirth can lead to infection of newborns with- in the first 6 days after birth, characterized primarily by sepsis or pneumonia, and less commonly by meningitis [62]. Introduction of national guidelines for administration of antibiotics during childbirth in the 1990s reduced early sepsis in newborns caused by Streptococcus agalactiae by 80%. However, even today GBS remains the leading cause of infant mortality and morbidity [63]. The main risk factors for infections in newborn are: presence of infec- tion in the mother, gestational age of less than 37 weeks, premature rupture of the fetal membranes for 18 hours or more, intra-amniotic infection, young maternal age and the presence of pessary [64]. In 2010, Centers for Disease Control and Prevention reviewed the basic principles for preventing early-onset infection caused by Streptococcus agalactiae: antenatal screening for infection at 35-37 weeks of gestation, timely antibiotic prophylaxis, especially in women with the risk of preterm labor [65]. Listeriosis. The major cause of epidemic and sporadic listeriosis infection is the food transmission of Listeria monocytogenes. Listeriosis is a food-borne infection. The bacterium enters the human body with food, which in turn is infected during manufacture and storage. These products include unpasteurized milk, cheese and other dairy products; undercooked poultry meat, cooked meat (hot dogs, meat delicacies and pate) [66]. Published on 21 February 2017, the results of a study by the Madison School of Veterinary Medicine (USA) showed that listeriosis can lead to miscarriage early in pregnancy (first trimester) [67]. Earlier listeriosis was recognized only in the third trimester and its effect at an early stage has not been studied. Sepsis is an early manifestation of infection in newborns and meningitis a late one [68]. Pregnant women are not recommended to consume unpasteurized dairy products, unwashed fresh fruits and vegetables, and under-processed meat to prevent listeria infection [69]. The role of Listeria as a causative agent of human diseases can be characterized as follows: they are causative agents of food infection; agents of a wide range of opportunistic infections; cause of human perinatal and neonatal pathology. Serological test is suggested to detect the presence of anti-listeriolysin O antibodies in blood [70]. Treatment includes administration of macrolides [71]. FEATURES OF THE COURSE OF PERINATAL INFECTIONS AT THE PRESENT STAGE 2273 PARASITIC INFECTIONS Malaria. Although malaria is largely restricted to tropical regions in Africa, Asia, and Latin America, frequent inter- national travel and migration have made it a disease that cannot be ignored in developed countries [72]. Malaria infection is quite a serious condition for pregnant women, due to the increased risk of adverse pregnancy outcomes, including spontaneous abortion, stillbirth, premature birth and low birth weight [73-75]. Due to the high risk for both the woman and the fetus, as well as the lack of full effect of chemoprevention on pregnant women and women planning pregnancy, travel to areas endemic to malaria should be avoided. Congenital malaria is rare. Signs and symptoms resemble newborn sepsis. Toxoplasmosis. Toxoplasmosis is a protozoal infection caused by Toxoplasma gondii. It is an infectious disease. Ways of transmission can be nutritional, zoonotic and from mother to child during pregnancy. Infected women are usually asymptomatic. Signs of a congenital infection can show up at birth. These include maculopapular rash, generalized lymphadenopathy, hep- atosplenomegaly, chorioretinitis, hydrocephalus, micro- cephaly, and intracranial calcification [76]. Routine serological screening is not indicated for preg- nant women, except in cases of HIV infection, since the presence of antibodies indicates immunity, especially if the woman is at risk before conception [77]. The diagnosis of maternal infection is based on the results of a serological test for the detection of toxoplasmospecific antibodies [78]. Patients with suspected toxoplasmosis should be tested for immunoglobulins IgG and IgM [79]. A positive IgG titer indicates past infection. A negative IgM test essentially eliminates recent infection, but a positive IgM test is difficult to interpret because toxoplasma-specific IgM antibodies can be detected within 18 months of acute infection. (More information on laboratory diagnosis of toxoplasmosis is available on the CDC website at http:// www.dpd.cdc.gov/dpdx/HTML/Toxoplasmosis.htm). Treatment of pregnant with acute toxoplasmosis reduces but does not exclude the risk of congenital infection. Detec- tion of acute maternal infection requires immediate start of treatment prior to evaluation of fetal status. Spiramycin accumulated in the placenta can reduce the risk of fetal transmission by 60%. If intrauterine infection is confirmed, it is recommended to add pyrimethamine, sulfanilamides (which is an exception only to congenital toxoplasmosis) and folic acid to the treatment regimen, which may con- tribute to a successful pregnancy outcome [80]. CONCLUSIONS Perinatal infections are a serious issue of today, requiring a multidisciplinary approach and the collaboration of doctors of different profiles. Prevalence among the pop- ulation, high rates of perinatal mortality, concealment under the mask of other disorders, and the absence of specific clinical symptoms in pregnant and newborns require careful consideration of this problem. Improving the quality of diagnosis and treatment of this pathological condition will help to minimize the risk of transmission of infection, as well as to avoid a number of pathological conditions in the neonatal period and the development of congenital infection. REFERENCES 1. Keighley C.L., Skrzypek H.J., Wilson A. et al. Infections in pregnancy. 2019;211(3):134-41. doi: 10.5694/mja2.50261. 2. Leeper C., Lutzkanin A. 3rd. Infections During Pregnancy. Prim Care. 2018;45(3):567-86. doi: 10.1016/j.pop.2018.05.013. 3. Zaplatnikov A.L., Korovin N.A., Korneva M.Yu., Cheburkin A.V. 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