Congenital malformations of infectious origin

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Infection of the fetus during organogenesis can induce teratogenesis and lead to pregnancy loss, the development of congenital anomalies or neonatal death. Although the impact of infectious factors on the incidence of congenital malformations is relatively low, infections that have teratogenic effects are a significant cause of perinatal morbidity and mortality on a global scale. The causative agents of the most common intrauterine infections with proven teratogenic effects are pathogens of the TORCH group (Toxoplasma, Others (Syphilis, Varicella-Zoster, Parvovirus B19), Rubella, Cytomegalovirus, Herpes). In most cases, TORCH group infections are not dangerous to the mother, but can lead to very serious consequences for the fetus. Therefore, timely detection of infection in the mother and monitoring of the fetus are extremely important for competent counseling of women about possible adverse outcomes and measures to prevent them. The review presents the data from recent studies on the epidemiology of congenital malformations of infectious origin, mechanisms of infectious teratogenesis, principles of prevention and treatment of infections with teratogenic effects, and methods of prenatal prognosis.

Conclusion: The development of effective strategies for predicting, preventing, and treating congenital infections requires research at all levels, namely, basic, translational, clinical, and population-based ones. Further investments in global epidemiological surveillance are necessary to promptly identify new infectious teratogens.

全文:

受限制的访问

作者简介

Elena Shipitsyna

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

编辑信件的主要联系方式.
Email: shipitsyna@inbox.ru
ORCID iD: 0000-0002-2309-3604

Dr. Bio. Sci., Leading Researcher at the Department of Medical Mirobiology

俄罗斯联邦, 199034, St. Petersburg, Mendeleyevskaya Line, 3

Olesya Bespalova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Email: shiggerra@mail.ru
ORCID iD: 0000-0002-6542-5953

Dr. Med. Sci., Deputy Director

俄罗斯联邦, 199034, St. Petersburg, Mendeleyevskaya Line, 3

Olga Talantova

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Email: olga_talantova@mail.ru
ORCID iD: 0000-0003-3520-599X

PhD, Senior Researcher at the Laboratory of Cytogenetics and Cytogenomics of Reproduction, Obstetrician-Gynecologist of the Medical Genetic Center

俄罗斯联邦, 199034, St. Petersburg, Mendeleyevskaya Line, 3

Igor Kogan

D.O. Ott Research Institute of Obstetrics, Gynecology and Reproduction

Email: ikogan@mail.ru
ORCID iD: 0000-0002-7351-6900

Corresponding Member of RAS, Dr. Med. Sci., Professor, Director

俄罗斯联邦, 199034, St. Petersburg, Mendeleyevskaya Line, 3

参考

  1. World Health Organization. Congenital disorders. Available at: https://www.who.int/health-topics/congenital-anomalies#tab=tab_1=tab_1
  2. Boyle B., Addor M., Arriola L., Barisic I., Csáky-szunyogh M., Bianchi F. et al. Estimating global burden of disease due to congenital anomaly : an analysis of european data. Arch. Dis. Child. Fetal Neonatal Ed. 2018; 103(1): F22-8. https://dx.doi.org/10.1136/archdischild-2016-311845
  3. Feldkamp M.L., Carey J.C., Byrne J.L.B., Krikov S., Botto L.D. Etiology and clinical presentation of birth defects: population based study. BMJ. 2017; 357: j2249. https://dx.doi.org/10.1136/BMJ.J2249
  4. Adams Waldorf K.M., McAdams R.M. Influence of infection during pregnancy on fetal development. Reproduction. 2013; 146(5): R151-62. https://dx.doi.org/10.1530/REP-13-0232
  5. Coyne C.B., Lazear H.M. Zika virus – reigniting the TORCH. Nat. Rev. Microbiol. 2016; 14(11): 707-15. https://dx.doi.org/10.1038/nrmicro.2016.125
  6. Colonna A., Buonsenso D., Pata D., Salerno G., Chieffo D.P.R., Romeo D.M. et al. Long-term clinical, audiological, visual, neurocognitive and behavioral outcome in children with symptomatic and asymptomatic congenital cytomegalovirus infection treated with valganciclovir. Front. Med. (Lausanne). 2020; 7: 268. https://dx.doi.org/10.3389/fmed.2020.00268
  7. Perera C.A. Congenital cataract following German measles in pregnancy. Sight Sav. Rev. 1946; 16(3): 135-7.
  8. Cauchemez S., Besnard M., Bompard P., Dub T., Guillemette-Artur P., Eyrolle-Guignot D. et al. Association between Zika virus and microcephaly in French Polynesia, 2013–15: a retrospective study. Lancet. 2016; 387(10033): 2125-32. https://dx.doi.org/10.1016/S0140-6736(16)00651-6
  9. Adams Waldorf K.M., Nelson B.R., Stencel-Baerenwald J.E., Studholme C., Kapur R.P., Armistead B. et al. Congenital Zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain. Nat. Med. 2018; 24(3): 368-74. https://dx.doi.org/10.1038/NM.4485
  10. Stegmann B.J., Carey J.C. TORCH Infections. Toxoplasmosis, Other (syphilis, varicella-zoster, parvovirus B19), Rubella, Cytomegalovirus (CMV), and Herpes infections. Curr. Womens Health Rep. 2002; 2(4): 253-8.
  11. European Commission. Prevalence charts and tables. Available at: https://eu-rd-platform.jrc.ec.europa.eu/eurocat/eurocat-data/prevalence_en
  12. Morris J.K., Springett A.L., Greenlees R., Loane M., Addor C., Arriola L. et al. Trends in congenital anomalies in Europe from 1980 to 2012. PLOS One. 2018; 13(4): e0194986. https://dx.doi.org/10.1371/journal.pone.0194986
  13. Wang Y., Li S., Ma N., Zhang Q., Wang H., Cui J. et al. The association of ToRCH infection and congenital malformations: a prospective study in China. Eur. J. Obstet. Gynecol. Reprod. Biol. 2019; 240: 336-40. https://dx.doi.org/10.1016/j.ejogrb.2019.04.042
  14. Voordouw B., Rockx B., Jaenisch T., Fraaij P., Mayaud P., Vossen A. et al. Performance of Zika assays in the context of Toxoplasma gondii, Parvovirus B19, Rubella Virus, and Cytomegalovirus (TORCH) diagnostic assays. Clin. Microbiol. Rev. 2019; 33(1): e00130-18. https://dx.doi.org/10.1128/CMR.00130-18
  15. Leruez-Ville M., Magny J.F., Couderc S., Pichon C., Parodi M., Bussières L. et al. Risk factors for congenital cytomegalovirus infection following primary and nonprimary maternal infection: a prospective neonatal screening study using polymerase chain reaction in saliva. Clin. Infect. Dis. 2017; 65(3): 398-404. https://dx.doi.org/10.1093/cid/cix337
  16. Рогозина Н.В., Васильев В.В., Иванова Р.А., Ушакова Г.М., Безверхая Н.С. Поражения органов и систем у детей, родившихся от матерей с острой цитомегаловирусной инфекцией. Инфекционные болезни: новости, мнения, обучение. 2023; 12(2): 57-64. [Rogozina N.V., Vasil’ev V.V., Ivanova R.A., Ushakova G.M., Bezverkhaya N.S. Lesions of organs and systems in children born from mothers with acute cytomegalovirus infection. Infectious Diseases: News, Opinions, Training. 2023; 12(2): 57-64 (in Russian)]. https://dx.doi.org/10.33029/2305-3496-2023-12-2-57-64
  17. Ssentongo P., Hehnly C., Birungi P., Roach M.A., Spady J., Fronterre C. et al. Congenital cytomegalovirus infection burden and epidemiologic risk factors in countries with universal screening: a systematic review and meta-analysis. JAMA Netw. Open. 2021; 4(8): e2120736. https://dx.doi.org/10.1001/jamanetworkopen.2021.20736
  18. Vande Walle C., Keymeulen A., Schiettecatte E., Acke F., Dhooge I., Smets K. et al. Brain MRI findings in newborns with congenital cytomegalovirus infection: results from a large cohort study. Eur. Radiol. 2021; 31(10): 8001-10. https://dx.doi.org/10.1007/S00330-021-07776-2
  19. Diogo M.C., Glatter S., Binder J., Kiss H., Prayer D. The MRI spectrum of congenital cytomegalovirus infection. Prenat. Diagn. 2020; 40(1): 110-24. https://dx.doi.org/10.1002/pd.5591
  20. Lucignani G., Guarnera A., Rossi-Espagnet M.C., Moltoni G., Antonelli A., Figà Talamanca L. et al. From fetal to neonatal neuroimaging in TORCH infections: A pictorial review. Children (Basel). 2022; 9(8): 1210. https://dx.doi.org/10.3390/children9081210
  21. Khalil A., Sotiriadis A., Chaoui R., da Silva Costa F., D’Antonio F., Heath P.T. et al. ISUOG practice guidelines: role of ultrasound in congenital infection. Ultrasound Obstet. Gynecol. 2020; 56(1): 128-51. https://dx.doi.org/10.1002/uog.21991
  22. Buca D., Di Mascio D., Rizzo G., Giancotti A., D’Amico A., Leombroni M. et al. Outcome of fetuses with congenital cytomegalovirus infection and normal ultrasound at diagnosis: systematic review and meta-analysis. Ultrasound Obstet. Gynecol. 2021; 57(4): 551-9. https://dx.doi.org/10.1002/uog.23143
  23. Mappa I., De Vito M., Flacco M.E., Di Mascio D., Antonio F., Rizzo G. Prenatal predictors of adverse perinatal outcome in congenital cytomegalovirus infection: a retrospective multicenter study. J. Perinat. Med. 2022; 51(1): 102-10. https://dx.doi.org/10.1515/jpm-2022-0286
  24. Shahar-Nissan K., Pardo J., Peled O., Krause I., Bilavsky E., Wiznitzer A. et al. Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial. Lancet. 2020; 396(10253): 779-85. https://dx.doi.org/10.1016/S0140-6736(20)31868-7
  25. Chatzakis C., Shahar-Nissan K., Faure-Bardon V., Picone O., Hadar E., Amir J. et al. The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis. Am. J. Obstet. Gynecol. 2024; 230(2): 109-17.e2. https://dx.doi.org/10.1016/j.ajog.2023.07.022
  26. Dzubay S.K., Gagliuso A.H., Arora M., Doshi U., Caughey A.B. Universal screening and valacyclovir for first trimester primary cytomegalovirus: a cost-effectiveness analysis. Am. J. Obstet. Gynecol. 2025; 233(3): 191.e1-9. https://dx.doi.org/10.1016/J.AJOG.2025.02.009
  27. Xiang J., Zhang H., Sun X., Zhang J., Xu Z., Sun J. et al. Utility of whole genome sequencing for population screening of deafness-related genetic variants and cytomegalovirus infection in newborns. Front. Genet. 2022; 13: 883617. https://dx.doi.org/10.3389/fgene.2022.883617
  28. Yang Y., Liu L., Yang Z., Wei X., Wei X., Chen Y. et al. Whole genome sequencing incidentally identified intrauterine cytomegalovirus infection in a fetus with fetal growth restriction: a case study. Ann. Clin. Case Rep. 2023; 8: 2384.
  29. Hu X., Wang H.Y., Otero C.E., Jenks J.A., Permar S.R. Lessons from acquired natural immunity and clinical trials to inform next-generation human cytomegalovirus vaccine development. Annu. Rev. Virol. 2022; 9(1): 491-520. https://dx.doi.org/10.1146/annurev-virology-100220-010653
  30. Hughes B., Clifton R., Rouse D., Saade G.R., Dinsmoor M.J., Reddy U.M. et al. Randomized trial of hyperimmune globulin for congenital CMV infection-2-year outcomes. N. Engl. J. Med. 2023; 389(19): 1822-4. https://dx.doi.org/10.1056/NEJMc2308286
  31. Chiopris G., Veronese P., Cusenza F., Procaccianti M., Perrone S., Daccò V. et al. Congenital cytomegalovirus infection: update on diagnosis and treatment. Microorganisms. 2020; 8(10): 1516. https://dx.doi.org/10.3390/microorganisms8101516
  32. Maldonado Y.A., Read J.S. Diagnosis, treatment, and prevention of congenital toxoplasmosis in the United States. Pediatrics. 2017; 139(2): e20163860. https://dx.doi.org/10.1542/peds.2016-3860
  33. Thiébaut R., Leproust S., Chêne G., Gilbert R. Effectiveness of prenatal treatment for congenital toxoplasmosis: a meta-analysis of individual patients’ data. Lancet. 2007; 369(9556): 115-22. https://dx.doi.org/10.1016/S0140-6736(07)60072-5
  34. Peyron F., L’ollivier C., Mandelbrot L., Wallon M., Piarroux R., Kieffer F. et al. Maternal and congenital Toxoplasmosis: diagnosis and treatment recommendations of a French multidisciplinary working group. Pathogens (Basel). 2019; 8(1): 24. https://dx.doi.org/10.3390/pathogens8010024
  35. Васильев В.В., Рогозина Н.В., Иванова Р.А. Проблема токсоплазмоза в амбулаторной практике. Часть III. Токсоплазмоз у беременных и врожденный токсоплазмоз. Российский семейный врач. 2023; 27(3): 5-11. [Vasiliev V.V., Rogosina N.V., Ivanova R.A. The problem of toxoplasmosis in outpatient practice. Part III. Toxoplasmosis in pregnants and congenital toxoplasmosis. Russian Family Doctor. 2023; 27(3): 5-11 (in Russian)]. https://dx.doi.org/10.17816/RFD568292
  36. Deganich M., Boudreaux C., Benmerzouga I. Toxoplasmosis infection during pregnancy. Trop. Med. Infect. Dis. 2022; 8(1): 3. https://dx.doi.org/10.3390/tropicalmed8010003
  37. Montoya J.G., Remington J.S. Management of Toxoplasma gondii infection during pregnancy. Clin. Infect. Dis. 2008; 47(4): 554-66. https://dx.doi.org/10.1086/590149
  38. Reef S.E., Strebel P., Dabbagh A., Gacic-Dobo M., Cochi S. Progress toward control of rubella and prevention of congenital rubella syndrome--worldwide, 2009. J. Infect. Dis. 2011; 204 Suppl. 1: S24-7. https://dx.doi.org/10.1093/infdis/jir155
  39. Баркинхоева Л.А., Тураева Н.В., Цвиркун О.В., Герасимова А.Г. Состояние иммунитета населения Российской Федерации к краснухе в период элиминации инфекции. Эпидемиология и вакцинопрофилактика. 2024; 23(3): 38-46. [Barkinkhoeva L.A., Turaeva N.V., Tsvirkun O.V., Gerasimova A.G. The state of immunity of the population of the Russian Federation to Rubella during the elimination of infection. Epidemiology and Vaccinal Prevention. 2024; 23(3): 38-46 (in Russian)]. https://dx.doi.org/10.31631/2073-3046-2024-23-3-38-46
  40. Samies N.L., James S.H. Prevention and treatment of neonatal herpes simplex virus infection. Antiviral. Res. 2020; 176: 104721. https://dx.doi.org/10.1016/j.antiviral.2020.104721
  41. De Rose D.U., Bompard S., Maddaloni C., Bersani I., Martini L., Santisi A. et al. Neonatal herpes simplex virus infection: From the maternal infection to the child outcome. J. Med. Virol. 2023; 95(8): e29024. https://dx.doi.org/10.1002/JMV.29024
  42. Fa F., Laup L., Mandelbrot L., Sibiude J., Picone O. Fetal and neonatal abnormalities due to congenital herpes simplex virus infection: a literature review. Prenat. Diagn. 2020; 40(4): 408-14. https://dx.doi.org/10.1002/pd.5587
  43. Bollaerts K., Riera-Montes M., Heininger U., Hens N., Souverain A., Verstraeten T. et al. A systematic review of varicella seroprevalence in European countries before universal childhood immunization: deriving incidence from seroprevalence data. Epidemiol. Infect. 2017; 145(13): 2666-77. https://dx.doi.org/10.1017/S0950268817001546
  44. Ahn K.H., Park Y.J., Hong S.C., Lee E.H., Lee J.S., Oh M.J. et al. Congenital varicella syndrome: a systematic review. J. Obstet. Gynaecol. 2016; 36(5): 563-6. https://dx.doi.org/10.3109/01443615.2015.1127905
  45. Bhavsar S.M., Mangat C. Congenital Varicella syndrome. 2023 Mar 6. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan–.
  46. Ion A., Orzan O.A., Bălăceanu-Gurău B. Varicella zoster virus infection and pregnancy: an optimal management approach. Pathogens. 2025; 14(2): 151. https://dx.doi.org/10.3390/pathogens14020151
  47. Nanthakumar M.P., Sood A., Ahmed M., Gupta J. Varicella zoster in pregnancy. Eur. J. Obstet. Gynecol. Reprod. Biol. 2021; 258: 283-7. https://dx.doi.org/10.1016/j.ejogrb.2021.01.009
  48. World Health Organization. Mother-to-child transmission of syphilis. 2022. Available at: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/stis/prevention/mother-to-child-transmission-of-syphilis
  49. Рахматулина М.Р., Мелехина Л.Е., Новоселова Е.Ю. Ретроспективный анализ заболеваемости сифилисом в Российской Федерации в 2009–2023 гг. и тенденции динамического развития эпидемиологического процесса. Вестник дерматологии и венерологии. 2025; 101(1): 7-27. [Rakhmatulina M.R., Melekhina L.E., Novoselova E.Yu. Retrospective analysis of syphilis incidence in the Russian Federation in 2009–2023 and trends in the dynamic development of the epidemiological process. Bulletin of Dermatology and Venereology 2025; 101(1): 7-27 (in Russian)]. https://dx.doi.org/10.25208/vdv16851
  50. David M., Hcini N., Mandelbrot L., Sibiude J., Picone O. Fetal and neonatal abnormalities due to congenital syphilis: a literature review. Prenat. Diagn. 2022; 42(5): 643-55. https://dx.doi.org/10.1002/PD.6135
  51. Кокорева С.П., Котлова В.Б., Ромашова В.В. Врожденный сифилис на современном этапе. Научный электронный журнал Академическая публицистика. 2021; 4: 633-9. [Kokoreva S.P., Kotlova V.B., Romashova V.V. Congenital Syphilis at the present stage. Scientific electronic Journal Akademicheskaya Publitsistika. 2021; 4: 633-9 (in Russian)].
  52. Rac M.W.F., Bryant S.N., McIntire D.D., Cantey J.B., Twickler D.M., Wendel G.D. et al. Progression of ultrasound findings of fetal syphilis after maternal treatment. Am. J. Obstet. Gynecol. 2014; 211(4): 426.e1-6. https://dx.doi.org/10.1016/j.ajog.2014.05.049
  53. Kagan K.O., Hoopmann M., Geipel A., Sonek J., Enders M. Prenatal parvovirus B19 infection. Arch. Gynecol. Obstet. 2024; 310(5): 2363-71. https://dx.doi.org/10.1007/S00404-024-07644-6
  54. Ornoy A., Ergaz Z. Parvovirus B19 infection during pregnancy and risks to the fetus. Birth Defects Res. 2017; 109(5): 311-23. https://dx.doi.org/10.1002/bdra.23588
  55. Tolfvenstam T., Broliden K. Parvovirus B19 infection. Semin. Fetal Neonatal Med. 2009; 14(4): 218-21. https://dx.doi.org/10.1016/j.siny.2009.01.007
  56. dos Santos A.L.S., Rosolen B.B., Ferreira F.C., Chiancone I.S., Pereira S.S., Pontes K.F.M. et al. Intrauterine Zika virus infection: an overview of the current findings. J. Pers. Med. 2025; 15(3): 98. https://dx.doi.org/10.3390/JPM15030098
  57. Martins M.M., da Cunha A.J.L.A., Robaina J.R., Raymundo C.E., Barbosa A.P., de Andrade Medronho R. Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: a systematic review and meta-analysis. PLoS One. 2021; 16(2): e0246643. https://dx.doi.org/10.1371/journal.pone.0246643
  58. Gilbert R.K., Petersen L.R., Honein M.A., Moore C.A., Rasmussen S.A. Zika virus as a cause of birth defects: Were the teratogenic effects of Zika virus missed for decades? Birth defects Res. 2023; 115(3): 265-74. https://dx.doi.org/10.1002/bdr2.2134
  59. Parums D.V. A review of emerging viral pathogens and current concerns for vertical transmission of infection. Med. Sci. Monit. 2024; 30: e947335. https://dx.doi.org/10.12659/MSM.947335

补充文件

附件文件
动作
1. JATS XML
下载
2. Рисунок. Показатели серопозитивности и рисков инфицирования матери, вертикальной трансмиссии и развития врожденной инфекции для цитомегаловирусной инфекции, токсоплазмоза, краснухи и вирусной инфекции Зика (адаптировано из [14])

下载 (191KB)
索引源数据

版权所有 © Bionika Media, 2025