Congenital cytomegalovirus infection: current challenges and possible solutions

Abstract

Congenital cytomegalovirus (CMV) infection is often associated with severe neurological damage, increased neonatal mortality, neurocognitive disorders, hearing loss and functional impairment in children. In the current article we present the incidence of congenital CMV based on the official statistics and actual figures, as well as clinical characteristics and algorithms for laboratory diagnosis of congenital and intranatal CMV. The management of CMV during pregnancy and active CMV in newborns is also discussed. Finally, we discuss the indications for administration of intravenous CMV immunoglobulin in pregnant women and newborns and valganciclovir in suspension in newborns, infants and young children.

Keywords:cytomegalovirus infection, pregnant women, newborns, cytomegalovirus immunoglobulin

Funding. The study had no sponsor support.

Conflict of interests. The author declare no conflict of interests.

For citation: Shakhgildyan V.I. Congenital cytomegalovirus infection: current challenges and possible solutions. Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2020; 8 (4): 61-72. DOI: https://doi.org/10.33029/2308-2402-2020-8-4-61-72 (in Russian)

References

1. Early diagnosis of speech disorders. Features of speech development in children with the consequences of perinatal pathology of the nervous system. Clinical guidelines. In: N.N. Volodin, V.M. Shklovsky (eds). Moscow: Rossiyskaya assotsiatsiya spetsialistov perinatal’noy meditsiny, 2015. (in Russian)

2. Sukhanova L.P. Perinatal problems of the reproduction of the population of Russia in the transition period. Moscow: Kanon +, 2006: 272 p. (in Russian)

3. Degtyarev D.N., Zaplatnikov A.L. Intrauterine infections. Cytomegalovirus infection. In: N.N. Volodin N.N. (ed.). Neonatology. National leadership. Short edition. Moscow: GEOTAR-Media, 2013: 725-31. (in Russian)

4. Neonatology: in 2 vols. In: T.L. Gomella, M.D. Cunningham, F.G. Eyal (eds); transl. from Engl.; D.N. Degtyarev (ed.). Moscow: BINOM. Laboratoriya znaniy, 2015: 708 p. (in Russian)

5. State report of the Office of Rospotrebnadzor in Moscow «On the state of sanitary and epidemiological welfare of the population in the city of Moscow in 2017». Moscow, 2018. URL: http://77.rospotrebnadzor.ru (in Russian)

6. Kenneson A., Cannon M.J. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol (Engl). 2007; 17 (4): 253-76.

7. Mussi-Pinhata M.M., Yamamoto A.Y. Natural history of congenital cytomegalovirus infection in highly seropositive populations. J Infect Dis. 2020; 221: 15-22.

8. Leruez-Ville M., Foulon I., Pass R., Ville Y. Cytomegalovirus infection during pregnancy: state of the science. Am J Obstet Gynecol. 2020; 223 (3): 330-49.

9. Dollard S.C., Grosse S.D., Ross D.S. New estimates of the prevalence of neurological and sensory sequelae and mortality associated with congenital cytomegalovirus infection. Rev Med Virol. 2007; 17 (5): 355-63.

10. Townsend C.L., Forsgren M., Ahlfors K., et al. Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom. Clin Infect Dis. 2013; 56 (9): 1232-9.

11. Halwachs-Baumann G., Genser B. Die konnatale zytomegalie Vi-rusinfetion. Wien, 2003: 133 s.

12. Order of the Ministry of Health of Russia dated 01.11.2012 No. 572n «On approval of the procedure for providing medical care in the field of "Obstetrics and Gynecology" (except for the use of assisted reproductive technologies)» (Appendix 5). (in Russian)

13. Letter of the Ministry of Health of the Russian Federation of 13.02.2020 No. 15-4/368-07 On clinical guidelines «Normal pregnancy» (ID288, developed by the Russian Society of Obstetricians and Gynecologists, approved in 2019) (in Russian)

14. Shakhgil’dyan V.I., Aleksandrova E.P., Kozyrina N.V., Shipulina O.Yu., Domonova E.A., Shakhgil’dian N.V. Cytomegalovirus infection in pregnant women and newborns: epidemiological analysis, new approaches to diagnosis and treatment. Akusherstvo i ginekologiya: novosti, mneniya, obuchenie [Obstetrics and Gynecology: News, Opinions, Training]. 2020; 8 (2): 80-94. DOI: https://doi.org/10.24411/2303-9698-2020-12008 (in Russian)

15. Kulakov V.I., Gurtovoy B.L., Ordzhonikidze N.V. Cytomegalovirus infection in obstetrics. Moscow: GEOTAR-Media, 2001: 32 p. (in Russian)

16. Stagno S., Ireland K.R. Congenital cytomegalovirus infection. In:S.L. Sacks, S.E. Straus, R.J. Whitley, P.D. Griffiths (eds). Clinical Management of Herpes Viruses. IOS Press, 1995: 329-40.

17. Johnson J., et al. Prevention of maternal and congenital cytomegalovirus infection. Clin Obstet Gynecol. 2012; 55 (2): 521-30.

18. Ornoy А. Fetal effects of primary and non-primary cytomegalovirus infection in pregnancy: are we close to prevention? Isr Med Assoc J. 2007; 9: 398-401.

19. Kisteneva L.B. The role of CMV infection in formation of perinatal pathology. Detskie infektsii [Children’s Infections]. 2013; (3): 44-7. (in Russian)

20. Shakhgildyan V.I. Diagnosis and treatment of cytomegalovirus infection in pregnant women and newborns. Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2017; (3): 70-82. (in Russian)

21. Pauline R.A., Spitzer A.R. Secrets of neonatology and perinatology. Transl. from Engl. In: N.N. Volodin (gen. ed.). Moscow: BINOM, 2013: 624 p. (in Russian)

22. Zaplatnikov A.L., Shakhgil’dyan V.I., Podzolkova N.M., et al. Is it possible to prevent the consequences of congenital cytomegalovirus infection? (the opinion of the obstetrician-gynecologist, neonatologist and infectiolo-gist). RMZH Meditsinskoe obozrenie [RMJ. Medical Review]. 2018; (10): 2-7. (in Russian)

23. Cytomegalovirus infection in children with autism spectrum disorder: systematic review and meta-analysis. J Autism Dev Disord. 2018; 48 (5): 1483-91.

24. Congenital, perinatal and neonatal infections. Transl. from Engl. In: A. Greenough, D. Osborne., S. Sutherland (eds). Moscow: Meditsina, 2000: 288 p. (in Russian)

25. Friese K., Kachel V. Infectious diseases of pregnant women and newborns. Transl. from German. Moscow: Meditsina, 2003: 424 p. (in Russian)

26. Korndewal M.J., Oudesluys-Murphy A.M., Kroes A.C., et al. Congenital cytomegalovirus infection: child development, quality of life and impact on daily life. Pediatr Infect Dis J. 2017; 36 (12): 1141-7.

27. de Vries J.J.C., van Zwet E.W., Dekker F.W., et al. The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: a population-based prediction model. Rev Med Virol. 2013; 23 (4): 241-9.

28. Shahgil’dyan V.I. Cytomegalovirus infection. In: Yushchuk N.D. (ed.); Viral Diseases: Textbook. Moscow: GEOTAR-Media, 2016: 540 p. (in Russian)

29. Mangusheva Ya.R., Khaertynova I.M., Maltseva 1.1. Cetomegalovirus infection in children. Prakticheskaya meditsina [Practical Medicine]. 2014; 7 (83): 11-6. (in Russian)

30. Kagan K.O., Enders M., Schampera M.S., et al. Prevention of maternal-fetal transmission of cytomegalovirus after primary maternal infection in the first trimester by biweekly hyperimmunoglobulin administration. Ultrasound Obstet Gynecol. 2019; 53 (3): 383-9.

31. Leung J., Cannon M.J., Grosse S.D., Bialek S.R. Laboratory testing and diagnostic coding for cytomegalovirus among privately insured infants in the United States: a retrospective study using administrative claims data. BMC Pediatr. 2013; 13: 90.

32. Enders G., Daiminger A., Bader U., et al. Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol. 2011; 52 (3): 244-6.

33. Leruez-Ville M., Magny J.-F., Couderc S., 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.

34. Shakhgil’dyan V.I., Shipulina O.Yu., Sil’ts V.V., et al. Diagnostics of cytomegalovirus infection in HIV-infected pregnant women and determination of risk factors for antenatal and perinatal infection of the fetus with cytomegalovirus. Akusherstvo i ginekologiya [Obstetrics and Gynecology]. 2005; (2): 24-9. (in Russian)

35. Rahav G., Gabbay R., Ornoy A., et al. Primary versus nonprimary cytomegalovirus infection during pregnancy, Israel. Emerg Infect Dis. 2007; 13 (11): 1791-3.

36. Mussi-Pinhata M.M., Yamamoto A.Y., Aragon D.C., et al. Seroconversion for cytomegalovirus infection during pregnancy and fetal infection in a highly seropositive population: «the BraCHS Study». J Infect Dis. 2018; 218 (8): 1200-4.

37. Shahar-Nissan K., Pardo J., Peled O., et al. Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy. In: ID Week. Washington, 2019.

38. Leruez-Ville M., et al. In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicenter, open-label, phase II study. Am J Obstet Gynecol. 2016; 215 (4): 462.e1-10.

39. NeoCyotect. Instructions for the use of a medicinal product for medical use [Electronic resource]. URL: URL: https://www.rlsnet.ru/tn_index_id_35536.htm (date of access July 02, 2020) (in Russian)

40. Nigro G., Adler S.P., La Torre R., Best A.M. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med. 2005; 353: 1350-62.

41. Visentin S., Manara R., Milanese L., Da Roit A. Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age. Clin Infect Dis. 2012; 55 (4): 497-503.

42. Revello M.G. A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med. 2014; 370 (14): 1316-26.

43. Hughes B.L. A randomized trial to prevent congenital CMV. In: ID Week. Washington, 2019.

44. Hamprecht K., Kagan K.-O., Goelz R. Hyperimmune globulin to prevent congenital CMV infection. N Engl J Med. 2014; 370 (26): 2543.

45. Rawlinson W.D., Boppana S.B., Fowler K.B., et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis. 2017; 17 (6): e177-88. DOI: http://doi.org/10.1016/S1473-3099(17)30143-3 [Electronic resource]

46. Nigro G., Capretti I., Manganello A.M., et al. Primary maternal cytomegalovirus infections during pregnancy: association of CMV hyperimmune globulin with gestational age at birth and birth weight. J Matern Fetal Neonatal Med. 2015; 28: 1-4.

47. Mace M., Sissoeff L., Rudent A., Grangeot-Keros L. A serological testing algorithm for the diagnosis of primary CMV infection in pregnant women. Prenat Diagn. 2004; 24 (11): 861-3.

48. Petrova G.V., Shakhgil’dyan V.I., Chistozvonova E.A. Experience of using the antiviral therapy of generalized congenital cytomegalovirus infection. Detskie infektsii [Children’s Infections]. 2016; 15 (2): 61-8. (in Russian)

49. Coll O., Benoist G., Ville Y., et al. Guidelines on CMV congenital infection. Recommendations and guidelines for perinatal practice. J Perinat Med. 2009; 37: 433-45.

50. Bonalumi S., Trapanese A., Santamaria A., et al. Cytomegalovirus infection in pregnancy: review of the literature. J Prenat Med. 2011; 5 (1): 1-8.

51. Cahill A.G., Odibo A.O., Stamilio D.M., Macones G.A. Screening and treating for primary cytomegalovirus infection in pregnancy: where do we stand? A decision-analytic and economic analysis. Am J Obstet Gynecol. 2009; 201 (5): 466.e1-7.

52. Shakhgil’dyanV.I.,Yadrikhinskaya M.S., Orlovskiy A. A., Shipulina O.Yu., Domonova E.A., Tishkevich O.A., et al. Concentration of CMV DNA in biological materials is the key to diagnosis of cytomegalovirus pneumonia in patients with HIV infection. Zhurnal infektologii [Journal of Infectology]. 2019; 11 (3 suppl 1): 109-17. (in Russian)

53. Degtyareva A.V., Zubkov V.V., Nepsha O.S., et al. Experience of using ganciclovir in the treatment of generalized forms of congenital cytomegalovirus infection. Akusherstvo i ginekologiya [Obstetrics and gynecology]. 2012; (5): 103-8. (in Russian)

54. Valganciclovir effective in infants with cytomegalovirus. In: ID Week. 2013. Abstr. LB-1. Present October 5, 2013. URL: www.antibiotic.ru/index.php-article=2367

55. Kimberlin D.W., Jester P.M., Sanchez P.J., et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015; 372: 933-43.

56. Baranov A.A. The state of health of children in the Russian Federation. Pediatriya [Pediatrics]. 2012; 91 (3): 9-14. (in Russian)

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)

CHIEF EDITOR
CHIEF EDITOR
Degtyarev Dmitriy Nikolaevich
Doctor of Medical Sciences, Professor, Deputy Director for Scientific Research of the V.I. Kulakov Obstetrics, Gynecology and Perinatology National Medical Research Center of Ministry of Healthсаre of the Russian Federation, Head of the Chair of Neonatology at the Clinical Institute of Children's Health named after N.F. Filatov, I.M. Sechenov First Moscow State Medical University, Chairman of the Ethics Committee of the Russian Society of Neonatologists, Moscow, Russian Federation

ORCID iD 0000-0001-8975-2425

Journals of «GEOTAR-Media»