Congenital and postnatal cytomegalovirus infections

Česká verzia

Authors: D. Smíšková ¹; P. Hubáček ²
Authors place of work: Klinika infekčních nemocí, 2. LF UK a FN Bulovka, Praha ¹; Ústav lékařské mikrobiologie, 2. LF UK a FN Motol, Praha ²
Published in the journal: Čes-slov Neonat 2022; 28 (2): 112-116.
Category: Reviews

Summary

Congenital cytomegalovirus infection is the most common congenital infection worldwide (0.2−6 % of live births, 0.2−0.6 % in countries with a higher economic standard). It is the most common cause of non-genetic sensorineural hearing loss and has a significant role in neurological developmental disorders. The risks of transmission to the fetus are fundamentally different for primary infection (30−35 %) and for reactivation or reinfection (1.1−1.7 %). About 90 % of newborns are asymptomatic at the time of birth, but 10−15 % develop hearing impairment or neurodevelopmental disorder in the first years of life.

Prenatal clinical manifestations include intrauterine growth retardation, ventriculomegaly, microcephaly or intracranial calcification, whereas low birth weight, microcephaly, hypotonia, petechial exanthema, blueberry muffins, hepatosplenomegaly, thrombocytopenia, neutropenia, hepatopathy, hyperbilirubinemia, hearing impairment or chorioretinitis are seen postnatally.

The diagnosis should be established as soon as possible, the recommended screening test is the examination of saliva or urine (PCR), followed by quantitative viremia and viruria.

The treatment is started in the first 4 weeks of life in newborns with a gestational age of over 32 weeks with CNS involvement and/ or severe involvement of other organs (liver, bone marrow, lungs, eye). The basic virostatic agent is intravenous ganciclovir or oral valganciclovir. The duration of treatment is 6 months, in indicated cases up to 1 year.

The follow-up of children with congenital CMV infection should last until at least 4 years of age, regular evaluation of hearing, neurodevelopmental outcome and vision are necessary.

Keywords:

cytomegalovirus – sensorineural hearing loss – congenital infection – postnatal infection – ganciclovir – valganciclovir

Zdroje

1. Chiopris G, Veronese P, Cusenza F, et al. Congenital cytomegalovirus infection: update on diagnosis and treatment. Microorganisms 2020; 8(10).

2. Leruez-Ville M, Magny JF, Couderc S, et al. Risk factors for congenital cytomegalovirus infection following primary and non-primary maternal infection: a prospective neonatal screening study using polymerase chain reaction in saliva. Clin Infect Dis 2017; 65(3): 398−404.

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

4. Maidji E, Genbacev O, Chang HT, Pereira L. Developmental regulation of human cytomegalovirus receptors in cytotrophoblasts correlates with distinct replication sites in the placenta. J Virol 2007; 81(9): 4701−4712.

5. Longo S, Borghesi A, Tzialla C, et al. IUGR and infections. Early Hum Dev 2014; 90 Suppl 1: S42−44.

6. Barton M, Forrester AM, McDonald J. Update on congenital cytomegalovirus infection: prenatal prevention, newborn diagnosis and management. Paediatr Child Health 2020; 25(6): 395−396.

7. Chatzakis C, Ville Y, Makrydimas G, et al. Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences. American Journal of Obstetrics and Gynecology 2020; 223(6): 870−883.e11.

8. Goderis J, De Leenheer E, Smets K, et al. Hearing loss and congenital CMV infection: a systematic review. Pediatrics 2014; 134(5): 972−982.

9. Britt WJ. Maternal immunity and the natural history of congenital human cytomegalovirus infection. Viruses 2018; 10(8).

10. Cannon MJ, Griffiths PD, Aston V, et al. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit? Rev Med Virol 2014; 24(5): 291−307.

11. Sampath V, Narendran V, Donovan EF, et al. Nonimmune hydrops fetalis and fulminant fatal disease due to congenital cytomegalovirus infection in a premature infant. J Perinatol 2005; 25(9): 608−611.

12. Lanzieri TM, Chung W, Flores M, et al. Hearing loss in children with asymptomatic congenital cytomegalovirus infection. Pediatrics 2017; 139(3).

13. Kadambari S, Whittaker E, Lyall H. Postnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage? Arch Dis Child Fetal Neonatal 2020; 105(3): 334−339.

14. Rawlinson WD, Boppana SB, Fowler KB, et al. Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis and therapy. The Lancet Infectious diseases 2017; 17(6): e177−e188.

15. Boppana SB, Ross SA, Novak Z, et al. Dried blood spot real- time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA 2010; 303(14): 1375−1382.

16. Ross SA, Ahmed A, Palmer AL, et al. Newborn dried blood spot polymerase chain reaction to identify infants with congenital cytomegalovirus- associated sensorineural hearing loss. The Journal of pediatrics 2017; 184: 57−61.e1.

17. Smiljkovic M, Le Meur JB, Malette B, et al. Blood viral load in the diagnostic workup of congenital cytomegalovirus infection. Journal of clinical virology (the official publication of the Pan American Society for Clinical Virology) 2020; 122: 104231.

18. Kimberlin DW, Jester PM, Sanchez PJ, et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 2015; 372(10): 933−943.

19. Bilavsky E, Shahar-Nissan K, Pardo J, et al. Hearing outcome of infants with congenital cytomegalovirus and hearing impairment. Archives of disease in childhood 2016; 101(5): 433−438.

20. Gwee A, Curtis N, Connell TG, et al. Ganciclovir for the treatment of congenital cytomegalovirus: what are the side effects? Pediatr Infect Dis J 2014; 33(1): 115.

21. Revello MG, Tibaldi C, Masuelli G, et al. Prevention of primary cytomegalovirus infection in pregnancy. EBioMedicine 2015; 2(9): 1205−1210.

22. Khalil A, Jones C, Ville Y. Congenital cytomegalovirus infection: management update. Curr Opin Infect Dis 2017; 30(3): 274−280.

23. Zammarchi L, Lazzarotto T, Andreoni M, et al. Management of cytomegalovirus infection in pregnancy: is it time for valacyclovir? Clin Microbiol Infect 2020; 26(9): 1151−1154.

24. Bardanzellu F, Fanos V, Reali A. Human breast milk-acquired cytomegalovirus infection: certainties, doubts and perspectives. Curr Pediatr Rev 2019; 15(1): 30−41.

25. Garofoli F, Civardi E, Zanette S, et al. Literature review and an italian hospital experience about post-natal CMV infection acquired by breast-feeding in very low and/or extremely low birth weight infants. Nutrients 2021; 13(2).

26. Schleiss MR, Bierle CJ, Swanson EC, et al. Vaccination with a live attenuated cytomegalovirus devoid of a protein kinase r inhibitory gene results in reduced maternal viremia and improved pregnancy outcome in a guinea pig congenital infection model. J Virol 2015; 89(19): 9727−9738.