Primary and acquired cytomegalovirus infection in newborns
AbstractThe newborn is one of the most vulnerable periods of life to cytomegalovirus infection (CMVI). The frequency of congenital CMVI varies from 0.5 to 6.1% and leads to a high level of disability in children. The outcomes of neonatal CMVI depend on the timeliness of diagnosis and the prescription of correct treatment for the disease.
The aim of the study was to analyze the frequency, clinical manifestations and treatment regimens of neonatal cytomegalovirus infection in a perinatal center.
Material and methods. On the basis of the Ekaterinburg Clinical Perinatal Center for the period 2021–2022 a retrospective clinical cohort study was conducted. According to the inclusion criteria, 48 children were selected for the study, including 18 children with congenital CMVI and 22 children with acquired CMVI infection. Primary medical documentation was analyzed: an individual developmental record of a newborn and a medical record of an inpatient. Extensive indicators were calculated.
Results and discussion. Among newborns with clinical manifestations of CMVI, in 33 (65%) cases, birth weight was less than 1500 g. The clinical form of CMVI was registered in 18 (37%) children, of which 6 newborns had early detection of CMV and 12 newborns had late detection. Treatment was with ganciclovir (14 to 21 days). Severe CMVI in 4 newborns, one of them had congenital CMVI (pneumonia), and 3 children had acquired CMVI (2 children with pneumonia and 1 child with sepsis). All children with severe disease, in combination with ganciclovir, received therapy with human immunoglobulin anticytomegalovirus for intravenous administration (NeoCytotect).
Conclusion. For early diagnosis of CMVI in newborns, it is necessary to test children with clinical symptoms, as well as children with a birth weight of up to 1500 g. Testing of mother’s breast milk for the presence of CMV should be considered. It has been confirmed that the clinical picture of CMVI can manifest itself in severe forms of pneumonia and sepsis, and the data obtained indicate the need to expand the indications for prescribing human anticytomegalovirus immunoglobulin in the complex therapy of CMVI.
Keywords:newborn; cytomegalovirus infection; polymerase chain reaction; ganciclovir;
human immunoglobulin anticytomegalovirus
Funding. The study had no sponsor support.
Conflict of interest. Shestak E.V. gave lectures with the support of the Medipal company, which distributes the drug NeoCytotect; Starkov V.Yu. declared no conflict of interest.
Contribution. The concept and design of the study – Shestak E.V., Starkov V.Yu., collection and processing of materials – Starkov V.Yu.; writing the text – Shestak E.V.; editing – Shestak E.V.
For citation: Shestak E.V., Starkov V.Yu. Primary and acquired cytomegalovirus infection in newborns. Infektsionnye bolezni: novosti, mneniya, obuchenie [Infectious Diseases: News, Opinions, Training]. 2024; 13 (1): 35–41. DOI: https://doi.org/10.33029/2305-3496-2024-13-1-35-41 (in Russian)
References
1. Harrison G.J. Cytomegalovirus. In: J.D. Cherry, G.J. Harrison, S.L. Kaplan, W. Steinbach, P. Hotez et al. (eds). Feigin and Cherry’s Textbook of Pediatric Infectious Diseases. 8th ed. Elsevier, Saunders, 2019: 1429.
2. Cannon M.J. Congenital cytomegalovirus (CMV) epidemiology and awareness. J Clin Virol. 2009; 46 (suppl 4): S6–10. DOI: https://doi.org/10.1016/j.jcv.2009.09.002
3. Lanzieri T.M., Dollard S.C., Bialek S.R., Grosse S.D. Systematic review of the birth prevalence of congenital cytomegalovirus infection in developing countries. Int J Infect Dis. 2014; 22: 44–8. DOI: https://doi.org/10.1016/j.ijid.2013.12.010
4. Kenneson A., Cannon M.J. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007; 17 (4): 253–76. DOI: https://doi.org/10.1002/rmv.535
5. Puhakka L., Lappalainen M., Lönnqvist T., et al. The burden of congenital cytomegalovirus infection: a prospective cohort study of 20 000 infants in Finland. J Pediatric Infect Dis Soc. 2019; 8 (3): 205–12. DOI: https://doi.org/10.1093/jpids/piy027
6. Goderis J., De Leenheer E., Smets K., Van Hoecke H., et al. Hearing loss and congenital CMV infection: a systematic review. Pediatrics. 2014; 134 (5): 972–82. DOI: https://doi.org/10.1542/peds.2014-1173
7. Picone O., Vauloup-Fellous C., Cordier A.G., et al. A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome. Prenat Diagn. 2013; 33 (8): 751–8. DOI: https://doi.org/10.1002/pd.4118
8. Mehler K., Oberthuer A., Lang-Roth R., Kribs A. High rate of symptomatic cytomegalovirus infection in extremely low gestational age preterm infants of 22–24 weeks’ gestation after transmission via breast milk. Neonatology. 2014; 105 (1): 27–32. DOI: https://doi.org/10.1159/000355306
9. Josephson C.D., Caliendo A.M., Easley K.A., et al. Blood transfusion and breast milk transmission of cytomegalovirus in very low-birth-weight infants: a prospective cohort study. JAMA Pediatr. 2014; 168 (11): 1054–62. DOI: https://doi.org/10.1001/jamapediatrics.2014.1360
10. Dreher A.M., Arora N., Fowler K.B., et al. Spectrum of disease and outcome in children with symptomatic congenital cytomegalovirus infection. J Pediatr. 2014; 164 (4): 855–9. DOI: https://doi.org/10.1016/j.jpeds.2013.12.007
11. Kylat R.I., Kelly E.N., Ford-Jones E.L. Clinical findings and adverse outcome in neonates with symptomatic congenital cytomegalovirus (SCCMV) infection. Eur J Pediatr. 2006; 165 (11): 773–8. DOI: https://doi.org/10.1007/s00431-006-0172-6
12. Maschmann J., Hamprecht K., Dietz K., Jahn G., Speer C.P. Cytomegalovirus infection of extremely low-birth weight infants via breast milk. Clin Infect Dis. 2001; 33 (12): 1998–2003. DOI: https://doi.org/10.1086/324345
13. Rivera L.B., Boppana S.B., Fowler K.B., Britt W.J., et al. Predictors of hearing loss in children with symptomatic congenital cytomegalovirus infection. Pediatrics. 2002; 110 (4): 762–7. DOI: https://doi.org/10.1542/peds.110.4.762
14. Boppana S.B., Pass R.F., Britt W.J., Stagno S., Alford C.A. Symptomatic congenital cytomegalovirus infection: neonatal morbidity and mortality. Pediatr Infect Dis J. 1992; 11 (2): 93–9. DOI: https://doi.org/10.1097/00006454-199202000-00007
15. Gunkel J., Wolfs T.F., de Vries L.S., Nijman J. Predictors of severity for postnatal cytomegalovirus infection in preterm infants and implications for treatment. Expert Rev Anti Infect Ther. 2014; 12 (11): 1345–55. DOI: https://doi.org/10.1586/14787210.2014.966080
16. Clinical recommendations «Normal pregnancy» (approved by the Ministry of Health of Russia) [Electronic resource]. Moscow, 2020. URL: https://cr.minzdrav.gov.ru/recomend/288_1 (date of access September 24, 2023). (in Russian)
17. Turner K.M., Lee H.C., Boppana S.B., Carlo W.A., Randolph D.A. Incidence and impact of CMV infection in very low birth weight infants. Pediatrics. 2014; 133 (3): e609–15. DOI: https://doi.org/10.1542/peds.2013-2217
18. Boppana S.B., Ross S.A., Fowler K.B. Congenital cytomegalovirus infection: clinical outcome. Clin Infect Dis. 2013; 57 (suppl 4): S178–81. DOI: https://doi.org/10.1093/cid/cit629
19. Alarcon A., Martinez-Biarge M., Cabañas F., Hernanz A., et al. Clinical, biochemical, and neuroimaging findings predict long-term neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection. J Pediatr. 2013; 163 (3): 828–34.e1. DOI: https://doi.org/10.1016/j.jpeds.2013.03.014
20. Clinical recommendations «Congenital cytomegalovirus infection» (approved by the Ministry of Health of Russia) [Electronic resource]. Moscow, 2023. URL: https://cr.minzdrav.gov.ru/schema/260_2 (date of access September 24, 2023). (in Russian)
21. American Academy of Pediatrics. Cytomegalovirus infection. In: D.W. Kimberlin, E.D. Barnett, R. Lynfield, M.H. Sawyer (eds). Red Book: 2021–2024 Report of the Committee on Infectious Diseases. 32nd ed. Itasca, IL: American Academy of Pediatrics, 2021: 294.
22. Luck S.E., Wieringa J.W., Blázquez-Gamero D., et al. Congenital cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management. Pediatr Infect Dis J. 2017; 36 (12): 1205–13. DOI: https://doi.org/10.1097/INF.0000000000001763
23. Kimberlin D.W., Lin C.Y., Sánchez P.J., et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr. 2003; 143 (1): 16–25. DOI: https://doi.org/10.1016/s0022-3476(03)00192-6
24. Kimberlin D.W., Jester P.M., Sánchez P.J., et al. Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med. 2015; 372 (10): 933–43. DOI: https://doi.org/10.1056/NEJMoa1404599
25. Royackers L., Rector E., Verhaert N., Desloovere C. Long-term audiological follow-up of children with congenital cytomegalovirus. B-ENT. 2013; suppl 21: 57–64.
26. Michaels M.G., Greenberg D.P., Sabo D.L., Wald E.R. Treatment of children with congenital cytomegalovirus infection with ganciclovir. Pediatr Infect Dis J. 2003; 22 (6): 504–9. DOI: https://doi.org/10.1097/01.inf.0000069767.43169.2d
27. Leung J., Grosse S.D., Yockey B., Lanzieri T.M. Ganciclovir and valganciclovir use among infants with congenital cytomegalovirus: data from a multicenter electronic health record dataset in the United States. J Pediatric Infect Dis Soc. 2022; 11 (8): 379–82. DOI: https://doi.org/10.1093/jpids/piac034
28. Gwee A., Curtis N., Connell T.G., Garland S., Daley A.J. Ganciclovir for the treatment of congenital cytomegalovirus: what are the side effects? Pediatr Infect Dis J. 2014; 33 (1): 115. DOI: https://doi.org/10.1097/INF.0000000000000032
29. Wang Y., Smith K.P. Safety of alternative antiviral agents for neonatal herpes simplex virus encephalitis and disseminated infection. J Pediatr Pharmacol Ther. 2014; 19 (2): 72–82. DOI: https://doi.org/10.5863/1551-6776-19.2.72
30. Weng Y.H., Chu S.M., Lien R.I., Chou Y.H., Lin T.Y. Clinical experience with ganciclovir and anti-cytomegalovirus immunoglobulin treatment for a severe case of congenital cytomegalovirus infection. Chang Gung Med J. 2003; 26 (2): 128–32.
31. Aslam M., Anderson J.L., Guglietti D., Cardwell D. CMV-induced neonatal thrombocytopenia: a case report and review of the literature. Am J Perinatol. 2007; 24 (7): 429–34. DOI: https://doi.org/10.1055/s-2007-984409
32. Belyaeva I.А., Bombardirova E.P., Potekhina T.V., Gurskaya A.S. Cytomegalovirus infection in infants: course variants, modern approaches to therapy (clinical cases). Pediatricheskaya farmakologiya [Pediatric Pharmacology]. 2018; 15 (2): 168–74. DOI: https://doi.org/10.15690/pf.v15i2.1873 (in Russian)
33. Vaynshteyn N.P., Britanishskaya E.A., Krivova N.A., Mitina Yu.Yu., Matveeva T.V. Clinical case of a congenital cytomegalovirus infection at preterm infant. Neonatologiya: novosti, mneniya, obuchenie [Neonatology: News, Opinions, Training]. 2017; (2): 99–106. DOI: https://doi.org/10.24411/2308-2402-2017-00033 (in Russian)
34. Rogozina N.V., Vasil’ev V.V., Grineva A.A., Mikhaylov A.V., et al. Ante- and postnatal diagnostics and complex treatment of congenital cytomegalovirus infection. Rossiyskiy vestnik perinatologii i pediatrii [Russian Bulletin of Perinatology and Pediatrics]. 2019; 64 (6): 89–93. DOI: https://doi.org/10.21508/1027-4065-2019-64-6-89-93 (in Russian)
35. Jin H.D., Demmler-Harrison G.J., Coats D.K., et al. Long-term visual and ocular sequelae in patients with congenital cytomegalovirus infection. Pediatr Infect Dis J. 2017; 36 (9): 877–82. DOI: https://doi.org/10.1097/INF.0000000000001599
36. Goelz R., Meisner C., Bevot A., Hamprecht K., et al. Long-term cognitive and neurological outcome of preterm infants with postnatally acquired CMV infection through breast milk. Arch Dis Child Fetal Neonatal Ed. 2013; 98 (5): F430–3. DOI: https://doi.org/10.1136/archdischild-2012-303384
37. Gunkel J., de Vries L.S., Jongmans M., et al. Outcome of preterm infants with postnatal cytomegalovirus infection. Pediatrics. 2018; 141 (2): e20170635. DOI: https://doi.org/10.1542/peds.2017-0635
38. Bevot A., Hamprecht K., Krägeloh-Mann I., Brosch S., et al. Long-term outcome in preterm children with human cytomegalovirus infection transmitted via breast milk. Acta Paediatr. 2012; 101 (4): e167–72. DOI: https://doi.org/10.1111/j.16512227.2011.02538.x