Congenital cytomegalovirus infection cases and follow-up findings in Antalya, Turkey

Abstract

Objective: To investigate the presence of cCMV infection and the CMV-DNA virus in the newborns who applied for newborn hearing screening test (NHST) and CMV-DNA viruria with physical, mental-motor development and hearing status of cCMV cases in the second year of age. Patients and Methods: CMV-DNA was investigated in 1150 newborns’ oral swabs (0-21 days) by polymerase chain reaction kit and urine of patients with positive CMV-DNA in saliva. Transient Evoked Otoacoustic Emission test was performed for NHST. Results: CMV-DNA was posititve in saliva of 38 (3.3%) newborns and urine of 10 out of 37 newborns. The prevalence of cCMV was 0.87% (95% CI=0.697-1.042). All newborns passed the NHST. In newborns with cCMV:jaundice in 60% (6/10), low birthweight in 40% (4/10), small for gestational age in 50% (5/10) of them. Jaundice was the most significant variable (P<0.001, OR:23.411, 95% CI=5.772-94.960) and bilirubin levels were slightly elevated. In the second year of 8 cases, CMV-DNA viruria was detected in all of them and sensorineural hearing loss was detected in one infant. Conclusion: The cCMV infection rate is 0.87% in a population with high maternal seropositivity.When diagnosing cCMV, saliva may give false-positive results and urine should be tested. Bilirubin levels may not be as high as expected in cCMV cases in highly seroimmune populations and sequelaes may occur in the following years.

Keywords

• Congenital CMV infection
• High seroprevalence population
• Urine
• Saliva
• CMV-DNA PCR

References

1. Manicklal S, Emery VC, Lazzarotto T, et al. The “silent” global burden of congenital Cytomegalovirus. Clin Microbiol Rev 2013;26:86-102. doi: 10.1128/CMR.00062-12
2. Grosse S, Ross DS, Dollard SC. Congenital Cytomegalovirus infection as a cause of permanent bilateral hearing loss: a quantitative assessment. J Clin Virol 2018;41:57-62. doi: 10.1016/j.jcv.2007.09.004
3. Mussi-Pinhata MM, Yamamoto AY, Moura Brito RM, et al. Birth prevalence and natural history of congenital Cytomegalovirus infection in a highly seroimmune population. Clin Infect Dis 2009;49:522-8. doi: 10.1086/600882.
4. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital Cytomegalovirus (CMV) infection. Rev Med Virol 2007;17:253-76. doi: 10.1002/ rmv.535
5. Ataman S, Colak D, Günseren F, et al. Investigation of Cytomegalovirus seroepidemiology in Antalya with a population-based cross-sectional study and review of related data in Turkey. Mikrobiyol Bul 2007;41:545-55.
6. Satilmiş A, Güra A, Ongun H, et al. CMV seroconversion in pregnants and the incidence of congenital CMV infection. Turk J Pediatr 2007;49:30-6.
7. Uysal A, Taner CE, Cüce M, et al. Cytomegalovirus and rubella seroprevalence in pregnant women in Izmir/Turkey: follow-up and results of pregnancy outcome. Arch Gynecol Obstet 2012;286:605-8. doi: 10.1007/s00404.012.2353-z
8. Parlak M, Çim N, Nalça Erdin B, et al. Seroprevalence of Toxoplasma, Rubella, and Cytomegalovirus among pregnant women in Van. Turk J Obstet Gynecol 2015;12:79-82. doi: 10.4274/tjod.35902

9. Sahiner F, Cekmez, Cetinkaya FM, et al. Congenital Cytomegalovirus infections and glycoprotein B genotypes in live-born infants: a prevalence study in Turkey. Infect Dis (Lond) 2015;47:465-71. doi: 10.3109/23744.235.2015.1018316
10. Zeytinoğlu A, Terek D, Arslan A, et al. Investigation of congenital CMV infection with the presence of CMV DNA in saliva samples of new born babies. Mikrobiyol Bul 2019;53:53- 60. doi: 10.5578/mb.67724
11. Chiopris G, Veronese P, Cusenza F, et al. Congenital Cytomegalovirus Infection: Update on Diagnosis and Treatment. Microorganisms 2020;8:1-17. doi: 10.3390/ microorganisms8101516
12. Royackers L, Rector E, Verhaert N, et al. Long-term audiological follow-up of children with congenital cytomegalovirus. B-ENT 2013;Suppl 21:57-64.
13. Joint Committee on Infant Hearing of the American Academy of Pediatrics et al. Supplement to the JCIH 2007 position statement: principles and guidelines for early intervention after confirmation that a child is deaf or hard of hearing. Pediatrics 2013;131: e1324-49. doi:10.1542/ peds.2013-0008
14. Luck SE, Wieringa JW, Blázquez-Gamero D, et al. Congenital Cytomegalovirus: A European Expert Consensus Statement on Diagnosis and Management. Pediatr Infect Dis J 2017;36:1205- 13. doi: 10.1097/INF.000.000.0000001763
15. Fowler KB, Ross SA, Shimamura M, et al. Racial and Ethnic Differences in the Prevalence of Congenital Cytomegalovirus Infection. J Pediatr 2018;200:196-201.e1. doi: 10.1016/j. jpeds.2018.04.043
16. Noyola DE, Mejía-Elizondo AR, Canseco-Lima JM, et al. Congenital Cytomegalovirus infection in San Luis Potosi, Mexico. Pediatr Infect Dis J 2003;22:89-90. doi: 10.1097/00006.454.200301000-00022
17. Marin LJ, Santos de Carvalho Cardoso E, Bispo Sousa SM, et al. Prevalence and clinical aspects of CMV congenital Infection in a low-income population. Virol J 2016;13:148. doi: 10.1186/s12985.016.0604-5
18. Schlesinger Y, Reich D, Eidelman AI, et al. Congenital Cytomegalovirus infection in Israel: screening in different subpopulations. Isr Med Assoc J 2005;7:237-40.
19. Wang S, Wang T, Zhang W, et al. Cohort study on maternal Cytomegalovirus seroprevalence and prevalence and clinical manifestations of congenital infection in China. Medicine (Baltimore) 2017;96:e6007. doi: 10.1097/ MD.000.000.0000006007
20. Van der Sande MA, Kaye S, Miles DJ, et al. Risk factors for and clinical outcome of congenital Cytomegalovirus infection in a peri-urban West-African birth cohort. PLoS One 2007;2:e492. doi: 10.1371/journal.pone.0000492
21. Dar L, Pati SK, Patro AR, et al. Congenital Cytomegalovirus infection in a highly seropositive semi-urban population in India. Pediatr Infect Dis J 2008;27:841-843. doi: 10.1097/ INF.0b013e3181723d55
22. Javid N, Cheraghali F, Moradi A, et al. Newborn Screening for Congenital Cytomegalovirus Infection in Iran. Pediatr Infect Dis J 2016;35:1052. doi: 10.1097/INF.000.000.0000001257
23. Boppana SB, Ross SA, Shimamura M, et al. Saliva Polymerase- Chain-Reaction Assay for Cytomegalovirus Screening in Newborns. N Engl J Med 2011;364:2111-8. doi: 10.1056/ NEJMoa1006561
24. Gunkel J, Wolfs TF, de Vries LS, et al. Predictors of severity for postnatal Cytomegalovirus infection in preterm infants and implications for treatment. Expert Rev Anti Infect Ther 2014;12:1345-55. doi: 10.1586/14787.210.2014.966080
25. Yılmaz E, Öcal FD, Yılmaz ZV, et al. Early initiation and exclusive breastfeeding: Factors influencing the attitudes of mothers who gave birth in an baby friendly hospital. Turk J Obtet Gynecol 2017;14:1-9. doi: 10.4274/tjod.90018
26. Hacettepe University Institute of Population Studies 2013 Turkey Demographic and Health Survey, T.R. Ministry of Development and TÜBİTAK, Ankara. https://dhsprogram. com/pubs/pdf/FR352/FR352.pdf. (Accessed on August 16, 2022)
27. Koyano S, Inoue N, Nagamori T. Newborn screening of congenital Cytomegalovirus infection using saliva can be influenced by breast feding. Arch Dis Child Fetal Neonatal Ed 2013;98:F182. doi: 10.1136/archdischild-2012-302230
28. Fujii T, Oka A, Morioka I, et al. Japanese Congenital Cytomegalovirus Study Group. Newborn Congenital Cytomegalovirus Screening Based on Clinical Manifestations and Evaluation of DNA-based Assays for In Vitro Diagnostics. Pediatr Infect Dis J 2017;3:942-6. doi: 10.1097/ INF.000.000.0000001630
29. Ornoy A, av-Citrin O. Fetal effects of primary and secondary Cytomegalovirus infection in pregnancy. Reprod Toxicol 2006;21:399-409. doi: 10.1016/j.reprotox.2005.02.002
30. Fowler KB, Stagno S, Pass RF, et al. The outcome of congenital Cytomegalovirus infection in relation to maternal antibody status. N Engl J 1992;326:663-7. doi: 10.1056/ NEJM199.203.053261003
31. Lilleri D, Kabanova A, Revello MG, et al. Fetal human Cytomegalovirus transmission correlates with delayed maternal antibodies to gH/gL/pUL128-130-131 complex during primary infection. PLoS One 2013;8:e59863. doi: 10.1371/journal.pone.0059863
32. Fornara C, Cassaniti I, Zavattoni M, et al. Human Cytomegalovirus-specific memory CD4+ T-cell response and its correlation with virüs transmission to the fetus in pregnant women with primary infection. Clin Infect Dis 2017;65:1659- 65. doi: 10.1093/cid/cix622
33. Çelikel E, Tezer H, Kanik-Yüksek S, et al. Evaluation of immunocompetent children with cytomegalovirus infection: importance of neurodevelopmental follow-up. Eur J Pediatr 2015;174:1101-7. doi: 10.1007/s00431.015.2513-9
34. Fowler KB, McCollister FP, Sabo DL, et al. A Targeted Approach for Congenital Cytomegalovirus Screening Within Newborn Hearing Screening. Pediatrics 2017;139:e20162128. doi: 10.1542/peds.2016-2128
35. Fletcher KT, Horrell EMW, Ayugi J, et al. The Natural History and Rehabilitative Outcomes of Hearing Loss in Congenital Cytomegalovirus: A Systematic Review. Otol Neurotol 2018;39:854-64. doi: 10.1097/MAO.000.000.0000001861