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Diagnostic Clues for Congenital Cytomegalovirus Infection: Association with Newborn Hearing Screening Tests

  • Kim, Jiyeon (Department of Pediatrics, Cheil General Hospital & Women's Healthcare Center) ;
  • Lee, Yeon Kyung (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Ko, Sun Young (Department of Pediatrics, College of Medicine, The Catholic University of Korea) ;
  • Shin, Son Moon (Department of Pediatrics, Cheil General Hospital & Women's Healthcare Center)
  • Received : 2018.11.16
  • Accepted : 2019.03.20
  • Published : 2019.05.28

Abstract

Purpose: To investigate clinical markers for the diagnosis of congenital cytomegalovirus (CMV) infection and determine the correlation between abnormal newborn hearing screening results and asymptomatic congenital CMV infection. Methods: Medical records of newborns with congenital CMV infection, born at Cheil General Hospital & Women's Healthcare Center from July 2008 to June 2018, were retrospectively reviewed. Infants with congenital CMV infection were classified into "symptomatic," "asymptomatic," and "asymptomatic with isolated abnormal automated auditory brainstem response (AABR)" groups. Clinical data were analyzed based on this classification. Results: Among the 59,424 live births, congenital CMV infection was found in 25 neonates, including 19 symptomatic (0.03%) infants, two asymptomatic, and four asymptomatic with isolated abnormal AABR. Diagnostic clues for the identification of congenital CMV infection were intrauterine growth restriction (IUGR), including microcephaly in 10 infants (40.0%), abnormal AABR in four (16.0%), initial complicated signs in four (16.0%), and abnormal findings on brain ultrasonography in three (12.0%). Other less common markers included petechiae, abnormal findings on antenatal ultrasonography, and co-twin with CMV infection. During the recent 10 years, 53,094 of 59,424 newborns (89.3%) had AABR for hearing screening and 493 (0.9%) did not pass. Among them, 477 (96.8%) were screened for CMV, and results were positive for seven (1.5%). Among the seven infants, four had asymptomatic congenital CMV infection. Overall, 0.8% of the newborns with abnormal AABR (four of 477 infants) were diagnosed as having asymptomatic congenital CMV infection. Conclusion: The incidence of symptomatic congenital CMV infection was 0.03%, and 0.8% of infants who failed in the newborn hearing screening tests had asymptomatic congenital CMV infection. The most common clinical marker to diagnose congenital CMV infection was IUGR, including microcephaly, and the second isolated marker was abnormal AABR.

Keywords

References

  1. van Zuylen WJ, Hamilton ST, Naing Z, Hall B, Shand A, Rawlinson WD. Congenital cytomegalovirus infection: clinical presentation, epidemiology, diagnosis and prevention. Obstet Med 2014;7:140-6. https://doi.org/10.1177/1753495x14552719
  2. Kim CS. Congenital and perinatal cytomegalovirus infection. Korean J Pediatr 2010;53:14-20. https://doi.org/10.3345/kjp.2010.53.1.14
  3. Britt WJ. Cytomegalovirus. In: Kliegman RM, Stanton BF, Geme III JW, Schor NF, Behrman RE, editors. Nelson textbook of pediatrics. 20th ed. Philadelphia: Elsevier Saunders, 2015:1590-4.
  4. Fowler KB, Boppana SB. Congenital cytomegalovirus infection. Semin Perinatol 2018;42:149-54. https://doi.org/10.1053/j.semperi.2018.02.002
  5. Lim Y, Lyall H. Congenital cytomegalovirus: who, when, whatwith and why to treat? J Infect 2017;74 Suppl 1:S89-94. https://doi.org/10.1016/S0163-4453(17)30197-4
  6. Manicklal S, Emery VC, Lazzarotto T, Boppana SB, Gupta RK. The "silent" global burden of congenital cytomegalovirus. Clin Microbiol Rev 2013;26:86-102. https://doi.org/10.1128/CMR.00062-12
  7. Goderis J, De Leenheer E, Smets K, Van Hoecke H, Keymeulen A, Dhooge I. Hearing loss and congenital CMV infection: a systematic review. Pediatrics 2014;134:972-82. https://doi.org/10.1542/peds.2014-1173
  8. Stehel EK, Shoup AG, Owen KE, Jackson GL, Sendelbach DM, Boney LF, et al. Newborn hearing screening and detection of congenital cytomegalovirus infection. Pediatrics 2008;121:970-5. https://doi.org/10.1542/peds.2006-3441
  9. Sohn YM, Park KI, Lee C, Han DK, Lee WY. Congenital cytomegalovirus infection: incidence and clinical outcome. J Korean Pediatr Soc 1991;34:1365-72.
  10. Lee YA, Lee K, Jo IS, Chung WG. Diagnosis of cytomegalovirus infection in neonatal and infantile periods using polymerase chain reaction. J Korean Pediatr Soc 1996;39:1271-9.
  11. Paik SH, Lee YK, Ko SY, Kim KA, Kim MJ, Han BH, et al. Clinical features of congenital cytomegalovirus infection in neonates. Korean J Perinatol 2002;13:413-9.
  12. Kim DW, Kwack H, Jung SH, Kang IS, Lee HJ, Choi JH, et al. Cytomegalovirus infection in children: the significance of CMV specific IgM antibody test and virus isolation in the urine. J Korean Pediatr Soc 1992;35:890-901.
  13. Kim JH, Seo EA, Lim JH, Park SH, Lee WB, Lee KS, et al. Congenital asymptomatic cytomegalovirus infection: a comparison of specific IgM antibody test and pp65 antigenemia assay. J Korean Pediatr Soc 1998;41:163-9.
  14. Park K, Kim H, Ko SY, Shin SM, Lee YK, Han BH. Clinical significance of neonatal lenticulostriate vasculopathy: association with congenital cytomegalovirus infection. Neonatal Med 2017;24:171-7. https://doi.org/10.5385/nm.2017.24.4.171
  15. Kim JH, Chung SH, Choi YS, Lee BS, Kim KS, Kim EA. Clinical features and neurodevelopmental outcomes of infants with congenital cytomegalovirus infection: single NICU experience. Neonatal Med 2013;20:214-20. https://doi.org/10.5385/nm.2013.20.2.214
  16. Cannon MJ, Schmid DS, Hyde TB. Review of cytomegalovirus seroprevalence and demographic characteristics associated with infection. Rev Med Virol 2010;20:202-13. https://doi.org/10.1002/rmv.655
  17. Seo S, Cho Y, Park J. Serologic screening of pregnant Korean women for primary human cytomegalovirus infection using IgG avidity test. Korean J Lab Med 2009;29:557-62.
  18. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 2007;17:253-76. https://doi.org/10.1002/rmv.535
  19. Luck SE, Wieringa JW, Blazquez-Gamero D, Henneke P, Schuster K, Butler K, et al. Congenital cytomegalovirus: a European expert consensus statement on diagnosis and management. Pediatr Infect Dis J 2017;36:1205-13. https://doi.org/10.1097/INF.0000000000001763
  20. Diener ML, Zick CD, McVicar SB, Boettger J, Park AH. Outcomes from a hearing-targeted cytomegalovirus screening program. Pediatrics 2017;139.
  21. Rawlinson WD, Palasanthiran P, Hall B, Al Yazidi L, Cannon MJ, Cottier C, et al. Neonates with congenital cytomegalovirus and hearing loss identified via the universal newborn hearing screening program. J Clin Virol 2018;102:110-5. https://doi.org/10.1016/j.jcv.2018.03.006
  22. Ronchi A, Shimamura M, Malhotra PS, Sanchez PJ. Encouraging postnatal cytomegalovirus (CMV) screening: the time is NOW for universal screening! Expert Rev Anti Infect Ther 2017;15:417-9. https://doi.org/10.1080/14787210.2017.1303377
  23. Cannon MJ, Griffiths PD, Aston V, Rawlinson WD. Universal newborn screening for congenital CMV infection: what is the evidence of potential benefit? Rev Med Virol 2014;24:291-307. https://doi.org/10.1002/rmv.1790
  24. Gantt S, Dionne F, Kozak FK, Goshen O, Goldfarb DM, Park AH, et al. Cost-effectiveness of universal and targeted newborn screening for congenital cytomegalovirus infection. JAMA Pediatr 2016;170:1173-80. https://doi.org/10.1001/jamapediatrics.2016.2016
  25. Grosse SD, Dollard SC, Kimberlin DW. Screening for congenital cytomegalovirus after newborn hearing screening: what comes next? Pediatrics 2017;139:e20163837. https://doi.org/10.1542/peds.2016-3837
  26. Medoro A, Malhotra P, Shimamura M, Hounam G, Findlen U, Wozniak P, et el. "Targeted" screening for cytomegalovirus (CMV)-related hearing loss: it's time for universal CMV screening in the NICU! Open Forum Infect Dis 2017;4(Suppl 1):S691.
  27. Boppana SB, Ross SA, Novak Z, Shimamura M, Tolan RW Jr, Palmer AL, et al. Dried blood spot real-time polymerase chain reaction assays to screen newborns for congenital cytomegalovirus infection. JAMA 2010;303:1375-82. https://doi.org/10.1001/jama.2010.423
  28. Boppana SB, Ross SA, Shimamura M, Palmer AL, Ahmed A, Michaels MG, et al. Saliva polymerase-chain-reaction assay for cytomegalovirus screening in newborns. N Engl J Med 2011;364:2111-8. https://doi.org/10.1056/NEJMoa1006561

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