Infección congénita por citomegalovirus
Congenital cytomegalovirus infection
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Romero, H., Ruiz, G., & Contreras, M. E. (2013). Infección congénita por citomegalovirus. Revista Repertorio De Medicina Y Cirugía, 22(4), 237–247. https://doi.org/10.31260/RepertMedCir.v22.n4.2013.751
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Este artículo presenta el estado del arte de la infección congénita por citomegalovirus en recién nacidos, considerada de importante prevalencia en la población. Se documentan las características más relevantes y algunos aspectos relacionados con la inmunidad y la epigenética del virus para facilitar el entendimiento de la patogenia, el tratamiento y las secuelas. Con ello se proporcionan herramientas para la identificación de los factores de riesgo y de las principales manifestaciones clínicas tanto en la infección sintomática como en la asintomática, para que el clínico mejore el diagnóstico e incida en el pronóstico del curso de la infección. Se hace referencia a los lineamientos y recomendaciones actualizadas para la prevención, tratamiento y seguimiento de los pacientes en riesgo y con infección instaurada. Abreviaturas: CMV, citomegalovirus; RN, recién nacido (s); CM VH, citomegalovirus humano.
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1. Lazzarotto T, Lanari M. Why is cytomegalovirus the most frequent cause of congenital infection?. Expert Rev Anti Infect Ther. 2011 Oct; 9(10):841-3.
2. Buonsenso D, Serranti D, Gargiullo L, Ceccarelli M, Ranno O, Valentini P. Congenital cytomegalovirus infection: current strategies and future perspectives. Eur Rev Med Pharmacol Sci. 2012 Jul; 16(7):919-35.
3. Sinzger C, Grefte A, Plachter B, Gouw AS. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol. 1995 Apr; 76 (Pt 4):741-50.
4. Rodríguez M, Juárez G, Astudillo J, Hasbún J, Parra M. Infección congénita por citomegalovirus: nuevos aspectos terapéuticos. Rev. chil. obstet. ginecol. 2008:73(6): 402-5.
5. Manara R, Balao L, Baracchini C, Drigo P, D’Elia R, Ruga EM. Brain magnetic resonance findings in symptomatic congenital cytomegalovirus infection. Pediatr Radiol. 2011: 41:962-70.
6. Cannon MJ, Hyde TB, Schmid DS. Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med Virol. 2011 Jul; 21(4):240-55.
7. Kawasaki H. Pluripotent stem cells are protected from cytomegalovirus infection at multiple points: implications of a new pathogenesis for congenital anomaly caused by cytomegalovirus. Congenit Anom (Kyoto). 2012 Sep; 52(3):147-54.
8. Vide Tavares M, Domingues AP, Tavares M, Malheiro E, Tavares F, Moura P. Cytomegalovirus: is there a place for screening during pregnancy?. Acta Med Port. 2011 Dec; 24 Suppl 4:1003-8.
9. Alarcon Allen A, Baquero-Artigao F. Review and guidelines on the prevention, diagnosis and treatment of post-natal cytomegalovirus infection. An Pediatr (Barc). 2011 Jan; 74(1):52.e1-52.e13.
10. Lim SL, Tan WC, Tan LK. Awareness of and attitudes toward congenital cytomegalovirus infection among pregnant women in Singapore. Int J Gynaecol Obstet. 2012 Jun; 117(3):268-72.
11. Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ. Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med. 2001 May 3; 344(18):1366-71.
12. Alarcon A, Baquero F, Figueras N et al. Consensus document from the Spanish Society of Paediatric Infectious Diseases (SEIP) on the diagnosis and treatment of congenital cytomegalovirus infection. An Pediatr (Barc). 2009 Dec;71(6):535-47.
13. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007 Jul-Aug; 17(4):253-76.
14. Tian C, Ali SA, Weitkamp JH. Congenital Infections, Part I: Cytomegalovirus, Toxoplasma, Rubella, and Herpes Simplex. NeoReviews. 2010; 11:e436-e446.
15. Cheeran MC, Lokensgard JR, Schleiss MR. Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clin Microbiol Rev. 2009 Jan;22(1):99-126.
16. Rodríguez M. Juárez G, Astudillo J, HasbúnJ, Parra M. Infección congénita por citomegalovirus: nuevos aspectos terapéuticos. REV CHIL OBSTET GINECOL 2008; 73(6): 402 - 405.
17. Coll O, Benoist G, Ville Y, Weisman LE, Botet F, Anceschi MM, et. al. Guidelines on CMV congenital infection. J Perinat Med. 2009; 37(5):433-45.
18. Luck S, Sharland M. Postnatal cytomegalovirus: innocent bystander or hidden problem?. Arch Dis Child Fetal Neonatal Ed. 2009 Jan; 94(1):F58-64.
19. Mofenson LM, Brady MT, Danner SP, Dominguez KL, Hazra R, Handelsman E, et. al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009 Sep 4; 58(RR-11):1-166.
20. Marchant A, Appay V, Van Der Sande M, et. al. Mature CD8 (+) T lymphocyte response to viral infection during fetal life. J Clin Invest. 2003 Jun; 111(11):1747-55. 21. Ross SA, Boppana SB. Congenital cytomegalovirus infection: outcome and diagnosis. Semin Pediatr Infect Dis. 2005 Jan; 16(1):44-9.
22. Karltorp E, Hellstrom S, Lewensohn-Fuchs I, Carlsson-Hansen E, Carlsson PI, Engman ML. Congenital cytomegalovirus infection - a common cause of hearing loss of unknown aetiology. Acta Paediatr. 2012 Aug; 101(8):e357-62.
23. Yamamoto AY, Mussi-Pinhata MM, Isaac Mde L, et. al. Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population. Pediatr Infect Dis J. 2011 Dec; 30(12):1043-6.
24. Malm G, Grondahl EH, Lewensohn-Fuchs I. Congenital cytomegalovirus infection: a retrospective diagnosis in a child with pachygyria. Pediatr Neurol. 200 May; 22(5):407-8.
25. Koklu E, Karadag A, Tunc T, Altun D, Sarici SU. Congenital cytomegalovirus infection associated with severe lung involvement in a preterm neonate: a causal relationship?. Eur J Pediatr. 2009 Nov; 168(11): 1409-12.
26. Martins S, Rocha G, Silva G, Calistru A, Pissarra S, Guimaraes H. Blueberry muffin baby. A rare presentation of congenital cytomegalovirus Infection. Acta Med Port. 2011 Dec; 24 (Suppl 3):703-8.
27. Campos Arca S, Fernández Rial M, Pardo Pumar I, Luaces C, García Piñó J, Moral Santamarina E. Hidrops fetal por infección congénita por citomegalovirus: tratamiento posneonatal prolongado con valganciclovir. Rev Chil Obstet Ginecol. 2012; 77(1): 44-49.
28. Sakaguchi H, Yamamoto T, Ono S, Akashi A, Tsuda E, Watanabe K. An infant case of dilated cardiomyopathy associated with congenital cytomegalovirus infection. Pediatr Cardiol. 2012 Jun; 33(5):824-6.
29. Del Pizzo J. Focus on diagnosis: congenital infections (TORCH). Pediatr Rev. 2011 Dec; 32(12):537-42.
30. Sampedro Martinez A, Martinez LA, Teatino PM, Rodriguez-Granger J. Diagnosis of congenital infection. Enferm Infecc Microbiol Clin. 2011 Dec; 29 Suppl 5:15-20.
31. Koyano S, Inoue N, Nagamori T, Moriuchi H, Azuma H. Newborn screening of congenital cytomegalovirus infection using saliva can be influenced by breast feeding. Arch Dis Child Fetal Neonatal Ed. 2013 Mar;98(2):F182.
32. Pass RF. Diagnosis and management of cytomegalovirus infection in the newborn. Pediatr Ann. 2002 Nov; 31(11):719-25.
33. Lim SL, Tan WC, Tan LK. Awareness of and attitudes toward congenital cytomegalovirus infection among pregnant women in Singapore. Int J Gynaecol Obstet. 2012 Jun; 117(3): 268-72.
34. Distéfano A, González CA, Pardón F, Sarubi MA, Canero-Velazco C. Diagnóstico de la infección congénita por citomegalovirus en muestras de sangre seca de recién nacidos en la tarjeta de Guthrie. Una técnica promisoria. Arch Argent Pediatr. 2008; 106(2):132-137.
35. Sinzger C, Grefte A, Plachter B, Gouw AS, The TH, Jahn G. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol. 1995 Apr; 76 (Pt 4):741-50.
36. Din ES, Brown CJ, Grosse SD, et. al. Attitudes toward newborn screening for cytomegalovirus infection. Pediatrics. 2011 Dec; 128(6):e1434-42.
37. Kharrazi M, Hyde T, Young S, Amin MM, Cannon MJ, Dollard SC. Use of screening dried blood spots for estimation of prevalence, risk factors, and birth outcomes of congenital cytomegalovirus infection. J Pediatr. 2010 Aug; 157(2):191-7.
38. Forman M, Valsamakis A, Arav-Boger R. Dried urine spots for detection and quantification of cytomegalovirus in newborns. Diagn Microbiol Infect Dis. 2012 Aug; 73(4):326-9.
39. Gandhoke I, Aggarwal R, Hussain SA, et. al. Congenital CMV infection; diagnosis in symptomatic infants. Indian J Med Microbiol. 2009 Jul-Sep; 27(3):222-5.
40. Griffiths PD. The 2001 Garrod lecture. The treatment of cytomegalovirus infection.J Antimicrob Chemother. 2002 Feb; 49(2):243-53.
41. Kadambari S, Williams EJ, Luck S, Griffiths PD, Sharland M. Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev. 2011 Nov; 87(11):723-8.
42. Kimberlin DW, Acosta EP, Sanchez PJ. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008 Mar 15; 197(6):836-45.
43. Baquero-Artigao F, Romero Gomez MP. Prolonged treatment with valganciclovir in an infant with congenital cytomegalovirus infection. An Pediatr (Barc). 2009 Jun; 70(6):578-81.
44. del Rosal T, Blazquez D, Noguera-Julian A, et. al. Treatment of symptomatic congenital cytomegalovirus infection beyond the neonatal period. J Clin Virol. 2012 Sep; 55(1):72-4.
45. Gandhi RS, Fernández-Álvarez JR, Rabe. H. Management of congenital cytomegalovirus infection: an evidence-based approach. Act Pediatr. 2010 99:509-15.
46. Adler SP, Nigro G, Pereira L. Recent advances in the prevention and treatment of congenital cytomegalovirus infections. Semin Perinatol. 2007 Feb; 31(1):10-8.
47. Griffiths PD. Burden of disease associated with human cytomegalovirus and prospects for elimination by universal immunisation. Lancet Infect Dis. 2012 Oct; 12(10):790-8.
48. Wang D, Li F, Freed DC, et. al. Quantitative analysis of neutralizing antibody response to human cytomegalovirus in natural infection. Vaccine. 2011 Nov 8; 29(48):9075-80.
49. Korver AM, de Vries JJ, Oudesluys-Murphy AM. Congenital cytomegalovirus infection: prevention is better than treatment. J Pediatr. 2011 Nov; 159(5):877.
50. Noyola DE, Matienzo-Serment L, Rodriguez-Vidal SO, Ochoa-Perez UR, PinaGranja JM, Garcia-Sepulveda CA. Congenital cytomegalovirus infection in newborn infants from the state of San Luis Potosi, Mexico. Salud Publica Mex. 2011 Nov-Dec; 53(6):513-5.
51. Amir J, Wolf DG, Levy I. Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir. Eur J Pediatr. 2010 Sep; 169(9):1061-7.
2. Buonsenso D, Serranti D, Gargiullo L, Ceccarelli M, Ranno O, Valentini P. Congenital cytomegalovirus infection: current strategies and future perspectives. Eur Rev Med Pharmacol Sci. 2012 Jul; 16(7):919-35.
3. Sinzger C, Grefte A, Plachter B, Gouw AS. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol. 1995 Apr; 76 (Pt 4):741-50.
4. Rodríguez M, Juárez G, Astudillo J, Hasbún J, Parra M. Infección congénita por citomegalovirus: nuevos aspectos terapéuticos. Rev. chil. obstet. ginecol. 2008:73(6): 402-5.
5. Manara R, Balao L, Baracchini C, Drigo P, D’Elia R, Ruga EM. Brain magnetic resonance findings in symptomatic congenital cytomegalovirus infection. Pediatr Radiol. 2011: 41:962-70.
6. Cannon MJ, Hyde TB, Schmid DS. Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med Virol. 2011 Jul; 21(4):240-55.
7. Kawasaki H. Pluripotent stem cells are protected from cytomegalovirus infection at multiple points: implications of a new pathogenesis for congenital anomaly caused by cytomegalovirus. Congenit Anom (Kyoto). 2012 Sep; 52(3):147-54.
8. Vide Tavares M, Domingues AP, Tavares M, Malheiro E, Tavares F, Moura P. Cytomegalovirus: is there a place for screening during pregnancy?. Acta Med Port. 2011 Dec; 24 Suppl 4:1003-8.
9. Alarcon Allen A, Baquero-Artigao F. Review and guidelines on the prevention, diagnosis and treatment of post-natal cytomegalovirus infection. An Pediatr (Barc). 2011 Jan; 74(1):52.e1-52.e13.
10. Lim SL, Tan WC, Tan LK. Awareness of and attitudes toward congenital cytomegalovirus infection among pregnant women in Singapore. Int J Gynaecol Obstet. 2012 Jun; 117(3):268-72.
11. Boppana SB, Rivera LB, Fowler KB, Mach M, Britt WJ. Intrauterine transmission of cytomegalovirus to infants of women with preconceptional immunity. N Engl J Med. 2001 May 3; 344(18):1366-71.
12. Alarcon A, Baquero F, Figueras N et al. Consensus document from the Spanish Society of Paediatric Infectious Diseases (SEIP) on the diagnosis and treatment of congenital cytomegalovirus infection. An Pediatr (Barc). 2009 Dec;71(6):535-47.
13. Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007 Jul-Aug; 17(4):253-76.
14. Tian C, Ali SA, Weitkamp JH. Congenital Infections, Part I: Cytomegalovirus, Toxoplasma, Rubella, and Herpes Simplex. NeoReviews. 2010; 11:e436-e446.
15. Cheeran MC, Lokensgard JR, Schleiss MR. Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention. Clin Microbiol Rev. 2009 Jan;22(1):99-126.
16. Rodríguez M. Juárez G, Astudillo J, HasbúnJ, Parra M. Infección congénita por citomegalovirus: nuevos aspectos terapéuticos. REV CHIL OBSTET GINECOL 2008; 73(6): 402 - 405.
17. Coll O, Benoist G, Ville Y, Weisman LE, Botet F, Anceschi MM, et. al. Guidelines on CMV congenital infection. J Perinat Med. 2009; 37(5):433-45.
18. Luck S, Sharland M. Postnatal cytomegalovirus: innocent bystander or hidden problem?. Arch Dis Child Fetal Neonatal Ed. 2009 Jan; 94(1):F58-64.
19. Mofenson LM, Brady MT, Danner SP, Dominguez KL, Hazra R, Handelsman E, et. al. Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics. MMWR Recomm Rep. 2009 Sep 4; 58(RR-11):1-166.
20. Marchant A, Appay V, Van Der Sande M, et. al. Mature CD8 (+) T lymphocyte response to viral infection during fetal life. J Clin Invest. 2003 Jun; 111(11):1747-55. 21. Ross SA, Boppana SB. Congenital cytomegalovirus infection: outcome and diagnosis. Semin Pediatr Infect Dis. 2005 Jan; 16(1):44-9.
22. Karltorp E, Hellstrom S, Lewensohn-Fuchs I, Carlsson-Hansen E, Carlsson PI, Engman ML. Congenital cytomegalovirus infection - a common cause of hearing loss of unknown aetiology. Acta Paediatr. 2012 Aug; 101(8):e357-62.
23. Yamamoto AY, Mussi-Pinhata MM, Isaac Mde L, et. al. Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population. Pediatr Infect Dis J. 2011 Dec; 30(12):1043-6.
24. Malm G, Grondahl EH, Lewensohn-Fuchs I. Congenital cytomegalovirus infection: a retrospective diagnosis in a child with pachygyria. Pediatr Neurol. 200 May; 22(5):407-8.
25. Koklu E, Karadag A, Tunc T, Altun D, Sarici SU. Congenital cytomegalovirus infection associated with severe lung involvement in a preterm neonate: a causal relationship?. Eur J Pediatr. 2009 Nov; 168(11): 1409-12.
26. Martins S, Rocha G, Silva G, Calistru A, Pissarra S, Guimaraes H. Blueberry muffin baby. A rare presentation of congenital cytomegalovirus Infection. Acta Med Port. 2011 Dec; 24 (Suppl 3):703-8.
27. Campos Arca S, Fernández Rial M, Pardo Pumar I, Luaces C, García Piñó J, Moral Santamarina E. Hidrops fetal por infección congénita por citomegalovirus: tratamiento posneonatal prolongado con valganciclovir. Rev Chil Obstet Ginecol. 2012; 77(1): 44-49.
28. Sakaguchi H, Yamamoto T, Ono S, Akashi A, Tsuda E, Watanabe K. An infant case of dilated cardiomyopathy associated with congenital cytomegalovirus infection. Pediatr Cardiol. 2012 Jun; 33(5):824-6.
29. Del Pizzo J. Focus on diagnosis: congenital infections (TORCH). Pediatr Rev. 2011 Dec; 32(12):537-42.
30. Sampedro Martinez A, Martinez LA, Teatino PM, Rodriguez-Granger J. Diagnosis of congenital infection. Enferm Infecc Microbiol Clin. 2011 Dec; 29 Suppl 5:15-20.
31. Koyano S, Inoue N, Nagamori T, Moriuchi H, Azuma H. Newborn screening of congenital cytomegalovirus infection using saliva can be influenced by breast feeding. Arch Dis Child Fetal Neonatal Ed. 2013 Mar;98(2):F182.
32. Pass RF. Diagnosis and management of cytomegalovirus infection in the newborn. Pediatr Ann. 2002 Nov; 31(11):719-25.
33. Lim SL, Tan WC, Tan LK. Awareness of and attitudes toward congenital cytomegalovirus infection among pregnant women in Singapore. Int J Gynaecol Obstet. 2012 Jun; 117(3): 268-72.
34. Distéfano A, González CA, Pardón F, Sarubi MA, Canero-Velazco C. Diagnóstico de la infección congénita por citomegalovirus en muestras de sangre seca de recién nacidos en la tarjeta de Guthrie. Una técnica promisoria. Arch Argent Pediatr. 2008; 106(2):132-137.
35. Sinzger C, Grefte A, Plachter B, Gouw AS, The TH, Jahn G. Fibroblasts, epithelial cells, endothelial cells and smooth muscle cells are major targets of human cytomegalovirus infection in lung and gastrointestinal tissues. J Gen Virol. 1995 Apr; 76 (Pt 4):741-50.
36. Din ES, Brown CJ, Grosse SD, et. al. Attitudes toward newborn screening for cytomegalovirus infection. Pediatrics. 2011 Dec; 128(6):e1434-42.
37. Kharrazi M, Hyde T, Young S, Amin MM, Cannon MJ, Dollard SC. Use of screening dried blood spots for estimation of prevalence, risk factors, and birth outcomes of congenital cytomegalovirus infection. J Pediatr. 2010 Aug; 157(2):191-7.
38. Forman M, Valsamakis A, Arav-Boger R. Dried urine spots for detection and quantification of cytomegalovirus in newborns. Diagn Microbiol Infect Dis. 2012 Aug; 73(4):326-9.
39. Gandhoke I, Aggarwal R, Hussain SA, et. al. Congenital CMV infection; diagnosis in symptomatic infants. Indian J Med Microbiol. 2009 Jul-Sep; 27(3):222-5.
40. Griffiths PD. The 2001 Garrod lecture. The treatment of cytomegalovirus infection.J Antimicrob Chemother. 2002 Feb; 49(2):243-53.
41. Kadambari S, Williams EJ, Luck S, Griffiths PD, Sharland M. Evidence based management guidelines for the detection and treatment of congenital CMV. Early Hum Dev. 2011 Nov; 87(11):723-8.
42. Kimberlin DW, Acosta EP, Sanchez PJ. Pharmacokinetic and pharmacodynamic assessment of oral valganciclovir in the treatment of symptomatic congenital cytomegalovirus disease. J Infect Dis. 2008 Mar 15; 197(6):836-45.
43. Baquero-Artigao F, Romero Gomez MP. Prolonged treatment with valganciclovir in an infant with congenital cytomegalovirus infection. An Pediatr (Barc). 2009 Jun; 70(6):578-81.
44. del Rosal T, Blazquez D, Noguera-Julian A, et. al. Treatment of symptomatic congenital cytomegalovirus infection beyond the neonatal period. J Clin Virol. 2012 Sep; 55(1):72-4.
45. Gandhi RS, Fernández-Álvarez JR, Rabe. H. Management of congenital cytomegalovirus infection: an evidence-based approach. Act Pediatr. 2010 99:509-15.
46. Adler SP, Nigro G, Pereira L. Recent advances in the prevention and treatment of congenital cytomegalovirus infections. Semin Perinatol. 2007 Feb; 31(1):10-8.
47. Griffiths PD. Burden of disease associated with human cytomegalovirus and prospects for elimination by universal immunisation. Lancet Infect Dis. 2012 Oct; 12(10):790-8.
48. Wang D, Li F, Freed DC, et. al. Quantitative analysis of neutralizing antibody response to human cytomegalovirus in natural infection. Vaccine. 2011 Nov 8; 29(48):9075-80.
49. Korver AM, de Vries JJ, Oudesluys-Murphy AM. Congenital cytomegalovirus infection: prevention is better than treatment. J Pediatr. 2011 Nov; 159(5):877.
50. Noyola DE, Matienzo-Serment L, Rodriguez-Vidal SO, Ochoa-Perez UR, PinaGranja JM, Garcia-Sepulveda CA. Congenital cytomegalovirus infection in newborn infants from the state of San Luis Potosi, Mexico. Salud Publica Mex. 2011 Nov-Dec; 53(6):513-5.
51. Amir J, Wolf DG, Levy I. Treatment of symptomatic congenital cytomegalovirus infection with intravenous ganciclovir followed by long-term oral valganciclovir. Eur J Pediatr. 2010 Sep; 169(9):1061-7.
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