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Cytomegalovirus infection in pregnancy

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Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Due to the severe risk of long-term sequelae, prenatal cytomegalovirus infection is of particular importance amongst intrauterine viral infections. This review summarizes the current knowledge about CMV infection in pregnancy.

Methods

A search of the Medline and Embase database was done for articles about CMV infection in pregnany. We performed a detailed review of the literature in view of diagnosis, epidemiology and management of CMV infection in pregnancy.

Results

The maternal course of the infection is predominantly asymptomatic; the infection often remains unrecognized until the actual fetal manifestation. Typical ultrasound signs that should arouse suspicion of intrauterine CMV infection can be distinguished into CNS signs such as ventriculomegaly or microcephaly and extracerebral infection signs such as hepatosplenomegaly or hyperechogenic bowel. Current treatment strategies focus on hygienic measures to prevent a maternal CMV infection during pregnancy, on maternal application of hyperimmunoglobulines to avoid materno-fetal transmission in case of a maternal seroconversion, and on an antiviral therapy in case the materno-fetal transmission have occurred.

Conclusion

CMV infection in pregnancy may result in a severe developmental disorder of the newborn. This should be taken into account in the treatment of affected and non-affected pregnant women.

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References

  1. Kagan KO, Goelz R, Hamprecht K (2016) Cytomegalovirusinfektion in der Schwangerschaft. Gynäkologe. doi:10.1007/s00129-016-3923-0

    Google Scholar 

  2. Enders G, Daiminger A, Bäder U et al (2011) Intrauterine transmission and clinical outcome of 248 pregnancies with primary cytomegalovirus infection in relation to gestational age. J Clin Virol 52:244–246. doi:10.1016/j.jcv.2011.07.005

    Article  PubMed  Google Scholar 

  3. Picone O, Vauloup-Fellous C, Cordier AG et al (2013) A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome. Prenat Diagn 33:751–758. doi:10.1002/pd.4118

    Article  CAS  PubMed  Google Scholar 

  4. Revello MG, Furione M, Rognoni V et al (2014) Cytomegalovirus DNAemia in pregnant women. J Clin Virol 61:590–592. doi:10.1016/j.jcv.2014.10.002

    Article  CAS  PubMed  Google Scholar 

  5. Hamprecht K (2017) Update CMV, personal communication

  6. Kenneson A, Cannon MJ (2007) Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol 17:253–276. doi:10.1002/rmv.535

    Article  PubMed  Google Scholar 

  7. Britt W (2015) Controversies in the natural history of congenital human cytomegalovirus infection: the paradox of infection and disease in offspring of women with immunity prior to pregnancy. Med Microbiol Immunol 204:263–271. doi:10.1007/s00430-015-0399-9

    Article  CAS  PubMed  Google Scholar 

  8. De Paschale M, Agrappi C, Manco MT et al (2009) Incidence and risk of cytomegalovirus infection during pregnancy in an urban area of Northern Italy. Infect Dis Obstet Gynecol. doi:10.1155/2009/206505

    PubMed  PubMed Central  Google Scholar 

  9. Hamprecht K, Jahn G (2007) Human cytomegalovirus and congenital virus infection. Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz 50:1379–1392. doi:10.1007/s00103-007-0194-x

    Article  CAS  PubMed  Google Scholar 

  10. Yinon Y, Farine D, Yudin MH (2010) Screening, diagnosis, and management of cytomegalovirus infection in pregnancy—PubMed—NCBI. Obstet Gynecol Surv 65:736–743. doi:10.1097/OGX.0b013e31821102b4

    Article  PubMed  Google Scholar 

  11. Manicklal S, Emery VC, Lazzarotto T et al (2013) The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev 26:86–102. doi:10.1128/CMR.00062-12

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Society for Maternal-Fetal Medicine (SMFM), Hughes BL, Gyamfi-Bannerman C (2016) Diagnosis and antenatal management of congenital cytomegalovirus infection. Am J Obstet Gynecol 214:B5–B11. doi:10.1016/j.ajog.2016.02.042

    Article  Google Scholar 

  13. Lazzarotto T, Boppana SB (2013) The “silent” global burden of congenital cytomegalovirus. Clin Microbiol Rev 26:86–102. doi:10.1128/CMR.00062-12

    Article  PubMed  PubMed Central  Google Scholar 

  14. AWMF (2014) Labordiagnostik schwangerschaftsrelevanter Virusinfektionen S2 k-Leitlinie AWMF Registernummer 0093/001. 1–209

  15. Hyde TB, Schmid DS, Cannon MJ (2010) Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol 20:311–326. doi:10.1002/rmv.659

    Article  PubMed  Google Scholar 

  16. Yamamoto AY, Mussi-Pinhata MM, Boppana SB et al (2010) Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus-immune maternal population. Am J Obstet Gynecol 202(297):e1–e8. doi:10.1016/j.ajog.2009.11.018

    Google Scholar 

  17. Wang C, Zhang X, Bialek S, Cannon MJ (2011) Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection. Clin Infect Dis 52:e11–e13. doi:10.1093/cid/ciq085

    Article  PubMed  Google Scholar 

  18. Voigt S, Schaffrath Rosario A, Mankertz A (2016) Cytomegalovirus seroprevalence among children and adolescents in Germany: data from the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), 2003–2006. Open Forum Infect Dis. doi:10.1093/ofid/ofv193

    PubMed  Google Scholar 

  19. Bodéus M, Kabamba-Mukadi B, Zech F et al (2010) Human cytomegalovirus in utero transmission: follow-up of 524 maternal seroconversions. J Clin Virol 47:201–202. doi:10.1016/j.jcv.2009.11.009

    Article  PubMed  Google Scholar 

  20. Lipitz S, Yinon Y, Malinger G et al (2013) Risk of cytomegalovirus-associated sequelae in relation to time of infection and findings on prenatal imaging. Ultrasound Obstet Gynecol 41:508–514. doi:10.1002/uog.12377

    Article  CAS  PubMed  Google Scholar 

  21. Bilavsky E, Pardo J, Attias J et al (2016) Clinical implications for children born with congenital cytomegalovirus infection following a negative amniocentesis. Clin Infect Dis 63:33–38. doi:10.1093/cid/ciw237

    Article  PubMed  Google Scholar 

  22. Hamprecht K, Bissinger AL, Arellano-Galindo J et al (2014) Intrafamilial transmission of human cytomegalovirus (HCMV): long-term dynamics of epitope-specific antibody response in context of avidity maturation. J Clin Virol 60:119–126. doi:10.1016/j.jcv.2014.03.006

    Article  CAS  PubMed  Google Scholar 

  23. Schoppel K, Kropff B, Schmidt C et al (1997) The humoral immune response against human cytomegalovirus is characterized by a delayed synthesis of glycoprotein-specific antibodies. J Infect Dis 175:533–544

    Article  CAS  PubMed  Google Scholar 

  24. Prince HE, Lapé-Nixon M (2014) Role of cytomegalovirus (CMV) IgG avidity testing in diagnosing primary CMV infection during pregnancy. Clin Vaccine Immunol 21:1377–1384. doi:10.1128/CVI.00487-14

    Article  PubMed  PubMed Central  Google Scholar 

  25. Karacan M, Batukan M, Çebi Z et al (2014) Screening cytomegalovirus, rubella and toxoplasma infections in pregnant women with unknown pre-pregnancy serological status—PubMed—NCBI. Arch Gynecol Obstet 290:1115–1120. doi:10.1007/s00404-014-3340-3

    Article  CAS  PubMed  Google Scholar 

  26. Kling C, Kabelitz D (2014) Congenital HCMV and assisted reproduction: why not use the chance for primary screening? Arch Gynecol Obstet 291:1205–1211. doi:10.1007/s00404-014-3583-z

    Article  PubMed  Google Scholar 

  27. Leruez-Ville M, Stirnemann J, Sellier Y et al (2016) Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis. Am J Obstet Gynecol 215(342):e1–e9. doi:10.1016/j.ajog.2016.03.052

    Google Scholar 

  28. Malinger G, Lev D, Lerman-Sagie T (2011) Imaging of fetal cytomegalovirus infection. Fetal Diagn Ther 29:117–126. doi:10.1159/000321346

    Article  PubMed  Google Scholar 

  29. Teissier N, Fallet-Bianco C, Delezoide A-L et al (2014) Cytomegalovirus-induced brain malformations in fetuses. J Neuropathol Exp Neurol 73:143–158. doi:10.1097/NEN.0000000000000038

    Article  PubMed  Google Scholar 

  30. Gabrielli L, Bonasoni MP, Lazzarotto T et al (2009) Histological findings in foetuses congenitally infected by cytomegalovirus. J Clin Virol 46:S16–S21. doi:10.1016/j.jcv.2009.09.026

    Article  PubMed  Google Scholar 

  31. Hui L, Wood G (2014) Perinatal outcome after maternal primary cytomegalovirus infection in the first trimester: a practical update and counseling aid. Prenat Diagn 35:1–7. doi:10.1002/pd.4497

    Article  PubMed  Google Scholar 

  32. Guerra B, Simonazzi G, Puccetti C et al (2008) Ultrasound prediction of symptomatic congenital cytomegalovirus infection. Am J Obstet Gynecol 198:380.e1–380.e7. doi:10.1016/j.ajog.2007.09.052

    Article  Google Scholar 

  33. Benoist G, Salomon LJ, Jacquemard F et al (2008) The prognostic value of ultrasound abnormalities and biological parameters in blood of fetuses infected with cytomegalovirus. BJOG 115:823–829. doi:10.1111/j.1471-0528.2008.01714.x

    Article  CAS  PubMed  Google Scholar 

  34. Liesnard C, Donner C, Brancart F et al (2000) Prenatal diagnosis of congenital cytomegalovirus infection: prospective study of 237 pregnancies at risk. Obstet Gynecol 95:881–888

    CAS  PubMed  Google Scholar 

  35. Enders G, Bäder U, Lindemann L et al (2001) Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome. Prenat Diagn 21:362–377. doi:10.1002/pd.59

    Article  CAS  PubMed  Google Scholar 

  36. Donner C, Liesnard C, Brancart F, Rodesch F (1994) Accuracy of amniotic fluid testing before 21 weeks’ gestation in prenatal diagnosis of congenital cytomegalovirus infection. Prenat Diagn 14:1055–1059

    Article  CAS  PubMed  Google Scholar 

  37. Enders M, Daiminger A, Exler S et al (2017) Prenatal diagnosis of congenital cytomegalovirus infection in 115 cases: a 5 years’ single center experience. Prenat Diagn 198:380. doi:10.1002/pd.5025

    Google Scholar 

  38. Renzette N, Pokalyuk C, Gibson L et al (2015) Limits and patterns of cytomegalovirus genomic diversity in humans. Proc Natl Acad Sci USA 112:E4120–E4128. doi:10.1073/pnas.1501880112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Pass RF, Zhang C, Evans A et al (2009) Vaccine prevention of maternal cytomegalovirus infection. N Engl J Med 360:1191–1199. doi:10.1056/NEJMoa0804749

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Adler SP (2015) Prevention of maternal-fetal transmission of cytomegalovirus. EBIOM 2:1027–1028. doi:10.1016/j.ebiom.2015.08.004

    Article  Google Scholar 

  41. Hamilton ST, van Zuylen W, Shand A et al (2014) Prevention of congenital cytomegalovirus complications by maternal and neonatal treatments: a systematic review. Rev Med Virol 24:420–433. doi:10.1002/rmv.1814

    Article  CAS  PubMed  Google Scholar 

  42. Revello MG, Tibaldi C, Masuelli G et al (2015) Prevention of primary cytomegalovirus infection in pregnancy. EBIOM 2:1205–1210. doi:10.1016/j.ebiom.2015.08.003

    Article  Google Scholar 

  43. Maidji E, Nigro G, Tabata T et al (2010) Antibody treatment promotes compensation for human cytomegalovirus-induced pathogenesis and a hypoxia-like condition in placentas with congenital infection. Am J Pathol 177:1298–1310. doi:10.2353/ajpath.2010.091210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Nigro G, Adler SP, La Torre R et al (2005) Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med 353:1350–1362. doi:10.1056/NEJMoa043337

    Article  CAS  PubMed  Google Scholar 

  45. Revello MG, Lazzarotto T, Guerra B et al (2014) A randomized trial of hyperimmune globulin to prevent congenital cytomegalovirus. N Engl J Med 370:1316–1326. doi:10.1056/NEJMoa1310214

    Article  CAS  PubMed  Google Scholar 

  46. Buxmann H, Stackelberg OMV, Schlößer RL et al (2012) Use of cytomegalovirus hyperimmunoglobulin for prevention of congenital cytomegalovirus disease: a retrospective analysis. J Perinat Med 40:1–8. doi:10.1515/jpm-2011-0257

    Article  Google Scholar 

  47. Rawlinson WD, Boppana SB, Fowler KB et al (2017) Congenital cytomegalovirus infection in pregnancy and the neonate: consensus recommendations for prevention, diagnosis, and therapy. Lancet Infect Dis. doi:10.1016/S1473-3099(17)30143-3

    PubMed  Google Scholar 

  48. Thürmann PA, Sonnenburg-Chatzopoulos C, Lissner R (1995) Pharmacokinetic characteristics and tolerability of a novel intravenous immunoglobulin preparation. Eur J Clin Pharmacol 49:237–242

    Article  PubMed  Google Scholar 

  49. Hamprecht K, Kagan KO, Goelz R (2014) Hyperimmune globulin to prevent congenital CMV infection. N Engl J Med 370:2543. doi:10.1056/NEJMc1405377#SA1

    Article  PubMed  Google Scholar 

  50. Visentin S, Manara R, Milanese L et al (2012) Early primary cytomegalovirus infection in pregnancy: maternal hyperimmunoglobulin therapy improves outcomes among infants at 1 year of age. Clin Infect Dis 55:497–503. doi:10.1093/cid/cis423

    Article  CAS  PubMed  Google Scholar 

  51. Malek A, Sager R, Kuhn P et al (1996) Evolution of maternofetal transport of immunoglobulins during human pregnancy. Am J Reprod Immunol 36:248–255

    Article  CAS  PubMed  Google Scholar 

  52. Leruez-Ville M, Ghout I, Bussières L et al (2016) In utero treatment of congenital cytomegalovirus infection with valacyclovir in a multicentre, open-label, phase II study. Am J Obstet Gynecol. doi:10.1016/j.ajog.2016.04.003

    Google Scholar 

  53. Goderis J, De Leenheer E, Smets K et al (2014) Hearing loss and congenital CMV infection: a systematic review. Pediatrics 134:972–982. doi:10.1542/peds.2014-1173

    Article  PubMed  Google Scholar 

  54. Fowler KB, McCollister FP, Sabo DL et al (2017) A targeted approach for congenital cytomegalovirus screening within newborn hearing screening. Pediatrics 139:e20162128. doi:10.1542/peds.2016-2128

    Article  PubMed  Google Scholar 

  55. Gantt S, Dionne F, Kozak FK et al (2016) Cost-effectiveness of universal and targeted newborn screening for congenital cytomegalovirus infection. JAMA Pediatr 170:1173–1178. doi:10.1001/jamapediatrics.2016.2016

    Article  PubMed  Google Scholar 

  56. Kimberlin DW, Lin C-Y, Sánchez PJ et al (2003) Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus disease involving the central nervous system: a randomized, controlled trial. J Pediatr 143:16–25

    Article  CAS  PubMed  Google Scholar 

  57. Oliver SE, Cloud GA, Sánchez PJ et al (2009) Neurodevelopmental outcomes following ganciclovir therapy in symptomatic congenital cytomegalovirus infections involving the central nervous system. J Clin Virol 46(Suppl 4):S22–S26. doi:10.1016/j.jcv.2009.08.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kimberlin DW, Jester PM, Sánchez PJ et al (2015) Valganciclovir for symptomatic congenital cytomegalovirus disease. N Engl J Med 372:933–943. doi:10.1056/NEJMoa1404599

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of obstetrics and gynecology, University of Tuebingen, Calwerstrasse 7, 72076, Tübingen, Germany

    Karl Oliver Kagan

  2. Institute for Medical Virology and Epidemiology of Viral Diseases, University of Tuebingen, Elfriede-Aulhorn-Straße 6, 72076, Tübingen, Germany

    Klaus Hamprecht

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  1. Karl Oliver Kagan
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Author contributions

KOK and KH: both authors have contributed equally in terms of project development, manuscript writing, and editing.

Corresponding author

Correspondence to Karl Oliver Kagan.

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Funding

K Hamprecht is a member of the Scientific Advisory Board of the Initiative for the Prevention of Congenital Cytomegaly Disorders (ICON). All related honoraria are paid into a UKT Institute for Medical Virology grant account to support the Tuebingen Congenital CMV Study.

Conflict of interest

K Hamprecht is a member of the Scientific Advisory Board of the Initiative for the Prevention of Congenital Cytomegaly Disorders (ICON). All related honoraria are paid into a UKT Institute for Medical Virology grant account to support the Tuebingen Congenital CMV Study.

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Kagan, K.O., Hamprecht, K. Cytomegalovirus infection in pregnancy. Arch Gynecol Obstet 296, 15–26 (2017). https://doi.org/10.1007/s00404-017-4380-2

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