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Published in: BMC Infectious Diseases 1/2017

Open Access 01-12-2017 | Research article

Symptomatic congenital cytomegalovirus disease following non-primary maternal infection: a retrospective cohort study

Authors: Eran Hadar, Elizabeta Dorfman, Ron Bardin, Rinat Gabbay-Benziv, Jacob Amir, Joseph Pardo

Published in: BMC Infectious Diseases | Issue 1/2017

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Abstract

Background

Scarce data exist about screening, diagnosis and prognosis of non-primary Cytomegalovirus (CMV) during pregnancy. We aimed to examine antenatal diagnosis of maternal non-primary CMV infection and to identify risk factors for congenial CMV disease.

Methods

Retrospective cohort of 107 neonates with congenital symptomatic CMV infection, following either primary (n = 95) or non-primary (n = 12) maternal CMV infection. We compared the groups for the manifestations and severity of congenial CMV disease, as well as for possible factors associated with the risk of developing CMV related infant morbidity.

Results

Disease severity is not similar in affected newborns, with a higher incidence of abnormal brain sonographic findings, following primary versus non-primary maternal CMV infection (76.8% vs. 8.3%, p < .001). Symptomatic congenital CMV disease following a non-primary infection is more frequent if gestational hypertensive disorders and/or gestational diabetes mellitus have ensued during pregnancy (33.3% vs. 9.9%, p <0.038), as well as if any medications were taken throughout gestation (50% vs. 16.8%, p <0.016). CMV-IgM demonstrates a low detection rate for non-primary maternal infection during pregnancy compared to primary infection (25% vs. 75.8%, p = 0.0008).

Conclusion

Non-primary maternal CMV infection has an impact on the neonate. Although not readily diagnosed during pregnancy, knowledge of risk factors may aid in raising clinical suspicion.
Literature
1.
go back to reference Stagno S, Whitley RJ. Herpesvirus infections of pregnancy. Part I: cytomegalovirus and Epstein-Barr virus infections. N Engl J Med. 1985;313(20):1270–4.CrossRefPubMed Stagno S, Whitley RJ. Herpesvirus infections of pregnancy. Part I: cytomegalovirus and Epstein-Barr virus infections. N Engl J Med. 1985;313(20):1270–4.CrossRefPubMed
2.
go back to reference Stagno S, Pass RF, Dworsky ME, Alford CA. Maternal cytomegalovirus infection and perinatal transmission. Clin Obstet Gynecol. 1982;25(3):563–76.CrossRefPubMed Stagno S, Pass RF, Dworsky ME, Alford CA. Maternal cytomegalovirus infection and perinatal transmission. Clin Obstet Gynecol. 1982;25(3):563–76.CrossRefPubMed
3.
go back to reference 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;344(18):1366–71.CrossRefPubMed 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;344(18):1366–71.CrossRefPubMed
4.
go back to reference Raynor BD. Cytomegalovirus infection in pregnancy. Semin Perinatol. 1993;17(6):394–402.PubMed Raynor BD. Cytomegalovirus infection in pregnancy. Semin Perinatol. 1993;17(6):394–402.PubMed
5.
go back to reference Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton PD, et al. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA. 1986;256(14):1904–8.CrossRefPubMed Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton PD, et al. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA. 1986;256(14):1904–8.CrossRefPubMed
7.
go back to reference Stagno S, Pass RF, Dworsky ME, Henderson RE, Moore EG, Walton PD, et al. Congenital cytomegalovirus infection: the relative importance of primary and recurrent maternal infection. N Engl J Med. 1982;306(16):945–9.CrossRefPubMed Stagno S, Pass RF, Dworsky ME, Henderson RE, Moore EG, Walton PD, et al. Congenital cytomegalovirus infection: the relative importance of primary and recurrent maternal infection. N Engl J Med. 1982;306(16):945–9.CrossRefPubMed
8.
go back to reference Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med. 1992;326(10):663–7.CrossRefPubMed Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med. 1992;326(10):663–7.CrossRefPubMed
9.
go back to reference Boppana SB, Fowler KB, Britt WJ, Stagno S, Pass RF. Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus. Pediatrics. 1999;104(1 Pt 1):55–60.CrossRefPubMed Boppana SB, Fowler KB, Britt WJ, Stagno S, Pass RF. Symptomatic congenital cytomegalovirus infection in infants born to mothers with preexisting immunity to cytomegalovirus. Pediatrics. 1999;104(1 Pt 1):55–60.CrossRefPubMed
10.
go back to reference Townsend CL, Forsgren M, Ahlfors K, Ivarsson SA, Tookey PA, Peckham CS. Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom. Clin Infect Dis. 2013;56(9):1232–9.CrossRefPubMedPubMedCentral Townsend CL, Forsgren M, Ahlfors K, Ivarsson SA, Tookey PA, Peckham CS. Long-term outcomes of congenital cytomegalovirus infection in Sweden and the United Kingdom. Clin Infect Dis. 2013;56(9):1232–9.CrossRefPubMedPubMedCentral
11.
go back to reference Ross SA, Fowler KB, Ashrith G, Stagno S, Britt WJ, Pass RF, et al. Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity. J Pediatr. 2006;148(3):332–6.CrossRefPubMed Ross SA, Fowler KB, Ashrith G, Stagno S, Britt WJ, Pass RF, et al. Hearing loss in children with congenital cytomegalovirus infection born to mothers with preexisting immunity. J Pediatr. 2006;148(3):332–6.CrossRefPubMed
12.
go back to reference Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007;17(4):253–76.CrossRefPubMed Kenneson A, Cannon MJ. Review and meta-analysis of the epidemiology of congenital cytomegalovirus (CMV) infection. Rev Med Virol. 2007;17(4):253–76.CrossRefPubMed
13.
go back to reference Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol. 2008;41(3):192–7.CrossRefPubMed Lazzarotto T, Guerra B, Lanari M, Gabrielli L, Landini MP. New advances in the diagnosis of congenital cytomegalovirus infection. J Clin Virol. 2008;41(3):192–7.CrossRefPubMed
14.
go back to reference Rutter D, Griffiths P, Trompeter RS. Cytomegalic inclusion disease after recurrent maternal infection. Lancet. 1985;2:1182–6.CrossRefPubMed Rutter D, Griffiths P, Trompeter RS. Cytomegalic inclusion disease after recurrent maternal infection. Lancet. 1985;2:1182–6.CrossRefPubMed
15.
go back to reference Ahlfors K, Harris S, Ivarsson S, Svanberg L. Secondary maternal cytomegalovirus infection causing symptomatic congenital infection. N Engl J Med. 1981;305:284.PubMed Ahlfors K, Harris S, Ivarsson S, Svanberg L. Secondary maternal cytomegalovirus infection causing symptomatic congenital infection. N Engl J Med. 1981;305:284.PubMed
16.
go back to reference Wang G, Zhang X, Bialek S, Cannon MJ. Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection. Clin Infect Dis. 2011;52:e11–3.CrossRefPubMed Wang G, Zhang X, Bialek S, Cannon MJ. Attribution of congenital cytomegalovirus infection to primary versus non-primary maternal infection. Clin Infect Dis. 2011;52:e11–3.CrossRefPubMed
17.
go back to reference de Vries JJ, Zwet EW, Dekker FW, Kroes AC, Verkerk PH, Vossen AC. The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: a population-based prediction model. Rev Med Virol. 2013;23:241–9.CrossRefPubMed de Vries JJ, Zwet EW, Dekker FW, Kroes AC, Verkerk PH, Vossen AC. The apparent paradox of maternal seropositivity as a risk factor for congenital cytomegalovirus infection: a population-based prediction model. Rev Med Virol. 2013;23:241–9.CrossRefPubMed
18.
go back to reference Stagno S, Reynolds DW, Huang ES, Thames SD, Smith RJ, Alford CA. Congenital cytomegalovirus infection. N Engl J Med. 1977;296(22):1254–8.CrossRefPubMed Stagno S, Reynolds DW, Huang ES, Thames SD, Smith RJ, Alford CA. Congenital cytomegalovirus infection. N Engl J Med. 1977;296(22):1254–8.CrossRefPubMed
19.
go back to reference Schopfer K, Lauber E, Krech U. Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy. Arch Dis Child. 1978;53(7):536–9.CrossRefPubMedPubMedCentral Schopfer K, Lauber E, Krech U. Congenital cytomegalovirus infection in newborn infants of mothers infected before pregnancy. Arch Dis Child. 1978;53(7):536–9.CrossRefPubMedPubMedCentral
20.
go back to reference Fowler KB, Stagno S, Pass RF. Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980–1990. J Infect Dis. 1993;168:552–6.CrossRefPubMed Fowler KB, Stagno S, Pass RF. Maternal age and congenital cytomegalovirus infection: screening of two diverse newborn populations, 1980–1990. J Infect Dis. 1993;168:552–6.CrossRefPubMed
21.
go back to reference Hadar E, Salzer L, Dorfman E, Amir J, Pardo J. Antenatal risk factors for symptomatic congenital CMV disease following primary maternal CMV infection. J Perinat Med. 2016;44(3):339–44.CrossRefPubMed Hadar E, Salzer L, Dorfman E, Amir J, Pardo J. Antenatal risk factors for symptomatic congenital CMV disease following primary maternal CMV infection. J Perinat Med. 2016;44(3):339–44.CrossRefPubMed
22.
go back to reference Kyriazopoulou V, Bondis J, Frantzidou F, Athanasiadis A, Diza E, Simitsopoulou M, et al. Prenatal diagnosis of fetal cytomegalovirus infection in seropositive pregnant women. Eur J Obstet Gynecol Reprod Biol. 1996;69(2):91–5.CrossRefPubMed Kyriazopoulou V, Bondis J, Frantzidou F, Athanasiadis A, Diza E, Simitsopoulou M, et al. Prenatal diagnosis of fetal cytomegalovirus infection in seropositive pregnant women. Eur J Obstet Gynecol Reprod Biol. 1996;69(2):91–5.CrossRefPubMed
23.
go back to reference Zalel Y, Gilboa Y, Berkenshtat M, Yoeli R, Auslander R, Achiron R, et al. Secondary cytomegalovirus infection can cause severe fetal sequelae despite maternal preconceptional immunity. Ultrasound Obstet Gynecol. 2008;31(4):417–20.CrossRefPubMed Zalel Y, Gilboa Y, Berkenshtat M, Yoeli R, Auslander R, Achiron R, et al. Secondary cytomegalovirus infection can cause severe fetal sequelae despite maternal preconceptional immunity. Ultrasound Obstet Gynecol. 2008;31(4):417–20.CrossRefPubMed
24.
go back to reference Huang ES, Alford CA, Reynolds DW, Stagno S, Pass RF. Molecular epidemiology of cytomegalovirus infections in women and their infants. N Engl J Med. 1980;303(17):958–62.CrossRefPubMed Huang ES, Alford CA, Reynolds DW, Stagno S, Pass RF. Molecular epidemiology of cytomegalovirus infections in women and their infants. N Engl J Med. 1980;303(17):958–62.CrossRefPubMed
Metadata
Title
Symptomatic congenital cytomegalovirus disease following non-primary maternal infection: a retrospective cohort study
Authors
Eran Hadar
Elizabeta Dorfman
Ron Bardin
Rinat Gabbay-Benziv
Jacob Amir
Joseph Pardo
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-2161-3

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