Antenatal Detection of Congenital Cytomegalovirus Infection (A Comparative Study between Serological and Molecular Identification of Cytomegalovirus Infection)
Keywords:
Cytomegalovirus Infection; Prenatal Diagnosis; CMV enzyme immunoassay, PCR ,AmniocentesisAbstract
Cytomegalovirus, or CMV, is a common virus that infects most people worldwide. CMV infection is usually harmless and rarely causes illness. A healthy immune system can hold the virus in check. However, if a person's immune system is seriously weakened in any way, the virus can become active and cause CMV disease. The samples consisted of 120 pregnant women, prospectively screened for CMV by serology from March 2012 to November 2012. The women were presenting for routine antenatal care at a tertiary referral women's hospital Maternal and Children Hospital (M.C.H.) Buridah ,Elqassem, All subjects gave written consent. CMV IgG and IgM were detected in patient serum by using a commercial microparticle enzyme immunoassay,and determination of the presence of CMV genome by PCR in Amniotic Fluid. The age range of the pregnant women was 18 to 46 years, with no significant difference seen between the mean age of seropositive and seronegative women. The CMV seropositivity rate for the pregnant women showed that, overall, 76.8% women were CMV IgG positive at pregnancy. Pregnant women were considered in high risk due to (i) documented seroconversion to positively for CMV from 3 months before conception to the end of the first trimester of pregnancy (four patients) (ii) CMV symptoms (increase in liver enzyme levels and/or fever) and presence of CMV immunoglobulin M (IgM) (five patients) (iii) intrauterine growth retardation as detected by ultrasound (three patients). PCR was used to detect excretion of CMV from the amniotic fluid in 5 of six cases(83.3%) were sero positive,and 1 false negative(16.7%) ,In group without infection , PCR was positive in 1 case ( 1 false positive). Congenital CMV infection is a major health problem that should be approached on the basis of which women should be enrolled in prenatal diagnostic programs, which clinical specimens should be tested, and which laboratory procedures should be adopted for the diagnosis of congenital CMV transmission or infection. Determination of the presence of CMV genome by PCR in amniotic fluid can be considered as a rapid ,non invasive and accurate tool for the prenatal diagnosis of congenital CMV infection but negative results cannot rule out of infection ,So that diagnosis of this infection based on correlation between serological and PCR Identification.
References
Alfirevic, Z., Sundberg, K., Brigham, S., 2003. posting date. Amniocentesis and chorionic villus sampling for
prenatal diagnosis. Cochrane Database Syst. Rev., [Online.]
Ahlfors, K., Ivarsson, S.A., Harris, S., 1999. Report on a long-term study of maternal and congenital
cytomegalovirus infection in Sweden, review of prospective studies available in the literature. Scand. J. Infect.
Dis., 31,443-457. [PubMed].
Australian Bureau of Statistics., 1997. Population profile incorporating demographic and social indicators from
the ABS 1996 census of population and housing. Australian Bureau of Statistics, Canberra, Australia.
Bodeus, M., Feyder, S., Goubau, P., 1998. Avidity of IgG antibodies distinguishes primary from non-primary
cytomegalovirus infection in pregnant women. Clin. Diagn. Virol., 9,9-16. [PubMed].
Bodeus, M., Goubau, P., 1999. Predictive value of maternal-IgG avidity for congenital human cytomegalovirus
infection. J. Clin. Virol., 12,3-8. [PubMed].
Faedo, M., Ford, C.E., Mehta, R., Blazek, K., Rawlinson, W.D., 2004. Mouse mammary tumor-like virus is
associated with p53 nuclear accumulation and progesterone receptor positivity but not estrogen positivity in
human female breast cancer. Clin. Cancer Res., 10,4417-4419. [PubMed].
Bodeus, M., Hubinont, C., Bernard, P., Bouckaert, A., Thomas, K., Goubau, P., 1999. Prenatal diagnosis of
human cytomegalovirus by culture and polymerase chain reaction, 98 pregnancies leading to congenital
infection. Prenatal Diagn., 19, 314-317.
Boppana, S.B., Fowler, K.B., Britt, W.J., Stagno, S., Pass, R.F., 1999. Symptomatic congenital cytomegalovirus
infection in infants born to mothers with preexisting immunity to cytomegalovirus. Pediatrics., 104, 55-60.
[PubMed].
Boppana, S.B., Rivera, L.B., Fowler, K.B., Mach, M., Britt, W.J., 2001. Intrauterine transmission of
cytomegalovirus to infants of women with preconceptional immunity. N. Engl. J. Med., 344,1366-1371.
[PubMed].
Breborowicz, G.H., 2001. Limits of fetal viability and its enhancement. Early Pregnancy 5,49-50. [Online.]
http,//www.earlypregnancy.org. [PubMed].
Dahle, A.J., Fowler, K.B., Wright, J.D., Boppana, S.B., Britt, W.J., Pass, R.F., 2000. Longitudinal investigation of
hearing disorders in children with congenital cytomegalovirus. J. Am. Acad. Audiol., 11,283-290. [PubMed].
Daiminger, A., Bader, U., Eggers, M., Lazzarotto, T., Enders, G., 1999. Evaluation of two novel enzyme
immunoassays using recombinant antigens to detect cytomegalovirus-specific immunoglobulin M in sera from
pregnant women. J. Clin. Virol., 13,161-171. [PubMed].
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. Prenatal Diagn., 14,1055-1059.
Faedo, M., Ford, C.E., Mehta, R., Blazek, K., Rawlinson, W.D., 2004. Mouse mammary tumor-like virus is
associated with p53 nuclear accumulation and progesterone receptor positivity but not estrogen positivity in
human female breast cancer. Clin. Cancer Res., 10,4417-4419. [PubMed].
Fernando, S., Pearce, J.M., Booth, J.C., 1993. Lymphocyte responses and virus excretion as risk factors for
intrauterine infection with cytomegalovirus. J. Med. Virol., 41,108-113. [PubMed].
Fowler, K.B., Stagno, S., Pass, R.F., 1993. Maternal age and congenital cytomegalovirus infection, screening of
two diverse newborn populations, 1980-1990. J. Infect. Dis., 168,552-556. [PubMed].
Fowler, K.B., Stagno, S., Pass, R.F., 2003. Maternal immunity and prevention of congenital cytomegalovirus
infection. JAMA 289,1008-1011. [PubMed].
Fowler, K.B.D., McCollister, F.P.E., Dahle, A.J.P., Boppana, S.M.D., Britt, W.J.M.D., Pass, R.F.M.D., 1997.
Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital
cytomegalovirus infection. J. Pediatr., 130,624-630. [PubMed].
Fox, J.C., Kidd, I.M., Griffiths, P.D., Sweny, P., Emery, V.C., 1995. Longitudinal analysis of cytomegalovirus load
in renal transplant recipients using a quantitative polymerase chain reaction, correlation with disease. J. Gen.
Virol., 76,309-319. [PubMed].
Gaytant, M.A., Rours, G.I., Steegers, E.A., Galama, J.M., Semmekrot, B.A., 2003. Congenital cytomegalovirus
infection after recurrent infection, case reports and review of the literature. Eur. J. Pediatr., 162,248-253.
[PubMed].
Fowler, K.B., Stagno, S., Pass, R.F., 2003. Maternal immunity and prevention of congenital cytomegalovirus
infection., JAMA 289,1008-1011. [PubMed].
Fowler, K.B.D., McCollister, F.P.E., Dahle, A.J.P., Boppana, S.M.D., Britt, W.J.M.D., Pass, R.F.M.D., 1997.
Progressive and fluctuating sensorineural hearing loss in children with asymptomatic congenital
cytomegalovirus infection. J. Pediatr., 130,624-630. [PubMed].
Fox, J.C., Kidd, I.M., Griffiths, P.D., Sweny, P., Emery, V.C.. 1995. Longitudinal analysis of cytomegalovirus load
in renal transplant recipients using a quantitative polymerase chain reaction, correlation with disease. J. Gen.
Virol., 76,309-319. [PubMed].
Gaytant, M.A., Rours, G.I., Steegers, E.A., Galama, J.M., Semmekrot, B.A., 2003. Congenital cytomegalovirus
infection after recurrent infection, case reports and review of the literature. Eur. J. Pediatr., 162,248-253.
[PubMed].
Gaytant, M.A., Steegers, E.A., Semmekrot, B.A., Merkus, H.M., Galama, J.M., 2002. Congenital cytomegalovirus
infection, review of the epidemiology and outcome. Obstet. Gynecol. Surv., 57,245-256. [PubMed].
Gottlieb, S.L., Douglas, J.M., Jr., Schmid, D.S., Bolan, G., Iatesta, M., Malotte, C.K., Zenilman, J., Foster, M.,
Baron A.E., Steiner, J.F., Peterman, T.A., Kamb, M.L., Project, R.S.G., 2002. Seroprevalence and correlates of
herpes simplex virus type 2 infection in five sexually transmitted-disease clinics. J. Infect. Dis, 186,1381-1389.
[PubMed].
Grangeot-Keros, L., Mayaux, M.J., Lebon, P., Freymuth, F., Eugene, G., Stricker, R., Dussaix, E., 1997. Value of
cytomegalovirus (CMV) IgG avidity index for the diagnosis of primary CMV infection in pregnant women. J.
Infect. Dis., 175,944-946. [PubMed].
Griffiths, P.D., 2002. Strategies to prevent CMV infection in the neonate. Semin. Neonatol., 7,293-299.
[PubMed].
Guerra, B., Lazzarotto, T., Quarta, S., Lanari, M., Bovicelli, L., Nicolosi, A., Landini, M.P., 2000. Prenatal
diagnosis of symptomatic congenital cytomegalovirus infection. Am. J. Obstet. Gynecol., 183,476-482.
[PubMed].
Hagay, Z.J., Biran, G., Ornoy, A., Reece, E.A.,1996. Congenital cytomegalovirus infection, a long-standing
problem still seeking a solution. Am. J. Obstet. Gynecol., 174,241-245. [PubMed].
Halwachs-Baumann, G., Wilders- Truschnig, M., Enzinger, G., Eibl, M., Linkesch, W., Dornbusch, H.J., Santner
B.I., Marth, E., Kessler, H.H., 2001. Cytomegalovirus diagnosis in renal and bone marrow transplant recipients,
the impact of molecular assays. J. Clin. Virol., 20,49-57. [PubMed].
Kreimer, A.R., Alberg, A.J., Viscidi, R., Gillison, M.L., 2004. Gender differences in sexual biomarkers and
behaviors associated with human papillomavirus-16, -18, and -33 seroprevalence. Sex. Transm. Dis., 31,247-
[PubMed].
Lazzarotto, T., Galli, C., Pulvirenti, R., Rescaldani, R., Vezzo, R., La Gioia, A., Martinelli, C., La Rocca, S., Agresti,
G., Grillner, L., Nordin, M., van Ranst, M., Combs, B., Maine, G.T., Landini, M.P., 2001. Evaluation of the Abbott
AxSYM cytomegalovirus (CMV) immunoglobulin M (IgM) assay in conjunction with other CMV IgM tests and a
CMV IgG avidity assay. Clin. Diagn. Lab. Immunol., 8,196-198. [PubMed].
Lazzarotto, T., Spezzacatena, P., Pradelli, P., Abate, D.A., Varani, S., Landini, M.P., 1997. Avidity of
immunoglobulin G directed against human cytomegalovirus during primary and secondary infections in
immunocompetent and immunocompromised subjects. Clin. Diagn. Lab. Immunol., 4,469-473. [PubMed].
Lazzarotto, T., Varani, S., Gabrielli, L., Spezzacatena, P., Landini, M.P., 1999. New advances in the diagnosis of
congenital cytomegalovirus infection. Intervirol., 42,390-397. [PubMed].
Liesnard, C., Donner, C., Brancart, F., Gosselin, F., Delforge, M.L., Rodesch, F., 2000. Prenatal diagnosis of
congenital cytomegalovirus infection, prospective study of 237 pregnancies at risk. Obstet. Gynecol., 95,881-
[PubMed].
Maine, G.T., Lazzarotto, T., Landini, M.P., 2001. New developments in the diagnosis of maternal and
congenital CMV infection. Expert Rev. Mol. Diagn., 1,19-29. [PubMed].
Maine, G.T., Stricker, R., Schuler, M., Spesard, J., Brojanac, S., Iriarte, B., Herwig, K., Gramins, T., Combs, B.,
Wise, J., Simmons, H., Gram, T., Lonze, J., Ruzicki, D., Byrne, B., Clifton, J.D., Chovan, L.E., Wachta, D., Holas, C.,
Wang, D., Wilson, T., 2000. Development and clinical evaluation of a recombinant-antigen-based
cytomegalovirus immunoglobulin M automated immunoassay using the Abbott AxSYM analyzer. J. Clin.
Microbiol., 38,1476-1481. [PubMed].
Revello, M.G., Gerna, G., 2002. Diagnosis and management of human cytomegalovirus infection in the mother,
fetus, and newborn infant. Clin. Microbiol. Rev., 15,680-715. [PubMed].
Revello, M.G., Zavattoni, M., Sarasini, A., Percivalle, E., Simoncini, L., Gerna, G., 1998. Human cytomegalovirus
in blood of immunocompetent persons during primary infection, prognostic implications for pregnancy. J.
Infect. Dis., 177,1170-1175. [PubMed].
Whitley, R.J, Kimberlin, D.W., 1997. Treatment of viral infections during pregnancy and the neonatal period.
Clin. Perinatol., 24,267-283. [PubMed].
Yoshinaga-Itano, C., 2003. Early intervention after universal neonatal hearing screening, impact on outcomes.
Mental Retardation and Developmental Disabilities Res. Rev., 9,252-266.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2015 A. Hany, M.R.C. O.G. Abdel-Hafeez, F. M. Gamal, M. D. Gad, A. Abeer, M. D. Abdelmonem
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.