Cytomegalovirus DNA detection in pregnant women with a high IgG avidity index: a valuable tool for diagnosing non-primary infections?

Abstract

Background/Aim

Congenital human cytomegalovirus infection (cCMV) is the commonest congenital infection, and it can result in hearing loss and neurodevelopmental delay. Even if primary infections are more frequent and cause more severe congenital cCMV manifestations compared to NPIs, and despite partial protection from maternal immunity, the highest birth prevalence of cCMV is observed in seropositive women with non-primary CMV infection (NPI). Given that NPI contribute significantly to the overall burden of cCMV, their accurate diagnosis of NPI remains clinically important. Considering that the serological testing for CMV infection is not always reliable, we sought to determine whether detection of CMV DNA in pregnant women with a high IgG avidity index (AI) can help diagnose NPI.

Materials and methods

Human CMV serology screening (IgG, IgM, and IgG AI) was performed for confirmation of CMV infection in serum samples from mainly pregnant women with indications of CMV infection due to IgG⁺ and IgM⁺-positive samples in other laboratories. Pregnant women (or those with termination of pregnancy during the last period) with adequate IgG levels to perform IgG AI were included. Demographic data and mean gestation week at the time of screening were recorded. Serological testing was performed using CE-IVD commercial kits. CMV DNAemia detection by real time PCR (RT-PCR) was applied to confirm suspected CMV infection.

Results

Nine-hundred and thirty-four pregnant women CMV IgG positive with adequate IgG titers for AI testing were included in the study. The percentage of women with a high AI was 71.8% (671/934); among them, nearly 2.4% (16/671) had presence of CMV DNA. Also, 12.4% of women (116/934) had intermediate IgG AI and 15.7% of women (147/934) had low IgG AI. The presence of CMV DNA was observed in 13.8% (16/116) and 39.5% (58/147) of the groups with intermediate and low IgG AI, respectively. A high CMV IgG AI was associated with a negative CMV PCR status (p-value <.00001).

Conclusions

CMV DNA was present in 2.4% of seropositive women with high IgG AI, indicating active NPI and thus, harboring the risk of cCMV sequelae to the fetus. Moreover, the incidence of NPI may have been underestimated due to single timepoint testing. In order to detect CMV NPI in a seropositive woman, regular and frequent serology testing as well as detection of CMV DNAemia are required which render the whole diagnostic process impractical and not cost-effective.

Keywords:

• Congenital CMV infection
• IgG avidity
• CMV DNAemia
• immunoglobulin
• pregnancy

Ethical approval

This study was conducted in accordance with the 1964 Declaration of Helsinki and its amended versions. Considering that all samples were collected, processed, and analyzed as part of the routine laboratory screening for congenital infections, no formal consent was deemed necessary for this study. Moreover, in light of the retrospective character of the study, it was deemed that this study could be exempted from institutional ethics approval based on local ethical guidelines. We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Acknowledgments

The authors wish to thank Dr. Andreas F. Mentis, M.D., Ph.D., for his critical comments, as well as Dr. Nithya Rao Velliyuir Nott, Ph.D. for critical feedback on the manuscript.

Disclosure statement

IK and AK are employees of the Diagnostic Services Laboratory of the Hellenic Pasteur Institute, which provides diagnostic services on congenital CMV and other infectious diseases. No potential conflict of interest was reported by the author(s).

Author contributions

IK: performed the diagnostic analyses and recorded the data. JJ: conducted the statistical analysis. IG: conducted the statistical analysis. AFAM: conceived and designed the study, interpreted the statistical analyses, supervised the study, and drafted the first version of the manuscript with input from all other authors. All authors: read and approved the final version of the manuscript.

Data availability statement

Raw data are available upon reasonable request.

Additional information

Funding

Irene García has been partially supported by the Spanish Ministry of Sciences, Innovation and Universities and the European Regional Development Fund through project PGC2018-096956-B-C43. The sponsor was not involved in study design, in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.