In Reply

Primary Human Cytomegalovirus (HCMV) Infection in Pregnancy by Dr. med. Horst Buxmann, Prof. Dr. med. Dr. rer. nat. Klaus Hamprecht, Prof. Dr. med. Matthias Meyer-Wittkopf, and em. Prof. Dr. med. Klaus Friese in issue 4/2017

We thank Stranzinger and Kling for their positive comments, the valuable additional points, and the critical remarks in response to our article (1).

Stranzinger quite rightly points out the fact that in the German-speaking region, insufficient data exist on congenital infections with human cytomegalovirus (HCMV) in the context of occupational legal aspects. The subsequent problem of primary infection with HCMV in pregnancy is—in addition to important medical aspects—of economic relevance for those affected because of restrictions on employment in parts. Unfortunately, recommendations for maternity protection and employment protection vis-à-vis potential viral exposure at work have not yet been harmonized across Germany‘s federal states.

The review article in Deutsches Ärzteblatt was subject to restrictions on space and scope. For this reason, the risks of HCMV transmission in the workplace was not included in our article (1).

We share Stranzinger‘s assessment, that pregnant women who work in areas with exposure to HCMV should be comprehensively informed about hygiene measures to prevent HCMV transmission; we also support her call for longitudinal studies to determine the risk of HCMV infection in workplaces. Extensive studies have been reported that investigated horizontal HCMV transmission from infants to pregnant women in the USA, but such data exist only marginally for Germany (2).

Kling is right in saying that the relative reported timing of the acquisition of the infection (before or around the time of conception, or in the 1–3 trimesters) can help to roughly categorize the potential risk for the manifestation of symptomatic congenital HCMV infection of the neonate. To this end, the primary infection of the mother is diagnosed by using a low concentration of HCMV-IgG and low HCMV-IgG avidity in mostly low HCMV-IgM indices. As explained in the 2014 S2k guideline for the diagnosis of viral infections in pregnancy by the Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF), any HCMV-IgM reactivity should be confirmed by using an immunoblot test. It is well known that HCMV-IgM reactivity is often non-specifically persistent and can be detected co-reactively with other viral infections.

On the basis of a recent international consensus recommendation, universal HCMV antibody screening in pregnancy is not recommended (3). The authors advise conducting selective HCMV-IgG screening at the start of the pregnancy—as is customary in Israel, the US (Hawaii, Utah, Texas), Australia, and Belgium, as well as in population-based studies (Italy, France). The objective is to identify HCMV seronegative pregnant women at risk and to provide hygiene information/education to prevent viral transmission (and potential additional tests for HCMV-IgG).

Especially this population is at the greatest risk for symptomatic congenital HCMV infection of the neonate (4, 5), particularly in a country with a low prevalence of HCMV, such as Germany. The data do not allow a reliable estimate of the incidence of congenital HCMV infections as a result of recurring HCMV infection in pregnant women. Preconceptual HCMV antibody screening makes sense from the perspective of preimplantation diagnostic evaluation and is included in the AWMF guideline—in contrast to the international consensus recommendation. The 2014 AWMF guideline strongly recommends selective HCMV-IgG screening of women with occupational or private exposure owing to contact with infants, whereas it gives merely a low-level recommendation for universal HCMV-IgG screening.

DOI: 10.3238/arztebl.2017.0505

On behalf of the authors

Dr. med. H. Buxmann

Universitätsklinikum Frankfurt

Klinik für Kinder- und Jugendmedizin, Schwerpunkt Neonatologie

Prof. Dr. med. Dr. rer. nat. K. Hamprecht

Universitätsklinikum Tübingen

Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten

Conflict of interest statement
Dr. Buxmann, Prof. Meyer-Wittkopf and Prof. Hamprecht are members of the Scientific Advisory Board of the online platform ICON (Initiative for the Prevention of Congenital HCMV Infections) and have received reimbursements of travel costs, congress and lecture fees related to their work in this role from Biotest AG, Dreieich, Germany.

In addition, Dr. Buxmann and Prof. Hamprecht have received research funding (third-party funding) from Biotest AG, Dreieich, Germany.

Prof. Hamprecht has also received reimbursement of continuing education and travel costs as well as lecture fees from Abbott, Roche and Siemens. He has made all lecture fees available to the Tübinger HCMV Congenital Study via a third-party funding account of the University Hospital Tübingen (UKT).

References

1. Buxmann H, Hamprecht K, Meyer-Wittkopf M, Friese K: Primary human cytomegalovirus (HCMV) infection in pregnancy. Dtsch Arztebl Int 2017; 114: 45–52

2. Hamprecht K, Bissinger AL, Arellano-Galindo J, et al.: Intrafamilial transmission of human cytomegalovirus (HCMV): long-term dynamics of epitope-specific antibody response in context of avidity maturation. J Clin Virol 2014; 60: 119–26

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

4. Picone O, Vauloup-Fellous C, Cordier AG, et al.: A series of 238 cytomegalovirus primary infections during pregnancy: description and outcome. Perinatal Diagnosis 2013; 33: 751–8

5. Bilavsky E, Pardo J, Attias J, et al.: Clinical implications for children born with congenital cytomegalovirus infection following a negative amniocentesis. Clin Infect Dis 2016; 63: 33–8