Seroprevalence of CMV IgG and IgM in Korean women of childbearing age

Abstract Background The aim of this study was to investigate the seroprevalence of cytomegalovirus (CMV) infection using the serologic status of CMV IgG and IgM antibodies in Korean women of childbearing age. Methods We retrospectively reviewed CMV IgG and IgM test results from Korean women aged 15–49 years who underwent testing between January 2009 and December 2019. Seroprevalence of CMV IgG and IgM by year and age was investigated. Results The study period was 11 years, and among 6837 samples tested, 95.8% were CMV IgG–positive. The seropositivity in women aged 15‐ <20 years was significantly lower (77.5%) than older age groups. Among 6837 total CMV IgG tests, 75.9% (5186) had concurrently measured CMV IgM results among which 2.4% were IgM‐positive. Conclusion Considering the low CMV seropositivity of women younger than 20 years, they may need prenatal education for CMV infection.


| INTRODUC TI ON
Cytomegalovirus (CMV) is a human herpes virus affecting 66%-90% of adults worldwide. 1 While the primary infection is often asymptomatic, CMV establishes a lifelong latent infection that can become active in both immunocompetent and immunosuppressed carriers. 2 CMV infection during pregnancy can result in congenital infection of the foetus. 2 The range of disease severity of congenital CMV infection is very wide, from normal development to sensorineural hearing loss, chorioretinitis, and cognitive or neurologic deficits that may be mild or severe. 2,3 For diagnosis of CMV infection, serology tests, such as CMV IgG and IgM, can be used. 2,4 Seroepidemiologic studies (seropositivity) using these tests can provide information on disease control because individuals with no history of exposure to CMV infection may be at high risk of primary infection, and seropositive individuals can experience reactivation of latent CMV. 1 Recent studies have reported changes in global seroepidemiology of CMV based on geographic, ethnic, cultural and socioeconomic factors. 1,5,6 Previous studies' different ethnic populations used different analytical platforms and different seroprevalence of CMV over different study periods. 1,5 However, limited data are available for CMV seroprevalence in the Korean population. 7,8 Previous studies performed in Korean women include only CMV IgG seroprevalence without CMV IgM seroprevalence or information on age of subjects, which is important in CMV seroprevalence; data analysed were from earlier than 2015; or there were a limited number of study subjects. 1,6,8 Therefore, we aimed to investigate recent seroprevalence of CMV IgG and IgM test results in Korean women overall and by year and age in this study.

| MATERIAL S AND ME THODS
We retrospectively reviewed the laboratory information system data from Green Cross Laboratories between 1 January 2009 and Green Cross Laboratories, one of the largest referral clinical laboratories in South Korea, provides clinical specimen analysis services including CMV IgG and CMV IgM chemiluminescence immunoassays (Architect i2000SR; Abbott Laboratories). A 'reactive (+)'result interpretation for the CMV IgG assay was any with ≥6.0 AU/ml. For qualitative interpretation of the CMV IgM assay, a 'reactive (+)' result was defined as that with ≥1.00 index, a 'non-reactive (−)' result was that with <0.85 index, and 'grey zone' results were for 0.85-0.99 index.
Patients with missing data for age or sex were excluded. Because the aim of this study was to investigate seroprevalence in Korean women of childbearing age, repetitive test results were excluded.
All data were anonymized prior to statistical analysis. A public da-

| RE SULTS
During the 11-year study period, 7436 CMV IgG tests from 6837 Korean women aged 15-49 years were obtained from the labora-  Table 1. Seroprevalence of CMV IgG and IgM in Korean women by age and year is summarized in Table 2. Annual changes in the rate of 'non-reactive' CMV IgG

| DISCUSS ION
We investigated seroprevalence of CMV IgG and IgM in Korean women of childbearing age (15-49 years) over 11 years. The overall seroprevalence in Korean women was 95.8%, higher than the global CMV seroprevalence of 86.0%. 1 The rate of positive CMV IgG was lowest (less than 80%) in women younger than 20 years. Previous studies performed in Korean women reported that overall CMV IgG seroprevalence was 98.1% in pregnant women investigated in 2008 6 and 97.0% in women of childbearing age (15-49 years) investigated during 1995-2015. 8 In a later study, the seroprevalence of CMV IgG in women aged 15-19 years was 83.8%, comparable to that in the present study. 8 In the present study, CMV IgG seronegativity by year ranged from 1.8% to 7.7% (Figure 1). This is a large difference that is most likely due to the age make up of women tested in a given year (  9 and Africa (ranged from 0% to 15.5% through systematic review of the literature). 10 A previous study performed in the United States using NHANES III 1998-1994 reported overall 5.3% CMV IgM prevalence in 12-to 19-year-old women. 11 Overall CMV IgM seroprevalence in the present study (2.4%) was comparable to that of other studies performed in Korea, Norway and the United States. 5,7,11 Difference in seroprevalence might be due to differences in pre-analytical (ethnic and cultural differences) and analytical factors (analytical platform). 1,5 The incidence of congenital CMV infection among previously seronegative pregnant women in the United States ranges from 0.7% to 4.0%. 12 A previous study performed in the United States of giving birth to a child with congenital CMV infection in their subsequent pregnancies than women in the general population, education and prevention strategies for mothers in this age group may be needed. 2,13 In this study, about 3.0% of test results were IgG+/IgM+ (2.3%), IgG-/IgM+ (0.1%), or IgG+/IgM grey zone (0.6%), indicating subjects requiring further laboratory tests to distinguish primary CMV infection from past CMV infection/reactivation. 4 A previous study performed in pregnant Korean women reported rates of CMV IgG+/ IgM+1.3% and CMV IgG+/IgM grey zone 0.4% comparable to the present study. 7 A previous study performed in pregnant Japanese women reported IgG+/IgM+ (4.3%), IgG-/IgM+ (0.2%) and IgG+/IgM grey zone (1.2%), rates about two times higher than those of the present study. 14 Although there was no significant difference between annual number of congenital CMV infection and CMV IgG or IgM results in this study, the number of congenital CMV infections was more than five to 10 times higher than that of congenital rubella infection, with fewer than 10 annual cases under nationwide disease control with an immunization programme. 6 However, the efficacy of a national health screening programme for CMV infection still needs to be investigated. 4,14,15 Future studies regarding the efficacy of CMV screening in large populations are needed.
One limitation of this study was the lack of clinical information, such as symptoms of infection. However, because 25%-50% of pregnant women with primary CMV infection are asymptomatic, serologic tests can provide important information. 2

TA B L E 2 Seroprevalence of CMV IgG and IgM in Korean women by age and year
Year 2009  2010  2011  2012  2013  2014  2015  2016  2017  2018  2019  Total   CMV IgG   15-<20 years, total (n)  19  25  14  20  25  26  18  17  10  6  1  181 Non-reactive (n)  4  7  3  3  3  10  7  6  3  1  0  47   Reactive (n)  15  18  11  17  22  16  11  11  7  5  1  In conclusion, this study investigated seroprevalence of CMV IgG and IgM in Korean women of childbearing age. Considering the rate of seronegative CMV IgG in women younger than 20 years, education and prevention for young mothers may be needed. The results of this study could be used as foundational knowledge for strengthening disease control and prevention of congenital CMV infection.

CO N FLI C T O F I NTE R E S T
None declared.

AUTH O R CO NTR I B UTI O N S
All authors contributed to manuscript preparation; R. Choi

DATA AVA I L A B I L I T Y S TAT E M E N T
The datasets generated and analysed during the current study are available from the corresponding authors on reasonable request.