Cytomegalovirus (CMV) seroprevalence among women at childbearing age, maternal and congenital CMV infection: policy implications of a descriptive, retrospective, community-based study

Abstract

Background Maternal CMV infection during pregnancy, either primary or non-primary, may be associated with fetal infection and long-term sequelae. While guidelines recommend against it, screening for CMV in pregnant women is a prevalent clinical practice in Israel. Our aim is to provide updated, local, clinically relevant, epidemiological information about CMV seroprevalence among women at childbearing age, the incidence of maternal CMV infection during pregnancy and the prevalence of congenital CMV (cCMV), as well as to provide information about the yield of CMV serology testing. Methods We performed a descriptive, retrospective study of women at childbearing age who were members of Clalit Health Services in the district of Jerusalem and had at least one gestation during the study period (2013–2019). We utilized serial serology tests to determine CMV serostatus at baseline and at pre/periconception and identified temporal changes in CMV serostatus. We then conducted a sub-sample analysis integrating inpatient data on newborns of women who gave birth in a single large medical center. cCMV was defined as either positive urine CMV-PCR test in a sample collected during the first 3 weeks of life, neonatal diagnosis of cCMV in the medical records, or prescription of valganciclovir during the neonatal period. Results The study population Included 45,634 women with 84,110 associated gestational events. Initial CMV serostatus was positive in 89% women, with variation across different ethno-socioeconomic subgroups. Based on consecutive serology tests, the detected incidence rate of CMV infection was 2/1000 women follow-up years, among initially seropositive women, and 80/1000 women follow-up years, among initially seronegative women. CMV infection in pregnancy was identified among 0.2% of women who were seropositive at pre/periconception and among 10% of women who were seronegative. In a subsample, which included 31,191 associated gestational events, we identified 54 newborns with cCMV (1.9/1000 live births). The prevalence of cCMV among newborns of women who were seropositive at pre/periconception was lower than among newborns of women who were seronegative (2.1 vs. 7.1/1000). Frequent serology tests among women who were seronegative at pre/periconception detected most primary CMV infections in pregnancy that resulted in cCMV (21/24). However, among women who were seropositive, serology tests prior to birth detected none of the non-primary infections that resulted in cCMV (0/30). Conclusions In this retrospective community-based study among women of childbearing age characterized by multiparity and high seroprevalence of CMV, we find that consecutive CMV serology testing enabled to detect most primary CMV infections in pregnancy that led to cCMV in newborns but failed to detect non-primary CMV infections in pregnancy. Conducting CMV serology tests among seropositive women, despite guidelines' recommendations, has no clinical value, while it is costly and introduces further uncertainties and distress. We thus recommend against routine CMV serology testing among women who were seropositive in a prior serology test. We recommend CMV serology testing prior to pregnancy only among women known to be seronegative or women whose serology status is unknown.

Implementation of pooled saliva tests for universal screening of cCMV infection

“…While it is somewhat lower than the 4–7 per 1,000 birth prevalence previously reported in two small studies 39 , 47 and in one similar-scale study 48 in Israel, the findings highlight the importance of ongoing large-scale screening in defining the true population prevalence of cCMV. In this regard, it is noteworthy that the population of Jerusalem uniquely consists of segregated communities characterized by different maternal fertility and seroprevalence rates 49 . As cCMV prevalence varies considerably according to ethnic grouping, ethnicity and maternal seroprevalence 1 , 4 , 9 , 12 , 50 , it will be important to further assess the prevalence of cCMV in distinct subpopulations.…”

Features of cellular immunity in newborns with cytomegalovirus infection

“…Dadashova 1 , X.F. Aliуeva 1 1 Scientific Research Institute of Obstetrics and Gynecology, 2 Lenkoran Perinatal Center, Baku, Azerbaijan Keywords: newborn, immune system, viruses, cytomegalovirus infection, cellular immunity Cytomegalovirus infection (CMVI) is gaining increasing significance in modern clinical medicine [1][2][3][4][5][6][7][8]. As a cause of mortality in cases of monospecific disease origin or as a competing condition, CMVI ranks fourth after influenza, herpes, and adenovirus infections.…”

Decoding human cytomegalovirus for the development of innovative diagnostics to detect congenital infection

“…In developed countries, 4 in 10 women of reproductive age are seronegative for HCMV, and 5-10% of these women will experience a primary HCMV infection during their pregnancy. 26 , 27 In the United States, seroprevalence increases with age and varies by race/ethnicity, resulting in the highest cCMV prevalence in black (9.5/1000 live births), followed by Hispanic white (3.0/1000 live births) and non-Hispanic white (2.7/1000 live births) newborns. 10 These differences remain after controlling for household income level, education, marital status, area of residence, census region, family size, country of birth, and type of medical insurance.…”