This is the first study in over two decades to provide important epidemiological data on the seroprevalence of CMV amongst pregnant women in Singapore. Our data estimated 71.7% of our antenatal population to be seropositive for CMV IgG. This is 15.3% lower than the seropositivity rate for CMV IgG reported by Wong and colleagues in 1998 (18), and supports our initial hypothesis that the proportion of women seropositive for CMV IgG is likely to have fallen with improved hygiene and socioeconomic conditions in Singapore.
This seroprevalence rate is higher than that reported in France (15), similar to Italy (19) and Finland (20), and lower than countries like Japan (21), China (22), Romania (23), and Pakistan(24), where seroprevalence rates close to 100% have been reported (Table I). The chronologic change of CMV seroprevalence observed in our country is similar to that reported in other countries, such as Spain and Germany, which observed statistically significant decreases in IgG positivity in their population over the past decade (25,26). Interestingly, this change has not been universal among developed countries, even within Asia. South Korea continued to report a high seroprevalence of CMV at 94.1% between 2006 and 2015, without significant change in CMV seropositivity since 1995 (27).
Wong and colleagues (18) previously studied the influence of age on CMV seropositivity, and reported an increased seroprevalence in women above 30 years of age (80.8% for age >30 vs 76.5% for age ≤30). This trend has persisted, and our study found a seroprevalence of 73.0% in women aged 30 years and older versus 68.9% in those under 30 years of age (P=0.66). The 100% CMV IgG positivity reported in the <20-year age group is unlikely to be representative of the seroprevalence in that age group as only two samples were available for analysis in that cohort.
Table I.
CMV seroprevalence in pregnant women of different countries
|
Leruez-Ville et al, 2017 (15)
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Trombetta et al, 2021 (19)
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Our study, 2021
|
Kaneko et al, 2023 (21)
|
Waseem et al, 2017 (24)
|
Country
|
France
|
Italy
|
Singapore
|
Japan
|
Pakistan
|
Number of participants (n)
|
2378
|
360
|
385
|
1163
|
172
|
CMV seroprevalence in antenatal population (%)
|
61
|
70.8
|
71.7
|
82.5
|
99.4
|
A declining trend in CMV seropositivity in women of reproductive age is important from a public health standpoint for two reasons. Firstly, as larger proportion of women will now be at risk of acquiring primary CMV infection during pregnancy, primary prevention efforts will be more important. Our data suggests that more than a quarter (109/385, 28.3%) of women were seronegative for CMV at the start of their pregnancy.
Primary CMV infections have a higher risk of vertical transmission, symptomatic congenital infection and more severe sequelae compared to non-primary infections (28). These incidences can be reduced through preventative measures such as hygiene interventions (29,30). Examples include avoiding contact with infected bodily fluids (e.g. saliva, tears and urine), hand hygiene and regular cleaning of potential fomites such as diaper change areas and toys (31). These measures need to be undertaken during the preconception period and throughout pregnancy and are particularly important for women living in households with young children as they are a frequent source of CMV and can shed the virus for extended periods after infection (32).
The lack of public health education on CMV is reflected in a local study published by Lim and colleagues, who reported that only 20% of pregnant women attending antenatal care had heard of CMV (33). With a larger proportion of pregnant women who are now at risk of primary CMV infections, public health interventions focusing on improving prenatal education of CMV infections in pregnancy and behavioural modifications to reduce the risk of acquisition are urgently needed.
The second important public health consideration is that with fewer women being seropositive, it is anticipated that the incidence of congenital CMV infections is likely to rise. This means that secondary prevention efforts such as antenatal screening and treatment will become more important as well. Antenatal serological screening can be done in the first trimester to detect periconceptional and first trimester primary infections that pose the highest risk of fetal sequalae (14). Treatment wise, data from Shahar-Nissan and colleagues has suggested that daily administration of 8 grams of valaciclovir in women with primary CMV infection acquired early in pregnancy resulted in a 71% reduction in the rate of fetal transmission when compared to placebo (34). A recent systematic review similarly concluded that prenatal valacyclovir administration with maternal primary CMV infection reduces the risk of congenital CMV infection, with a low risk of reversible acute renal failure (35).
In terms of cost, cost-effectiveness studies on screening for congenital CMV infection have shown the prevalence of congenital CMV infection to be an important factor influencing incremental cost-effectiveness ratios (36). Offering screening therefore may become more cost-effective in light of these updated lower seroprevalence rates where a larger proportion of women are at risk. Further studies evaluating the cost-effectiveness of universal maternal CMV screening with subsequent antenatal valacyclovir treatment in the local context are needed.
In conclusion, the seroprevalence of CMV in pregnant women has decreased compared to 20 years ago. As a larger proportion of pregnancies are now at risk of congenital CMV, primary and secondary prevention efforts to reduce the incidence of primary CMV infections during pregnancy will become more important. This study provides a much-needed update on the changing CMV seroprevalence in the antenatal population in Singapore, more than 20 years after the first study of its kind. The sample size of this study is also three times larger than that of the previous study. We acknowledge the study’s limitation in terms of its single-centre nature; nevertheless, it remains representative of the national data as samples were randomly selected and include the varying demographics of pregnant women in Singapore. A multicenter cohort study with a larger number of participants will be helpful to provide a better picture on the overall CMV seroprevalence in the antenatal population in Singapore.