First-trimester cytomegalovirus screening found to be cost-effective

Screening for primary cytomegalovirus (CMV) during the first trimester may be cost-effective by allowing treatment provision, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Over 50% of US individuals are infected by CMV by the age of 40 years. In pregnancy, this can lead to congenital cytomegalovirus (cCMV), which is the primary infectious source of birth defects in US offspring.² This has led to increased focus in managing this condition among clinicians and researchers.¹

“However, universal screening for CMV during pregnancy has long been opposed in the US, as screening is complex, given the need for differentiation between primary and secondary infections, and previously, no treatments were known to prevent vertical transmission of CMV,” wrote investigators.

Screening and treatment pathways

As new CMV treatments have emerged in recent years, investigators built a decision-analytic model to evaluate the cost-effectiveness of first-trimester primary CMV screening. Inputs for the model were found through searches of the PubMed database, with a theoretical cohort of 2,869,141 patients established.

Study groups included patients receiving primary CMV in the first trimester and those without screening. Baseline primary CMV rates in US patients were used to determine true primary CMV cases. When undergoing screening, patients received testing with a serum IgG, followed by assessment with a serum IgM.

In the model, valacyclovir treatment was only applied to patients identified with primary CMV. False negative screenings or cases of no screening in patients with primary CMV were assumed to have cCMV identified by abnormal ultrasound findings. It was also assumed that treatment would not be given to patients with no screening or without positive results.

Cost considerations

An analysis of a randomized controlled trial and 2 cohort studies were referenced to estimate CMV transmission rates to the fetus in patients with and without treatment. A branch was also included for women diagnosed with CMV but declining amniocentesis.

Alongside vertical CMV transmission, stillbirths, abortions, neonatal deaths, neurodevelopmental disability, hearing loss, quality-adjusted life years (QALYs), and costs were reported as outcomes, with the latter based on a societal perspective. Costs and QALYs were both discounted at an annual rate of 3%.

Relevant costs included excess cCMV management costs in the first year of life and costs of valacyclovir treatment and CMV screening, obtained from Centers for Medicare and Medicaid Services databases. Literature was assessed for all other costs.

Findings on cost-effectiveness

There were 2,869,141 pregnant patients included in the theoretical cohort, with CMV screening and treatment linked to 2898 less vertical transmissions, 94 fewer abortions, 19 fewer stillbirths, and 11 fewer neonatal deaths. Screening and treatment were also linked to reductions in hearing loss and neurodevelopmental disability of 460 and 263, respectively.

Overall, universal screening was estimated to save 242.2 million dollars and lead to 3437 additional QALYs. Additionally, the willingness to pay threshold was never crossed, indicating no significant changes from an individual variable’s uncertainty. The model also highlighted a negative correlation between the efficacy of screening and the utility of hearing loss.

Cost-effectiveness was even reported when reducing the specificity of the tests by over 60%. In a univariable sensitivity analysis, the cost-effectiveness of universal screening was increased up to 17-fold vs the current cost of screening tests. Finally, a multivariable analysis indicated cost-effectiveness from universal screening in 100% of samples.

Implications

The results indicated cost-effectiveness from primary CMV infection screening in the first trimester followed by treatment with valacyclovir. Investigators recommended further research to address contradictions between this data and prior cost-effectiveness studies.

“To support that effort, further primary research, particularly with larger sample sizes, is needed to provide more evidence that valacyclovir or other CMV treatments are effective and safe in pregnancy,” wrote investigators.

References

1. Dzubay SK, Gagliuso AH, Arora M, et al. Universal screening and valacyclovir for first trimester primary cytomegalovirus: a cost-effectiveness analysis. Am J Obstet Gynecol. 2025;233:191.e1-9. doi:10.1016/j.ajog.2025.02.009
2. Saldan A, Forner G, Mengoli C, Gussetti N, Palù G, Abate D. Testing for cytomegalovirus in pregnancy. J Clin Microbiol. 2017;55(3):693-702. doi:10.1128/JCM.01868-16