Universal screening and valacyclovir for first trimester primary cytomegalovirus: a cost-effectiveness analysis

Abstract

Background: Universal prenatal screening for cytomegalovirus is not currently recommended in the United States, as no effective interventions have previously been available. With growing evidence that treating maternal first trimester primary cytomegalovirus infections with valacyclovir reduces vertical transmission, universal screening may become an important tool in congenital cytomegalovirus prevention.

Objective: This study examined the cost-effectiveness of a universal screening approach for maternal cytomegalovirus in the first trimester of pregnancy followed by valacyclovir treatment in positive cases for prevention of the sequelae of congenital cytomegalovirus.

Study design: A decision-analytic model was constructed to compare outcomes of universal screening and subsequent valacyclovir treatment in a theoretical cohort of 2,869,141 individuals, the estimated number of pregnant people in the United States who receive prenatal care by the first trimester. Individuals found to be immunoglobulin G positive, immunoglobulin M positive, and to have low immunoglobulin G avidity were considered to have primary cytomegalovirus infection and received valacyclovir. Outcomes included cases of vertical cytomegalovirus transmission, abortions, stillbirths, neonatal deaths, cases of hearing loss, cases of neurodevelopmental disabilities, costs, and quality-adjusted life years. Model inputs were derived from literature. Sensitivity analyses were performed via tornado analysis, univariable sensitivity analysis, and multivariable sensitivity analysis with Monte Carlo simulation.

Results: In our study, universal screening in the first trimester for primary cytomegalovirus and subsequent treatment with valacyclovir in positive cases decreased adverse outcomes by preventing 2898 vertical transmissions, 94 abortions, 19 stillbirths, 11 neonatal deaths, 460 cases of hearing loss, and 263 cases of neurodevelopmental disability. Universal screening and subsequent treatment was the dominant strategy as it saved 242.2 million dollars and led to 3437 additional quality-adjusted life years. Tornado analysis demonstrated that there were no threshold values which would change the model results, when all variables were varied across a predetermined range. Univariable sensitivity analyses demonstrated that even with decreasing specificity of screening tests, decreasing maternal utility of neonatal hearing loss, and increasing the price of screening up to 17 times the current cost, universal screening remained the cost-effective strategy. Monte Carlo analysis demonstrated that the screening strategy remained cost-saving in 100% of trials.

Conclusion: Our results demonstrate that screening for first trimester primary cytomegalovirus may be a cost-saving intervention, as identification of cases allows for the provision of treatment, which in turn reduces vertical cytomegalovirus transmission and costly sequelae.

Keywords: congenital infections; infectious disease; preventive health; public health; screening.