Cell-free DNA versus sequential screening for fetal chromosomal abnormalities varied by age: a cost-effectiveness analysis

Abstract

Cell-free DNA (cfDNA) and sequential screening (SS) are frequently used for prenatal genetic screening. Though cfDNA has higher detection rates for common aneuploidies, SS may better identify risk for other nontargeted aneuploidies. We compared the cost-effectiveness of cfDNA versus SS for detection of fetal chromosome abnormalities across varied age cohorts. A decision-analytic model compared cfDNA versus SS for diagnosis of chromosomal abnormalities across different maternal age cohorts stratified by 5-year increments of < 20, 20-24, 25-29, 30-34, 35-39, 40-44, and >45 years. Chromosomal abnormalities included trisomy 21 (T21), trisomy 18 (T18), trisomy 13 (T13), 45X syndrome, sex chromosome abnormalities (SCA), and other nontargeted chromosomal abnormalities . Probabilities, costs, and utilities were derived from literature and varied in sensitivity analysis. The primary outcome was incremental cost per quality-adjusted life year (QALY). We also considered affected neonates, missed prenatal diagnoses, procedure-related loss (PRL), pregnancy termination (TOP), stillbirth, and neonatal death (NND). The cost-effectiveness threshold was $100,000/QALY. SS was cost-effective for detection of all fetal chromosome abnormalities until age 39. Cell-free DNA was only cost-effective starting at age 40, with an Incremental Cost Effectiveness Ratio (ICER) of $51,919/QALY (40-44 years) and ICER $16,830/QALY ( >44 years). In all maternal age cohorts, cfDNA led to more frequent identification of T21, T18, T13, 45X and SCA but fewer other nontargeted chromosomal abnormalities. cfDNA was associated with more terminations and fewer stillbirths, NND, and PRL. The model was sensitive to the prevalence of T21. When varying the prevalence of T21 in the age 35-39 cohort cfDNA was cost effective when the prevalence of T21 was greater than 0.017 which corresponds with the prevalence of T21 at a maternal age of 39. Compared to cfDNA, SS is a cost-effective screening method for fetal chromosome abnormalities for pregnant persons under the age of 40 at a population-based level.View Large Image Figure ViewerDownload Hi-res image Download (PPT)