885: Cell-free fetal DNA screening for detection of microdeletion syndromes: A cost-effectiveness analysis

Abstract

Copy number variants including microdeletion syndromes are poorly detected through traditional screening. While they can be diagnosed with invasive testing with chromosomal microarray analysis, cell-free DNA (cf DNA) screening is also currently available for detection of select microdeletions. Our study aims to investigate the costs and outcomes associated with detection of five microdeletion syndromes, using cf DNA to screen for microdeletions and aneuploidy compared to cf DNA for aneuploidy alone but in conjunction with ultrasound. A decision-analytic model was constructed using TreeAge software to compare cf DNA with microdeletions versus cf DNA with aneuploidies plus ultrasound in a theoretical cohort of 4,000,000 pregnancies for detection of 22q11.2, Prader-Willi, Angelman, Cri-du-chat, and 1p36 deletion syndromes. All probabilities, costs, and utilities were derived from literature. The primary outcome was incremental cost per quality-adjusted life year (QALY) in addition to terminations and procedure-related losses. Because the microdeletion results are available on all cf DNA testing, we set the incremental cost of cf DNA microdeletion screening to zero at baseline, but varied the cost in sensitivity analysis. Screening with cf DNA for microdeletions among all pregnant women would result in 75 fewer anomalous neonates as compared to cf DNA with ultrasound (Table). This reduction is due to increased termination rates of fetuses with microdeletions in this group. Routine use of cf DNA with microdeletions resulted in more procedure- related losses and losses of normal fetuses. cf DNA with microdeletions would improve effectiveness by 752 QALYs and decrease cost by $83,524,493. When we varied the specificity of the screening test, we found that it remained cost-effective down to a specificity of 92%. With a threshold of $100,000/QALY, microdeletion screening is cost- effective up until an incremental cost over cf DNA for aneuploidy alone of $39.60 (Figure). For fetal detection of subchromosomal abnormalities in pregnancy, cf DNA with microdeletions is a cost-effective strategy compared to cf DNA for aneuploidies and ultrasound. The test characteristics of cf DNA with microdeletions require greater examination and study before being routinely recommended.View Large Image Figure ViewerDownload Hi-res image Download (PPT)