Applications for cell‐free fetal DNA testing beyond common aneuploidy

Key content Cell‐free fetal DNA (cffDNA) screening test performance for sex chromosome aneuploidies (SCAs), copy number variants (CNVs), rare autosomal trisomies (RATs) and single gene disorders. cffDNA screening for detection of pre‐eclampsia and malignancy. Investigation of recurrent miscarriage using cffDNA. Alternative approaches to interrogating free fetal DNA. Learning objectives To appreciate there is a lack of robust evidence regarding cffDNA screening test performance for expanded applications. To understand that some but not all countries endorse SCA screening and screening for some CNVs such as 22q.11.2 microdeletion syndrome. To be aware that expanded applications of cffDNA screening pose interpretational and ethical challenges. To be aware that the diagnostic confirmatory test of choice following a high‐chance screening result for the aforementioned conditions is an amniocentesis. Ethical issues Indirect sex determination may occur with SCA screening. Expanded applications for cffDNA screening in the UK fall outside recommendations.