Society for Maternal-Fetal Medicine Consult Series #74:Cell-free DNA screening for aneuploidies: Updated guidance

In this Consult, we provide updated guidance on the evolving applications of cell-free DNA (cfDNA) screening, including its use in detecting sex chromosome aneuploidies and microdeletions and its application in multifetal gestations. We compare cfDNA test performance with conventional screening methods and offer recommendations for managing inconclusive results and unexpected secondary findings. The following are the Society for Maternal-Fetal Medicine's (SMFM's) recommendations: (1) we recommend that cfDNA screening for common aneuploidies (trisomies 21, 18, and 13) be made routinely available to all obstetrical patients (GRADE 1B); (2) we recommend cfDNA as the most sensitive and specific screening test for common fetal aneuploidies (trisomies 21, 18, and 13) in any patient population. After pretest counseling, every patient has the right to pursue or decline prenatal genetic screening and diagnostic testing (GRADE 1B); (3) we recommend that screening for sex chromosome aneuploidies be made available to obstetrical patients as an “opt-in” consideration with appropriate pretest counseling (GRADE 1C); (4) we do not recommend routine general population screening for any microdeletion condition. Patients who choose to undergo cfDNA screening for 22q11.2 deletion specifically should do so only after appropriate pretest counseling. Pregnant people who are interested in obtaining information regarding the risk for fetal copy number variants should be offered diagnostic testing as opposed to cfDNA screening for microdeletion syndromes (GRADE 1C); (5) we recommend cfDNA as a first-line screening option for trisomy 21 detection in twin gestations (GRADE 1B); (6) although the numbers of affected pregnancies are limited, the detection rates associated with trisomy 18 and 13 appear to be consistently high in twin gestations, and cfDNA screening for these conditions is recommended (GRADE 1B); (7) because of a lack of data, cfDNA screening for sex chromosome aneuploidy in twin gestations and cfDNA screening for higher-order multiples are not recommended (GRADE 1C); (8) we do not recommend the routine use of cfDNA testing for large genome-wide copy number deletions or duplications (GRADE 1C). This document replaces SMFM Consult Series #36: Prenatal aneuploidy screening using cfDNA.