Clinician‐reported chorionicity and zygosity assignment using single‐nucleotide polymorphism‐based cell‐free DNA: Lessons learned from 55,344 twin pregnancies

OBJECTIVE: Prenatal chorionicity assessment relies on ultrasound, which can be confounded by many factors. Noninvasive assessment of zygosity is possible using single nucleotide polymorphism (SNP)‐based cell‐free DNA testing. Our objective was to determine the relationship between provider‐reported chorionicity and SNP‐cfDNA assignment of twin zygosity. METHODS: All twin pregnancy blood samples received by a reference laboratory between September 27, 2017 and September 8, 2021 were included. Chorionicity assignment was requested on the requisition, recorded as; monochorionic (MC), dichorionic, or “don't know”. SNP‐cfDNA zygosity results, monozygotic (MZ) or dizygotic (DZ), were correlated with chorionicity assignment. RESULTS: 59,471 twin samples (median gestational age = 12.0 weeks at draw) were received and analyzed; 55,344 (93.1%) received zygosity assignment. SNP‐cfDNA reported 16,673 (30.1%) MZ and 38,671 (69.9%) as DZ. Provider‐reported chorionicity was compared to the zygosity assignment for each case. Of 6283 provider‐reported MC twins, 318 (5.1%) were reported as DZ using SNP‐cfDNA. CONCLUSION(S): One in 20 suspected MC twin pregnancies were reported as DZ using SNP‐cfDNA. Approximately 30% of 55,344 twin pregnancies were found to be MZ, including cases where chorionicity was unknown. SNP‐cfDNA zygosity assessment is a useful adjunct assessment for twin pregnancies, particularly those reported as MC or without determined chorionicity.