Ultrasound and SNP-based cell-free DNA zygosity testing in twin pregnancies

Introduction The importance of prenatal determination of chorionicity for the management of twin pregnancies is well recognized. However, research on the contribution of prenatal evaluation of zygosity to the management of twins is limited. We assessed the utility of adding SNP-based cell-free DNA (cfDNA) zygosity testing to ultrasound chorionicity assessment for the clinical management of twin pregnancies.Methods Prospective observational study involving 13 United States practices with proficiency in prenatal ultrasound. Patients diagnosed by ultrasound with twins in the first trimester were assessed with cfDNA screening for zygosity. Ultrasound assessment of chorionicity was performed prior to cfDNA results. Placental pathology was used as the gold standard for chorionicity assessment. Gestational age at delivery and standardized birthweights were compared, based on chorionicity and zygosity.Results 110 twin pregnancies were included. Among 79 dichorionic (DC) cases confirmed by placental pathology, one (1.3%) was misclassified as monochorionic (MC) by ultrasound, but was dizygous (DZ) by cfDNA, consistent with DC. Of 31 monozygotic (MZ) twins by cfDNA, confirmed as MC by pathology, ultrasound misclassified one (3.6%) as DC. Median gestational age at delivery was earlier for MZ twin pregnancies (35.0 weeks) compared to DZ (36.9 weeks, p = 0.02). After adjusting for fetal sex and gestational age at birth, MZDC twins had significantly lower birthweights (p = 0.006) and birthweight percentiles (p = 0.004) than DZDC twins.Conclusions Based on postpartum placental pathology as the reference standard for determining MC versus DC, cfDNA zygosity testing appears to aid in the prenatal assignment of chorionicity. Larger studies are needed to confirm the value of zygosity testing in the management of twin pregnancies.