OC17.03: Correlation of SNP‐based prenatal cfDNA and clinical findings of a complete mole with a coexisting fetus

Complete hydatidiform mole with a coexisting fetus (CHMCF) is associated with high risk for pregnancy complications including fetal loss, pre-eclampsia, preterm birth, and invasive trophoblastic disease. We report on SNP-based prenatal cell free DNA (cfDNA) screening reported as having an atypical SNP pattern compatible with CHMCF. The study included cfDNA samples received 6/1/2014 - 11/30/2023. The analysis was restricted to results with complex, but distinct SNP-patterns compatible with a twin or triploid pregnancy and with evidence for complete uniparental disomy, a combination suspicious for CHMCF. Gestational age and clinical findings from the test requisition form and, where available, pregnancy outcomes, were reviewed. Of 4,901,007 prenatal cfDNA samples received, 75 had a SNP profile apparently consistent with CHMCF (1 in 63,350). Mean gestation at screening was 13 weeks. Clinical information was available in 55/75 (73.3%) cases. 3/55 (5.5%) were IVF pregnancies. In 40/55 (72.7%), ultrasound findings, placental pathology, or HCG levels were compatible with the presence of a complete or partial molar placenta, with at least 13/55 (23.6%) consistent with CHMCF. Fetal abnormalities detected by ultrasound were reported in 4 (7.3%) cases. Mean gestation at cfDNA testing in cases without evident abnormal ultrasound findings was 14 weeks and might have been too early to identify fetal or placental abnormalities. Specific SNP-based cfDNA patterns provided early identification of CHMCF or triploid pregnancies, with most (73%) having prenatal findings compatible with molar change. Given the high risk of pregnancy complications associated with CHMCF, these rare results should receive prompt referral for high-risk pregnancy management, detailed ultrasound evaluation, placental pathology at delivery, and pre- and postpartum surveillance of serum HCG levels.