Prenatal genetic diagnosis and pregnancy outcomes of the surviving co-twin after spontaneous single intrauterine fetal demise.

Spontaneous single intrauterine fetal demise (SSIUFD) in twin pregnancies is a special condition of stillbirth. When SSIUFD occurs, clinical attention understandably shifts to the surviving co‑twin. This study aimed to investigate the genetic profiles and perinatal outcomes of surviving co-twins following SSIUFD. This retrospective study reviewed 88 twin pregnancies complicated by spontaneous SSIUFD that underwent invasive prenatal testing between January 2015 and December 2024. Cases of elective fetal reduction and those with unknown chorionicity were not included. The cohort included 54 dichorionic diamniotic (DCDA) and 34 monochorionic diamniotic (MCDA) pregnancies. According to gestational age at the single twin demise, they were classified into the first-trimester SSIUFD (≤ 12 weeks’ gestation) and the second-trimester SSIUFD group (> 12 weeks’ gestation). Genetic evaluation was performed using karyotyping and/or single nucleotide polymorphism (SNP) array analysis on samples of amniotic fluid (n = 85) and cord blood (n = 3). The prognosis of the surviving co-twins including prenatal ultrasound monitoring and delivery outcome were collected and analyzed according to the gestational age at fetal demise and chorionicity. Of 88 cases, 24 (27.3%) cases underwent invasive prenatal diagnosis because of SSIUFD alone, while the remaining 64 (72.7%) cases had additional clinical indications. Among the 24 cases tested for SSIUFD alone, no clinically significant chromosomal abnormalities were detected (0/24, 0%). A low incidence of chromosomal abnormalities (1.1%, 1/88) was observed, with one case of trisomy 21 in a MCDA pregnancies, both twins exhibiting concordant ultrasound anomalies. SNP array analysis revealed no pathogenic submicroscopic variants in 68 analyzed cases. Among 83 cases with follow-up information available, MCDA pregnancies showed significantly higher termination rates than DCDA (19.4% vs. 1.9%, p < 0.05), primarily due to severe anomalies or subsequent fetal demise followed SSIUFD. Overall, term deliveries occurred in 81.9% and preterm birth (PTB) in 9.6%, with comparable PTB rates (p > 0.05) between DCDA (13.5%) and MCDA (6.5%) groups, or between the first- (6.0%) and the second-trimester SSIUFD group (15.2%). Our findings do not provide evidence for an increased detection rate of chromosomal abnormalities in surviving co-twins after SSIUFD, particularly in surviving co-twins without other indications. Surviving co-twins from MCDA pregnancies are associated with a higher risk of adverse outcomes, including termination due to fetal malformations and subsequent fetal demise. This highlights the importance of close ultrasound monitoring in these cases.