Pregnancy Outcomes in Women With Vascular Ehlers-Danlos Syndrome: A Systematic Review of Maternal and Fetal Complications.

The Ehlers-Danlos syndromes (EDS) comprise a clinically and genetically heterogeneous group of heritable connective tissue disorders marked by skin hyperextensibility, joint hypermobility, and tissue fragility. Vascular EDS (vEDS) is an autosomal dominant disorder caused by pathogenic variants in COL3A1, the gene encoding type III collagen. The diagnosis of vEDS is confirmed by identifying a pathogenic variant in COL3A1. This systematic review was conducted according to the PRISMA guidelines. Major outcomes included maternal, fetal, and neonatal complications in EDS pregnancies. A comprehensive search was conducted using electronic databases, including PubMed, Cochrane Library, and ScienceDirect, from inception to April 2026. vEDS showed the highest risk profile, with maternal mortality ranging between 0.10% and 50%; however, this wide range is attributed to the inclusion of old studies, in which recent advancements in genetic testing and fetal genotyping were not used. The most common reported obstetric complications were preeclampsia, postpartum hemorrhage, and severe perineal tears. Premature rupture of membranes and preterm premature rupture of membranes were strongly associated with fetal EDS. Preterm birth is the most common complication, ranging between 8.9% and 48.8% of pregnancies across the included studies. Fetal EDS and COL3A1 mutations were more commonly associated with pregnancy complications than the maternal disease itself. Pregnancies complicated by EDS are associated with maternal, fetal, and neonatal complications. vEDS is associated with an increased risk of maternal mortality and a high prevalence of preterm birth. This systematic review underscores the significance of fetal EDS status and COL3A1 variants as a strong predictor of EDS pregnancy complications.