Highlight
Vein of Galen malformation (VOGM) is a severe congenital cerebrovascular anomaly with high perinatal mortality and neurodevelopmental impairment risk, especially in fetuses exhibiting widened falcine sinus diameters. A novel, ultrasound-guided in utero embolization procedure targeting the prosencephalic venous varix demonstrated feasibility and potential clinical benefits in improving survival and neurodevelopmental outcomes. However, this intervention carries increased risk of unscheduled and preterm deliveries, which must be carefully balanced against its benefits.
Study Background and Disease Burden
Vein of Galen malformation (VOGM) represents the most common congenital cerebrovascular anomaly characterized by abnormal arteriovenous shunting within the prosencephalic veins. This leads to significant hemodynamic burden on the fetal and neonatal circulatory system, predisposing to high-output cardiac failure, progressive brain injury, and poor neurodevelopmental outcomes. Severity correlates with the size of the mediolateral falcine sinus—an enlarged falcine sinus (>7 mm) portends a 90% mortality risk and a very low chance for normal developmental milestones at 6 months under current standard postnatal care.
Conventional postnatal management includes staged endovascular embolization, but the window for optimal intervention is often limited, and significant brain injury or cardiac failure may already be established by birth. Hence, there is a clinical unmet need to identify strategies to intervene antenatally to mitigate these risks and improve survival and developmental outcomes.
Study Design
This study, conducted at a single US center and approved by the institutional review board, enrolled fetuses diagnosed with VOGM, possessing a falcine sinus width of 7 mm or greater and without major brain injury based on fetal magnetic resonance imaging (MRI). Enrollment started on September 30, 2022, with follow-up extending through April 10, 2025.
The primary intervention was ultrasound-guided in utero embolization via transuterine, transcranial needle access. This approach involved microcatheterization of the prosencephalic venous varix with deployment of detachable coils to reduce abnormal arteriovenous shunting. Pre- and postembolization fetal MRI and echocardiography assessed anatomical and hemodynamic changes. Main outcomes focused on neonatal mortality and neurodevelopmental milestones at 6 months and beyond.
Key Findings
Seven fetuses were enrolled, with five successfully undergoing fetal embolization. The cohort’s mean maternal age was 32.4 years (range, 22-36), with fetuses at a mean gestational age of 35 weeks and 6/7 days (range, 33 6/7 to 37 1/7 weeks). The sex distribution was nearly balanced (3 females and 4 males). Prior to intervention, the mean falcine sinus diameter was 10.3 mm—associated with a 90% predicted mortality under conventional postnatal care and only 9% predicted likelihood of achieving six-month developmental milestones.
Post-intervention, overall mortality was 43%, substantially reduced from expectations. Among the embolized patients, 60% survived, with three surviving children aged 8, 18, and 24 months displaying no neurodevelopmental delays. This suggests that fetal embolization may improve survival and cognitive outcomes. Furthermore, four of seven patients required additional neonatal embolization procedures post-birth, indicating ongoing management necessity.
Hemodynamically, fetal echocardiography revealed a mean cardiac output decrease of 33.4% (range, 16%-46%) following fetal embolization, reflecting successful reduction of arteriovenous shunting. However, adverse events included a high rate (71.4%) of unscheduled deliveries among patients, with three of five unscheduled deliveries occurring preterm—a mean of 3.2 days post-intervention—highlighting increased risk of preterm birth associated with the procedure.
Expert Commentary
This pioneering interventional study provides compelling preliminary evidence that targeted, ultrasound-guided in utero embolization can feasibly transcend previous therapeutic barriers for severe VOGM with large falcine sinus diameters. The observed reduction in mortality and preserved neurodevelopment in some cases offers hope for modifying the disease trajectory at its earliest stages.
Nevertheless, the intervention is not without risks. The frequent unscheduled and preterm deliveries, potential maternal procedural risks, and the need for subsequent neonatal embolization illustrate considerable challenges. Experts emphasize that patient selection criteria must remain stringent, and multidisciplinary collaboration involving maternal-fetal medicine, pediatric neurology, interventional neuroradiology, and neonatology is essential.
Limitations include the small sample size and short-term follow-up. Larger multicenter trials and longer-term neurodevelopmental assessments are required to validate efficacy, safety, and to optimize timing and techniques.
Conclusion
In utero embolization for fetal Vein of Galen malformation represents a novel interventional advance with promising early outcomes in select high-risk fetuses. This modality holds potential to improve survival and neurodevelopmental prognosis by mitigating fetal hemodynamic compromise. However, increased rates of unscheduled and preterm delivery post-procedure necessitate cautious risk-benefit assessment. Future research should focus on refining procedural safety, expanding patient cohorts, and integrating multidisciplinary care pathways to translate this innovative approach into broader clinical practice.
References
- Orbach DB, Shamshirsaz AA, Wilkins-Haug L, et al. In Utero Embolization for Fetal Vein of Galen Malformation. JAMA. 2025;334(10):878-885. doi:10.1001/jama.2025.12363.
- Berenstein A, Lasjaunias P. Surgical Neuroangiography: Clinical and Endovascular Treatment Aspects in Adults and Children. 2nd ed. Springer; 2004.
- Wildgruber M, Riedel C, Jahnke K, et al. Congenital vein of Galen malformations: Prediction of postnatal outcome with prenatal MR imaging. Radiology. 2018;288(2):588-597. doi:10.1148/radiol.2018170991.
