Preliminary study results published in the Journal of the American Medical Association (JAMA) have shown that in-utero embolisation may be a feasible option in the management of foetal vein of Galen malformation (VOGM), having led to improvements in survival and overall outcomes across seven eligible patients treated at a single centre.
In their report summarising these new data, Darren Orbach (Boston Children’s Hospital, Boston, USA) and colleagues also posit that any potential reduction in mortality, brain injury and neurodevelopmental delays must be weighed against an increased risk of unscheduled, preterm delivery as a result of the procedure.
“To our knowledge, this is the first systematic effort to treat any congenital cerebrovascular condition through a foetal surgical approach by changing the dynamics of foetal brain blood flow,” Orbach et al write.
The researchers enrolled a total of seven foetal patients with VOGM and wide mediolateral falcine sinus diameters—a population known to suffer a heightened risk for mortality, brain injury, and neurodevelopmental delay—in a single-centre, single-group intervention study in the USA. Eligible foetuses had VOGM, no major brain injury on foetal magnetic resonance imaging (MRI), and a falcine sinus width of ≥7mm. In the study, foetal embolisations were ultrasound guided, and involved transuterine, transcranial needle access and microcatheterisation of the prosencephalic venous varix with detachable coils.
Across the seven enrolled patients (mean maternal age, 32.4 years; mean foetal gestational age, 251 days; four males), five ultimately underwent successful embolisation. Orbach et al note that the mean falcine diameter of 10.3mm corresponded to a 90% rate of expected mortality and a 9% likelihood of reaching six-month milestones with standard postnatal care at experienced centres. However, in the study, the overall mortality rate was 43%, while 43% of patients were meeting milestones at six months, and all three embolised patients who survived—aged eight, 18 and 24 months at time of study publication—did so without any neurodevelopmental delays. Foetal echocardiography revealed a mean reduction in cardiac output of 33.4% after embolisation.
The investigators also report that four of the seven enrolled patients (57.1%) underwent additional neonatal embolisation. Five of these seven patients (71.4%) had unscheduled deliveries due to circumstances relating to foetal embolisation, and three of these five were premature births taking place at an average of 3.2 days post-intervention.
“These early results demonstrate the feasibility of this in-utero approach,” Orbach et al write in JAMA. “Further studies are needed to rigorously assess outcomes, including mortality and neurodevelopmental morbidity, with comparison [versus] current standard-of-care postnatal management at expert centres.”
In their paper, the authors also relay multiple important lessons learned from the two foetal patients in whom embolisation could not be performed, including the fact that, in one case, transcranial needle access was not achieved. They note that “one of the most technically challenging aspects of the foetal intervention is crossing the skull with a needle using manual drilling”, and highlight the fact that a learning curve of “several attempts” appears to exist for successfully achieving transcranial access—a finding that was replicated across the two foetal surgeons within the study.
According to Orbach et al, another major observation that emerged was the significant rate of unscheduled delivery associated with the embolisation procedures.
“Notably, these pregnancy complications have not been seen with such frequency following other needle-based foetal interventions, such as those for congenital heart disease,” they add. “While there are multiple differences between foetal VOGM and foetal cardiac interventions, two stand out as potentially relevant: mean gestational age at the time of intervention [26 weeks for cardiac interventions vs 36 weeks for VOGM] and location of uterine entry [upper segment for cardiac interventions vs lower segment for VOGM]. Nevertheless, the exact aetiology of the resulting early delivery after VOGM embolisation remains unknown.”
The authors go on to state that, while these early, promising results suggest that it remains possible to continue with in-utero embolisation at the currently specified range of gestational ages, another option may be to consider restricting this window to ≥37 weeks, followed by scheduled delivery within 1–2 days.
Orbach et al conclude that, even after taking into account its limitations—including a small sample size, lack of randomised controls and relatively short follow-up period—this study provides preliminary evidence supporting the feasibility of foetal embolisation for VOGM, with a potential improvement in outcomes for foetuses harbouring the highest-risk malformations.
