- In utero embolization of fetuses with vein of Galen malformation (VOGM) was feasible, according to early results from a single-center intervention study.
- The three survivors out of seven participants who underwent fetal embolization were 8, 18, and 24 months of age as of April 10, and all were without neurodevelopmental delay.
- Risk of pre-term delivery warrants further study, researchers noted.
In utero embolization of high-risk vein of Galen malformation (VOGM) was feasible for fetuses, early results from a single-center intervention study showed.
Five of the seven attempts at this procedure successfully blocked off these abnormal, direct connections between veins and arteries in the brain that lead to very high venous blood pressure, with three treated fetuses surviving past the neonatal period to meet milestones at 6 months of age, reported Darren Orbach, MD, PhD, of Boston Children's Hospital, and colleagues in JAMA.
The three survivors -- ages 8, 18, and 24 months as of April 10 -- showed no signs of the neurodevelopmental delay that usually accompanies the condition.
"While major advances have been made in the treatment of infants with VOGM in the past several decades, the overall mortality rate remains stubbornly high, and the likelihood of excellent neurodevelopmental outcome remains stubbornly low," Orbach told MedPage Today in an email.
Indeed, the patients in the study had a mean pretreatment falcine sinus diameter of 10.3 mm, which would have been expected to confer "90% mortality and only 9% likelihood of reaching milestones at 6 months under conventional postnatal management," Orbach and colleagues noted.
"Since newborns with VOGM present within hours or days of birth with very aggressive pathophysiology, it became apparent to us that if an intervention before birth were feasible, that might be a very promising avenue for significant improvement in outcomes," Orbach explained.
"This fetal surgery is the first we are aware of that aims to change the brain blood flow in utero," he said. "Thus, though there were compelling theoretical grounds for optimism, both the safety of the surgical approach and the efficacy of the intervention were unknown when we launched the clinical trial. Fortunately, the first patient in the trial in whom we were able to successfully perform the fetal surgery had a fantastic clinical outcome. But of course, it is vital to replicate such results in other patients."
"We were therefore excited to see that the first group of our enrolled subjects showed a dramatic reduction in mortality and neurodevelopmental morbidity, as compared to standard postnatal management," he continued.
However, five patients (71.4%) had unplanned early deliveries due to circumstances related to fetal intervention. Three of these were pre-term, at a mean of 3.2 days post-intervention.
"Any potential reduction in mortality, brain injury, and neurodevelopmental delays must be weighed against an increased risk of unscheduled, preterm delivery," the group thus cautioned, although Orbach called it "gratifying that the improved outcomes for the enrolled subjects were clearly present, despite the risk of earlier delivery."
While commending the attempt to find a fetal treatment for a difficult disease state in which there are no good treatment options for some large malformation patients, Johanna Fifi, MD, of Mount Sinai Health System in New York City and immediate past president of the Society of NeuroInterventional Surgery, agreed that the risks are notable.
"The induction of premature labor is quite concerning, as postnatal treatment outcome is correlated with gestational age and size of the neonate," Fifi, who was not involved in the study, told MedPage Today in an email. "Therefore, any potential benefit must be weighed against this risk. In addition, fetal treatment risk after term must be compared to postnatal embolization risk."
Mean gestational age at the time of attempted fetal surgery was just shy of 37 weeks, Orbach and colleagues noted. Fetal MRI and echocardiography were performed before and after embolization.
Additional findings were that, among the five fetuses with successful embolization, combined cardiac output dropped 33.4% on average, addressing the risk of heart failure from the congenital condition.
Furthermore, four out of the five embolized fetuses showed no new parenchymal brain findings on postnatal MRI. The other "showed a small focus of hemorrhage in the right occipital lobe and growth of the subdural hematomas compared with the fetal scan." This child had severe high-output heart failure related to the vascular malformation immediately after birth, was not stable enough to undergo postnatal embolization, and died.
The three survivors who underwent successful fetal embolization did not show signs of parenchymal injury on follow-up MRI.
Maternal spinal anesthesia was used for the procedure, while fetuses received an intramuscular injection of fentanyl, vecuronium, and atropine after being positioned by external manipulation by the fetal surgeon.
Fetal embolization utilized ultrasound guidance with transuterine, transcranial needle access and microcatheterization of the falcine sinus and prosencephalic venous varix with detachable coils.
Of the two cases where the embolization procedure was not successful in utero, one died and the other survived with intracranial hemorrhage and seizures after multiple rounds of postnatal embolization.
Limitations included the study's small sample size and lack of a randomized control group, Orbach and colleagues noted. The follow-up period also was relatively short. And due to the geographic dispersion of participants, neurodevelopmental follow-up in partnership with local primary pediatricians was needed, "thus potentially introducing lack of uniformity."
Generalization to other centers is unknown, they added, and the "technical learning curve associated with the fetal procedure and the risk of procedure-related preterm delivery underscore the need for further technique refinement and broader multicenter validation."
While "we cannot firmly conclude yet that this procedure is safe and effective," Orbach said, "we have demonstrated feasibility, and we are excited to complete a clinical trial."
Disclosures
The study was supported by the Gerber Foundation, Haas Family Cerebrovascular Interventions Research Fund, and Sage Schermerhorn Chair in Image-Guided Therapy.
A co-author reported personal fees from UpToDate and grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development outside the submitted work.
Fifi did not report any relevant disclosures.
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