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First Ever In-Utero Brain Surgery in US Went Off Without a Hitch

Researchers at the American Stroke Association, a division of the American Heart Association successfully performed the world’s first in-utero surgery on a 34-week fetus and two days gestational age to mend a possibly fatal developmental condition through the treatment of a vascular malformation referred to as Galen malformation in the brain of a fetus ahead of birth, as comprehensively outlined by the researchers in Stroke—the association’s flagship peer-reviewed journal.

What is Galen Malformation

Vein of Galen malformation (VOGM) is a rare prenatal condition where the arteries carrying high-pressure blood from the heart to the brain are connected directly to a main collecting vein deep in the brain instead of capillaries that regulate blood flow.

This abnormality causes serious complications after birth, putting immense pressure on the heart and lungs, which may result in pulmonary hypertension, heart failure, and other life-threatening conditions.

VOGM is usually detected during a prenatal ultrasound and is confirmed by an MRI in the late second or third trimester of pregnancy.

Fetus In Good Health After Surgery

The researchers performed the surgery with the guidelines of an ongoing clinical trial at the Boston Children’s Hospital and Brigham and Women’s Hospital with the United States Food and Drug Administration as the overseer.

“In our ongoing clinical trial, we are using ultrasound-guided transuterine embolization to address the vein of Galen malformation before birth, and in our first treated case, we were thrilled to see that the aggressive decline usually seen after birth simply did not appear,” the lead study author Darren B. Orbach, M.D., Ph.D., co-director of the Cerebrovascular Surgery & Interventions Center at Boston Children’s Hospital said. “We are pleased to report that at six weeks, the infant is progressing remarkably well, on no medications, eating normally, gaining weight, and is back home. There are no signs of any negative effects on the brain.”

The infant was delivered two days by induction of vaginal birth after the surgery in what the researchers described as a premature rupture of membranes when performing in-utero embolization.

They also confirmed progressive stabilization of cardiac output through echocardiography. The infant in question did not require any cardiovascular support or additional surgery in the wake of the in-utero treatment and was observed in the Neonatal intensive care unit (NICU) for a few weeks following birth mainly because of the prematurity condition – the newborn is safely at home.

At the time, the researchers performed a normal neurological exam on the infant, which showed no evidence of strokes, fluid buildup, or brain hemorrhage – MRI.

“While this is only our first treated patient and it is vital that we continue the trial to assess the safety and efficacy in other patients, this approach has the potential to mark a paradigm shift in managing vein of Galen malformation where we repair the malformation prior to birth and head off the heart failure before it occurs, rather than trying to reverse it after birth,” Orbach said. “This may markedly reduce the risk of long-term brain damage, disability or death among these infants.”

“While this is only our first treated patient and it is vital that we continue the trial to assess the safety and efficacy in other patients, this approach has the potential to mark a paradigm shift in managing vein of Galen malformation where we repair the malformation prior to birth and head off the heart failure before it occurs, rather than trying to reverse it after birth,” Orbach who is also an associate professor of radiology at Harvard Medical School added. “This may markedly reduce the risk of long-term brain damage, disability or death among these infants.”

According to medical statistics, the most common joint congenital vascular brain malformation appears once in every 60,000 births. The globally approved standard of care for VOGM patients comes after birth.

The procedure encompasses an embolization, a catheter-based procedure with a target to close off the direct artery-to-vein connection within the malformation—to block the extra blood flow to the brain and the infant’s heart.

However, this procedure is very delicate and often fails to reverse the heart failure condition. Besides, there’s usually a high chance of severe brain damage having already occurred ahead of the procedure.

Infants who live through VOGM see their lives become complicated as a result of life-long cognitive disabilities and other life-threatening conditions.

“The fetal intervention team at Boston Children’s Hospital and Brigham and Women’s Hospital have successfully devised another in utero procedure that may be very impactful in a specific group of patients diagnosed with vein of Galen malformation,” said Gary M. Satou, M.D., FAHA, the director of pediatric echocardiography at UCLA Mattel Children’s Hospital and co-director of the UCLA Fetal Cardiology Program and who was not involved with this particular medical research.

Satou is an accomplished pediatric cardiologist with a proven record of success. In addition to serving as the former chair of the Congenital Cardiac Defects committee for the American Heart Association’s Young Hearts Council, Satou is a highly respected clinical professor in the pediatrics department at the prestigious David Geffen School of Medicine at UCLA.

“As always, a number of these fetal cases will need to be performed and followed in order to establish a clear pattern of improvement in both neurologic and cardiovascular outcomes,” Satou said in a statement. “Thus, the national clinical trial will be crucial in order to achieve adequate data and, hopefully, successful outcomes.”

Limitations of In-Utero Brain Surgery Still Exist

According to Derdeyn, M.D., a neuro-interventional radiologist at the University of Iowa Health Care who performs VOGM embolizations on neonates says that despite the successful first in-utero brain surgery, the procedure possesses numerous limitations.

Although Derdeyn was not involved with the study, he agrees that there is a need to address the condition way before the psychological events that come at birth lead to life-threatening heart failure.

“There are caveats; one successful case is not enough experience for us to conclude that the risks of this procedure are worth the benefits. Safety issues may crop up in future procedures, and this approach through the veins may not be consistently successful in preventing heart failure. The procedure described here is designed to reduce the flow through the malformation and not to cure it,” Derdeyn cautioned.

He (Derdeyn) was keen to mention that “the positive hemodynamic changes that they observed in utero and after birth – reduction in flow, reduction in size of the draining vein, reversal of the abnormal reversed flow in the aorta – are really encouraging.”

Derdeyn who is also the Krabbenhoft Professor of Radiology and chair and department executive officer of the department of radiology at the University of Iowa Health Care Carver College of Medicine and a past chair of the American Heart Association’s Stroke Council, described the post-birth findings as “the most exciting and surprising aspects of this case report.”

“This is pioneering work being done in a very careful and responsible way,” Derdeyn concluded his statement.

The research was co-authored by E. Wilkins-Haug, M.D.; Carol B. Benson, M.D.; Wayne Tworetzky, M.B. Ch.B.; Shivani D. Rangwala, M.D.; Stephanie H. Guseh, M.D.; Nicole K. Gately, R.N.; Jeffrey N. Stout, Ph.D.; Arielle Mizrahi-Arnaud, M.D.; and Alfred P.

Sage Schermerhorn Chair for Image-Guided Therapy (DBO) in Boston Children’s Hospital’s Radiology Department funded the study with a grant.

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