Researchers perform in utero surgery to fix life-threatening developmental condition

For the first time, researchers have successfully performed in utero surgery to repair a life-threatening developmental condition by treating an aggressive vascular malformation, called the Vein of Galen malformation, in the brain of a fetus before birth, according to a new report. research published today in Strokethe flagship peer-reviewed journal of the American Stroke Association, a division of the American Heart Association.

Vein of Galen malformation (VOGM) is a rare prenatal condition in which arteries supplying high-flow, high-pressure blood to the brain from the heart connect directly to one of the major deep collecting veins at the base of the brain, rather than capillaries that are needed to slow blood flow and supply oxygen to surrounding brain tissue. Due to changes in the infant’s vascular physiology during and after childbirth, the high flow rate of the malformation has an even more severe effect on the heart and brain after birth, placing enormous strain on the infant’s heart and lungs. new born. This can lead to pulmonary hypertension, heart failure, or other life-threatening conditions. VOGM is most often first observed during a prenatal ultrasound and is definitively diagnosed by MRI at the end of the second or third trimester of pregnancy.

Researchers performed in utero embolization on a fetus with VOGM at 34 weeks and 2 days of gestational age, as the first patient treated in an ongoing clinical trial at Boston Children’s Hospital and Brigham and Women’s Hospital, conducted under United States oversight. Administration of food and drugs.

In our ongoing clinical trial, we are using ultrasound-guided transuterine embolization to treat venous Galen’s malformation before birth, and in our first treated case, we were delighted to see that the aggressive decline usually seen after birth n simply did not appear. We are happy to report that at six weeks the infant is progressing remarkably well, taking no medications, eating normally, gaining weight and is back home. There are no signs of negative effects on the brain.”

Darren B. Orbach, MD, Ph.D., lead study author, co-director of the Cerebrovascular Surgery & Interventions Center at Boston Children’s Hospital, and associate professor of radiology at Harvard Medical School

Due to premature rupture of membranes during in utero embolization, the infant was delivered by induction of vaginal delivery two days later. Echocardiography after birth showed progressive normalization of cardiac output. In this case, the newborn did not require cardiovascular support or surgery following in utero treatment and was monitored in the NICU for several weeks after birth due to prematurity before being discharged. at home. Meanwhile, the newborn had a normal neurological exam and showed no stroke, fluid accumulation or hemorrhage on brain MRI.

“Although this is only our first patient treated and it is vital that we continue the trial to assess the safety and efficiency in other patients, this approach has the potential to mark a paradigm shift in the management of Vein of Galen malformation where we repair the malformation before birth and prevent heart failure before it occurs, rather than trying to reverse it after birth,” Orbach said. “This can significantly reduce the risk of long-term brain damage, disability or death in these infants.”

VOGM, the most common congenital vascular brain malformation, is estimated to occur in one in 60,000 births. The current standard of care for VOGM is treatment after birth with embolization, a catheter-based procedure to close connections direct artery-vein into the malformation and block excessive blood flow to the brain and heart. However, embolization itself is high risk and not always successful in reversing heart failure. Additionally, serious brain damage may have already occurred, which can lead to lifelong cognitive impairment and life-threatening conditions for the infant, or even death.

“The fetal intervention team at Boston Children’s Hospital and Brigham and Women’s Hospital has successfully developed another in utero procedure that could have a significant impact on a specific group of patients diagnosed with a Galen malformation vein” , said Gary M. Satou, MD, FAHA, the director of pediatric echocardiography at UCLA’s Mattel Children’s Hospital and co-director of UCLA’s fetal cardiology program and who was not involved in the ‘study. Satou, a pediatric cardiologist, is the past chair of the American Heart Association’s Congenital Heart Defects Committee of the Young Hearts Council and a clinical professor in the Department of Pediatrics at UCLA’s David Geffen School of Medicine.

“As always, a number of these fetal cases will need to be performed and followed up to establish a clear pattern of improved neurological and cardiovascular outcomes,” Satou said. “Thus, the national clinical trial will be crucial to obtain adequate data and hopefully positive results.”

The procedure was not without its limitations, noted Colin P. Derdeyn, MD, a neurointerventional radiologist at the University of Iowa Health Care who performs VOGM embolizations on newborns and who was not involved in the study.

“The key advance here is to intervene before the physiological events of birth can cause 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 arise in future procedures, and this approach through the veins may not be successful in preventing heart failure. The procedure described here is designed to reduce flow to through the malformation and not to cure it,” said Derdeyn, Krabbenhoft Professor of Radiology and Chair and Chair of the Department of Radiology at the University of Iowa’s Carver College of Medicine and former chair of the the American Heart Association.

“However, the positive hemodynamic changes they observed in utero and after birth – reduced flow, reduced draining vein size, reversal of abnormal reverse flow in the aorta – are really encouraging. some of the most exciting and surprising aspects of this case report,” he said. “This is pioneering work done in a very careful and responsible way.”

Co-authors are Louise E. Wilkins-Haug, MD; Carol B. Benson, MD; Wayne Tworetzky, MB Ch.B.; Shivani D. Rangwala, MD; Stephanie H. Guseh, MD; Nicole K. Gately, registered nurse; Jeffrey N. Stout, Ph.D.; Arielle Mizrahi-Arnaud, MD; and Alfred P. See, MD Author disclosures are listed in the manuscript.

The study was funded by a grant from the Sage Schermerhorn Chair in Image-Guided Therapy (BOD) from the Department of Radiology at Boston Children’s Hospital.