May 5, 2023 – In a novel operation, doctors have successfully repaired a malformation within the brain of a fetus within the womb.
The team of Boston Children's Hospital and Brigham and Women's Hospital used ultrasound guidance to repair the vein of a condition called Galen's malformation, which causes excessive blood flow and might result in neurological and cardiac complications, including heart failure, severe brain injury, and death shortly after birth.
The operation was performed on a 34-week-old fetus and brought remarkable results. Since birth, the little girl, who was already identified within the womb as being at high risk of significant complications from the malformation, has not required any medication for heart failure or further surgery.
Repeated echocardiograms after the girl's birth showed a big improvement in cardiac function, and an MRI of the brain showed no injury and a standard neurological examination.
“This is incredibly exciting. We hope that this baby and others with this disease who receive this surgery in the womb in the future will be able to live normal lives,” said lead researcher Darren B. Orbach, MD, PhD.
“We were delighted that the aggressive decline that is usually seen after birth simply did not occur,” he said. “We are happy to report that at 6 weeks the baby is doing remarkably well, needs no medication, is eating normally, is gaining weight and is back home. There is no evidence of any adverse brain effects.”
Malformation of the vein of Galen
Orbach said that the vein of Galen This malformation, which occurs in about one in 60,000 births, is an abnormality wherein the arteries are connected on to the veins somewhat than to the capillaries needed to slow blood flow and provide oxygen to the encircling brain tissue.
“The arterial and venous systems are fundamentally very different. The arterial system has high pressure and high flow, while the venous system has low pressure and low flow. They should not be directly connected,” he said.
The most extreme type of such an anomaly is the Vena of Galen malformation. It develops early in a baby's growth process and has been shown to cause a big increase in blood flow to the brain, which increases over time and might sometimes cause the guts to work twice as hard.
It is assumed that the placenta protects against this, as most babies don’t have any physiological problems within the womb. However, crises can occur after birth, because the extremely high blood flow places an amazing strain on the guts.
Typically, babies develop heart failure as their first major symptom shortly after birth, Orbach said. “Although the anatomical problem is in the brain, the clinical manifestation is high-flow heart failure. The heart is trying to do double work pumping blood to the malformation and immediately back to the heart, and that blood is not serving a useful function.”
“These newborns can become very sick. They need a lot of medications to support their cardiovascular system and we need to take measures to reduce blood flow,” he said.
Brain injuries are also a typical problem. “The blood flow to the brain is completely disrupted. The blood is diverted through the malformation instead of circulating through the brain tissue,” said Orbach.
“The mortality rate of sick babies would be very high (up to 90%) without specialized care. Even for babies who receive specialized care in a specialized center, the mortality rate is 30-40% and those who survive are at high risk of neurological and cognitive impairment,” he said.
Current treatment for babies born with the condition involves inserting a catheter into the arteries to shut the malformation.
But Orbach said some babies are born too sick to be operated on. “The heart failure and brain damage are so severe that no matter what we do, we can't reverse them, and those babies usually don't survive. With fetal surgery, we're trying to help those babies who can't be treated with the current postnatal approach,” he said.
Although other fetal surgeries are actually performed routinely, this might be the primary surgery within the womb involving the cerebrovascular system.
“There were a lot of uncertainties,” Orbach said. “We didn't even know if we would see our instruments on ultrasound.” To model the procedure, the researchers had a phantom skull and brain constructed of a fetus with a vena galena malformation, which was critical to FDA approval of the study.
If the study shows success in the opposite patients, the technique may very well be introduced in other centers. “There definitely needs to be fetal surgery and neurointerventional teams that are familiar with the vena of Galen malformation and are prepared to treat complications after delivery, regardless of the outcome. But we are not the only center with these capabilities, so if our study is successful, the hope is that other teams in specialized children's hospitals around the world can do the same,” he said.