The team from Boston Children’s Hospital and Brigham and Women’s Hospital used ultrasound guidance to repair the vein of Galen malformation, which causes excessively high blood flow, resulting in both neurologic and cardiac complications.
The surgery was performed in a fetus at 34 weeks’ gestational age, with remarkable results. Since birth, the baby girl, who was identified in utero as being at high risk of suffering serious complications of the malformation, has required no medication to treat heart failure and no postnatal surgery.
Repeated echocardiograms after birth displayed marked improvement in cardiac output, and brain MRI showed no brain injury and a normal neurologic exam.
“This is incredibly exciting. The hope is that this baby, and others with this condition who receive this in utero surgery in future, will go on to have a normal life,” lead researcher Darren B. Orbach, MD, PhD, said in an interview.
“We were thrilled to see that the aggressive decline usually seen after birth simply did not appear. We are pleased to report that at 6 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,” he added.
Dr. Orbach, codirector of the Cerebrovascular Surgery & Interventions Center at Boston Children’s Hospital, and colleagues described this first case report of the in utero vein of Galen malformation repair in a research letter, published online in the journal Stroke.
Vein of Galen malformation
Dr. Orbach explained that vein of Galen malformation, which occurs in around 1 in every 60,000 births, is a cerebrovascular anomaly in which the arterial system is directly connected to the venous system rather than to capillaries that are necessary to slow blood flow and deliver oxygen to surrounding brain tissue.
“The arterial and venous systems are fundamentally very different. The arterial system is high pressure, high flow; while the venous system is low pressure, low flow. They shouldn’t be directly connected,” he noted.
The vein of Galen malformation is the most extreme version of such an anomaly. Developing in early gestation, it is associated with a large increase in blood flow through the brain which grows over time and can sometimes result in twice the total cardiac output of the body or even more, Dr. Orbach said.
The placenta is believed to be protective as most babies don’t have overt physiologic problems in utero, but they can run into crisis after birth, with the abnormally high blood flow causing an immense stress to the heart.
Babies typically present with heart failure as their first major symptom soon after birth, Dr. Orbach said. “Although the anatomical problem is in the brain, the clinical manifestation is high-output heart failure. The heart is trying to do double its normal work, pumping the blood to the malformation and immediately back to the heart and that blood is not performing any useful function.
“These newborns can get very sick. They need multiple medications to support their cardiovascular system and we need to do procedures to try and reduce the blood flow,” he explained.
Brain injury is also a common problem. “The brain circulation is very abnormal. The blood is being shunted through the malformation rather than circulating through the brain tissue which can become ischemic,” Dr. Orbach commented.
“The babies who get sick would have a very high mortality (up to 90%) without expert care. Even those who do receive expert care at a specialty center have a mortality rate of 30% to 40% and those who survive have a high risk of neurologic and cognitive impairment,” he added.
The current treatment for babies born with the condition involves transarterial embolization, by which a catheter is inserted into the arterial system to enable the malformation to be occluded by various techniques.
But Dr. Orbach pointed out that some babies are born too sick to have the postnatal intervention. “The heart failure and brain injury is so overwhelming that no matter what we do, we cannot reverse it, and these babies normally do not survive. What we are doing with the fetal surgery is trying to help those babies who cannot be treated with the current postnatal approach,” he said.
The first stage of this research involved trying to identify these very-high-risk babies in utero, and the researchers found that on fetal MRI a particular measurement of one of the venous sinuses that drains the main malformation was a good predictor of how the baby would fare after birth. The babies predicted to do poorly from this test are the targets for the fetal surgery.
The technique used for the postnatal intervention is too technically challenging to perform in utero. “So we have developed a different approach for the in utero surgery that involves navigating into the accepting vein in the malformation with a needle under ultrasound guidance, and then packing the vein with metal coils to dramatically reduce the blood flow,” Dr. Orbach explained.
This procedure was performed in this first patient on March 15. The surgery was part of a clinical trial that is planned to include 20 cases in total.
“The immediate goal is to see whether we can transform those fetuses who are at very high risk of getting sick after birth into babies who do well in the [neonatal] ICU and are able to be sent home for elective treatment at a few months of age,” Dr. Orbach noted. “The study is continuing as it is vital that we continue and show efficacy and safety in other patients as well,” he added.
Dr. Orbach said the results of this first case were extremely encouraging. “Each stage was exciting – the technical success of the procedure, and then seeing the [blood] flow diminish on the ultrasound right there during the procedure; then the next day we did a fetal echocardiogram, and we could see that the abnormal cardiac output was dramatically reduced, and a fetal MRI scan also showed the malformation was already coming down in size.”
The baby was born prematurely 2 days after the procedure because of ruptured membranes with a birth weight of 1.9 kg (4.2 lb). She has not required any cardiovascular support or postnatal embolization.
“We were waiting with bated breath until the baby was born to see how she did clinically. I was trying to be conservative in my expectations, but it was quickly apparent that she was going to do great,” he said. Now at home, she has some oxygen treatment for the first few weeks, “but right now her neurological status is completely intact and essentially she looks like any other baby,” Dr. Orbach commented.
It is not yet known whether the infant will need any additional procedures. “We will follow her closely and make a decision on whether further treatment is needed based on whether the malformation is growing or not,” Dr. Orbach said. Longer term follow-up will also assess secondary problems sometimes seen, such as learning problems and seizures.
Although other fetal surgeries are now routinely performed, this is believed to be the first in utero surgery aimed at the cerebrovascular system.
“There were a lot of uncertainties,” Dr. Orbach said. “We didn’t even know if we would be able to see our instruments on ultrasound.” To model the procedure, the researchers had a phantom fetal skull and brain constructed with a vein of Galen malformation, which was key to obtaining Food and Drug Administration approval for the study.
If the study shows success in the other patients too, the technique could be rolled out to other centers. “There definitely needs to be fetal surgery and neurointerventional teams familiar with vein of Galen malformation in place, and ready to manage complications after delivery regardless of outcome. But we are not the only center with those capabilities, so if our trial pans out, yes, the hope is that other teams in specialist children’s hospitals around the world could do this too,” he added.