Brain surgery on a fetus

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She doesn’t know it yet, but a baby girl living somewhere near Boston has made history. The seven-week-old is one of the first people to have undergone an experimental brain operation while still in the womb. It might have saved her life.

Before she was born, this little girl developed a dangerous condition that led blood to pool in a 14-millimeter-wide pocket in her brain. The condition could have resulted in brain damage, heart problems, and breathing difficulties after birth. It could have been fatal.

Her parents signed up for a clinical trial of an in-utero surgical treatment to see if doctors could intervene before any of these outcomes materialized. It seems to have worked. The team behind the operation now plans to treat more fetuses in the same way. Other, similar brain conditions might benefit from the same approach. For conditions like these, fetal brain surgery could be the future.

The baby’s condition, known as vein of Galen malformation, was first noticed during a routine ultrasound scan at 30 weeks of pregnancy. The condition occurs when a vein connects with an artery in the brain. These two types of vessels have different functions and should be kept separate—arteries ferry high-pressure flows of oxygenated blood from the heart, while thin-walled veins carry low-pressure blood back the other way.

When the two combine, the high-pressure blood flow from an artery can stretch the thin walls of the vein. “Over time the vein essentially blows up like a balloon,” says Darren Orbach, a radiologist at Boston Children’s Hospital in Massachusetts, who treats babies born with the condition.

The resulting balloon of blood can cause serious problems for a baby. “It’s stealing blood from the rest of the circulation,” says Mario Ganau, a consultant neurosurgeon at Oxford University Hospitals in the UK, who was not involved in this particular case. Other parts of the brain can end up being starved of oxygenated blood, causing brain damage, and there’s a risk of bleeding in the brain. The extra pressure put on the heart to pump blood can lead to heart failure. And other organs can suffer too—especially the lungs and kidneys, says Ganau.

Fetuses with the condition are thought to be protected by the placenta to some degree. But that changes from the moment the umbilical cord is clamped at birth. “All of a sudden there’s this enormous burden placed right on the newborn heart,” says Orbach. “Most babies with this condition will become very sick, very quickly.”

Several teams are attempting to treat the condition before this can happen—while the fetus is still inside the womb. Orbach is a member of one such team. He and his colleagues at Boston Children’s Hospital and Brigham and Women’s Hospital, also in Boston, registered a clinical trial in 2020 to test whether fetal brain surgery might help.

The girl’s mother was referred to Orbach’s clinical trial. On March 15, at 34 weeks, she underwent the experimental operation—a two-hour procedure that involved a range of medical professionals.

First, the mother was given a spinal anesthetic to prevent her from feeling anything in the lower half of her body. She remained awake for the procedure, though, says Orbach. “She was wearing headphones and listening to music,” he says.

The second step involved physically moving the fetus around in the uterus, to make sure that the brain could be accessed from the front. Before the surgery began, the fetus was given an injection to prevent pain and movement.

Doctors then used ultrasound imaging to help them guide a needle through the mother’s abdomen, the uterus wall, and the fetus’s skull and into the malformation in the brain. Members of the team fed a tiny catheter through the needle to deliver a series of tiny platinum coils into the blood-filled pocket. Once each was released, it expanded, helping to block the point where the artery joined the vein.

As they worked, the team members closely monitored blood flow in the fetus’s brain. Once they saw that it had returned to healthy levels, they stopped injecting coils and carefully removed the needle.

The baby girl was born healthy a couple of days later, says Orbach, who coauthored a report on the case that was published in the journal Stroke. She didn’t need any treatment for the malformation. “The brain looks great,” he says. She was monitored in hospital for a few weeks and is now home and doing well, he tells me.

“This is a very elegant and exciting solution to a difficult problem,” says Ibrahim Jalloh, a consultant neurosurgeon at Cambridge University Hospitals NHS Foundation Trust in the UK, who was not involved in the case. “We need to wait for further cases … to work out the risks, but I suspect given the really quite poor outcomes in [newborns with severe malformations], this will be the way forward,” he says.

“This is a really exciting breakthrough,” says Greg James, a pediatric neurosurgeon at Great Ormond Street Hospital in London. Timo Krings, a neuroradiologist at the University of Toronto, shares his sentiments. “It’s giving a chance to kids who would otherwise have very little possibility of survival,” he says. Both add that it will be important to work out who might be the best candidates for this kind of fetal surgery. The procedure comes with risks and might be worthwhile only for severe cases where there is also a good chance of recovery, for example.

Orbach and his colleagues aren’t the only ones investigating fetal brain surgery for vein of Galen malformations. Krings is working with Karen Chen at Texas Children’s Hospital and her colleagues on a similar trial, and he has heard that another baby was born in Paris following a similar procedure. Chen says she knows of another unpublished attempt that took place in Mexico, although that baby sadly died at 10 days old. “It’s a very hot topic,” Krings says. “It has kind of been a race to see who would publish first.”

Operations like this one might prove useful in treating other conditions, such as other blood vessel problems or brain tumors, he says. Ganau, too, thinks “many conditions that we deal with in the very first weeks of life” could potentially be treated in the uterus.

“It was such a dramatic outcome that I’m certainly hopeful and optimistic,” says Orbach.

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