She doesn’t know yet, but a little girl living somewhere near Boston made history. The seven-week-old girl is one of the first people to have undergone experimental brain surgery while still in the womb. That could have saved her life.
Even before she was born, the little girl developed a dangerous disease that caused her blood to pool in a 14 millimeter wide sac in her brain. This condition could have resulted in brain damage, heart problems, and breathing difficulties after birth, and could have been fatal.
The parents signed up for a clinical trial of in-utero surgery to see if doctors could prevent it. It seems to have worked. The team behind the operation are now planning to treat more fetuses in the same way. Other, similar brain diseases could benefit from the same approach. For conditions like these, fetal brain surgery could be the future.
30th week of pregnancy: Malformation found in the brain
The baby’s condition, known as Galen’s vein malformation, was first detected during a routine ultrasound scan at 30 weeks’ gestation. This condition occurs when a vein joins an artery in the brain. These two types of vessels have different functions and should be kept separate: arteries carry oxygen-rich blood away from the heart at high pressure, while thin-walled veins return blood at low pressure in the other direction.
When the two come together, the high-pressure flow of blood from an artery can stretch the thin walls of the vein. “Over time, the vein balloons out,” 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 the baby. “It’s draining blood from the rest of the system,” says Mario Ganau, a neurosurgeon at Oxford University Hospitals in the UK, who was not involved in the case. This deprives other parts of the brain of oxygen-rich blood, which can lead to brain damage, and there is a risk of bleeding in the brain. The extra pressure put on the heart to pump blood can lead to heart failure. Other organs can also be affected, especially the lungs and kidneys, says Ganau.
It is believed that fetuses with this condition are protected to some extent by the placenta. However, that changes the moment the umbilical cord is clamped at birth. “Suddenly an enormous burden weighs on the heart of the newborn,” says Orbach. “Most babies with this condition get very sick very quickly.”
Brain surgery on the fetus – the future?
Several teams try to treat the disease before it can develop – while the fetus is still in the womb. Orbach is a member of such a team. He and his colleagues at Boston Children’s Hospital and Brigham and Women’s Hospital, also in Boston, have registered a 2020 clinical trial to test whether fetal brain surgery might help.
The girl’s mother was referred to Orbach’s clinical trial. On March 15, at week 34, she underwent the experimental surgery – a two-hour procedure involving a number of doctors.
First, the mother was given spinal anesthesia to prevent feeling anything in the lower half of her body. However, she remained awake during the procedure, Orbach says. “She was wearing headphones and listening to music,” he says.
The second step was to position the fetus in an appropriate position in the uterus so that the brain was accessible from the front. Before the operation began, the fetus received an injection to prevent pain and movement.
Platinum coils for the brain
With the help of ultrasound images, the doctors then inserted a needle through the mother’s abdomen, the uterine wall and the skull of the fetus down to the abnormality in the brain. Team members inserted a tiny catheter through the needle to insert a series of tiny platinum coils, called coils, into the blood-filled pocket. Once released, they expanded and helped block the point where the artery entered the vein.
During their work, team members closely monitored blood flow in the fetus’s brain. When they saw that blood flow had returned to a healthy level, they stopped injecting the coils and carefully removed the needle.
The girl was born healthy a few days later, says Orbach, who co-authored a report on the case published in Stroke magazine. She did not need treatment for the deformity. “The brain looks great,” he says. She was monitored in the hospital for a few weeks and is now at home where she is fine, 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’ll have to wait for more cases… to determine the risks, but I suspect that given the really, really bad results at [Neugeborenen mit schweren Fehlbildungen] will be the way forward,” he says.
“Opportunity for children who would otherwise have little chance of survival”
“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 opinion. “It’s a chance for children who would otherwise have little chance of survival,” he says. Both add that it will be important to find out who are the best candidates for this type of fetal surgery. The procedure involves risks and might only be worthwhile for severe cases where there is also a good chance of recovery, for example.
Orbach and his colleagues are not the only ones studying fetal brain surgery for Galen vein malformations. Krings is working with Karen Chen and her colleagues at the University of Texas on a similar study, and he has heard that another baby was born in Paris using a similar procedure. Chen says she is aware of another unpublished trial that took place in Mexico, although sadly this baby died at 10 days old. “It’s a very hot topic,” says Krings. “It’s kind of a race to see who’s going to release it first.”
Surgery like this could prove useful in treating other conditions, such as other blood vessel problems or brain tumors, he says. Ganau agrees that “many diseases that we deal with in the first few weeks of life” could potentially be treated in utero.
“It was such a dramatic result that I’m very hopeful and optimistic,” says Orbach.
(jl)