For 1 in 2,000 infants born in the US, hydrocephalus puts pressure on the brain that can cause irreparable damage and even death. Current treatment methods can only take place after birth, when the damage may have already occurred. Now, a team at Cincinnati Children’s has successfully performed prenatal endoscopic third ventriculostomy (ETV) on lamb models—with outstanding results. Further research could lead to safe and effective treatment of hydrocephalus in the human womb, possibly preventing prenatal brain damage and other complications.

Led by Jose Peiro, MD, PhD, director of endoscopic fetal surgery in the Fetal Care Center, the team has already earned recognition from the International Pediatric Endosurgery Group for this work. Peiro has a track record of groundbreaking research in fetal surgery and prenatal intervention and is also working on the development of artificial amniotic fluid that is less acidic and more nutrient-rich than saline or Ringer’s solution.

“This is the first time the ETV procedure has been conducted this way in any model,” Peiro says. “While other researchers have inserted a camera into the fetal lamb brain, they did not complete the ventriculostomy. This is the innovative part, and it will give us the opportunity to study the effects of the surgery and increase our skills before implementing this procedure in humans.”

The next step, however, is to examine the molecular and cellular changes that occur in brains impacted by this condition.

“We will be working with microscopes to examine the development and neural progenitor cells in the brain that are improved by this technique,” he says. “That will also allow us to study the long-term effects on these animals postnatally.”

Ultimately, Peiro says, his team plans to pursue Institutional Review Board approval for a clinical trial that will prove fetal ETV is feasible and safe in humans.

Prenatal Intervention Could Save Lives—and Futures

Fetal ultrasound can reveal whether an unborn child has a build-up of cerebrospinal fluid in the cerebral ventricles. If accumulation is detected, fetal magnetic resonance imaging (MRI) can help to determine the severity of the condition.

Unfortunately, ventricular derivation with shunt devices or ETV (after birth) are currently the only surgical interventions available to treat congenital hydrocephalus.

“During the first days of life, these babies need a shunt that can remove the extra fluid and provide decompression,” Peiro says. “But, by then, it’s too late. The brain has already been harmed.

As a result, he says, these children have neurodevelopmental and cognitive problems that will require lifelong care. In some cases, fetal hydrocephalus can be fatal.

Fetal ETV in the Fetal Lamb Model

Attempts to develop an in-utero fetal intervention for hydrocephalus have been ongoing for nearly 40 years, Peiro says. Neurosurgeons have tried placing ventricular amniotic shunts to relieve pressure on the brain, but this strategy has been unsuccessful. 

“Many times, these little tubes get dislodged, blocked or the amniotic fluid backflows into the ventricle,” he says.

Surgery teams have tried to re-engineer shunts to make them more effective. However, Peiro and his group wanted to approach this problem in a different way.

“We wanted to be more original and look for a solution that fixes the problem without leaving a device in the brain,” he says. “We turned to the best animal model for fetal therapy—the fetal lamb. Our results demonstrate that the ventricles do reduce in pressure and decrease in size. These outcomes show we were successful and that it’s feasible to do this procedure. Our goal is that one day moms with babies who have this condition can come to us for this procedure. We’ll be very happy to add another procedure to the fetal surgery arsenal that we currently offer for other conditions.”