The tumor was so massive that maternal fetal medicine specialist Michael Zaretsky, MD, was surprised it wasn’t blocking the ventricular blood flow.
“In my entire career of three decades,” says fetal cardiologist Bettina Cuneo, MD. “I’ve probably seen a tumor as big as this less than 10 times.”
It was early in the second trimester. The diagnosis was tuberous sclerosis-associated rhabdomyoma, confirmed with fetal MRI by the presence of associated tumors in the brain. Rhabdomyomas tend to grow most in the third trimester.
Without treatment, Drs. Cuneo and Zaretsky knew, the fetus likely wouldn’t survive.
There was one option, but it was unconventional.
A maternally administered mTOR inhibitor for fetal rhabdomyoma
Generally used as immunosuppressants, mTOR inhibitors shrink tuberous sclerosis-associated tumors by inhibiting cell proliferation. They’re an effective treatment after birth.
But the fetus couldn’t wait that long. Drs. Cuneo and Zaretsky would have to deliver the treatment using the mother as a vehicle. That had only been tried a few times. Drs. Cuneo and Zaretsky had actually discussed the few available case reports.
“I remember walking into the room and kind of nonchalantly mentioning mTOR inhibitors,” recalls Dr. Zaretsky, Medical Director of the Colorado Fetal Care Center at Children’s Hospital Colorado. “It was kind of like, okay, let’s do it.”
“We were on the same page,” Dr. Cuneo adds.
The maternal risk of mTOR inhibitors
The treatment wasn’t without risks, particularly to the mother. Because the mTOR pathway plays a key role in breaking down cholesterol, mTOR inhibitors raise triglyceride levels. And the dose — which would have to make it through the mother’s metabolism before it could reach the placenta — would be significant. Significant enough, certainly, to worry about pancreatitis due to elevated triglycerides.
Still, after hearing the risks, the mother agreed it was the right way to go. And though her triglyceride levels did go over 1,000 — which was concerning for the mother — for the fetus, it was an unqualified success.
Verifying rhabdomyoma shrinkage via fetal MRI
Drs. Cuneo and Zaretsky confirmed it four weeks later with another fetal MRI: Not only had the tumor stopped growing, it had actually shrunk substantially relative to the size of the fetal heart.
“We anticipated that, because mediation in the size of the heart tumor had been reported before,” says Dr. Zaretsky. “But we did also wonder if the associated brain tumors would also get smaller, and it turns out they were not affected. So we’re the first to report that.”
Drs. Cuneo and Zaretsky helped deliver the baby at the Colorado Fetal Care Center a little early — 37 weeks, due to the mother’s elevated triglyceride levels and concerns about fetal health. But the baby was relatively healthy.
After a short neonatal intensive care unit stay of eight days, the family was discharged and returned to their home in New Mexico. Since estrogen feeds the proliferation of tuberous sclerosis-associated tumors, once affected babies are born, the tumors shrink on their own and often eventually disappear.
“The baby’s cardiac function is quite remarkable,” says Dr. Zaretsky, “despite what we saw prenatally.”