Med school team takes part in milestone study on fetal surgery

Francois Luks, a pediatric surgeon, and Stephen Carr, a maternal-fetal medicine specialist, were the sole U.S. participants in a groundbreaking international research trial aimed at testing the benefit of fetal surgery for a disease or defect.

by Wendy Y. Lawton

At just 17 weeks, the twins' hearts were weak. The blood vessels lacing through the placenta weren't in balance. One twin's heart pumped too much blood, a process so sapping that the fetus wasn't growing. Meanwhile, the other twin's body was swamped with blood, enlarging its heart and taxing its kidneys.

Without intervention, both of these unborn babies would likely die of heart failure.

Francois Luks, a pediatric surgeon, and Stephen Carr, a maternal-fetal medicine specialist, scrubbed in. They cut half-inch incisions into the mother's belly, snaked in a slender steel scope and, using a laser, began to separate the connecting blood vessels in the placenta. In less than an hour, the Medical School professors were done. The mother was discharged in two days. Both twins recovered and were born 20 weeks later.

This surgery, performed last March in a Hasbro Children's Hospital operating room, was part of a groundbreaking international research trial aimed at testing in-utero laser therapy for this placental disease, called Twin-Twin Transfusion Syndrome, or TTTS. Results of the study, published this month in the New England Journal of Medicine, provided the first rigorous evidence that fetal surgery is a benefit for a disease or defect.

The trial took place between 1999 and 2003 in France, Belgium and the United States - with Luks and Carr being the only stateside physicians to take part. A total of 142 pregnant women enrolled. All carried identical twins, ages 15 to 26 weeks, with TTTS. Of the total, 72 women received the laser surgery. The other 70 received amnioreduction, a procedure that drains amniotic fluid from the placenta to prevent preterm labor and improve blood flow between twins.

The trial was stopped early because it was clear that laser surgery was superior. With the laser, the chance of survival for one or more twins was 76 percent. With amnioreduction, that rate was 51 percent. Put another way: Out of the 144 twins treated with the laser, 81 lived. Out of the 140 twins treated with amnioreduction, 54 lived.

The surgery is far from perfect. Because so many unborn babies die or develop permanent organ and brain damage even with surgical intervention, an accompanying editorial in the Journal asked: "Is this as good as it gets?"

Yet the study was a milestone. And Luks said it will have an impact on fetal medicine - a budding medical subfield fraught with clinical hurdles and ethical minefields.

"Clinically, this procedure will be more accepted nationwide," Luks said. "More importantly, the study should spark more research in fetal surgery."

Luks is a surgeon with the Fetal Treatment Program, a collaboration among the Medical School, Hasbro Children's Hospital and Women & Infants Hospital of Rhode Island. Much of the program's work is focused on TTTS surgery. Luks, through Hasbro Children's, and Carr, through Women & Infants, have teamed up to perform about 20 laser surgeries. They've also removed neck tumors that would make it impossible for newborns to breathe on their own.

These surgeries, like all fetal treatments, are aimed at correcting conditions that threaten the life of unborn children. Fetal medicine encompasses a wide range of treatments, from administering drugs to pregnant women to help their unborn children, to inserting catheters in fetuses to drain dangerous fluids.

But the real frontier is complex surgery to correct birth defects. The pioneering institution is UCSF Children's Hospital, where the first fetal surgery in the world was performed in 1981. Today, UCSF physicians remove tumors, repair diaphragmatic hernias, correct urinary track obstructions and close lesions on the spinal cords of unborn babies with spina bifida.

This work - particularly spina bifida surgery - has attracted skepticism and controversy. It's unproven, critics say, unethical or simply too risky.

Luks acknowledges that fetal medicine has limits.

For example, despite advances in ultrasound imaging, diagnosing defects is still difficult. Operating in utero also poses unique challenges. Surgeons must safely get through the mother's abdomen and the placenta before they can operate on their intended patient. Fetuses are also small and frail, floating in a sea of amniotic fluid, making surgical precision and proper instrumentation imperative.

Research is tough, too, because human gestation is hard to match in animals. "Gestation for mice is a few weeks," Luks said. "That's a pretty narrow window for research."

And there are the ethical issues.

"Fetal surgery requires performing a procedure on a woman who doesn't need treatment," Luks said. "While the fetus is sick, the mother is an innocent bystander. So do you expose her to the risks of surgery? This is why we only perform surgery in life-threatening situations."

But the current success and future promise of fetal medicine ensure that it will grow.

Next month, the National Institute of Child Health & Human Development will convene a panel of experts to discuss future directions of fetal diagnosis, treatment and research.

At the end of the two-day meeting, panelists will draft a plan spelling out which surgical approaches are the most effective, which disease states should be research priorities and what is the best clinical trial design for fetal surgery. The plan will also address the structure of effective fetal therapy programs - with Brown's Fetal Treatment Program held up as one of three national models. Luks will make the presentation.