Spina bifida study offers new hope for fetal surgery

Children who received fetal surgery to correct the most severe form of spina bifida were far more likely to walk as toddlers than those who had surgery after birth, concluded a new study led by researchers at the Children's Hospital of Philadelphia.

The seven-year study confirmed some of the highest hopes of believers in the procedure, once thought to be speculative.

It also raises new questions, including how to improve results while lessening risks for the mother and baby.

Doctors at Children's are bracing for a rush of interest from parents and surgeons alike. And they are cautioning both that, while the results are strong, the complicated procedure isn't for every case.

"This is a landmark study in the history of fetal surgery, and is going to have enormous implications for the treatment of these children," said Timothy Crombleholme, a former Children's surgeon who runs the Fetal Care Center at Cincinnati Children's Hospital Medical Center. Crombleholme plans to offer it in Cincinnati as soon as next week.

Spina bifida is the most common birth defect of the central nervous system, affecting about 1,500 babies born each year in the United States and holding steady in recent years despite efforts to prevent it by fortifying foods with folic acid.

Its most severe form, called myelomeningocele, occurs when the spinal canal does not close, allowing a sac with the spinal cord and fluid to protrude from the middle to lower back. It can cause paralysis, lack of bladder control, and a buildup of fluid on the brain, sometimes requiring a shunt, which is prone to infection and can compromise IQ.

Children whose lesions were closed while still in the womb required a shunt half as often as those who had surgery after birth, the study found.

A New England Journal of Medicine editorial published online Wednesday with the results said the $22.4 million study - $5.8 million went to Children's - provided "a major step in the right direction." But it cautioned doctors, too.

The study showed considerable risks for the mother and baby. Many more babies who got prenatal surgery - about 46 percent, compared with 5 percent in the postnatal group - delivered at or before reaching 34 weeks gestational age.

A typical full term is between 38 and 42 weeks. Early births can come with complications, including respiratory distress and low birth weight.

The study comes 30 years after the first open fetal surgery was performed by Michael Harrison at the University of California San Francisco on a fetus with a dangerous urinary-tract obstruction.

Scott Adzick, now chief of surgery at Children's, was a fellow under Harrison in the 1980s. Working with sheep, Adzick studied the potential for treating spina bifida in utero, then "a completely crazy idea," he said.

The risks to the mother and fetus were thought to be too great for a nonfatal condition. But the surgery was evolving.

Adzick and others began to show that the spinal cord was damaged by exposure to amniotic fluids and by the fetus bumping against the walls of the uterus. If the cord could be protected early on, researchers reasoned, some damage might be averted.

In 1995, Adzick moved to Children's, where he and nurse Lori Howell built the Center for Fetal Diagnosis and Treatment.

Leslie Sutton, Children's chief of neurosurgery, was immediately interested. "I take care of these kids when they're older," he said. "I know how much disability they have."

In 1997, the first such surgery was done at Vanderbilt University Medical Center in Nashville. Children's began a year later.

In a prenatal surgery, Sutton followed the same process as in a postnatal one. He freed the spinal cord from surrounding tissue. Then he placed it in the spinal canal and sealed three layers of tissue over it. But instead of an hour to do it, he had 15 minutes.

Early cases showed a surprising outcome. Myelomeningocele, the worst form, can cause the back of the brain to shift downward - called hindbrain herniation - sometimes causing the buildup of fluid on the brain. But prenatal surgery often reversed the condition.

Still, results were not uniform and there had been no full accounting of the procedure's risks and benefits. But interest was growing.

Through "force of personality or persuasion," Adzick said, investigators at Vanderbilt, Children's, and UCSF persuaded doctors at other surgery centers not to perform any fetal surgeries for spina bifida while they conducted the Management of Myelomeningocele Study, or MOMS. Vanderbilt was later removed from the surgical portion of the study for failing to follow protocol.

Qualifying families were randomly assigned to postnatal or prenatal surgery. The study was intended for 200 families, split between the two groups. But the surgeons received an e-mail Dec. 7 saying the trial had ended with 183 enrolled. An independent group overseeing analysis of the children's progress determined that the benefits of fetal surgery were clear.

A week later, researchers gathered in Washington. Adzick and other researchers mugged for a photo just before cutting into a cake that read, in yellow icing, "Congratulations MOMS!!"

The benefits for prenatal patients were greater than some had expected:

40 percent had a shunt placed at age 1, compared with 82 percent in the postnatal group.

64 percent had some measure of hindbrain herniation, though much of that was mild. In the postnatal group, 96 percent had it, and it was more severe.

At age 21/2, 42 percent could walk without orthotics or assistive devices, compared with 21 percent in the postnatal group.

The treatment can now be offered as a standard of care for myelomeningocele, the study's authors said. But that does not mean that it's appropriate for everyone.

About 13 percent of mothers screened for the trial were excluded because they weighed too much.

Giovanna and Louis Capuano of Dennis Township, Cape May County, know the stress of deciding whether to move forward with the surgery. Their daughter, Mia Lisa, was the 10th fetus with myelomeningocele operated on at Children's.

Now 11, Mia Lisa, wears leg braces - not as often as she's supposed to - but she is an active, astute sixth grader who dances, draws, and attends acrobatics classes. She has never needed a shunt.

Her parents and Adzick conceded that Mia Lisa was among Children's highest-performing patients. But the Capuanos are hoping the study will help other families make the decision they did. They also hope it will change how people view their daughter.

"You can't look in the textbook [for spina bifida] and see that information and compare that to her," her mother said. "She is different because she had this surgery."

Crombleholme said the real test of the MOMS results would come years from now, when the children are Mia Lisa's age or older. Some effects of spina bifida, including loss of mobility and the need for a shunt, can worsen over time.

The researchers have applied for another federal grant to follow up. They will also compare the cost of fetal surgery with the long-term cost for the two groups.

In the meantime, they'll be answering calls. Howell said she had heard from expectant mothers who caught wind of the results, and Sutton's fellow surgeons are calling for advice: How can they do what he does?