The first comprehensive follow-up of 29 babies, born after undergoing fetal surgery at Vanderbilt University Medical Center to repair spina bifida shows a significant reduction in the need for shunts to relieve hydrocephalus.
The follow-up study of the babies who underwent the surgery to repair myelomeningocele, the most common congenital anomaly of the central nervous system and a major cause of serious developmental disability, was published on Wednesday in the Journal of the American Medical Association. It is the first large published study by the physicians who perform the procedure - Drs. Joseph P. Bruner, associate professor of Obstetrics and Gynecology and director of Fetal Diagnosis and Therapy, and Noel B. Tulipan, associate professor of Neurological Surgery and director of Pediatric Neurosurgery. Other authors include Drs. Ray L. Paschall, assistant professor of Anesthesiology, Frank H. Boehm, professor of Obstetrics and Gynecology and director of the Division of Maternal-Fetal Medicine, William F. Walsh, professor of Pediatrics and Chief of Nurseries at Vanderbilt University Hospital, Sandra R. Silva, Research Fellow in the Department of Obstetrics and Gynecology, Marta Hernanz-Schulman, professor of Radiology and Radiological Sciences, Lisa H. Lowe, assistant professor of Radiology and Radiological Sciences and George W. Reed, Ph.D., associate professor of Preventive Medicine.
The 29 babies who underwent fetal surgery were compared to 23 babies born with spina bifida at VUMC, who did not have the fetal surgery repair. All of the babies were over six months of age. "The most dramatic finding is that the need for these children to have shunts was significantly reduced in the fetal surgery babies. In the control patients (those who were not in the surgical group), 91 percent received a shunt within the first few days of life. Only 59 percent of the study patients received a shunt, and the shunt was placed on average two months later than in the control group. That's a marked improvement."
Bruner said the shunt finding is important because shunts lead to more hospitalizations in children with spina bifida. The average shunt must be replaced two times during a child's lifetime.
"No shunts or fewer shunts is a significant benefit to patients, hospitals and insurance companies," Bruner said. "It will decrease the overall rate of hospitalization and care these children will receive," Bruner said.
The study also shows that there is a significant reduction of hindbrain herniation (Chiari Malformation) into the spinal canal in the patients who have undergone the fetal surgery. This may explain the decreased need for shunts, Bruner said.
Tulipan said the reduction in shunting of hydrocephalus translates into a marked reduction in the burden that spina bifida places on affected patients, their families and the health care system.
Tulipan believes the reduction in the severity of the Chiari malformation may be the study's most important finding.
"This is the first convincing evidence that a congenital malformation of the nervous system can actually be reversed," Tulipan said.
The study also confirmed what the fetal surgery team had noticed earlier - the more normal shape of the brains of the children who had the spina bifida repair inutero.
"If you do MRI scans of children who have spina bifida and mix them with MRIs of children who don't have spina bifida, it takes a neurosurgeon about two seconds to pick out the scans of the children with spina bifida," Bruner said. "If you do the same thing, with the scans of the children who have had intrauterine surgery, the neurosurgeon can no longer easily pick out the scan of the affected child. What we do restores the brain to a more normal shape and configuration."
Bruner said it is unclear what this finding means, but it will be the focus of future research by the fetal surgery team. Another finding of the JAMA study is that there is low maternal risk involved in the procedure.
"This is still risky surgery, but it's a lot less risky than originally thought," Bruner said. "The complication rates that we have experienced - preterm labor, infection, bleeding -- are much less than in other published studies with similar procedures," Bruner said. "Part of the reason is that this is an elective surgery. It does not have to be done and doesn't have to be done at any certain time. It may be that our patients are healthier and in better condition at the time of surgery."
Bruner said the study does not demonstrate any improvement in leg function in the surgical group, but added the surgeries all occurred after 24 weeks gestation. The fetal surgery team is now performing the repairs as early as 20 weeks. "Potentially, earlier repair will offer better results," Bruner said.
There have been 64 fetal surgeries to repair spina bifida to date and 57 children have been born. The patients have come to VUMC from 27 states and Canada. Although other fetal surgery programs exist, there are none doing the particular technique that Bruner and Tulipan have performed or performing as many cases. A less invasive endoscopic procedure, performed by the physicians in 1994, proved unsuccessful.
Bruner and Tulipan are now working with other medical centers across the United States who want to establish fetal surgery centers.
Bruner said that only time will allow the team to assess how the children are developing. But the technique has already shown far-reaching benefits.
"It has led to improved techniques for the diagnosis of spina bifida and the development of several instruments and techniques used in the surgery itself," Bruner said. "It has also improved our understanding of the biology of what happens to the uterus when it is operated on during pregnancy. This will be of enormous benefit to all pregnancies affected by birth defects. Finally, it has broken down a huge barrier that has prevented children with non-lethal malformations from obtaining surgery," he said, explaining that fetal surgery originally was only offered as a life-saving procedure. Now, many more babies with birth defects have the option of intrauterine therapy.
Bruner said he is "very optimistic" about the future of the surgery - a future that will more than likely include more fetal surgery repairs for congenital hydrocephalus. So far, the team has only performed one. Neal Borkowski, born May 12, 1999, is developing well at home in Knoxville. Minimizing risks will be another area of focus.
"There have been slow and steady improvements in preventing pre-term labor and in treating small babies for the entire time I've been practicing. If those incremental improvements improve, this surgery will only become better with fewer risks."
Tulipan shares Bruner's optimism and believes the JAMA publication gives merit to the procedure.
"Up until this publication, fetal myelomeningocele repair has been considered highly experimental or even radically experimental. Publication of our results has been limited to case reports and brief presentations at scientific meetings," Tulipan said. "This publication, in a highly respected medical journal, moves us closer to the mainstream and may convince physicians that the procedure has merit."
"I'm optimistic that with further work we will achieve even greater improvements in outcome, and additional reductions in the rate of premature delivery. When this happens I am convinced this procedure will become the standard therapy for spina bifida."