Building on Decades of Research
Starting two decades ago, pioneering animal studies by Adzick and collaborators such as Martin Meuli, M.D. (now Surgeon-in-Chief at Zurich Children’s Hospital in Switzerland) showed that the timing of the myelomeningocele repair was important, a finding borne out by clinical experience in fetal surgery done before the MOMS trial. “The damage to the spinal cord and nerves is progressive during pregnancy, so there’s a rationale for performing the repair by the 26th week of gestation, rather than after birth,” said Sutton.
The abnormal spinal development underlying myelomeningocele triggers a cascade of disabling consequences, including weakness or paralysis below the level of the defect on the spinal column. In addition, leakage of cerebrospinal fluid through the open spina bifida defect results in herniation of the brainstem down into the spinal canal in the neck—a condition called hindbrain herniation. Hindbrain herniation obstructs the flow of cerebrospinal fluid within the brain, leading to hydrocephalus, a life-threatening buildup of fluid that can injure the developing brain. Surgeons must implant a shunt, a hollow tube that drains fluid from the brain into the child’s abdominal cavity. However, shunts may become infected or blocked, often requiring a series of replacements over a patient’s lifetime.
What the Study Found
The current study reports data on 158 patients who were followed at least one year after surgery. Clinicians who were independent of the surgical teams and blinded (not informed which of the two surgeries a given child received) evaluated the children from the study at one year of age and again at age 30 months.
-At one year of age, 40 percent of the children in the prenatal surgery group had received a shunt, compared to 83 percent of the children in the postnatal group. During pregnancy, all the fetuses in the trial had hindbrain herniation. However, at age 12 months, one-third (36 percent) of the infants in the prenatal surgery group no longer had any evidence of hindbrain herniation, compared to only 4 percent in the postnatal surgery group.
-At age 30 months, children in the prenatal group had significantly better scores in measurements of motor function. While the ability to walk depends on the level of the spina bifida lesion, the study found a twofold increase in the proportion of children able to walk without crutches or other assistive devices—42 percent in the prenatal group compared to 21 percent in the postnatal group.
-As with any surgery, fetal surgery carries risks. Fetal surgery in this study raised the risk of premature birth and scarring in the mother’s uterus. “Additionally, the surgical site in the uterus used for fetal surgery requires that the mother will have to undergo a cesarean section for any subsequent births,” said study co-author Mark P. Johnson, M.D., obstetrics director at the Center for Fetal Diagnosis and Treatment (CFDT).
“The mothers, children and families who participated in this MOMS trial, and who are continuing to be available for follow-up studies, have made an important contribution to our knowledge and treatment of spina bifida,” said Lori J. Howell, R.N., M.S., Executive Director of the CFDT, and a study co-author. “Because of their involvement, we are better able to accurately counsel other families about what it will mean to have a child with spina bifida—and to offer a rigorously tested, innovative prenatal surgical treatment.”
Next Steps in Fetal Surgery
Although the trial results mark a milestone in spina bifida treatment, not every woman carrying a fetus with spina bifida may be a suitable candidate for fetal surgery. For example, severely obese women were not included in the current study because they have a higher risk of surgical complications. Adzick noted that further research will continue to refine surgical techniques and improve methods to reduce the risks to mothers and fetuses.
In the meantime, concluded Adzick, “Both the experimental outcomes of animal studies and the results of the MOMS trial suggest that prenatal surgery for myelomeningocele stops the exposure of the developing spinal cord to amniotic fluid and thereby averts further neurological damage in utero. In addition, by stopping the leak of cerebrospinal fluid from the myelomeningocele defect, prenatal surgery reverses hindbrain herniation in utero. We believe this in turn mitigates the development of hydrocephalus and the need for shunting after birth.”