Prenatal surgery for the most severe form of the birth defect spina bifida doubled the number of children who were able to walk unassisted by the age of 30 months and halved the percentage who had to have shunts implanted after birth to remove water from the brain, researchers reported Wednesday.
The surgery, however, presented some risks to both children and mothers: Infants were more likely to be born preterm and mothers suffered a thinning of the uterine wall that would require all future births to end in a caesarean section.
The prenatal surgery is "certainly not a cure," said Dr. N. Scott Adzick of the Children's Hospital of Philadelphia, who led the study reported in the New England Journal of Medicine. But on balance, he added, "we believe it is now the standard of care" for the condition.
Spina bifida occurs when the spinal sheath does not fully close around the spinal cord during development. In the most serious and most common form, called myelomeningocele, the spine protrudes through an opening of the spinal column where it is sometimes enclosed in a fluid-filled sac.
The disorder affects about 1,500 children in the United States every year. In addition, an unknown number of women terminate their pregnancies because their fetus is diagnosed with it.
The severity of the condition depends on the location of the opening on the spinal cord — the higher the lesion, the more disabling the effects. Typically, those afflicted experience weakness and/or paralysis in the area below the defect, making it difficult to walk without assistance or impossible to move the legs and feet, as well as partial or complete loss of bladder and bowel function.
They are also susceptible to hydrocephalus, a life-threatening buildup of fluid on the brain. This can be treated by inserting a shunt, but the shunts are prone to infection and typically must be replaced many times over a patient's lifetime.
It is not clear what causes spina bifida, but women can sharply reduce the risk by consuming 400 micrograms of folic acid a day. For women who have already had a pregnancy affected by the defect, authorities recommend that they consume 4,000 micrograms a day. More recent research shows that deficiencies of vitamin B12 also increase the risk. Health officials now recommend a minimum of 2.4 micrograms a day of B12 for women of childbearing age.
Pediatric surgeons commonly operate on spina bifida infants within 24 hours after birth to close the spine and protect the spinal cord, but by then the damage has been done.
Studies conducted with sheep by Adzick and colleagues when he was at UC San Francisco showed that exposure of the spinal cord to toxins in the amniotic fluid produces much of the damage associated with myelomeningocele and that preventing such exposure by the 26th week of gestation minimizes damage.
Based on these findings, Adzick and others went on to perform prenatal surgery, and by 2003 had operated on about 200 fetuses with what appeared to be good success. But questions remained about the potential harm to mother and child. To address the concerns, the Eunice Kennedy Shriver National Institute of Child Health and Human Development organized a study to enroll 200 women whose fetuses had the disorder.
All the fetuses had hindbrain herniation, a severe complication in which the base of the brain is pulled into the spinal canal. During the course of the study, all centers that performed the surgery agreed to stop doing it and funnel all patients to one of the three participating centers: Children's Hospital of Philadelphia, UC San Francisco and Vanderbilt University Medical Center. There, half got prenatal surgery between the 19th and 16th week of gestation and half got surgery within 24 hours after birth.
The study was halted eight weeks ago after 183 women had been enrolled because the results were unequivocal.
At 1 year of age, two infants in each group had died. Shunts had been placed in 40% of those who had undergone prenatal surgery, compared with 83% of those who had postnatal surgery. And more than a third of those who had undergone prenatal surgery no longer had any evidence of hindbrain herniation, compared with 4% of those in the postnatal group.
At 30 months, 42% of the children who had prenatal surgery were able to walk independently, compared with 21% of those in the other group. That improvement occurred despite the fact that, on average, the prenatal surgery group had more severe lesions.
The primary risk was preterm birth: On average, those who had the prenatal surgery were born at 34 weeks, compared with 37 weeks for the other group. The team is monitoring the children to determine if there are any long-term effects on development from the premature birth.
The surgery still leaves much to be desired but is nonetheless "a major step in the right direction," wrote Dr. Joe Leigh Simpson of Florida International University and Dr. Michael F. Greene of Massachusetts General Hospital in an editorial accompanying the report.
"The surgery is not for everyone," said Dr. Diana L. Farmer, who led the UC San Francisco team. The main reason for excluding women from the study was obesity, which is, unfortunately, a risk factor for both spina bifida and complications during surgery. The team also excluded infants with severe deformities of the spine that would make surgery difficult or impossible.