A Randomized Trial of Prenatal Versus Postnatal Repair of Myelomeningocele

Abstract

Myelomeningocele is one of the most common birth defects, characterized by a defect in the bony spine and resultant extrusion of the spinal cord into a sac filled with cerebrospinal fluid. It occurs in 3 to 4 per 10,000 live births in the United States, and the death rate of live-born infants with this condition is about 10%. It has been suggested that the final neurologic deficit results from failure of neural-tube formation as well as spinal cord injury due to prolonged exposure of neural elements to the intrauterine environment, and studies in animal models have suggested that prenatal repair of a spina bifida-like lesion preserves neurologic function and improves hindbrain herniation. In utero repair of myelomeningocele in humans was first performed in 1997, and in the next 5 years, the procedure was performed in more than 200 fetuses. Although prenatal repair data in early studies suggested a dramatic improvement in hindbrain herniation compared with historic controls, this was accompanied by an increased risk of preterm birth and uterine dehiscence, as well as an increased risk of fetal or neonatal death. The randomized study compared the safety and efficacy of prenatal repair of myelomeningocele with that of a standard postnatal repair. Eligible women were randomly assigned to undergo either prenatal surgery before 26 weeks of gestation (n = 91) or standard postnatal repair (n = 92). The first of 2 primary outcomes at 12 months' corrected postnatal age was a composite of fetal or neonatal death or the need for a cerebrospinal fluid shunt; the second at 30 months of age was a composite score of the Mental Development Index of the Bayley Scales of Infant Development II and the child's motor function. The trial was stopped prematurely after an interim analysis found there to be a benefit to prenatal surgery. A total of 158 women were included in the final analysis for outcomes up to 12 months and 134 for outcomes up to 30 months. The first primary outcome occurred among significantly fewer infants in the prenatal surgery group compared with the postnatal surgery group (prenatal group: 68% vs. postnatal group: 98%); the relative risk (RR) was 0.70 (with a 97.7% confidence interval [CI]: 0.58–0.84; P < 0.001). Rates of shunt placement were lower in the prenatal surgery group (40%) than in the postnatal-surgery group (82%); the RR was 0.48 (with a 97.7% CI: 0.36–0.64; P < 0.001). Compared with the postnatal surgery group, prenatal surgery was associated with significant improvement in the second primary outcome, a composite score of mental development and motor function at 30 months (P = 0.007). There was also improvement in several secondary outcomes: the proportion of infants with no evidence of hindbrain herniation at 12 months of age was higher with prenatal surgery, and significantly more children were ambulatory at 30 months of age (P = 0.01). Despite these benefits, prenatal surgery increased the risk of preterm delivery and repair site uterine dehiscence at delivery. These findings from a randomized multicenter study are consistent with previous early data, and the investigators concluded that the potential benefits of prenatal surgery must be balanced against the risk of preterm birth and fetal or neonatal morbidity.