NEURAL TUBE DEFECTS FETAL SURGERY

FETAL SURGERY FOR TREATMENT OF NEURAL TUBE DEFECTS
Over the past decade, fetal surgery for NTDs (specifically, myelomeningocele) has developed. Interest in this approach to the treatment of NTDs stems from a growing body of literature that supports the 2-hit hypothesis. Initially, most investigators believed that all the neurologic deficits seen in NTDs resulted from the neurulation defect that occurs during days 26-28 of gestation. However, with skin in utero theoretically decreases the damage to the exposed neural structures. In addition, it has been suggested that the loss of CSF through the central canal can be halted by in utero closure of the neural placode, thereby reversing some of the potentially devastating neurologic sequelae of NTDs.

The 2 neurologic sequelae of major concern are shunt-dependent hydrocephalus and hindbrain injury from progressive hindbrain herniation through the foramen magnum (Chiari II malformation). In 1999, Vanderbilt University researchers, led by pediatric neurosurgeon Noel Tulipan, MD, and obstetrician Joseph P. Bruner, MD, reported in JAMA their experience with in utero surgery for NTD over the previous decade. This was a single-institution nonrandomized, observational study conducted between 1990 and 1999. A cohort of 29 patients with isolated myelomeningocele underwent intrauterine repair of the NTD between 24 and 30 weeks of gestation. These patients were compared to 23 lesion-matched controls who underwent postnatal surgery. The main outcome measure was requirement for placement of a ventriculoperitoneal shunt for the treatment of hydrocephalus.

Results of the study have been promising. NTD patients who underwent in utero surgery experienced a lower incidence of hydrocephalus than the control group (59% versus 91%). Also, a reduced incidence of hindbrain herniation was evident in the in utero group (38% versus 95%). One death occurred in the in utero group, as did an increased risk of oligohydramnios (48% versus 4%), and an earlier age of delivery by about 4 weeks. Regardless, the results have encouraged a group of investigators from both Vanderbilt and Children's Hospital of Pennsylvania (CHOP) to propose that a few select centers investigate whether this approach will yield durable results. (CHOP published their results in The Lancet in 1998). Since that proposal, the NIH has funded grants to study the efficacy of in utero surgery in this patient population. Currently, the following 3 centers are conducting this research: CHOP/University of Pennsylvania, Vanderbilt, and the University of California at San Francisco.

Specific questions to be answered are as follows:
• Will the decreased rate of shunt dependency hold up through time?
• Will the decreased incidence of hindbrain herniation translate into a decreased incidence of hindbrain-related neurologic complications?
• Will the decreased incidence in hydrocephalus and hindbrain herniation translate into improved neurologic status for both the hindbrain structures and the lower extremities?
• Will the significant risks to the fetus and mother be outweighed by the long-term potential benefits to the NTD-affected child?