In utero meconium exposure increases spinal cord necrosis in a rat model of myelomeningocele.

BACKGROUND/PURPOSE The rationale for in utero repair of myelomeningocele has been supported experimentally by the observation of preserved neural function after prenatal closure of surgically created defects compared with nonrepaired controls. The mechanism of injury to the exposed neural elements is unknown. Postulated mechanisms include trauma to the herniated neural elements or progressive injury from amniotic fluid exposure as gestation proceeds. A component of amniotic fluid that may contribute to neural injury is meconium. In the current study the effect of human meconium on the exposed spinal cord in a fetal rat model of myelomeningocele was examined. METHODS Twenty time-dated pregnant rats underwent laparotomy at 181/2 days of gestation. The exposed uterus was bathed in ritrodrine for tocolysis. The amniotic cavity was opened over the dorsal midline of the fetal rat, and, under a dissecting microscope (x25), a 2- to 3-level laminectomy was performed. Under magnification (x40), the translucent dura was opened using a 25-gauge needle as a knife. Two fetuses per dam were operated on. In the control group, the amniotic fluid was restored with saline solution, whereas in the experimental group a solution of Human meconium diluted (10%) in saline was used to restore the amniotic fluid. Fetuses were harvested by cesarean section at 211/2 days' gestational age. The liveborn pups were then killed and fixed in 10% formaline. Sections 10 micrometer thick were stained with H&E and studied by light microscopy for evidence of spinal cord injury. RESULTS Seven of 20 (35%) experimental rat pups and 6 of 20 (30%) control rat pups were liveborn. All liveborn pups had severe paralysis of the hindlimbs and tail, so that functional differences between the 2 groups could not be detected. Histologic examination of 13 spinal cords at the site of surgical exposure showed that necrosis of neural tissue in 5 of 7 meconium-exposed rat pups was increased when compared with that observed in the 6 fetuses exposed to amniotic fluid without meconium. In general, inflammation was greater and repair processes appeared delayed in meconium-exposed rat pups. CONCLUSIONS Exposure of the spinal cord of fetal rats to amniotic fluid by surgically created myelomeningocele leads to severe functional impairment. Histologically recognizable necrosis of neural elements was increased in those animals that were exposed to diluted human meconium in the amniotic fluid. The results support the hypothesis that meconium may contribute to the pathophysiology of spinal cord injury observed in myelomeningocele.