Fetal surgery for spina bifida: Past, present, future

Abstract

Open spina bifida or myelomeningocele (MMC) is a common birth defect that is associated with significant lifelong morbidity. Little progress has been made in the postnatal surgical management of the child with spina bifida. Postnatal surgery is aimed at covering the exposed spinal cord, preventing infection, and treating hydrocephalus with a ventricular shunt. Experimental and clinical evidence suggest that the primary cause of the neurologic defects associated with MMC is not simply incomplete neurulation, but rather chronic mechanical and amniotic-fluid induced chemical trauma that progressively damages the exposed neural tissue during gestation. The cerebrospinal fluid leak through the MMC leads to hindbrain herniation and hydrocephalus. In utero repair of open spina bifida is now performed in selected patients and presents an additional therapeutic alternative for expectant mothers carrying a fetus with MMC. In the past, studies in animal models and clinical case series laid the groundwork for a clinical trial to test the safety and efficacy of fetal MMC repair. In the present, a prospective, randomized study (the MOMS trial) has shown that fetal surgery for MMC before 26 weeks’ gestation may preserve neurologic function, reverse the hindbrain herniation of the Chiari II malformation, and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, this study also demonstrates that fetal surgery is associated with significant risks related to the uterine scar and premature birth. In the future, research will expand our understanding of the pathophysiology of MMC, evaluate the long-term impact of in-utero intervention, and to refine timing and technique of fetal MMC surgery using tissue engineering technology.

Tissue Engineering Strategies for Fetal Myelomeningocele Repair in Animal Models

“…The MOMS trial demonstrated conclusively that fetal surgery improves the 12- and 30-month outcomes of MMC patients, with a reduction in hindbrain herniation and the need for shunting and significant improvement in functional neurological outcomes, including the ability to walk without orthotics, setting a new standard for the treatment of eligible MMC fetuses. However, open fetal surgery for MMC is not a cure, with most patients demonstrating some degree of residual neurological deficit and some fetuses demonstrating no benefit over predicted neurological function [2]. Thus, it is clear that further improvements in the prenatal treatment of MMC fetuses are needed.…”

“…The application of an invasive procedure with significant potential risk to the mother was felt to be justified due to the devastating neurological consequences of MMC, including lower extremity paralysis, neurogenic bladder and hindbrain herniation [1,2]. The rationale for fetal treatment is based on the ‘two-hit' hypothesis, where the first ‘hit' is the primary failure of neurulation, and the second ‘hit' is the injury to exposed neural elements caused by exposure to amniotic fluid and mechanical trauma within the amniotic space [3].…”

Fetal Myelomeningocele Closure: Technical Considerations

“…Neurological benefit was difficult to demonstrate. If the technical difficulties with prematurity and graft placement can be overcome, these strategies could eventually prove useful [17]. …”

Morphometric Analysis of Lumbar Pedicles in Patients with Spinal Dysraphism

“…These defects occur in 1 of 3,000 live births and are often associated with complex medical symptoms such as mental retardation, orthopedic disabilities and paralysis [1]. Treatment includes surgical repair either at birth or midgestationally and involves closure of the neural tube with maximal preservation of neuronal and surrounding tissue [1,2].…”

“…These defects occur in 1 of 3,000 live births and are often associated with complex medical symptoms such as mental retardation, orthopedic disabilities and paralysis [1]. Treatment includes surgical repair either at birth or midgestationally and involves closure of the neural tube with maximal preservation of neuronal and surrounding tissue [1,2]. Despite aggressive treatment, patients with the diagnosis of myelomeningoceles carry a 5-year mortality rate of just under 14%, while those who survive often progress to have severer spinal deformities, such as kyphosis and scoliosis [1].…”