Fetal surgery for neural tube defects

Abstract

Open spina bifida remains a major source of disability despite an overall decrease in incidence. It is frequently diagnosed prenatally and can thus --potentially --be treated by fetal surgery. Animal studies and preliminary human studies strongly suggest that at least a portion of the neurological abnormalities seen in these patients are secondary, and occur in mid-gestation. It is estimated that approximately 400 fetal operations have now been performed for myelomeningocele world wide. Despite this large experience, the technique remains of unproven benefit. Preliminary results suggest that fetal surgery results in reversal of hindbrain herniation (the Chiari II malformation), a decrease in shunt-dependent hydrocephalus, and possibly improvement in leg function, but these findings might be explained by selection bias and changing management indications. A randomized prospective trial (the MOMS trial) is currently being conducted by three centers in the United States, and is estimated to be completed in 2009.

Vascular and apoptotic changes in the placode of myelomeningocele mice during the final stages of in utero development

“…3,[31][32][33][34] In contrast, deficits in the lower limbs and in urodynamic function in patients submitted to MMC correction, through either fetal or classic postnatal surgery, were similar to those of controls. 14,30,27 Attending to these data, the potential benefits of in utero repair of MMC are under scrutiny in a randomized trial designed to compare the clinical outcomes of patients with MMC treated with either fetal or postnatal surgery. 2 Recently, using a mouse model of MMC, we documented astrocytic proliferation during gestation together with neuronal degeneration, after embryonic Day 16.5 (full-term gestation: 19 days), predominantly in the dorsal part of the placode.…”

Cell sheet Transplantation in the Treatment of Fetal Myelomeningocele

“…We also could expect that the use of the cell sheet technology is more advantageous compared with other cell delivery modality in light of a higher cell density as well as a highly efficient regenerative potential. Actually, the cell sheet-based tissue engineering has been medically accepted and successfully applied in the field of regeneration of pathologically affected myocardium, cornea, epithelium, esophagus, lung, liver, pancreas, thyroid, and periodontal tissues [4,9]. Naturally, cell sheet technology might work better in the fetal biological environment where highly proliferative stem cells are actively working in the amniotic fluid as well as in a variety of fetal tissues.…”

“…Usually, MMC is a non-fatal but neurologically devastating congenital anomaly that leaves affected children with lifelong motor paralysis of the lower extremities, skeletal deformities, urinary and fecal incontinence, sexual dysfunction, and cognitive disabilities [1][2][3][4]. Surgical correction of fetal MMC has been predominantly performed to suppress the progression of in utero histological damages of the exposed spinal cord expecting clinical amelioration of postnatal neurological dysfunction although it could reportedly be associated with several fetomaternal risks including preterm birth with prematurity.…”

Anesthesia for In Utero Repair of Myelomeningocele

“…12,27 Early studies looking at open in utero repair of myelomeningocele in humans suggested a reduction in hindbrain herniation, but risks to both the fetus and mother were apparent. 19,20 These findings led to the development and recent publication of an unmasked, randomized, prospective clinical trial examining the potential benefit of open fetal surgery, The Management of Myelomeningocele Study (MOMS).…”