MOMS Trial - History

History

1980 - Fetal surgical techniques using animal models were first developed at the University of California, San Francisco by Dr. Michael R. Harrison, Dr. N. Scott Adzick and research colleagues.

1994 - The surgical model that is most similar to simulating the human disease is the fetal lamb model of myelomeningocele (MMC) introduced by Meuli and Adzick in 1994. The MMC-like defect was surgically created at 75 days of gestation (term 145 to 150 days) by a lumbo-sacral laminectomy. Approximately 3 weeks after creation of the defect a reversed latissimus dorsi flap was used to cover the exposed neural placode and the animals were delivered by cesarean section just prior term. Human MMC-like lesions with similar neurological deficit were found in the control newborn lambs. In contrast, animals that underwent closure had near-normal neurological function and well-preserved cytoarchitecture of the covered spinal cord on histopathological examination. Despite mild paraparesis, they were able to stand, walk, perform demanding motor test and demonstrated no signs of incontinence. Furthermore, sensory function of the hind limbs was present clinically and confirmed electrophysiologically. Further studies.showed that this model when combined with a lumbar spinal cord myelotomy leads to the hindbrain herniation characteristic of the Chiari II malformation and that in utero surgery restores normal hindbrain anatomy.

Surgeons at Vanderbilt University, led by Dr. Joseph Bruner, attempted to close spina bifida in 4 human fetuses using a skin graft from the mother using specialized telescope called a laparoscope. Four cases were performed before stopping the procedure - two of the four fetuses died.

1998 - Dr. N. Scott Adzick and team at The Children’s Hospital of Philadelphia performed open fetal surgery for spina bifida in an early gestation fetus (22 week gestation fetus) with a successful outcome.

Surgeons at Vanderbilt University, led by Dr. Noel Tulipan, made an incision in the mother's uterus to obtain better exposure to fetuses of 28 to 30 weeks gestation. All 4 fetuses were born premature but with evidence of reversal of their chiari II malformation. Only 2 of the 4 required ventricular shunts after birth. Fetal surgery after 25 weeks has not shown benefit in subsequent studies

Subsequently, 4 medical centers conducted 253 open spina bifida repairs prior to the MOMs trial. The outcomes were mixed and the only comparison groups were other children that had not undergone repair after birth in the past.