Endoscopic surgery for the antenatal treatment of myelomeningocele: the CECAM trial.

BACKGROUND: A recent randomized clinical trial named Management of Myelomeningocele Study (MOMS trial) showed that prenatal correction of open spina bifida (OSB) via open fetal surgery was associated with improved infant neurological outcomes relative to postnatal repair, but at the expense of increased maternal morbidity. OBJECTIVE: We sought to report the final results of our phase I trial (Cirurgia Endoscópica para Correção Antenatal da Meningomielocele [CECAM]) on the feasibility, safety, potential benefits, and side effects of the fetoscopic treatment of OSB using our unique surgical technique. STUDY DESIGN: Ten consecutive pregnancies with lumbosacral OSB were enrolled in the study. Surgeries were performed percutaneously under general anesthesia with 3 ports and partial carbon dioxide insufflation. After appropriate surgical positioning of the fetus, the neuroplacode was released with scissors and the skin was undermined to place a biocellulose patch over the lesion. The skin was closed over the patch using a single running stitch. Preoperative, postoperative, and postnatal magnetic resonance imaging were performed to assess hindbrain herniation. Neurodevelopmental evaluation was performed before discharge and at 3, 6, and 12 months. All cases were delivered by cesarean delivery, at which time the uterus was assessed for evidence of thinning or dehiscence. RESULTS: The median gestational age at the time of surgery was 27 weeks (range 25-28 weeks). Endoscopic repair was completed in 8 of 10 fetuses. Two cases were unsuccessful due to loss of uterine access. The mean gestational age at birth was 32.4 weeks with a mean latency of 5.6 weeks between surgery and delivery (range 2-8 weeks). There was 1 fetal and 1 neonatal demise, and 1 unsuccessful case underwent postnatal repair. Of the 7 infants available for analysis, complete reversal of hindbrain herniation occurred in 6 of 7 babies. Three babies required ventriculoperitoneal shunting or third ventriculostomy. Functional motor level was the same or better than the anatomical level in 6 of 7 cases. There was no significant maternal morbidity and no evidence of myometrial thinning or dehiscence. However, surgeries were complicated by premature rupture of membrane and prematurity. CONCLUSION: Our study suggests that the antenatal treatment of OSB using a fetoscopic approach and our unique surgical technique can result in a watertight seal, reversal of the hindbrain herniation, and better than expected motor function. Our technique differs substantially from the classic repair of OSB used in prior open fetal surgery and fetoscopic studies, in which the dura mater is dissected and the defect is closed in multiple layers. Instead, we use a biocellulose patch placed over the lesion and simple closure of the skin. As such, our technique is an alternative to the current paradigms in the antenatal treatment of OSB. Our clinical outcomes are in line with the results of our extensive prior animal work. Maternal benefits of our approach and technique include minimal morbidity and no myometrial legacy. Current limitations of the approach include potential loss of access, premature rupture of membranes, and attendant prematurity. Phase II trials are needed to prevent these complications and to further assess the risks and benefits of our distinct surgical approach and technique.

Fetoscopic single-layer repair of open spina bifida using a cellulose patch: preliminary clinical experience.

OBJECTIVE: To report our preliminary clinical experience in the antenatal correction of open spina bifida (OSB) using a fetoscopic approach and a simplified closure technique. METHODS: Four fetuses with lumbar-sacral defects were operated in utero from 25 to 27 weeks. Surgeries were performed percutaneously under general anesthesia using three trocars and partial carbon dioxide insufflation. After dissection of the neural placode, the surrounding skin was closed over a cellulose patch using a single continuous stitch. RESULTS: Surgical closure was successful in three of the four cases. All successful cases showed improvement of the hindbrain herniation and no neonatal neurosurgical repair was required in two cases. Delivery occurred between 31 and 33 weeks, and no fetal or neonatal deaths occurred. Ventriculoperitoneal shunting was not needed in two out of the 3 successful cases. CONCLUSIONS: Our preliminary experience suggests that definitive fetoscopic repair of OSB is feasible using our innovative surgical technique. A phase I trial for the fetoscopic correction of OSB with this technique is currently being conducted.

Successful fetal surgery for the repair of a 'myelomeningocele-like' defect created in the fetal rabbit.

OBJECTIVE: To study the correction of a 'myelomeningocele-like' defect in fetal rabbits. METHODS: Twelve pregnant rabbits had a spinal defect surgically created in 40 of their fetuses at 23 days of gestation. Immediate repair was performed in 30 fetuses (group I), and 10 remained uncorrected (group II). After 30 days, the fetuses were harvested and the anatomopathological aspects where compared using Fisher's exact test. RESULTS: Three different techniques to apply a cellulose graft were used for correction in 8 (technique A), 7 (technique B), and 15 animals (technique C), but only one (technique C) was successful. The survival rate at 30 days was 66.7% (10/15) in group I and 80% (8/10) in group II. A 'myelomeningocele-like' defect was present in all fetuses in group II, while in group I the defect was successfully repaired in 80% of the surviving fetuses (p < 0.01). CONCLUSION: The surgically created spinal defect was successfully repaired, and also the fetal rabbit could be established as a model for the study of intrauterine correction of a myelomeningocele-like defect.

Estudo de uma nova técnica para criação cirúrgica de um defeito semelhante a meningomielocele em fetos de coelhos / Study of a new technique to surgical create of a myelomeningocele like defect in the fetal rabbit

OBJETIVO: Avaliar a sobrevida fetal usando uma nova técnica cirúrgica para criação de um defeito semelhante a meningomielocele em fetos de coelho. MÉTODOS: Foram utilizadas seis coelhas da linhagem Nova Zelândia que tiveram um defeito espinhal criado em seus fetos no 23º dia de gestação. O defeito foi criado em 19 fetos e a tentativa de correção foi feita em 15 casos (grupo I), 4 fetos permaneceram sem correção (grupo II). No 30º dia de gestação, os fetos foram submetidos a avaliação anátomo-patológica. RESULTADOS: No 30º dia a meningomielocele estava presente em todos os fetos sobreviventes. A sobrevida total foi de 73,68 por cento (14/19), 11 fetos sobreviveram no grupo I, e 3 no grupo II. CONCLUSÃO: A técnica modificada apresenta sobrevida fetal satisfatória, no modelo experimental de criação de defeito espinhal em fetos.

Origin of amnion and implications for evaluation of the fetal genotype in cases of mosaicism.

OBJECTIVE: To investigate presence of trisomy in amniotic epithelium (uncultured amnion) and mesenchyme (cultured amnion) from mosaic cases to understand the origins of these tissues and their relationship to pregnancy outcome. METHODS: Polymerase chain reaction (PCR) of microsatellite loci was used to determine the presence of trisomy (of meiotic origin only) in amnion samples from 33 placentas previously ascertained because of a prenatal diagnosis of trisomy mosaicism that was predominantly confined to the placental tissues. RESULTS: In 16 (48%) of 33 cases, trisomy was confirmed to be present by molecular analysis of uncultured amnion. In contrast, cytogenetic analysis of cultured amnion showed trisomy in only 2 of 20 informative cases. The molecular detection of trisomy in amnion was strongly associated with poor pregnancy outcome (intrauterine growth restriction, fetal anomalies and/or intrauterine/neonatal death) even when analysis was limited to cases negative for the trisomy on amniotic fluid (N = 22, p = 0.0005). CONCLUSIONS: We infer that amniotic mesenchyme (usually diploid) derives from early embryonic mesoderm of the primitive streak and not from the hypoblast as is commonly cited. Trisomy in amniotic epithelium suggests that high numbers of abnormal cells were present in the epiblast, and this correlates with poor outcome even when the subsequently derived fetus and amniotic mesenchyme appear to carry only diploid cells.

A different technique to create a 'myelomeningocele-like' defect in the fetal rabbit.

OBJECTIVE: To evaluate the fetal survival rate using a modified technique to surgically create a 'myelomeningocele-like' defect in a rabbit model. METHODS: Six white New Zealand rabbits had a spinal defect created in their fetuses at 23 days of gestation. At 30 days of gestation, the fetuses were harvested for anatomo-pathologic evaluation. RESULTS: The defect was created in 19 fetuses and an attempt to correct it was made in 15 cases (group I), and 4 fetuses where left without correction (group II). At 30 days, a 'myelomeningocele-like' defect was present in all surviving fetuses. The total survival rate was 73.68% (14/19); 11 fetus survived in group I and 3 in group II. CONCLUSION: The technical modifications, including fetal positioning and exposure of its back prior to the incision of the lamina, associated with a different technique for myometrium closure, offer an alternative and probably safer method to surgically create a spinal defect in the fetal rabbit.