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.

Introduction

Open spina bifida (OSB) results in injury of spinal cord tissue at the level of the bone lesion as well as in hindbrain herniation. Affected individuals require lifelong support and rehabilitation. Early work had suggested that prenatal repair of OSB could prevent or ameliorate damage to the medulla and reverse the hindbrain herniation.1, 2 A recent randomized clinical trial named Management of Myelomeningocele Study (MOMS trial) showed that prenatal correction of OSB via open fetal surgery resulted in improved infant neurological outcomes relative to postnatal repair, but at the expense of increased maternal morbidity.³ Therefore, efforts to reduce maternal risk in the antenatal treatment of OSB are warranted.⁴

Initial attempts to treat OSB using a fetoscopic approach were not encouraging.5, 6 However, Kohl and his group7, 8, 9 reported the use of a percutaneous endoscopic technique with 3 ports and partial carbon dioxide (CO₂) insufflation. The outcomes of the 19 initial patients⁷ and the subsequent 51 patients8, 9 treated by the same group with this technique have been recently reported. Although less invasive than open fetal surgery, this endoscopic technique seemed laborious because it requires dissection of the dura mater and multiple-layer closure.10, 11

Our group first tested the use of biocellulose in rabbit12, 13 and ovine14, 15, 16, 17, 18, 19 models of OSB. The technique involved placing (but not suturing) a biocellulose patch over the spinal defect, followed by skin closure. The biocellulose patch produced a watertight seal by inducing the formation of neoduramater.¹⁷ Translation of this animal work into a clinically applicable fetoscopic technique required a joint effort between our group (Brazilian Fetal Network) and the USFetus Consortium. In 2013, we were approved by the Brazilian National Ethics Committee to begin a phase I trial with 10 patients. The results of the first 4 cases were reported as a preliminary experience to justify continuation of the trial.²⁰ In this article we provide the final results of the Cirurgia Endoscópica para Correção Antenatal da Meningomielocele (CECAM) trial in a total of 10 patients.