G.L. Acacio

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.

Abstract 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.

Neoskin development in the fetus with the use of a three-layer graft: an animal model for in utero closure of large skin defects

Objective: To assess the ability of a three-layer graft in the closuse of large fetal skin defects. Methods: Ovine fetuses underwent a large (4 × 3 cm) full-thickness skin defect over the lumbar region at 105 days’ gestation (term = 140 days). A bilaminar artificial skin was placed over a cellulose interface to cover the defect (3-layer graft). The skin was partially reapproximated with a continuous nylon suture. Pregnancy was allowed to continue and the surgical site was submitted to histopathological analysis at different post-operative intervals. Results: Seven fetuses underwent surgery. One maternal/fetal death occurred, and the remaining 6 fetuses were analyzed. Artificial skin adherence to the wound edges was observed in cases that remained in utero for at least 15 days. Neoskin was present beneath the silicone layer of the bilaminar artificial skin. Conclusions: Our study shows that neoskin can develop in the fetus using a 3-layer graft, including epidermal growth beneath the silicone layer of the bilaminar skin graft. These findings suggest that the fetus is able to reepithelialise even large skin defects. Further experience is necessary to assess the quality of this repair.

Percutaneous fetoscopic closure of large open spina bifida using a bilaminar skin substitute

We have described previously our percutaneous fetoscopic technique for the treatment of open spina bifida (OSB). However, approximately 20–30% of OSB defects are too large to allow primary skin closure. Here we describe a modification of our standard technique using a bilaminar skin substitute to allow closure of large spinal defects. The aim of this study was to report our clinical experience with the use of a bilaminar skin substitute and a percutaneous fetoscopic technique for the prenatal closure of large OSB defects.

OC16.01: Fetoscopic repair of spina bifida also improves postnatal motor outcomes

Objectives: The uptake of cell-free DNA (cfDNA) testing has resulted in a decrease in invasive prenatal diagnosis (IPD), but atypical chromosomal abnormalities may be missed. We analyzed the chromosomal abnormalities detected by cfDNA as a contingent approach in a single public centre with universal Down syndrome screening (DSS). Methods: In this retrospective cohort study, we compared the types of chromosomal abnormalities detected by IPD using cytogenetic +/chromosomal microarray analysis (CMA) after a positive cfDNA testing as a contingent approach (group 1) versus a positive DSS (group 2) from August 2011 to July 2016 using descriptive analysis and Chi-square test. IPD was publicly funded while cfDNA was self-financed. Results: Of 2,132 women with a positive DSS, 721 chose cfDNA testing and 1,411 direct IPD. Of 721 cfDNA testing (group 1), two failed, one showed an inconclusive result and 29 (4.0%) abnormal results. Of the latter, 27 had known outcomes after IPD including 74.1% common Trisomies, 3.7% mosaicism, 14.8% sex chromosomal abnormalities (SCA), 3.7% atypical aneuploidy, and 3.7% confined placental mosacism. Of 1,411 direct IPD (group 2), 193 (13.7%) showed chromosomal abnormalities including 66.8% common Trisomies, 11.9% mosaicism, 7.8% SCA, 5.3% atypical aneuploidies including those by CMA and 8.3% balanced translocation. Compared to direct IPD (group 2), the proportion and types of chromosomal abnormalities detected by IPD after a positive cfDNA testing (group 1) was different (p < 0.001) with a low/no detection rate of mosacism, atypical aneuploidies and balanced translocations though comparable detection rate of common Trisomies and SCA. Conclusions: The detection rate of mosaicism, atypical aneuploidies, and balanced translocation after using cfDNA as contingent approach was low/no. This could be related to women’ characteristics or limitation of cfDNA. Women should be carefully assessed and adequately counselled on cfDNA vs. IPD after a positive DSS.

OC16.02: Percutaneous fetoscopic 3‐layer closure of large open spina bifida defects using a bilaminar skin substitute

83 to 450 minutes. A total of 42 cases already delivered (4 uneventful vaginal), no uterine dehiscence observed. PPROM occurred in 34/42 (81%) cases. Fetuses remained in utero on average for 6,1w (5d to 13w). Mean GA at delivery was 32,6w, only 16,7% below 30w, mean birthweight was 1906g (890 to 2960g). No intrauterine demise occurred. Two neonatal deaths due to sepsis occurred. VP shunt was placed in 42% cases and two infants died due to shunt related infection. Long-term follow up was obtained in 38 cases, mean 8,9 months. The functional level of the lesion was assessed in total 23 cases and was found to be one or more levels better than the anatomical level in 70%. Conclusions: Entirely percutaneous fetoscopic correction is feasible and safer than open fetal approach; however, it is associated with an increased risk of PPROM. Fetoscopic correction can be used in cases were open surgery cannot. The CECAM technique statistically significantly improves motor outcome, when compared to MOMS trial results, so it is not only safer for mothers but also better for babies.

P09.28: Laser therapy for fetal treatment in complicated monochorionic twin pregnancies: experience in Brazil

rupture of the membranes, the median gestational age at delivery was 36.1 weeks (range 34.1–39.1), with a median weight of 2215 gr (range 1750–2850). No single case of brain damage was detected among the survivors, as assessed by both clinical examination and imaging techniques. Conclusion: Although the number of cases is small, our initial results doing cord occlusion by bipolar forceps are comparable with those reported by others.