Fetoscopic Myelomeningocele Repair

Fetoscopic Myelomeningocele Repair

Prenatal myelomeningocele (MMC) repair has significant advantages over postnatal repair, as was demonstrated by the Management of Myelomeningocele Study (MOMS) in 2011 1)

MOMS Trial.


Prenatal surgery for spina bifida via open fetal surgery with hysterotomy decreases the rate of ventriculoperitoneal shunt placement and improves motor function compared to standard postnatal surgery. Maternal risks of open fetal surgery are primarily related to complications of the hysterotomy including thinning or rupture that begins in the index pregnancy but persists for every future pregnancy. Minimizing maternal risks is the largest impetus to explore and optimize a minimally invasive fetoscopic alternative. Techniques vary from using a complete percutaneous approach to open fetoscopy, which requires laparotomy but is minimally invasive to the uterus. This allows vaginal delivery at term and no scar complications are reported thus far. Fetal short-term neurosurgical outcomes compare favorably with improvement in hindbrain herniation >70% and decreased need for treatment for hydrocephalus between 40-45% after prenatal surgery performed either fetoscopically or through open fetal surgery 2).

The fetoscopic procedure takes about 2.5 hours. A general anesthetic is first given to the mother. That anesthetic relaxes the uterus and the fetus before the fetus receives intramuscular pain medication. Carbon dioxide is inserted into the uterus to improve visualization of the spinal defect. The repair is performed by inserting 2-millimeter instruments through tiny ports.


The number of cases operated correlates with the outcome of SB fetal closure and ranges from 35 cases for standard-hysterotomy to ≥56-57 cases for minimally invasive modifications. The observations provide important information for institutions eager to establish a new fetal center, develop a new technique or train their team, and inform referring clinicians, potential patients and third-parties 3).


Early outcome urodynamic testing analyses demonstrated a lower incidence of high-risk bladders in Fetoscopic Myelomeningocele Repair patients with a trend toward clinically significant improvement compared to prenatal open in regard to all evaluated metrics. Larger, prospective, confirmatory studies are needed to further evaluate the potential benefits of Fetoscopic Myelomeningocele Repair on bladder safety and health 4).


Following fetoscopic closure of spina bifida, the MOMS MgSO4 regimen is associated with an increased risk of pulmonary edema than a more flexible regimen 5).

An Institutional review board-approved retrospective analysis of all patients undergoing all forms of Myelomeningocele repair with inclusion criteria and exclusion criteria based on the MOMS trial was performed. Bladder safety assessment required initial urodynamic testingrenal bladder ultrasound (RBUS), and/or voiding cystourethrography (VCUG) within the 1st year of life. Follow-up analyses within the cohorts required follow-up studies within 18 months after initial evaluations. Outcomes assessed included bladder-risk-categorization based on the CDC UMPIRE study (high, intermediate, and safe), hydronephrosis (HN), and vesicoureteral reflux (VUR). A single reader evaluated each urodynamic testing.

Initial urodynamic testing in 93 patients showed that the prevalence of high-risk bladders was 35% Fetoscopic Myelomeningocele Repair versus 36% traditional postnatal repair (PSTNR) and 60% prenatal open. Follow-up urodynamic testing showed only 8% of Fetoscopic Myelomeningocele Repair were high-risk compared to 35% prenatal open and 36% traditional postnatal repair. Change from initial to follow-up bladder-risk-category did not reach significance (p = .0659); however, 10% postnatal repair worsened to high-risk on follow-up, compared to none in either prenatal group. A subanalysis of follow-up urodynamic testing between the prenatal cohorts also was not significant (p = .055). Only 8% of Fetoscopic Myelomeningocele Repair worsened or stayed high-risk compared to 35% with prenatal open (p = .1). Hydronephrosis was significantly different at initial and subsequent follow-up between the groups with the least in the Fetoscopic Myelomeningocele Repair group.

Early outcome urodynamic testing analyses demonstrated a lower incidence of high-risk bladders in Fetoscopic Myelomeningocele Repair patients with a trend toward clinically significant improvement compared to prenatal open in regard to all evaluated metrics. Larger, prospective, confirmatory studies are needed to further evaluate the potential benefits of Fetoscopic Myelomeningocele Repair on bladder safety and health 6).


To evaluate if magnesium sulfate (MgSO4) titration following fetoscopic spina bifida closure is associated with fewer maternal complications than the Management of Myelomeningocele Study (MOMS) tocolytic regimen.

This prospective cohort study included 73 consecutive patients undergoing fetoscopic closure of spina bifida between 2015 and 2020. A policy of using the MgSO4 regimen per the MOMS trial was changed to a flexible one in which MgSO4 was titrated according to the frequency of the uterine contractions following surgery. The frequency of maternal pulmonary edema, low maternal oxygen saturation requiring oxygen supplementation, atelectasis, hypocalcemia and preterm delivery was compared before and after the policy was changed.

A higher proportion of women in the group that used the MOMS MgSO4 regimen had pulmonary edema compared to those in the flexible one [26.1% (6/23) vs. 6% (3/50); p= 0.024). Multivariate analysis showed that the MOMS tocolytic regimen was independently associated with a higher risk of pulmonary edema (aOR: 8.57; 95% CI: 1.54-47.7; p= 0.014) than a flexible one. There was no difference in the rate of preterm delivery.

Following fetoscopic closure of spina bifida, the MOMS MgSO4 regimen is associated with an increased risk of pulmonary edema than a more flexible regimen 7).


The Management Of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida (SB). Developed alternative techniques may reduce maternal risks yet should do without compromising on fetal neuroprotective effects.

Joyeux et al., searched Medline, Web of Science, Embase, Scopus, and Cochrane databases and the grey literature to identify relevant articles without language restriction from January 1980 until October 2018. They systematically reviewed and selected studies reporting all consecutive procedures and with a postnatal follow-up ≥12 months. They also had to report outcome variables necessary to measure the learning curve defined by fetal safety and efficacy. Two independent authors retrieved the data, assessed the quality of the studies, and categorized observations into blocks of 30 patients. For the meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the learning curve, we used two complementary methods. With the group splitting method, competency was defined when the procedure provided comparable results to the MOMS trial for 12 outcome variables representative for (1) the immediate surgical outcome, (2) short-term neonatal neuroprotection, and (3) long-term neuroprotection at ≥12 months. Then, when the patients’ raw data were available, they performed cumulative sum (CUSUM) analysis based on a composite binary outcome defining a successful surgery. It combined four clinically relevant variables for safety (fetal death within 7 days) and for efficacy (neuroprotection at birth).

They included 17/6024 (0.3%) studies with low and moderate risks of bias. Fetal SB closure was performed via standard-hysterotomy (n=11), mini-hysterotomy (n=1) or fetoscopy [exteriorized-uterus single-layer (n=1), percutaneous single-layer (n=3) or percutaneous two-layer closure (n=1)]. Only outcomes for the standard-hysterotomy could be meta-analyzed. Overall, outcomes significantly improved with experience. Competency was reached after 35 consecutive cases for standard-hysterotomy and was predicted to be achieved after ≥57 cases for mini-hysterotomy and ≥56 for percutaneous two-layer fetoscopy. For percutaneous and uterus-exteriorized single-layer fetoscopy, competency was not respectively reached by cases 81 and 28 available for analysis.

The number of cases operated correlates with the outcome of SB fetal closure and ranges from 35 cases for standard-hysterotomy to ≥56-57 cases for minimally invasive modifications. The observations provide important information for institutions eager to establish a new fetal center, develop a new technique or train their team, and inform referring clinicians, potential patients and third-parties 8).


Fetal spina bifida repair (fSBR) has proven effective in the reversibility of hindbrain herniation, lower rate of shunt-dependent hydrocephalus, and independent ambulation. Besides distinct advantages, there are also concerns related to fSBR. One of these is the postnatal occurrence of inclusion cysts (IC).

In a prospective study, 48 children who underwent fSBR were followed up in the University Children’s Hospital ZurichSwitzerland.

Postnatal assessment included clinical examinationcystometry, and Spinal magnetic resonance imaging. Indication for IC resection was the evidence of a spinal mass on MRI in the presence of deteriorating motor or bladder function, pain, or considerable growth of the IC.

Fourteen children (30%) developed IC, all within the first 2 years of life. Six children underwent IC resection; 4 children due to deteriorating function, 2 children due to doubling of the mass on MRI within 1 year. Following IC resection, 4/6 children (67%) demonstrated altered motor function and 6 children (100%) were diagnosed with neurogenic bladder dysfunction.

Systematic follow-up of patients with a history of fSBR revealed a high incidence of IC. Whether these are of dysembryogenic or iatrogenic origin, remains unclear. Since both IC per se and IC resection may lead to loss of neurologic function, IC can be considered a “third hit.” 9).


Surgical management of spinal dysraphism often requires the use of dural substitutes. Amniotic membrane (AM) has drawn the interest of clinicians for its valuable concentration of cytokines and factors capable of promoting wound healing, re-epithelialization, inhibiting fibrosis and regulating angiogenesis. These beneficial qualities could make AM an interesting dural substitute for spina bifida repair. In this study, we describe the use of banked homologous AM as a dural substitute for the repair of spinal dysraphism in newborns. Our purpose is to test the mechanical characteristics, as well as the safety and effectiveness of AM in preventing postoperative complications and re-tethering.

The AM patch was carefully detached from the chorion of donors undergoing caesarean section, rinsed in saline solution, and cryopreserved in liquid nitrogen. Five newborns were treated using AM: three affected by open spinal dysraphism and two by spina bifida occulta. The AM patch was used as a dural substitute with two different positions and purposes: the amnion-side down covering the placode to prevent adhesions or placed extradurally facing the dura to avoid scarring and facilitating the sliding of the dural sac itself under the extradural tissue layers.

RESULTS: No adverse events occurred, and the surgical wounds healed without complications. MRI scans taken at 3 and 6 months after surgery showed a satisfying de-tethering of the spinal cord with no obvious evidence of new adherence formation.

CONCLUSIONS: We present a multimodal interposition technique using AM as a reconstructive and anti-adhesive tissue for the treatment of open myelomeningocele (MMC) and lipomeningocele (LMC) treatment. In our experience, AM proved its efficacy in restoring the dural sac integrity without complications. We support the use of AM as a promising dural substitute, speculating on how the use of AM could potentially change reconstructive strategies for spinal dysraphism 10).


Sepulveda et al. reported the experience with prenatal repair of open spina bifida (OSB) from 2 centers in Chile.

Women with a second-trimester fetus with OSB were offered intrauterine neurosurgical repair following the protocol from the Management of Myelomeningocele Study (MOMS) trial. Pediatric follow-up with infants reaching 12 and 30 months of life was also reviewed.

Fifty-eight fetuses with OSB underwent intrauterine repair at an average (±SD) gestational age of 24.8 ± 0.9 weeks. There were 3 (5.1%) intrauterine deaths. The average gestational age at delivery of the remaining 55 cases was 33.3 ± 3.6 weeks, and the average birth weight was 2,172 ± 751 g. Delivery before 30 weeks occurred in 11 cases (20.0%). Two (3.6%) neonatal deaths (<28 days) occurred. At 12 months, a ventriculoperitoneal shunt or an endoscopic third ventriculostomy was required in 25% of the cases. At 30 months, 72.4% of the infants were able to walk.

Prenatal neurosurgical repair of OSB is a complex and challenging intervention. Major complications include perinatal death and severe prematurity. No major maternal complications occurred in our series. A reduction in the need for cerebrospinal fluid diversion and an improved ability to walk seems to be the greatest long-term advantages of this procedure 11).


1)

Adzick NS, Thom EA, Spong CY, Brock JW 3rd, Burrows PK, Johnson MP, Howell LJ, Farrell JA, Dabrowiak ME, Sutton LN, Gupta N, Tulipan NB, D’Alton ME, Farmer DL; MOMS Investigators. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med. 2011 Mar 17;364(11):993-1004. doi: 10.1056/NEJMoa1014379. Epub 2011 Feb 9. PMID: 21306277; PMCID: PMC3770179.
2)

Miller JL, Groves ML, Baschat AA. Fetoscopic spina bifida repair. Minerva Ginecol. 2019 Apr;71(2):163-170. doi: 10.23736/S0026-4784.18.04355-1. Epub 2018 Nov 27. PMID: 30486637.
3) , 8)

Joyeux L, De Bie F, Danzer E, Russo FM, Javaux A, Peralta CFA, De Salles AAF, Pastuszka A, Olejek A, Van Mieghem T, De Coppi P, Moldenhauer J, Whitehead WE, Belfort MA, Lapa DA, Acacio GL, Devlieger R, Hirose S, Farmer DL, Van Calenbergh F, Adzick NS, Johnson MP, Deprest J. Learning curves of open and endoscopic fetal spina bifida closure: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2019 Jul 4. doi: 10.1002/uog.20389. [Epub ahead of print] Review. PubMed PMID: 31273862.
4) , 6)

Gerber JA, Stocks BT, Zhu H, Castillo H, Castillo J, Borden AN, Tu DD, Whitehead WE, Austin PF. Prevalence of high-risk bladder categorization with prenatal and postnatal myelomeningocele repair types. Neurourol Urodyn. 2021 Feb 19. doi: 10.1002/nau.24629. Epub ahead of print. PMID: 33604950.
5) , 7)

Lehoczky L, Southworth AB, Martinez GZ, Belfort MA, Shamshirsaz AA, Shamshirsaz A, Cortes MS, Nassr AA, Donepudi R, Whitehead WE, Johnson R, Meshinchi N, Espinoza J. Magnesium sulfate titration reduces maternal complications following fetoscopic closure of spina bifida. Prenat Diagn. 2021 Feb 16. doi: 10.1002/pd.5923. Epub ahead of print. PMID: 33591585.
9)

Heye P, Moehrlen U, Mazzone L, Weil R, Altermatt S, Wille DA, Scheer I, Meuli M, Horst M. Inclusion Cysts after Fetal Spina Bifida Repair: A Third Hit? Fetal Diagn Ther. 2018 Sep 10:1-7. doi: 10.1159/000491877. [Epub ahead of print] PubMed PMID: 30199879.
10)

Marton E, Giordan E, Gioffrè G, Canova G, Paolin A, Mazzucco MG, Longatti P. Homologous cryopreserved amniotic membrane in the repair of myelomeningocele: preliminary experience. Acta Neurochir (Wien). 2018 Jun 1. doi: 10.1007/s00701-018-3577-x. [Epub ahead of print] PubMed PMID: 29858946.
11)

Sepulveda W, Corral E, Alcalde JL, et al. Prenatal Repair of Spina Bifida: A 2-Center Experience with Open Intrauterine Neurosurgery in Chile [published online ahead of print, 2020 Sep 16]. Fetal Diagn Ther. 2020;1-9. doi:10.1159/000509242

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