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Introduction: No evidence-based protocols exist for fetal cardiac monitoring during fetoscopic myelomeningocele (fMMC) repair and intraprocedural spectral Doppler data are limited. We determined the feasibility of continuous fetal echocardiography during fMMC repair and correlated Doppler changes with qualitative fetal cardiac function during each phase of fMMC repair., Methods: Patients undergoing fMMC repair had continuous fetal echocardiography interpreted in real-time by pediatric cardiology. Fetal data included fetal heart rate (FHR), qualitative cardiac function, mitral and tricuspid valve inflow waveforms, and umbilical artery (UA), umbilical vein (UV), ductus arteriosus (DA), and ductus venosus (DV) Dopplers., Results: UA abnormalities were noted in 14/25 patients, UV abnormalities were observed in 2 patients, and DV and DA abnormalities were each noted in 4 patients. Qualitative cardiac function was normal for all patients with the exception of one with isolated left ventricular dysfunction during myofascial flap creation, concurrent with an abnormal UA flow pattern. All abnormalities resolved by the first postoperative day., Conclusions: Continuous fetal echocardiography was feasible during all fMMC repairs. Spectral Doppler changes in the UA were common during fMMC procedures but qualitative cardiac dysfunction was rare. Abnormalities in the UV, DV, and DA Dopplers, FHR, and cardiac function were less common findings., (© 2024 S. Karger AG, Basel.)

Introduction: The Management of Myelomeningocele Study (MOMS) eligibility criteria preclude in utero surgery for fetal spina bifida (fSB) when the maternal body mass index (BMI) is ≥35 kg/m2. Some centers still respect this criterion, while others, like ours, do not. This study aimed to assess whether maternal and fetal safety is compromised with higher maternal BMIs., Methods: Data of 192 patients with open fSB repair at our center were retrospectively analyzed. According to their BMI, patients were divided into three groups: group 1 (BMI <30 kg/m2), group 2 (BMI 30-35 kg/m2), and group 3 (BMI >35 kg/m2). Subgroup analysis was performed to assess differences in maternal and fetal outcomes. Additionally, complications were divided into grades 1 to 5 according to their severity and outcome consequences and compared among groups., Results: Out of 192 patients, 146 (76.0%) had a BMI <30 kg/m2, 28 (14.6%) had a BMI 30-35 kg/m2, and 18 (9.4%) had a BMI >35 kg/m2. Significant differences occurring more often in either group 2 or 3 compared to group 1 were maternal wound seroma (50% or 56% vs. 32%, p = 0.04), amniotic fluid leakage (14% or 6% vs. 2%, p = 0.01) as well as vaginal bleeding (11% or 35% vs. 9%, p = 0.01). On the contrary, duration of tocolysis with atosiban was shorter in patients with BMI >30 kg/m2 (4 or 5 vs. 6 days, p = 0.01). When comparing severity of maternal or fetal complications, grade 1 intervention-related complications occurred significantly more often in group 3 compared to group 1 or 2 (78% vs. 45% or 57%, p = 0.02). Gestational age at delivery was around 36 weeks in all groups without significant differences., Conclusion: This investigation did not identify clinically relevant maternal and/or fetal outcome problems related to BMIs >35 kg/m2. Additional studies are however needed to confirm our results., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Spina bifida is the most common congenital anomaly of the central nervous system and the first non-fatal fetal lesions to be addressed by fetal intervention. While research in spina bifida has been performed in rodent, nonhuman primate, and canine models, sheep have been a model organism for the disease. This review summarizes the history of development of the ovine model of spina bifida, previous applications, and translation into clinical studies. Initially used by Meuli et al. [Nat Med. 1995;1(4):342-7], fetal myelomeningocele defect creation and in utero repair demonstrated motor function preservation. The addition of myelotomy in this model can reproduce hindbrain herniation malformations, which is the leading cause of mortality and morbidity in humans. Since inception, the ovine models have been validated numerous times as the ideal large animal model for fetal repair, with both locomotive scoring and spina bifida defect scoring adding to the rigor of this model. The ovine model has been used to study different methods of myelomeningocele defect repair, the application of various tissue engineering techniques for neuroprotection and bowel and bladder function. The results of these large animal studies have been translated into human clinical trials including Management of Meningocele Study (MOMS) trial that established current standard of care for prenatal repair of spina bifida defects, and the ongoing trials including the Cellular Therapy for In Utero Repair of Myelomeningocele (CuRe) trial using a stem cell patch for repair. The advancement of these life savings and life-altering therapies began in sheep models, and this notable model continues to be used to further the field including current work with stem cell therapy., (© 2023 S. Karger AG, Basel.)

Introduction: We hypothesize that after publication of the quintessence of the MOMS trial, eligibility criteria for prenatal spina bifida (SB) repair may be modified if a tenable argumentation underlies this decision., Methods: Our first 154 fetal surgery patients were analyzed with particular focus on how many, which, and why the original eligibility criteria, set forth by the MOMS Trial Protocol, were disobeyed, and what the eventually detectable, negative and positive impacts of these deviations on outcomes were., Results: A total of 152 patients (2 missing consent) were included (100%). In 69 patients (45.4%), a total of 89 eligibility criteria were disobeyed. In 54 (35.6%) cases, the following maternal criteria were concerned: gestational age at operation of >25+6 weeks in 17 (11.2%), uterine pathologies in 13 (8.6%) women, preoperative BMI ≥35 kg/m2 in 12 (7.9%), previous hysterotomy in 7 (4.6%), previous prematurity in 3 (2%), HIV/hepatitis B in 2 (1.3%), psychosocial issues in 2 (1.3%), and placenta praevia in 1 (0.7%). In 32 (21.1%) cases, fetal criteria were disobeyed 34 times: Fetal anomaly unrelated to SB in 19 (12.5%), no/minimal evidence of hindbrain herniation in 13 (8.6%), and severe kyphosis in 2 (1.3%). We could not identify cases where non-observation of criteria led to clear-cut maternal and/or fetal disadvantages., Conclusion: This study shows that MOMS trial eligibility criteria for prenatal SB repair should be modified or even abandoned with adequate medical and ethical argumentation, and with written parental informed consent after non-directive, full disclosure counseling. This clear-cut change of paradigm is a necessity as it leads toward personalized medicine, allowing more fetuses to benefit from fetal surgery than would have benefitted with the former, published, MOMS criteria in place., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Given the maternal morbidity of open fetal surgery, the development of prenatal fetoscopic repair for spina bifida aperta (SBA) is encouraged., Objective: We hereby report the early results from our center, using a laparotomy-assisted CO2-fetoscopic approach., Methods: This study was conducted in patients with an SBA < T1 and >S1, <26 weeks of gestation, with Chiari II. Fetoscopic repair was performed using 2 operating trocars in the uterus exteriorized through a transverse laparotomy. Endoscopy was performed under humidified and heated CO2 insufflation. Following dissection of the lesion, a 1-layer approach was performed with a muscle/skin flap sutured over a patch of Duragen. Main outcomes were watertight repair at birth and the need for postnatal neurosurgical surgery including shunting within 6 months., Results: Of 87 women assessed for prenatal therapy, 7 were included. Surgery was performed at 24 (23-26) weeks' gestation. There was no fetal demise. Conversion to hysterotomy was not performed, although surgery could not be performed in 1 case because of fetal position. Severe preeclampsia developed postoperatively in 1 case. In the other 6 cases, follow-up was uneventful except for premature rupture membranes which occurred in 3/6 cases at 30, 34, and 36+5 weeks' gestation. Gestational age at delivery was 32 + 5 (31-36 + 5) weeks' gestation. Repair was watertight at birth except in 2 cases which required complementary postnatal surgical repair. Reverse hindbrain herniation during pregnancy was observed in 4/6 cases. In 3/6 cases, shunting was necessary within 6 months after birth. At 12 months, a functional gain of ≥2 metameric levels was observed in 3 cases of the 6 survivors., Conclusion: Laparotomy-assisted fetoscopic repair is a reasonable option for women who choose and are eligible for antenatal surgery, both in terms of maternal and perinatal morbidity., (© 2022 S. Karger AG, Basel.)

Introduction: Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes., Objective: The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure., Methods: Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010-June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations., Results: The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location., Conclusions: An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes., (© 2021 S. Karger AG, Basel.)

Background: Fetal surgery, such as for meningomyelocele repair, has a clear clinical fetal benefit. In patients who undergo in utero repair of meningomyelocele, for example, there is reduced long-term disease morbidity. However, despite the beneficial effects of early intervention, women who undergo fetal interventions have an increased risk of preterm labor and delivery. Several surgery-related factors have been described but no specific anesthesia-related factors., Objective: The aim of this study was to determine if any aspects of the perioperative anesthetic management influenced maternal complications following in utero surgery., Methods: This was a retrospective chart review of the anesthetic management of mothers and fetuses who presented for open and fetoscopic myelomeningocele repair, between 2011 and 2015, at Texas Children's Fetal Center®., Results: Forty-six women underwent open or fetoscopic repair of neural tube defects at our institution. We found the maternal heart rate in the postoperative period to be associated with a higher likelihood of preterm labor, but not delivery. The odds of having preterm delivery was higher for nulliparous patients and those with lower intraoperative diastolic pressure., Conclusions: Our findings confirm what has been previously reported regarding the association of nulliparity with preterm delivery. Additionally, this study highlights the importance of maintaining stable perioperative hemodynamics during the intraoperative and postoperative phases of care for patients undergoing in utero surgery., (© 2020 S. Karger AG, Basel.)

Introduction: Prenatal closure of open spina bifida via open fetal surgery improves neurologic outcomes for infants in selected pregnancies. Fetoscopic techniques that are minimally invasive to the uterus aim to provide equivalent fetal benefits while minimizing maternal morbidities, but the optimal technique is undetermined. We describe the development, evolution, and feasibility of the laparotomy-assisted 2-port fetoscopic technique for prenatal closure of fetal spina bifida in a newly established program., Methods: We conducted a retrospective cohort study of women consented for laparotomy-assisted fetoscopic closure of isolated fetal spina bifida. Inclusion and exclusion criteria followed the Management of Myelomeningocele Study (MOMS). Team preparation involved observation at the originating center, protocol development, ancillary staff training, and surgical rehearsal using patient-matched models through simulation prior to program implementation. The primary outcome was the ability to complete the repair fetoscopically. Secondary maternal and fetal outcomes to assess performance of the technique were collected prospectively., Results: Of 57 women screened, 19 (33%) consented for laparotomy-assisted 2-port fetoscopy between February 2017 and December 2019. Fetoscopic closure was completed in 84% (16/19) cases. Over time, the technique was modified from a single- to a multilayer closure. In utero hindbrain herniation improved in 86% (12/14) of undelivered patients at 6 weeks postoperatively. Spontaneous rupture of membranes occurred in 31% (5/16) of fetoscopic cases. For completed cases, median gestational age at birth was 37 (range 27-39.6) weeks and 50% (8/16) of women delivered at term. Vaginal birth was achieved in 56% (9/16) of patients. One newborn had a cerebrospinal fluid leak that required postnatal surgical repair., Conclusion: Implementation of a laparotomy-assisted 2-port fetoscopic spina bifida closure program through rigorous preparation and multispecialty team training may accelerate the learning curve and demonstrates favorable obstetric and perinatal outcomes., (© 2021 S. Karger AG, Basel.)

Objectives: The aim of the study was to describe the feasibility of open fetal microneurosurgery for intrauterine spina bifida (SB) repair and to compare perinatal outcomes with cases managed using the classic open fetal surgery technique., Methods: In this study, we selected a cohort of consecutive fetuses with isolated open SB referred to our fetal surgery center in Queretaro, Mexico, during a 3.5-year period (2016-2020). SB repair was performed by either classic open surgery (6- to 8-cm hysterotomy with leakage of amniotic fluid, which was replaced before uterine closure) or open microneurosurgery, which is a novel technique characterized by a 15- to 20-mm hysterotomy diameter, reduced fetal manipulation by fixing the fetal back, and maintenance of normal amniotic fluid and uterine volume during the whole surgery. Perinatal outcomes of cases operated with the classic open fetal surgery technique and open microneurosurgery were compared., Results: Intrauterine SB repair with a complete 3-layer correction was successfully performed in 60 cases either by classic open fetal surgery (n = 13) or open microneurosurgery (n = 47). No significant differences were observed in gestational age (GA) at fetal intervention (25.4 vs. 25.1 weeks, p = 0.38) or surgical times (107 vs. 120 min, p = 0.15) between both groups. The group with open microneurosurgery showed a significantly lower rate of oligohydramnios (0 vs. 15.4%, p = 0.01), preterm rupture of the membranes (19.0 vs. 53.8%, p = 0.01), higher GA at birth (35.1 vs. 32.7 weeks, p = 0.03), lower rate of preterm delivery <34 weeks (21.4 vs. 61.5%, p = 0.01), and lower rate of perinatal death (4.8 vs. 23.1%, p = 0.04) than the group with classic open surgery. During infant follow-up, the rate of hydrocephalus requiring ventriculoperitoneal shunting was similar between both groups (7.5 vs. 20%, p = 0.24). All patients showed an intact hysterotomy site at delivery., Conclusion: Intrauterine spina repair by open fetal microneurosurgery is feasible and was associated with better perinatal outcomes than classic open fetal surgery., (© 2021 S. Karger AG, Basel.)

Objective: Function of the lower extremities after prenatal myelomeningocele (MMC) repair is best assessed with ambulatory function at 30-36 months of age, but parents often ask about function before this milestone. Lower extremity movement can be assessed by ultrasound (US) and at the newborn exam (NE), but correlation between US, NE, and ambulation is not firmly established., Methods: This was a retrospective correlation study of fetuses that underwent open prenatal MMC repair at SSM Cardinal Glennon Fetal Care Institute, St. Louis, MO, between January 2011 and June 2017. Movement at the ankles, knees, and hips was assessed by US after open repair on postoperative days (PODs) 0-5 and at 32 weeks gestation. NE was performed by physical therapy or neurosurgery within the first month of life, and pediatric follow-up between 30 and 36 months of age was obtained to document ambulation., Results: Forty-two fetuses were included. Joint movement seen on US varied by POD: it was present on POD 1 in 7% of fetuses and 62% by POD 5. Degree of ventriculomegaly, lesion level, and lesion length did not have a significant effect on US, NE, or ambulation. Knee movement on POD 3 correlated with knee movement at NE (k = 0.58, p < 0.01), but only later knee movement correlated with ambulation (k = 0.28-0.46, p = 0.01). Hip movement at 32 weeks was the only single joint assessment that correlated with NE and ambulation (k = 0.45 and 0.46, p = 0.03 and 0.01, respectively)., Conclusion: Lower extremity movement increases between POD 1 and POD 5 in fetuses after open fetal MMC repair. Knee and hip movement on US at 32 weeks correlates with ambulation at 30-36 months. These data may inform counseling, and direct therapy and spark prospective investigations., (© 2020 S. Karger AG, Basel.)

Introduction: Depressive risk is higher for mothers of infants with chronic medical conditions. The present study examined maternal depressive risk and associations with parent and child outcomes among mothers of young children who were randomized to either prenatal or postnatal surgical closure for myelomeningocele., Methods: Using the Management of Myelomeningocele Study database, maternal depressive risk was examined at 3 time points as follows: prior to birth, 12 months, and 30 months post birth. Separate multivariate analyses examined associations among change in depressive risk (between baseline and 30 months), parenting stress, and child outcomes at 30 months., Results: Mean scores were in the minimal depressive risk range at all the time points. Post birth depressive risk did not differ by prenatal versus postnatal surgery. Mean change scores reflected a decrease in depressive risk during the first 30 months. Only 1.1-4.5% of mothers reported depressive risk in the moderate to severe range across time points. Increased depressive risk during the first 30 months was associated with increased parenting stress scores and slightly lower child cognitive scores at 30 months., Conclusion: Most mothers reported minimal depressive risk that decreased over time, regardless of whether their infant underwent prenatal or postnatal surgery. Only a small percentage of mothers endorsed moderate to severe depressive risk, but an increase in depressive risk over time was associated with higher parental stress and slightly lower child cognitive development., (© 2021 S. Karger AG, Basel.)

Background: The inherent morbidity associated with fetal ovine models of myelomeningocele (MMC) has created challenges for long-term survival of lambs. We aimed to develop a fetal ovine surgical spinal exposure model which could be used to evaluate long-term safety after direct spinal cord application of novel therapeutics for augmentation of in utero MMC repair., Methods: At gestational age (GA) 100-106, fetal lambs underwent surgical intervention. Laminectomy of L5-L6 was performed, dura was removed, and an experimental product was directly applied to the spinal cord. Paraspinal muscles and skin were closed and the fetus was returned to the uterus. Lambs were delivered via cesarean section at GA 140-142. Lambs were survived for 3 months with regular evaluation of motor function by the sheep locomotor rating scale. Spinal angulation was evaluated by magnetic resonance imaging at 2 weeks and 3 months., Results: Five fetal surgical intervention lambs and 6 control lambs who did not undergo surgical intervention were included. All lambs survived to the study endpoint of 3 months. No lambs had motor function abnormalities or increased spinal angulation., Conclusion: This model allows for long-term survival after fetal spinal cord exposure with product application directly onto the spinal cord., (© 2021 S. Karger AG, Basel.)

Objective: To report the experience with prenatal repair of open spina bifida (OSB) from 2 centers in Chile., Methods: 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., Results: 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., Discussion: 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 seem to be the greatest long-term advantages of this procedure., (© 2020 S. Karger AG, Basel.)

Introduction: The Management of Myelomeningocele Study was a multicenter randomized trial to compare prenatal and standard postnatal repair of myelomeningocele (MMC). Neonatal outcome data for 158 of the 183 randomized women were published in The New England Journal of Medicine in 2011., Objective: Neonatal outcomes for the complete trial cohort (N = 183) are presented outlining the similarities with the original report and describing the impact of gestational age as a mediator., Methods: Gestational age, neonatal characteristics at delivery, and outcomes including common complications of prematurity were assessed., Results: Analysis of the complete cohort confirmed the initial findings that prenatal surgery was associated with an increased risk for earlier gestational age at birth. Delivery occurred before 30 weeks of gestation in 11% of neonates that had fetal MMC repair. Adverse pulmonary sequelae were rare in the prenatal surgery group despite an increased rate of oligohydramnios. There was no significant difference in other complications of prematurity including patent ductus arteriosus, sepsis, necrotizing enterocolitis, periventricular leukomalacia, and intraventricular hemorrhage., Conclusion: The benefits of prenatal surgery outweigh the complications of prematurity., (© 2020 S. Karger AG, Basel.)

Introduction: The main aim of the fetal surgery of myelomeningocele (MMC) is the improvement in prognosis for children with this defect and at the same time high safety of the procedure for mother and fetus., Objective: The aim of the study was to determine the effectiveness of alternative hysterotomy technique for fetal surgery of MMC in prevention of essential perinatal complications., Methods: Forty-nine pregnant women diagnosed with fetal MMC (fMMC) who underwent classic hysterotomy without the use of stapler formed the study cohort. Two cases of intrauterine fetal death or neonatal death in the immediate perioperative period in the study group (SG) were excluded from further analyses. In the historical control group (46 patients) from our center hysterotomy was performed according to Management of Myelomeningocele Study (MOMS) protocol. The study cohort's outcomes were compared with the historical controls and with post-MOMS results in Children's Hospital of Philadelphia (CHOP) and Vanderbilt University Medical Center (VUMC)., Results: In the SG we did not observe delivery before 30 weeks of gestation (0/47; 0%) and the incidence of chorionamniotic membrane separation (CMS, 3/47; 6%) and preterm premature rupture of membranes (PPROM, 7/47; 15%) was lower compared to the other groups. Preterm delivery as a result of uterine contractions occurred significantly less frequently in the SG (8/47; 17%). Fetal surgery with classic hysterotomy resulted in rare use of magnesium sulfate (3/47; 6%)., Conclusions: The alternative hysterotomy technique for fetal surgery of MMC results in low occurrences of CMS, PPROM, preterm delivery, and the rare use of tocolytics., (© 2020 S. Karger AG, Basel.)

Introduction: The Management of Myelomeningocele Study, a.k.a. the MOMS trial, was published in 2011 in the New England Journal of Medicine. This prospective randomized controlled trial proved to be a milestone publication that provided definitive evidence that fetal surgery is a novel standard of care for select fetuses with spina bifida aperta (SB). The goal of our study is to assess whether our center can match these benchmark results., Materials and Methods: Our study was conducted according to the MOMS protocol using the same inclusion and exclusion criteria and looked at the same outcome parameters that were used in the MOMS trial. Zurich and MOMS results were compared., Results: We enrolled 20 patients between December 2010 and May 2015 all of whom underwent fetal surgery for SB. Among 51 different outcome variables, there were only 3 favorable (multiplicity-adjusted) significant differences (gestational age at birth, hindbrain herniation, and psychomotor development). There were no statistically significant differences regarding any other parameters., Conclusion: Our findings confirm that rigorous apprenticeship, training, and comprehensive prospective data collection enable centers like the Zurich Center for Fetal Diagnosis and Therapy to achieve benchmark results for open fetal surgery for myelomeningocele and myeloschisis. These results justify the existence and continuation of our program. Outcome documentation is an essential element of quality management. It is medically and ethically fundamental for fetal medicine and surgery centers offering high-end innovative medical care., (© 2019 S. Karger AG, Basel.)

Background: Fetal myelomeningocele (fMMC) repair yields superior outcomes to postnatal repair and is increasingly offered at select fetal centers., Objectives: To report the fMMC referral process from initial referral to evaluation and surgical intervention in a large fetal referral center., Methods: We conducted a retrospective cohort study of patients referred to Texas Children's Fetal Center for fMMC between September 2013 and January 2018, reviewing the process from referral to final disposition. The stepwise evaluation included a phone interview followed by multidisciplinary consultation at our fetal center. We modified the Management of Myelomeningocele Study inclusion and exclusion criteria to allow a maternal body mass index of 35-40 on an individual basis., Results: A total of 204 referrals were contacted for a phone interview; 175 (86%) pursued outpatient evaluation, and 80 (46%) of them qualified for repair. Among the eligible patients, 37 (46%) underwent fetoscopic repair, 20 (25%) underwent open repair, and 17 (21%) declined prenatal surgery. Of the 89 noneligible patients (53%) excluded upon outpatient evaluation, 64 (72%) were excluded for fetal and 17 (19%) for maternal reasons. No hindbrain herniation (16%) and maternal BMI and/or hypertension (5%) were the most common reasons for fetal and maternal exclusion, respectively. A total of 31% of our referral population underwent fetal surgery., Conclusions: A small percentage of fMMC referrals ultimately undergo prenatal surgery. Stepwise evaluation and multidisciplinary teams are key to the success of large referral programs., (© 2019 S. Karger AG, Basel.)

Introduction: Open fetal myelomeningocele (fMMC) repair is nowadays a therapeutic option in selected cases. We aimed to evaluate changes in maternal and fetal outcome after fMMC repair during the first 8 years of experience at a tertiary referral fetal medicine center in Switzerland. -Materials and Methods: Between 2010 and 2018, fMMC repair and delivery of the neonate via planned cesarean section was performed in 67 cases. Cases were retrospectively stratified into 2 groups: a "training phase" (TP) with supervision from an external surgeon during 11 operations (2010-2014, 15 cases) followed by an "experienced phase" (EP, 2014-2018, 52 cases); each phase lasted about 4 years. Both phases were compared with regard to various maternal and fetal outcome parameters., Results: Analyses did not reveal differences between TP and EP in major outcome parameters such as gestational age at delivery, chorionic membrane separation, or the incidence of placental abruption. Although more complex surgical techniques were applied in EP (e.g., dermal closure using a rotational flap), surgery time was not different from TP. At the same time, surgical complications such as oligohydramnios (27 vs. 8%, p = 0.046) with MRI-confirmed leakage (13 vs. 4%, nonsignificant) and subchorionic hematoma (20 vs. 2%, p = 0.009) were less common in EP than TP., Conclusions: This study shows that the level of competence at our center with regard to major perinatal outcome parameters was already high in the first years of fMMC repair. However, more complex surgical techniques and significantly less minor complications were observed during the most recent years., (© 2019 S. Karger AG, Basel.)

Background: Fetal repair of myelomeningocele (MMC) with placental mesenchymal stromal cells (PMSCs) rescues ambulation in the ovine model up to 48 h postnatally. Outcomes past 48 h are unknown as MMC lambs have not been survived past this timepoint., Objective: We aimed to survive lambs for 6 months following the fetal repair of MMC with PMSCs., Methods: Fetal MMC lambs were repaired with PMSCs. Lambs received either no additional treatment or postnatal bracing and physical therapy (B/PT). Motor function was assessed with the sheep locomotor rating (SLR). Lambs with an SLR of 15 at birth were survived for 6 months or until a decline in SLR less than 15, whichever came first. All lambs underwent a perimortem MRI., Results: The lambs with no postnatal treatment (n = 2) had SLR declines to 7 and 13 at 29 and 65 days, respectively, and were euthanized. These lambs had a spinal angulation of 57° and 47°, respectively. The B/PT lamb (n = 1) survived for 6 months with a sustained SLR of 15 and a lumbar angulation of 42°., Conclusion: Postnatal physical therapy and bracing counteracted the inherent morbidity of the absent paraspinal muscles in the ovine MMC model allowing for survival and maintenance of rescued motor function of the prenatally treated lamb up to 6 months., (© 2020 S. Karger AG, Basel.)

Background: Fetal myelomeningocele (fMMC) repair is a therapeutic option in selected cases. This study aimed to identify risk factors for preterm birth (PTB) following open fMMC repair., Methods: Sixty-seven women underwent fMMC repair and delivered a baby between 2010 and 2018 at our center. Demographic, surgical, and pregnancy complications, including potential risk factors for PTB such as preterm premature rupture of membranes (PPROM), chorioamniotic membrane separation (CMS), and placental abruption were evaluated., Results: Maternal body mass index, maternal age, parity, previous uterine surgery, gestational age at fetal surgery, total surgery duration, surgical subcutaneous hematoma, oligohydramnios, and amniotic fluid leakage were not identified as risk factors for PTB. CMS (p = 0.028, 92 vs. 52%) and PPROM (p = 0.001, 95 vs. 52%) were highly associated with PTB. Placental abruption was found more often in women after fMMC repair than in a general obstetrical population (12 vs. 1%) and ended in premature birth in all cases (p = 0.024, 100 vs. 60%). However, the majority of women delivered at a gestational age >35 weeks., Conclusions: In our study cohort, risk factors for PTB were PPROM, CMS, and placental abruption, whereas surgery duration did not influence outcome. We conclude that the surgery technique should aim to minimize CMS and amniotic fluid leakage., (© 2019 S. Karger AG, Basel.)

Introduction: The ovine model is the gold standard large animal model of myelomeningocele (MMC); however, it has a high rate of fetal loss. We reviewed our experience with the model to determine risk factors for fetal loss., Methods: We performed a retrospective review from 2009 to 2018 to identify operative factors associated with fetal loss (early fetal demise, abortion, or stillbirth). Operative risk factors included gestational age at operation, operative time, reduction of multiple gestations, amount of replaced amniotic fluid, ambient temperature, and method of delivery., Results: MMC defects were created in 232 lambs with an overall survival rate of 43%. Of the 128 fetuses that died, 53 (42%) had demise prior to repair, 61 (48%) aborted, and 14 (11%) were stillborn. Selective reduction of multiple gestations in the same uterine horn was associated with increased fetal demise (OR 3.03 [95% CI 1.29-7.05], p = 0.01). Later gestational age at MMC repair and Cesarean delivery were associated with decreased abortion/stillbirth (OR 0.90 [95% CI 0.83-0.90], p = 0.03, and OR 0.37 [95% CI 0.16-0.31], p = 0.02), respectively., Conclusion: Avoiding selective reduction, repairing MMC later in gestation, and performing Cesarean delivery decreases the rate of fetal loss in the ovine MMC model., (© 2020 S. Karger AG, Basel.)

Introduction: Open fetal repair of myelomeningocele (MMC) is an option for prenatally diagnosed spina bifida. Historically, high-dose volatile anesthetic was used for uterine relaxation but is associated with fetal cardiovascular depression. We examined the impact of administering a supplemental remifentanil infusion on the concentration of inhaled anesthetic required for intraoperative uterine relaxation., Methods: We retrospectively analyzed 22 consecutive patients who underwent open fetal MMC repair with desflurane anesthesia from 2014 to 2018. The anesthetic protocol was modified to include high-dose opioid with remifentanil in 2016. We examined intraoperative end-tidal desflurane concentrations, vasopressor use, incidence of umbilical artery Doppler abnormalities, and incidence of preterm labor and delivery., Results: Patients (n = 11) who received desflurane and remifentanil (Des/Remi) were compared to patients (n = 11) who received desflurane (Des) alone. Intraoperatively, the maximum end-tidal desflurane required to maintain uterine relaxation was lower in the Des/Remi group (7.9 ± 2.2% vs. 13.1 ± 1.2%, p < 0.001). The mean phenylephrine infusion rate was also lower in the Des/Remi group (36 ± 14 vs. 53 ± 10 mcg/min, p = 0.004)., Discussion: Use of opioid with supplemental remifentanil was associated with lower volatile anesthetic dosing and decreased vasopressor use; fetal outcomes were not different. Remifentanil may allow for less volatile anesthetic use while maintaining adequate uterine relaxation., (© 2020 S. Karger AG, Basel.)

Background: Open maternal-fetal surgery for in utero closure of myelomeningocele (MMC) has become an accepted treatment option for prenatally diagnosed open neural tube defects. Historically, this option has been limited to women with BMI < 35 due to concern for increasing complications in patients with obesity., Objective: The aim of this study was to evaluate maternal, obstetric, and fetal/neonatal outcomes stratified by maternal BMI classification in women who undergo open maternal-fetal surgery for fetal myelomeningocele (fMMC) closure., Methods: A single-center fMMC closure registry was queried for maternal demographics, preoperative factors, fetal surgery outcomes, delivery outcomes, and neonatal outcomes. Data were stratified based on maternal BMI: <30, 30-34.99, and ≥35-40, corresponding to normal weight/overweight, obesity class I, and obesity class II. Statistical analysis was performed using statistical software SAS v.9.4 (SAS Institute Inc., Cary, NC, USA)., Results: A total of 264 patients were analyzed, including 196 (74.2%) with BMI <30, 54 (20.5%) with BMI 30-34.99, and 14 (5.3%) with BMI ≥ 35-40. Maternal demographics and preoperative characteristics were similar among the groups. Operative time increased with increasing BMI; otherwise, perioperative outcomes were similar among the groups. Obstetric and neonatal outcomes were similar among the groups., Conclusion: Increasing maternal BMI did not result in a negative impact on maternal, obstetric, and fetal/neonatal outcomes in a large cohort of patients undergoing open maternal-fetal surgery for fMMC closure. Further study is warranted to determine the generalizability of these results., (© 2020 S. Karger AG, Basel.)

Introduction: Despite undoubtable benefits of open fetal myelomeningocele (fMMC) repair, there are considerable maternal risks. The aim of this study was to evaluate and systematically categorize maternal complications after open fMMC repair., Methods: We analyzed data of 40 fMMC repairs performed at the Zurich Center for Fetal Diagnosis and Therapy. Maternal complications were classified according to a 5-level grading system based on a classification of surgical complications proposed by Clavien and Dindo., Results: We observed no grade 5 complication (death of a patient). Five (12.5%) women demonstrated severe grade 4 complications: 1 case of uterine rupture in a nullipara at 36 gestational weeks (GW), a third-degree atrioventricular block which needed short mechanical resuscitation, a bilateral lung embolism requiring intensive care unit (ICU) management due to low-output syndrome, and chorioamnionitis and urosepsis both requiring ICU management at 31 GW. Twenty-six (65%) women had minor (grade 1-3) complications., Conclusions: Only one grade 4 complication (uterine rupture, 2.5%) was a clear-cut direct consequence of fetal surgery. The other four grade 4 complications (10%) occurred in the context of, but cannot unequivocally be attributed to, fetal surgery, since they may occur also in other circumstances. The classification system used is a tenable step towards stringent documentation of maternal complications., (© 2018 S. Karger AG, Basel.)

Introduction: The surgically induced fetal lamb model is the most commonly used large animal model of myelomeningocele (MMC) but is subject to variation due to surgical technique during defect creation., Material and Methods: Thirty-one fetal lambs underwent creation of the MMC defect, followed by defect repair with either an extracellular matrix (ECM) patch (n = 10) or ECM seeded with placental mesenchymal stromal cells (n = 21). Postnatal hindlimb function was assessed using the Sheep Locomotor Rating (SLR) scale. Postmortem magnetic resonance imaging of the lumbar spine was used to measure the level and degree of spinal angulation, as well as cross-sectional area of remaining vertebral bone., Results: Median level of angulation was between the 2nd and 3rd lumbar vertebrae, with a median angle of 24.3 degrees (interquartile range 16.2-35.3). There was a negative correlation between angulation degree and SLR (r = -0.44, p = 0.013). Degree of angulation also negatively correlated with the normalized cross-sectional area of remaining vertebral bone (r = -0.75, p < 0.0001)., Discussion: Surgical creation of fetal MMC leads to varying severity of spinal angulation in the ovine model, which affects postnatal functional outcomes. Postnatal assessment of spinal angulation aids in standardization of the surgical model of fetal MMC repair., (© 2019 S. Karger AG, Basel.)

Introduction: The use of perioperative tocolytic agents in fetal surgery is imperative to prevent preterm labor. Indomethacin, a well-known tocolytic agent, can cause ductus arteriosus (DA) constriction. We sought to determine whether a relationship exists between preoperative indomethacin dosing and fetal DA constriction., Materials and Methods: This is an IRB-approved, single-center retrospective observational case series of 42 pregnant mothers who underwent open fetal myelomeningocele repair. Preoperatively, mothers received either 1 (QD) or 2 (BID) indomethacin doses. Maternal anesthetic drug exposures and fetal cardiac dysfunction measures were collected from surgical and anesthesia records and intraoperative fetal echocardiography. Pulsatility Index was used to calculate DA constriction severity. Comparative testing between groups was performed using t- and chi-square testing., Results: DA constriction was observed in all fetuses receiving BID indomethacin and in 71.4% of those receiving QD dosing (p = 0.0002). Severe DA constriction was observed only in the BID group (35.7%). QD indomethacin group received more intraoperative magnesium sulfate (p < 0.0001). Minimal fetal cardiac dysfunction (9.5%) and bradycardia (9.5%) were observed in all groups independent of indomethacin dosing., Conclusions: DA constriction was the most frequent and severe in the BID indomethacin group. QD indomethacin and greater magnesium sulfate dosing was associated with reduced DA constriction., (© 2018 S. Karger AG, Basel.)

Introduction: Optimal uterine relaxation is achieved through higher minimum alveolar concentration (MAC) of inhalational anesthetics, increasing risks to mother and fetus. Our objective was to determine if earlier administration of magnesium sulfate would reduce the requirement of inhalational anesthetics in fetal myelomeningocele repair., Materials and Methods: Prospective observational study of fetal myelomeningocele repair was performed from September 2011 to August 2017. Groups compared were: (1) magnesium sulfate at uterine closure; (2) magnesium sulfate at maternal skin incision. Maternal demographics, anesthetic agents, intraoperative complications, and pregnancy outcomes were reviewed. A Student t test was used for analysis., Results: There were 30 cases in group 1 and 21 cases in group 2. There was no difference in gestational age at intervention (24.92 ± 0.62 vs. 25.22 ± 0.47 weeks, p = 0.07) or at delivery (34.83 ± 2.77 vs. 33.98 ± 3.83 weeks, p = 0.38) between groups 1 and 2, respectively. The maximum MAC of sevoflurane was significantly lower in group 2 (1.84 ± 0.25 vs. 1.05 ± 0.28, p < 0.0001). There was no difference in the average dose of phenylephrine used., Discussion: Magnesium sulfate infusion initiated earlier in open fetal surgery reduces the total anesthetic exposure to the fetus., (© 2018 S. Karger AG, Basel.)

Objective: This study presented outcomes of classical hysterotomy with modified antiprostaglandin therapy for intrauterine repair of foetal myelomeningocele (fMMC) performed in a single perinatal centre., Study Design: Forty-nine pregnant women diagnosed with fMMC underwent classic hysterotomy with anti-prostaglandin management, complete amniotic fluid replacement and high dose indomethacin application., Results: The average gestational age (GA) at delivery was 34.4 ± 3.4 weeks, with no births before 30 weeks GA. There were 2 foetal deaths. Complete reversal of hindbrain herniation (HH), assessed in magnetic resonance imaging at 30-31 weeks GA was found in 72% of foetuses (mostly with HH grade I prior to fMMC repair). Our protocol resulted in rare use of magnesium sulphate (6%), low incidence of chorioamniotic membrane separation - chorioamniotic membrane separation (6%), preterm premature rupture of membranes - preterm premature rupture of membranes (pPROM; 15%) and preterm labour - preterm labour (PTL; 17%). The postoperative wound continuity of the uterus was usually stable (in 72% of patients), with low frequency of scar thinning (23%)., Conclusion: Our protocol results in rare use of tocolytics, and the low occurrences of CMS, pPROM and PTL in relation to other study cohorts: Management of Myelomeningocele Study, Children's Hospital of Philadelphia, and Vanderbilt University Medical Centre., (© 2019 S. Karger AG, Basel.)

Background: In utero repair has become an accepted therapy to decrease the rate of ventriculoperitoneal shunting and improve neurologic function in select cases of myelomeningocele. The Management of Myelomeningocele Study (MOMS) trial excluded patients with a BMI >35 due to concerns for increased maternal complications and preterm delivery, limiting the population that may benefit from this intervention., Objectives: The aim of this study was to evaluate outcomes associated with extending the maternal BMI criteria to 40 in open fetal repair of myelomeningocele., Method: Retrospective review of fetal closure of myelomeningocele at a quaternary referral center between 2013 and 2016 with maternal BMI ranging from 35 to 40., Results: Eleven patients with a BMI >35 were identified. The average BMI was 37. The average maternal age at the time of evaluation was 27 years. The average gestational age at fetal surgery was 24 weeks. Gestational age at birth was an average of 32 weeks. There was one perinatal death immediately following the fetal intervention. The shunt rate at 1 year was 45% (5/11 patients)., Conclusions: In this single-institution review of expanded BMI criteria for fetal repair of myelomeningocele, we did not observe any adverse maternal outcomes associated with maternal obesity; however, the gestational age at delivery was 2 weeks earlier compared to the MOMS trial., (© 2019 S. Karger AG, Basel.)

Objective: The aim of this study was to assess the feasibility and the effectiveness of a fetoscopic myelomeningocele (MMC) repair with a running single suture using a 2-port access in the sheep model., Methods: Eighteen fetuses underwent surgical creation of a MMC defect at day 75. Fetuses were then randomized into 3 groups. Four fetuses remained untreated (control group). In the other 14 fetuses, a prenatal repair was performed at day 90: 7 fetuses had an open repair (oMMC), and 7 fetuses had a fetoscopic repair (fMMC) using a single-layer running suture through a 2-port access. Lambs were sacrificed at term, and histological examinations were performed., Results: Hindbrain herniation was observed in all live lambs in the control group. A complete closure of the defect was achieved in all the lambs of the fMMC group. A complete healing of the defect and no hindbrain herniation were observed in all live lambs of the oMMC and fMMC groups. The durations of surgeries were not statistically different between the oMMC and the fMMC groups (60 vs. 53 min, p = 0.40), as was the risk of fetal loss (fMMC: 1/7, oMMC: 3/7, p = 0.56)., Discussion: Fetoscopic repair of MMC can be performed using a single-layer running suture through a 2-port access and may be promising to reduce the risk of premature rupture of membranes., (© 2018 S. Karger AG, Basel.)

Introduction: After the successful results of in utero myelomeningocele (MMC) repair presented by the Management of Myelomeningocele Study, the concept of fetal surgery was introduced in our institution in 2011. Since then, we have been able to follow prospectively a group of patients with attention to urological care. In the present study, we were interested in estimating urinary and fecal continence in this new subset of patients., Material and Methods: We selected from our database patients aged 5 years or older for evaluation of urinary and fecal continence. We reviewed all charts and completed a questionnaire to study aspects of urinary and fecal continence., Results: We identified 14 patients, i.e., 4 (28.6%) males and 10 (71.4%) females. The mean age at MMC surgery was 25.6 gestational weeks. The uro-dynamic class was high-risk in 6 (42.9%), incontinent in 4 (28.6%), hypocontractile in 1 (7.1%), and normal in 3 (21.4%) patients. Three patients had undergone surgery (2 augmentations, i.e., 1 in association with a left colon ACE Macedo-Malone procedure and 1 mini-sling urethroplasty). Twelve patients underwent clean intermittent catheterization (CIC) (85.7%). Only 3 (21.4%) patients had no urinary leakage. Eleven patients (78.6%) used diapers. Eight patients (57.2%) underwent retrograde rectal irrigation and 11 (78.6%) complained of fecal loss. Eleven patients (78.6%) did not report an impact on their self-esteem., Conclusion: Despite the use of CIC in 85.7% of the cases, the continence rate in MMC patients operated on in utero was low and 78.6% of the patients used diapers. This data can be used to educate parents about future conditions of their 5-year-old children and may stimulate the debate regarding further attempts (surgical or not) to improve fecal and urinary continence., (© 2019 S. Karger AG, Basel.)

Background/objectives: The Management of Myelomeningocele (MMC) Study (MOMS) showed that prenatal repair of MMC resulted in improved neurological outcomes but was associated with high rates of obstetrical complications. This study compares outcomes of open and fetoscopic MMC repair., Data Sources: PubMed and Embase studies reporting outcomes of fetal MMC repair published since the completion of the MOMS., Results: We analyzed 11 studies and found no difference in mortality or the rate of shunt placement for hydrocephalus. Percutaneous fetoscopic repair was associated with higher rates of premature rupture of membranes (91 vs. 36%, p < 0.01) and preterm birth (96 vs. 81%, p = 0.04) compared to open repair, whereas fetoscopic repair via maternal laparotomy reduced preterm birth. The rate of dehiscence and leakage from the MMC repair site was higher after both types of fetoscopic surgery (30 vs. 7%, p < 0.01), while the rate of uterine dehiscence was higher after open repair (11 vs. 0%, p < 0.01)., Discussion: Fetoscopic repair is a promising alternative to open fetal MMC repair with a lower risk of uterine dehiscence; however, fetoscopic techniques should be optimized to overcome the high rate of dehiscence and leakage at the MMC repair site. A fetoscopic approach via maternal laparotomy reduces the risk of preterm birth., (© 2017 S. Karger AG, Basel.)

Objective: We reviewed our experience with open fetal surgical myelomeningocele repair to assess the efficacy of a new modification of the hysterotomy closure technique regarding hysterotomy complication rates at the time of cesarean delivery., Methods: A modification of the standard hysterotomy closure was performed on all patients undergoing prenatal myelomeningocele repair. The closure consisted of an interrupted full-thickness #0 polydioxanone (PDS) retention suture as well as a running #0 PDS suture to re-approximate the myometrial edges, and the modification was a third imbricating layer resulting in serosal-to-serosal apposition. A standard omental patch was placed per our routine. Both operative reports and verbal descriptions of hysterotomy from delivering obstetricians were reviewed., Results: A total of 49 patients underwent prenatal repair of myelomeningocele, 43 having adequate follow-up for evaluation. Of those, 95.4% had completely intact hysterotomy closures, with only 1 partial dehiscence (2.3%) and 1 thinned scar (2.3%). There were no instances of uterine rupture., Discussion: In patients undergoing this modified hysterotomy closure technique, a much lower than expected complication rate was observed. This simple modified closure technique may improve hysterotomy healing and reduce obstetric morbidity., (© 2017 S. Karger AG, Basel.)

Introduction: Umbilical artery (UA) Doppler ultrasound is used to assess uteroplacental insufficiency. Absent or reversed end diastolic flow (AREDF) in the UA is associated with increased perinatal mortality in fetuses with intrauterine growth restriction. We describe the incidence of UA Doppler abnormalities during open fetal surgery., Methods: We conducted a retrospective review of patients undergoing open in utero myelomeningocele (MMC) repair between 2008 and 2015. Intermittent UA Dopplers were performed during key portions of all cases. Our primary outcome was the rate of any AREDF. Secondary outcomes included analysis of absent versus reversed end diastolic flow (EDF), vasopressor use, and volatile anesthetic and clinical outcomes., Results: Thirty-four of 47 fetuses developed UA Doppler abnormalities intraoperatively. Nineteen had absent EDF and 15 had reversed EDF. No AREDF was present before induction, and all AREDF resolved by postoperative day 1. Ten of 19 (52.6%) patients who received sevoflurane had reversed EDF, versus 5/28 (17.9%) for desflurane, odds ratio (95% CI) 5.11 (1.36-19.16), p = 0.02. One intraoperative fetal death occurred in the AREDF group., Discussion: AREDF is a common phenomenon during open MMC repair. Anesthetic agent choice may influence this risk. Future studies of UA flow during fetal surgery are needed to further evaluate the impact of intraoperative AREDF on fetal well-being., (© 2017 S. Karger AG, Basel.)

Background: One of the intraoperative challenges of fetal spina bifida repair is skin closure when there is an extended skin defect. Thus, we examined whether distally pedicled random pattern transposition flaps (TFs) are a valid option to overcome this problem., Subjects and Methods: All patients undergoing in utero repair of spina bifida with application of a TF for back skin closure were analyzed focusing on intraoperative flap characteristics and postoperative flap performance., Results: In 30 (70%) of the 43 fetuses a primary skin closure was achieved, in 5 (12%) a skin substitute was used, and in 8 (18%) a TF was applied. Flap raising and insertion was uneventful and perfusion was sufficient in all 8 fetuses (100%). In 3 fetuses (37%) the donor sites were closed primarily, and in 5 (63%) a skin substitute was used for coverage. At birth, 7 flaps were viable and provided robust skin coverage over the center of the former lesion. Complications included a small skin defect with CSF leakage in 1 patient (13%)., Conclusion: During open fetal spina bifida repair, TFs can be safely and efficaciously used to obtain solid and durable skin coverage over lesions too large to allow conventional primary skin closure., (© 2017 S. Karger AG, Basel.)

Objectives: The Management of Myelomeningocele Study (MOMS Trial) has inspired many fetal therapy centers (FTCs) to offer open fetal surgery for myelomeningocele (MMC). This is an initial effort to create a candidate model that can be applicable to many parts of Asia., Material and Methods: A limited selection of specialists from 4 established FTCs in Thailand, Hong Kong, India, and Singapore met for a round table discussion. Experts from Children's Hospital of Philadelphia (CHOP) involved in the Trial moderated the session. The practice suggestions in this statement were from a targeted literature review and expert opinion., Results: A high prevalence of MMC in Asia supports an effort to adopt the procedure, but only in established FTCs with good maternal and neonatal ancillary supports. The falling incidence of MMCs may affect case volume and maintenance of skill. A regional approach was recommended. Fetal benefits have to be weighed against maternal risks, with a consideration of recent outcome data from the endoscopic approach. Responsible FTCs need standardized diagnosis and management, with their long-term outcome data available for an audit., Conclusions: It is envisaged that the information presented by this multidisciplinary team would be useful for FTCs in Asia or elsewhere that plan to establish more advanced fetal care in the future., (© 2017 S. Karger AG, Basel.)

Introduction: The Management of Myelomeningocele Study (MOMS) compared prenatal with postnatal surgery for fetal myelomeningocele (MMC). We sought to understand how subspecialists interpreted the trial results and whether their practice has changed., Materials and Methods: Cross-sectional, mailed survey of 1,200 randomly selected maternal-fetal medicine (MFM) physicians, neonatologists, and pediatric surgeons., Results: Of 1,176 eligible physicians, 670 (57%) responded. Compared to postnatal closure, 33% viewed prenatal closure as "very favorable" and 60% as "somewhat favorable." Most physicians reported being more likely to recommend prenatal surgery (69%), while 28% were less likely to recommend pregnancy termination. In multivariable analysis, neonatologists were more likely to report prenatal closure as "very favorable" (OR 1.6; 95% CI: 1.03-2.5). Pediatric surgeons and neonatologists were more likely to recommend prenatal closure (OR 2.1; 95% CI: 1.3-3.3, and OR 2.9; 95% CI: 1.8-4.6) and less likely to recommend termination (OR 3.8; 95% CI: 2.2-6.7, and OR 4.7; 95% CI: 2.7-8.1). In addition, physicians with a higher tolerance for prematurity were more likely to report prenatal closure as "very favorable" (OR 1.02; 95% CI: 1.00-1.05)., Discussion: In light of the MOMS trial, the vast majority of pediatric subspecialists and MFMs view prenatal MMC closure favorably. These attitudes vary by specialty and risk tolerance., (© 2017 S. Karger AG, Basel.)

Objective: To present the feasibility of fetal myelomeningocele (MMC) repair through a mini-hysterotomy and to describe the perinatal results from our initial experience., Methods: A descriptive study of cases of fetal MMC correction via mini-hysterotomy performed between 2014 and 2016., Results: Forty-five women underwent fetal surgery and 87% (39/45) delivered. A complete multilayer correction of the MMC was possible in all cases. There were no maternal, fetal or neonatal deaths. No maternal or fetal complications occurred from fetal MMC correction until maternal hospital discharge. The average gestational age (GA) at surgery was 24.5 weeks (standard deviation, SD: 1.7; range: 20.7-26.9). The median hysterotomy length was 3.05 cm (SD: 0.39; range: 2.50-3.50). One patient (1/39; 2.6%) experienced chorioamniotic separation. Nine patients (9/39; 23.1%) had premature preterm rupture of membranes at a median GA of 34.1 weeks (range: 31.1-36.0). The average GA at delivery was 35.3 weeks (SD: 2.2; range: 27.9-39.1). Ninety-five percent (37/39) of our patients had an intact hysterotomy site at delivery. Ventriculoperitoneal shunt placement was necessary for 7.7% (3/39) of the neonates., Conclusion: Fetal MMC repair is feasible through a mini-hysterotomy. This approach appears to be associated with reduced risks of very preterm delivery and maternal, fetal and neonatal complications., (© 2016 S. Karger AG, Basel.)

Objective: The aim of this study was to assess fetal hemodynamics during intrauterine open surgery for myelomeningocele (MMC) repair by describing fetal heart rate (FHR) monitoring in detail related to each part of the procedure., Methods: A study was performed with 57 fetuses submitted to intrauterine MMC repair between the 24th and 27th week of gestation. Evaluations of FHR were made in specific periods: before anesthesia, after anesthesia, at the beginning of laparotomy, during uterus abdominal withdrawal, hysterotomy, neurosurgery (before incision, during early skin manipulation, spinal cord releasing, and at the end of neurosurgery), abdominal cavity reintroduction, and abdominal closure, and at the end of surgery. Means ± standard deviations of FHR were established for each period, and analysis of variance with repeated measures was used to assess differences between these periods. The mean differences were assessed with 95% confidence intervals and were analyzed by Tukey's multiple comparison test., Results: The mean FHR during the specific periods mentioned above was 140.2, 140, 139.2, 138.8, 135.1, 133.9, 123.1, 134.0, 134.5, 137.9, and 139.9 bpm, respectively (p < 0.0001). Comparing the different periods, the highest frequencies were observed in the initial and final moments. The neurosurgery stage presents lower frequencies, especially during the release of the spinal cord., Conclusion: FHR monitoring revealed interesting findings in terms of physiological fetal changes during MMC repair, especially during neurosurgery, which was the most critical period., (© 2015 S. Karger AG, Basel.)

Introduction: Fetal amniotic membranes (FM) have been shown to preserve spinal cord histology in the fetal sheep model of myelomeningocele (MMC). This study compares the effectiveness of placenta-derived mesenchymal stromal cells (PMSCs) from early-gestation versus term-gestation placenta to augment FM repair to improve distal motor function in a sheep model., Methods: Fetal lambs (n = 4) underwent surgical MMC creation followed by repair with FM patch with term-gestation PMSCs (n = 1), FM with early-gestation PMSCs (n = 1), FM only (n = 1), and skin closure only (n = 1). Histopathology and motor assessment was performed., Results: Histopathologic analysis demonstrated increased preservation of spinal cord architecture and large neurons in the lamb repaired with early-gestation cells compared to all others. Lambs repaired with skin closure only, FM alone, and term-gestation PMSCs exhibited extremely limited distal motor function; the lamb repaired with early-gestation PMSCs was capable of normal ambulation., Discussion: This pilot study is the first in vivo comparison of different gestational-age placenta-derived stromal cells for repair in the fetal sheep MMC model. The preservation of large neurons and markedly improved motor function in the lamb repaired with early-gestation cells suggest that early-gestation placental stromal cells may exhibit unique properties that augment in utero MMC repair to improve paralysis., (© 2015 S. Karger AG, Basel.)

Introduction: Fetal surgery for myelomeningocele (MMC) results in better outcomes compared to postnatal treatment. However, risks are present. We describe our experience with intraoperative fetal echocardiography during repair of MMC and report on the management of serious cardiovascular events., Material and Methods: The subjects included fetuses with intent to repair MMC from January 2011 to February 2014. The protocol involved continuous echocardiography in a looping, sequential manner of systolic function, heart rate and tricuspid and mitral valve regurgitation., Results: A total of 101 cases intended fetal MMC repair; 100 completed surgery. Intraoperative ventricular dysfunction was present in 60% (20 mild, 25 moderate, 15 severe). Heart rate <100 bpm was noted in 11 cases. Tricuspid valve regurgitation was present in 35% (26 mild, 7 moderate, 2 severe); mitral valve regurgitation was present in 19% (15 mild, 4 moderate). Serious cardiovascular events were experienced in 7 cases, which affected the conduct of surgery and/or outcome. In 4 of these, medications were given via the umbilical vein and external cardiac compressions were performed. Fetal echocardiography was used to gauge the efficacy of compressions and to guide resuscitation., Discussion: Cardiovascular compromise is common during fetal surgery for MMC. Intraoperative fetal echocardiography is recommended as a growing number of centers contemplate offering this form of novel, but potentially risky, therapy., (© 2014 S. Karger AG, Basel.)

Introduction: Myelomeningocele patients deal with multiple medical issues, including lower extremity neurological deficits, bowel and bladder incontinence and the sequelae of hydrocephalus secondary to a Chiari II malformation. In utero intervention holds the promise of reversing some of the sequelae and improving outcome., Material and Methods: Between 1998 and 2003 (preceding the formal Management of Myelomeningocele Study, MOMS), an initial group of 58 patients underwent in utero repair of their myelomeningocele between 21 and 25 weeks' gestation. Long-term (5-year) follow-up has occurred in this cohort of patients. Previous reports have documented decreased incidence of ventriculoperitoneal shunting and neuromotor functioning, showing improved outcomes compared with historical controls., Results: Overall, 4 fetal deaths occurred, while the majority of patients returned for follow-up for up to 5 years after closure. Phone follow-up has also been conducted for those who could not return. To date, 10 patients (18.5%) have successfully toilet-trained, while 2 patients have bowel continence and 1 has bladder continence but requires enemas; 2 patients who successfully toilet-trained developed spinal dermoid cysts requiring surgical resection., Discussion: Historically, in utero repair of myelomeningocele patients yields a greater percentage of patients who have achieved continence compared with those undergoing postnatal repair. The MOMS trial will compare contemporary urological outcomes of those patients undergoing either prenatal or postnatal repair in a randomized fashion. The results of this trial showed a decreased need for ventriculoperitoneal shunting in those patients who underwent in utero repair as well as an improvement in lower extremity function., (© 2014 S. Karger AG, Basel.)

Myelomeningocele (MMC), the most severe form of spina bifida, is a common and devastating malformation. Over two decades of experimental work in animal models have led to the development and clinical application of open fetal surgery for the repair of the MMC defect. This approach offers improved neurofunctional outcomes and is now a clinical option for the management of prenatally diagnosed MMC in selected patients. However, there are still opportunities for further improvement in the prenatal treatment of MMC. A less invasive approach would allow for an application earlier in gestation, with a reduction in maternal and fetal risks and the potential for reduced neurological injury. Tissue engineering offers a realistic and appealing alternative approach for the prenatal treatment of MMC. This review discusses the rationale for tissue engineering in MMC, addresses recent experimental progress and describes potential future directions., (© 2014 S. Karger AG, Basel.)

Background: Fetal myelomeningocele (fMMC) repair has become accepted as a standard of care option in selected circumstances. We reviewed our outcomes for fMMC repair from referral and evaluation through surgery, delivery and neonatal discharge., Material and Methods: All patients referred for potential fMMC repair were reviewed from January 1, 2011 through March 7, 2014. Maternal and neonatal data were collected on the 100 patients who underwent surgery., Results: 29% of those evaluated met the criteria and underwent fMMC repair (100 cases). The average gestational age was 21.9 weeks at evaluation and 23.4 weeks at fMMC repair. Complications included membrane separation (22.9%), preterm premature rupture of membranes (32.3%) and preterm labor (37.5%). Average gestational age at delivery was 34.3 weeks and 54.2% delivered at ≥35 weeks. The perinatal loss rate was 6.1% (2 intrauterine fetal demises and 4 neonatal demises); 90.8% of women delivered at the Children's Hospital of Philadelphia and 3.4% received transfusions. With regard to the neonates, 2 received ventriculoperitoneal shunts prior to discharge; 71.1% of neonates had no evidence of hindbrain herniation on MRI. Of the 80 neonates evaluated, 55% were assigned a functional level of one or more better than the prenatal anatomic level., Conclusion: In an experienced program, maternal and neonatal outcomes for patients undergoing fMMC repair are comparable to results of the MOMS trial., (© 2014 S. Karger AG, Basel.)

Myelomeningocele (MMC) is one of the most common serious congenital malformations. Typically this condition has been treated with closure of the MMC defect shortly after birth. In general, surgery for MMC aims to provide a multilayered closure to provide protection to the neural elements, prevent leakage of spinal fluid and reduce infection risks. A randomized controlled trial, the Management of Myelomeningocele Study (MOMS), has shown that closure during the fetal period can be performed relatively safely and can result in significant benefit to the child. Whereas the surgical technique of prenatal closure of an MMC defect is similar to a postnatal closure, there are some important technical differences. The goal of this paper is to describe the technique of fetal closure of MMC defects, highlight the unique steps that are needed for this surgery and delineate some potential pitfalls., (© 2014 S. Karger AG, Basel.)

Myelomeningocele (MMC), one of the most common congenital malformations, can result in severe lifelong disabilities,including paraplegia, hydrocephalus, Chiari II malformation(CM-II), incontinence, sexual dysfunction, skeletal deformations and mental impairment. MMC was the first nonlethal anomaly to be treated by fetal surgery. Experimental and clinical evidence suggests that the primary cause of the neurologic deficit associated with MMC is not simply incomplete neurulation but rather chronic mechanical injury and amniotic fluid-induced chemical trauma that progressively damages the exposed neural tissue during gestation. Case series and a prospective, randomized study show that fetal surgery for MMC before 26 weeks' gestation may preserve neurologic function, reverse the hindbrain herniation of the CM-II and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, these studies also demonstrate that fetal surgery is associated with significant maternal and fetal risks. Consequently, further research is warranted to further expand our understanding of the pathophysiology of MMC, to evaluate the long-term impact of in utero intervention and to refine the timing and technique of fetal MMC surgery.