Management Of Myelomeningocele Study Trial Research Articles

Postnatal Myelomeningocele Repair in the United States: Rates and Disparities Before and After the Management of Myelomeningocele Study Trial.

Evolving technologies have influenced the practice of myelomeningocele repair (MMCr), including mandatory folic acid fortification, advances in prenatal diagnosis, and the 2011 Management of Myelomeningocele Study (MOMS) trial demonstrating benefits of fetal over postnatal MMCr in select individuals. Postnatal MMCr continues to be performed, especially for those with limitations in prenatal diagnosis, health care access, anatomy, or personal preference. A comprehensive, updated national perspective on the trajectory of postnatal MMCr volumes and patient disparities is absent. We characterize national trends in postnatal MMCr rates before and after the MOMS trial publication (2000-2010 vs 2011-2019) and examine whether historical disparities persist. This retrospective, cross-sectional analysis queried Nationwide Inpatient Sample data for postnatal MMCr admissions. Annual and race/ethnicity-specific rates were calculated using national birth registry data. Time series analysis assessed for trends relative to the year 2011. Patient, admission, and outcome characteristics were compared between pre-MOMS and post-MOMS cohorts. Between 2000 and 2019, 12 426 postnatal MMCr operations were estimated nationwide. After 2011, there was a gradual, incremental decline in the annual rate of postnatal MMCr. Post-MOMS admissions were increasingly associated with Medicaid insurance and the lowest income quartiles, as well as increased risk indices, length of stay, and hospital charges. By 2019, race/ethnicity-adjusted rates seemed to converge. The mortality rate remained low in both eras, and there was a lower rate of same-admission shunting post-MOMS. National rates of postnatal MMCr gradually declined in the post-MOMS era. Medicaid and low-income patients comprise an increasing majority of MMCr patients post-MOMS, whereas historical race/ethnicity-specific disparities are improving. Now more than ever, we must address disparities in the care of MMC patients before and after birth.

Fetal MRI prior to intrauterine surgery of open neural tube defects: What does the radiologist need to know.

The management of myelomeningocele study trial showed significant prognostic improvement in fetal repair before 26weeks of gestation. Hence, surgery in utero represents the best treatment option for open-neural tube defects (NTDs). Fetal surgery of open-NTDs has specific inclusion and exclusion criteria, which can be adequately studied with fetal MRI. The main concern: the spine (spinal defects other than Myelomeningocele and Myeloschisis, the level of the lesion higher than T1 or lower than S1 and the degree of kyphosis ≥ 30°), the skull/brain (no cerebellum herniation and Chiari II malformation and the presence of any intracranial abnormality unrelated to open NTDs), the uterus (cervix length less than 2cm, multiple gestations and placental and uterine abnormalities) and any other fetal abnormality not attributed to spinal defect. In this review, we describe the fundamental role of fetal MRI in supporting therapeutic decisions in pre-surgery intrauterine planning through the accurate and comprehensive description of findings, providing a proposal of a structured report. In addition, we describe how post-surgical MRI is important in investigating the effectiveness of surgery and detecting repairing complications.

Primary vs patch-based skin closure for in-utero spina bifida repair.

During in-utero spina bifida (SB) repair, closure of large defects is often challenging, requiring tissue graft for watertight skin closure. No prior studies have compared primary skin closure vs patch-based repair. Our objective was to compare neonatal and 1-year outcomes associated with these two types of skin closure for in-utero SB repair. This was a prospective cohort study of 102 patients undergoing open prenatal SB repair from September 2011 to August 2021 at a single institution. All patients met the inclusion criteria of the Management of Myelomeningocele Study (MOMS), and the surgical procedure for in-utero SB repair was similar to that described in the MOMS trial. During the surgery, if primary skin approximation was not feasible due to the large size of the defect, the decision was at the discretion of the pediatric neurosurgeon to utilize a patch for closure. Neonatal outcomes at birth and 1-year outcomes were compared between the primary skin and patch-based closure groups. Of 102 patients included in the study, 70 (68.6%) underwent primary skin closure and 32 (31.4%) patch-based closure. The patch type included acellular bovine skin matrix (Durepair®; n = 31) and human acellular dermal matrix (Alloderm®; n = 1). Fetuses with myeloschisis were more likely to require patch-based repair than those with myelomeningocele. The median time of fetal repair was 4 min longer for patch-based compared with primary skin closure (37 vs 33 min; P = 0.001). Following patch-based repair, neonates had a longer length of stay in the neonatal intensive care unit (NICU) by 24 days (adjusted risk ratio, 2.40 (95% CI, 1.41-4.29)) compared to those that underwent primary skin closure. There was no difference between the two groups in the other neonatal outcomes, including the need for ventriculoperitoneal shunt placement and cerebrospinal fluid leakage. Outcome at 1 year of age was available for 90 infants. Need for wound revision within their first year after birth was more common in infants who underwent patch-based vs those with primary skin closure (19.4% vs 5.1%; P = 0.05). There was no difference between the two groups in other 1-year outcomes, including the need for ventriculoperitoneal shunt placement by 1 year of age and surgery for tethered cord. Patch-based closure during SB repair is often needed in fetuses with myeloschisis and is associated with prolonged fetal surgery time, long NICU stay and need for wound revision within the first year after birth. Further studies are required to identify optimal patches for SB repair or alternative methods to improve outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Myelomeningocele Surgery over the 10 Years Following the MOMS Trial: A Systematic Review of Outcomes in Prenatal versus Postnatal Surgical Repair.

Background and Objectives: Myelomeningocele is the most severe form of spina bifida, a congenital neural tube defect arising from an incomplete neural tube closure during early development with damage worsening with advancing gestational age. The Management of Myelomeningocele Study (MOMS) Trial proved that surgery performed before 26 weeks of gestation significantly improved the prognosis, significantly changing treatment paradigms. This article aims to provide a review of the changes and updates in spina bifida repair over the 10-year period following the MOMS Trial. Material and methods: We performed a systematic review in the PubMed and Cochrane databases as well as a hand-search of high-impact journals using the reference list of all identified articles, searching for randomized controlled trials and observational studies. Results: We identified 27 articles published between 2011 and 2021 that fulfilled the inclusion criteria and review them in the present study. Conclusions: With growing experience and with the improvement of prenatal open and fetoscopic techniques, the outcome of SB-associated conditions could be improved and the risks to both the mother and the fetus reduced. A continuous follow-up of the treated infants and further randomized trials are essential to study the complications and advantages or disadvantages of any given treatment strategy.

Open intrauterine repair of spina bifida aperta: Historical aspects, current availability, and clinical outcomes from the Latin American Spina Bifida Consortium

To determine the historical aspects, current availability, and clinical outcomes of open intrauterine repair of spina bifida aperta (IRSBA) in Spanish-speaking Latin American countries. Cases were collected from centers with at least 2 years of experience and a minimum of 10 open IRSBA interventions by December 2020. Clinical variables were compared to the results of the Management of Myelomeningocele Study (MOMS) trial. Clinical experience with 314 cases from seven centers was reviewed. Most cases (n=189, 60.2%) were performed between 24 and 25.9 weeks' gestation. Delivery at less than 30 weeks' gestation occurred in 36 cases (11.5%) and the overall perinatal mortality rate was 5.4% (17 of 314). The rate of maternal complications was low, including the need for blood transfusion (n=3, 0.9%) and dehiscence or a thin uterine scar (n=4, 1.3%). No cases of maternal death were recorded. Fifteen neonates required additional surgical repair of the spinal defect (4.8%) and 63 of 167 infants (37.7%) required a cerebrospinal fluid diversion procedure. Only two of the seven centers reported preliminary experience with fetoscopic IRSBA. Clinical experience and outcomes were within the expected results reported by the MOMS trial. There is still very limited experience with fetoscopic IRSBA in this part of the world.

Fetal myelomeningocele repair: a narrative review of the history, current controversies and future directions.

Fetal surgery is a relatively new field of medicine. The purpose of this narrative review is to present the history of how fetal surgery became the standard of care for myelomeningocele (MMC), the current controversies of this treatment, and active areas of research that may change how MMC is treated. Fetal surgery for MMC emerged out of the University of California, San Francisco in the 1980s in the laboratory of Dr. Michael Harrison. Initial research focused on testing the hypothesis that the in utero repair of MMC could improve outcomes in the ovine model. Evidence from this model suggested that in utero repair decreases the secondary damage to the exposed neural tissue and improves post-natal neurologic outcomes, opening the door for human intervention. This was followed by the Management of Myelomeningocele Study (MOMS), which was a multicenter randomized controlled trial comparing the prenatal versus postnatal MMC repair. The MOMS trial was stopped early due to the improved outcomes of the prenatal repair, establishing the open fetal MMC repair as the standard of care. Since the MOMS trial, two primary areas of controversy have arisen: the operative approach and criteria for the repair. The three operative approaches include open, endoscopic and a hybrid approach combining open and endoscopic. Several of the inclusion and exclusion criteria from the MOMS trial have been challenged, to include body mass index, gestational diabetes, other fetal abnormalities, maternal infections and Rh alloimmunization. New areas of research have also emerged, exploring cell based therapies to improve fetal outcomes, alternatives to fetal surgery and alternatives to primary skin closure of the fetus.

Comparison of Follow-Up Length-Matched Single-Center Myelomeningocele Postnatal Closure Cohort to the Management of Myelomeningocele Study (MOMS) Trial Results

Objective: We sought to compare our large single-institution cohort of postnatal myelomeningocele closure to the 2 arms of the Management of Myelomeningocele Study (MOMS) trial at the designated trial time points, as well as assess outcomes at long-term follow-up among our postnatal cohort. Methods: A single-institutional retrospective review of myelomeningocele cases presenting from 1995 to 2015 at Children’s Hospital of Pittsburgh was performed. We compared outcomes at 12 and 30 months to both arms of the MOMS trial and compared our cohort’s outcomes at those designated time points to our long-term outcomes. Univariate statistical analysis was performed as appropriate. Results: One-hundred sixty-three patients were included in this study. All patients had at least 2-year follow-up, with a mean follow-up of 10 years (range 2–20 years). There was no difference in the overall distribution of anatomic level of defect. Compared to our cohort, the prenatal cohort had a higher rate of tethering at 12 months of age, 8 versus 1.8%. Conversely, the Chiari II decompression rate was higher in our cohort (10.4 vs. 1.0%). At 30 months, the prenatal cohort had a higher rate of independent ambulation, but our cohort demonstrated the highest rate of ambulation with or without assistive devices among the 3 groups. When comparing our cohort at these early time points to our long-term follow-up data, our cohort’s ambulatory function decreased from 84 to 66%, and the rate of detethering surgery increased almost 10-fold. Conclusions: This study demonstrated that overall ambulation and anatomic-functional level were significantly better among our large postnatal cohort, as well as having significantly fewer complications to both fetus and mother, when compared to the postnatal cohort of the MOMS trial. Our finding that ambulatory ability declined significantly with age in this patient population is worrisome for the long-term outcomes of the MOMS cohorts, especially given the high rates of cord tethering at early ages within the prenatal cohort. These findings suggest that the perceived benefits of prenatal closure over postnatal closure may not be as substantial as presented in the original trial, with the durability of results still remaining a concern.

Magnesium sulfate titration reduces maternal complications following fetoscopic closure of spina bifida.

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 (adjusted odds ratio: 8.57; 95% confidence interval: 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.

Learning curves of open and endoscopic fetal spina bifida closure: systematic review and meta-analysis.

The Management of Myelomeningocele Study (MOMS) trial demonstrated the safety and efficacy of open fetal surgery for spina bifida aperta (SBA). Recently developed alternative techniques may reduce maternal risks without compromising the fetal neuroprotective effects. The aim of this systematic review was to assess the learning curve (LC) of different fetal SBA closure techniques. MEDLINE, Web of Science, EMBASE, Scopus and Cochrane databases and the gray literature were searched to identify relevant articles on fetal surgery for SBA, without language restriction, published between January 1980 and October 2018. Identified studies were reviewed systematically and those reporting all consecutive procedures and with postnatal follow-up ≥ 12 months were selected. Studies were included only if they reported outcome variables necessary to measure the LC, as defined by fetal safety and efficacy. Two authors independently retrieved data, assessed the quality of the studies and categorized observations into blocks of 30 patients. For meta-analysis, data were pooled using a random-effects model when heterogeneous. To measure the LC, we used two complementary methods. In the group-splitting method, competency was defined when the procedure provided results comparable to those in the MOMS trial for 12 outcome variables representing the immediate surgical outcome, short-term neonatal neuroprotection and long-term neuroprotection at ≥ 12 months of age. Then, when raw patient data were available, we performed cumulative sum analysis based on a composite binary outcome defining successful surgery. The composite outcome combined four clinically relevant variables for safety (absence of extreme preterm delivery < 30 weeks, absence of fetal death ≤ 7 days after surgery) and efficacy (reversal of hindbrain herniation and absence of any neonatal treatment of dehiscence or cerebrospinal fluid leakage at the closure site). Of 6024 search results, 17 (0.3%) studies were included, all of which had low, moderate or unclear risk of bias. Fetal SBA closure was performed using standard hysterotomy (11 studies), mini-hysterotomy (one study) or fetoscopy by either exteriorized-uterus single-layer closure (one study), percutaneous single-layer closure (three studies) or percutaneous two-layer closure (one study). Only outcomes for standard hysterotomy could be meta-analyzed. Overall, outcomes improved significantly 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 exteriorized-uterus single-layer fetoscopy, competency was not reached in the 81 and 28 cases available for analysis, respectively, and LC prediction analysis could not be performed. The number of cases operated is correlated with the outcome of fetal SBA closure, and the number of operated cases required to reach competency ranges from 35 for standard hysterotomy to ≥ 56-57 for minimally invasive modifications. Our observations provide important information for institutions looking to establish a new fetal center, develop a new fetal surgery technique or train their team, and inform referring clinicians, potential patients and third parties. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Maternal-fetal surgery during the coronavirus disease 2019 pandemic

Maternal-fetal surgery during the coronavirus disease 2019 pandemic

MOMS Plus: Single-Institution Review of Outcomes for Extended BMI Criteria for Open Fetal Repair of Myelomeningocele

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.

Use of plastic wound retractor at hysterotomy site in prenatal repair of myelomeningocele: a new technique

Objective: To describe the use of a self-retaining thermoplastic polyurethane wound retractor for the management of hysterotomy during prenatal repair of myelomeningocele.Methods: The preliminary experience with 16 consecutive cases of open surgery for prenatal repair of myelomeningocele using a new technique is presented. Under general anesthesia, the gravid uterus was partially exteriorized through a low transverse abdominal incision and a high 3–4-cm midline vertical mini-hysterotomy was performed. After chorioamniotic membranes were opened with scissors, the internal ring of the retractor was placed into the amniotic cavity to compress the chorioamniotic membranes against the internal uterine wall and permit full retraction of the hysterotomy. Once the neurosurgical intervention was completed, the retractor was removed manually and uterine and abdominal incisions were closed using conventional techniques. Intra- and post-operative complications, as well as short-term pregnancy outcomes, were evaluated.Results: Intrauterine surgery was performed at a mean gestational age of 25.3 weeks and all except two of the interventions were completed within 3.0 h. When compared with the technique described in the Management of Myelomeningocele study (MOMS) trial, the use of the retractor was associated with a lower, although statistically nonsignificant, rate of chorioamniotic membrane separation (20/78 (26%) versus 2/16 (13%), respectively), preterm rupture of membranes (36/78 (46%) versus 4/16 (25%), respectively), and persistent oligohydramnios (16/78 (21%) versus 1/16 (6%), respectively) as well as higher gestational age at delivery (34.1 weeks ± 3.1 versus 36.0 weeks ± 1.93, respectively) and birthweight (2383 g ± 688 versus 2790 g ± 529, respectively). There were no intra- or post-operative complications associated with the use of the device. Only one (6%) of the hysterotomy scars was noted to be thin at the time of the cesarean delivery and no cases of dehiscence occurred.Conclusions: The use of a plastic wound retractor at the hysterotomy site provides a less traumatic approach than the conventional technique for the management of the uterine incision during open intrauterine surgery. Our experience with this technique was associated with short-term pregnancy outcomes that are similar and perhaps even superior to the technique reported in the MOMS trial. Because the device is inexpensive, easy to use, and widely available, its use during open intrauterine surgery should be considered. However, further clinical experience is required to reach a definitive conclusion regarding whether this technique should be incorporated into the protocol of prenatal repair of myelomeningocele.

68: Prenatal open hysterotomy vs. two-port exteriorized uterus fetoscopic myelomeningocele repair. perinatal outcomes from a single center

To assess obstetrical and perinatal outcomes after fetal open or fetoscopic myelomeningocele (MMC) repair. Retrospective cohort study from 2011-2018. 66 patients diagnosed with fetal MMC who underwent a prenatal repair in our center via open-hysterotomy (N=33) or fetoscopic repair (N=33) were included. All patients fulfilled Management of Myelomeningocele Study (MOMS) inclusion and exclusion criteria. Open-hysterotomy repair was performed as reported in MOMS trial. Our standardized fetoscopic repair is a two port, exteriorized uterus, technique in CO2, using interrupted sutures for the neurosurgical repair.13 of the fetosocpic and 8 of the open repaired patients received a dural patch. Obstetrical and perinatal outcomes were compared between groups using Student's t-test for independent samples or Mann-Whitney U test if they had normal or non-normal distribution, respectively. Chi-square or Fisher's exact tests were used to compare qualitative data. Duration of surgery and spinal defect repair were lengthier in the fetoscopic group. There were no differences in intraoperative fetal bradycardia or postoperative complications. Fetoscopically repaired cases were delivered later [38.6 (29.9-40.9) weeks vs. 35.7 (27.3-37.9) weeks; p<0.01] with higher birth weight [3120(1375-4430)grams vs. 2611 (624-3623)grams; p<0.01] and a lower rate of cesarean delivery (43% vs. 100%; p<0.01). Intact surgical sites were seen in all 14 fetoscopic cases delivered by c-section and in 21 of open cases (p<0.01). Uterine adhesions were more common after open repair (36% vs. 14%; p<0.01). One neonatal death occurred after an open repair due to extreme preterm birth and sepsis. Fetoscopic repair has a lengthier surgery but similar postoperative complications to open repair, while offering significant benefits including higher gestational age at birth, vaginal delivery and a decreased risk of adhesions and scar dehiscence.

220: Prenatal open vs. two-port exteriorized uterus fetoscopic myelomeningocele repair. Neurosurgical outcomes from a single center

To assess neurosurgical and motor outcomes after an open-hysterotomy or fetoscopic fetal myelomeningocele (MMC) repair. Retrospective cohort study from 2011-2018. 66 patients diagnosed with fetal MMC who underwent a prenatal repair in our center via open-hysterotomy (N=33) or fetoscopic repair (N=33) were included. All patients fulfilled the Management of Myelomeningocele Study (MOMS) inclusion and exclusion criteria. Open-hysterotomy repair technique was performed as reported in MOMS trial. Our standardized fetoscopic repair is a two port, exteriorized uterus technique in CO2, using interrupted sutures for the neurosurgical repair. 13 and 8 of the fetoscopic and open repaired cases respectively, received a dural patch. Neurosurgical outcomes were compared between groups using Student's t-test for independent samples or Mann-Whitney U test if they had normal or non-normal distribution respectively for quantitative data. Chi-square or Fisher's exact test were used to compare qualitative data. Rate of complete hind brain herniation reversal assessed by MRI six weeks after prenatal repair, was similar between both groups [Fetoscopic: 23/32 (71.9%) vs.Open:21/33 (63.6%); p=0.47]. There were no significant differences between the groups in the rates of CSF leak, revision of repair at birth, need for ventriculo-peritoneal shunt placement or need for endoscopic third ventriculostomy (ETV) during the first year of life. Evaluation of functional and anatomical levels of the spinal defect also showed similar rates of improvement. Minimally invasive fetoscopic MMC repair shows comparable neurosurgical and motor outcomes to the open- hysterotomy approach.

Fetal surgery for myelomeningocele: Obstetric evolution and short-term perinatal outcomes of a cohort of 21 cases

ResumenObjetivo:Describir la técnica quirúrgica, evolución obstétrica y resultados perinatales de una cohorte de pacientes sometidas a cirugía intrauterina para reparación de una disrafia fetal abierta (DFA).Métodos:Análisis prospectivo de 21 casos consecutivos de DFA con diagnóstico y tratamiento quirúrgico prenatal en nuestra institución entre 2015 y 2017. La técnica de la cirugía fetal (QF) fue similar a la descripta en el estudio MOMS, excepto que se utilizó histerotomía con asa bipolar. Los cuidados postoperatorios, nacimiento y cuidados neonatales se realizaron en la misma institución. Se analizaron complicaciones perioperatorias de la QF, la evolución obstétrica y los resultados perinatales.Resultados:La QF se realizó a una edad gestacional media de 25.8 semanas (24.1-27.6). La edad gestacional media al nacer fue 34.2 semanas (29.2-37.1). El tiempo quirúrgico medio fue 138 min (101-187) con tendencia descendente y el tiempo de internación medio, 7.1 días (4-32). El 52% (11/21) de las pacientes experimentó rotura prematura de membranas (RPM). Ninguna paciente requirió transfusiones postcesárea. No hubo casos de desprendimiento placentario, rotura uterina ni muertes maternas. La cicatrización de la histerorafia fue normal en 95% de las pacientes. La sobrevida perinatal fue del 95% (20/21, una muerte intrauterina secundaria a banda amniótica). La necesidad de cierre cutáneo postnatal (CCP) fue del 5%. Ninguno de los casos (20) reparados con tejidos fetales requirió CCP. El 70% (14/20) de los pacientes no requirió ningún tratamiento para hidrocefalia. Cuatro pacientes (20%) requirieron una derivación ventriculoperitoneal (DVP) y dos adicionales, una tercer ventriculostomía endoscópica (ETV) (10%). El nivel funcional motor neonatal (NFN) fue mejor que el nivel anatómico prenatal (NAP) en 45% (9/20), igual en 50% (10/20) y peor en 5% (1/20).Conclusiones:El presente estudio confirma que la cirugía fetal de disrafias abiertas se asocia a un mayor riesgo de parto prematuro y rotura prematura de membranas, pero reduce significativamente la necesidad de tratamiento postnatal de hidrocefalia y mejora la función motora a corto plazo. Nuestros resultados son similares a los publicados en el ensayo aleatorizado MOMS.

Prenatal surgery for myelomeningocele: review of the literature and future directions

Open spina bifida or myelomeningocele (MMC) is one of the most common serious congenital malformations. Historically, this condition has been treated with closure of the MMC defect shortly after birth. The goal of postnatal closure is to cover the exposed spinal cord and prevent infection. However, postnatal surgery does not reverse or prevent the neurologic injury seen in MMC, reverse hindbrain herniation, or prevent hydrocephalus. The neurologic defects result from primary incomplete neurulation and secondary chronic prenatal damage to the exposed neural elements through mechanical and chemical trauma. In a hope to reduce the numerous surgical procedures, medical complications, and lifelong disabilities associated with MMC, the proposal of prenatal closure was put forth more than two decades ago. After promising results in animal models and some clinical series, a randomized controlled trial, the Management of Myelomeningocele Study (MOMS), was conducted. The MOMS trial demonstrated that closure during the prenatal period could be performed relatively safely and can result in significant benefit to the child. Specifically, prenatal closure results in improved motor function, reduced hindbrain herniation, and reduced need for a cerebral spinal fluid diversion. Long-term outcomes of the patients in the MOMS trial continues in the MOMS 2 study as these children grow. Additionally, investigations are underway on modifications to the open fetal MMC closure techniques.

First 60 fetal in-utero myelomeningocele repairs at Saint Louis Fetal Care Institute in the post-MOMS trial era: hydrocephalus treatment outcomes (endoscopic third ventriculostomy versus ventriculo-peritoneal shunt).

The published results of the Management of Myelomeningocele Study (MOMS) trial in 2011 showed improved outcomes (reduced need for shunting, decreased incidence of Chiari II malformation, and improved scores of mental development and motor function) in the fetal prenatal repair group compared to the postnatal group. Historically, endoscopic third ventriculostomy (ETV) remains as a controversial hydrocephalus treatment option with high failure rates in pediatric patients with a history of myelomeningocele (MMC). We report hydrocephalus treatment outcomes in the fetal in-utero myelomeningocele repair patients who underwent repair at our Saint Louis Fetal Care Institute following the MOMS trial. We looked carefully at ETV outcomes in this patient population and we identified risk factors for failure. At our Saint Louis Fetal Care Institute, we followed the maternal and fetal inclusion and exclusion criteria used by the MOMS trial. The records of our first 60 fetal MMC repairs performed at our institute between 2011 and 2017 were examined. We retrospectively reviewed the charts, prenatal fetal magnetic resonance imaging (MRI) and ultrasound (US) imaging findings, postnatal brain MRI, and Bayley neurodevelopment testing results for infants and children who underwent surgical treatment of symptomatic hydrocephalus (VP shunt versus ETV). Multiple variables possibly related to ETV failure were considered for identifying risk factors for ETV failure. Between May 2011 and March 2017, 60 pregnant female patients underwent the prenatal MMC repair for their fetuses between 20 and 26weeks' gestational age (GA) utilizing the standard hysterotomy for exposure of the fetus, and microsurgical repair of the MMC defect. All MMC defects underwent successful in-utero repair, with subsequent progression of the pregnancy. At the time of this study, 58 babies have been born, 56 are alive since there were 2 mortalities in the neonatal period due to prematurity. One patient was excluded given lack of consent for research purposes. From the remaining 55 patient included in this study, a total of 30 infants and toddlers underwent treatment of hydrocephalus (ETV and VPS groups). Twenty-five patients underwent ETV (24 primary ETV and 1 after shunt failure). Nineteen patients underwent shunt placements (6 primary/13 after ETV failure). Mean GA at time of MMC repair for the ETV group was 24+6/7weeks (range 22+4/7 to 25+6/7). Mean follow up for patients who had a successful ETV was 17.25months (range 4-57months). Bayley neurodevelopmental testing results were examined pre- and post-ETV. Overall ETV success rate was 11/24 (45.8%) at the time of this study. The total number of patients who underwent shunt placement was 19/55 (34.5%), while shunting rate was 40% in the MOMS trial. Using a simple logistic regression analysis to identify predictors of ETV failure, ETV age ≤6months and gestational age ≥23weeks at repair of myelomeningocele were significant predictors for ETV failure while in-utero ventricular stability ≤4mm and in-utero ventricular size post-repair ≤15.5mm were significant predictors for ETV success. None of the listed variables independently predicted classification into ETV success versus ETV failure groups when entered into multiple logistic regression analysis. ETV, as an alternative to initial shunting, may continue to show promising results for treating fetal MMC repair patient population who present with symptomatic hydrocephalus during infancy and early childhood. Although our overall CSF diversion rate (ETV and VPS groups) in our fetal MMC group is higher than the MOMS trial, our shunting rate is lower given our higher incidence of patients with successful ETV. To our knowledge, this is the largest reported ETV series in patients who underwent fetal MMC repair. ETV deserves a closer look in the setting of improved hindbrain herniation in fetal in-utero MMC repair patients. In our series, young age (less than 6months) and late GA at time of fetal MMC repair (after 23weeks GA) were predictors for ETV failure, while in-utero stability of ventricular size (less than 4mm) and in-utero ventricular size post-repair ≤15.5mm were predictors for ETV success. Larger series and potential prospective randomized studies are required for further evaluation of risk factors for ETV failure in the fetal MMC patient population.

Specialty-Based Variation in Applying Maternal-Fetal Surgery Trial Evidence

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.

A comparison of the MOMS trial results to a contemporaneous, single-institution, postnatal closure cohort.

We evaluate a single-institution cohort of mothers contemporaneous with the Management of Myelomeningocele Study (MOMS) trial to determine the generalizability of MOMS results and compare shunt rates. A retrospective chart review identified patients with myelomeningocele born between 2003 and 2009. We applied MOMS eligibility criteria and compared sociodemographic variables between patients at our institution who would have been eligible or ineligible and MOMS participants. Finally, we applied the original MOMS primary outcome and the revised primary outcome to our cohort. Of the 78 patients, 55 (70.5%) were eligible for the MOMS trial. Mean maternal age, race, and marital status were different from both MOMS groups. Comparing our series to MOMS postnatal shows fewer female infants (44.9 vs. 63.8%, p=0.017) and more thoracic lesions (12.8 vs. 3.8%, p=0.038). Shunt rates in our cohort (84.6%) were higher than MOMS prenatal and similar to MOMS postnatal (44.0 and 83.7%, respectively). Fewer children met the original primary outcome than the postnatal group (84.6 vs. 97.8%, p=0.002). There was no significant difference between our cohort and the prenatal group (84.6 vs. 72.5%, p=0.058). When applying the revised criteria, we find the opposite: a significant difference between local and MOMS prenatal (84.6 vs. 49.5%, p<0.001) but no difference between the local group and MOMS postnatal (84.6 vs. 87.0%, p=0.662). Mothers in our cohort differ from mothers enrolled in MOMS via several sociodemographic factors. Baseline fetal characteristics show a significantly higher functional lesion level in between our cohort and MOMS. Treatment of hydrocephalus in our series tracks almost identically with original MOMS shunt criteria. Revision of the criteria led to greater concordance between meeting criteria and receiving a shunt in MOMS patients, but changes the results in our series.

Long-term neurofunctional outcome, executive functioning, and behavioral adaptive skills following fetal myelomeningocele surgery

Myelomeningocele (MMC) represents the first nonlethal anomaly to be treated by prenatal intervention. Case series and a prospective, randomized study show that fetal surgery for MMC before 26 weeks' gestation may preserve neurological function. Long-term follow-up is a fundamental component to evaluate the overall efficacy of any new medical or surgical procedure. To further delineate the long-term impact of fMMC surgery, we continued to follow children treated in our institution before the Management of Myelomeningocele Study trial by the means of parental questionnaires to assess changes in functional, developmental, and cognitive status as these unique patients grow older. The objective of the study was to evaluate the long-term neurological outcome, executive functioning (EF), and behavioral adaptive skills (BAS) following fetal myelomeningocele (fMMC) surgery. Prior to the Management of Myelomeningocele Study trial, 54 patients underwent fMMC surgery at our institution. Parents of 42 children (78%) participated in structured questionnaires focusing on neurofunctional outcome. EF and BAS were measured by the Behavior Rating Inventory of Executive Function (BRIEF) and the Adaptive Behavioral Assessment System II. The BRIEF is organized into 3 primary indices including the following: Global Executive Composite, Metacognition Index, and Behavioral Regulation Index. The Adaptive Behavioral Assessment System II results in a general adaptive composite score. Based on SD intervals, EF and BAS were categorized as being average, borderline, or impaired. At a median follow-up age of 10 years (range, 8-14 years), 33 (79%) are community ambulators, 3 (9%) are household ambulators, and 6 (14%) are wheelchair dependent. Preschool ambulation was predictive of long-term ambulation (P < .01), whereas the need for tethered cord surgery was associated with persistent deterioration of ambulatory status (P= .007). Normal bladder function was found in 26%. Although the majority scored within the average range for the Behavioral Regulation Index, Metacognition Index, and Global Executive Composite indices, significantly more children who had fMMC surgery had deficits in EF in all 3 BRIEF indices compared with the population norms. The general adaptive composite scores were also more likely to fall below average following fMMC surgery. Normal early neurodevelopmental outcomes were predictive of normal EF and BAS (P < .01). Need for shunting was associated with a significant impairment of BAS (P= .02). The present study suggests that fMMC surgery improves long-term functional outcome. The majority of fMMC children can successfully complete everyday tasks at home and at school. Abnormalities of BAS appear to be more common than impairments in EF and therefore offer an area for early screening and interventional therapy for these at-risk children. Non-shunted fMMC children with normal early neurodevelopmental outcome are less likely to experience problems with EF and BAS. fMMC surgery improves long-term ambulatory status. Symptomatic spinal cord tethering with or without intradural inclusion cyst is associated with functional loss. More than expected fMMC children are continent, but bowel and bladder control continue to be an ongoing challenge for the fMMC children.