Prenatal MMC Repair Research Articles

Regression of Chiari malformation type 2 following early postnatal meningomyelocele repair-a retrospective observation from an institutional series of patients.

Spontaneous regression of Chiari malformation type 2 (CM2) is observed rarely, as CM2 is associated with meningomyelocele (MMC) that issurgically repaired either pre- or early postnatally. While the radiological regression of CM2 occurs frequently following prenatal repair of MMC, it has been reported in only a few studies after postnatal repair. From the consecutive series of children with postnatally repaired MMC, we reviewed the clinical and radiological data regarding CM2, particularly its regression either spontaneously or following CSF diversion. Eighteen children underwent postnatal repair of MMC between February 2011 and April 2023. CM2 was present in 16 (89%), and hydrocephalus in 15 children (83%), requiring shunting in 14 of them. During the mean clinical observation time (from birth to April 2023) of 59 ± 51months, three children with CM2 (19%) underwent 1-2 foramen magnum decompressions (FMD), five children (28%) 1-4 surgical untethering procedures and 13 children with shunted hydrocephalus (93%) 1-5shunt revisions. Out of sixteen children with CM2, we observed regression of CM2 on MRI in only one case (6%) during the mean radiological follow-up (from birth to the last MRI taken) of 49 ± 51months. In our experience, spontaneous regression of CM2 in children with postnatally repaired MMC occurs quite rarely. Pathophysiological mechanisms behind the development of CM2 in children with MMC remain unclear, but our observation supports the hypothesis of an association between the downward displacement of the hindbrain and the low intraspinal pressure secondary to CSF leakage in children born with MMC.

Prenatal Neurosurgical Counseling for Myelomeningocele and Treatment-Determining Factors for Fetal Repair.

Spina bifida guidelines recommend neurosurgical involvement in prenatal counseling (nPNC) to inform decision-making between prenatal and postnatal MMC repair. This study examines whether families with myelomeningocele (MMC) presenting to one fetal center had timely nPNC encounters, and assesses modifiable and non-modifiable treatment-determining factors. History and timing of nPNC were quantified among infants undergoing postnatal and prenatal MMC repair, pregnant patients referred, and MMC studies in a fetal MRI database (2015-2023). Fetal repair exclusions, presentation timing, social determinants, and reported rationale for not selecting offered fetal therapy were assessed. Nearly all patients (34/35; 97%) engaged in nPNC, 82% prior to 24 weeks GA. Fourteen patients were excluded from fetal repair for lack of hindbrain herniation (43%), obstetric exclusions (21%), fetal exclusions (21%), suspected closed defect (7%), and delayed presentation (7%). These patients ultimately underwent postnatal repair (71%), and pregnancy termination (14%). The 20 fetal-repair-eligible patients selected fetal repair (50%), postnatal repair (45%), and pregnancy termination (5%). Reasons for declining fetal repair included risk (55%) and cost (22%). Among MMC families presenting to a regional fetal therapy center, nPNC was widely extended, in a mostly timely fashion. Very few were deterred from fetal repair by potentially modifiable barriers.

MRI analysis of neurodevelopmental anatomy in myelomeningocele: prenatal vs postnatal repair.

Compared with postnatal repair, prenatal myelomeningocele (MMC) repair is associated with improved motor function and decreased need for cerebrospinal fluid (CSF) diversion. It is unknown how prenatal surgery alters neuroanatomical structures identifiable on magnetic resonance imaging (MRI). The purpose of this study was to use MRI to compare neurodevelopmental anatomy in patients undergoing fetal MMC repair compared with those undergoing postnatal repair. This was a retrospective review of neonates who underwent prenatal or postnatal MMC repair at our institution between 2016 and 2021. Imaging data, including prenatal ultrasound and pre- and postnatal MRI examinations, if available, were retrieved. We analyzed anatomical findings characteristically seen on MRI of the neuroaxis in patients with MMC and compared imaging findings between patients with prenatal vs postnatal MMC repair. The study population included 61 patients who underwent surgical repair for MMC during the 6-year study period, of whom 25 underwent prenatal repair and 36 postnatal repair. CSF diversion was required in 24% of the prenatally repaired cohort vs 67% of the postnatally repaired cohort (P = 0.001). On postnatal MRI, a syrinx was present in 13% of the prenatally repaired cohort vs 42% in the postnatally repaired cohort (P = 0.02). Postnatal corpus callosal (CC) morphology was abnormal in 54% of the prenatally repaired cohort vs 53% of the postnatally repaired cohort (P = 0.92), while falx morphology was normal in 92% of the prenatally repaired cohort vs 34% of the postnatally repaired cohort (P < 0.001). On postnatal MRI, patients in the prenatally repaired cohort had a shorter tentorium-to-foramen-magnum distance compared with those in the postnatally repaired cohort (mean, 18.43 mm vs 22.42 mm; P = 0.01), a larger foramen magnum diameter (mean, 22.87 mm vs 18.94 mm; P < 0.001) and a smaller degree of hindbrain herniation (mean, 1.53 mm vs 8.72 mm; P < 0.001). The cerebral aqueduct was patent in 79% of the prenatally repaired cohort vs 100% of the postnatally repaired cohort on postnatal MRI (P = 0.008). Between the two cohorts, at postnatal MRI there was no significant difference in the presence of gray-matter heterotopia, presence of the septum pellucidum or size of the massa intermedia. We report variations in developmental neuroanatomy in patients with MMC, including rates of CC dysgenesis, gray-matter heterotopia and additional cranial and spinal MRI findings. Compared to postnatal surgery, prenatal surgery is associated with changes to infratentorial anatomy, with minimal effect on supratentorial brain development. This information will be useful in counseling parents affected by fetal MMC and in understanding how prenatal repair of MMC affects brain development. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal surgery in fetal myelomeningocele with severe ventriculomegaly.

Prenatal myelomeningocele (MMC) repair is performed to decrease risk for treatment of hydrocephalus after birth and to preserve motor function. Some centers may not consider patients candidates for surgery if severe ventriculomegaly is present and there is no expected benefit in decreased risk for hydrocephalus treatment. This study sought to compare postnatal outcomes of fetuses with MMC and severe ventriculomegaly (>15mm) who underwent prenatal repair, with fetuses with severe ventriculomegaly who underwent postnatal repair and fetuses with ventriculomegaly (<15mm) who underwent prenatal repair. This was a retrospective study of fetuses with MMC that underwent prenatal or postnatal repair between 2012 and 2021 at a single institution. The cohort was divided based on preoperative fetal ventricular size into two groups, those with severe ventriculomegaly (≥15 mm) and those without severe ventriculomegaly (<15 mm). Fetal ventricular size was measured by MRI prior to surgery using the standardized approach and the mean of the left and right ventricle was used for analysis. Motor function of lower extremities was assessed at the time of referral by ultrasound and if flexion-extension movements of the ankle were seen, it was considered as preserved S1 motor function. Postnatal outcomes including motor function of lower extremities assessed at birth and need for diversion procedure for hydrocephalus treatment during the first year of life were collected and compared between groups. Data was presented as median and range or number and percentages as appropriate. P value >0.05 was considered statistically significant. Multivariate regression analysis was used to adjust for potential confounders. 154 patients were included in this study: 145 patients underwent fetal surgery (101 fetoscopic and 44 open hysterotomy) and 9 patients with severe ventriculomegaly underwent postnatal repair. Among the 145 patients who underwent fetal surgery, 22 presented with severe ventriculomegaly. Prenatally repaired fetuses with severe ventriculomegaly at referral were at a significantly higher need for hydrocephalus treatment by 12 months than those without severe ventriculomegaly (62% vs. 29%, p<0.01). However, motor function assessment at birth was similar between both prenatally repaired groups (OR=0.92, 95% CI [0.33-2.59], p=0.88) adjusted for the anatomical level of the lesion. The prenatally repaired group with severe ventriculomegaly had better preserved motor function levels at birth compared to the postnatal repair group with severe ventriculomegaly (L3 with 11.1% S1 motor function; p=<0.01 and p=<0.01). Prenatally repaired patients with severe ventriculomegaly had an 18.9 times chance of having an intact motor function at birth [95% CI (1.2 - 290.1)] adjusted for ethnicity, presence of clubfeet at referral, and gestational age at delivery compared to postnatal repair. There was not a significant difference in the need for hydrocephalus treatment in the first year of life between prenatal and postnatal repair of patients with severe ventriculomegaly (61.9% vs 87.5%, p=0.18). Although fetuses with MMC and severe ventriculomegaly do not seem to benefit from fetal surgery in terms of postnatal hydrocephalus treatment, they benefit from increased chance of preserved motor function at birth. Results from this study highlight the benefits of having prenatal MMC repair for cases with severe ventriculomegaly at referral to preserve motor function. This article is protected by copyright. All rights reserved.

Sleep-related breathing disorders in infants with spina bifida repaired prenatally and postnatally.

Advances in prenatal repair of myelomeningocele (MMC) have improved outcomes involving different organ systems. There is limited data on respiratory outcomes following prenatal surgical repair. We hypothesize there is no difference in respiratory outcomes between spina bifida (SB) patients who have undergone prenatal versus postnatal repair. We performed a retrospective study of 46 infants <1 year with SB seen at Children's Hospital Los Angeles from 2004-2022. Demographic data, timing of closure, neonatal course, Chiari II malformation (CIIM), ventriculoperitoneal shunt (VPS), polysomnography (PSG) results, and need for supplemental oxygen were collected. Unpaired t-test and Chi-square Test were used to analyze results. 31/46 had prenatal repair of MMC; average age at repair was 27 weeks post-conception (PCA). Average age at postnatal repair was 37 PCA. There was no difference in age at PSG. There was no difference in CIIM presence (p=0.61). 60% of patients with postnatal repair and 23% in the prenatal group underwent VPS placement (p=0.01). Patients with SB who've undergone closure of neural tube defect have persistent central apneas, obstructive apneas, and significant hypoxemia. There were no differences in the frequency or severity of sleep-disordered breathing in those with prenatal repair versus postnatal repair.

Head growth in patients with myelomeningocele treated with prenatal and postnatal surgery.

The need for permanent CSF diversion is lower in patients who have undergone prenatal surgery for myelomeningocele (MMC) than in those who have undergone postnatal closure. Differences in brain development and head growth between treatment groups are not known, particularly for those who do not require surgical treatment for hydrocephalus. The objective of this study was to determine differences in head growth and to generate MMC-specific head circumference (HC) growth curves for patients who underwent either prenatal or postnatal surgery. The authors retrospectively identified patients from St. Louis Children's Hospital who were treated for MMC between 2016 and 2021. HC data were obtained from birth until the most recent follow-up or hydrocephalus treatment. Nonlinear least-squares regression analysis was performed to fit the data into four models: two-term power, Gompertz, West ontogenetic, and Weibull. Subsequently, the curves were assessed for their utility in predicting hydrocephalus treatment. Sixty-one patients (29 females [47.5%], 25 [41%] underwent prenatal surgery, mean gestational age at birth 36.6 weeks) were included in the study. The Weibull model best fit the HC data (prenatal adjusted R2 = 0.95, postnatal adjusted R2 = 0.95), while the Gompertz model had the worst fit (prenatal adjusted R2 = 0.56, postnatal adjusted R2 = 0.39) across both cohorts. Prenatal MMC repair patients had significantly larger HC measurements than their postnatal repair counterparts. The 50th percentile of the Weibull curve was determined as a useful threshold for hydrocephalus treatment: children with HC measurements that crossed and remained above this threshold were significantly more likely to have hydrocephalus treatment regardless of time of MMC repair (prenatal relative risk [RR] 10.0 [95% CI 1.424-70.220], sensitivity 85.7% [95% CI 0.499-0.984], and specificity 82.4% [95% CI 0.600-0.948]; postnatal RR 4.750 [95% CI 1.341-16.822], sensitivity 90.5% [95% CI 0.728-0.980], and specificity 75.0% [95% CI 0.471-0.924]). The HC growth curves of the MMC patients treated prenatally were significantly larger than the WHO HC curves (p < 0.001). The Weibull model was identified as the HC growth curve with the best fit for MMC patients and serves as a useful predictor of hydrocephalus treatment. For MMC patients with hydrocephalus, prenatal repair patients fit the model well but postnatal repair patients did not, potentially indicating different mechanisms of hydrocephalus development. Those treated prenatally had significantly larger HC measurements compared with both the general population and those treated postnatally. Further study is needed to understand the long-term cognitive outcomes and optimal management of clinically asymptomatic patients with large HC measurements who were treated prenatally for MMC.

Fetal surgery for spina bifida – An upcoming standard of care

Open spina bifida or myelomeningocele (MMC) is one of the most common serious congenital malformations that have been historically treated with a repair after birth. However, this “repair” does not avert neurological injury, reverse hindbrain herniation, or prevent hydrocephalus. With the intention to reduce numerous medical procedures, lifelong morbidities, and medical complications, fetal surgery was proposed about a quarter century ago. Fetal surgery has become the standard of care for MMC, especially after the advent of the Management of Myelomeningocele Study (MOMS) trial. Dr. Michael Harrison from the University of California was the first to birth this idea in the 1980s. While earlier research was carried out on ovine models, it was deduced that intrauterine repair reduces the secondary damage to exposed neural tissue and improves post-natal neurological outcomes. After the promising results in animal models and some clinical series, it paved the way for a prospective multicenter randomized controlled trial that compared prenatal versus postnatal MMC repair, with the aim to prove its efficacy and safety with Level-1 evidence- the MOMS. However, it was stopped early due to the improved prenatal repair outcomes, thus establishing open fetal MMC repair as the standard of care. We aim to discuss the origin story of this remarkable procedure, its rationales and advantages for the unborn child and mother and its short-term and long-term superiority and limitations. The operative procedure and the criteria with other essential aids in its diagnosis have also been discussed briefly. We also intend to eliminate the apprehension faced toward this procedure by the supporting team of obstetricians, anesthetists, neonatologists, and radiologists essential to making this procedure a success.

The value and limitations of using predetermined criteria in decision making for maternal-fetal interventions.

Maternal-fetal interventions &#x2013; such as prenatal fetal myelomeningocele (MMC) repair &#x2013; are at the forefront of clinical innovation within maternal-fetal medicine, pediatric surgery, and neonatology. Many centers determine eligibility for innovative procedures using inclusion and exclusion criteria based on seminal studies, such as the &#x201C;Management of Myelomeningocele Study&#x201D; for prenatal MMC repair. What if a person&#x2019;s clinical presentation does not conform to predetermined criteria for maternal-fetal intervention? Does changing criteria on a case-by-case basis (i.e., ad hoc) constitute innovation in practice and flexible personalized care or transgression of commonly held standards with potential negative consequences? We outline a principle-based, bioethically-justified method for answering these questions using fetal MMC repair as an example. We give special attention to the historical origins of inclusion and exclusion criteria; risks and benefits to the pregnant person and the fetus; and team dynamics. This article is protected by copyright. All rights reserved.

Fetal Surgery for Myelomeningocele: Neurosurgical Perspectives.

More than 30years have elapsed since it was recognised that folic acid supplementation could substantially reduce the risk of open neural tube defects (ONTDs). During that time, many countries have adopted policies of food fortification with demonstrable reduction in the incidence of both cranial and spinal ONTDs. Improved prenatal detection and termination has also resulted in a reduction in the number of affected live births. Nonetheless, in the USA about 1500 children, and in the UK around 500 children are born each year with myelomeningocele (MMC) and so the management of MMC and its complications continues to constitute a significant clinical workload for many paediatric neurosurgical units around the world.Until recently, the options available following antenatal diagnosis of MMC were termination of pregnancy or postnatal repair. As a result of the MOMS trial, prenatal repair has become an additional option in selected cases (Adzick et al., N Engl J Med 364(11):993-1004, 2011). Fetal surgery for myelomeningocele is now offered in more than 30 centres worldwide. The aim of this chapter is to review the experimental basis of prenatal repair of MMC, to critically evaluate the neurosurgical implications of this intervention and to describe the technique of 'open' repair, comparing this with emerging minimally invasive alternatives.

Neuropathology Evaluation of in Utero Correction of Myelomeningocele and Complications of Late-Onset GBS Infection

Background: Myelomeningocele (MMC) causes significant morbidity and mortality. Efforts have been directed to correct this defect in utero. The neuropathology literature on antenatally repaired MMC and associated complications in humans is limited. Case report: A 12-day-old female, who underwent prenatal MMC repair via a two-layer closure (dural replacement patch, primary skin closure), was born at 34 weeks’ gestation. Her group B streptococcus positive mother received appropriate antepartum prophylactic antibiotics. She remained stable until day 11 of life when she underwent rapid clinical deterioration. Despite aggressive intervention, she expired on day 12. Review of placental pathology showed maternal and fetal inflammatory response. Autopsy revealed Gram-positive cocci and inflammation within the basilar leptomeninges and lumbosacral region. Neural and dermal elements were present within the MMC repair. Conclusion: This case documents integration of the dermal matrix patch to neural elements, adhering the spinal cord to scar tissue, the clinical implications of which remain unclear.

Impact of the volume of the myelomeningocele sac on imaging, prenatal neurosurgery and motor outcomes: a retrospective cohort study

To investigate the association of the myelomeningocele (MMC) volume with prenatal and postnatal motor function (MF) in cases who underwent a prenatal repair. Retrospective cohort study (11/2011 to 03/2019) of 63 patients who underwent a prenatal MMC repair (37 fetoscopic, 26 open-hysterotomy). At referral, measurements of the volume of MMC was performed based on ultrasound scans. A large MMC was defined as greater than the optimal volume threshold (ROC analysis) for the prediction of intact MF at referral (2.7 cc). Prenatal or postnatal intact motor function (S1) was defined as the observation of plantar flexion of the ankle based on ultrasound scan or postnatal examination. 23/63 participants presented a large MMC. Large MMC lesions was associated with an increased risk of having clubfeet by 9.5 times (CI%95[2.1–41.8], p < 0.01), and reduces the chances of having an intact MF at referral by 0.19 times (CI%95[0.1–0.6], p < 0.01). At birth, a large MMC reduces the chance of having an intact MF by 0.09 times (CI%95[0.01–0.49], p < 0.01), and increases the risk of having clubfeet by 3.7 times (CI%95[0.8–18.3], p = 0.11). A lower proportion of intact MF and a higher proportion of clubfeet pre- or postnatally were observed in cases with a large MMC sac who underwent a prenatal repair.Trial registration: Clinicaltrials.gov NCT02230072 and NCT03794011 registered on September 3rd, 2014 and January 4th, 2019.

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.

Open fetal surgery for myelomeningocele repair in France

IntroductionOpen fetal myelomeningocele (MMC) surgery is currently the standard of care option for prenatal MMC repair. We described the population referred to our center and reviewed outcome after open fetal MMC repair. Material and methodsAll patients referred to our center for MMC were reviewed from July 2014 to June 2020. For all the patients who underwent fetal MMC repair, surgical details, maternal characteristics and data from the neonatal to the three-years-old evaluations were collected. ResultsAmong the 126 patients referred to our center, 49.2% were eligible and 27.4% (n = 17) of them underwent fetal MMC repair. Average gestational age at fetal surgery was 24+6 weeks. There was no case of fetal complication and the only maternal complication was one case of transfusion. We recorded 70% of premature rupture of membranes and 47% of premature labor. Average gestational age at delivery was 34+2 weeks and no patient delivered before 30 weeks. There was no case of uterine scar dehiscence or maternal complication during cesarean section. After birth, 59% of the children had a hindbrain herniation reversal. At 1-year-old, 42% were assigned a functional level of one or more better than expected according to the prenatal anatomic level and 25% required a ventriculoperitoneal shunt. At 3-year-old, all the children attended school and 75% were able to walk with orthotics or independently. ConclusionOpen fetal surgery enables anatomical repair of the MMC lesion, a potential benefit on cerebral anomalies and motor function, with a low rate of perinatal and maternal complications.

Diffusion tensor imaging in children following prenatal myelomeningocele repair and its predictive value for the need and timing of subsequent CSF diversion surgery for hydrocephalus.

The aim of this study was to investigate diffusion tensor imaging (DTI), an objective and noninvasive neuroimaging technique, for its potential as an imaging biomarker to predict the need and timing of CSF diversion surgery in patients after prenatal myelomeningocele (MMC) repair. This was a retrospective analysis of data based on 35 pediatric patients after prenatal MMC repair (gestational age at birth 32.68 ± 3.42 weeks, range 24-38 weeks; 15 females and 20 males). A logistic regression analysis was used to classify patients to determine the need for CSF diversion surgery. The model performance was compared between using the frontooccipital horn ratio (FOHR) alone and using the FOHR combined with DTI values (the genu of the corpus callosum [gCC] and the posterior limb of the internal capsule [PLIC]). For patients who needed to be treated surgically, timing of the procedure was used as the clinical outcome to test the predictive value of DTI acquired prior to surgery based on a linear regression analysis. Significantly lower fractional anisotropy (FA) values in the gCC (p = 0.014) and PLIC (p = 0.037) and higher mean diffusivity (MD) values in the gCC (p = 0.013) were found in patients who required CSF diversion surgery compared with those who did not require surgery (all p values adjusted for age). Based on the logistic regression analysis, the FOHR alone showed an accuracy of performance of 0.69 and area under the receiver operating characteristic curve (AUC) of 0.60. The performance of the model was higher when DTI measures were used in the logistic regression model (accuracy = 0.77, AUC = 0.84 for using DTI values in gCC; accuracy = 0.75, AUC = 0.84 for using DTI values in PLIC). Combining the DTI values of the gCC or PLIC and FOHR did not improve the model performance when compared with using the DTI values alone. In patients who needed CSF diversion surgery, significant correlation was found between DTI values in the gCC and the time interval between imaging and surgery (FA: ρ = 0.625, p = 0.022; MD: ρ = -0.6830, p = 0.010; both adjusted for age and FOHR). The authors' data demonstrated that DTI could potentially serve as an objective biomarker differentiating patients after prenatal MMC repair regarding those who may require surgery for MMC-associated hydrocephalus. The predictive value for the need and timing of CSF diversion surgery is highly clinically relevant for improving and optimizing decision-making for the treatment of hydrocephalus in this patient population.

Functional Motor Skills in Children Who Underwent Fetal Myelomeningocele Repair: Does Anatomic Level Matter?

In this study, we evaluated children who underwent prenatal myelomeningocele (MMC) repair to investigate the influence of the anatomical level of the lesion on functional motor skills and congenital orthopedic malformations. This cross-sectional study evaluated children who underwent prenatal correction. The anatomical level of the lesion was classified by observing the magnetic resonance of the spine. The sensory/motor assessment was performed by physical examination to classify the status of ambulation, functional level, and functional performance according to chronological age using the Pediatric Evaluation of Disability Inventory (PEDI-CAT) scale. One hundred cases were evaluated; for 60%, lesions were located in the upper lumbar region and for 40%, they were located in the lower lumbar and sacral regions. The functionality, measured by the PEDI-CAT scale, showed a normal average according to age (mean 50), with 71% of children being community ambulators. Congenital orthopedic malformations were also unrelated to the injury levels, except for knee dislocation in relation to upper lumbar injury. At the functional level, we observed that for the majority, the levels of function of at least 2 vertebrae were below the anatomical level. There were no differences in functional motor skills, walking pattern, or congenital orthopedic malformation when compared with the anatomical level of injury in patients who underwent prenatal repair of MMC, except for congenital knee dislocation.

Perspectives on urological care in spina bifida patients.

Spina bifida (SB) is a neurogenetic disorder with a complex etiology that involves genetic and environmental factors. SB can occur in two major forms of open SB or SB aperta and closed SB or SB occulta. Myelomeningocele (MMC), the most common neural tube defects (NTDs), occurs in approximately 1 in 1,000 births. Considering non-genetic factors, diminished folate status is the best-known factor influencing NTD risk. The methylenetetrahydrofolate reductase (MTHFR) gene has been implicated as a risk factor for NTDs. The primary disorder in the pathogenesis of MMC is failed neural tube closure in the embryonic spinal region. The clinical manifestation of SB depends on clinical type and severity. SB can be detected in the second trimester using ultrasound which will reveal specific cranial signs. The management of MMC traditionally involves surgery within 48 h of birth. Prenatal repair of MMC is recommended for fetuses who meet maternal and fetal Management of Myelomeningocele Study (MOMS) specified criteria. Urological manifestations of SB include urinary incontinence, urolithiasis, sexual dysfunction, renal dysfunction, and urinary tract infection. Renal failure is among the most severe complications of SB. The most important role of the urologist is the management of neurogenic bladder. Medical management with clean intermittent catheterization and anticholinergic treatment is generally considered the gold standard of therapy. However, when this therapy fails surgical reconstruction become the only remaining option. This review will summarize the pathogenesis, risk factors, genetic contribution, diagnostic test, and management of SB. Lastly, the urologic outcomes and therapies are reviewed.

Intrauterine surgery: how far we have come in 30 years.

Intrauterine surgery: how far we have come in 30 years.

Postoperative Ultrasound as a Predictor of Newborn Function and Ambulation after Open Fetal Myelomeningocele Repair

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.

Progressive hydrocephalus despite early complete reversal of hindbrain herniation after prenatal open myelomeningocele repair.

Open prenatal myelomeningocele (MMC) repair is typically associated with reversal of in utero hindbrain herniation (HBH) and has been posited to be associated with a reduction in both postoperative prenatal and immediate postnatal hydrocephalus (HCP) risks. However, the long-term postnatal risk of HCP following HBH reversal in these cases has not been well defined. The authors describe the results of a long-term HCP surveillance in a cohort of patients who underwent prenatal MMC repair at their institution. A retrospective review of all prenatal MMC repair operations performed at the Mayo Clinic between 2012 and 2017 was conducted. Pertinent data regarding the clinical courses of these patients before and after MMC repair were summarized. Outcomes of interest were occurrences of HBH and HCP and the need for intervention. A total of 9 prenatal MMC repair cases were identified. There were 7 cases in which MRI clearly demonstrated prenatal HBH, and of these 86% (6/7) had evidence of HBH reversal after repair and prior to delivery. After a mean postnatal follow-up of 20 months, there were 3 cases of postnatal HCP requiring intervention. One case that failed to show complete HBH reversal after MMC repair required early ventriculoperitoneal shunting. The other 2 cases were of progressive, gradual-onset HCP despite complete prenatal HBH reversal, requiring endoscopic third ventriculostomy with choroid plexus cauterization at ages 5 and 7 months. Although prenatal MMC repair can achieve HBH reversal in a majority of well-selected cases, the prevention of postnatal HCP requiring intervention appears not to be predicated on this outcome alone. In fact, it appears that in a subset of cases in which HBH reversal is achieved, patients can experience a progressive, gradual-onset HCP within the 1st year of life. These findings support continued rigorous postnatal surveillance of all prenatal MMC repair patients, irrespective of postoperative HBH outcome.

Thirty-day medical and surgical readmission following prenatal versus postnatal myelomeningocele repair.

Hospital readmission is an important quality metric that has not been evaluated in prenatal versus postnatal myelomeningocele (MMC) repair. This study compares hospital readmission outcomes between these two groups as well as their etiologies. The medical records of patients who had undergone MMC repair in the period from 2011 to 2017 at a single academic medical center were retrospectively reviewed. Collected clinical data included surgery and defect details, neonatal intensive care unit (NICU) stay, and any readmissions or surgical procedures up to 1 year after surgery. Patient and defect characteristics, readmission outcomes at 30 and 60 days and 1 year after discharge from the NICU, and cerebrospinal fluid (CSF) diversion surgery rates were analyzed with the two-tailed t-test and/or k-sample test on the equality of medians. A total of 24 prenatal and 34 postnatal MMC repairs were completed during the study period. Prenatally repaired patients were born more prematurely (p < 0.001) and with lower birth weights (p < 0.001), although the NICU stay was similar between the two groups (p = 0.59). Fewer prenatally repaired patients were readmitted at 30 days (p = 0.005), 90 days (p = 0.004), and 1 year (p = 0.007) than the postnatal repair group. Hydrocephalus was the most common readmission etiology, and 29% of prenatal repair patients required CSF diversion at 1 year versus 81% of the postnatal repair group (p < 0.01). Prenatal patients who required CSF diversion had a higher body weight (p = 0.02) and an older age (p = 0.01) at the time of CSF diversion surgery than the postnatal group. Patients with prenatal MMC repair had fewer hospital readmissions at 30 days, 60 days, and 1 year than the postnatal repair group, despite similar NICU lengths of stay. The prenatal repair group had lower requirements for CSF diversion at 1 year and was older with greater body weights at the time of CSF diversion surgery, compared to those of the postnatal repair group. Future study of hospital quality metrics such as readmissions should be performed to better understand outcomes of these two procedures.