The impact of a biocellulose-based repair of fetal open spina bifida on the need to untether the cord: is it time to unify techniques for prenatal repair?

OBJECTIVE: To report the need for cord untethering after prenatal repair of open spina bifida using a unique biocellulose-based technique performed at a later gestational age. METHODS: An observational cohort study was conducted to determine the incidence of tethered cord syndrome. Between May 2013 and May 2022, we performed 172 procedures using the percutaneous fetoscopic approach in fetuses at 26-28 weeks of gestation. After placode dissection, a biocellulose patch was placed to cover the placode, a myofascial flap (when possible) was dissected, and the skin was closed. Owing to death or loss to follow-up, 23 cases were excluded. Cord tethering syndrome was defined as symptoms of medullary stretching, and the infants were evaluated and operated on by local neurosurgeons after an magnetic resonance imaging examination. Infants over 30-month had ambulation and neurodevelopment evaluations (PEDI scale). RESULTS: Among 172 cases operated at a median gestational age of 26.7 weeks and delivered at 33.2 weeks, 149 cases were available for postnatal follow-up, and cord untethering was needed in 4.4% of cases (6/136; excluding 13 cases younger than 12 months). Cerebrospinal fluid diversion and bladder catheterization were needed in 38% and 36% of cases, respectively. Of the 78 cases evaluated at 30 months, 49% were ambulating independently, and 94% had normal social function. CONCLUSION: The biocellulose-based technique was associated with a low rate of cord tethering, wich may be attributed to the lack of the duramater suture during prenatal repair, the formation of a neoduramater and/or later gestational age of surgery.

Length of hysterotomy for fetal spina bifida repair is associated with prematurity risk.

OBJECTIVE: To investigate whether prenatal repair of spina bifida aperta through mini-hysterotomy results in less prematurity, as compared to standard hysterotomy, when adjusting for known prematurity risks. METHODS: We performed a bi-centric, propensity score matched, controlled study, that is, adjusting for factors earlier reported to result in premature delivery or membrane rupture, in consecutive women having prenatal repair either through stapled hysterotomy or sutured mini-hysterotomy (≤3.5 cm). Matches were pairwise compared and cox-regression analysis was performed to define the hazard ratio of delivery <37 weeks. RESULTS: Of 346 meeting the MOMS-criteria, 78 comparable pairs were available for matched-controlled analysis. Mini-hysterotomy patients were younger and had a higher BMI. Mini-hysterotomy was associated with a 1.67-lower risk of delivery <37 weeks (hazard ratio: 0.60; 95% CI: 0.42-0.85; p = 0.004) and 1.72 for delivery <34 + 6 weeks (hazard ratio: 0.58; 95% CI: 0.34-0.97; p = 0.037). The rate of intact uterine scar at birth (mini-hysterotomy: 98.7% vs. hysterotomy: 90.4%; p = 0.070), the rate of reversal of hindbrain herniation within 1 week after surgery (88.9% vs. 97.4%; p = 0.180) and the rate of cerebrospinal fluid leakage (0% vs. 2.7%; p = 0.50) were comparable. CONCLUSION: Prenatal spina bidifa repair through mini-hysterotomy was associated with a later gestational age at delivery and a comparable intact uterus rate without apparent compromise in neuroprotection.

Fetal Spina Bifida Repair in Obese Mothers: Is Maternal and Fetal Safety Compromised?

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.

Effect of cervical and lumbosacral spina bifida cystica on volumes of intracranial structures in children.

PURPOSE: Spina bifida is a major disorder that occurs when the membranes of the spinal cord and medulla fail to close during the embryonic period and affects the individual for the rest of life. Some physical, mental, and social difficulties can be observed in the lives of children with spina bifida after surgery. The aim of this study is to determine what kind of volumetric changes occur in the brain when spina bifida occurs in different regions of the cord. METHODS: The volume of intracranial structures of 14 children aged 1 to 9 years (7 cervical, 7 lumbosacral) with different levels of spina bifida compared with vol2Brain. RESULTS: Spina bifida occurring in the cervical region was found to cause a greater volumetric reduction in subcortical structures, cortex and gyrus than spina bifida occurring in the lumbosacral region. CONCLUSION: We believe that our study will help clinicians involved in the management of this disorder.

Perforation of cavum septi pellucidi in open spina bifida and need for hydrocephalus treatment by 1 year of age.

OBJECTIVE: In-utero repair of an open neural tube defect (ONTD) reduces the risk of developing severe hydrocephalus postnatally. Perforation of the cavum septi pellucidi (CSP) may reflect increased intraventricular pressure in the fetal brain. We sought to evaluate the association of perforated CSP visualized on fetal imaging before and/or after in-utero ONTD repair with the eventual need for hydrocephalus treatment by 1 year of age. METHODS: This was a retrospective cohort study of consecutive patients who underwent laparotomy-assisted fetoscopic ONTD repair between 2014 and 2021 at a single center. Eligibility criteria for surgery were based on those of the Management of Myelomeningocele Study (MOMS), although a maternal prepregnancy body mass index of up to 40 kg/m2 was allowed. Fetal brain imaging was performed with ultrasound and magnetic resonance imaging (MRI) at referral and 6 weeks postoperatively. Stored ultrasound and MRI scans were reviewed retrospectively to assess CSP integrity. Medical records were reviewed to determine whether hydrocephalus treatment was needed within 1 year of age. Parametric and non-parametric tests were used as appropriate to compare outcomes between cases with perforated CSP and those with intact CSP as determined on ultrasound at referral. Logistic regression analysis was performed to assess the predictive performance of various imaging markers for the need for hydrocephalus treatment. RESULTS: A total of 110 patients were included. Perforated CSP was identified in 20.6% and 22.6% of cases on preoperative ultrasound and MRI, respectively, and in 26.6% and 24.2% on postoperative ultrasound and MRI, respectively. Ventricular size increased between referral and after surgery (median, 11.00 (range, 5.89-21.45) mm vs 16.00 (range, 7.00-43.5) mm; P < 0.01), as did the proportion of cases with severe ventriculomegaly (ventricular width ≥ 15 mm) (12.7% vs 57.8%; P < 0.01). Complete CSP evaluation was achieved on preoperative ultrasound in 107 cases, of which 22 had a perforated CSP and 85 had an intact CSP. The perforated-CSP group presented with larger ventricles (mean, 14.32 ± 3.45 mm vs 10.37 ± 2.37 mm; P < 0.01) and a higher rate of severe ventriculomegaly (40.9% vs 5.9%; P < 0.01) compared to those with an intact CSP. The same trends were observed at 6 weeks postoperatively for mean ventricular size (median, 21.0 (range, 13.0-43.5) mm vs 14.3 (range, 7.0-29.0) mm; P < 0.01) and severe ventriculomegaly (95.0% vs 46.8%; P < 0.01). Cases with a perforated CSP at referral had a lower rate of hindbrain herniation (HBH) reversal postoperatively (65.0% vs 88.6%; P = 0.01) and were more likely to require treatment for hydrocephalus (89.5% vs 22.7%; P < 0.01). The strongest predictor of the need for hydrocephalus treatment within 1 year of age was lack of HBH reversal on MRI (odds ratio (OR), 36.20 (95% CI, 5.96-219.12); P < 0.01) followed by perforated CSP on ultrasound at referral (OR, 23.40 (95% CI, 5.42-100.98); P < 0.01) and by perforated CSP at 6-week postoperative ultrasound (OR, 19.48 (95% CI, 5.68-66.68); P < 0.01). CONCLUSIONS: The detection of a perforated CSP in fetuses with ONTD can reliably identify those cases at highest risk for needing hydrocephalus treatment by 1 year of age. Evaluation of this brain structure can improve counseling of families considering fetal surgery for ONTD, in order to set appropriate expectations about postnatal outcome. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Revisiting MOMS criteria for prenatal repair of spina bifida: upper gestational-age limit should be raised and assessment of prenatal motor function rather than anatomical level improves prediction of postnatal function.

OBJECTIVES: To determine if the lower-extremity neurological motor function level in fetuses with open spina bifida deteriorates within the 4-week interval between a first prenatal motor assessment at around 22 weeks of gestation and a second evaluation, prior to 'late' prenatal surgery, defined as surgery at 26-28 weeks and, in certain situations, up to 30 weeks, and to assess the association between prenatal presurgical motor-function level, anatomical level of the lesion and postnatal motor-function level. METHODS: This was a two-center cohort study of 94 singleton fetuses with open spina bifida which underwent percutaneous repair using the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique between December 2016 and January 2022. All women underwent two prenatal systematic ultrasound evaluations, approximately 4 weeks apart, with the second one being performed less than 1 week before surgery, and one postnatal evaluation via physical examination within 2 months of birth. Motor-function classification was from spinal level T12 to S1, according to key muscle function. Each leg was analyzed separately; in case of discrepancy between the two legs, the worst motor-function level was considered for analysis. Motor-function-level evaluations were compared with each other and with the anatomical level as observed on ultrasound. Independent predictors of a postnatal reduction in motor-function level were assessed using a logistic regression model. RESULTS: Prenatal motor-function level was assessed at a median gestational age of 22.5 (interquartile range (IQR), 20.7-24.3) and 26.7 (IQR, 25.4-27.3) weeks, with a median interval of 4.0 (IQR, 2.4-6.0) weeks. The median gestational age at surgery was 27.0 (IQR, 25.9-27.6) weeks and the postnatal examination was at median age of 0.8 (IQR, 0.3-5.4) months. There was no significant difference in motor-function level between the two prenatal evaluations (P = 0.861). We therefore decided to use the second prenatal evaluation for comparison with postnatal motor function and anatomical level. Overall, prenatal and postnatal motor function evaluations were significantly different from the anatomical level (preoperative assessment, P = 0.0015; postnatal assessment, P = 0.0333). Comparing prenatal with postnatal motor-function level, we found that 87.2% of babies had similar or improved motor function compared with that prior to prenatal surgery. On logistic regression analysis, lower anatomical level of defect and greater difference between anatomical level and prenatal motor-function level were identified as independent predictors of postnatal motor function (odds ratio, 0.237 (95% CI, 0.095-0.588) (P = 0.002) and 3.44 (95% CI, 1.738-6.813) (P < 0.001), respectively). CONCLUSIONS: During a 4-week interval between first ultrasound evaluation and late fetal surgical repair of open spina bifida, motor function does not change significantly, suggesting that late repair, ≥ 26 weeks, does not impact negatively on motor-function outcome. Compared with the anatomical level of the lesion, preoperative neurological motor-function assessment via ultrasound is more predictive of postnatal motor function, and should be included in preoperative counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Longitudinal MRI in the context of in utero surgery for open spina bifida: A descriptive study.

INTRODUCTION: Fetal surgery for open spina bifida (OSB) requires comprehensive preoperative assessment using imaging for appropriate patient selection and to evaluate postoperative efficacy and complications. We explored patient access and conduct of fetal magnetic resonance imaging (MRI) for prenatal assessment of OSB patients eligible for fetal surgery. We compared imaging acquisition and reporting to the International Society of Ultrasound in Obstetrics and Gynecology MRI performance guidelines. MATERIAL AND METHODS: We surveyed access to fetal MRI for OSB in referring fetal medicine units (FMUs) in the UK and Ireland, and two NHS England specialist commissioned fetal surgery centers (FSCs) at University College London Hospital, and University Hospitals KU Leuven Belgium. To study MRI acquisition protocols, we retrospectively analyzed fetal MRI images before and after fetal surgery for OSB. RESULTS: MRI for fetal OSB was accessible with appropriate specialists available to supervise, perform, and report scans. The average time to arrange a fetal MRI appointment from request was 4 ± 3 days (range, 0-10), the average scan time available was 37 ± 16 min (range, 20-80 min), with 15 ± 11 min (range, 0-30 min) extra time to repeat sequences as required. Specific MRI acquisition protocols, and MRI reporting templates were available in only 32% and 18% of units, respectively. Satisfactory T2-weighted (T2W) brain imaging acquired in three orthogonal planes was achieved preoperatively in all centers, and 6 weeks postoperatively in 96% of FSCs and 78% of referring FMUs. However, for T2W spine image acquisition referring FMUs were less able to provide three orthogonal planes presurgery (98% FSC vs. 50% FMU, p < 0.001), and 6 weeks post-surgery (100% FSC vs. 48% FMU, p < 0.001). Other standard imaging recommendations such as T1-weighted (T1W), gradient echo (GE) or echoplanar fetal brain and spine imaging in one or two orthogonal planes were more likely available in FSCs compared to FMUs pre- and post-surgery (p < 0.001). CONCLUSIONS: There was timely access to supervised MRI for OSB fetal surgery assessment. However, the provision of images of the fetal brain and spine in sufficient orthogonal planes, which are required for determining eligibility and to determine the reversal of hindbrain herniation after fetal surgery, were less frequently acquired. Our evidence suggests the need for specific guidance in relation to fetal MRI for OSB. We propose an example guidance for MRI acquisition and reporting.

Simple prenatal imaging predictors for postnatal cerebrospinal fluid diversion surgery in fetuses undergoing in utero surgery for spina bifida.

OBJECTIVES: To determine simple prenatal imaging parameters that can easily be acquired to predict the need for postnatal CSF diversion (PCD) surgery in fetuses undergoing open fetal surgery for open spina bifida (OSB). METHODS: All fetuses with OSB that underwent open fetal surgery between June 2017 and June 2021 with available follow-up outcomes were included. Imaging parameters including clivus-supraocciput angle (CSA) on magnetic resonance imaging, transcerebellar diameter (TCD) and lateral ventricle size (Vp) on ultrasound (US), were collected pre- and postoperatively. The requirement for PCD surgery was determined at 1 year of age. The predictive strength of each parameter was determined by Receiver Operating Characteristic curve analysis. RESULTS: Among 36 babies eligible for the analyses, 41.7% required PCD by one year of age. Pre-operative Vp (AUC 0.71; 95% confidence interval [CI] 0.54-0.88; p = 0.03), TCD (AUC 0.72; 95% CI 0.55-0.89; p = 0.02) and CSA (AUC 0.72; 95% CI 0.51-0.93; p = 0.04) were fair predictors for PCD surgery. After fetal surgery, TCD (AUC 0.93; 95% CI 0.83-1.00; p < 0.0001) and CSA (AUC 0.94; 95% CI 0.83-1.00; p = 0.0005) were outstanding predictors of PCD, whereas post-operative Vp was a fair predictor (AUC 0.71, 95% CI 0.54-0.88, p = 0.03). CONCLUSION: Post-operative CSA and TCD were outstanding predictors for the need for PCD surgery.

Duration of fetoscopic spina bifida repair does not affect the central nervous system in fetal lambs.

BACKGROUND: Prenatal spina bifida aperta repair improves neurologic outcomes yet comes with a significant risk of prematurity and uterine scar-related complications. To reduce such complications, different fetoscopic techniques, for example, with varying numbers of ports, are being explored. This has an effect on the duration of the procedure, potentially affecting central nervous system development. Both the condition and anesthesia can affect the central nervous system, particularly the hippocampus, a region crucial for prospective and episodic memory. Previous animal studies have shown the potential influence of anesthesia, premature delivery, and maternal surgery during pregnancy on this area. OBJECTIVE: This study aimed to compare the effects of 2- vs 3-port fetoscopic spina bifida aperta repair in the fetal lamb model using neuron count of the hippocampus as the primary outcome. STUDY DESIGN: Based on the hippocampal neuron count from previous lamb experiments, we calculated that we required 5 animals per group to achieve a statistical power of ≥ 80%. A spina bifida aperta defect was developed in fetal lambs at 75 days of gestation (term: 145 days). At 100 days, fetuses underwent either a 2-port or 3-port fetoscopic repair. At 143 days, all surviving fetuses were delivered by cesarean delivery, anesthetized, and transcardially perfused with a mixture of formaldehyde and gadolinium. Next, they underwent neonatal brain and spine magnetic resonance imaging after which these organs were harvested for histology. Hippocampus, frontal cortex, caudate nucleus, and cerebellum samples were immunostained to identify neurons, astrocytes, microglia, and markers associated with cell proliferation, myelination, and synapses. The degree of hindbrain herniation and the ventricular diameter were measured on magnetic resonance images and volumes of relevant brain and medulla areas were segmented. RESULTS: Both treatment groups included 5 fetuses and 9 unoperated littermates served as normal controls. The durations for both skin-to-skin (341±31 vs 287±40 minutes; P=.04) and fetal surgery (183±30 vs 128±22; P=.01) were longer for the 2-port approach than for the 3-port approach. There was no significant difference in neuron density in the hippocampus, frontal cortex, and cerebellum. In the caudate nucleus, the neuron count was higher in the 2-port group (965±156 vs 767±92 neurons/mm2; P=.04). There were neither differences in proliferation, astrogliosis, synaptophysin, or myelin. The tip of the cerebellar vermis was closer to the foramen magnum in animals undergoing the 2-port approach than in animals undergoing the 3-port approach (-0.72±0.67 vs -2.47±0.91 mm; P=.009). There was no significant difference in the ratio of the hippocampus, caudate nucleus, or cerebellar volume to body weight. For the spine, no difference was noted in spine volume-to-body weight ratio for the lower (L1-L2), middle (L3-L4), and higher (L5-L6) levels. Compared with controls, in repaired animals, the cerebellar vermis tip laid closer to the foramen magnum, parietal ventricles were enlarged, and medulla volumes were reduced. CONCLUSION: In the experimental spina bifida fetal lamb model, a 2-port repair took 40% longer than a 3-port repair. However, there was no indication of any relevant morphologic differences in the fetal brain.

Prenatal Spina Bifida Repair: Defendable Trespassing of MOMS Criteria Results in Commendable Personalized Medicine.

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.

Assessment of longitudinal brain development using super-resolution magnetic resonance imaging following fetal surgery for open spina bifida.

OBJECTIVES: Prenatal surgery is offered for selected fetuses with open spina bifida (OSB) to improve long-term outcome. We studied the effect of fetal OSB surgery on brain development using advanced magnetic resonance imaging (MRI) techniques to quantify the volume, surface area and shape of cerebral structures and to analyze surface curvature by means of parameters that correspond to gyrification. METHODS: We compared MRI data from 29 fetuses with OSB before fetal surgery (mean gestational age (GA), 23 + 3 weeks) and at 1 and 6 weeks after surgery, with that of 36 GA-matched control fetuses (GA range, 21 + 2 to 36 + 2 weeks). Automated super-resolution reconstruction provided three-dimensional isotropic volumetric brain images. Unmyelinated white matter, cerebellum and ventricles were segmented automatically and refined manually, after which volume, surface area and shape parameter (volume/surface area) were quantified. Mathematical markers (shape index (SI) and curvedness) were used to measure gyrification. Parameters were assessed according to lesion type (myelomeningocele vs myeloschisis (MS)), postoperative persistence of hindbrain herniation (HH) and the presence of supratentorial anomalies, namely partial agenesis of the corpus callosum (pACC) and heterotopia (HT). RESULTS: Growth in ventricular volume per week and change in shape parameter per week were higher at 6 weeks after surgery in fetuses with OSB compared with controls (median, 2500.94 (interquartile range (IQR), 1689.70-3580.80) mm3 /week vs 708.21 (IQR, 474.50-925.00) mm3 /week; P < 0.001 and 0.075 (IQR, 0.047-0.112) mm/week vs 0.022 (IQR, 0.009-0.042) mm/week; P = 0.046, respectively). Ventricular volume growth increased 6 weeks after surgery in cases with pACC (P < 0.001) and those with persistent HH (P = 0.002). During that time period, the change in unmyelinated white-matter shape parameter per week was decreased in OSB fetuses compared with controls (0.056 (IQR, 0.044-0.092) mm/week vs 0.159 (IQR, 0.100-0.247) mm/week; P = 0.002), particularly in cases with persistent HH (P = 0.011), MS (P = 0.015), HT (P = 0.022), HT with corpus callosum anomaly (P = 0.017) and persistent HH with corpus callosum anomaly (P = 0.007). At 6 weeks postoperatively, despite OSB fetuses having a lower rate of change in curvedness compared with controls (0.061 (IQR, 0.040-0.093) mm-1 /week vs 0.094 (IQR, 0.070-0.146) mm-1 /week; P < 0.001), reversing the trend seen at 1 week after surgery (0.144 (IQR, 0.099-0.236) mm-1 /week vs 0.072 (IQR, 0.059-0.081) mm-1 /week; P < 0.001), gyrification, as determined using SI, appeared to be increased in OSB fetuses overall compared with controls. This observation was more prominent in fetuses with pACC and those with severe ventriculomegaly (P-value range, < 0.001 to 0.006). CONCLUSIONS: Following fetal OSB repair, volume, shape and curvedness of ventricles and unmyelinated white matter differed significantly compared with those of normal fetuses. Morphological brain changes after fetal surgery were not limited to effects on the circulation of cerebrospinal fluid. These observations may have implications for postnatal neurocognitive outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Biocellulose patch technique for fetoscopic repair of open spina bifida in twin pregnancy.

OBJECTIVES: Twin pregnancy is currently an exclusion criterion for prenatal repair of open spina bifida (OSB). The main objective of this study was to report on our experience of treating twin pregnancies with OSB using the skin-over-biocellulose for antenatal fetoscopic repair (SAFER) technique. We also discuss reconsideration of the current exclusion criteria for fetal OSB repair. METHODS: Eight fetuses with OSB from seven twin pregnancies underwent successful prenatal repair. Six pregnancies were dichorionic diamniotic with only one twin affected, and one was monochorionic diamniotic with both twins affected. Percutaneous fetoscopy was performed under CO2 insufflation of the sac of the affected twin. Neurosurgical repair was performed using a biocellulose patch to protect the placode, with the skin sutured to hold the patch in place, with or without a myofascial flap. Neurodevelopment was assessed using the pediatric evaluation of disability inventory scale in babies older than 6 months of adjusted age, whereas the Alberta scale was used for babies younger than 6 months of adjusted age. RESULTS: All 14 fetuses were liveborn and none required additional repair. Gestational age at surgery ranged from 27.3 to 31.1 weeks, and gestational age at birth ranged from 31.6 to 36.0 weeks. Four out of eight affected twins developed sepsis, but had a good recovery. No sequela of prematurity was found in any of the unaffected twins. Short-term neurodevelopment was normal in all evaluated unaffected twins (5/5) and in all but one affected twins (7/8). In the affected group, only one baby required ventriculoperitoneal shunt placement. CONCLUSIONS: Prematurity is frequent after fetal surgery, and the risk is increased in twin pregnancy. Nevertheless, prenatal surgery using the SAFER technique is feasible, with low risk to both twins and their mother when performed by a highly experienced team. Long-term cognitive assessment of the unaffected twin is needed. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal predictors of need for cerebrospinal fluid diversion in infants following prenatal repair of open spina bifida; systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate prenatal predictors of the need for cerebrospinal fluid diversion in infants following prenatal repair of open spina bifida. DATA SOURCES: A systematic search was performed to identify relevant studies published from inception until June 2022 in the English language using the databases PubMed, Scopus, and Web of Science. STUDY ELIGIBILITY CRITERIA: We included retrospective and prospective cohort studies and randomized controlled trials reporting on prenatal repair of open spina bifida. METHODS: The random-effects model was used to pool the mean differences or odds ratios and the corresponding 95% confidence intervals. Heterogeneity was assessed using the I2 value. RESULTS: A total of 9 studies including 948 pregnancies undergoing prenatal repair of open spina bifida were included in the final analysis. Prenatal factors that were significantly associated with the need for postnatal cerebrospinal fluid diversion were gestational age at surgery ≥25 weeks (odds ratio, 4.2; 95% confidence interval, 1.8-9.9; I2=54%; P=.001), myeloschisis (odds ratio, 2.2; 95% confidence interval, 1.1-4.1; I2=0.0%; P=.02), preoperative lateral ventricle width ≥15 mm (odds ratio, 4.5; 95% confidence interval, 2.9-6.9; I2=0.0%; P<.0001), predelivery lateral ventricle width (mm) (mean difference, 8.3; 95% confidence interval, 6.4-10.2; I2=0.0%; P<.0001), and preoperative lesion level at T12-L2 (odds ratio, 2.5; 95% confidence interval, 1.03-6.3; I2=68%; P=.04). Factors that significantly reduced the need for postnatal shunt placement were gestational age at surgery <25 weeks (odds ratio, 0.3; 95% confidence interval, 0.15-0.6; I2=67%; P=.001) and preoperative lateral ventricle width <15 mm (odds ratio, 0.3; 95% confidence interval, 0.2-0.4; I2=0.0%; P<.0001). CONCLUSION: This study demonstrated that among fetuses that underwent surgical repair of open spina bifida, having gestational age at surgery of ≥25 weeks, preoperative lateral ventricle width of ≥15 mm, myeloschisis lesion type, and preoperative lesion level above L3 was predictive of the need for cerebrospinal fluid diversion during the first year of life.

Patient empowerment improves follow-up data collection after fetal surgery for spina bifida: institutional audit.

OBJECTIVES: To define and grade fetal and maternal adverse events following fetal surgery for spina bifida and to report on the impact of engaging patients in collecting follow-up data. METHODS: This prospective single-center audit included 100 consecutive patients undergoing fetal surgery for spina bifida between January 2012 and December 2021. In our setting, patients return to their referring unit for further pregnancy care and delivery. On discharge, referring hospitals were requested to return outcome data. For this audit, we prompted patients and referring hospitals to provide data in cases of missing outcomes. Outcomes were categorized as missing, returned spontaneously or returned following additional request, by the patient and/or referring center. Postoperative maternal and fetal complications until delivery were defined and graded according to Maternal and Fetal Adverse Event Terminology (MFAET) and the Clavien-Dindo classification. RESULTS: There were no maternal deaths, but severe maternal complications occurred in seven women (anemia in pregnancy, postpartum hemorrhage, pulmonary edema, lung atelectasis, urinary tract obstruction and placental abruption). No cases of uterine rupture were reported. Perinatal death occurred in 3% of fetuses and other severe fetal complications in 15% (perioperative fetal bradycardia/cardiac dysfunction, fistula-related oligohydramnios, chorioamnionitis and preterm prelabor rupture of membranes (PPROM) before 32 weeks). PPROM occurred in 42% of patients and, overall, delivery took place at a median gestational age of 35.3 weeks (interquartile range, 34.0-36.6 weeks). Information provided following additional request, from both centers and patients but mainly from the latter, reduced missing data by 21% for gestational age at delivery, 56% for uterine-scar status at birth and 67% for shunt insertion at 12 months. Compared with the generic Clavien-Dindo classification, the MFAET system ranked complications in a more clinically relevant way. CONCLUSIONS: The nature and rate of severe complications following fetal surgery for spina bifida were similar to those reported in other large series. Spontaneous return of outcome data by referring centers was low, yet patient empowerment improved data collection. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Global Policy and Practice for Intrauterine Fetal Resuscitation During Fetal Surgery for Open Spina Bifida Repair.

Importance: Globally accepted recommendations suggest that a woman should be between 19 weeks and 25 weeks plus 6 days of pregnancy to be considered eligible for fetal closure of open spina bifida. A fetus requiring emergency delivery during surgery is therefore potentially considered viable and thus eligible for resuscitation. There is little evidence, however, to support how this scenario is addressed in clinical practice. Objective: To explore current policy and practice for fetal resuscitation during fetal surgery for open spina bifida in centers undertaking fetal surgery. Design, Setting, and Participants: An online survey was designed to identify current policies and practices in place to support fetal surgery for open spina bifida, exploring experiences and management of emergency fetal delivery and fetal death during surgery. The survey was emailed to 47 fetal surgery centers in 11 countries where fetal spina bifida repair is currently performed. These centers were identified through the literature, the International Society for Prenatal Diagnosis center repository, and an internet search. Centers were contacted between January 15 and May 31, 2021. Individuals volunteered participation through choosing to complete the survey. Main Outcomes and Measures: The survey comprised 33 questions of mixed multiple choice, option selection, and open-ended formats. Questions explored policy and practice supporting fetal and neonatal resuscitation during fetal surgery for open spina bifida. Results: Responses were obtained from 28 of 47 centers (60%) in 11 countries. Twenty cases of fetal resuscitation during fetal surgery during the last 5 years were reported across 10 centers. Four cases of emergency delivery during fetal surgery after maternal and/or fetal complications during the last 5 years were reported across 3 centers. Fewer than half the 28 centers (n = 12 [43%]) had policies in place to support practice in the event of either imminent fetal death (during or after fetal surgery) or the need for emergency fetal delivery during fetal surgery. Twenty of 24 centers (83%) reported preoperative parental counseling on the potential need for fetal resuscitation prior to fetal surgery. The gestational age at which centers would attempt neonatal resuscitation after emergency delivery varied from 22 weeks and 0 days to more than 28 weeks. Conclusions: In this global survey study of 28 fetal surgical centers, there was no standard practice about how fetal resuscitation or subsequent neonatal resuscitation was managed during open spina bifida repair. Further collaboration between professionals and parents is required to ensure sharing of information to support knowledge development in this area.

Expert ultrasonographic evaluation in fetuses with spina bifida: An essential prerequisite to select candidate to fetal surgery.

Suggested management flowchart in presence of a prenatal diagnosis of open spina bifida.

Advances in Fetal Surgical Repair of Open Spina Bifida.

Spina bifida remains a common congenital anomaly of the central nervous system despite national fortification of foods with folic acid, with a prevalence of 2-4 per 10,000 live births. Prenatal screening for the early detection of this condition provides patients with the opportunity to consider various management options during pregnancy. Prenatal repair of open spina bifida, traditionally performed by the open maternal-fetal surgical approach through hysterotomy, has been shown to improve outcomes for the child, including decreased need for cerebrospinal fluid diversion surgery and improved lower neuromotor function. However, the open maternal-fetal surgical approach is associated with relatively increased risk for the patient and the overall pregnancy, as well as future pregnancies. Recent advances in minimally invasive prenatal repair of open spina bifida through fetoscopy have shown similar benefits for the child but relatively improved outcomes for the pregnant patient and future childbearing.

Presurgery motor level assessment for prediction of motor level at birth in fetuses undergoing prenatal repair of open spina bifida: time to abandon anatomical level in counseling.

OBJECTIVES: First, to investigate the correlation between prenatal presurgery anatomical and motor levels of the lesion with motor level at birth in cases undergoing prenatal repair of open spina bifida and, second, to identify factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. METHODS: This was an observational study of singleton pregnancies undergoing prenatal repair of open spina bifida, conducted between March 2011 and May 2022. All fetuses underwent an ultrasound assessment at 20-24 weeks of gestation to determine the motor and anatomical levels of the lesion before surgery. The anatomical level of the lesion was defined as the highest open posterior vertebral arch. The motor level was determined by systematic observation of the lower limb movements and was defined as the most distal active muscle present. Prenatal repair was performed at 23-26 weeks. At birth, motor level was assessed by a rehabilitation specialist by physical examination. Cases of intrauterine death or termination of pregnancy and those delivered at other sites were excluded from the neonatal assessment. The agreement between presurgery motor level and motor level at birth, and between presurgery anatomical level and motor level at birth, was assessed using the weighted kappa index (wκ). Logistic regression analysis was used to assess factors leading to a loss of two or more motor levels between the presurgery and postnatal assessments. RESULTS: Presurgery motor and anatomical levels were assessed in 61 fetuses at a median gestational age of 22.7 (interquartile range (IQR), 21.6-24.4) weeks. Prenatal repair was performed at a median gestational age of 24.6 (IQR, 23.7-25.7) weeks. Motor level at birth was assessed in 52 neonates after exclusion of nine fetuses due to loss to follow-up or fetal loss. There was moderate agreement between presurgery motor level and motor level at birth (wκ = 0.42; 95% CI, 0.21-0.63), with a median difference of 0 (IQR, -2 to 9) levels. Factors leading to a loss of two or more motor levels between the presurgery ultrasound assessment and postnatal examination were higher presurgery anatomical level (odds ratio (OR), 0.59 (95% CI, 0.35-0.98); P = 0.04) and larger difference between the anatomical and motor levels before surgery (OR, 1.85 (95% CI, 1.12-3.06); P = 0.017). None of the other ultrasound, surgery-related or neonatal variables assessed was associated significantly with a loss of two or more motor levels. There was slight agreement between the presurgery anatomical level of the lesion and motor level at birth (wκ = 0.07; 95% CI, -0.02 to 0.15). CONCLUSIONS: There is moderate agreement between fetal motor level of the lesion before prenatal repair of open spina bifida and motor level at birth, as opposed to only slight agreement between presurgery anatomical level and motor level at birth. A loss of two or more motor levels between the presurgery and postnatal assessments is associated with a higher presurgery anatomical level and with a larger difference between the presurgery anatomical and motor levels. Consequently, motor level, rather than the anatomical level, should be used for prenatal counseling. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Local host response of commercially available dural patches for fetal repair of spina bifida aperta in rabbit model.

OBJECTIVE: Fetal surgery for spina bifida aperta (SBA) by open hysterotomy typically repairs anatomical native tissue in layers. Increasingly, fetoscopic repair is performed using a dural patch followed by skin closure. We studied the host response to selected commercially available patches currently being used in a fetal rabbit model for spina bifida repair. METHODS: SBA was surgically induced at 23-24 days of gestation (term = 31 days). Fetal rabbits were assigned to unrepaired (SBA group), or immediate repair with Duragen™ or Durepair™. Non-operated littermates served as normal controls. At term, spinal cords underwent immunohistochemical staining including Nissl and glial fibrillary acidic protein. We hypothesized that spinal cord coverage with a dural patch and skin closure would preserve motor neuron density within the non-inferiority limit of 201.65 cells/mm2 and reduce inflammation compared to unrepaired SBA fetuses. RESULTS: Motor neuron density assessed by Nissl staining was conserved both by Duragen (n = 6, 89.5; 95% CI -158.3 to -20.6) and Durepair (n = 6, 37.0; 95% CI -132.6 to -58.5), whereas density of GFAP-positive cells to quantify inflammation was lower than in unrepaired SBA-fetuses (SBA 2366.0 ± 669.7 cells/mm2 vs. Duragen 1274.0 ± 157.2 cells/mm2 ; p = 0.0002, Durepair 1069.0 ± 270.7 cells/mm2 ; p < 0.0001). CONCLUSIONS: Covering the rabbit spinal cord with either Duragen or Durepair followed by skin closure preserves motor neuron density and reduces the inflammatory response.