Proposal for standardized prenatal assessment of fetal open dysraphisms by the European reference network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies (ITHACA) and eUROGEN.

Open dysraphisms, that is, myelomeningocele and myeloschisis, are rare diseases associated with a risk of severe disability, including lower limb motor and sensory deficiency, sphincter deficiency, and potential intellectual deficiency. Open dysraphism is diagnosed in Europe in 93.5% of cases. In case of suspicion of fetal open dysraphism, a detailed fetal morphologic assessment is required to confirm the diagnosis and exclude associated structural anomalies, as well as genetic assessment. In case of isolated fetal open dysraphism, assessment of prognosis is based on fetal imaging including the level of the lesion, the presence or not of a sac, the presence and nature of intra cranial anomalies, and the anatomical and functional evaluation of the lower extremities. Based on these biomarkers, a personalized prognosis as well as comprehensive information about prenatal management alternatives will allow parents to decide on further management options. Standardization of prenatal assessment is essential to compare outcomes with benchmark data and make assessment of surgical innovation possible. Herein, we propose a protocol for the standardized ultrasound assessment of fetuses with isolated open dysraphism.

Incidence and patterns of abnormal corpus callosum in fetuses with isolated spina bifida aperta.

OBJECTIVE: To determine the incidence and characterise corpus callosum (CC) abnormalities in fetuses with spina bifida aperta (SBA) between 18 and 26 weeks of gestation. METHODS: This was a retrospective study on fetuses with isolated SBA and who were assessed for fetal surgery. Digitally stored ultrasound images of the brain were reviewed for the presence/absence of the CC, and the length and diameter of its constituent parts (rostrum, genu, body and splenium). We used regression analysis to determine the relationship between CC abnormalities and gestational age, head circumference, ventricle size, lesion level and lesion type. RESULTS: Nearly three-quarters of fetuses with isolated SBA had an abnormal CC (71.7%, 76/106). Partial agenesis was most common in the splenium (18.9%, 20/106) and the rostrum (13.2%, 14/106). The most common abnormal pattern was of a short CC with normal diameter throughout. Of note, 20.8% (22/106) had a hypoplastic genu and 28.3% (30/106) had a thick body part. Larger lateral ventricle size was associated with partial agenesis of the CC (odds ratio [OR]: 0.14, p < 0.001) and inversely associated with a shorter CC (OR: 2.60, p < 0.01). CONCLUSION: An abnormal CC is common in fetuses with isolated SBA who are referred for fetal surgery.

Fetal Surgery for Open Spina Bifida in Canada: Initial Results.

OBJECTIVE: Fetal myelomeningocele closure results in better infant outcomes than postnatal closure at the cost of potential prematurity and maternal morbidity. Our aim is to describe the setup of a fetal myelomeningocele closure program in Canada and document its outcomes. METHODS: We conducted a retrospective review of all open fetal myelomeningocele closure surgeries performed at the Ontario Fetal Centre in its first 3 years of operation (2017-2020). Maternal and fetal baseline characteristics, surgical details, pregnancy outcomes, and infant follow-up until 1 year of age were recorded. RESULTS: Twenty-seven women underwent fetal myelomeningocele closure surgery, 10 of whom (37%) resided outside of Ontario. Mean gestational age at surgery was 25.0 ± 0.7 weeks. All surgeries were technically uncomplicated and no fetal deaths occurred. There was a significant negative correlation between increasing experience and skin-to-skin surgical time (R²â€¯= 0.36; P = 0.001). Of the 26 patients who have delivered, 4 (15.4%) experienced preterm prelabour rupture of membranes. Mean gestational age at delivery was 34.9±3.0 weeks. All but 1 patient delivered by cesarean. Maternal complications occurred in 9 women (34.6%). There were no maternal deaths, but 3 (11.5%) infant deaths. Of the 14 surviving infants who have reached at least 1 year of age, 5 (35.7%) underwent ventriculo-peritoneal shunting. Of the 9 infants who have not yet reached 1 year of age, 3 (33.3%) underwent endoscopic third ventriculostomy and none underwent shunting. CONCLUSION: Fetal open spina bifida closure can be performed in Canada, with results similar to those reported by other international expert centres. Long-term follow-up is ongoing.

Spina bifida screening in the first trimester using ultrasound biparietal diameter measurement adjusted for crown-rump length or abdominal circumference.

OBJECTIVE: Compare the performance of first trimester ultrasound biparietal diameter (BPD) screening for open spina bifida (OSB) when BPD is adjusted for crown-rump length (CRL) or abdominal circumference (AC). METHODS: For 63 OSB and 24 265 unaffected pregnancies, BPD was expressed as multiple of the normal median (MoM) based on CRL and on AC, and as the ratio BPD/AC. Screening performance was assessed by the Mahalanobis distance, the observed detection rate with normal fifth and 10th percentile cut-offs and the area under the receiver-operator characteristic curve (AUC). RESULTS: Mahalanobis distance for BPD MoM was considerably higher when based on AC than on CRL: 1.69 versus 1.14. Screening performance was also higher: using a fifth percentile cut-off, the detection rate was 59% compared with 41%; using a 10th percentile cut-off, the rates were 63% and 51%. Whilst the false-positives rates were slightly higher too-5.3% versus 5.1% and 10.8% versus 9.9%-the AUC was statistically significantly higher: 0.872 (95% CI, 0.816-0.928) compared with 0.735 (95% CI, 0.664-0.806). BPD/AC had intermediate performance. CONCLUSION: The best results are obtained when AC, rather than CRL, is used to express BPD values in MoMs. First trimester OSB screening can detect half to two-thirds of cases.

Impact on spina bifida screening of shifting prenatal Down syndrome maternal serum screening from the second trimester to the first.

OBJECTIVES: Shifting screening for trisomy 21 to the first trimester has resulted in the loss of maternal serum alpha-fetoprotein screening for spina bifida. The aim of this study was to study the impact on open spina bifida prenatal screening. STUDY DESIGN: We reviewed prenatally diagnosed cases of spina bifida over three years: 2009 (only second-trimester screening, MSM2T), 2010 (transient period) and 2011 (majority first-trimester screening, MSM1T). Cases were assigned to three groups based on maternal serum markers (MSM2T, MSM1T and 'not performed'). Gestational age at diagnosis of spina bifida was compared between these three groups and between the years 2009 and 2011. RESULTS: Median gestational ages at diagnosis of the 742 spina bifida cases between the three groups were 22 weeks [18+6 -23], 22+1  weeks [21+3 -23] and 21+4  weeks [14+1 -23], respectively (P < 0.005). The diagnosis was made at 14-20 weeks in 34.7% for MSM2T group versus 8.5% for MSM1T (P < 0.001). Spina bifida diagnosis at 14-20 weeks declined from 38.8% in 2009 to 13.3% in 2011 (P < 0.001). CONCLUSION: Loss of maternal serum alpha-fetoprotein had a tangible effect on the gestational age at diagnosis of spina bifida and resulted in a decrease of 25% of cases of spina bifida detected before 20 weeks. © 2017 John Wiley & Sons, Ltd.

Biparietal/transverse abdominal diameter ratio ≤ 1: potential marker for open spina bifida at 11-13-week scan.

OBJECTIVE: In the first trimester of pregnancy, a biparietal diameter (BPD) below the 5(th) percentile is a simple marker that enables the prenatal detection of half of all cases of open spina bifida. We hypothesized that relating the BPD measurement to the transverse abdominal diameter (TAD) might be another simple and effective screening method. In this study we assessed the performance of using the BPD/TAD ratio during the first trimester of pregnancy in screening for open spina bifida. METHODS: A total of 20,551 first-trimester ultrasound scans (11-13 weeks' gestation), performed between 2000 and 2013, were analyzed retrospectively; there were 26 cases of open spina bifida and 17,665 unaffected pregnancies with a crown-rump length of 45-84 mm and a record of both BPD and TAD measurements. RESULTS: The mean (± SD) BPD/TAD ratio was 1.00 ± 0.06 for fetuses with spina bifida and 1.13 ± 0.06 for those without (P < 0.0001). A BPD ≤ 5(th) percentile enabled the prenatal detection of 46.2% of spina bifida cases, while a BPD/TAD ratio of ≤ 1.00 detected 69.2%. If we considered cases in which either BPD was ≤ 5(th) percentile or BPD/TAD ratio was ≤ 1, we identified 76.9% of cases. In the latter case, the false-positive rate was 5.1%, while that for using a combination of both BPD ≤ 5th percentile and BPD/TAD ratio ≤ 1 was 0.6%, with a sensitivity of 38.5%. The positive predictive value of using a combination of BPD ≤ 5th percentile and BPD/TAD ratio ≤ 1 for detecting spina bifida was 8.5%. CONCLUSIONS: Between 11 and 13 weeks' gestation, relating BPD to TAD improves considerably the diagnostic performance of using BPD measurement alone in screening for open spina bifida. Screening using this marker is simple and applicable to a large population.

[Spina bifida aperta in a sheep lamb]. / Spina bifida aperta bei einem Schaflamm.

The case report describes the symptoms and diagnostic methods of a spina bifida aperta in a new born lamb. The most relevant clinical findings were recumbency immediately after birth with normal consciousness and suckling reflexes, alterations of the skin and coat in the lumbosacral region as well as dysuria. The biochemical and haematological screening of the blood indicated no abnormalities. While the radiological examination of the spine showed no clear evidence of the cause of the clinical sings the ultrasound and computed tomography examination revealed an incomplete closure of the vertebral arch between the 4th lumbar and the 3rd sacral vertebrae. Additionally, a hernia with similar density to the spinal cord was present in the same region of the spine. Based on the findings the lamb was euthanized. The pathological examination confirmed the incomplete closure of the vertebral arch and moreover a myelomeningocele has been diagnosed. In the histopathological examination the white and grey matter were separated in the area of the macroscopic visible lesions. Due to non-specific clinical symptoms imagining diagnostics can be crucial to confirm the diagnosis of this rare syndrome.

First-trimester ultrasound of the cerebral lateral ventricles in fetuses with open spina bifida: a retrospective cohort study.

BACKGROUND: Beyond 18 weeks of gestation, an increased size of the fetal lateral ventricles is reported in most fetuses with open spina bifida. In the first trimester of pregnancy, the definition of ventriculomegaly is based on the ratio of the size of the choroid plexus to the size of the ventricular space or the entire fetal head. However, contrary to what is observed from the midtrimester of pregnancy, in most fetuses with open spina bifida at 11 to 13 weeks of gestation, the amount of fluid in the ventricular system seems to be reduced rather than increased. OBJECTIVE: This study aimed to compare the biometry of the lateral ventricles at 11 0/7 to 13 6/7 weeks of gestation between normal fetuses and those with confirmed open spina bifida. STUDY DESIGN: This was a retrospective cohort study that included all cases of isolated open spina bifida detected at 11 0/7 to 13 6/7 weeks of gestation over a period of 5 years and a group of structurally normal fetuses attending at our center over a period of 1 year for the aneuploidy screening as controls. Transventricular axial views of the fetal brain obtained from cases and controls were extracted from the archive for post hoc measurement of cerebral ventricles. The choroid plexus-to-lateral ventricle length ratio, sum of the choroid plexus-to-lateral ventricle area ratio, choroid plexus area-to-fetal head area ratio, and mean choroid plexus length-to-occipitofrontal diameter ratio were calculated for both groups. The measurements obtained from the 2 groups were compared, and the association between each parameter and open spina bifida was investigated. RESULTS: A total of 10 fetuses with open spina bifida were compared with 358 controls. Compared with controls, fetuses with open spina bifida showed a significantly smaller size of the cerebral ventricle measurements, as expressed by larger values of choroid plexus-to-lateral ventricle area ratio (0.49 vs 0.72, respectively; P<.001), choroid plexus-to-lateral ventricle length ratio (0.70 vs 0.79, respectively; P<.001), choroid plexus area-to-fetal head area ratio (0.28 vs 0.33, respectively; P=.006), and choroid plexus length-to-occipitofrontal diameter ratio (0.52 vs 0.60, respectively; P<.001). The choroid plexus-to-lateral ventricle area ratio was found to be the most accurate predictor of open spina bifida, with an area under the curve of 0.88, a sensitivity of 90%, and a specificity of 82%. CONCLUSION: At 11 0/7 to 13 6/7 weeks of gestation, open spina bifida is consistently associated with a reduced amount of fluid in the lateral cerebral ventricles of the fetus, as expressed by a significantly increased choroid plexus-to-lateral ventricle length ratio, choroid plexus-to-lateral ventricle area ratio, choroid plexus area-to-fetal head area ratio, and choroid plexus length-to-occipitofrontal diameter ratio.

Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers.

OBJECTIVE: Screening at 11-13 weeks with ultrasound biparietal diameter (BPD) can detect half of open spina bifida cases. Maternal serum α-fetoprotein (AFP) levels at 15-19 weeks are increased 3- to 4-fold, in open spina bifida. We assessed whether combined screening using BPD, AFP, and other serum markers at 11-13 weeks would increase detection. STUDY DESIGN: Maternal AFP levels were measured on serum stored at 11-13 weeks in 44 open spina bifida and 182 unaffected pregnancies, and results were expressed in multiples of the median (MoM) for gestational age. All samples had been measured for free ß-human chorionic gonadotropin (ß-hCG) and pregnancy-associated plasma protein (PAPP)-A. A multivariate Gaussian model was used to predict screening performance from the serum data and BPD measurements on 80 cases, including 36 previously published. RESULTS: The median AFP level in cases was 1.201 MoM, significantly higher than in unaffected pregnancies (P < .01, 1 tail). The median free ß-hCG was significantly reduced to 0.820 MoM (P < .02), but the median PAPP-A was similar in cases and controls. Modeling predicted the following: BPD alone would detect 50% of cases for a 5% false-positive rate or 63% for 10%; adding AFP increases detection by 2%; and a combined test with BPD, AFP, and free ß-hCG detects 58% for 5% or 70% for 10%. CONCLUSION: Combining AFP and BPD with free ß-hCG as part of first-trimester aneuploidy screening would also allow early detection about two-thirds of cases with open spina bifida.

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.

Myelomeningocele (open spina bifida) - surgical management.

Myelomeningocele has been recognized since ancient times although written descriptions began not before the 17th century. Among all serious congenital malformations, myelomeningocele is unique that is has a steady and considerable prevalence while being compatible with life. It has a dismal prognosis when left untreated where virtually all die within the first year while aggressive treatment have a profound effect on survival and quality of life. Effective surgical treatment became possible parallel to the treatment of hydrocephalus in the late 1950s. Advent of the shunt systems undoubtedly changed the morbidity and mortality rates due to associated hydrocephalus. Aggressive and effective treatment improved survival rates but also those suffering physical and mental disabilities have increased as well. Ethical and socioeconomic concerns have led to proposal for selective treatment criteria which have raised arguments on medical and ethico-legal rounds. After the swing of the pendulum between early treatment in all affected children and selective treatment of those who fulfilled the criteria for good prognosis, early myelomeningocele repair is practiced widely unless the infant is critically ill.Incidence of myelomeningocele has been decreasing especially in the Western world, partly due to prenatal diagnosis and elective terminations, dietary folate supplementation. Still, it is the most common central nervous system malformation and one of the leading causes of paraplegia, worldwide. Unfortunately, gains in the management of myelomeningocele have been mainly on antenatal diagnosis and prevention while efforts on understanding its cause, mechanisms involved are still tentative. Concerning the surgical management, no revolutionary modification improving outcome has been introduced unlike other fields of neurosurgery.Medical management of a child with myelomeningocele requires a lifelong effort of several disciplines including urology, orthopedics physical and social therapy besides neurosurgery. The initial and probably the most crucial step begin with proper repair of the lesion. The aim of surgery, with its simplest definition should be towards maintaining the medical condition of the newborn. In other words, consequences of an open spinal cord segment with associated malformations have to be avoided with appropriate measures. Comparable to the surgical treatment of any congenital malformation, myelomeningocele repair consist of reversing the failed steps of normal neural tube closure. This requires a thorough understanding of the normal and abnormal embryological sequence of events in formation of the spinal cord. Although the purpose of this chapter is to describe the basic concepts and technique of myelomeningocele repair, contemporary information and progress on epidemiology, and etiology and embryology is presented with discussion of controversial issues regarding the selection process, optimal time for surgery and technical modifications.

A Nature-Inspired Search Space Reduction Technique for Spine Identification on Ultrasound Samples of Spina Bifida Cases.

Spina bifida is a birth defect caused by incomplete closing around the spinal cord. Spina bifida is diagnosed in a number of different ways. One approach involves searching for a deformity in the spinal axis via ultrasound. Although easy to apply, this approach requires a highly trained clinician to locate the abnormality due to the noise and distortion present in prenatal ultrasound images. Accordingly, visual examination of ultrasound images may be error prone and subjective. A computerized support system that would automatically detect the location of the spinal deformity may be helpful to the clinician in the diagnostic process. Such a software system first and foremost would require an algorithm for the identification of the entire (healthy or unhealthy) spine in the ultrasound image. This paper introduces a novel flocking dynamics based approach for reducing the size of the search space in the spine identification problem. Proposed approach accepts bone-like blobs on the ultrasound images as bird flocks and combine them into bone groups by calculating the migration path of each flock. Presented results reveal that the method is able to locate correct bones to be grouped together and reduce search space (i.e. number of bones) up to 68%.

First trimester cerebral appearance in the presence of closed spina bifida with myelomeningocele, part of the oeis complex.

Our communication presents a prenatally detected case with severe spinal defect detected in the first trimester of pregnancy, accompanied by a large skin-covered myelomeningocele but normal cranio-cerebral structural appearance.These findings suggest that in the first trimester, the extent of the spinal defect, the cerebrospinal fluid leakage to a large, but skin-covered, meningocele and fixation of the spinal cord at the lesion are not sufficient to determine downward hindbrain displacement and the development of secondary signs for open spina bifida.Therefore, we suggest a careful evaluation of the fetal cerebral features if a meningocele is detected. The presence of the skin covering the lesion may not be evident in the first trimester, but the absence of intracranial open spina bifida markers may indicate a 'closed' spinal defect, which generally associates a good neurological outcome. Also, studies aimed to investigate the accuracy of the intracranial features for open spina bifida detection should consider the possibility of 'closed' myelomeningoceles to avoid incorrect correlations.

Fetal myelomeningocele diagnosed in the antenatal period: Maternal-fetal characteristics and their relationship with pregnancy decision-making.

BACKGROUND: Spina bifida is the most common fetal anomaly of the central nervous system, which affects approximately 1:1000 live births in the United States. Myelomeningocele (MMC) is the most common presentation of spina bifida, representing half of these cases. Given the deformation to the spinal cord and the nerve roots, this defect may result in significant morbidity to infants and major life-long disabilities. In this study we aimed to identify maternal and fetal characteristics associated with expectant management or termination of pregnancy in the setting of antenatally diagnosed MMC. We hypothesized that the level of the defect would correlate with patient's decision to continue the pregnancy. METHODS: A retrospective cohort analysis was performed with patients who had presented to the Cleveland Clinic Fetal Care Center between 2005-2017. RESULTS: Our data showed 36% of patients with antenatal diagnosis of MMC elected for second trimester terminations versus 64% who chose to continue their pregnancy and deliver either by cesarean section or vaginal delivery. Based on ultrasound findings, there were no significant differences between these two groups. Maternal body mass index was significantly higher in those who continued pregnancies (p = 0.036). In addition, the fetal diagnostic methods chosen by patients were significantly different. Those who elected to terminate were more likely to pursue amniocentesis (p = 0.03) and less likely to opt for MRI characterization of the fetus (p = 0.007). CONCLUSION: We conclude, in the setting of fetal MMC diagnosed during pregnancy, patients often rely less on the associated ultrasonographic findings. Personal decisions likely influence the choice of other fetal diagnostic modalities. Other than BMI, we did not see an association between maternal factors and decisions regarding second trimester pregnancy termination.

Does a myelomeningocele sac compared to no sac result in decreased postnatal leg function following maternal fetal surgery for spina bifida aperta?

OBJECTIVE: A fetus with large sac S1 myelomeningocele (MMC) but bilateral talipes prompted the question, 'Does the presence or size of an MMC sac affect postnatal leg function?' STUDY DESIGN: An MMC database with prenatal, birth, and a minimum of 1-year follow-up evaluation was reviewed. All fetuses had in-utero MMC repair at 20 + 0 to 25 + 6 weeks at a single institution. Fifty-four fetuses had prenatal evaluation, with 48 children completing a birth and a 1-year evaluation of leg function. RESULTS: An MMC sac was present in 38/54 (70%) of fetuses evaluated in-utero and had been present in 35/48 (73%) of children evaluated at 1 year of age. Although leg function evaluated at 1 year was better than expected in the 'no sac' group (p = 0.059), this did not reach statistical significance. CONCLUSION: The presence of an MMC sac may increase postnatal lower limb morbidity.