Ivonne Bedei

Introduction: Hindbrain herniation (HBH) is a feature of Chiari II malformation in fetuses with open spinal dysraphism (OSD) and constitutes an eligibility criterion for prenatal repair in many fetal surgery protocols. Bulging of the posterior atlanto-occipital membrane (PAOM) is frequently observed in association with vermian descent; however, its significance in the absence of HBH remains unclear. Case Presentation: We report two fetuses with OSD who initially showed no HBH on fetal MRI but presented with isolated CSF-filled PAOM bulging. In both cases, repeat MRI within 2 weeks demonstrated interval development of HBH to C1, thereby fulfilling criteria for prenatal repair. Case 1 presented at 22.3 weeks with L4 myelomeningocele, mild ventriculomegaly and preserved motor function. Prenatal repair was performed at 26.0 weeks. Case 2 presented at 20.3 weeks with L5 myelomeningocele, normal ventricles, and intact motor function. Prenatal repair was performed at 25.3 weeks. In both fetuses, postoperative MRI demonstrated reversal of HBH, whereas PAOM bulging persisted. Conclusion: PAOM bulging may be associated with the subsequent development of HBH, but this observation requires confirmation in larger longitudinal cohorts. In fetuses with OSD and absent HBH at initial assessment, the presence of PAOM bulging may warrant consideration of short-interval follow-up MRI while prenatal repair remains an option.

Objective: Spinal dysraphism (SD) results from incomplete neural tube closure and encompasses a heterogeneous group of congenital anomalies with genetic and environmental etiologies. Although genetic contributions are recognized, causative variants remain insufficiently defined, and the clinical implications of extended genetic testing on parental decision‐making are not well characterized. This study evaluated the diagnostic utility of extended genetic testing, including exome sequencing (ES), in fetuses with prenatally diagnosed SD and its influence on clinical management. Methods: We retrospectively analyzed 150 pregnancies with a prenatal diagnosis of SD referred to our center between July 2021 and May 2025. All cases underwent detailed phenotyping, genetic counseling, and were offered extended genetic testing, including karyotyping, chromosomal microarray (CMA), and trio‐based ES. Results: Genetic testing, including karyotyping (110/110), CMA (61, 55.5%), and ES (66, 60.0%), was performed in 110 fetuses. Genetic anomalies were detected in 19 fetuses (17.3%). ES revealed or confirmed 16 pathogenic, likely pathogenic, or uncertain variants in 14/66 (21.21%) fetuses, including one with three distinct variants. Notably, twelve of these fetuses would not have been identified without ES. Although no definitive causative molecular variants were detected, ES results influenced the parental decision to terminate the pregnancy in four cases. Conclusion: ES increases diagnostic yield in SD and may influence prenatal decision‐making.

Objective: To provide an updated overview of international clinical practice in prenatal repair of open spinal dysraphism (OSD), focusing on evolving eligibility criteria, surgical techniques, and diagnostic standards. Methods: A structured online survey was distributed to 83 fetal surgery centers worldwide. The questionnaire addressed surgical techniques, maternal and fetal eligibility and diagnostic standards. Descriptive analyses were performed to identify current trends and practice variations. Results: 38 centers from 16 countries participated in the survey (response rate 45.8%). Open fetal surgery remains the most common approach (51.4%) though 47.4% reported offering multiple techniques, including fetoscopic methods. Compared with the MOMS criteria, 42.4% performed surgery beyond 25.6 weeks of gestation, 52.4% accepted a BMI 35%–40% and 28.6% acc epted even a BMI of 41%–45%, and 42.4% treated women with prior uterine surgery. Most centers (87.9%) combined ultrasound and MRI for preoperative imaging. Genetic evaluation was heterogeneous: 66.7% required karyotyping, 63.6% required chromosomal microarray, 18.2% non‐invasive testing, and 6.1% required none. Prognostic indicators such as ventriculomegaly and motor function increasingly influence selection decisions. Conclusion: International practice in prenatal OSD repair shows broadening maternal eligibility, diversification of surgical approaches, and variable diagnostic strategies. These findings highlight a shift toward individualised care and emphasise the need for further studies to evaluate the impact of practice adaptations.

Background/Objectives: Fetoscopic repair of open spinal dysraphism (OSD) is a rare intrauterine procedure performed in specialized fetal surgery centers. Conducted under restrictive fluid management and continuous tocolysis, it poses substantial challenges to maternal hemodynamic stability. Blood pressure optimization with vasopressor boluses is often required, yet intraoperative hemodynamic data remain limited. Methods: This prospective observational study was conducted between December 2023 and January 2025 during fetoscopic repair of OSD at Marburg University Hospital, Germany. Maternal hemodynamics were continuously monitored using pulse contour analysis with the Acumen IQ sensor and HemoSphere platform (Edwards Lifesciences, Irvine, CA, USA). To stabilize arterial pressure, cafedrine/theodrenaline (Akrinor, Ratiopharm, Ulm, Germany) was administered as intravenous boluses. Hemodynamic parameters were analyzed immediately before and after each bolus. Fetal heart rate was assessed as a secondary parameter at predefined intraoperative time points when available. Results: A total of 13 patients and 110 vasopressor boluses were analyzed. Reported values reflect median percent changes; parentheses indicate the total range. Following maternal blood pressure optimization, mean arterial pressure increased by 13.7% (5.9–21.6), systemic vascular resistance index by 23.1% (8.3–36.7), and dP/dtmax by 21.7% (6.3–29.9): p < 0.001 for all. Cardiac index and stroke volume index decreased by −6.7% (−11.8 to −0.6), p < 0.001, and −4.3% (−9.8 to 1.8), p = 0.048, respectively. Fetal heart rate remained stable (+0.4% (−0.8 to 1.5); p = 0.470). A total of 38 HPI alerts were followed by hypotension, with a median latency of 120 s (80–235); 73 alerts were not followed by hypotension during the observation period. Conclusions: Intermittent cafedrine/theodrenaline boluses significantly increased arterial pressure, dP/dtmax, and systemic vascular resistance under conditions of fluid restriction and tocolysis-induced vasodilation. Maternal heart rate remained stable, and cardiac output showed only minor reductions. Fetal heart rate was unchanged following maternal blood pressure treatment, indicating no adverse fetal response to C/T within the observed intraoperative period.

Introduction: Various treatment options for the prenatal open spina bifida (OSB) repair have evolved over the past decades, including the laparotomy-assisted fetoscopic repair. However, little is known about the fetal vascular regulation during the laparotomy-assisted fetoscopic repair. Therefore, we aimed to describe cardiovascular effects during the intervention in our cohort. Methods: A total of 26 fetuses underwent laparotomy-assisted fetoscopic repair at a single center between July 2021 and July 2024 and were prospectively included in this study. The intervention was performed using a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach. Fetal heart rate (FHR) and pulsed-wave Doppler flow measurement of the pulsatility index (PI) in the umbilical artery (UA) and middle cerebral artery (MCA) were recorded at 13 defined time points throughout the surgery. The occurrence of absent or reverse end-diastolic (ARED) UA flow was documented. The MCA waveform was assessed for signs of fetal vasoconstriction (M-sign). Results: The mean gestational age at surgery was 25 weeks. A significant increase in the PI in the UA before laparotomy (PI: 1.22 ± 0.24) and after laparotomy (PI: 1.75 ± 0.37) was observed (p < 0.001). An ARED flow was recorded in 13.3% of cases after maternal general anesthesia, but not before and at the latest on the first day after surgery. MCA PI decreased nonsignificantly during the intervention. Before surgery, the M-sign was present in 6 fetuses; however, during surgery, it was seen only in 1 fetus. There were no significant changes in FHR during surgery except for a drop after gas insufflation (FHR: 129 ± 5; FHR: 125 ± 7.0, p < 0.001) compared to the FHR before surgery. During the postoperative course, the FHR increased significantly (day 0: 141 ± 10; day 4: 143 ± 9.8, p = 0.003). Conclusion: Our study shows changes in the UA PI and the occurrence of ARED during laparotomy-assisted fetoscopic repair. FHR remained stable during surgery. Furthermore, the findings confirm the transient nature of these changes. The occurrence of Doppler and waveform abnormalities was related to maternal-fetal anesthesia and the procedure itself.

Background: Antibodies of the mother, which are directed against paternal antigens on platelets of the child, can lead to the destruction of the fetal blood cells in the circulation after diaplacental passage. The clinical picture of fetal-neonatal alloimmune thrombocytopenia (FNAIT) is characterized by bleeding, of which intracranial bleeding is particularly feared. Our understanding of the pathophysiology of FNAIT and its targeted prophylaxis and therapy has improved significantly in recent years. Summary: FNAIT by anti-HPA-1a is the best studied. How exactly the mother is immunized is not known for certain, but, in clinically apparent cases, immunization usually occurs in the first pregnancy of an HLA-DRB3*01:01-positive, HPA-1a-negative woman. There is no convincing basis for assigning immunization against HPA-5b and against HLA class I any significance in the development of fetal thrombocytopenia. Newborns of mothers with anti-HPA-1a present a broad clinical picture ranging from isolated, clinically unremarkable thrombocytopenia to intracranial hemorrhage (ICH; in approx. 1–10% of cases). ICH usually occurs intrauterine (before week 28). There are indications that, in addition to the fetal platelets, the placenta can also be affected by anti-HPA-1a. As there are no screening programmes, the index diagnosis of FNAIT is random. It is made by serological and genetic laboratory tests. Predicting outcome in a subsequent pregnancy is problematic if the child is antigen-positive. Key Messages: With a first-born child with severe thrombocytopenia, the probability of a recurrence of severe thrombocytopenia is around 70%. Without ICH, the probability of ICH in the subsequent pregnancy is low but not zero, and with ICH the recurrence rate is high. There is no established laboratory diagnostic method to predict the severity of thrombocytopenia or the occurrence of ICH. Prophylaxis with immunoglobulins (IVIgs) is considered effective. Pharmaceutics that block placental transport are currently undergoing clinical trials and may replace IVIgs in the future. Intrauterine platelet transfusions should no longer be performed. For the mature, thrombocytopenic newborn without internal hemorrhage, a platelet transfusion is advisable for platelet counts <25 g/L.

Objective: To report the natural history of fetuses with open spinal dysraphism (OSD) without hindbrain herniation (HBH) during second‐trimester evaluation.Methods: A multicenter retrospective cohort study was conducted across three prenatal centers to evaluate fetuses with OSD. We reviewed cases with postnatally confirmed OSD without prenatal HBH at 19–27 weeks. Standardized prenatal evaluation consisted of repetitive ultrasound and magnetic resonance imaging. Postnatal outcome measures involved imaging, intraoperative findings and neurological function tests.Results: Among 280 fetuses with OSD, evaluated at a median gestational age of 21 weeks, a total of 12 (4%) lacked HBH. Moderate ventriculomegaly was observed in 33% of cases without HBH. Corpus callosum anomalies were not detected. Postnatally, HBH was present in 50%, while the shunt rate remained low (20%). In 80%, postnatal motor function (MF) was equal to or better based on the anatomical level. In 33%, MF after birth declined in comparison to the first fetal functional assessment in the second trimester.Conclusion: Fetuses with OSD and absent HBH in the second trimester demonstrate a low postnatal shunt rate. MF was frequently impaired at the initial second‐trimester assessment, and in about a third of cases, postnatal MF seemed to have worsened. These findings may inform counseling and question the place of fetal surgery for this subgroup.

It is evident that Turner syndrome (TS) impacts almost all developmental stages of the fetal heart with congenital heart disease (CHD) being seen in 23%–50% of individuals. Although the spectrum of CHDs in TS is well‐established, with left‐sided lesions predominating, the influence of specific karyotypes on the prevalence and types of CHDs remains incompletely understood. The primary objective of this systematic review/meta‐analysis was to quantitatively synthesize the existing evidence on the association between specific karyotypes in TS and the risk of various CHDs. A systematic literature search was conducted through December 2023 to identify studies reporting the prevalence of CHDs in relation to TS karyotype. The quality of the individual studies was assessed using the Joanna Briggs Institute critical appraisal tools for systematic reviews. The overall estimates were pooled using both fixed‐ and random‐effects models. Sensitivity and subgroup analysis were performed. Twenty‐five studies were included in the analysis. TS individuals with a 45,X karyotype showed a significantly higher likelihood of bicuspid aortic valve (BAV) (pooled OR, 3.14 [95% CI: 2.49–3.94]), aortic coarctation (CoA) (pooled OR, 4.16 [95% CI: 2.74–6.31]), and partial anomalous pulmonary venous return (PAPVR) (pooled OR, 4.86 [2.31–10.2]) compared with TS individuals with a non‐45,X karyotype. In addition, TS individuals with a 45,X karyotype also showed a significantly higher likelihood of BAV (pooled OR, 2.72 [95% CI: 1.62–4.56]) when compared with TS individuals with 45,X/46,XX mosaicism. TS individuals with a 45,X karyotype showed a significantly higher risk of BAV (pooled OR, 2.13 [95% CI: 1.42–3.21]) and CoA (pooled OR, 4.52 [95% CI: 1.58–13.0]) when compared with TS individuals with an isochromosome Xq. A significantly higher likelihood of BAV was also found in 45,X compared to other karyotypes (e.g., 45,X/46,XY and TS karyotypes with ring X chromosome). Some heterogeneity was evident, but publication was low. This meta‐analysis confirms a strong association between the 45,X karyotype and increased prevalence of BAV, CoA, and PAPVR in TS. While 45,X/46,XX mosaicism and karyotypes with an isochromosome Xq mitigate risk, the findings emphasize the need for large‐scale studies to refine risk assessment and management strategies.

Objectives: Many patients with sex chromosome abnormalities (SCAs) are diagnosed late in life or remain undiagnosed, leading to delayed or inadequate medical intervention and care. This study aimed to develop a reliable, rapid and cost-effective test for identifying SCAs using a blood sample – an essential step toward establishing a neonatal screening program. Methods: A total of 360 blood samples (180 SCA patients, and 180 controls) were obtained from four cross-sectional studies of adult patients with SCAs and age-matched controls. Informed consent was collected, and all procedures followed the Declaration of Helsinki. Multiplex quantitative fluorescence polymerase chain reaction (QF-PCR) utilizing short tandem repeat (STR) and X-linked segmental duplication (SD) markers was performed. Results were analyzed using an automated algorithm. Deviant results were manually reviewed to differentiate errors in the PCR process from those in automated data analysis. Results: Following automated data analysis of QF-PCR results, the method accurately identified 174 SCA patients (sensitivity: 96.7 %) and 171 controls (specificity: 95.0 %). Mosaic karyotypes were particularly challenging to diagnose. Manual reanalysis of the QF-PCR results corrected all false positives, achieving 100 % specificity. Conclusions: This method is promising for reliable SCA detection in blood samples, offering cost-effectiveness and scalability. The specificity following automated data analysis was not satisfactory. The underlying PCR technique, however, demonstrated 100 % specificity, indicating that refining the automated analysis algorithm would significantly reduce false positive results. With further refinements, we believe this test would be highly suitable for further evaluation in a newborn screening setting.