Dr. med. Ivonne Bedei

@article{pmid41388734,

title = {Uncovering the Genetic Landscape of Spinal Dysraphism: A Retrospective Analysis of 150 Fetal Cases},

author = {I Bedei and A Feresin and R Zemet and D Berner and D Polidori and K Fröbius and A Skakkebæk and R Axt-Fliedner and M Shoukier and C Keil},

doi = {10.1002/pd.70037},

issn = {1097-0223},

year  = {2025},

date = {2025-12-01},

journal = {Prenat Diagn},

abstract = {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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSION: ES increases diagnostic yield in SD and may influence prenatal decision-making.},

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@article{pmid40651522,

title = {Minipuberty in girls with Turner syndrome provides insight into reproductive potential-a prospective cohort study},

author = {Sanne van der Coelen and Casper P Hagen and Sapthami Nadesapillai and Ivonne Bedei and Gerhard Binder and Gianni Bocca and Aneta Gawlik-Starzyk and Noah Gruber and Sabine E Hannema and Anders Juul and Elena Lundberg and Theo Sas and Saartje Straetemans and Annemarie Verrijn Stuart and Małgorzata Więcek and Ronald Peek and Didi Braat and Kathrin Fleischer and Antonius Eduard van Herwaarden and Janielle van der Velden},

doi = {10.1016/j.fertnstert.2025.07.003},

issn = {1556-5653},

year  = {2025},

date = {2025-12-01},

journal = {Fertil Steril},

volume = {124},

number = {6},

pages = {1314--1323},

abstract = {OBJECTIVE: To study reproductive hormone levels during minipuberty in girls with Turner syndrome and compare with girls without Turner syndrome.nnDESIGN: Prospective cohort study.nnSUBJECTS: Infant girls with Turner syndrome.nnEXPOSURE: Blood samples were drawn at 3 and 9 months of age for analysis of reproductive hormones. Karyotype was analyzed in 30 lymphocytes and, if available, in 100 buccal cells. Hormone levels in girls with Turner syndrome were compared with reference values of a control group.nnMAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol, antimüllerian (AMH), inhibin B, and testosterone levels.nnRESULTS: Fourteen girls with 45,X; five girls with 45,X/46,XX; and four girls with a structural aberration of the X chromosome were included. Follicle-stimulating hormone and luteinizing hormone levels were significantly higher, and estradiol, AMH, and inhibin B levels were significantly lower in girls with Turner syndrome compared with reference values at both time points. In girls with Turner syndrome with undetectable AMH levels, gonadotropin levels increased after 3 months, whereas in girls with Turner syndrome with detectable AMH levels, gonadotropin levels decreased after 3 months to levels within the reference range.nnCONCLUSION: Hypothalamus-pituitary-gonadal axis hormone levels during minipuberty in girls with Turner syndrome differ from reference values. The window for assessing ovarian function extends beyond 3 months of age because gonadotropin levels tend to increase in cases with absent ovarian activity, as demonstrated by undetectable AMH, inhibin B, and estradiol levels.},

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@article{pmid41303089,

title = {Blood Pressure Optimization During Fetoscopic Repair of Open Spinal Dysraphism: Insights from Advanced Hemodynamic Monitoring},

author = {Benjamin Vojnar and Michael Belfort and Caitlin D Sutton and Corinna Keil and Ivonne Bedei and Gerald Kalmus and Hinnerk Wulf and Siegmund Köhler and Christine Gaik},

doi = {10.3390/jcm14228055},

issn = {2077-0383},

year  = {2025},

date = {2025-11-01},

journal = {J Clin Med},

volume = {14},

number = {22},

abstract = {: 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. : 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. : 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):  < 0.001 for all. Cardiac index and stroke volume index decreased by -6.7% (-11.8 to -0.6),  < 0.001, and -4.3% (-9.8 to 1.8),  = 0.048, respectively. Fetal heart rate remained stable (+0.4% (-0.8 to 1.5);  = 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. : 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.},

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}

@article{pmid41298113,

title = {Evolving Practices in Prenatal Open Spinal Dysraphism: A Global Survey of Selection Criteria, Surgical Techniques, and Diagnostic Trends},

author = {Corinna Keil and Noemi Wiora and Eyal Krispin and Anita Windhorst and Roland Axt-Fliedner and Ivonne Bedei},

doi = {10.1002/pd.70031},

issn = {1097-0223},

year  = {2025},

date = {2025-11-01},

journal = {Prenat Diagn},

abstract = {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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSION: 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.},

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@article{pmid41089465,

title = {Diagnosis and Management of Fetal and Neonatal Alloimmune Thrombocytopenia: An Update 2025},

author = {Ulrich J Sachs and Ivonne Bedei and Sandra Wienzek-Lischka and Nina Cooper and Harald Ehrhardt and Roland Axt-Fliedner and Gregor Bein},

doi = {10.1159/000547985},

issn = {1660-3796},

year  = {2025},

date = {2025-10-01},

journal = {Transfus Med Hemother},

volume = {52},

number = {5},

pages = {318--333},

abstract = {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.nnSUMMARY: 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.nnKEY 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.},

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@article{pmid41037504,

title = {Effects of in utero Open Spina Bifida Repair Using a Laparotomy-Assisted Fetoscopic Approach on the Fetal Cardiovascular System},

author = {Annika Albrecht and Justus G Reitz and Ivonne Bedei and Anita C Windhorst and Corinna Keil and Siegmund Köhler and Aline Wolter and Nicolas Schmitt and Gerald Kalmus and Benjamin Sass and Maximilian Schulze and Roland Axt-Fliedner},

doi = {10.1159/000548623},

issn = {1421-9964},

year  = {2025},

date = {2025-10-01},

journal = {Fetal Diagn Ther},

pages = {1--10},

abstract = {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.nnMETHODS: 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).nnRESULTS: 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).nnCONCLUSION: 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.},

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pubstate = {published},

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@article{pmid40086886,

title = {Intrauterine Therapy},

author = {Ingo Gottschalk and Eva Christin Weber and Ivonne Bedei and Roland Axt-Fliedner and Brigitte Strizek and Christoph Berg},

doi = {10.1055/a-2524-5787},

issn = {1438-8782},

year  = {2025},

date = {2025-10-01},

journal = {Ultraschall Med},

volume = {46},

number = {5},

pages = {440--471},

abstract = {Since the first intrauterine interventions were carried out in the 1970 s under what today would be considered basic conditions, the range of prenatal interventions has steadily expanded, as has the frequency with which these interventions are carried out at specialized centers. Although most of these procedures are minimally invasive, they are invariably associated with considerable risks for the fetus and, depending on the surgical method, also for the expectant mother. For this reason, most centers worldwide limit themselves to interventions for fetal diseases which, if untreated, have a fatal course or experience a significant deterioration in the postnatal prognosis during the course of intrauterine development. This is all the more significant as only a small proportion of prenatal interventions have been successfully investigated in controlled clinical trials. The only exceptions are laser therapy for feto-fetal transfusion syndrome, intrauterine closure of spina bifida, and tracheal occlusion for diaphragmatic hernia with severe pulmonary hypoplasia. This article is intended to provide an overview of the fetal conditions that are candidates for intrauterine therapy and of the evidence for the individual interventions.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid40627407,

title = {Open Spinal Dysraphism Without Hindbrain Herniation-Natural History and Postnatal Outcome},

author = {I Bedei and C C Kik and R Axt-Fliedner and P L J DeKoninck and W Ventura and S Köhler and M Schulze and T Struffert and M Kolodziej and D Diehl and B Sass and J K H Spoor and C Keil},

doi = {10.1002/pd.6855},

issn = {1097-0223},

year  = {2025},

date = {2025-08-01},

journal = {Prenat Diagn},

volume = {45},

number = {9},

pages = {1106--1114},

abstract = {OBJECTIVE: To report the natural history of fetuses with open spinal dysraphism (OSD) without hindbrain herniation (HBH) during second-trimester evaluation.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSION: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid40103208,

title = {Reliable detection of sex chromosome abnormalities by quantitative fluorescence polymerase chain reaction},

author = {Camilla Mains Balle and Dorte L Lildballe and Ivonne Bedei and Ruth Luschka and Anne Skakkebæk and Simon Chang and Zeynep Agirman and Jan Keller and Axel Weber and Ramón E Schäfer and Johannes Becker-Follmann and Claus H Gravholt},

doi = {10.1515/cclm-2024-1400},

issn = {1437-4331},

year  = {2025},

date = {2025-07-01},

journal = {Clin Chem Lab Med},

volume = {63},

number = {8},

pages = {1519--1527},

abstract = {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.nnMETHODS: 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.nnRESULTS: 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.nnCONCLUSIONS: 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.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid40557696,

title = {The Impact of Karyotype on Congenital Heart Diseases in Turner Syndrome: A Systematic Review and Meta-Analysis},

author = {Francisco Álvarez-Nava and Melissa L Crenshaw and Ivonne Bedei and Marisol Soto and Andréa T Maciel-Guerra and Anne Skakkebæk},

doi = {10.1002/ajmg.c.32146},

issn = {1552-4876},

year  = {2025},

date = {2025-06-01},

journal = {Am J Med Genet C Semin Med Genet},

volume = {199},

number = {2},

pages = {93--106},

abstract = {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.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid40040490,

title = {Non-Invasive Prenatal Testing by Cell-Free DNA (cfNIPT) for Detecting Turner Syndrome With Mosaicism and Structural Variants-Prenatal Findings and Postnatal Outcomes},

author = {Ivonne Bedei and Johanna Bruder and Ida C B Lund and Simon H Thomsen and Ida Vogel and Andrea T Maciel-Guerra and Francisco Alvarez-Nava and Melissa L Crenshaw and Roland Axt-Fliedner and Claus H Gravholt and Anne Skakkebæk},

doi = {10.1002/ajmg.c.32136},

issn = {1552-4876},

year  = {2025},

date = {2025-06-01},

journal = {Am J Med Genet C Semin Med Genet},

volume = {199},

number = {2},

pages = {124--133},

abstract = {Turner Syndrome (TS) is a sex chromosomal disorder associated with karyotype heterogeneity. Although TS can be associated with severe prenatal findings, most often linked to the 45, X karyotype, the majority of TS fetuses have no overt phenotype, resulting in delayed diagnosis and management. The objective of this study is to assess the efficacy of non-invasive prenatal testing by cell-free DNA (cfNIPT) in detecting TS fetuses with different TS karyotype variants and to examine the phenotypic variations and clinical outcomes.Data on pregnancies with confirmed or suspected TS from 2000 to 2024 were collected from specialists in fetal ultrasound in Germany. In addition, a small number of Danish cases with 45, X mosaicism in the placenta was included. Data were collected regarding cfNIPT results, karyotypes, prenatal ultrasound findings, and pregnancy outcomes.Of the 114 cases included, 100 (87.7%) had a high-risk cfNIPT result for monosomy X, 53 (46.5%) were true positives (TP), and 47 (41.2%) were false positives (FP). Fourteen (12.3%) were false negatives (FN). No differences in congenital malformation or nuchal translucency were seen between TP and FN. Data on karyotype were available for 67 cases. Fourty (59.7%) had a 45, X karyotype, 16 (23.9%) 45, X mosaicism, and 11 (16.4%) had a structural variant. The 45, X karyotype was associated with a higher prevalence of congenital malformation and increased nuchal translucency (ps ≤ 0.001). The live birth rate was higher in cases with 45, X mosaicism or structural variants compared to cases with a 45, X karyotype (ps ≤ 0.03). Postnatal phenotypes were often mild.cfNIPT represents a valuable tool for the early identification of fetuses with TS karyotype variants, enabling timely intervention and targeted management. However, the high false-positive rate underscores the need for careful counseling.},

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tppubtype = {article}

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@article{pmid38914189,

title = {Amniocentesis in pregnancies at or beyond 24 weeks: an international multicenter study},

author = {Roni Zemet and Mohamad Ali Maktabi and Alexandra Tinfow and Jessica L Giordano and Thomas M Heisler and Qi Yan and Roni Plaschkes and Jenny Stokes and Jennifer M Walsh and Siobhán Corcoran and Erica Schindewolf and Kendra Miller and Asha N Talati and Kristen A Miller and Karin Blakemore and Kate Swanson and Jana Ramm and Ivonne Bedei and Teresa N Sparks and Angie C Jelin and Neeta L Vora and Juliana S Gebb and David A Crosby and Michal Berkenstadt and Boaz Weisz and Ronald J Wapner and Ignatia B Van Den Veyver},

doi = {10.1016/j.ajog.2024.06.025},

issn = {1097-6868},

year  = {2025},

date = {2025-04-01},

journal = {Am J Obstet Gynecol},

volume = {232},

number = {4},

pages = {402.e1--402.e16},

abstract = {BACKGROUND: Amniocentesis for genetic diagnosis is most commonly done between 15 and 22 weeks of gestation but can be performed at later gestational ages. The safety and genetic diagnostic accuracy of amniocentesis have been well-established through numerous large-scale multicenter studies for procedures before 24 weeks, but comprehensive data on late amniocentesis remain sparse.nnOBJECTIVE: To evaluate the indications, diagnostic yield, safety, and maternal and fetal outcomes associated with amniocentesis performed at or beyond 24 weeks of gestation.nnSTUDY DESIGN: We conducted an international multicenter retrospective cohort study examining pregnant individuals who underwent amniocentesis for prenatal diagnostic testing at gestational ages between 24w0d and 36w6d. The study, spanning from 2011 to 2022, involved 9 referral centers. We included singleton or twin pregnancies with documented outcomes, excluding cases where other invasive procedures were performed during pregnancy or if amniocentesis was conducted for obstetric indications. We analyzed indications for late amniocentesis, types of genetic tests performed, their results, and the diagnostic yield, along with pregnancy outcomes and postprocedure complications.nnRESULTS: Of the 752 pregnant individuals included in our study, late amniocentesis was primarily performed for the prenatal diagnosis of structural anomalies (91.6%), followed by suspected fetal infection (2.3%) and high-risk findings from cell-free DNA screening (1.9%). The median gestational age at the time of the procedure was 28w5d, and 98.3% of pregnant individuals received results of genetic testing before birth or pregnancy termination. The diagnostic yield was 22.9%, and a diagnosis was made 2.4 times more often for fetuses with anomalies in multiple organ systems (36.4%) compared to those with anomalies in a single organ system (15.3%). Additionally, the diagnostic yield varied depending on the specific organ system involved, with the highest yield for musculoskeletal anomalies (36.7%) and hydrops fetalis (36.4%) when a single organ system or entity was affected. The most prevalent genetic diagnoses were aneuploidies (46.8%), followed by copy number variants (26.3%) and monogenic disorders (22.2%). The median gestational age at delivery was 38w3d, with an average of 59 days between the procedure and delivery date. The overall complication rate within 2 weeks postprocedure was 1.2%. We found no significant difference in the rate of preterm delivery between pregnant individuals undergoing amniocentesis between 24 and 28 weeks and those between 28 and 32 weeks, reinforcing the procedure's safety across these gestational periods.nnCONCLUSION: Late amniocentesis, at or after 24 weeks of gestation, especially for pregnancies complicated by multiple congenital anomalies, has a high diagnostic yield and a low complication rate, underscoring its clinical utility. It provides pregnant individuals and their providers with a comprehensive diagnostic evaluation and results before delivery, enabling informed counseling and optimized perinatal and neonatal care planning.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid39547350,

title = {Monitoring and management of hemolytic disease of the fetus and newborn based on an international expert Delphi consensus},

author = {Hiba J Mustafa and Enaja V Sambatur and Alireza A Shamshirsaz and Sonia Johnson and Kenneth J Moise and Ahmet A Baschat and E J T Joanne Verweij and Ali Javinani and Mark D Kilby and Enrico Lopriore and Rebecca Rose and Roland Devlieger and Saul Snowise and Ulrich J Sachs and Asma Khalil and },

doi = {10.1016/j.ajog.2024.11.003},

issn = {1097-6868},

year  = {2025},

date = {2025-03-01},

journal = {Am J Obstet Gynecol},

volume = {232},

number = {3},

pages = {280--300},

abstract = {The study aimed to develop structured, expert-based clinical guidance on the prenatal and postnatal management of hemolytic disease of the fetus and newborn. A Delphi procedure was conducted among an international panel of experts in fetal medicine, neonatology, and hematology. Experts were selected based on their expertise, relevant publications, and affiliations. The domains were (i) prenatal workup, (ii) prenatal monitoring and management, (iii) intrauterine transfusion (IUT), (iv) delivery, and (v) postnatal management. The predefined cut-off for consensus was ≥70% agreement. One hundred-seven experts representing 25 countries across 6 continents completed the first round, and 100 (93.5%) completed the subsequent rounds. 75.3% agreed on using cfDNA to determine fetal antigen status, particularly for RhD, Kell, and Rhc antigens. The critical titer, requiring fetal monitoring via ultrasound, is considered when the threshold of ≥16 is for non-Kell antigens. 70.0% agreed on the use of maternal IVIg in pregnancies with prior IUT <24 weeks or fetal/neonatal death due to HDFN. The minimum GA for IUT is 16 to 18 weeks, and the maximum is 35 to 35 weeks. Postnatal management consensus was reached for the following: anemia labs should be investigated in the affected neonates before hospital discharge (92.0% agreement), and if they received IUT, the labs should be repeated within 1 week of discharge (84.0% agreement). 96.0% agreed that exchange transfusions should be centralized in hospitals with sufficient exposure and experience, and 92.0% agreed that the hemoglobin cut-off level to consider transfusion following hospital discharge is 7 g/dL, and the newborns need to be monitored until 2 to 3 months of age (96.0% agreement).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39654393,

title = {The Intrauterine Treatment of Open Spinal Dysraphism},

author = {Corinna Keil and Benjamin Sass and Maximilian Schulze and Siegmund Köhler and Roland Axt-Fliedner and Ivonne Bedei},

doi = {10.3238/arztebl.m2024.0239},

issn = {1866-0452},

year  = {2025},

date = {2025-01-01},

journal = {Dtsch Arztebl Int},

volume = {122},

number = {2},

pages = {33--37},

abstract = {BACKGROUND: Open spinal dysraphism is a congenital malformation that causes major morbidity. Its consequences include sensory and motor impairment as well as bladder- and bowel dysfunction. It is often also associated with prenatal ventriculomegaly, which, in turn, necessitates postnatal treatment with a ventriculoperitoneal shunt in approximately 80% of cases. Prenatal therapy with coverage of neural tube defect can reduce the shunt rate and preserve motor function. In this review, we describe the different surgical procedures and their outcomes.nnMETHODS: This review is based on publications that were retrieved by a selective literature search in the MEDLINE, Web of Science, EMBASE, Scopus, and Cochrane databases, employing pertinent keywords. Studies of all types (except case reports) that were published in English or German in the period 2010-2024 were included.nnRESULTS: The randomized, controlled MOMS trial showed that intrauterine surgery for defect closure resulted in less progressive neural tissue damage than postnatal surgery and reduced the need for shunting by approximately half (40% vs. 82%). Since the publication of these results, various prenatal surgical procedures have been established, including hysterotomy-assisted, percutaneous fetoscopic, and laparotomy-assisted fetoscopic closure. The individual surgical methods yield comparable results in terms of motor function and shunt rate. A problem with these procedures is that they increase the likelihood of preterm birth, to an extent that varies from one type of procedure to another.nnCONCLUSION: Prenatal surgery improves motor function and reduces the shunt rate but long-term outcomes beyond adolescence are still lacking. Transparent and interdisciplinary counseling is essential in prenatal communication to inform parents not only about the potential benefits of this treatment, but also about its limitations and risks.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39792381,

title = {Variations and Opportunities in Postnatal Management of Hemolytic Disease of the Fetus and Newborn},

author = {Derek P de Winter and E J T Joanne Verweij and Anne Debeer and Roland Devlieger and Liesbeth Lewi and Sarah Verbeeck and Paul Maurice and Jean-Marie Jouannic and Marie-Gabrielle Guillemin and Agnès Mailloux and Maria Cristina Pessoa Dos Santos and Cynthia Amaral de Moura Sá Pacheco and Maria Elisabeth Lopes Moreira and Marcella Martins de Vasconcelos Vaena and Kajsa Bohlin and Eleonor Tiblad and Emilie Thorup and Olav Bjørn Petersen and Maria Sanchez-Holgado and Aurora Viejo Llorente and Borna Poljak and Asma Khalil and Kévin Le Duc and Louise Ghesquiere and Jana Lozar Krivec and Aneta Soltirovska-Šalamon and Christof Dame and Jessica D Blank and Alexander Hohnecker and Matthew Saxonhouse and Ngina K Connors and Annegret Geipel and Johanna Rath and Smriti Prasad and Lizelle van Wyk and Lut Geerts and Rahel Schuler and Nina Thon and Leah Leibovitch and Stav Cohen and Arturo Alejandro Canul-Euan and Edmond Kelly and Kamini Raghuram and Francesco Cavigioli and Sofia Fatima Guiseppina Colombo and Ziju Elanjikal and Jessica Brayley and Daniel Pfurtscheller and Gerhard Pichler and Ángel Guillermo Alcázar Grisi and Edgar Juan José Chávez Navarro and Joana Pereira-Nunes and Henrique Soares and Ming Zhou and María José Garcia Borau and Elisenda Moliner Calderón and Maria Fernanda Galletti and Gonzalo Luis Mariani and David Mackin and Fergal Malone and Andrea Lampland and Wing Ting Tse and James Castleman and Johanna G van der Bom and Masja de Haas and Enrico Lopriore and },

doi = {10.1001/jamanetworkopen.2024.54330},

issn = {2574-3805},

year  = {2025},

date = {2025-01-01},

journal = {JAMA Netw Open},

volume = {8},

number = {1},

pages = {e2454330},

abstract = {IMPORTANCE: Preventive efforts in pregnancy-related alloimmunization have considerably decreased the prevalence of hemolytic disease of the fetus and newborn (HDFN). International studies are therefore essential to obtain a deeper understanding of the postnatal management and outcomes of HDFN. Taken together with numerous treatment options, large practice variations among centers may exist.nnOBJECTIVES: To assess variations in postnatal management and outcomes of HDFN among international centers and to identify opportunities to improve care.nnDESIGN, SETTING, AND PARTICIPANTS: In this international, retrospective, cohort study, 31 expert centers from 22 countries retrieved data on neonates with HDFN managed between January 1, 2006, and July 1, 2021. Statistical analysis was performed from July 19, 2023, to October 28, 2024.nnMAIN OUTCOMES AND MEASURES: Main outcomes included the frequency of exchange transfusions, administration of intravenous immunoglobulin, administration of erythropoiesis-stimulating agents, and red blood cell transfusions, as well as the association of gestational age at birth with exchange transfusion frequency and risk factors for adverse neonatal outcomes.nnRESULTS: The study included 1855 neonates (median gestational age at birth, 36.4 weeks [IQR, 35.0-37.3 weeks]; 1034 boys [55.7%]), of whom 1017 (54.8%) received any form of antenatal treatment. Most neonates (1447 [78.0%]) had anti-D antibodies. Exchange transfusions were performed in 436 neonates (23.5%), with proportions in exchange transfusion frequency varying from 0% to 78% among centers. Intravenous immunoglobulin was administered to 429 of 1743 neonates (24.6%), with proportions varying from 0% to 100% among centers. A higher gestational age at birth was associated with a reduction in exchange transfusion frequency in neonates with intrauterine transfusion, decreasing from approximately 38.2% (13 of 34) at 34 weeks to 16.8% (18 of 107) after 37 weeks and 0 days. A weekly increase in gestational age at birth was associated with a 43.3% decrease (95% CI, 36.1%-49.7%) in the likelihood of adverse neonatal outcomes, and neonates who received an exchange transfusion were 1.55 (95% CI, 1.10-2.18) times more likely to experience unfavorable outcomes.nnCONCLUSIONS AND RELEVANCE: In this cohort study of neonates with HDFN managed at 31 centers in 22 countries, significant practice variations in the postnatal management of HDFN were identified, highlighting the lack of, and need for, consensus. The study suggests that there is a potential beneficial clinical association of waiting for delivery until after 37 weeks and 0 days with frequency of exchange transfusions among neonates with HDFN. The framework to implement international guidelines is provided.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39527958,

title = {Variations in antenatal management and outcomes in haemolytic disease of the fetus and newborn: an international, retrospective, observational cohort study},

author = {Derek P de Winter and Enrico Lopriore and Emilie Thorup and Olav Bjørn Petersen and Morten H Dziegiel and Karin Sundberg and Roland Devlieger and Luc de Catte and Liesbeth Lewi and Anne Debeer and Véronique Houfflin-Debarge and Louise Ghesquiere and Charles Garabedian and Kévin Le Duc and Eugenia Antolin and Nieves Mendez and James Castleman and Wing Ting Tse and Jean-Marie Jouannic and Paul Maurice and Jane Currie and Emma Mullen and Lut Geerts and Kerry Rademan and Asma Khalil and Borna Poljak and Smriti Prasad and Eleonor Tiblad and Kajsa Bohlin and Annegret Geipel and Johanna Rath and Fergal Malone and David Mackin and Yoav Yinon and Stav Cohen and Greg Ryan and Evangelia Vlachodimitropoulou and Karl-Philipp Gloning and Stefan Verlohren and Beate Mayer and Mariano Lanna and Stefano Faiola and Tanja Premru Sršen and Lilijana Kornhauser Cerar and Saul Snowise and Luming Sun and Lucas Otaño and César Hernan Meller and Ngina K Connors and Matthew Saxonhouse and Aline Wolter and Ivonne Bedei and Philipp Klaritsch and Sarah Jauch and Eduardo Teixeira da Silva Ribeiro and Fernando Maia Peixoto Filho and Raigam Jafet Martinez-Portilla and Alexandra Matias and Obdulia Alejos Abad and Juan Parra Roca and Ángel Guillermo Alcázar Grisi and Edgar Juan José Chávez Navarro and Johanna G van der Bom and Masja de Haas and Ejt Joanne Verweij and },

doi = {10.1016/S2352-3026(24)00314-4},

issn = {2352-3026},

year  = {2024},

date = {2024-12-01},

journal = {Lancet Haematol},

volume = {11},

number = {12},

pages = {e927--e937},

abstract = {BACKGROUND: Advances in haemolytic disease of the fetus and newborn have led to numerous treatment options. We report practice variations in the management and outcomes of haemolytic disease of the fetus and newborn in at-risk pregnancies.nnMETHODS: In this international, retrospective, observational cohort study, data from cases with moderate or severe haemolytic disease of the fetus and newborn were retrieved from 31 centres in 22 countries. Eligible participants had pregnancies with haemolytic disease of the fetus that led to fetal death at 16 + 0 weeks or later, those treated antenatally with intrauterine transfusion or intravenous immunoglobulins, or neonates without antenatal treatment who were treated with intensive phototherapy, exchange transfusion, or red blood cell transfusions. All patients had confirmed maternal alloantibodies and an antigen-positive fetus incompatible with the maternal alloantibody. Patients with ABO-incompatibility only were excluded. We assessed serological diagnostics and referrals, antenatal treatment and timing, complications, delivery route, and gestational age at birth. Outcomes were analysed in all eligible participants who had complete data available.nnFINDINGS: 2443 pregnancies with haemolytic disease of the fetus and newborn treated between Jan 1, 2006, and July 1, 2021, were shared by the centres and analysed between Dec 1, 2021, and March 1, 2023. 23 pregnancies were excluded due to missing information and we included 2420 for further analysis. 1764 (72·9%) of 2420 pregnancies were affected by D-antibodies. 95 (3·9%) of 2420 pregnancies resulted in fetal death. Of the 2325 liveborn neonates, 1349 (58·1%) received any form of antenatal treatment and 976 (41·9%) were only treated postnatally. Median gestational age at referral was 20·4 weeks (IQR 14·9-28·0) and ranged between medians of 10·0 and 26·3 weeks between centres. Severe hydrops at first intrauterine transfusion was present in 185 (14·5%) of 1276 pregnancies, with proportions ranging between 0 and 42% between centres. A median of two intrauterine transfusions (IQR 1-4) were done per pregnancy. The fetal access sites used in intrauterine transfusions varied widely between centres. Non-lethal complications in intrauterine transfusions by transfusion site occurred at a lower rate in intrahepatic approaches (2·0%, 95% CI 1·1-3·3) than in placental insertion (6·9%, 5·8-8·0) and free loop (13·3%, 8·9-18·9). The use and indication for intravenous immunoglobulin administration varied widely. Neonates with intrauterine transfusion were born at a median gestational age of 35·6 weeks (IQR 34·0-36·7), ranging between medians of 33·2 and 37·3 weeks between centres, while neonates without antenatal treatment were born at a median gestational age of 37·3 (IQR 36·3-38·1), ranging between medians of 34·9 and 38·9 weeks between centres.nnINTERPRETATION: We found considerable variation in antenatal management and outcomes in haemolytic disease of the fetus and newborn between sites in different countries. Our study shows the capacity of the field to gather valuable data on a rare disease and to optimise care.nnFUNDING: None.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39115062,

title = {Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn},

author = {Kenneth J Moise and Leona E Ling and Dick Oepkes and Eleonor Tiblad and E J T Joanne Verweij and Enrico Lopriore and John Smoleniec and Ulrich J Sachs and Gregor Bein and Mark D Kilby and Russell S Miller and Roland Devlieger and François Audibert and Stephen P Emery and Kara Markham and Mary E Norton and Olga Ocón-Hernández and Pranav Pandya and Leonardo Pereira and Robert M Silver and Rory Windrim and James B Streisand and Jocelyn H Leu and Arpana Mirza and Valerie Smith and Lisa B Schwartz and May Lee Tjoa and Shumyla Saeed-Khawaja and Yosuke Komatsu and James B Bussel and },

doi = {10.1056/NEJMoa2314466},

issn = {1533-4406},

year  = {2024},

date = {2024-08-01},

journal = {N Engl J Med},

volume = {391},

number = {6},

pages = {526--537},

abstract = {BACKGROUND: In early-onset severe hemolytic disease of the fetus and newborn (HDFN), transplacental transfer of maternal antierythrocyte IgG alloantibodies causes fetal anemia that leads to the use of high-risk intrauterine transfusions in order to avoid fetal hydrops and fetal death. Nipocalimab, an anti-neonatal Fc receptor blocker, inhibits transplacental IgG transfer and lowers maternal IgG levels.nnMETHODS: In an international, open-label, single-group, phase 2 study, we assessed treatment with intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) administered from 14 to 35 weeks' gestation in participants with pregnancies at high risk for recurrent early-onset severe HDFN. The primary end point was live birth at 32 weeks' gestation or later without intrauterine transfusions as assessed against a historical benchmark (0%; clinically meaningful difference, 10%).nnRESULTS: Live birth at 32 weeks' gestation or later without intrauterine transfusions occurred in 7 of 13 pregnancies (54%; 95% confidence interval, 25 to 81) in the study. No cases of fetal hydrops occurred, and 6 participants (46%) did not receive any antenatal or neonatal transfusions. Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks' gestation or later and one fetus before fetal loss at 22 weeks and 5 days' gestation. Live birth occurred in 12 pregnancies. The median gestational age at delivery was 36 weeks and 4 days. Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion and 5 received only simple transfusions. Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood. No unusual maternal or pediatric infections were observed. Serious adverse events were consistent with HDFN, pregnancy, or prematurity.nnCONCLUSIONS: Nipocalimab treatment delayed or prevented fetal anemia or intrauterine transfusions, as compared with the historical benchmark, in pregnancies at high risk for early-onset severe HDFN. (Funded by Janssen Research and Development; UNITY ClinicalTrials.gov number, NCT03842189.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39124733,

title = {Prenatal Diagnosis, Course and Outcome of Patients with Truncus Arteriosus Communis},

author = {Aline Wolter and Annika Haessig and Andrii Kurkevych and Jan Weichert and Stephan Bosselmann and Gunther Mielke and Ivonne Alexandra Bedei and Johanna Schenk and Ellydda Widriani and Roland Axt-Fliedner},

doi = {10.3390/jcm13154465},

issn = {2077-0383},

year  = {2024},

date = {2024-07-01},

journal = {J Clin Med},

volume = {13},

number = {15},

abstract = {: The objective of our study was to assess the prenatal course, associated anomalies and postnatal outcome and the predictive value of various prenatal parameters for survival in prenatally diagnosed cases of truncus arteriosus communis (TAC). : We evaluated cases from four centers between 2008 and 2021. : In 37/47 cases (78.7%), classification into a Van Praagh sbtype was possible, most had TAC type A1 (18/37 = 48.6%). In 33/47 (70.2%) with available valve details on common trunk valve, most presented with tricuspid valves (13/33 = 39.4%). In the overall sample, 14/47 (29.8%) had relevant insufficiency, and 8/47 (17%) had stenosis. In total, 37/47 (78.7%) underwent karyotyping, with 15/37 (40.5%) showing abnormal results, mainly 22q11.2 microdeletion (9/37 = 24.3%). Overall, 17/47 (36.2%) had additional extracardiac anomalies (17/47 = 36.2%). Additional intracardiac anomalies were present in 30/47 (63.8%), or 32/47 (68.1%) if coronary anomalies were included. Four (8.5%) had major defects. Two (4.3%) intrauterine deaths occurred, in 10 (21.3%) cases, the parents opted for termination, predominantly in non-isolated cases (8/10 = 80.0%). A total of 35/47 (74.5%) were born alive at 39 (35-41) weeks. Three (8.6%) pre-surgical deaths occurred in non-isolated cases. In 32/35 (91.4%), correction surgery was performed. The postoperative survival rate was 84.4% (27/32) over a median follow-up of 51.5 months. Initial intervention was performed 16 (1-71) days postpartum, and 22/32 (68.8%) required re-intervention. Regarding prenatal outcome-predicting parameters, no significant differences were identified between the survivor and non-survivor groups. : There exist limited outcome data for TAC. To our knowledge, this is the largest multicenter, prenatal cohort with an intention-to-treat survival rate of almost 85%.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38748847,

title = {Clinical practice guidelines for the care of girls and women with Turner syndrome},

author = {Claus H Gravholt and Niels H Andersen and Sophie Christin-Maitre and Shanlee M Davis and Anthonie Duijnhouwer and Aneta Gawlik and Andrea T Maciel-Guerra and Iris Gutmark-Little and Kathrin Fleischer and David Hong and Karen O Klein and Siddharth K Prakash and Roopa Kanakatti Shankar and David E Sandberg and Theo C J Sas and Anne Skakkebæk and Kirstine Stochholm and Janielle A van der Velden and  and Philippe F Backeljauw},

doi = {10.1093/ejendo/lvae050},

issn = {1479-683X},

year  = {2024},

date = {2024-06-01},

journal = {Eur J Endocrinol},

volume = {190},

number = {6},

pages = {G53--G151},

abstract = {Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38792648,

title = {Prenatal Diagnosis of Fryns Syndrome through Identification of Two Novel Splice Variants in the  Gene-A Case Series},

author = {Aruna Marchetto and Susanne Leidescher and Theresia van Hoi and Niklas Hirschberger and Florian Vogel and Siegmund Köhler and Ivonne Alexandra Bedei and Roland Axt-Fliedner and Moneef Shoukier and Corinna Keil},

doi = {10.3390/life14050628},

issn = {2075-1729},

year  = {2024},

date = {2024-05-01},

journal = {Life (Basel)},

volume = {14},

number = {5},

abstract = {Fryns syndrome (FS) is a multiple congenital anomaly syndrome with different multisystemic malformations. These include congenital diaphragmatic hernia, pulmonary hypoplasia, and craniofacial dysmorphic features in combination with malformations of the central nervous system such as agenesis of the corpus callosum, cerebellar hypoplasia, and enlarged ventricles. We present a non-consanguineous northern European family with two recurrent cases of FS: a boy with multiple congenital malformations who died at the age of 2.5 months and a female fetus with a complex developmental disorder with similar features in a following pregnancy. Quad whole exome analysis revealed two likely splicing-affecting disease-causing mutations in the  gene: a synonymous mutation c.2619G>A, p.(Leu873=) in the last nucleotide of exon 29 and a 30 bp-deletion c.996_1023+2del (NM_176787.5) protruding into intron 12, with both mutations in  configuration in the affected patients. Exon skipping resulting from these two variants was confirmed via RNA sequencing. Our molecular and clinical findings identified compound heterozygosity for two novel splice-affecting variants as the underlying pathomechanism for the development of FS in two patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39917608,

title = {Initial experience with the anaesthetic management of fetoscopic spina bifida repair at a German University Hospital: A case series of 15 patients},

author = {Nicolas Schmitt and Ann-Kristin Schubert and Hinnerk Wulf and Corinna Keil and Caitlin Dooley Sutton and Ivonne Bedei and Gerald Kalmus},

doi = {10.1097/EA9.0000000000000047},

issn = {2767-7206},

year  = {2024},

date = {2024-04-01},

journal = {Eur J Anaesthesiol Intensive Care},

volume = {3},

number = {2},

pages = {e0047},

abstract = {Spina bifida aperta (SBA) is a serious neural tube defect that can lead to a range of disabilities and health complications in affected individuals. In recent years, fetoscopic surgical repair has emerged as a promising new approach to treat spina bifida prenatally, offering the potential for improved outcomes compared with traditional open surgery. As one of the few centres in Europe to offer this innovative technique, the Departments of Obstetrics and Gynaecology, Neurosurgery, and Anaesthesiology and Intensive Care Medicine at the University Medical Centre of Marburg (UKGM Marburg) have faced unique challenges in developing and establishing standards of care for the pregnant patients undergoing this complex procedure. In this publication, we aim to present details of our initial experience with the first 15 patients and propose a clinical concept for the rather complex perioperative management of these patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38398455,

title = {Monitoring of Women with Anti-Ro/SSA and Anti-La/SSB Antibodies in Germany-Status Quo and Intensified Monitoring Concepts},

author = {Ivonne Alexandra Bedei and David Kniess and Corinna Keil and Aline Wolter and Johanna Schenk and Ulrich J Sachs and Roland Axt-Fliedner},

doi = {10.3390/jcm13041142},

issn = {2077-0383},

year  = {2024},

date = {2024-02-01},

journal = {J Clin Med},

volume = {13},

number = {4},

abstract = { The fetuses of pregnant women affected by anti-Ro/anti-La antibodies are at risk of developing complete atrioventricular heart block (CAVB) and other potentially life-threatening cardiac affections. CAVB can develop in less than 24 h. Treatment with anti-inflammatory drugs and immunoglobulins (IVIG) can restore the normal rhythm if applied in the transition period. Routine weekly echocardiography, as often recommended, will rarely detect emergent AVB. The surveillance of these pregnancies is controversial. Home-monitoring using a hand-held Doppler is a promising new approach.  To obtain an overview of the current practice in Germany, we developed a web-based survey sent by the DEGUM (German Society of Ultrasound in Medicine) to ultrasound specialists. With the intention to evaluate practicability of home-monitoring, we instructed at-risk pregnant women to use a hand-held Doppler in the vulnerable period between 18 and 26 weeks at our university center.  There are trends but no clear consensus on surveillance, prophylaxis, and treatment of anti-Ro/La positive pregnant between specialists in Germany. Currently most experts do not offer home-monitoring but have a positive attitude towards its prospective use. Intensified fetal monitoring using a hand-held Doppler is feasible for pregnant women at risk and does not lead to frequent and unnecessary contact with the center.  Evidence-based guidelines are needed to optimize the care of anti-Ro/La-positive pregnant women. Individual risk stratification could help pregnancy care of women at risk and is welcmed by most experts. Hand-held doppler monitoring is accepted by patients and prenatal medicine specialists as an option for intensified monitoring and can be included in an algorithm for surveillance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38363396,

title = {Two-dimensional speckle tracking echocardiography in fetuses with critical aortic stenosis before and after fetal aortic valvuloplasty},

author = {Justus G Reitz and Johanna M Meier and Christoph Berg and Eva C Weber and Ulrich Gembruch and Aline Wolter and Vanessa Sterzbecher and Ivonne Bedei and Roland Axt-Fliedner},

doi = {10.1007/s00404-024-07376-7},

issn = {1432-0711},

year  = {2024},

date = {2024-02-01},

journal = {Arch Gynecol Obstet},

abstract = {BACKGROUND: Critical aortic stenosis (AS) in fetuses may progress to hypoplastic left heart syndrome (HLHS) with need for postnatal single ventricular (SV) palliation. Fetal aortic valvuloplasty (FAV) is performed to achieve postnatal biventricular (BV) circulation. However, the impact of FAV on fetal myocardial function is difficult to measure. Prediction of postnatal circulatory status and, therefore, counseling is challenging.nnMETHODS: Retrospective study of fetuses with critical AS who underwent FAV. Global Longitudinal Peak Systolic Strain (GLPSS) of the left ventricle (LV) and right ventricle (RV) were retrospectively analyzed before and after intervention. Fisher's Exact Test and Mann-Whitney-U Test were used for univariant statistical analysis.nnRESULTS: 23 fetuses with critical AS were included. After intervention fetuses demonstrated more negative LV-GLPSS mean values post- vs. pre-intervention (- 5.36% vs. - 1.57%; p < 0.05). RV-GLPSS was decreased in all fetuses, there was no peri-interventional change. 20 fetuses were born alive. Postnatally, 10 had BV and 10 SV circulation. Improved post-interventional LV-GLPSS strain values correlated with BV outcome (p < 0.05). Pre-interventional continuous LV-GLPSS values correlated with postnatal SV vs. BV outcome (p < 0.05).nnCONCLUSION: In some fetuses, LV myocardial function assessed by speckle tracking echocardiography (STE) improves after FAV. Improved post-interventional LV-GLPSS correlates with biventricular postnatal outcome. Furthermore, pre-interventional LV- and RV-GLPSS correlate with postnatal outcome. Further studies are needed to asses, if pre-interventional STE parameters might predict which fetuses will benefit from FAV with postnatal BV circulation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37698345,

title = {Perforation of cavum septi pellucidi in open spina bifida and need for hydrocephalus treatment by 1 year of age},

author = {M Sanz Cortes and R M Johnson and H Sangi-Haghpeykar and I Bedei and L Greenwood and A A Nassr and R Donepudi and W Whitehead and M Belfort and A R Mehollin-Ray},

doi = {10.1002/uog.27480},

issn = {1469-0705},

year  = {2024},

date = {2024-01-01},

journal = {Ultrasound Obstet Gynecol},

volume = {63},

number = {1},

pages = {60--67},

abstract = {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.nnMETHODS: 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/m 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.nnRESULTS: 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).nnCONCLUSIONS: 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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38337754,

title = {Associated Anomalies and Outcome in Patients with Prenatal Diagnosis of Aortic Arch Anomalies as Aberrant Right Subclavian Artery, Right Aortic Arch and Double Aortic Arch},

author = {Roland Axt-Fliedner and Asia Nazar and Ivonne Bedei and Johanna Schenk and Maleen Reitz and Stefan Rupp and Christian Jux and Aline Wolter},

doi = {10.3390/diagnostics14030238},

issn = {2075-4418},

year  = {2024},

date = {2024-01-01},

journal = {Diagnostics (Basel)},

volume = {14},

number = {3},

abstract = {We aimed to evaluate retrospectively associated anomalies and outcome in prenatal aortic arch anomalies (AAAs). We included ninety patients with aberrant right subclavian artery (ARSA), right aortic arch (RAA) with mirror image branching (RAA-mirror) or aberrant left subclavian artery (RAA-ALSA) and double aortic arch (DAA) between 2011 and 2020. In total, 19/90 (21.1%) had chromosomal anomalies, the highest rate being within the ARSA subgroup (17/46, 37%). All (13/13) of the RAA-mirror subgroup, 10/27 (37.0%) of RAA-ALSA, 13/46 (28.3%) of ARSA and 0/4 within the DAA subgroup had additional intracardiac anomaly. The rate of extracardiac anomalies was 30.7% in RAA-mirror, 28.3% in ARSA, 25.0% in DAA and 22.2% in the RAA-ALSA subgroup. A total of 42/90 (46.7%) had isolated AAAs: three (7.1%) with chromosomal anomalies, all trisomy 21 (3/26, 11.5%) within the ARSA subgroup. Out of 90, 19 (21.1%) were lost to follow-up (FU). Two (2.2%) intrauterine deaths occurred, and six (6.7%) with chromosomal anomalies terminated their pregnancy. In total, 63 (70.0%) were liveborn, 3/63 (4.8%) with severe comorbidity had compassionate care and 3/60 (5.0%) were lost to FU. The survival rate in the intention-to-treat cohort was 53/57 (93%). Forty-one (77.4%) presented with vascular ring/sling, two (4.9%) with RAA-ALSA developed symptoms and one (2.4%) needed an operation. We conclude that intervention due to vascular ring is rarely necessary. NIPT could be useful in isolated ARSA cases without higher a priori risk for trisomy 21 and after exclusion of other anomalies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38013494,

title = {Prenatal diagnosis and postnatal outcome of closed spinal dysraphism},

author = {Ivonne Bedei and Eyal Krispin and Magdalena Sanz Cortes and Hennie Lombaard and Roni Zemet and William E Whitehead and Michael A Belfort and Thierry A G M Huisman},

doi = {10.1002/pd.6454},

issn = {1097-0223},

year  = {2023},

date = {2023-11-01},

journal = {Prenat Diagn},

abstract = {OBJECTIVE: To evaluate the prenatal diagnosis of closed dysraphism (CD) and its correlation with postnatal findings and neonatal adverse outcomes.nnMETHODS: A retrospective cohort study including pregnancies diagsnosed with fetal CD by prenatal ultrasound (US) and magnetic resonance imaging (MRI) at a single tertiary center between September 2011 and July 2021.nnRESULTS: CD was diagnosed prenatally and confirmed postnatally in 12 fetuses. The mean gestational age of prenatal imaging was 24.2 weeks, in 17% the head circumference was ≤fifth percentile and in 25% the cerebellar diameter was ≤fifth percentile. US findings included banana sign in 17%, and lemon sign in 33%. On MRI, posterior fossa anomalies were seen in 33% of cases, with hindbrain herniation below the foramen magnum in two cases. Mean clivus-supraocciput angle (CSA) was 74°. Additional anomalies outside the CNS were observed in 50%. Abnormal foot position was demonstrated prenatally in 17%. Neurogenic bladder was present in 90% of patients after birth.nnCONCLUSION: Arnold Chiari II malformation and impaired motor function can be present on prenatal imaging of fetuses with CD and may be associated with a specific type of CD. Prenatal distinction of CD can be challenging. Associated extra CNS anomalies are frequent and the rate of neurogenic urinary tract dysfunction is high.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37568553,

title = {Implementation and Assessment of a Laparotomy-Assisted Three-Port Fetoscopic Spina Bifida Repair Program},

author = {Corinna Keil and Siegmund Köhler and Benjamin Sass and Maximilian Schulze and Gerald Kalmus and Michael Belfort and Nicolas Schmitt and Daniele Diehl and Alice King and Stefanie Groß and Caitlin D Sutton and Luc Joyeux and Mirjam Wege and Christopher Nimsky and Wiliam E Whitehead and Eberhard Uhl and Thierry A G M Huisman and Bernd A Neubauer and Stefanie Weber and Helmut Hummler and Roland Axt-Fliedner and Ivonne Bedei},

doi = {10.3390/jcm12155151},

issn = {2077-0383},

year  = {2023},

date = {2023-08-01},

journal = {J Clin Med},

volume = {12},

number = {15},

abstract = {Open spina bifida (OSB) is a congenital, non-lethal malformation with multifactorial etiology. Fetal therapy can be offered under certain conditions to parents after accurate prenatal diagnostic and interdisciplinary counseling. Since the advent of prenatal OSB surgery, various modifications of the original surgical techniques have evolved, including laparotomy-assisted fetoscopic repair. After a two-year preparation time, the team at the University of Giessen and Marburg (UKGM) became the first center to provide a three-port, three-layer fetoscopic repair of OSB via a laparotomy-assisted approach in the German-speaking area. We point out that under the guidance of experienced centers and by intensive multidisciplinary preparation and training, a previously described and applied technique could be transferred to a different setting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35304733b,

title = {Analysis of the Results of Sonographic Screening Examinations According to the Maternity Guidelines Before and After the Introduction of the Extended Basic Screening (IIb Screening) in Hesse},

author = {Christine Schmand and Björn Misselwitz and Helge Hudel and Ivonne Bedei and Aline Wolter and Johanna Schenk and Corinna Keil and Siegmund Köhler and Roland Axt-Fliedner},

doi = {10.1055/a-1778-3585},

issn = {1438-8782},

year  = {2023},

date = {2023-08-01},

journal = {Ultraschall Med},

volume = {44},

number = {4},

pages = {e175--e183},

abstract = {AIM OF THE STUDY: The aim of the study is to examine the detection rates of malformations before and after the introduction of extended basic screening in Hesse by the Federal Joint Committee (Gemeinsamer Bundesausschuss, GQH) on July 1, 2013.nnMETHOD: This is a retrospective, mainly exploratory data analysis of quality assurance data from the Office for Quality Assurance in Hesse (GQH). The data was collected in the period from January 1, 2010 to December 31, 2016 in the obstetric departments of the Hessian hospitals using documentation forms. The classification and evaluation of the diagnoses is based on ICD-10-GM-2019.nnRESULTS: At least one malformation is present in 0.7% of the cases. With a share of 30.0%, most of the congenital malformations are from the musculoskeletal system. 12.2% of the malformations come from the facial cleft, closely followed by malformations of the circulatory system with 11.3%. The highest prenatal detection rate (PDR) is found in congenital malformations of the nervous system at 56.8%. The lowest PDR is found in those of the genital organs with 2.1%. The PDR of cardiovascular malformations is 32.9%. Overall, a PDR of 25.2% is achieved. There was no change in the number of prenatal malformation diagnoses after the introduction of extended basic ultrasound. The distribution of malformation diagnoses not detected prenatally to the organ systems also has not changed after the introduction.nnCONCLUSION: The introduction of extended basic ultrasound did not bring the desired improvement with regard to the PDR in Hesse. Alternative approaches should be considered.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37240614,

title = {Comparison of the Results of Prenatal and Postnatal Echocardiography and Postnatal Cardiac MRI in Children with a Congenital Heart Defect},

author = {Marios Mamalis and Tamara Koehler and Ivonne Bedei and Aline Wolter and Johanna Schenk and Ellyda Widriani and Roland Axt-Fliedner},

doi = {10.3390/jcm12103508},

issn = {2077-0383},

year  = {2023},

date = {2023-05-01},

journal = {J Clin Med},

volume = {12},

number = {10},

abstract = {OBJECTIVE: In fetuses with suspicion of congenital heart disease (CHD), assessment by segmental fetal echocardiography is of great importance. This study sought to examine the concordance of expert fetal echocardiography and postnatal MRI of the heart at a high-volume paediatric heart centre.nnMETHODS: The data of two hundred forty-two fetuses have been gathered under the condition of full pre- and postnatal and the presence of a pre- and postnatal diagnosis of CHD. The haemodynamically leading diagnosis was determined for each test person and was then sorted into diagnostic groups. The diagnoses and diagnostic groups were used for the comparison of diagnostic accuracy in fetal echocardiography.nnRESULTS: All comparisons between the diagnostic methods for detection of congenital heart disease showed an "almost perfect" (Cohen's Kappa > 0.9) strength of agreement for the diagnostic groups. The diagnosis made by prenatal echocardiography showed a sensitivity of 90-100%, a specificity and a negative predictive value of 97-100%, and a positive predictive value of 85-100%. The diagnostic congruence resulted in an "almost perfect" strength of agreement for all evaluated diagnoses (transposition of great arteries, double outlet right ventricle, hypoplastic left heart, tetralogy of Fallot, atrioventricular septal defect). An agreement of Cohen's Kappa > 0.9 was achieved for all groups, with exception of the diagnosis of double outlet right ventricle (0.8) in prenatal echocardiography compared to postnatal echocardiography. This study came to the result of a sensitivity of 88-100%, a specificity and negative predictive value of 97-100%, and a positive predictive value of 84-100%. The performance of cardiac magnetic resonance imaging (MRI) as an additional measure to echocardiography had an added value in the description of the malposition of the great arteries when diagnosed with double outlet right ventricle and in the detailed description of the anatomy of the lung circulation.nnCONCLUSIONS: Prenatal echocardiography could be shown to be a reliable method for detection of congenital heart disease when regarding the slightly lower accuracy of diagnosis for double outlet right ventricle and right heart anomalies. Furthermore, the impact of examiner experience and the consideration of follow-up examinations for further improvement of diagnosis accuracy may not be underestimated. The main advantage of an additional MRI is the possibility to obtain a detailed anatomic description of the blood vessels of the lung and the outflow tract. The conduction of further studies that include false-negative and false-positive cases, and studies that are not set within the high-risk-group, as well as studies in a less specialized setting, would allow the completion and investigation of possible differences and discrepancies when comparing the results that have been obtained in this study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36726284,

title = {Multicenter clinical experience with non-invasive cell-free DNA screening for monosomy X and related X-chromosome variants},

author = {Ivonne Bedei and Tascha Gehrke and Karl-Philipp Gloning and Matthias Meyer-Wittkopf and Daria Willner and Martin Krapp and Alexander Scharf and Jan Degenhardt and Kai-Sven Heling and Peter Kozlowski and Kathrin Trautmann and Kai M Jahns and Annegret Geipel and Jan-Erik Baumüller and Lucas Wilhelm and Ingo Gottschalk and Andreas Schröer and Alexander Graf and Aline Wolter and Johanna Schenk and Axel Weber and Ignatia B Van den Veyver and Roland Axt-Fliedner},

doi = {10.1002/pd.6320},

issn = {1097-0223},

year  = {2023},

date = {2023-02-01},

journal = {Prenat Diagn},

volume = {43},

number = {2},

pages = {192--206},

abstract = {OBJECTIVE: We aimed to investigate how the presence of fetal anomalies and different X chromosome variants influences Cell-free DNA (cfDNA) screening results for monosomy X.nnMETHODS: From a multicenter retrospective survey on 673 pregnancies with prenatally suspected or confirmed Turner syndrome, we analyzed the subgroup for which prenatal cfDNA screening and karyotype results were available. A cfDNA screening result was defined as true positive (TP) when confirmatory testing showed 45,X or an X-chromosome variant.nnRESULTS: We had cfDNA results, karyotype, and phenotype data for 55 pregnancies. cfDNA results were high risk for monosomy X in 48/55, of which 23 were TP and 25 were false positive (FP). 32/48 high-risk cfDNA cases did not show fetal anomalies. Of these, 7 were TP. All were X-chromosome variants. All 16 fetuses with high-risk cfDNA result and ultrasound anomalies were TP. Of fetuses with abnormalities, those with 45,X more often had fetal hydrops/cystic hygroma, whereas those with "variant" karyotypes had different anomalies.nnCONCLUSION: Both, 45,X or X-chromosome variants can be detected after a high-risk cfDNA result for monosomy X. When there are fetal anomalies, the result is more likely a TP. In the absence of fetal anomalies, it is most often an FP or X-chromosome variant.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36600414,

title = {Turner syndrome-omphalocele association: Incidence, karyotype, phenotype and fetal outcome},

author = {Ivonne Bedei and Karl-Philipp Gloning and Luc Joyeux and Matthias Meyer-Wittkopf and Daria Willner and Martin Krapp and Alexander Scharf and Jan Degenhardt and Kai-Sven Heling and Peter Kozlowski and Kathrin Trautmann and Kai M Jahns and Annegret Geipel and Ismail Tekesin and Michael Elsässer and Lucas Wilhelm and Ingo Gottschalk and Jan-Erik Baumüller and Cahit Birdir and Andreas Schröer and Felix Zöllner and Aline Wolter and Johanna Schenk and Tascha Gehrke and Alicia Spaeth and Roland Axt-Fliedner},

doi = {10.1002/pd.6302},

issn = {1097-0223},

year  = {2023},

date = {2023-02-01},

journal = {Prenat Diagn},

volume = {43},

number = {2},

pages = {183--191},

abstract = {OBJECTIVE: Omphalocele is known to be associated with genetic anomalies like trisomy 13, 18 and Beckwith-Wiedemann syndrome, but not with Turner syndrome (TS). Our aim was to assess the incidence of omphalocele in fetuses with TS, the phenotype of this association with other anomalies, their karyotype, and the fetal outcomes.nnMETHOD: Retrospective multicenter study of fetuses with confirmed diagnosis of TS. Data were extracted from a detailed questionnaire sent to specialists in prenatal ultrasound.nnRESULTS: 680 fetuses with TS were included in this analysis. Incidence of small omphalocele in fetuses diagnosed ≥12 weeks was 3.1%. Including fetuses diagnosed before 12 weeks, it was 5.1%. 97.1% (34/35) of the affected fetuses had one or more associated anomalies including increased nuchal translucency (≥3 mm) and/or cystic hygroma (94.3%), hydrops/skin edema (71.1%), and cardiac anomalies (40%). The karyotype was 45,X in all fetuses. Fetal outcomes were poor with only 1 fetus born alive.nnCONCLUSION: TS with 45,X karyotype but not with X chromosome variants is associated with small omphalocele. Most of these fetuses have associated anomalies and a poor prognosis. Our data suggest an association of TS with omphalocele, which is evident from the first trimester.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36556157,

title = {The Value of Delta Middle Cerebral Artery Peak Systolic Velocity for the Prediction of Twin Anemia-Polycythemia Sequence-Analysis of a Heterogenous Cohort of Monochorionic Twins},

author = {Anthea de Sainte Fare and Ivonne Bedei and Aline Wolter and Johanna Schenk and Ellydda Widriani and Corinna Keil and Siegmund Koehler and Franz Bahlmann and Brigitte Strizek and Ulrich Gembruch and Christoph Berg and Roland Axt-Fliedner},

doi = {10.3390/jcm11247541},

issn = {2077-0383},

year  = {2022},

date = {2022-12-01},

journal = {J Clin Med},

volume = {11},

number = {24},

abstract = {Introduction: Twin anemia-polycythemia sequence (TAPS) is a complication in monochorionic-diamniotic (MCDA) twin pregnancies. This study analyzes whether the prenatal diagnosis using delta middle cerebral artery-peak systolic velocity (MCA-PSV) > 0.5 multiples of the median (MoM) (delta group) detects more TAPS cases than the guideline-based diagnosis using the MCA-PSV cut off levels of >1.5 and <1.0 MoM (cut-off group), in a heterogenous group of MCDA twins. Methods: A retrospective analysis of 348 live-born MCDA twin pregnancies from 2010 to 2021 with available information on MCA-PSV within one week before delivery and hemoglobin-values within 24 h postnatally were considered eligible. Results: Among postnatal confirmed twin pairs with TAPS, the cut-off group showed lower sensitivity than the delta group (33% vs. 82%). Specificity proved higher in the cut-off group with 97% than in the delta group at 86%. The risk that a TAPS is mistakenly not recognized prenatally is higher in the cut-off group than in the delta group (52% vs. 18%). Conclusions: Our data shows that delta MCA-PSV > 0.5 MoM detects more cases of TAPS, which would not have been diagnosed prenatally according to the current guidelines. In the collective examined in the present study, TAPS diagnostics using delta MCA-PSV proved to be a more robust method.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34652254b,

title = {Fetal therapy of LUTO (lower urinary tract obstruction) - a follow-up observational study},

author = {Corinna Keil and Ivonne Bedei and Lara Sommer and Martin Koemhoff and Roland Axt-Fliedner and Siegmund Köhler and Stefanie Weber},

doi = {10.1080/14767058.2021.1988562},

issn = {1476-4954},

year  = {2022},

date = {2022-12-01},

journal = {J Matern Fetal Neonatal Med},

volume = {35},

number = {25},

pages = {8536--8543},

abstract = {PURPOSE: Fetal megacystis (MC) can be severe and is mainly caused by fetal lower urinary tract obstruction (LUTO). Mortality of fetal LUTO can be high as a result of pulmonary hypoplasia and/or (chronic) renal insufficiency. Several technical procedures for vesicoamniotic shunting (VAS) were developed to improve fetal MC outcomes.



MATERIAL AND METHODS: We present the outcome of nine fetuses with MC who received VAS in the prenatal period (14 + 6 to 27 + 6 weeks GA) using the Somatex intrauterine shunt system. MC was defined as an increased longitudinal measurement of the bladder >15 mm. The median follow-up time after birth was 18 months.



RESULTS: Eight Fetuses had uncomplicated VAS intervention. One case developed PPROM 24 h after VAS leading to abortion. Pregnancy was later terminated in further two cases. All six live-born infants received intensive care treatment. Invasive-mechanical ventilation was necessary in one case who died 24 h post-partum of severe cardiac depression. Five infants who survived the follow-up time developed chronic renal insufficiency (CRI), with one infant developing end-stage renal failure requiring peritoneal dialysis.



CONCLUSION: Overall, 5 of 9 LUTO fetuses (55%) undergoing VAS with the Somatex intrauterine shunt system showed long-term survival beyond the neonatal period of 28 d (5/9; 55%) with varying morbidity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36498602,

title = {The Evolution and Developing Importance of Fetal Magnetic Resonance Imaging in the Diagnosis of Congenital Cardiac Anomalies: A Systematic Review},

author = {Marios Mamalis and Ivonne Bedei and Bjoern Schoennagel and Fabian Kording and Justus G Reitz and Aline Wolter and Johanna Schenk and Roland Axt-Fliedner},

doi = {10.3390/jcm11237027},

issn = {2077-0383},

year  = {2022},

date = {2022-11-01},

journal = {J Clin Med},

volume = {11},

number = {23},

abstract = {Magnetic Resonance Imaging (MRI) is a reliable method, with a complementary role to Ultrasound (US) Echocardiography, that can be used to fully comprehend and precisely diagnose congenital cardiac malformations. Besides the anatomical study of the fetal cardiovascular system, it allows us to study the function of the fetal heart, remaining, at the same time, a safe adjunct to the classic fetal echocardiography. MRI also allows for the investigation of cardiac and placental diseases by providing information about hematocrit, oxygen saturation, and blood flow in fetal vessels. It is crucial for fetal medicine specialists and pediatric cardiologists to closely follow the advances of fetal cardiac MRI in order to provide the best possible care. In this review, we summarize the advance in techniques and their practical utility to date.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35956203,

title = {Is Fetal Hydrops in Turner Syndrome a Risk Factor for the Development of Maternal Mirror Syndrome?},

author = {Ivonne Alexandra Bedei and Alexander Graf and Karl-Philipp Gloning and Matthias Meyer-Wittkopf and Daria Willner and Martin Krapp and Sabine Hentze and Alexander Scharf and Jan Degenhardt and Kai-Sven Heling and Peter Kozlowski and Kathrin Trautmann and Kai Jahns and Anne Geipel and Ismail Tekesin and Michael Elsässer and Lucas Wilhelm and Ingo Gottschalk and Jan-Erik Baumüller and Cahit Birdir and Felix Zöllner and Aline Wolter and Johanna Schenk and Tascha Gehrke and Corinna Keil and Jimmy Espinosa and Roland Axt-Fliedner},

doi = {10.3390/jcm11154588},

issn = {2077-0383},

year  = {2022},

date = {2022-08-01},

journal = {J Clin Med},

volume = {11},

number = {15},

abstract = {Mirror syndrome is a rare and serious maternal condition associated with immune and non-immune fetal hydrops after 16 weeks of gestational age. Subjacent conditions associated with fetal hydrops may carry different risks for Mirror syndrome. Fetuses with Turner syndrome are frequently found to be hydropic on ultrasound. We designed a retrospective multicenter study to evaluate the risk for Mirror syndrome among pregnancies complicated with Turner syndrome and fetal hydrops. Data were extracted from a questionnaire sent to specialists in maternal fetal medicine in Germany. Out of 758 cases, 138 fulfilled our inclusion criteria and were included in the analysis. Of the included 138, 66 presented with persisting hydrops at or after 16 weeks. The frequency of placental hydrops/placentomegaly was rather low (8.1%). Of note, no Mirror syndrome was observed in our study cohort. We propose that the risk of this pregnancy complication varies according to the subjacent cause of fetal hydrops. In Turner syndrome, the risk for Mirror syndrome is lower than that reported in the literature. Our observations are relevant for clinical management and parental counseling.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35304733,

title = {Analysis of the Results of Sonographic Screening Examinations According to the Maternity Guidelines Before and After the Introduction of the Extended Basic Screening (IIb Screening) in Hesse},

author = {Christine Schmand and Björn Misselwitz and Helge Hudel and Ivonne Bedei and Aline Wolter and Johanna Schenk and Corinna Keil and Siegmund Köhler and Roland Axt-Fliedner},

doi = {10.1055/a-1778-3585},

issn = {1438-8782},

year  = {2022},

date = {2022-03-01},

journal = {Ultraschall Med},

abstract = {AIM OF THE STUDY: The aim of the study is to examine the detection rates of malformations before and after the introduction of extended basic screening in Hesse by the Federal Joint Committee (Gemeinsamer Bundesausschuss, GQH) on July 1, 2013.



METHOD: This is a retrospective, mainly exploratory data analysis of quality assurance data from the Office for Quality Assurance in Hesse (GQH). The data was collected in the period from January 1, 2010 to December 31, 2016 in the obstetric departments of the Hessian hospitals using documentation forms. The classification and evaluation of the diagnoses is based on ICD-10-GM-2019.



RESULTS: At least one malformation is present in 0.7% of the cases. With a share of 30.0%, most of the congenital malformations are from the musculoskeletal system. 12.2% of the malformations come from the facial cleft, closely followed by malformations of the circulatory system with 11.3%. The highest prenatal detection rate (PDR) is found in congenital malformations of the nervous system at 56.8%. The lowest PDR is found in those of the genital organs with 2.1%. The PDR of cardiovascular malformations is 32.9%. Overall, a PDR of 25.2% is achieved. There was no change in the number of prenatal malformation diagnoses after the introduction of extended basic ultrasound. The distribution of malformation diagnoses not detected prenatally to the organ systems also has not changed after the introduction.



CONCLUSION: The introduction of extended basic ultrasound did not bring the desired improvement with regard to the PDR in Hesse. Alternative approaches should be considered.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35327684,

title = {Neonatal Outcome and Treatment Perspectives of Preterm Infants at the Border of Viability},

author = {Rahel Schuler and Ivonne Bedei and Frank Oehmke and Klaus-Peter Zimmer and Harald Ehrhardt},

doi = {10.3390/children9030313},

issn = {2227-9067},

year  = {2022},

date = {2022-02-01},

journal = {Children (Basel)},

volume = {9},

number = {3},

abstract = {Decision-making at the border of viability remains challenging for the expectant parents and the medical team. The preterm infant is dependent on others making the decision that will impact them for a lifetime in hopefully their best interest. Besides survival and survival without neurodevelopmental impairment, other relevant outcome measures, such as the quality of life of former preterm infants and the impact on family life, need to be integrated into prenatal counselling. Recommendations and national guidelines continue to rely on arbitrarily set gestational age limits at which treatment is not recommended, can be considered and it is recommended. These guidelines neglect other individual prognostic outcome factors like antenatal steroids, birth weight and gender. Besides individual factors, centre-specific factors like perinatal treatment intensity and the attitude of healthcare professionals significantly determine the futures of these infants at the border of viability. A more comprehensive approach regarding treatment recommendations and relevant outcome measures is necessary.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35204956,

title = {New Challenges with Treatment Advances in Newborn Infants with Genetic Disorders and Severe Congenital Malformations},

author = {Rahel Schuler and Ivonne Bedei and Frank Oehmke and Klaus-Peter Zimmer and Harald Ehrhardt},

doi = {10.3390/children9020236},

issn = {2227-9067},

year  = {2022},

date = {2022-02-01},

journal = {Children (Basel)},

volume = {9},

number = {2},

abstract = {Advances in the prognosis of relevant syndromes and severe congenital malformations in infants during the last few decades have enabled the treatment and survival of an ever-increasing number of infants, whose prospects were previously judged futile by professional health care teams. This required detailed counselling for families, which frequently started before birth when a diagnosis was made using genetic testing or ultrasound. Predictions of the estimated prognosis, and frequently the more-or-less broad range of prospects, needed to include the chances of survival and data on acute and long-term morbidities. However, in the interest of a having an informed basis for parental decision-making with a professional interdisciplinary team, this process needs to acknowledge the rights of the parents for a comprehensive presentation of the expected quality of life of their child, the potential consequences for family life, and the couple's own relationship. Besides expert advice, professional psychological and familial support is needed as a basis for a well-founded decision regarding the best treatment options for the child. It needs to be acknowledged by the professional team that the parental estimate of a "good outcome" or quality of life does not necessarily reflect the attitudes and recommendations of the professional team. Building a mutually trusting relationship is essential to avoid decision conflicts.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34652254,

title = {Fetal therapy of LUTO (lower urinary tract obstruction) - a follow-up observational study},

author = {Corinna Keil and Ivonne Bedei and Lara Sommer and Martin Koemhoff and Roland Axt-Fliedner and Siegmund Köhler and Stefanie Weber},

doi = {10.1080/14767058.2021.1988562},

issn = {1476-4954},

year  = {2021},

date = {2021-10-01},

journal = {J Matern Fetal Neonatal Med},

pages = {1--8},

abstract = {PURPOSE: Fetal megacystis (MC) can be severe and is mainly caused by fetal lower urinary tract obstruction (LUTO). Mortality of fetal LUTO can be high as a result of pulmonary hypoplasia and/or (chronic) renal insufficiency. Several technical procedures for vesicoamniotic shunting (VAS) were developed to improve fetal MC outcomes.



MATERIAL AND METHODS: We present the outcome of nine fetuses with MC who received VAS in the prenatal period (14 + 6 to 27 + 6 weeks GA) using the Somatex intrauterine shunt system. MC was defined as an increased longitudinal measurement of the bladder >15 mm. The median follow-up time after birth was 18 months.



RESULTS: Eight Fetuses had uncomplicated VAS intervention. One case developed PPROM 24 h after VAS leading to abortion. Pregnancy was later terminated in further two cases. All six live-born infants received intensive care treatment. Invasive-mechanical ventilation was necessary in one case who died 24 h post-partum of severe cardiac depression. Five infants who survived the follow-up time developed chronic renal insufficiency (CRI), with one infant developing end-stage renal failure requiring peritoneal dialysis.



CONCLUSION: Overall, 5 of 9 LUTO fetuses (55%) undergoing VAS with the Somatex intrauterine shunt system showed long-term survival beyond the neonatal period of 28 d (5/9; 55%) with varying morbidity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33585987,

title = {Natural history of pulmonary atresia with intact ventricular septum (PAIVS) and critical pulmonary stenosis (CPS) and prediction of outcome},

author = {Aline Wolter and Natalia Markert and Jan Sebastian Wolter and Andrii Kurkevych and Jan Degenhardt and Jochen Ritgen and Rüdiger Stressig and Christian Enzensberger and Ivonne Bedei and Carina Vorisek and Johanna Schenk and Oliver Graupner and Markus Khalil and Josef Thul and Christian Jux and Roland Axt-Fliedner},

doi = {10.1007/s00404-020-05929-0},

issn = {1432-0711},

year  = {2021},

date = {2021-01-01},

journal = {Arch Gynecol Obstet},

volume = {304},

number = {1},

pages = {81--90},

abstract = {OBJECTIVES: To analyse prenatal parameters predicting biventricular (BV) outcome in pulmonary atresia with intact ventricular septum/critical pulmonary stenosis (PAIVS/CPS).



METHODS: We evaluated 82 foetuses from 01/08 to 10/18 in 3 centres in intervals 1 (< 24 weeks), 2 (24-30 weeks) and 3 (> 30 weeks).



RESULTS: 61/82 (74.4%) were livebirths, 5 (8.2%) lost for follow-up, 3 (4.9%) had compassionate care leaving 53 (64.6% of the whole cohort and 86.9% of livebirths) with intention to treat. 9 died, 44/53 (83.0%) survived. 24/38 (63.2%) with information on postnatal outcome had BV outcome, 14 (36.8%) non-BV outcome (2 × 1.5 circulation). One with BV outcome had prenatal valvuloplasty. Best single parameter for BV outcome was tricuspid/mitral valve (TV/MV) ratio (AUC 0.93) in intervals 2 and 3 (AUC 0.92). Ventriculo-coronary-arterial communications (VCAC) were present in 11 (78.6%) in non-BV outcome group vs. 2 (8.3%) in BV outcome group (p < 0.001). Tricuspid insufficiency (TI)-Vmax > 2.5 m/s was present in BV outcome group in75.0% (18/24) vs. 14.3% (2/14) in non-BV outcome group. Including the most predictive markers (VCAC presence, TI- Vmax  < 2.5 m/s, TV/MV ratio < cutoff) to a score, non-BV outcome was correctly predicted when > 1 criterion was fulfilled in all cases. After recently published criteria for foetal intervention, only 4/9 (44.4%) and 5/14 (35.7%) in our interval 2 + 3 with predicted non-BV outcome would have been candidates for intervention. Two (1 × intrauterine intervention) in interval 2, two in interval 3 reached BV outcome and one 1.5 circulation without intervention.



CONCLUSION: TV/MV ratio as simple parameter has high predictive value. After our score, non-BV outcome was correctly predicted in all cases. Criteria for foetal intervention must further be evaluated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33805390,

title = {Chances and Challenges of New Genetic Screening Technologies (NIPT) in Prenatal Medicine from a Clinical Perspective: A Narrative Review},

author = {Ivonne Bedei and Aline Wolter and Axel Weber and Fabrizio Signore and Roland Axt-Fliedner},

doi = {10.3390/genes12040501},

issn = {2073-4425},

year  = {2021},

date = {2021-01-01},

journal = {Genes (Basel)},

volume = {12},

number = {4},

abstract = {In 1959, 63 years after the death of John Langdon Down, Jérôme Lejeune discovered trisomy 21 as the genetic reason for Down syndrome. Screening for Down syndrome has been applied since the 1960s by using maternal age as the risk parameter. Since then, several advances have been made. First trimester screening, combining maternal age, maternal serum parameters and ultrasound findings, emerged in the 1990s with a detection rate (DR) of around 90-95% and a false positive rate (FPR) of around 5%, also looking for trisomy 13 and 18. With the development of high-resolution ultrasound, around 50% of fetal anomalies are now detected in the first trimester. Non-invasive prenatal testing (NIPT) for trisomy 21, 13 and 18 is a highly efficient screening method and has been applied as a first-line or a contingent screening approach all over the world since 2012, in some countries without a systematic screening program. Concomitant with the rise in technology, the possibility of screening for other genetic conditions by analysis of cfDNA, such as sex chromosome anomalies (SCAs), rare autosomal anomalies (RATs) and microdeletions and duplications, is offered by different providers to an often not preselected population of pregnant women. Most of the research in the field is done by commercial providers, and some of the tests are on the market without validated data on test performance. This raises difficulties in the counseling process and makes it nearly impossible to obtain informed consent. In parallel with the advent of new screening technologies, an expansion of diagnostic methods has begun to be applied after invasive procedures. The karyotype has been the gold standard for decades. Chromosomal microarrays (CMAs) able to detect deletions and duplications on a submicroscopic level have replaced the conventional karyotyping in many countries. Sequencing methods such as whole exome sequencing (WES) and whole genome sequencing (WGS) tremendously amplify the diagnostic yield in fetuses with ultrasound anomalies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}