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

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

Fetal Endoscopic Tracheal Intubation: Modification of the Fetal Endoscopic Tracheal Intubation Procedure to Establish an Airway in a Fetus with a Congenital Cervical Teratoma.

INTRODUCTION: FETI is a technique where the fetal airway is secured in-utero via intubation by percutaneous endoscopic fetal tracheoscopy under ultrasound guidance. FETI has been described in large fetal neck masses with anatomical airway compression as a feasible airway management strategy and a potential alternative to an EXIT procedure in select cases. CASE PRESENTATION: This report describes the use of a modified FETI procedure under continuous fetoscopic and ultrasound guidance, in a fetus with a large cervical teratoma causing airway displacement and compression. Following the FETI procedure, an uncomplicated caesarean section was performed. The endotracheal tube was in place at the time of birth, and a patent airway was confirmed. CONCLUSION: The modified FETI procedure described in this report represents another technique that can be used to establish an airway in fetuses with challenging upper airway anatomy, potentially mitigating the risks associated with an EXIT procedure.

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case-series.

OBJECTIVES: To characterize a suggestive prenatal imaging pattern of Aicardi syndrome using ultrasound and MR imaging. METHODS: Based on a retrospective international series of Aicardi syndrome cases from tertiary centers encountered over a 20-year period (2000-2020), we investigated the frequencies of the imaging features in order to characterize an imaging pattern highly suggestive of the diagnosis. RESULTS: Among 20 cases included, arachnoid cysts associated with a distortion of the interhemispheric fissure were constantly encountered associated with complete or partial agenesis of the corpus callosum (19/20, 95%). This triad in the presence of other CNS disorganization, such as polymicrogyria (16/17, 94%), heterotopias (15/17, 88%), ventriculomegaly (14/20, 70%), cerebral asymmetry [14/20, 70%]) and less frequently extra-CNS anomaly (ocular anomalies [7/11, 64%], costal/vertebral segmentation defect [4/20, 20%]) represent a highly suggestive pattern of Aicardi syndrome in a female patient. CONCLUSION: Despite absence of genetic test to confirm prenatal diagnosis of AS, this combination of CNS and extra-CNS fetal findings allows delineation of a characteristic imaging pattern of AS, especially when facing dysgenesis of the corpus callosum.

The randomized Tracheal Occlusion To Accelerate Lung growth (TOTAL)-trials on fetal surgery for congenital diaphragmatic hernia: reanalysis using pooled data.

BACKGROUND: Two randomized controlled trials compared the neonatal and infant outcomes after fetoscopic endoluminal tracheal occlusion with expectant prenatal management in fetuses with severe and moderate isolated congenital diaphragmatic hernia, respectively. Fetoscopic endoluminal tracheal occlusion was carried out at 27+0 to 29+6 weeks' gestation (referred to as "early") for severe and at 30+0 to 31+6 weeks ("late") for moderate hypoplasia. The reported absolute increase in the survival to discharge was 13% (95% confidence interval, -1 to 28; P=.059) and 25% (95% confidence interval, 6-46; P=.0091) for moderate and severe hypoplasia. OBJECTIVE: Data from the 2 trials were pooled to study the heterogeneity of the treatment effect by observed over expected lung-to-head ratio and explore the effect of gestational age at balloon insertion. STUDY DESIGN: Individual participant data from the 2 trials were reanalyzed. Women were assessed between 2008 and 2020 at 14 experienced fetoscopic endoluminal tracheal occlusion centers and were randomized in a 1:1 ratio to either expectant management or fetoscopic endoluminal tracheal occlusion. All received standardized postnatal management. The combined data involved 287 patients (196 with moderate hypoplasia and 91 with severe hypoplasia). The primary endpoint was survival to discharge from the neonatal intensive care unit. The secondary endpoints were survival to 6 months of age, survival to 6 months without oxygen supplementation, and gestational age at live birth. Penalized regression was used with the following covariates: intervention (fetoscopic endoluminal tracheal occlusion vs expectant), early balloon insertion (yes vs no), observed over expected lung-to-head ratio, liver herniation (yes vs no), and trial (severe vs moderate). The interaction between intervention and the observed over expected lung-to-head ratio was evaluated to study treatment effect heterogeneity. RESULTS: For survival to discharge, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion was 1.78 (95% confidence interval, 1.05-3.01; P=.031). The additional effect of early balloon insertion was highly uncertain (adjusted odds ratio, 1.53; 95% confidence interval, 0.60-3.91; P=.370). When combining these 2 effects, the adjusted odds ratio of fetoscopic endoluminal tracheal occlusion with early balloon insertion was 2.73 (95% confidence interval, 1.15-6.49). The results for survival to 6 months and survival to 6 months without oxygen dependence were comparable. The gestational age at delivery was on average 1.7 weeks earlier (95% confidence interval, 1.1-2.3) following fetoscopic endoluminal tracheal occlusion with late insertion and 3.2 weeks earlier (95% confidence interval, 2.3-4.1) following fetoscopic endoluminal tracheal occlusion with early insertion compared with expectant management. There was no evidence that the effect of fetoscopic endoluminal tracheal occlusion depended on the observed over expected lung-to-head ratio for any of the endpoints. CONCLUSION: This analysis suggests that fetoscopic endoluminal tracheal occlusion increases survival for both moderate and severe lung hypoplasia. The difference between the results for the Tracheal Occlusion To Accelerate Lung growth trials, when considered apart, may be because of the difference in the time point of balloon insertion. However, the effect of the time point of balloon insertion could not be robustly assessed because of a small sample size and the confounding effect of disease severity. Fetoscopic endoluminal tracheal occlusion with early balloon insertion in particular strongly increases the risk for preterm delivery.

Fetal Meconium Peritonitis - Prenatal Findings and Postnatal Outcome: A Case Series, Systematic Review, and Meta-Analysis.

PURPOSE: To describe the postnatal outcome of fetal meconium peritonitis and identify prenatal predictors of neonatal surgery. METHODS: We retrospectively reviewed all fetuses with ultrasound findings suspicious for meconium peritonitis at a single center over a 10-year period. A systematic review and meta-analysis were then performed pooling our results with previous studies assessing prenatally diagnosed meconium peritonitis and postnatal outcome. Prenatal sonographic findings were analyzed to identify predictors for postnatal surgery. RESULTS: 34 cases suggestive of meconium peritonitis were diagnosed at our center. These were pooled with cases from 14 other studies yielding a total of 244 cases. Postnatal abdominal surgery was required in two thirds of case (66.5 %). The strongest predictor of neonatal surgery was meconium pseudocyst (OR [95 % CI] 6.75 [2.53-18.01]), followed by bowel dilation (OR [95 % CI] 4.17 [1.93-9.05]) and ascites (OR [95 % CI] 2.57 [1.07-5.24]). The most common cause of intestinal perforation and meconium peritonitis, found in 52.2 % of the cases, was small bowel atresia. Cystic fibrosis was diagnosed in 9.8 % of cases. Short-term neonatal outcomes were favorable, with a post-operative mortality rate of 8.1 % and a survival rate of 100 % in neonates not requiring surgery. CONCLUSION: Meconium pseudocysts, bowel dilation, and ascites are prenatal predictors of neonatal surgery in cases of meconium peritonitis. Fetuses with these findings should be delivered in centers with pediatric surgery services. Though the prognosis is favorable, cystic fibrosis complicates postnatal outcomes.

Isolated fetal neural tube defects associate with increased risk of placental pathology: Evidence from the Collaborative Perinatal Project.

INTRODUCTION: Neural tube defects (NTDs) are amongst the most common congenital anomalies and are associated with significant postnatal morbidity, but also with a higher incidence of low birthweight and fetal growth restriction. Despite the placenta being a critical determinant of fetal growth, placental development has not been extensively studied in fetuses with NTDs. METHODS: We performed a matched case-cohort study using data from the Collaborative Perinatal Project to assess the risk of placental pathology in pregnancies with an isolated fetal NTD (cases; n = 74) compared to those without any congenital anomalies (controls; n = 148). We hypothesised that cases would be at an increased risk of placental pathology compared to controls. Data were analysed using adjusted generalized linear and nominal logistic regression models. Results are presented as adjusted ß or adjusted odds ratio (aOR; 95% confidence interval). RESULTS: Cases had lower placental weight (ß = -22.2 g [-37.8 to -6.6]), surface area (ß = -9.6 cm2 [-18.3 to -1.0]) and birth length z-scores (ß = -0.4 [-0.7 to -0.001]) compared to controls. Cases were more likely to have a single umbilical artery (vs. two; 6 [8.1%] vs. 1 [0.7%]; aOR = 301 [52.6-1726]), placental hypermaturity (9 [12.2%] vs. 5 [3.4%]; aOR = 6.8 [3.1-14.7]), many (vs. few) Hofbauer cells (9 [12.2%] vs. 7 [4.7%]; aOR = 3.02 [1.2-7.3]), and stromal fibrosis (9 [12.2%] vs. 10 [6.8%]; aOR = 3.0 [1.4-6.3]) in placental terminal villi compared to controls. CONCLUSIONS: Fetuses with isolated NTDs may be at increased risk of placental pathology, which could be contributing to poor fetal growth in these pregnancies and subsequent postnatal morbidities.

Perinatal Outcome in Fetuses with Dislodged Thoraco-Amniotic Shunts.

OBJECTIVE: Fetal thoraco-amniotic shunts (TASs) can dislodge in utero, migrating internally into the fetal thorax or externally into the amniotic cavity. Our objective was to evaluate the perinatal and long-term outcome of fetuses with TAS dislodgement and conduct a review of the literature. METHODS: This is a retrospective review of all TAS inserted for primary pleural effusions and macrocystic congenital pulmonary airway malformations (CPAMs) in a tertiary fetal medicine center (1991-2020). Antenatal history, procedural factors, and perinatal and long-term outcomes were reviewed in all fetuses with dislodged shunts and compared to fetuses with shunts that did not dislodge. RESULTS: Of 211 TAS inserted at a mean gestational age of 27.8 weeks ± 5.47 (17.4-38.1 weeks), 187 (89%) were inserted for pleural effusions and 24 (11%) for macrocystic CPAMs. Shunts dislodged in 18 fetuses (8.5%), 17 (94%) of which were for pleural effusions. Shunts migrated into the chest wall/amniotic cavity or into the thorax among 7/18 (39%) and 11/18 (61%) fetuses, respectively. Eleven (61%) fetuses were initially hydropic, which resolved in 8 (72%) cases. Effusions were bilateral in 9 (50%), amnioreduction was required in 6 (33%), and fetal rotation in 8 cases (44%). Four (22%) fetuses underwent repeat shunting, 12 (67%) neonates required ventilatory support, and 2 (11%) neonates required chest tubes. There was no significant difference in technical factors or outcomes between infants with shunts that dislodged and those that did not. Among 11 intrathoracic shunts, 2 (18%) were removed postnatally and the remainder are in situ without any shunt-related or respiratory complications over a follow-up period of 9 months to 22 years. CONCLUSION: TAS dislodged antenatally in 8.5% of fetuses, with 2/3 of shunts migrating into the thorax, and nearly 25% requiring re-shunting. Retained intrathoracic shunts were well tolerated and may not necessarily require surgical removal after birth.

A novel "video-game" simulator for training fetoscopic laser coagulation of anastomoses in twin-to-twin transfusion syndrome.

 : We have developed a high-fidelity interactive "video-game" simulator in order to teach fetoscopic laser ablation of placental anastomoses for twin-twin transfusion syndrome This simulator may be used by teachers in order to provide metrics-based simulator education to multiple trainees, in both hands-on and distanced learning settings WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?: The use of simulation improves training of the fetoscopic laser techniques utilized in the treatment of twin-twin transfusion syndrome A number of mannequins have been developed to aid this education WHAT DOES THIS STUDY ADD?: Two new simulators are described for twin-twin transfusion syndrome training-silicone and digital The digital simulator is a novel digital video game virtual format This new format has enhanced interactivity and has the potential to enable distance learning.

Selective fetal reduction in complicated monochorionic twin pregnancies: A comparison of techniques.

OBJECTIVE: To compare perinatal outcomes associated with three methods of selective reduction in complicated monochorionic (MC) twin pregnancies: bipolar cord coagulation (BC), fetoscopic or ultrasound guided laser cord occlusion and radiofrequency ablation (RFA). METHODS: Retrospective cohort study of complicated MC twin pregnancies undergoing selective fetal reduction at a tertiary fetal center over a 20-year period. Obstetric and perinatal outcomes were compared. RESULTS: 105 procedures met inclusion criteria: 74 RFAs, 17 lasers and 14 BCs. Procedure duration was significantly shorter for RFA (27.4 ± 15.8 minutes) compared to BC (91.7 ± 38.7 minutes) and laser (83.4 ± 40.4 minutes), P < .0001). The incidence of preterm prelabor rupture of membranes (PPROM) and co-twin demise did not differ between groups, however preterm delivery <34 weeks occurred less frequently following RFA (29.7%), compared to laser (64.7%) or BC (42.9%) (P = .02); delivery <37 weeks was also less frequent following RFA (45.9%), compared to laser (76.5%) or BC (78.6%)(P = .01). The difference in preterm birth<34 weeks between RFA and laser was maintained after adjusting for cord occlusion indication and amnionicity (OR 3.96, 95% CI 1.27-12.31). CONCLUSIONS: In our experience, RFA procedures were simpler, faster and associated with a lower risk of preterm delivery <34 and <37 weeks, compared to laser or BC.

Directive clinique no 410 : Anomalies du tube neural : Prévention, dépistage, diagnostic et prise en charge de la grossesse.

OBJECTIF: La présente directive clinique révisée vise à fournir une mise à jour sur les aspects génétiques, la prévention, le dépistage, le diagnostic et la prise en charge des anomalies du tube neural. POPULATION CIBLE: Les femmes enceintes ou qui pourraient le devenir. Il convient d'offrir le dépistage des anomalies du tube neural à toutes les femmes enceintes. OPTIONS: Pour la prévention : un régime alimentaire riche en acide folique et des suppléments d'acide folique et de vitamine B12 selon une posologie d'après le niveau de risque. Pour le dépistage : l'échographie obstétricale du deuxième trimestre, le dépistage échographique du premier trimestre, le dosage de l'alphafœtoprotéine sérique maternelle et l'imagerie par résonance magnétique prénatale. Pour les tests génétiques : l'amniocentèse diagnostique avec analyse chromosomique sur micropuce et le dosage de l'alphafœtoprotéine et de l'acétylcholinestérase dans le liquide amniotique et le séquençage de l'exome fœtal. Pour la prise en charge de la grossesse : la réparation chirurgicale prénatale, la réparation chirurgicale postnatale et l'interruption de grossesse avec autopsie. Pour les grossesses subséquentes : les options de prévention et de dépistage et les conseils. RéSULTATS: La recherche et la mise en œuvre du traitement chirurgical fœtal en cas de diagnostic prénatal de myéloméningocèle ont ajouté une option thérapeutique fœtale importante aux options précédentes (réparation postnatale ou interruption de grossesse), mais cette nouvelle option comporte un risque accru de morbidité maternelle. La prévention, le dépistage, le diagnostic et le traitement des anomalies du tube neural se révèlent entraîner des améliorations importantes à la mère et au nourrisson en matière de santé et de qualité de vie. BéNéFICES, RISQUES ET COûTS: Le type et l'ampleur des bénéfices, risques et coûts attendus pour les patientes grâce à la mise en œuvre de la présente directive clinique par un établissement de soins de santé intègrent un canal maternel préconception et prénatal adéquat comprenant l'accès des patientes aux soins, les conseils, les analyses et examens, l'imagerie, le diagnostic et l'interprétation. Les bénéfices relatifs à l'autonomie de la patiente et au processus décisionnel sont énoncés dans la présente directive clinique. Les risques comprennent un diagnostic fœtal inattendu et les décisions de prise en charge subséquentes. Le fait que la patiente refuse les échographies habituelles et le retard du conseil ou d'accès aux soins en cas d'anomalie du tube neural comportent également des risques. L'analyse des coûts (personnels, familiaux, santé publique) ne fait pas partie de la portée de la présente directive clinique. DONNéES PROBANTES: Afin de mettre à jour et réviser la présente directive, une revue de la littérature ciblée et dirigée a été effectuée à l'aide des termes de recherche suivants : spina bifida, neural tube defect, myelomeningocele, prenatal diagnosis, fetal surgery, neural tube defect prevention, neural tube defect screening, neural tube defect diagnosis et neural tube defect management. Un processus d'examen par les pairs a été utilisé pour la validation et la clarté du contenu, avec des considérations appropriées d'ordre éthique. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant l'approche d'évaluation, de développement et d'évaluation (GRADE). Consulter l'annexe A en ligne (le tableau A1 pour les définitions et le tableau A2 pour les interprétations des recommandations fortes et faibles). PROFESSIONNELS CONCERNéS: Professionnels des soins de maternité qui offrent des soins préconception, prénataux, obstétricaux ou néonataux. La présente directive clinique convient également aux fins d'éducation des patientes. RECOMMANDATIONS (CLASSEMENT GRADE ENTRE PARENTHèSES).

Guideline No. 410: Prevention, Screening, Diagnosis, and Pregnancy Management for Fetal Neural Tube Defects.

OBJECTIVE: This revised guideline is intended to provide an update on the genetic aspects, prevention, screening, diagnosis, and management of fetal neural tube defects. TARGET POPULATION: Women who are pregnant or may become pregnant. Neural tube defect screening should be offered to all pregnant women. OPTIONS: For prevention: a folate-rich diet, and folic acid and vitamin B12 supplementation, with dosage depending on risk level. For screening: second-trimester anatomical sonography; first-trimester sonographic screening; maternal serum alpha fetoprotein; prenatal magnetic resonance imaging. For genetic testing: diagnostic amniocentesis with chromosomal microarray and amniotic fluid alpha fetoprotein and acetylcholinesterase; fetal exome sequencing. For pregnancy management: prenatal surgical repair; postnatal surgical repair; pregnancy termination with autopsy. For subsequent pregnancies: prevention and screening options and counselling. OUTCOMES: The research on and implementation of fetal surgery for prenatally diagnosed myelomeningocele has added a significant treatment option to the previous options (postnatal repair or pregnancy termination), but this new option carries an increased risk of maternal morbidity. Significant improvements in health and quality of life, both for the mother and the infant, have been shown to result from the prevention, screening, diagnosis, and treatment of fetal neural tube defects. BENEFITS, HARMS, AND COSTS: The benefits for patient autonomy and decision-making are provided in the guideline. Harms include an unexpected fetal diagnosis and the subsequent management decisions. Harm can also result if the patient declines routine sonographic scans or if counselling and access to care for neural tube defects are delayed. Cost analysis (personal, family, health care) is not within the scope of this clinical practice guideline. EVIDENCE: A directed and focused literature review was conducted using the search terms spina bifida, neural tube defect, myelomeningocele, prenatal diagnosis, fetal surgery, neural tube defect prevention, neural tube defect screening, neural tube defect diagnosis, and neural tube defect management in order to update and revise this guideline. A peer review process was used for content validation and clarity, with appropriate ethical considerations. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). INTENDED AUDIENCE: Maternity care professionals who provide any part of pre-conception, antenatal, delivery, and neonatal care. This guideline is also appropriate for patient education. RECOMMENDATIONS (GRADE RATINGS IN PARENTHESES).

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

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

Development of a Core outcome set for fetal Myelomeningocele (COSMiC): study protocol.

BACKGROUND: Open spina bifida (OSB) is one of the most common congenital central nervous system defects and leads to long-term physical and cognitive disabilities. Open fetal surgery for OSB improves neurological outcomes and reduces the need for ventriculoperitoneal shunting, compared to postnatal surgery, but is associated with a significant risk of prematurity and maternal morbidity. Fetoscopic surgery comes with less maternal morbidity, yet the question remains whether the procedure is neuroprotective and reduces prematurity. Comparison of outcomes between different treatment options is challenging due to inconsistent outcome reporting. We aim to develop and disseminate a core outcome set (COS) for fetal OSB, to ensure that outcomes relevant to all stakeholders are collected and reported in a standardised fashion in future studies. METHODS: The COS will be developed using a validated Delphi methodology. A systematic literature review will be performed to identify outcomes previously reported for prenatally diagnosed OSB. We will assess maternal (primary and subsequent pregnancies), fetal, neonatal and childhood outcomes until adolescence. In a second phase, we will conduct semi-structured interviews with stakeholders, to ensure representation of additional relevant outcomes that may not have been reported in the literature. We will include patients and parents, as well as health professionals involved in the care of these pregnancies and children (fetal medicine specialists, fetal surgeons, neonatologists/paediatricians and allied health). Subsequently, an international group of key stakeholders will rate the importance of the identified outcomes using three sequential online rounds of a modified Delphi Survey. Final agreement on outcomes to be included in the COS, their definition and measurement will be achieved through a face-to-face consensus meeting with all stakeholder groups. Dissemination of the final COS will be ensured through different media and relevant societies. DISCUSSION: Development and implementation of a COS for fetal OSB will ensure consistent outcome reporting in future clinical trials, systematic reviews and clinical practice guidelines. This will lead to higher quality research, better evidence-based clinical practice and ultimately improved maternal, fetal and long-term childhood outcomes. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42018104880 . Registered on December 5, 2018. Core Outcome Measures in Effectiveness Trials (COMET): 1187.

Fetal Diagnosis and Therapy during the COVID-19 Pandemic: Guidance on Behalf of the International Fetal Medicine and Surgery Society.

The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant recent information to allow us to optimize prenatal care delivery. We discuss potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders. Most fetal therapies are time sensitive and cannot be delayed. If personnel and resources are available, we should continue to offer procedures of proven benefit, acknowledging any fetal and maternal risks, including those to health care workers. There is, to date, minimal, unconfirmed evidence of spontaneous vertical transmission, though it may theoretically be increased with some procedures. Knowing a mother's preoperative SARS-CoV-2 status would enable us to avoid or defer certain procedures while she is contagious and to protect health care workers appropriately. Some fetal conditions may alternatively be managed neonatally. Counseling regarding fetal interventions which have a possibility of additional intra- or postoperative morbidity must be performed in the context of local resource availability. Procedures of unproven benefit should not be offered. We encourage participation in registries and trials that may help us to understand the impact of COVID-19 on pregnant women, their fetuses, and neonates.

Screening for preeclampsia in low-risk twin pregnancies at early gestation.

INTRODUCTION: Preeclampsia affects about 10% of twin pregnancies and significantly increases the risk of adverse pregnancy outcomes. However, screening models for preeclampsia in twin pregnancies remain elusive. The present study aimed to evaluate the performance of a multi-marker first trimester preeclampsia screening model in low-risk twin pregnancies. MATERIAL AND METHODS: Between 2014 and 2017, we prospectively assessed first trimester biomarkers for preeclampsia in a 'low-risk' twin pregnancy cohort at a single center. Multiple logistic regression was used to determine significant predictors for early preeclampsia (occurring prior to 34 weeks) and late preeclampsia (occurring after 34 weeks). The performance of the screening models fitted using the significant predictors was calculated using receiver operating characteristics curves, and internal validation was performed using bootstrapping. RESULTS: A total of 769 twin pregnancies were included in the study. Early preeclampsia and late preeclampsia developed in 27 (3.5%) and 59 (7.7%) cases, respectively. Logistic regression analyses showed that maternal age, body mass index, mean artery pressure and placental growth factor were significant predictors for early preeclampsia. Maternal age, body mass index, mean artery pressure and pregnancy-associated plasma protein A were significant for late preeclampsia. Uterine artery pulsatility index was not predictive of either early or late preeclampsia. For the fitted screening model of early and late preeclampsia, the areas under receiver operating characteristics curves were 0.82 (95% confidence interval [CI] 0.76-0.88) and 0.66 (95% CI 0.59-0.73), which were expected to decrease to 0.77 and 0.60, respectively, based on bootstrapping; the positive predictive values were 10.2% and 12.5%; and the estimated detection rates were 40.7% and 22.0%, respectively, at a false-positive rate of 10%. CONCLUSIONS: A multi-marker screening model for preeclampsia in low-risk twin pregnancies, using a modified version of Fetal Medicine Foundation predictors in singletons, does not perform well. Uterine artery pulsatility index is of little value in screening for preeclampsia in low-risk twin pregnancies.

SARS-CoV2 (COVID-19) infection: is fetal surgery in times of national disasters reasonable?

Even though the global COVID-19 pandemic may affect how medical care is delivered in general, most countries try to maintain steady access for women to routine pregnancy care, including fetal anomaly screening. This means that, also during this pandemic, fetal anomalies will be detected, and that discussions regarding invasive genetic testing and possibly fetal therapy will need to take place. For patients, concerns about Severe Acute Respiratory Syndrome-Corona Virus 2 will add to the anxiety caused by the diagnosis of a serious fetal anomaly. Yet, also for fetal medicine teams the situation gets more complex as they must weigh up the risks and benefits to the fetus as well as the mother, while managing a changing evidence base and logistic challenges in their healthcare system.

Impact of introduction of noninvasive prenatal testing on uptake of genetic testing in fetuses with central nervous system anomalies.

OBJECTIVE: To evaluate the impact of introduction of noninvasive prenatal testing (NIPT) on the uptake of invasive testing in pregnancies complicated by fetal central nervous system (CNS) anomalies. METHODS: Retrospective review of all singleton pregnancies complicated by fetal CNS anomalies seen at a single tertiary center between 2010 and 2017. Cases who had undergone invasive testing or NIPT prior to the diagnosis of the CNS anomaly were excluded. Cases were segregated according to whether they were seen prior to introduction of NIPT (group A, 2010-2013) or thereafter (group B, 2014-2017). We examined the rate of invasive and noninvasive genetic testing in each group. RESULTS: We retrieved 500 cases: 308 (62%) were isolated CNS anomalies, and 192 (38%) had additional structural anomalies. In the total cohort, 165 women (33%) underwent expectant management with no further prenatal genetic testing, 166 (33%) had invasive testing, 52 (10%) had NIPT, and 117 pregnancies (23%) were terminated without further prenatal investigations. The introduction of NIPT significantly decreased the number of pregnancies having no testing (44% group A vs 22% in group B, p < .0001), particularly in the group presenting with isolated ventriculomegaly, but did not affect the uptake of invasive testing (34% vs 32%, respectively; p = .61). NIPT would have missed 4% of pathogenic copy number variants (CNVs) in the group of cases with isolated brain anomalies and 11% of CNVs in cases with complex anomalies. CONCLUSIONS: Uptake of invasive prenatal testing in fetuses with brain anomalies was not affected by NIPT. However, the incidence of no genetic testing was significantly reduced. NIPT was a suboptimal testing strategy in this population as it missed a significant number of subchromosomal genetic anomalies.