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Objectives: First, to determine the uptake of prenatal exome sequencing (pES) and the diagnostic yield of pathogenic (causative) variants in a UK tertiary fetal medicine unit following the introduction of the NHS England Rapid Exome Sequencing Service for fetal anomalies testing (R21 pathway). Second, to identify how the decision to proceed with pES and identification of a causative variant affect perinatal outcomes, specifically late termination of pregnancy (TOP) at or beyond 22 weeks' gestation., Methods: This was a retrospective cohort study of anomalous fetuses referred to the Liverpool Women's Hospital Fetal Medicine Unit between 1 March 2021 and 28 February 2022. pES was performed as part of the R21 pathway. Trio exome sequencing was performed using an Illumina next-generation sequencing platform assessing coding and splice regions of a panel of 974 prenatally relevant genes and 231 expert reviewed genes. Data on demographics, phenotype, pES result and perinatal outcome were extracted and compared. Descriptive statistics and the χ-square or Fisher's exact test were performed using IBM SPSS version 28.0.1.0., Results: In total, 72 cases were identified and two-thirds of eligible women (n = 48) consented to trio pES. pES was not feasible in one case owing to a low DNA yield and, therefore, was performed in 47 cases. In one-third of cases (n = 24), pES was not proposed or agreed. In 58.3% (14/24) of these cases, this was because invasive testing was declined and, in 41.7% (10/24) of cases, women opted for testing and underwent chromosomal microarray analysis only. The diagnostic yield of pES was 23.4% (11/47). There was no overall difference in the proportion of women who decided to have late TOP in the group in which pES was agreed compared with the group in which pES was not proposed or agreed (25.0% (12/48) vs 25.0% (6/24); P = 1.0). However, the decision to have late TOP was significantly more frequent when a causative variant was detected compared with when pES was uninformative (63.6% (7/11) vs 13.9% (5/36); P < 0.0009). The median turnaround time for results was longer in cases in which a causative variant was identified than in those in which pES was uninformative (22 days (interquartile range (IQR), 19-34) days vs 14 days (IQR, 10-15 days); P < 0.0001)., Conclusions: This study demonstrates the potential impact of identification of a causative variant by pES on decision to have late TOP. As the R21 pathway continues to evolve, we urge clinicians and policymakers to consider introducing earlier screening for anomalies, developing robust guidance for late TOP and ensuring optimized support for couples. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To develop a standardized sonographic evaluation and reporting system for Cesarean scar pregnancy (CSP) in the first trimester, for use by both general gynecology and expert clinics., Methods: A modified Delphi procedure was carried out, in which 28 international experts in obstetric and gynecological ultrasonography were invited to participate. Extensive experience in the use of ultrasound to evaluate Cesarean section (CS) scars in early pregnancy and/or publications concerning CSP or niche evaluation was required to participate. Relevant items for the detection and evaluation of CSP were determined based on the results of a literature search. Consensus was predefined as a level of agreement of at least 70% for each item, and a minimum of three Delphi rounds were planned (two online questionnaires and one group meeting)., Results: Sixteen experts participated in the Delphi study and four Delphi rounds were performed. In total, 58 items were determined to be relevant. We differentiated between basic measurements to be performed in general practice and advanced measurements for expert centers or for research purposes. The panel also formulated advice on indications for referral to an expert clinic. Consensus was reached for all 58 items on the definition, terminology, relevant items for evaluation and reporting of CSP. It was recommended that the first CS scar evaluation to determine the location of the pregnancy should be performed at 6-7 weeks' gestation using transvaginal ultrasound. The use of magnetic resonance imaging was not considered to add value in the diagnosis of CSP. A CSP was defined as a pregnancy with implantation in, or in close contact with, the niche. The experts agreed that a CSP can occur only when a niche is present and not in relation to a healed CS scar. Relevant sonographic items to record included gestational sac (GS) size, vascularity, location in relation to the uterine vessels, thickness of the residual myometrium and location of the pregnancy in relation to the uterine cavity and serosa. According to its location, a CSP can be classified as: (1) CSP in which the largest part of the GS protrudes towards the uterine cavity; (2) CSP in which the largest part of the GS is embedded in the myometrium but does not cross the serosal contour; and (3) CSP in which the GS is partially located beyond the outer contour of the cervix or uterus. The type of CSP may change with advancing gestation. Future studies are needed to validate this reporting system and the value of the different CSP types., Conclusion: Consensus was achieved among experts regarding the sonographic evaluation and reporting of CSP in the first trimester. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To determine whether maternal cardiac adaptation at term differs between women with, and those without, gestational diabetes mellitus (GDM)., Methods: This was a prospective case-control study of pregnant women at term with or without GDM. For both cases and controls, only women without any comorbidity or form of pre-existing diabetes who had a singleton pregnancy without complication (such as pre-eclampsia or fetal growth restriction) were included. All women underwent conventional and speckle-tracking echocardiography to assess both the left- and right-heart geometry and function., Results: A total of 40 women with GDM and 40 healthy controls were enrolled. Women with GDM, compared with controls, had a significantly higher heart rate (83 ± 10 vs 75 ± 9 beats per min; P < 0.001), left ventricular (LV) relative wall thickness (0.43 ± 0.07 vs 0.37 ± 0.08; P < 0.001), LV early diastolic transmitral valve velocity (E) (0.80 ± 0.15 vs 0.73 ± 0.12 m/s; P = 0.026) and LV late diastolic transmitral valve velocity (A) (0.65 ± 0.13 vs 0.57 ± 0.11 m/s; P = 0.006). In women with GDM compared with controls, speckle-tracking analysis revealed a significant reduction in LV global longitudinal strain (GLS) (-16.29 ± 2.26 vs -17.61 ± 1.89; P = 0.012), LV endocardial GLS (-18.50 ± 2.59 vs -19.84 ± 2.35; P = 0.031) and LV epicardial GLS (-14.40 ± 2.01 vs -15.73 ± 1.66; P = 0.005). Right ventricular (RV) analysis revealed a reduced pulmonary acceleration time (58 ± 10 vs 66 ± 11 ms; P = 0.001) and RV E/A ratio (1.13 ± 0.18 vs 1.29 ± 0.35; P = 0.017), as well as a higher RV myocardial systolic annular velocity (0.16 ± 0.04 vs 0.14 ± 0.02; P = 0.023) and peak late diastolic transtricuspid valve velocity (0.46 ± 0.1 m/s vs 0.39 ± 0.08 m/s; P = 0.001), in women with GDM compared to controls., Conclusions: Our findings show that even a short period of exposure to hyperglycemia, as occcurs in women with GDM, is associated with significant maternal functional cardiac impairment at term. Given these findings, further study of postnatal maternal cardiovascular recovery after GDM pregnancy is warranted. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To explore whether early first-trimester ultrasound can predict the third-trimester sonographic stage of placenta accreta spectrum (PAS) disorder and to elucidate whether combining first-trimester ultrasound findings with the sonographic stage of PAS disorder can stratify the risk of adverse surgical outcome in women at risk for PAS disorder., Methods: This was a retrospective analysis of prospectively collected data from women with placenta previa, and at least one previous Cesarean delivery (CD) or uterine surgery, for whom early first-trimester (5-7 weeks' gestation) ultrasound images could be retrieved. The relationship between the position of the gestational sac and the prior CD scar was assessed using three sonographic markers for first-trimester assessment of Cesarean scar (CS) pregnancy, reported by Calí et al. (crossover sign (COS)), Kaelin Agten et al. (implantation of the gestational sac on the scar vs in the niche of the CS) and Timor-Tritsch et al. (position of the center of the gestational sac below vs above the midline of the uterus), by two different examiners blinded to the final diagnosis and clinical outcome. The primary aim of the study was to explore the association between first-trimester ultrasound findings and the stage of PAS disorder on third-trimester ultrasound. Our secondary aim was to elucidate whether the combination of first-trimester ultrasound findings and sonographic stage of PAS disorder can predict surgical outcome. Logistic regression analysis and area under the receiver-operating-characteristics curve (AUC) were used to analyze the data., Results: One hundred and eighty-seven women with vasa previa were included. In this cohort, 79.6% (95% CI, 67.1-88.2%) of women classified as COS-1, 94.4% (95% CI, 84.9-98.1%) of those with gestational-sac implantation in the niche of the prior CS and 100% (95% CI, 93.4-100%) of those with gestational sac located below the uterine midline, on first-trimester ultrasound, were affected by the severest form of PAS disorder (PAS3) on third-trimester ultrasound. On multivariate logistic regression analysis, COS-1 (odds ratio (OR), 7.9 (95% CI, 4.0-15.5); P < 0.001), implantation of the gestational sac in the niche (OR, 29.1 (95% CI, 8.1-104); P < 0.001) and location of the gestational sac below the midline of the uterus (OR, 38.1 (95% CI, 12.0-121); P < 0.001) were associated independently with PAS3, whereas parity (P = 0.4) and the number of prior CDs (P = 0.5) were not. When translating these figures into diagnostic models, first-trimester diagnosis of COS-1 (AUC, 0.94 (95% CI, 0.91-0.97)), pregnancy implantation in the niche (AUC, 0.92 (95% CI, 0.89-0.96)) and gestational sac below the uterine midline (AUC, 0.92 (95% CI, 0.88-0.96)) had a high predictive accuracy for PAS3. There was an adverse surgical outcome in 22/187 pregnancies and it was more common in women with, compared to those without, COS-1 (P < 0.001), gestational-sac implantation in the niche (P < 0.001) and gestational-sac position below the uterine midline (P < 0.001). On multivariate logistic regression analysis, third-trimester ultrasound diagnosis of PAS3 (OR, 4.3 (95% CI, 2.1-17.3)) and first-trimester diagnosis of COS-1 (OR, 7.9 (95% CI, 4.0-15.5); P < 0.001), pregnancy implantation in the niche (OR, 29.1 (95% CI, 8.1-79.0); P < 0.001) and position of the sac below the uterine midline (OR, 6.6 (95% CI, 3.9-16.2); P < 0.001) were associated independently with adverse surgical outcome. When combining the sonographic coordinates of the three first-trimester imaging markers, we identified an area we call high-risk-for-PAS triangle, which may enable an easy visual perception and application of the three methods to prognosticate the risk for CS pregnancy and PAS disorder, although it requires validation in large prospective studies., Conclusions: Early first-trimester sonographic assessment of pregnancies with previous CD can predict reliably ultrasound stage of PAS disorder. Combination of findings on first-trimester ultrasound with second- and third-trimester ultrasound examination can stratify the surgical risk in women affected by a PAS disorder. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Obesity is an increasing problem worldwide, with well recognized detrimental effects on cardiovascular health; however, very little is known about the effect of obesity on cardiovascular adaptation to pregnancy. The aim of the present study was to compare biventricular cardiac function at term between obese pregnant women and pregnant women with normal body weight, utilizing conventional echocardiography and speckle-tracking assessment., Methods: This was a prospective case-control study of 40 obese, but otherwise healthy, pregnant women with a body mass index (BMI) of ≥ 35 kg/m 2 and 40 healthy pregnant women with a BMI of ≤ 30 kg/m 2 . All women underwent a comprehensive echocardiographic examination and speckle-tracking assessment at term., Results: Obese pregnant women, compared with controls, had significantly higher systolic blood pressure (117 vs 109 mmHg; P = 0.002), cardiac output (6.73 vs 4.90 L/min; P < 0.001), left ventricular (LV) mass index (74 vs 64 g/m 2 ; P < 0.001) and relative wall thickness (0.43 vs 0.37; P < 0.001). Diastolic dysfunction was present in five (12.5%) controls and 16 (40%) obese women (P = 0.004). In obese women, compared with controls, LV global longitudinal strain (-15.59 vs -17.61%; P < 0.001), LV endocardial (-17.30 vs -19.84%; P < 0.001) and epicardial (-13.10 vs -15.73%; P < 0.001) global longitudinal strain as well as LV early diastolic strain rate (1.05 vs 1.24 /s; P = 0.006) were all significantly reduced. No differences were observed in the degree of LV twist and torsion between the two groups., Conclusions: Morbidly obese, but otherwise healthy, pregnant women at term had significant LV hypertrophy with evidence of diastolic dysfunction and impaired deformation indices compared with pregnant women of normal weight. These findings are likely to represent a maladaptive response of the heart to volume overload in obese pregnancy. The impact of theses changes on pregnancy outcome and long-term maternal outcome is unclear. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To quantify from the published literature survival and neurodevelopmental outcome of fetuses with prenatally detected isolated severe bilateral ventriculomegaly., Methods: MEDLINE, EMBASE and the Cochrane Library were searched electronically. Only cases with a prenatal diagnosis of apparently isolated severe ventriculomegaly and postnatal neurodevelopmental assessment were selected and included. Severe ventriculomegaly was defined as enlargement of the ventricular atria, with a diameter of greater than 15 mm in the transventricular plane. All cases in which the investigators were unable to detect associated structural abnormality, chromosomal abnormality or fetal infection, and in which the ventriculomegaly was therefore regarded as apparently isolated, were included. Those for which the etiology was identified prenatally were excluded, whereas those with postnatal identification of the underlying cause were not excluded, since this information was not available prenatally. The quality of the included studies was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies. Pregnancy outcomes such as termination, stillbirth, neonatal survival and developmental outcome of the baby, were recorded. The degree of disability was classified as no, mild or severe disability. Statistical assessment was performed by meta-analysis of proportions to combine data, weighting the studies using the inverse variance method and a random-effects model. Proportions and CIs were reported., Results: Eleven studies including 137 fetuses were found. Twenty-seven pregnancies underwent termination and were excluded. The remaining 110 fetuses with apparently isolated severe ventriculomegaly for which continuation of pregnancy was intended, form the study population. Overall quality assessed using NOS for cohort studies was good. Survival was reported in 95/110 (pooled proportion 87.9% (95% CI, 75.6-96.2%)) cases. In 15/110 (pooled proportion 12.1% (95% CI, 3.8-24.4%)), either stillbirth or neonatal demise was reported. No disability was reported in 41/95 survivors (pooled proportion 42.2% (95% CI, 27.5-57.6%)). However, 17/95 showed mild/moderate disability (pooled proportion 18.6% (95% CI, 7.2-33.8%)) and 37/95 were reported to have severe disability (pooled proportion 39.6% (95% CI, 30.0-50.0%))., Conclusions: Four-fifths of fetuses with severe ventriculomegaly survive and, of these, just over two-fifths show normal neurodevelopment. The overall survivors without disability account for more than one third of the total. Given that many cases undergo termination of pregnancy and require longer follow-up in order to detect subtle abnormalities, mortality and prevalence of developmental delay may be even higher than that reported in this paper. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)