OBJECTIVES:Improving and maintaining high detection rates for major congenital heart disease (CHD) is a priority for successful prenatal anatomy screening programmes. The primary objective of this study was to evaluate the utility of on-site multidimensional targeted training in fetal cardiac screening. METHODS:A prospective study evaluating a targeted fetal echocardiography (FE) training programme in two obstetric tertiary care units was established. The programme was designed and approved by a dedicated fetal cardiology team. The one-day intervention involved supervised hands-on sonography and a prescribed educational programme for sonographers and doctors. The programme was completed by 23 trainees. Evaluation of the programme involved pre and post-training questionnaires and retrospective evaluation of cardiac images from 10 randomly-selected anatomy screening examinations performed by each trainee before and after training. Images were assessed for both technical quality and 6 priority elements of cardiac screening taught in the programme. The results were described with summary statistics and non-parametric tests. RESULTS:1850 fetal cardiac images obtained before and after training by 21/23 trainees were assessed. Significant improvement was seen in the priority cardiac views obtained, for example from 24%(5/21) to 86%(18/21) for bifurcating pulmonary artery (P-value 0.001), from 33%(7/21) to 86%(17/21) for differential atrio-ventricular valve insertion (P-value 0.001), In addition, technical image quality improvements were observed following training as well as sonographer confidence. CONCLUSION:A targeted FE training programme can improve understanding of the priority elements required to exclude major CHD in prenatal screening, improve image quality, and sonographer confidence in cardiac screening.

Despite positive outcomes for novel targeted therapy screens in preclinical studies, the majority of follow on GBM clinical trials fail to meet their primary endpoints. This translational gap is partly due to models that do not accurately recapitulate the human GBM-TME and therefore fail to accurately predict patient treatment response. Here, we investigated the NFPp10a/NF5310 syngeneic mouse model of mesenchymal GBM, to assess its translational relevance for evaluating TME-targeting agents. Young and aging C57BL/6 mice bearing orthotopic NFPp10a/NF5310-Luc2 tumours underwent treatment with temozolomide (TMZ), tumour resection, anti-PD1 checkpoint blockade, and/or regorafenib (REGO). TME composition was evaluated using the murine microenvironment cell population (mMCP) counter method and multiplexed immunohistochemistry (multiple iterative labelling by antibody neodeposition). To assess translational relevance and conserved human response patterns, immune cell composition and gene expression changes were directly compared to primary human mesenchymal GBM tumours via further hypothesis generating MILAN analysis and by studying publically available ICI clinical trial data. NFPp10a/NF5310-Luc2 tumour-bearing mice showed resistance to monotherapy and neoadjuvant anti-PD1, with limited response also observed to REGO treatment. mMCP analysis revealed modest increases in CD8+ T-cells, B cells, and monocytes following anti-PD1 and REGO treatment. MILAN analysis further indicated increased cytotoxic T-cells following anti-PD1 therapy. Comparison to untreated-primary GBM and ICI-treated human GBM suggested similar exhausted CD8+ T-cell phenotypes, suggesting the NFPp10a/NF5310 TME reflects the mesenchymal GBM T-cell compartment. Overall, the NFPp10a/NF5310 model recapitulates the GBM-TME architecture and therapeutic resistance patterns observed in human GBM, supporting its use in evaluating select TME-targeting therapies. The NFPp10a/NF5310 glioblastoma model demonstrates clinically relevant response patterns and key tumour microenvironment features of mesenchymal glioblastoma, supporting its utility as a translational platform for therapeutic development.

OBJECTIVE:Obesity class III, defined as a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) exceeding 40, is associated with significant maternal and perinatal morbidity. The primary objective of this study was to evaluate the independent effect of class III obesity on mode of delivery and perinatal outcome. METHODS:A matched case-control study was conducted, involving pairing a cohort of 69 nulliparous patients with a BMI ≥ 40 to two control groups of pregnancies (70 with maternal BMI 30-39 and 70 with BMI < 30). Subjects were matched for gestational diabetes mellitus (GDM) status and maternal age. Exclusion criteria were multiparity, multiple gestation, pregnancy loss < 24 weeks' gestation and pre-pregnancy diabetes. Patterns across the BMI groups were tested using the Cochrane-Armitage trend test and the Mann-Kendall trend test. A P value less than 0.05 was considered statistically significant. RESULTS:While the planned cesarean delivery (CD) rate was similar across BMI categories, class III obesity was independently associated with a statistically significant increase in the requirement for intrapartum CD (n = 32/60 [53%, excluding elective prelabor CD]) compared with BMI 30-39 (n = 24/61 [39%, excluding elective prelabor CD]) and BMI < 30 (n = 16/62 [26%]) (P = 0.006). This increase was observed both in spontaneous and induced labor. The decision to induce labor was significantly higher in the class III obesity group (n = 49/69 [82%]) compared with BMI 30-39 (n = 44/70 [79%]) and BMI < 30 (n = 30/70 [49%]) (P < 0.001). The most prevalent complication was cesarean wound infection requiring re-hospitalization, occurring in 20% of the class III group. CONCLUSION:Almost 60% of nulliparous pregnancies complicated by class III obesity require CD, the majority being intrapartum. Adjusting for the potential influence of maternal age and GDM status on perinatal decision making provides valuable insight into the independent effect of class III obesity on delivery outcome. When safely feasible, efforts should be directed toward awaiting spontaneous labor to optimize the prospect of achieving vaginal birth.

OBJECTIVE:The most widely used population reference standard for fetal growth assessment in the United States is the Hadlock 1991 population reference. However, we detected discrepancies in the Hadlock 1991 publication between its stated methodology and its presentation of critical point values. This study investigates these discrepancies and their potential effects on clinical practice and research. STUDY DESIGN:The Hadlock 1991 table describing a fetal weight standard was recalculated from the Hadlock 1991 formula as printed in the body of the text. A difference was observed between the equation results and the table as published in the 1991 manuscript. These 2 methods for assessing estimated fetal weight percentiles were retrospectively applied to a cohort of all singleton growth ultrasounds performed at our institution since 2015. We also collected a sample of manuscripts in the literature that reference Hadlock 1991 to determine if methodology varied among previously published reports. RESULTS:The Hadlock 1991 equation does not produce the same critical point values for estimated fetal weight as the table presented in the manuscript. In our database of 176,060 ultrasound encounters for growth in singleton fetuses (78,660 patients), the Hadlock table, as compared to the Hadlock equation, would have resulted in underdiagnosis of fetal growth restriction in 5.1% (4009/78,660) of patients. Manuscripts that compared Hadlock 1991 to other growth standards tended to favor Hadlock 1991 if the equation was used, and disfavor it if the table was used. CONCLUSION:The Hadlock 1991 regression equation presented in the manuscript and the table are not the same. The table underdiagnoses fetal growth restriction and, potentially, impacts clinical intervention for fetuses at risk for growth abnormality. Inconsistencies in previous studies on the detection of fetal growth restriction using Hadlock 1991 may be attributed to these discrepancies. If increased detection of fetal growth restriction is desired, then Interpolation of the Hadlock 1991 table should be avoided and the equation preferred instead. Additional validation of these findings is required to ascertain clinical significance.

OBJECTIVES:Ultrasound-derived estimates of fetal size play an integral role in the prenatal management of twin pregnancy. These biometric measurements are conventionally plotted against singleton standards. We sought to establish fetal growth references for abdominal circumference, head circumference, biparietal diameter, femur diaphysis length and estimated fetal weight (EFW) in twin pregnancy. We also aimed to determine whether the performance of a twin fetal growth reference was superior to a singleton reference in the prediction of adverse perinatal outcome in twin pregnancies. METHODS:This was a retrospective analysis of data collected prospectively in the Evaluation of Sonographic Predictors of Restricted growth in Twins (ESPRiT) study, which was conducted at eight academic perinatal centers in Ireland, all with tertiary neonatal intensive care facilities. Only diamniotic twin pregnancies with two live fetuses were eligible for inclusion. Exclusion criteria were monoamnionicity, congenital abnormality, twin-to-twin transfusion syndrome or previable fetal demise (< 24 weeks' gestation). Using serial ultrasound observations, we applied fractional polynomial multilevel models to derive an equation for fetal centile determination. We compared these centiles with published singleton and twin fetal references, with particular focus on the Fetal Medicine Foundation (FMF) references. Using the last ultrasound examinations before delivery, we determined associations between biometric measures and a composite measure of adverse perinatal outcome (intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis or perinatal death), neonatal intensive care unit admission, preterm delivery (< 34 weeks) and birth-weight discordance ≥ 25%, based on the varied prevalence of these outcomes. We compared our results with the singleton and twin FMF reference ranges and the twin reference of the Southwest Thames Obstetric Research Collaborative (STORK) study. RESULTS:Among the 948 twin pairs that met the inclusion criteria, 776 (81.9%) dichorionic and 172 (18.1%) monochorionic twin pairs completed the prospective 2-weekly ultrasound surveillance program. Fetal biometric measurements were obtained in 15 274 ultrasound assessments (12 279 in dichorionic and 2995 in monochorionic twin pairs) from serial ultrasound assessments. The median number of ultrasound assessments per pregnancy was 8 (interquartile range, 7-9). Growth trajectories in this cohort were consistent with the FMF and STORK published twin cohorts and notably less consistent with the FMF singleton standard. Compared with the FMF singleton standards, the 50th centiles for twins were greater early in pregnancy and lower later in pregnancy for all biometric measures, in both dichorionic and monochorionic twin pregnancies. This crossover in growth occurred at approximately 28 weeks' gestation for dichorionic twins and earlier for monochorionic twins. The 50th centiles for EFW were comparable to the FMF twin standards for both monochorionic and dichorionic twins, but with lower 10th centiles for dichorionic twins in the third trimester. The current (ESPRiT) twin reference ranges, the STORK twin reference ranges and the FMF twin reference ranges showed larger and statistically significant (P < 0.01) odds ratios for multiple biometric measures and multiple adverse perinatal outcomes, for both monochorionic and dichorionic twins, not observed with the FMF singleton reference standard. CONCLUSIONS:In this analysis of data from the prospective ESPRiT cohort study, we confirm significant differences between twin fetal growth patterns and singleton standards, consistent with previous studies. Our results also offer some validation of the new FMF reference for EFW in twins. The outcome-based evidence from this study suggests that a twin-specific growth reference should be used in preference to a singleton chart for fetal growth evaluation in twin pregnancy. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The integrity of evidence synthesis is threatened by problematic randomised controlled trials (RCTs). These are RCTs where there are serious concerns about the trustworthiness of the data or findings. This could be due to research misconduct, including fraud, or due to honest critical errors. If these RCTs are not detected, they may be inadvertently included in systematic reviews and guidelines, potentially distorting their results. To address this problem, the INSPECT-SR (INveStigating ProblEmatic Clinical Trials in Systematic Reviews) tool has been developed to assess the trustworthiness of RCTs. This will allow problematic RCTs to be identified and excluded from systematic reviews. This paper describes the development of INSPECT-SR. The tool and an associated guidance document are presented.

Objective: This secondary analysis evaluates the logistics of achieving vaginal delivery following outpatient induction. This includes changes in Bishop score before and after cervical ripening, the need for additional ripening agents, time interval from induction to delivery, all of which provide invaluable information when developing an outpatient induction of labour service. Study design: We randomised healthy nulliparous women with no significant medical history, who agreed to elective induction of labour at 39 weeks' gestation, to one of three forms of initial cervical ripening at home: 12 h of Dilapan-S, 24 h of Dilapan-S, or 24 h of slow-release dinoprostone (Propess). Patients returned to the hospital after 12 or 24 h for either amniotomy or, if the cervix remained unripe, additional doses of Prostin. We present our experience with the development of a regulated protocol for outpatient induction of labour, as well as safety considerations, in order to assist those wishing to adopt such practice. Effectiveness of each induction agent, time to delivery, and length of hospital stay were assessed as part of this secondary analysis. Results: A total of 180/271 (66%) of all nulliparous women were delivered within 48 h of induction commencing, and 254/271 (94%) delivered within 72 h, inclusive of the time period spent at home. Participants in the Propess group were more likely to require early readmission than in the Dilapan-S groups (45% vs 9%). Patients randomised to Dilapan-S 12 hand Dilapan-S 24 h were more likely to require additional Prostin prior to amniotomy being possible (65% vs 34%). Those who did not require additional ripening had very high vaginal delivery rates ranging from 80% to 88%. Induction agent removal time to delivery was similar across all groups. The length of hospital stay ranged from a median of 76 to 88 h from readmission to discharge. Conclusion: Outpatient cervical ripening is an efficient and useful option for dealing with the logistical challenges facing busy Labour Wards, with the majority of nulliparous patients delivering within 48 h, including time spent at home. This resource-friendly option requires less time within the hospital setting for a carefully selected cohort.

Objective: To determine the accuracy of formulas for estimation of fetal weight in twin pregnancy. Methods: Inclusion criteria from the ESPRiT twin cohort were twin pregnancies that resulted in live-born twins without congenital anomalies or twin-twin transfusion syndrome, ultrasound examination within 3 days of delivery, birth weight (BW) > 500 g and gestational age > 24 weeks. A total of 63 formulas using various combinations of abdominal circumference (AC), femur length (FL), biparietal diameter (BPD) and head circumference (HC) for the estimation of fetal weight (EFW), were compared to BW for accuracy in 226 twin pregnancies/452 fetuses. Results: Using median percentage error (MPE), the most accurate formulas were the Hadlock formulas (1984, 1985 with MPE < 1%) incorporating AC, HC, and FL. The INTERGROWTH-21st formula, which incorporates AC and HC, marginally underestimated BW (MPE -3.7%). The Hadlock formulas were more likely to overestimate BW than underestimate it. Using small-for-gestational (SGA, EFW < 5th centile), the sensitivity for detection of low BW (BW < 5th centile) was 92%, 81% and 89% for the Hadlock 1984, Hadlock 1985 and INTERGROWTH-21st formulas, respectively. SGA prevalence was noted to be higher for the INTERGROWTH-21st formula for fetal factors. Conclusion: Among 63 proposed formulas for EFW, the Hadlock formulas incorporating HC, AC and FL were the most accurate in twins. However, the INTERGROWTH-21st standard, which incorporates AC and HC, did not show lower detection rates for LBW. The frequency and intensity of twin ultrasound surveillance is such that restriction of ultrasound examination to two parameters in ultrasound could be recommended without diminution of accuracy.

A major challenge following the ARRIVE Trial has been how to safely accommodate increasing numbers of nulliparous patients on the Labor Ward for induction of labour (IOL). Outpatient induction at home (H-IOL) has been suggested for normal-risk women, but there is a paucity of data regarding women’s experience of the process. Our objective was to perform a detailed survey of participants in the HOME INDUCTION RCT, who received either prostaglandin (Propess/Cervidil) or osmotic cervical dilator (Dilapan) to commence their induction at home. Normal-risk nulliparous women were randomized at 39 weeks to outpatient cervical ripening with 12 hours of Dilapan, 24 hours of Dilapan, or 24 hours of Propess. A questionnaire was administered (in person/by post) after delivery to assess patients’ experience with the process. Of 271 randomized patients, 113 (41%) completed the survey, with 104 (92%) recommending H-IOL, and 96 (85%) reporting no safety concerns with induction being initiated at home. On a scale of 1-10, (with 10 representing highest discomfort on insertion), patients regarded both methods favorably, rating Dilapan insertion 3.6/10 and Propess insertion 2.8/10 (p=0.46). Patients receiving Propess were significantly more likely to experience contractions at home (58% vs 10%, p< 0.001), and return to the hospital before 24 hours had passed (53% vs 9%, p< 0.001). A total of 82/113 (73%) respondents found the overall induction process to be a positive experience, 18% were unsure, and only 10% disagreed. There were no other significant differences between groups in terms of satisfaction scores. This RCT patient satisfaction data has confirmed that women find elective home IOL to be a positive experience, and almost all would recommend the experience to others. Our data also confirm that some negative commentary expressed about routine 39 week IOL after publication of the ARRIVE Trial, is not supported by prospectively collected data on patients’ own opinions and experiences, thereby supporting outpatient initiation of IOL amongst nulliparous patients.

Background Prenatal detection of critical congenital heart disease (CCHD) optimises perinatal decision-making and neonatal outcomes. The objective of this study was to determine the prenatal screening performance, care pathways and perinatal outcomes for prenatally and postnatally diagnosed cases of CCHD over a four-year period. Study design This retrospective cohort study in a tertiary centre and its two affiliated secondary sites examined all cases of CCHD, including cases of pregnancy termination and in-utero fetal death, neonatal death and liveborn babies that underwent cardiac catheterization or surgery in the first six weeks of life. Prenatal and postnatal data were ascertained from the first trimester assessment for all patients diagnosed prenatally. Cases requiring intervention that were first identified in the postnatal period were included to determine prenatal detection rates. Follow-up for all cases of CCHD continued to one year of age. Results In a consecutive cohort of 49,950 pregnancies in a 4-year period 01/2019 to 12/2022, a prenatal diagnosis of CCHD was made in 96 cases, yielding a prevalence of 1.9 per 1000 births. The prenatal detection for right duct-dependant heart pathology and congenital heart block was 100%, 85% for left duct-dependant pathology and 93% for transposition of the great arteries (TGA). In the prenatally diagnosed group, 37% of cases were complicated by extracardiac structural abnormalities, a genetic diagnosis or both. All cases of prenatal detection were identified in the context of routine anatomy screening rather than specialist Fetal Cardiac screening services. Almost half of all pregnancies complicated by CCHD did not undergo neonatal cardiac intervention, by virtue of parental choice determined either prenatally or after birth. An additional eight babies were diagnosed with CCHD in the neonatal period, such that the prenatal detection rate for CCHD was 92% (96/104, 95% CI = 84%-96%). Survival at 1-year for infants deemed suitable for CCHD surgery was 85%. Conclusion In a large unselected population, optimal rates of prenatal detection of critical congenital heart disease can be achieved by a protocolised approach to mid-trimester fetal anatomy ultrasound, underpinned by a programme of sonographer education and training. The cardiac abnormalities most likely to evade prenatal detection are left-sided obstructive lesions.