OBJECTIVE:To assess whether early antihypertensive treatment after Hypertensive Disorders of Pregnancy (HDP) influences subsequent development of cardiovascular complications. DESIGN AND SETTING:Population-based nationwide cohort of health data set in France. POPULATION:108 906 women with HDP (excluding pre-existing Chronic Hypertension (CH)) who delivered between 2010 and 2014, with 35 878 (33%) receiving at least one antihypertensive treatment in the month after giving birth. METHODS:Traditional Cox model, estimated 10-year cardiovascular risk. Extended Cox Step Function model and Restricted Mean Survival Time evaluated time trends. MAIN OUTCOME MEASURES:New-onset CH, heart failure, coronary, cerebrovascular, peripheral artery diseases and 2 composite events (one including CH, the other excluding it) over 10 years following giving birth. RESULTS:Women receiving early postnatal antihypertensive treatment had a higher long-term risk of complications over 10 years than non-treated women (CH: aHR = 3.067, 95% CI [2.996-3.139]; composite event including CH: aHR = 3.025 [2.956-3.096]; composite event excluding CH: aHR = 1.451 [1.305-1.614]). Treated women had events earlier than non-treated women, presenting a higher risk at the beginning of the postpartum period. The 10-year absolute risk for CH remained high in both groups: 44% for treated women and 18% for non-treated women. CONCLUSION:Our study shows that women receiving early postpartum antihypertensive treatment are at higher long-term cardiovascular risk, with 44% of them having CH within 10 years. Besides, approximately 1 in 5 women non-treated in the postpartum period subsequently developed CH, demonstrating that many high-risk women are not being identified in the peripartum period and may be missing opportunities for timely intervention.

Objective: This study compared insertion difficulties, shunt failure, reintervention rates, maternal adverse events, and neonatal outcomes among different shunt types used in fetal hydrothorax. Method: A retrospective multicenter cohort study (2012-2022) was conducted across 12 international centers. The primary outcome was the occurrence of complications, classified as insertion difficulties and shunt failure (dislocation, occlusion, or unexplained shunt failure). Secondary outcomes included reintervention rates, maternal complications, and neonatal survival. Results: Among 349 cases, 345 were included in the analysis of the outcome measures. Rodeck shunts had significantly fewer complications (19.5%) compared to Somatex (38.3%, OR 2.53, p = 0.016) and Harrison shunts (50.0%, OR 3.82, p < 0.001). Somatex shunts had the highest rate of incorrect positioning (16%), while dislocation was most frequent with Harrison shunts (31.1%). Reintervention rates were lowest for Rodeck (12.1%) and highest for Harrison (32.2%). Maternal body mass index, fetal hydrops, laterality and year of shunt placement did not significantly influence complication rates. No significant differences in live birth rates or gestational age at delivery were observed. Conclusions: The Rodeck shunt was associated with fewer insertion difficulties, better shunt performance and lower reintervention rates. There was no difference in perinatal survival among the three shunt types.

Abstract Introduction The randomized control Trial (RCT) of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE study) established its clinical efficacy for monitoring preterm fetal growth restriction (FGR). The objective of this study was to assess the clinical effectiveness of this protocol in a routine clinical setting with regards to the clinical outcomes, both overall and stratified by gestational age at FGR diagnosis. Material and Methods This is a retrospective cohort study of singleton pregnancies with preterm FGR between January 2013 and July 2024 in a tertiary Fetal Medicine Unit. FGR was defined as an estimated fetal weight or abdominal circumference <10th centile with an elevated umbilical artery pulsatility index >95th centile. Main outcomes collected included perinatal survival, interval from diagnosis to delivery, and delivery indications. Results 171 pregnancies met inclusion criteria. The median (IQR) gestation at FGR diagnosis and birth was 27+6 (25+5–29+4) and 30+3 (28+0–32+4) weeks, respectively. Overall intact neonatal survival was 90.6%, with the rate of stillbirth and neonatal death being 2.9% and 5.8%, respectively. FGR diagnosis prior to 26 weeks was associated with a three‐fold longer interval to birth compared with FGR diagnosis at 26+0–29+6 and ≥30 weeks (median of 31.0 vs. 10.0 and 14.0 days; p < 0.001). Below 32 weeks, the predominant indication for elective birth was abnormal computerized CTG with low short‐term variation (STV). Beyond 32 weeks' gestation, abnormal umbilical artery Doppler and maternal indications such as preeclampsia were more frequent. Conclusions The TRUFFLE monitoring protocol is clinically effective in managing early‐onset FGR outside a trial environment, achieving comparable perinatal outcomes to the original RCT. Routine integration of both Doppler and cCTG monitoring is crucial for optimal timing of birth with early FGR. Further research is needed to explore the benefits of more frequent or remote fetal monitoring.

OBJECTIVE:To develop antenatal prediction models for shoulder dystocia and birth trauma using routinely collected maternal and sonographic variables. DESIGN:Retrospective cohort study. SETTING:Single tertiary referral centre in the UK. POPULATION OR SAMPLE:All singleton term liveborn pregnancies delivered between January 2016 and November 2024 with a third-trimester ultrasound performed at or beyond 36 weeks' gestation. METHODS:Multivariable logistic regression was used to develop antenatal prediction models for shoulder dystocia and birth trauma, incorporating maternal characteristics and fetal biometry including abdominal circumference (AC; centile or mm) and estimated fetal weight (EFW; grams or centile). Model performance was assessed using tests for multicollinearity, discrimination (area under the ROC curve, AUC) and calibration. MAIN OUTCOME MEASURES:Shoulder dystocia and birth trauma, the latter defined as a composite of shoulder dystocia, postpartum haemorrhage requiring blood transfusion, caesarean delivery at full dilatation, or hypoxic-ischaemic encephalopathy (HIE ≥ 1). RESULTS:A total of 24 334 singleton term pregnancies were included; 432 (1.8%) were complicated by shoulder dystocia and 1210 (5.0%) by birth trauma. The model including maternal characteristics and AC centile demonstrated the best discrimination. For shoulder dystocia, the apparent AUC was 0.706 (95% CI 0.682-0.730); the optimism-corrected AUC after bootstrap validation was 0.699. For birth trauma, the apparent AUC was 0.669 (95% CI 0.654-0.685); the optimism-corrected AUC was 0.665. At a 10% false-positive rate, sensitivity was 31.5% for shoulder dystocia and 22.8% for birth trauma, compared with 20.4% and 14.0%, respectively, using EFW ≥ 90th centile. CONCLUSIONS:Antenatal models combining fetal AC centile with maternal risk factors outperform EFW-based thresholds currently used in clinical practice. Although discrimination was modest, the model may be useful for antenatal risk stratification and counselling, rather than as a stand-alone clinical test. Such models may help identify pregnancies at increased risk of delivery-related complications associated with fetal overgrowth and inform future studies evaluating targeted interventions.

Abstract Background Tommy’s Pathway: Clinical Decision Support Tool (the Tool/the Tommy’s Pathway), a web-based application for assessing risk of preterm birth and placental dysfunction, is provided as a dual-interface web-application, used by maternity care providers and maternity service users. The Tool utilises validated algorithms and rule engines to offer a more sophisticated assessment of risk than traditional checklist methods and offers instantaneous decision support by providing care recommendations according to risk and in line with evidenced-based clinical guidance. This novel intervention has the potential to reduce variation in care that could contribute to the higher rates of preterm birth and stillbirth seen in those from ethnic minority and socially deprived groups. We evaluated implementation of the Tommy’s Tool in five early-adopter NHS hospitals to inform a cluster randomised controlled trial. Methods We used online surveys, semi-structured interviews and focus groups to investigate: maternity service user and healthcare professional (HCP) experience; barriers and facilitators to implementation; reach (whether particular groups are excluded and why), fidelity (degree to which the intervention is delivered as intended), and unintended consequences. The NASSS framework (Non-adoption or Abandonment of technology by individuals and difficulties achieving Scale-up, Spread and Sustainability) informed analysis. Results 1181 women and 112 HCPs participated, completing 1260 online surveys, 8 focus groups and 29 semi-structured interviews. Findings highlighted the importance of ensuring the Tool was used in routine care management for all eligible service users. This informed development of an additional functionality to ensure that HCPs were able to create profiles for those who were unable or unwilling to sign up and create a profile themselves. Before this feature was introduced the proportion of service users registered on the Tool, was ~ 70%, compared to ~ 90% afterwards. Proportions of women from Asian and black ethnic groups, and those from the most deprived areas (IMD quintiles 1 & 2), also increased after the change, from 14.6%, 5.8% and 40.9% (of all maternity service users), to 16.9%, 14.2% and 52.4%, respectively. Further refinements will include translation into non-English languages. Conclusions The Tommy’s Tool has the potential to make the provision of optimal maternity care easier for healthcare professionals, which could reduce variation in care and ultimately improve outcomes. This study gave us the opportunity to evaluate early adopter implementation in order to optimise the Tool and its implementation strategy ahead of a cluster randomised controlled trial. Trial registration This study was prospectively registered on ISRCTN: ID13498237, on 31/01/2022.

Pregnancy represents a critical period during which the maternal cardiovascular system adapts to profound haemodynamic and metabolic demands. When these adaptive mechanisms are impaired, adverse pregnancy outcomes (APOs)-including hypertensive disorders of pregnancy, gestational diabetes, pre-term birth, small-for-gestational-age birth, and pregnancy loss-occur. Extensive epidemiological evidence demonstrates that APOs are not isolated obstetric events but early clinical markers of cardiometabolic dysfunction that identify women at increased risk of coronary artery disease, heart failure, stroke, chronic kidney disease, and premature cardiovascular mortality. Shared mechanisms include endothelial dysfunction, inflammation, and insulin resistance, establishing a continuum between obstetric complications and later cardiovascular disease. Early post-partum studies reveal persistent hypertension, adverse cardiac remodelling, and metabolic abnormalities that mediate much of the long-term excess cardiovascular risk. These findings redefine the 'fourth trimester' as a preventive window in which timely blood pressure surveillance, metabolic screening, and lifestyle optimization can yield durable cardiovascular benefit. Integrated cardio-obstetric care models, digital follow-up, and systematic transition to primary care are crucial for maintaining long-term prevention. Addressing persistent gaps in limited provider awareness, fragmented follow-up, and disparities across socially disadvantaged populations remains critical. Recognizing pregnancy complications as indicators of underlying cardiovascular vulnerability offers an opportunity to shift prevention upstream and promote lifelong cardiovascular health for women.

Purpose To develop a deep learning algorithm to automatically assess the posterior fossa on first-trimester US screening scans and identify open spina bifida (OSB) and cystic posterior fossa (CPF) anomalies. Materials and Methods This was the retrospective part of an international study involving 10 fetal medicine centers. Normal and abnormal (OSB, CPF anomaly) midsagittal fetal brain US images acquired between 11 and 14 weeks of gestation (July 2009-January 2024) with confirmed diagnosis at follow-up were evaluated. Images were manually annotated to delineate the posterior fossa. The dataset was split into a training/validation set (70%) and internal test set (30%). Three convolutional neural networks were trained via threefold cross-validation on the training/validation set, with predictions on the internal test set obtained by ensemble averaging across folds. Model performance in detecting OSB and CPF anomalies was evaluated for the whole cohort and for fetuses with OSB or CPF anomalies separately. Results Images from 251 fetuses were analyzed (mean gestational age [±SD], 12.7 weeks ± 0.65; 150 normal and 101 abnormal [43 OSB and 58 CPF anomalies] images). On the internal test, the MobileNetV3 Large Weights achieved the best performance: area under the receiver operating characteristic curve, 0.94 (95% CI: 0.88, 0.99); accuracy, 88% (67 of 76); recall, 81% (25 of 31); specificity, 93% (42 of 45); precision, 89% (25 of 28); negative predictive value, 88% (42 of 48); and F1 score, 0.85. OSB was classified more accurately (93% [52 of 56] vs 88% [57 of 65]; P = .38) and with higher recall (91% [10 of 11] vs 75% [15 of 20]), although the difference was not significant (P = .38). Conclusion MobileNetV3 Large Weights accurately assessed the fetal posterior fossa between 11 and 14 weeks of gestation, distinguishing normal images from those showing OSB or CPF anomalies. Clinical trial registration no. NCT0579047 Keywords: Artificial Intelligence, First Trimester Ultrasound Screening, Fetal Brain Anomalies, Deep Learning Supplemental material is available for this article. © RSNA, 2026 See also commentary by Rafful in this issue.

Importance:Hypertensive pregnancy increases risk of cognitive decline, stroke, and dementia, especially after preeclampsia. Women with prior hypertensive pregnancy show lower brain volumes, but it was unknown whether early postpartum blood pressure optimization could alter these outcomes. Objective:To evaluate whether an intervention designed to achieve better postpartum blood pressure control after a hypertensive pregnancy is associated with differences in brain volumes around 9 months post partum compared with usual care. Design, Setting, and Participants:This randomized clinical trial, the Physician Optimized Postpartum blood pressure self-management trial (POP-HT), was a prospective, open-label, blinded end-point study conducted at a single tertiary center in the UK. Participants were older than 18 years and had preeclampsia or gestational hypertension requiring antihypertensive treatment at hospital discharge. Enrollment began February 21, 2020; the last follow-up was on November 2, 2021; and the mean follow-up time was approximately 9 months. Secondary outcome analyses (primary results published 2022) were conducted May 2025. Interventions:Telemonitored self-management with research physician-guided titration or usual postnatal care. Main Outcomes and Measures:This substudy analyzed the secondary outcomes T1-weighted magnetic resonance imaging (MRI) brain volumes (gray matter, white matter, cerebrospinal fluid, subcortical structures) acquired approximately 9 months post partum. Analyses used linear regression models adjusted for total intracranial volume. Results:Of 252 eligible participants, 32 declined, and 220 were randomized (mean [SD] age, 33.4 [5.1] years). The T1 brain MRI of 157 participants was available for analysis; 96 participants (63%) had preeclampsia, and 56 (37%) had gestational hypertension. The intervention group (n = 81) had larger total white matter volumes (adjusted mean difference, 11.50 cm3; 95% CI, 2.04 to 20.96; P = .02) compared with the usual care group (n = 71). In usual care, participants with preeclampsia had smaller putamen (adjusted mean difference, -0.83 cm3; 95% CI, -1.20 to -0.46; P < .001), accumbens (adjusted mean difference, -0.15 cm3; 95% CI, -0.24 to -0.05; P = .003), and pallidum (adjusted mean difference, -0.13 cm3; 95% CI, -0.26 to -0.01; P = .04) volumes compared with those with gestational hypertension. These differences were not observed in the intervention group. Conclusions and Relevance:This study found that short-term postpartum optimization of blood pressure control after hypertensive pregnancy was associated with larger brain volumes during the first year post partum. Because brain volume is a surrogate of brain health linked to tissue preservation and cognitive outcomes, these findings suggest potential neurovascular benefits that were most pronounced among women with preeclampsia. Trial Registration:ClinicalTrials.gov Identifier: NCT04273854.

Hypertensive pregnancy increases risk of cognitive decline, stroke, and dementia, especially after preeclampsia. Women with prior hypertensive pregnancy show lower brain volumes, but it was unknown whether early postpartum blood pressure optimization could alter these outcomes. To evaluate whether an intervention designed to achieve better postpartum blood pressure control after a hypertensive pregnancy is associated with differences in brain volumes around 9 months post partum compared with usual care. This randomized clinical trial, the Physician Optimized Postpartum blood pressure self-management trial (POP-HT), was a prospective, open-label, blinded end-point study conducted at a single tertiary center in the UK. Participants were older than 18 years and had preeclampsia or gestational hypertension requiring antihypertensive treatment at hospital discharge. Enrollment began February 21, 2020; the last follow-up was on November 2, 2021; and the mean follow-up time was approximately 9 months. Secondary outcome analyses (primary results published 2022) were conducted May 2025. Telemonitored self-management with research physician-guided titration or usual postnatal care. This substudy analyzed the secondary outcomes T1-weighted magnetic resonance imaging (MRI) brain volumes (gray matter, white matter, cerebrospinal fluid, subcortical structures) acquired approximately 9 months post partum. Analyses used linear regression models adjusted for total intracranial volume. Of 252 eligible participants, 32 declined, and 220 were randomized (mean [SD] age, 33.4 [5.1] years). The T1 brain MRI of 157 participants was available for analysis; 96 participants (63%) had preeclampsia, and 56 (37%) had gestational hypertension. The intervention group (n = 81) had larger total white matter volumes (adjusted mean difference, 11.50 cm 3 ; 95% CI, 2.04 to 20.96; P = .02) compared with the usual care group (n = 71). In usual care, participants with preeclampsia had smaller putamen (adjusted mean difference, −0.83 cm 3 ; 95% CI, −1.20 to −0.46; P < .001), accumbens (adjusted mean difference, −0.15 cm 3 ; 95% CI, −0.24 to −0.05; P = .003), and pallidum (adjusted mean difference, −0.13 cm 3 ; 95% CI, −0.26 to −0.01; P = .04) volumes compared with those with gestational hypertension. These differences were not observed in the intervention group. This study found that short-term postpartum optimization of blood pressure control after hypertensive pregnancy was associated with larger brain volumes during the first year post partum. Because brain volume is a surrogate of brain health linked to tissue preservation and cognitive outcomes, these findings suggest potential neurovascular benefits that were most pronounced among women with preeclampsia. ClinicalTrials.gov Identifier: NCT04273854

Abstract Introduction Hypertensive disorders of pregnancy (HDP) and fetal growth restriction (FGR) are major manifestations of uteroplacental dysfunction and remain leading causes of maternal and perinatal morbidity. Current strategies for risk assessment rely on hospital‐based screening or diagnostic triage and do not provide continuous, personalized monitoring throughout pregnancy. Uric acid is closely linked to placental dysfunction, and salivary uric acid (sUA) reflects circulating concentrations, enabling noninvasive remote measurement. This study evaluated whether serial, smartphone‐enabled self‐testing of sUA could predict adverse pregnancy outcomes related to uteroplacental dysfunction. Material and Methods In this prospective observational cohort study, pregnant women were recruited at 20–22 weeks' gestation at a tertiary hospital. Participants performed weekly salivary self‐testing using colorimetric uric acid strips until delivery, with results captured via a smartphone application. Images were analyzed using RGB color metrics. Primary outcomes were HDP and/or FGR, defined using ISSHP and FIGO criteria, respectively. Logistic regression models incorporated 4 weeks of lagged RGB‐derived sUA metrics together with maternal characteristics. Model performance was assessed using area under the receiver operating characteristic curve (AUC) and calibration metrics, stratified by gestational age at outcome. Results Of 495 recruited participants, 318 women with complete longitudinal data were included in the final analysis; 36 (11.3%) developed HDP and/or FGR. A multivariable model combining maternal risk factors with 4 weeks of serial sUA measurements demonstrated good predictive performance. Discrimination was highest for preterm outcomes, with an AUC of 0.814 for prediction within 1 week at <37 weeks' gestation and prediction remained acceptable at term (AUC 0.732). Conclusions Remote serial self‐testing of salivary uric acid is feasible and shows good predictive ability for adverse pregnancy outcomes related to uteroplacental dysfunction. This noninvasive approach has potential to complement existing screening and surveillance strategies by enabling continuous, personalized risk assessment throughout pregnancy. Prospective validation in larger and more diverse populations is warranted.

Purpose To develop and validate an anatomy-aware, two-stage, end-to-end deep learning pipeline for fetal brain abnormality automated detection on standardized second-trimester brain US images. Materials and Methods This retrospective multicenter study included 319 fetal brain images (218 normal, 101 abnormal) between 19 weeks ± 0 and 23 weeks ± 6 of gestation from nine international fetal medicine centers, each with paired standard transventricular and transcerebellar axial plane images acquired at second-trimester US between January 2010 and December 2022. Abnormalities were confirmed by neonatal imaging or autopsy. Images were annotated for six key brain regions by two experienced fetal medicine specialists. An anatomy-aware, two-stage deep learning pipeline was developed, consisting of a You Only Look Once version 5-based object detector followed by a classification network using a Mini-ResNet feature extractor within a HexaNet architecture. The pipeline classified each image as normal or abnormal. Object detection performance was evaluated using mean average precision at an intersection-over-union threshold of 0.5 (mAP@0.5). Classification performance was assessed using the area under the receiver operating characteristic curve, sensitivity, specificity, and F1 score. Results The object detection model achieved a mAP@0.5 of 0.93 (95% CI: 0.90, 0.96) on the test dataset. The classification model achieved an area under the receiver operating characteristic curve of 0.96 (95% CI: 0.90, 1.00), a sensitivity of 87% (95% CI: 67, 100 [13 of 15]), a specificity of 91% (95% CI: 79, 100 [29 of 32]), and an F1 score of 0.84 (95% CI: 0.67, 0.96) for distinguishing normal from abnormal fetal brain images. Conclusion The developed model achieved high diagnostic performance for the detection of brain anomalies at routine fetal second-trimester US. Keywords: Artificial Intelligence, Machine Learning, Fetal Neurology, Neurosonography, Fetal Brain Malformation, YOLOv5, Neural Networks Supplemental material is available for this article. © RSNA, 2026 See also commentary by Rafful in this issue.

BACKGROUND:Hypertension induces structural and functional damage in multiple organs. Evidence of subclinical damage increases risk of vascular events and death but can be difficult to identify in the clinic. We developed a novel machine learning approach that quantifies current hypertension-associated multiorgan damage, mapping progression from health to advanced disease, in a pseudotemporal manner and predicts organ-specific disease progression trajectories. METHODS:We analyzed 566 multimodal imaging and nonimaging variables from 27 099 participants in the UK Biobank imaging substudy to develop a semisupervised contrastive trajectory inference (cTI) framework that models multiorgan alterations associated with hypertension exposure, including heart, brain, kidneys, vasculature, lungs, liver, and metabolic information. Model stability was validated through multiple internal validation steps, and external validity was tested on 5507 participants from the Atherosclerosis Risk in Communities study (ARIC). Clinical relevance was evaluated against existing risk scores and through ability to predict survival and incident multiorgan disease for up to 7 years, across both UK Biobank and ARIC. RESULTS:In the UK Biobank (mean age 63.27±7.48 years; 53.4% women) our global organ damage score (HyperScore) achieved an area under the curve of 0.964 (0.941-0.987) for identification of individuals with severe end-organ disease and robust stability in cross-validation with a mean root mean square error of 0.104±0.084. Survival odds differed significantly across HyperScore stages (P<0.001), whereas stratification by blood pressure was nonsignificant. We further revealed 6 hypertensive disease phenotypes (HyperTrajectory), characterized by predominant cardiac, lipoprotein, atherothrombosis, brain, cardiorenal, and liver features, respectively. External testing in ARIC confirmed stability of the model, with Jensen-Shannon distances as low as 0.10 for HyperScore distributions, without significant deviation in organ damage progression patterns (P>0.05) and consistent end-organ and outcome characteristics between ARIC and UK Biobank across HyperTrajectories. CONCLUSIONS:Machine learning-derived global organ damage scores are feasible in hypertension and enable identification of distinct hypertension-associated organ-disease phenotypes. New frameworks for hypertension assessment and monitoring using imaging to derive personalized risk assessment and phenotype-specific intervention may be achievable.

The Tommy’s Clinical Decision Support Tool is a web-based application that is used to assess risk of preterm birth and placental dysfunction. Utilising validated algorithms and rule engines, which are more accurate than current checklist methods, the Tool instantly recommends best evidenced-based care pathways. This personalisation of assessment and decision support could reduce preterm birth and stillbirth, whilst also addressing variation in care. This study aimed to develop the intervention and assess feasibility of implementation in four NHS maternity services to inform a planned cluster randomised controlled trial. We aimed to investigate barriers and facilitators to implementation; reach (whether particular groups are excluded and why), fidelity (degree to which the intervention is delivered as intended), and unintended consequences. The NASSS framework (Non-adoption or Abandonment of technology by individuals and difficulties achieving Scale-up, Spread and Sustainability) informed analysis. We used online surveys, semi-structured interviews and focus groups to investigate maternity service user and healthcare professional (HCP) experience. One thousand one hundred eighty-one maternity service users and 112 HCPs participated, completing 1260 online surveys, 8 focus groups and 29 semi-structured interviews (women: n = 24; HCPs: n = 23). Overall, the Tool appears acceptable and easy-to-use for both pregnant and HCP users, although the burden of introducing a novel intervention within an already overstretched service was identified as a potential barrier to successful implementation. Findings influenced developments of the device and implementation strategy ahead of the trial. Lessons learned highlighted the importance of: availability of the Tool to guide care for all, including pregnant users unable, or choosing not to engage with it; top-level and multidisciplinary buy-in; dedicated resources; preparation for transitional period; local champions across professions and settings; clarity in purpose, scope, potential benefits and evidence-base; mitigation of double data entry; IT infrastructure optimisation; flexibility in training and accessibility of implementation resources. Further refinements will include non-English translation of the pregnant user interface. Tommy’s Tool has the potential to make providing optimal maternity care easier for health professionals, which could reduce variation in care and ultimately improve outcomes. This study gave us the opportunity to evaluate implementation processes and identify potential barriers to successful implementation. By addressing these barriers, ahead of the trial, we have maximised the chance of the trial results being conclusive. this study was prospectively registered on ISRCTN:ID13498237, on 31/01/2022.

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. Early pregnancy pre-eclampsia screening can identify high-risk women to initiate low-dose preventive aspirin, yet implementation of these interventions is limited in sub-Saharan Africa. This multi-country, mixed-methods study explored implementation barriers and enablers to pre-eclampsia risk screening, preventive aspirin, and AI-ultrasound gestational age assessment in Ghana, Kenya, and South Africa. We conducted surveys, qualitative interviews, and focus group discussions with women, health workers, and stakeholders. We identified two critical gaps. Without appropriate training and counselling, “risk screening” may be misunderstood as pre-eclampsia detection, rather than estimating future risk early in pregnancy to inform prevention. Busy antenatal workflows, weak information and referral systems, poor aspirin availability, limited prescribing authority, concerns about aspirin safety, low trust in new technologies, and challenges communicating high-risk status might constrain implementation of preventive action. Risk screening should be embedded in antenatal care pathways that support aspirin initiation, adherence, counselling, follow-up and referral.

Introduction Measuring foetal heart rate (FHR) is critical for assessing foetal well-being, and traditional cardiotocography (CTG), though effective, has limitations such as cost, accessibility and observer bias. Newer non-invasive foetal ECG (NIFECG) devices offer more precise, reliable metrics for FHR variability and could enable remote monitoring, potentially improving early detection of foetal complications like hypoxia and stillbirth.Methods and analysis This is a single-centre prospective cohort study taking place in a tertiary maternity unit in the UK. Women with a singleton pregnancy over 26+0 weeks will be approached for participation in the control, foetal growth restriction (FGR) or diabetic groups. The NIFECG home monitoring schedule is 60 min daily for 7 days in the control group, daily from diagnosis until delivery for the FGR group, and daily from 36 weeks until delivery in the Insulin-dependent diabetic group. Longitudinal FHR raw ECG signals will be collected from participants across different gestational age ranges. Reference standards for FHR variability using metrics such as short-term variation, phase-rectified signal averaging acceleration and deceleration capacity will be established. The study will also aim to explore differences in FHR variability in FGR cases against controls and propose safety thresholds to guide decision-making for delivery.Ethics and dissemination Approvals have been obtained from the London Stanmore Research Ethics Committee and from the Medicines and Healthcare Regulatory Agency. The results will be published in peer-reviewed journals, presented at conferences and used by the commercial sponsor to pursue European Conformity regulatory compliance marking and future clinical studies.Trial registration number NCT06497205.

Background: Hypertensive disorders of pregnancy (HDP) are associated with significant cardiac remodeling during pregnancy and are important contributors to maternal morbidity and mortality. Whether acute adverse outcomes during HDP are associated with additional clinically relevant cardiac impairment has not been widely studied. Methods: A prospective observational study was conducted on 255 women with HDP who underwent transthoracic echocardiography during the peripartum period. Maternal echocardiographic parameters, including left ventricular morphology and function, were analyzed to determine their association with adverse maternal outcomes by univariate and multivariate analyses. The composite adverse maternal outcome was defined as at least one of the following: admission to a high dependence unit, acute renal injury, adverse cardio-pulmonary events, stroke and disseminated intravascular coagulation. Results: Adverse maternal outcomes occurred in 68 (26.7%) participants. Women with adverse outcomes had significantly higher left atrial volume index (LAVI) (28.8 [23.4-32.3] ml/m2 vs 26.6 [22.2-30.9] ml/m2, p=0.045) and E/e' ratio (7.8 [6.6-9.2] vs 7.0 [5.9-8.1], p=0.002) compared to those without complications. In multivariable analysis, both LAVI (adjusted OR 1.09 [1.02-1.16], p=0.009) and E/e? ratio (adjusted OR 1.25 [1.04-1.49], p=0.018) remained independently associated with adverse maternal outcomes after adjusting for maternal factors and clinical variables. Conclusions: Cardiac abnormalities, particularly in diastolic function, are more common in women with adverse maternal outcomes in HDP. Whether enhanced cardiovascular monitoring and management of these women in the peripartum period could have immediate and long-term health benefits requires further evaluation. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This was not a clinical trial. ### Funding Statement Veronica Giorgione received funding from the European Union?s Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No 765274 (iPLACENTA project). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval was obtained from the Local Ethics Committee (19/LO/0794). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are available on request.

Introduction Pre-eclampsia is a condition associated with significant maternal and neonatal morbidity and mortality. The prediction of pre-eclampsia in high-risk populations using angiogenic markers, such as serum placental growth factor (PlGF) assessment, has been shown to improve maternal outcomes and is recommended by the National Institute for Health and Care Excellence (NICE). However, such tests are not yet available at the point of care (POC). Glycosylated fibronectin (GlyFn) level for the prediction of pre-eclampsia development is available as a POC test (Lumella) and has the potential to aid rapid clinical decision making. This study aimed to test the hypothesis that the sensitivity of the GlyFn test is not inferior to that of the current gold standard of soluble fms-like tyrosine kinase (sFlt)/PlGF-based laboratory testing for pre-eclampsia.Methods and analysis This is a multicentre prospective study. Women at risk for pre-eclampsia based on predefined clinical and/or obstetric risk factors will be invited to participate in the study. The recruitment target is 400 participants. Consenting participants will have paired samples for sFlt/PlGF together with POC GlyFn testing. Two follow-up visits are planned at 2 and 4 weeks after the initial recruitment where repeat testing with both tests will be performed. The clinical team will be blinded to the results of the GlyFn test but not that of the sFlt/PlGF test. Clinical care will be based on established protocols incorporating maternal/fetal evaluation and the results of sFlt/PlGF levels. Maternal and neonatal outcome data will be collected to compare the sensitivity and specificity of the tests, with the primary outcome being delivery for pre-eclampsia within 4 weeks.Ethics and dissemination Ethical approval has been obtained from the Health Research Authority and Health and Care Research Wales Ethics Committee. The results of this study will be published in peer-reviewed journals and presented at scientific conferences.Trial registration number ISRCTN13430018

OBJECTIVES:To provide further evidence on the outcomes associated with fetal malformations of cortical development (MCD), currently informed by data from symptomatic paediatric cohorts, this study provides a new classification system. DESIGN:Multicentre retrospective cohort study. SETTING:Fetal medicine units of three tertiary centres in the United Kingdom and Italy. POPULATION:118 foetuses diagnosed with MCD by ultrasound and/or magnetic resonance imaging included. METHODS:The cases were classified according to their presumed aetiology (genetic, haemorrhage, dysgenesis, infection) and imaging findings (focal, diffuse, mantle, sulcation). Neurodevelopmental delay was classified as mild, moderate or severe. Cases with missing information on postnatal outcome were excluded. MAIN OUTCOME MEASURES:Postnatal neurodevelopmental outcome ascertained from the infant's neurological assessments according to international performance scales, depending on the age. RESULTS:There were 52/118 (44%) livebirths, 64/118 (54.2%) terminations of pregnancy (TOP) and 2/118 (1.6%) intrauterine demises. Twenty-five of 46 cases (54.3%, 95% CI 39-69.1) that survived the neonatal period had a normal or mildly delayed neurological development. The commonest aetiology was genetic, and the most frequent radiological finding was reduced sulcation. The best neurological outcome was found in children with focal lesions; those with diffuse hemispheric lesions had the worst one. CONCLUSION:This is the largest cohort of foetuses diagnosed with MCDs systematically classified by aetiology and radiological findings. In this retrospective cohort of liveborn survivors, over half had normal or mildly abnormal neurodevelopmental outcomes. Prognosis varied according to lesion pattern and suspected aetiology. Fetal MCDs in this study had better neurodevelopmental outcomes than previously reported, though findings should be interpreted with caution given selection and follow-up limitations.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research, related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has the remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG ([email protected]). The incidence of multiple pregnancy has increased over the years, mainly due to delayed childbirth and advanced maternal age at conception and the resultant widespread use of assisted reproduction techniques1. In addition to often involving the transfer of more than one embryo, in-vitro fertilization increases the frequency of monozygotic twinning2. The twin birth rate was reported to have increased in the USA by just under 70% between 1980 (19 per 1000 live births) and 2020 (31 per 1000 live births)3, though other reports demonstrated a decline in the twin birth between 2014 and 2018 in both the USA and UK4. Twin pregnancy is associated with a high risk of perinatal mortality and morbidity5-8. There is also an increased risk of maternal complications, such as hypertensive disorders of pregnancy9. In 2019, the stillbirth rate was 7.6 per 1000 twin births compared with 3.8 per 1000 singleton births10. Preterm birth prior to 37 weeks' gestation occurs in up to 60% of multiple pregnancies, while the risk of very preterm birth prior to 32 weeks is 10 times higher in twin compared with singleton pregnancies (10% vs 1%), contributing to the increased risk of neonatal mortality and long-term morbidity11-14. Compared with singleton pregnancies, twin pregnancies are at increased risk of iatrogenic preterm birth due to the greater incidence of maternal and fetal complications. This risk is significantly higher in monochorionic compared with dichorionic pregnancy5-8. Yet, multiple pregnancies are often excluded from research studies, with only 8% of trials on fetal growth restriction (FGR), 17% of those on pre-eclampsia and 2% of those on diabetes including multiple pregnancies15. Moreover, the majority of recommendations in national and international guidelines for the management of multiple pregnancy lack high-quality robust supporting evidence16. Ultrasound assessment of chorionicity, fetal biometry, anatomy, Doppler velocimetry and amniotic fluid volume is used to identify and monitor twin pregnancies at risk of adverse outcomes, such as twin-to-twin transfusion syndrome (TTTS) and FGR. As in singletons, impaired fetal growth can be assessed in twins by comparing biometry and Doppler velocimetry parameters against standards for uncomplicated pregnancy. This guidance will address the role of ultrasound in the care of uncomplicated twin pregnancies and those complicated by TTTS, selective FGR (sFGR), twin anemia–polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence, conjoined twins and single intrauterine death (IUD). The document provides guidance on the methods used to determine gestational age and chorionicity, screening for chromosomal and structural abnormalities, and screening for TTTS, TAPS, TRAP sequence, growth abnormalities and the risk of preterm birth. The management of higher-order multiple pregnancy will be covered in a separate document. The Cochrane Library and Cochrane Register of Controlled Trials were searched for relevant randomized controlled trials (RCTs), systematic reviews and meta-analyses, and a search of MEDLINE from 1966 to 2022 was carried out. The date of the last search was 31 December 2022. In addition, relevant conference proceedings and abstracts were searched. Databases were searched using the relevant MeSH terms, including all subheadings. This was combined with a keyword search using 'twin', 'multiple', 'pregnancy', 'ultrasound', 'twin-to-twin transfusion syndrome', 'fetal growth restriction', 'twin anemia polycythemia sequence', 'twin reversed arterial perfusion', 'acardiac twin', 'monochorionic monoamniotic', 'conjoined' and 'demise'. The National Library for Health and the National Guidelines Clearing House were also searched for relevant guidelines and reviews. Gray (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections and clinical trial registries. The search was limited to the English language. When possible, recommendations are based on, and explicitly linked to, the evidence that supports them, while areas lacking evidence are annotated as 'good practice points'. Details of the grades of recommendation and levels of evidence used in these Guidelines are given in Appendix 1. The most common practice for dating twin pregnancies is to use the CRL of the larger twin in the first trimester. Some studies have recommended the use of the smaller CRL or the mean CRL, which takes into account both fetuses17-20, as studies of pregnancies conceived via assisted reproductive technology have shown that the CRL of the smaller twin correlates best with the known gestational age. The disadvantage of using the smaller CRL is the potential for the operator to believe that, in CRL-discordant pairs, the larger twin is large-for-gestational age, therefore being falsely reassured that the smaller twin is growing appropriately. One study showed that using the larger CRL did not increase the proportion of neonates classified as small-for-gestational age (SGA)20. Recommending the use of the smaller CRL would entail a significant change in practice. Generally, it would alter the due date by only a few days, and it is uncertain whether this would result in any improvement in clinical outcomes. Therefore, pending further evidence to inform this question, the recommendation is to continue with the current practice of using the CRL of the larger twin to date twin pregnancies in the first trimester. If the woman presents after 14 weeks' gestation, the head circumference of the larger twin should be used to date the pregnancy. Every effort should be made to determine the chorionicity of a twin pregnancy. Chorionicity should be determined before 13 + 6 weeks of gestation using the ultrasound features of the intertwin septum (Figure 1). It is important to examine the entire intertwin septum carefully. In dichorionic diamniotic (DCDA) twin pregnancy, the twins are separated by a thick layer of fused chorionic membranes, with two thin amniotic layers, one on each side, giving the appearance of a 'full lambda' or 'twin peak sign', compared with only two thin amniotic layers separating the two fetuses in monochorionic diamniotic (MCDA) twin pregnancy (T-sign or empty lambda sign). In women presenting for the first time after 14 weeks of gestation, chorionicity is best determined using the same ultrasound signs, in particular by counting the membrane layers, and noting whether the fetal sex is discordant. The reliability of the number of placental masses is questionable, as dichorionic placentae are commonly adjacent to each other, appearing as a single mass, and 3% of monochorionic twin pregnancies have two placental masses on ultrasound, the presence of which does not preclude the presence of vascular anastomoses21. Conversely, approximately 5% of apparently monochorionic twins were reported to be dizygotic in a Danish series22, and this phenomenon is more common in conceptions after assisted reproduction23. It is likely that using a combination of ultrasound features, rather than a single feature, would be more accurate1. If it is not possible to determine chorionicity by transabdominal ultrasound imaging, this should be attempted using transvaginal sonography. If it is still not possible to determine chorionicity, a second opinion should be sought from a tertiary referral center. If the center is uncertain about the chorionicity, it is safest to classify the pregnancy as monochorionic1 (EVIDENCE LEVEL: 3). In monochorionic twin pregnancies, amnionicity (i.e. whether or not the twins share the same amniotic sac) can be determined from 8 weeks onwards, when the amniotic sac becomes visible on ultrasound scan. In case of doubt, absence of the intertwin membrane is best confirmed by transvaginal scan. Another useful finding is demonstration of cord entanglement, which is almost universal in MCMA twin pregnancy, using color and pulsed-wave Doppler ultrasound. Using pulsed-wave Doppler, two distinct arterial waveform patterns with different heart rates are seen within the same sampling gate (EVIDENCE LEVEL: 4). Pseudo- or partial monoamnionicity is a term used to describe MCDA twin pregnancy in which the intertwin membrane has ruptured spontaneously. The term iatrogenic monoamnionicity is used when the intertwin septum in MCDA twin pregnancy is disrupted as a complication of amniocentesis or other invasive fetal procedure24, 25. All MCMA twin pregnancies should be referred to a tertiary center with expertise in their management1. It is recommended that an ultrasound image of the intertwin septum demonstrating the chorionicity is stored electronically and that a hard copy is added to the medical records. As determination of chorionicity and amnionicity is most accurate in the first trimester, when the amnion and chorion have not yet fused, the first-trimester scan is paramount in twin pregnancy (EVIDENCE LEVEL: 4). It is important to follow a reliable, consistent strategy for antenatal twin labeling. Options include: labeling according to their site, either right and left, or lower and upper; or mapping in the first trimester according to the insertion of their cords relative to the placental edges and membrane insertion. In some healthcare settings, Twin A is the fetus on the right side, while Twin B is the one on the left. Categorical information, i.e. different sex or discordance for structural anomalies, can also be used when present, as they are not likely to change with advancing gestation. This information should be documented clearly in the woman's notes in order to ensure consistent labeling during follow-up scans26. Overall, it is advisable to describe each twin using as many features as possible, so as to enable others to identify them accurately; e.g. 'Twin A (female) is on the maternal right with a posterior placenta and marginal cord insertion'. For pregnancies with discordance, the labeling should be accompanied by a description such as 'Twin A, potential recipient'. It is important to acknowledge that labeling is less accurate (or not possible) in MCMA twin pregnancy, particularly in the absence of discordance. It should be borne in mind that the twins labeled as 'Twin A' and 'Twin B' during antenatal ultrasound scans may not necessarily be delivered in that order, particularly if the mode of delivery is Cesarean section27. It is important to alert parents and healthcare professionals attending the birth to this fact, especially in pregnancies in which the twins are discordant for structural abnormalities that are not obvious on external examination, for example congenital diaphragmatic hernia or cardiac defects. In such cases, an ultrasound scan should be performed just prior to delivery and also before instigating any specific neonatal intervention. In an uncomplicated dichorionic twin pregnancy, ultrasound imaging should be performed in the first trimester, again at around 20 weeks' gestation (second-trimester anomaly scan) and every 4 weeks thereafter, unless a complication is detected which might require more frequent scans (Figure 2)1. In an uncomplicated monochorionic twin pregnancy, an ultrasound scan should be performed in the first trimester, followed by scans every 2 weeks from 16 weeks onwards, as timely detection of TTTS has been shown to improve perinatal outcome (Figure 3)28, 29 (EVIDENCE LEVEL: 4). Currently, the optimal gestational age for delivery of uncomplicated dichorionic twins is considered to be between 37 + 0 and 37 + 6 weeks, and that for uncomplicated monochorionic twins between 36 + 0 and 36 + 6 weeks, as prolongation of pregnancy beyond this stage may increase the risk of perinatal mortality30. At each ultrasound assessment, the following should be evaluated: fetal biometry, amniotic fluid volume and umbilical artery (UA) Doppler (the latter from 20 weeks' gestation in monochorionic and from 24 weeks' gestation in dichorionic twin pregnancies) for both twins. Discordance in estimated fetal weight (EFW) should be calculated and documented at each scan from 20 weeks onwards. In monochorionic twin pregnancy, middle cerebral artery (MCA) peak systolic velocity (PSV) should be recorded from 20 weeks onwards, in order to screen for TAPS. In MCDA twins, the amniotic fluid volume (deepest vertical pocket (DVP)) should be assessed and documented at each ultrasound scan, to screen for TTTS. In twin pregnancy, screening for trisomy 21 can be performed in the first trimester using the combined test, which includes maternal age, NT measurement and serum free β-hCG and PAPP-A levels1. An alternative is the combination of maternal age and the NT recorded between 11 + 0 and 13 + 6 weeks of gestation, depending on the clinical context and/or healthcare setting. The phenomenon of a vanishing twin occurs in around one in five of all twin pregnancies and is more common in those conceived via assisted reproductive technology31, 32. In a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11–13 weeks' gestation in dichorionic pregnancies with a vanishing twin (an empty gestational sac or a dead embryo) with those in normal singleton pregnancies matched for method of conception and gestational age at examination, the levels of maternal serum free β-hCG were similar, while the PAPP-A levels were higher33. Using a modeling approach, similar performance of screening for trisomy 21 could be achieved in pregnancies with, compared to those without, a vanishing twin, provided that appropriate adjustments were made to the level of PAPP-A to account for the interval between embryonic demise and blood sampling. The researchers proposed that screening in twin pregnancies with a vanishing twin could potentially rely on a combination of maternal age, NT measurement and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A, and that maternal serum PAPP-A level could be included only after appropriate adjustment for the interval between embryonic demise and blood sampling33. Prospective validation of this approach is needed before its routine implementation in clinical practice. The risk of trisomy 21 in monochorionic and thus monozygotic twin pregnancy is calculated per pregnancy based on the average risk of both fetuses, whereas in dichorionic twin pregnancy the risk is calculated per fetus, because around 90% are dizygotic. It has been assumed previously that monochorionic twins would have the same chance of having Down syndrome as singletons, and dichorionic twins would have double the risk of at least one twin being affected34. However, this does not appear to be the case. It has been found that the observed-to-expected ratio of Down syndrome in twins is lower than that in singletons: 33.6% for monozygotic, 75.2% for dizygotic and 70.0% for all twins35, 36 (EVIDENCE LEVEL: 2++). The DR of the combined first-trimester test for Down syndrome may be lower in twin compared with singleton pregnancy1. However, a meta-analysis reported similar performance (89% for singletons, 86% for dichorionic twins and 87% for monochorionic twins, at a false-positive rate (FPR) of 5%)37 (EVIDENCE LEVEL: 2++). The likelihood of being offered invasive testing on the basis of a combined screening result is greater in twin compared with singleton pregnancy1. Moreover, invasive testing may carry a greater risk in twins38-40. A meta-analysis showed that the overall procedure-related loss rate following chorionic villus sampling (CVS) in twin pregnancy was 3.8%, and following amniocentesis it was 3.1%38. Other reports have cited lower loss rates: 2% following CVS and 1.5–2% following amniocentesis41. The risk was found to be similar for transabdominal vs transcervical approaches, use of a single-needle vs double-needle system, and single vs double uterine entry23, and may be attributable more to background risk factors rather than to the procedure itself42, 43 (See also 'Invasive prenatal diagnosis in twin pregnancy' section, below.) (EVIDENCE LEVEL: 2++). Screening and diagnostic testing for trisomies is more complex in twin compared with singleton pregnancy. It is important, therefore, that counseling prior to testing is provided by healthcare professionals with expertise in this area1. It is important to inform in advance women and their partners regarding the potentially complex decisions that they will need to make on the basis of the results of combined screening, bearing in mind the increased risk of invasive testing in twins, the possible discordance between dichorionic twins for fetal aneuploidy, and the risks of selective fetal reduction1. NIPT of fetal cfDNA in maternal blood for risk assessment for fetal trisomy 21 is now commonly used in clinical practice. It has the potential to overcome many of these complex issues, because it has a much higher DR and lower FPR than does the combined test44. In singletons, NIPT has a DR of > 99% for trisomy 21, with a FPR of 0.04%45. Several factors can affect the use of NIPT in twin pregnancy. First, in dichorionic twins, aneuploidy is usually discordant; if the normal twin contributes a greater fetal fraction to the cfDNA in the maternal blood, this can lead to a false-negative result46, 47. Second, NIPT has a higher failure rate in twin pregnancy, with dichorionicity, conception by in-vitro fertilization and greater maternal weight having been identified as significant predictors of failure of NIPT46, 48. Third, single-twin demise can render unreliable the results of NIPT. These early deaths are more likely to occur in an aneuploid fetus, and this can lead to unreliable results due to the continued release of cfDNA from the demised twin into the maternal circulation49, 50. Several studies have investigated the performance of NIPT in twin pregnancy. For trisomy 21, the reported DR ranges from 94% to 100%, with a failure rate of 2.9% to 9.4%45-47, 51. For trisomies 18 and 13, the DR was 60% in twins47, compared with 97.9% and 99%, respectively, in singletons45. A recent study that recruited over 1000 twin pregnancies concluded that NIPT using cfDNA testing is the most accurate screening test for trisomy 21 in twin pregnancy, with a DR of 100% and a FPR of 0%, and a low failure rate of 0.3% (lower than that reported in other studies)52. However, the performance of this test for trisomies 18 and 13 was less accurate52. An updated meta-analysis on this topic included 137 twin pregnancies with trisomy 21, 50 with trisomy 18 and 11 with trisomy 13, and over 7500 twin pregnancies unaffected by these three trisomies53. The pooled weighted DR and FPR for trisomy 21 were 99.0% and 0.02%, respectively; the equivalent figures for trisomy 18 were 93% and 0.01%, respectively, and those for trisomy 13 were 95% and 0.10%, respectively. In summary, NIPT using cfDNA is the most accurate screening test for trisomies in twin pregnancy. Nevertheless, the number of reported cases of a trisomy in twin pregnancy diagnosed using cfDNA testing remains low, and further evidence is needed (EVIDENCE LEVEL: 2++). When invasive testing for chromosomal or genetic analysis of twins is indicated or desired, it should be carried out by a fetal medicine expert. CVS is preferred in dichorionic twin pregnancy because it can be performed earlier than amniocentesis. Earlier diagnosis of any aneuploidy is particularly important in dichorionic twin pregnancy, given the lower risk of selective termination in the first compared with the second trimester54, 55. It is important to map carefully the position of the twins within the uterus. During amniocentesis in monochorionic twins, if monochorionicity has been confirmed before 14 weeks' gestation and the fetuses appear concordant for growth and anatomy, it is acceptable to sample only one amniotic sac. Otherwise, both amniotic sacs should be sampled because of the possibility of rare discordant chromosomal anomalies in monochorionic pregnancy. CVS in monochorionic pregnancy will sample only the single placenta, so will miss these rare discordant chromosomal anomalies. Discordance for most of the common human aneuploidies (trisomies 13, 18 and 21, Turner syndrome and triploidy) has been reported in monochorionic twin pairs56. In the event of heterokaryotypic monochorionic pregnancy, selective reduction by umbilical cord occlusion can be offered from 16 weeks onwards, with a survival rate of more than 80% for the healthy twin57, 58. When monochorionic twins are discordant for an abnormality, prior to invasive testing a discussion should take place regarding the complexity of selective termination, should this become necessary58 (EVIDENCE LEVEL: 3). A 2012 meta-analysis38 of amniocentesis in twin pregnancies reported a pooled 3.07% pregnancy loss rate, and a 2.54% loss rate before 24 weeks; for case–control studies, the pooled loss rates for twin pregnancies undergoing amniocentesis and for control twins were 2.59% vs 1.53% (relative risk, 1.81 (95% CI, 1.02–3.19)). No difference was found between single vs double uterine entry (EVIDENCE LEVEL: 2+). The same meta-analysis38, albeit with limited data for CVS, reported a pooled loss rate of 3.84% after CVS in twins. There were no significant differences between the transabdominal and transcervical approach, use of a single-needle system vs a double-needle system, or single uterine entry vs double uterine entry (EVIDENCE LEVEL: 2+). No significant differences in loss rates have been reported between CVS and amniocentesis in retrospective studies comparing the two methods. A study including twin pregnancy data from the years 1984–1990 reported a 3.2% loss rate after CVS vs 2.9% after amniocentesis59 (EVIDENCE LEVEL 2+). A more recent study found a non-significant difference, reporting loss rates of 3.85% and 4.0% after CVS and amniocentesis, respectively60 (EVIDENCE LEVEL: 2+). There are insufficient data to compare the loss rate related to CVS with the background risk in twins. A meta-analysis published in 202061 compared directly outcomes between women with twin pregnancy undergoing amniocentesis and those not undergoing amniocentesis, and between women undergoing CVS and those not undergoing CVS. It was found that, compared to the background rate of fetal loss, in pregnancies undergoing amniocentesis, there was no significant difference in the rate of fetal loss before 24 weeks of gestation (odds ratio (OR), 1.59; P = 0.06) or within 4 weeks after the procedure (OR, 1.38, P = 0.3). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4–3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9–4.6%) in those not undergoing amniocentesis. Similarly, there was no significant difference compared with the background rate in either overall fetal loss (OR, 1.61; P = 0.5) or fetal loss before 24 weeks of gestation (OR, 1.61; P = 0.5) following CVS. Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0–6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3–4.2%) in those not undergoing CVS. Those undergoing invasive testing may represent a selected population already at increased risk of miscarriage; two recent multicenter studies attempted to control for this while assessing the CVS procedure-related risk of miscarriage in twin pregnancy42, 43. The first study42 used multivariable logistic regression analysis with backward stepwise elimination, adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free β-hCG and PAPP-A multiples of the median (MoM). The authors reported that, after adjustment for maternal and pregnancy characteristics, CVS did not contribute significantly to the risk of fetal loss. They also found no significant association between fetal loss and the number of intrauterine needle insertions or needle size (LEVEL OF EVIDENCE 2++). The second of these studies43, from the same group, assessed the risk of death of at least one fetus in twin pregnancies that had CVS and those that did not, after propensity score matching (1:1 ratio) which created two comparable groups by balancing the maternal and pregnancy characteristics that led to CVS being performed. The authors reported that there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (OR, 0.81; 95% CI, 0.48–1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss: when the background risk was higher, the risk of fetal loss after CVS was lower (OR, 0.46; 95% CI, 0.23–0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS was higher (OR 2.45; 95% CI, 0.95–7.13) (LEVEL OF EVIDENCE 2++). In summary, the current evidence suggests that the contribution of amniocentesis or CVS to the risk of fetal loss in twin pregnancy is likely to be small, with procedure-related loss rates of less than 1% (though, paradoxically, the risk might be a little greater in pregnancies at lower background risk of fetal loss). The technique for amniocentesis and CVS in twin pregnancies is described in more detail in the ISUOG Practice Guidelines for invasive procedures for prenatal diagnosis62. In a dichorionic twin pregnancy, sampling of both amniotic sacs is recommended. There is a small (1.8%) risk of sampling the same sac twice with the two-puncture technique (one per sac). Using the single-puncture technique with intertwin membrane passage, the first 1–2 mL of amniotic fluid sampled after intertwin membrane passage should be discarded to avoid contamination from the first twin. If sampling of two sacs is clinically indicated, as in the case of monochorionic twin pregnancy, the two-puncture technique is recommended to avoid iatrogenic monoamnionicity (EVIDENCE LEVEL: 4). When performing CVS, it is recommended to sample the placenta near the cord insertion and to avoid the area around the dividing membrane in order to avoid unreliable or inaccurate results (which have been reported in 3–4% of cases) (EVIDENCE LEVEL: 4). A single-sampling approach around the amniotic equator is a reasonable option in monochorionic twin pregnancy (EVIDENCE LEVEL: 4). Determination of zygosity should be recommended for the laboratory analysis. It is preferred that the same operator performs the invasive diagnosis and the selective termination procedure, if needed, taking into account local protocols and the resources available. Although some studies have reported an association between first-trimester intertwin discordance in NT or CRL, or reversed a-wave in the ductus venosus (DV), and the development of TTTS, their predictive value is poor26, 63-66. NT discordance of 20% had a sensitivity of 52–64%, specificity of 78–80%, positive predictive value of 50% and negative predictive value of 86% for the development of TTTS67, 68. Discordance in NT of ≥ 20% is found in around 25% of monochorionic twin pregnancies, and the risk of early IUD or development of severe TTTS in these cases is more than 30%68. The risk of complications is less than 10% if the NT discordance is <20%68. An abnormal DV (reversed a-wave in at least one of the fetuses) will pick up only 38% of all monochorionic twin pregnancies that will subsequently develop TTTS, and, of those predicted to be at high risk, only 30% will ultimately develop TTTS65. Similarly, although intertwin discordance in CRL at 11–13 weeks' gestation is significantly associated with the risk of pregnancy loss ≥ 24 weeks, birth-weight discordance and preterm birth prior to 34 weeks' gestation, again, the predictive value is poor69, 70. Nevertheless, the management of twin pregnancy with CRL discordance ≥ 10% or NT discordance ≥ 20% should be discussed with a fetal medicine expert in accordance with local guidelines and depending on resource availability, and in these pregnancies there should be detailed ultrasound assessment and possibly testing for aneuploidy if fetal abnormalities are identified. The risk of fetal abnormality was found to be 25% in dichorionic twin pregnancies with CRL discordance ≥ 10%, compared with 4% in pregnancies with CRL discordance < 10%71. Also, CRL discordance at 7 + 0 to 9 + 6 weeks' gestation is a predictor of the risk of single fetal demise in the first trimester (DR, 74% for a FPR of 5%)72 (EVIDENCE LEVEL: 2++). At the first-trimester scan (between 11 + 0 and 13 + 6 weeks' gestation), twin fetuses should be assessed for the presence of a