Basky Thilaganathan

and 1 more

Authors’s replyDear Prof. Papageorghiou,We thank the authors for their thoughtful critique of our interrupted time series analysis (ITS) evaluating the impact of first-trimester preeclampsia screening with targeted aspirin prophylaxis on preterm birth (PTB)[1]. We welcome the opportunity to clarify several methodological choices and acknowledge areas where future work is needed.The concern regarding dilution of effect in the whole-population analysis is well made. However, we were explicit that our objective was to assess the population-level  impact of implementing the screening programme as it operates in routine care, where eligibility and uptake vary. While subgroup analyses by FMF-defined risk category may well be informative, without aspirin prophylaxis or other PTB prevention interventions in these lower-risk groups, we doubt that such analyses would be informative in our cohort without introducing substantial misclassification and potential bias. We agree that as data completeness improves, and risk-specific interventions are introduced, risk-stratified evaluations may become increasingly insightful.We also recognise that secular changes in demography and obstetric practice may influence PTB rates. Although ITS analysis explicitly models pre-intervention trends, we were unable to incorporate time-varying covariates due to the retrospective, population-based nature of the study and the inconsistent availability of key clinical variables in the accessible dataset. We appreciate the suggestion to explore negative-control outcomes but note the limitation of this approach in pragmatic implementation studies. A randomised control trial would best address these limitations; however, our data suggest that such a trial would be precluded by the sample size required.We agree that adherence to aspirin is central to achieving clinical effectiveness. Even though prescription rates were high (>98%), detailed data on adherence to therapy are not captured in routine records, which we acknowledge as a limitation. We postulate that the clinical effectiveness of our programme in reducing preterm preeclampsia would imply good compliance to aspirin prophylaxis. Our findings reflect real-world programme effectiveness rather than biological efficacy under optimised conditions[2].As expected, many PTB events in our cohort were spontaneous and therefore only partially modifiable by aspirin. For this reason, we do not interpret the neutral PTB trend as evidence against the value of FMF-based vascular risk stratification, but rather as an indication that additional complementary PTB prevention strategies - such as cervical assessment and infection screening - are required to achieve meaningful reductions in PTB at a population level.We appreciate the authors’ engagement with our work.Your sincerely,Basky Thilaganathan and Monica Minopoli, on behalf of all authorsDisclosure of interests: None declared.Contribution to authorship: Basky Thilaganathan and Monica Minopoli drafted the response. All other authors consented to content of this reply.

Natalia Abadia-Cuchi

and 13 more

Objectives: To provide further evidence on the outcomes associated with fetal malformations of cortical development (MCD), currently informed by data from symptomatic pediatric cohorts, providing a new classification system. Design: Multicenter retrospective cohort study. Setting: Fetal medicine units of three tertiary centers in United Kingdom and Italy. Population: 118 fetuses diagnosed with MCD by ultrasound and/or magnetic resonance imaging included. Methods: The cases were classified according to their presumed etiology (genetic, hemorrhage, dysgenesis, infection) and imaging findings (focal, diffuse, mantle, sulcation). Neurodevelopmental delay was classified as mild, moderate or severe. Cases with missing information on pregnancy or 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 (44%) livebirths, 64 (54.2%) terminations of pregnancy (TOP) and two (1.6%) intrauterine demises . 24 of 46 cases (54.3 %, 95% CI 39.01 -79.10) that survived the neonatal period had a normal or mildly delayed neurological development. The commonest etiology was genetic and the most frequent radiological finding was reduced sulcation. The best neurological outcome was found in children with focal lesions, and those with diffuse hemispheric lesions had the worst one. Conclusion: This is the largest cohort of fetuses diagnosed with MCDs systematically classified using etiology and radiological findings. Fetal MCDs have a better than previously expected postnatal neurodevelopmental outcome that is related to both the etiological classification and radiological findings: these results should be considered when counselling for a prenatal diagnosis of MCD.

Miriam Lopian

and 11 more

Objective: To assess whether combining estimated fetal weight (EFW) and fetal Doppler ultrasound parameters would provide information to optimise timing of birth in monochorionic twin pregnancies and prevent adverse perinatal outcomes. Study design: Retrospective multicentre cohort study. Setting: Three tertiary centres in the UK, Italy and Belgium. Population: 624 monochorionic twin pregnancies managed between 2013 and 2023. Methods: Univariable and multivariable analyses assessed the association between EFW and Doppler indices taken within two weeks of birth. Main Outcome Measures: Stillbirth or iatrogenic preterm birth before 34 weeks for non-reassuring fetal status. Results: The primary outcome occurred in 143 (22.9%) pregnancies with 70 cases of early PTB for fetal reasons and 73 cases of at least one IUD. Significant associations between biometric and Doppler parameters and adverse perinatal outcomes were found. The best-performing prediction models incorporated EFW discordance and umbilical artery pulsatility index (UA PI) discordance, achieving an AUC of 0.85 (95% CI 0.78-0.91) and EFW discordance and absent or reverse end diastolic flow of UA PI with an AUC of 0.86 (95% CI 0.80-0.92) . The model incorporating EFW and UA PI discordance could be applied to the largest proportion of pregnancies and outperformed the currently clinical sFGR classification in predicting adverse outcomes. Conclusion: A model incorporating intertwin EFW discordance and UA PI discordance outperforms the current clinical classification for prediction of adverse perinatal outcomes in monochorionic pregnancies. If confirmed by further external validation studies, these findings could contribute to build a tailored risk assessment in these pregnancies.

Veronica Giorgione

and 3 more

Author responseVeronica Giorgione1, *Basky Thilaganathan1,2, Alessandra Familiari3,4, Elisa Bevilacqua31. Fetal Medicine Unit, St George’s University Hospitals NHS Foundation Trust, London, UK.2. Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, London, UK.3. Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.4. Catholic University of the Sacred Heart, Rome, Italy.*basky@pobox.comDear Professor Papageorghiou,We thank Prof. Wright and colleagues for their thoughtful comments on our paper “Predicting Adverse Perinatal Outcomes in Dichorionic Twin Pregnancies” .1 We welcome the opportunity to clarify the issue of ultrasound timing and to present additional sensitivity analyses addressing their concerns.As noted by the authors, in our study estimated fetal weight (EFW) and Doppler measurements were obtained within two weeks of delivery or an adverse fetal event. This approach reflects standard clinical practice in twin pregnancy, where surveillance is intensified when fetal compromise is suspected. As detailed in the Methods, our aim was to build an antenatal prediction model using routinely collected variables rather than to investigate causal pathways leading to delivery. Importantly, all ultrasound assessments were performed within two weeks of the outcome of interest, and therefore the timing of scans does not invalidate the associations, but does influence how the model is used clinically.We feel it is important to re-iterate that the primary outcome of the study was stillbirth at any gestation or indicated birth before 34 weeks’ gestation for concerns over fetal wellbeing. As such, we included data from scans beyond 34 weeks in the original analysis because the majority of pregnancies progressed beyond this gestation regardless of whether they subsequently resulted in a livebirth or were stillborn.Nevertheless, to address the potential temporal overlap highlighted by Wright and Nicolaides, we performed a dedicated sensitivity analysis restricted to pregnancies in which the index scan occurred before 34 weeks’ gestation, which comprised 333 dichorionic twin pregnancies. The model combining EFW and umbilical artery (UA) pulsatility index discordance achieved an AUC of 0.87 (95% CI 0.81–0.93), with odds ratios of 1.06 (95% CI 1.03–1.08) and 1.06 (95% CI 1.04–1.08), respectively. Adding middle cerebral artery (MCA) Doppler or SGA 0.86–0.89). These results confirm that the predictive ability of fetal biometry and Doppler discordance remains robust when analyses are limited to measurements obtained entirely before the 34-week threshold.We acknowledge that, as in any observational study, ultrasound scheduling and clinical decisions may introduce elements of interventional bias. However, by restricting analyses only to ultrasound data collected at least two weeks before delivery or an adverse outcome, and confirming comparable performance in the <34 week subset, we believe the influence of such bias on our estimates is minimal. Future prospective studies with standardised scanning intervals could further validate these findings.In conclusion, our sensitivity analysis demonstrates that EFW and UA PI discordance measured before 34 weeks maintain high predictive accuracy for stillbirth or iatrogenic preterm birth <34 weeks, underscoring the robustness and clinical applicability of our model. We thank Prof. Wright and colleagues for prompting this clarification, which we believe strengthens the evidence base for antenatal risk stratification in dichorionic twin pregnancies.Sincerely,Veronica Giorgione, on behalf of all authors1. V Giorgione, M Trapani, M Lopian et al., “Predicting Adverse Perinatal Outcomes in Dichorionic Twin Pregnancies: A Multicentre Cohort Study” British Journal of Obstetrics and Gynaecology. 2025 Jun;132(7):983-990.

Claire Pegorie

and 6 more

Objective: To assess the clinical effectiveness of the TRUFFLE monitoring protocol in a routine clinical setting. Secondary objectives were evaluating timing and indications for delivery, stratified by gestational age at Fetal Growth Restriction (FGR) diagnosis. Design: Retrospective cohort study. Setting: Tertiary Fetal Medicine Unit. Population or Sample: Singleton pregnancies diagnosed with FGR between 2013 and 2024. Methods: FGR was defined as an estimated fetal weight or abdominal circumference <10th centile with an elevated umbilical artery pulsatility index >95th centile, diagnosed before 36 weeks’ gestation. Exclusion criteria were multiple pregnancies, major fetal anomalies, delivery before 26 weeks, and absence of TRUFFLE protocol monitoring. Main outcome measures: Perinatal survival, interval from diagnosis to delivery, and delivery indications. Results: 196 pregnancies met inclusion criteria. Median gestational age at FGR diagnosis was 28 +1 (26 +2-30 +3) weeks and 30 +6 (28 +3-33 +3) at delivery. Overall intact survival was 92.3%, with 2.6% stillbirths and 5.2% neonatal deaths. Diagnosis prior to 26 weeks allowed longer pregnancy prolongation (31 days compared to 10.5 days; p<0.001). Below 32 weeks, the predominant trigger for delivery was abnormal computerised CTG (low STV). Above 32 weeks, abnormal umbilical artery Doppler and maternal indications became more frequent. Conclusions: The TRUFFLE monitoring protocol is clinically effective in managing early-onset FGR outside a trial environment, achieving comparable perinatal outcomes. Routine integration of both Doppler and cCTG STV monitoring, is crucial for optimal timing of delivery. Further research is needed to assess if more frequent or remote fetal monitoring to improve outcomes. Funding: No funding was received.

G Blayney

and 3 more

Objective: To evaluate the impact of twin dating by ultrasound-measured crown-rump length (CRL) of the larger (CRL-L), smaller (CRL-S) or mean twin measurement (CRL-M) on the rates of preterm birth (PTB) and detection of fetal growth restriction. Design: A cohort study. Setting: A tertiary fetal medicine centre (London, UK). Population or sample: All twin pregnancies between 1998 and 2023 who underwent ultrasound assessment of first trimester CRL and fetal growth. Methods: Data collection included CRL measurement, estimated fetal weight (EFW), pregnancy outcome and birthweight (BW) for each twin. Pregnancies were retrospectively re-dated by CRL-S, CRL-L and CRL-M. Main outcome measures: Small for gestational age (SGA) <10 th centile and PTB rates. Results: Of the 1129 twin pairs median CRL was 61mm (IQR:56.0-66.0) and 63mm (IQR:58.4-68.9) for the smaller and larger twin respectively with a mean discordance of 4.0%. Prenatal SGA diagnosis occurred in 19.8% and 23.1% of smaller twins when dated by CRL-S and CRL-L respectively. When pregnancies were dated by CRL-M versus CRL-S or CRL-L there was no difference in prenatal SGA diagnosis (p=0.275 and p=0.419); SGA at birth (p=0.132 and p=0.325); or PTB (p=1.00 and p=0.765 respectively). Conclusions: Dating by the smaller, larger or mean-twin CRL doesn’t significantly alter rates of extreme preterm birth, SGA detection or SGA birth. Dating by the mean twin CRL reduces stigmatisation of the smaller twin, alleviating parental anxiety, whilst retaining the utility of accurate gestational age assessment without impacting on clinical outcomes.