Objective: Refine the programme theory for OptiBreech Care Design: Concurrent mixed methods implementation process evaluation Setting: 6 NHS hospitals in England participating in the OptiBreech 1 Feasibility Study Sample: 15 women planning a vaginal breech birth at term and 6 breech lead midwives Methods: Outcomes were recorded on case report forms and descriptively analysed. Interviews were recorded, transcribed and analysed using the Theoretical Framework of Acceptability. Iterative analysis informed subsequent interviews and the on-going process of implementation across sites. Main Outcome Measures: Acceptability of service delivery models and their outcomes. Results: Actively recruiting Trusts implemented services through a dedicated clinic and/or a proficient intrapartum support service, organised and provided primarily by a Breech Specialist Midwife. While we identified challenges, this model has achieved 93% fidelity to the intervention’s goal of ensuring attendance of OptiBreech-trained professionals at vaginal breech births, and it is highly acceptable to women. Our initial suggested model of a multi-disciplinary team composed of 5 obstetricians and 5 midwives does not appear feasible, due to very low overall current breech experience levels and the context of current pressures on NHS services. Conclusions: Appointment of a Breech Specialist Midwife, whose role is to co-ordinate a dedicated clinic, training and a proficient intrapartum care team, appears to be highly acceptable to women. This model appears to be a feasible implementation strategy, in order to test the safety and effectiveness of OptiBreech Care in a clinical trial, but further work needs to be done to develop sustainability.

BJOG-20-0640.R1 The evolving definition of pre-eclampsia

Risk assessment to target aspirin is accurate but not universalLow dose aspirin, for the prevention of early onset pre-eclampsia is an established antenatal intervention; it is safe, effective, cheap and accessible in many health care settings.Optimal implementation strategies including dose, timing and screening are currently debated. The evidence supports starting aspirin early (before 16 weeks), prescribe at night, give up to 150mg and continue until at least 36 weeks gestation ((Poon et al. Int J Gynaecol Obstet. 2019 May;145 Suppl 1(Suppl 1):1-33). From the women’s perspective, many may not be happy to routinely medicate an apparently normal pregnancy, to prevent an unknown or unfamiliar disease.Despite campaigns by APEC and others, too many women only hear of pre-eclampsia when it affects them. Generally, as perceived risks escalate the acceptance of taking aspirin is greater which improves compliance by both physicians prescribing, and by pregnant women. Any strategy that allows targeting of aspirin is likely to prevent unnecessary treatment and would be welcomed. It should be noted that the MBRAACE Report (Knight et al. University of Oxford 2019. ISBN: 978-0-9956854-8-2) called for a national patient direction for midwives to prescribe aspirin which has not yet happened.This current analysis compared two such strategies to target antenatal aspirin NICE guidance uses history to establish risk (Guy et al. BJOG 2020 xxxx). It is relatively simple, requiring either a combination of minor risk factors or a single major risk factor to dictate the need for aspirin. The FMF algorithm uses a combination of tests, including scans, blood pressure and blood markers to dictate risk; this requires skill and more resource which may not be consistently available in lower income settings.When compared in a real-world setting, in a London teaching hospital, the FMF algorithm had a screen positive rate that was half that of NICE, while aspirin was given to far more high-risk women. The FMF algorithm was changed to suit local circumstances, including details of the tests used (PAPPA, rather than PLGF) and thresholds adopted for treatment, but the real-world findings are impressive.The dosage of aspirin was higher in the FMF group, (150mg vs 75mg) which could explain some of the additional clinical benefit. Aspirin has recently been shown to impact on preterm birth when given routinely to all women who have never given birth in a low resource setting. In these settings, the cost and practicalities of implementing the algorithm maybe prohibitive. However, elements of the algorithm such as blood pressure measurement are simple and potentially more generalisable.It is exciting we have an intervention that can impact on one of the world’s most significant pregnancy disorders; but if resources allow, we clearly now have the tools to predict risk and improve outcomes. The challenge is how to deliver this to the global south, where most of pre-eclampsia occurs.At Action on Pre-Eclampsia, in the UK, we will continue to push for easy availability of aspirin. This paper is a welcome piece of the jigsaw and we hope it offers further tools in the armoury to defeat pre-eclampsia.No disclosures: Completed disclosure of interest forms are available to view online as supporting information.

Despite extensive research, the pathophysiology and prevention of pre-eclampsia remain elusive, diagnosis is challenging, and pre-eclampsia remains associated with adverse maternal and perinatal outcomes. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), have been identified as valuable biomarkers for preterm pre-eclampsia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high-risk women. PlGF-based testing is increasingly being implemented into clinical practice in several countries. This review provides healthcare providers with an understanding of the evidence for PlGF-based testing and describes the practicalities and challenges to implementation.

Objective: to establish a prognostic model informing optimal timing of delivery in women with late preterm preeclampsia. Design: development and validation of a prognostic model Setting: prospective cohort study, nested in the PHOENIX trial, in 36 maternity units across England and Wales. Population: women with late preterm pre-eclampsia (34+0-36+6 weeks’ gestation) Methods: prospective recruitment of women in whom blood samples for Placental Growth Factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) testing was obtained, alongside clinical data, for use within the ‘Prediction of complications in early-onset pre-eclampsia’ (PREP)-S model. Candidate variables were compared using standard methods (sensitivity, specificity, Receiver Operator Curve areas). Estimated probability of early delivery from PREP-S was compared to actual event rates by calibration. Main Outcome Measures: clinically indicated need for delivery for pre-eclampsia within seven days. Results: PlGF testing had high sensitivity (97.9%) for delivery within seven days, but negative predictive value was only 71.4%, with low specificity (8.4%). The area under the curve for PREP-S was 0.64 (standard error (SE) 0.03), for PlGF was 0.60 (SE 0.03), and 0.65 (0.03), and 0.64 (0.03) for PREP-S in combination with PlGF and sFlt-1:PlGF, respectively. Conclusions: PlGF-based testing does not add to clinical assessment to determine need for delivery in late preterm pre-eclampsia. Existing models developed in women with early onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia. Funding: NIHR HTA Monitoring Add on Studies Programme (reference 15/59/06). Keywords: placental growth factor, preeclampsia, prognosis

Dear Editor,We would like to comment on the systematic review by Li et al.(1)The use of steroid hormones in the first trimester is a serious issue as organogenesis takes place at this time and therefore there is the possibility of harm from not only congenital anomalies, but also long-term, and even inter-generational effects. Anyone investigating the use of steroid hormones in the first trimester should remember the diethylstilbestrol legacy of devastating harm. Oestrogen (C18H24O2) and diethylstilbestrol (C18H20O2) have similar molecular composition, but their effects are poles apart. In this review, the authors have combined progesterone with progestogens; however they are not the same, in the same way that oestrogen and diethylstilbestrol are not the same. Vaginal micronized progesterone, which we used in our large and high-quality trials (the PROMISE (2) and PRISM (3) trials), has identical molecular structure to natural progesterone, but the other drugs included in this review do not (Table 1). We chose to study vaginal micronized progesterone, as it is identical in structure to natural progesterone, and the available evidence and expert opinion suggested that this is least likely to cause harm. It is important to note that there is evidence of potential harm from dydrogesterone, particularly congenital heart disease.(4)The authors make a bold statement in the abstract about the effects of dydrogesterone on live birth rate. However, they don’t fully address the weaknesses in the evidence. Therefore, we wish to highlight the significant deficiencies in the two trials that contributed live birth data that led to the assertion of beneficial effects from dydrogesterone. Both studies were single centre, open-label studies without placebo control. El-Zibdeh et al did not randomise participants, but instead allocated patients to dydrogesterone on Saturdays, Mondays and Wednesdays, and to no treatment on Sundays, Tuesdays and Thursdays. The trial by Pandian RU was not just a single-centre, but also a single-author study, with insufficient details of the methods to assess its quality. Thus, the effectiveness evidence from these trials cannot be considered reliable.Approximately 80% (4038 of 5056) of the data used in this systematic review come from our PRISM trial.(3) The PRISM trial is a prospectively-registered, randomised, placebo-controlled, multi-centre trial conducted to the highest standards in the UK. The trial found a 3% increase in live birth rate, but with borderline statistical significance (RR, 1.03; 95% CI, 1.00 to 1.07; P=0.08). A pre-specified subgroup analysis in women with the dual risk factors of current pregnancy bleeding and one or more previous miscarriages found a 5% increase in live birth rate (RR, 1.09; 95% CI, 1.03-1.15; P=0.003). In those with three or more previous miscarriages, a 15% increase in live birth rate was observed (RR, 1.28; 95% CI, 1.08 to 1.51; P=0.004).(3, 5) No short-term safety concerns were identified. Based on these data, our recommendation is to consider vaginal micronized progesterone for women with early pregnancy bleeding and one or more previous miscarriages. As for the role of dydrogesterone, we need not only high-quality, randomised trial evidence of its effects but also credible evidence of its safety. As dydrogesterone is a synthetic progesterone-like drug, i.e. a progestogen but not progesterone, the burden of proof to demonstrate short- and long-term safety rests on those promoting this drug.