Summary Background Previous prospective cohort studies have shown that angiogenic factors have a high diagnostic accuracy in women with suspected pre-eclampsia, but we remain uncertain of the effectiveness of these tests in a real-world setting. We therefore aimed to determine whether knowledge of the circulating concentration of placental growth factor (PlGF), an angiogenic factor, integrated with a clinical management algorithm, decreased the time for clinicians to make a diagnosis in women with suspected pre-eclampsia, and whether this approach reduced subsequent maternal or perinatal adverse outcomes. Methods We did a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial in 11 maternity units in the UK, which were each responsible for 3000–9000 deliveries per year. Women aged 18 years and older who presented with suspected pre-eclampsia between 20 weeks and 0 days of gestation and 36 weeks and 6 days of gestation, with a live, singleton fetus were invited to participate by the clinical research team. Suspected pre-eclampsia was defined as new-onset or worsening of existing hypertension, dipstick proteinuria, epigastric or right upper-quadrant pain, headache with visual disturbances, fetal growth restriction, or abnormal maternal blood tests that were suggestive of disease (such as thrombocytopenia or hepatic or renal dysfunction). Women were approached individually, they consented for study inclusion, and they were asked to give blood samples. We randomly allocated the maternity units, representing the clusters, to blocks. Blocks represented an intervention initiation time, which occurred at equally spaced 6-week intervals throughout the trial. At the start of the trial, all units had usual care (in which PlGF measurements were also taken but were concealed from clinicians and women). At the initiation time of each successive block, a site began to use the intervention (in which the circulating PlGF measurement was revealed and a clinical management algorithm was used). Enrolment of women continued for the duration of the blocks either to concealed PlGF testing, or after implementation, to revealed PlGF testing. The primary outcome was the time from presentation with suspected pre-eclampsia to documented pre-eclampsia in women enrolled in the trial who received a diagnosis of pre-eclampsia by their treating clinicians. This trial is registered with ISRCTN, number 16842031. Findings Between June 13, 2016, and Oct 27, 2017, we enrolled and assessed 1035 women with suspected pre-eclampsia. 12 (1%) women were found to be ineligible. Of the 1023 eligible women, 576 (56%) women were assigned to the intervention (revealed testing) group, and 447 (44%) women were assigned to receive usual care with additional concealed testing (concealed testing group). Three (1%) women in the revealed testing group were lost to follow-up, so 573 (99%) women in this group were included in the analyses. One (<1%) woman in the co...

Oxidative stress is implicated in the pathophysiology of many reproductive complications including infertility, miscarriage, pre-eclampsia, fetal growth restriction and preterm labour. The presence of excess reactive oxygen species can lead to cellular damage of deoxyribonucleic acids, lipids and proteins. Antioxidants protect cells from peroxidation reactions, limiting cellular damage and helping to maintain cellular membrane integrity. There is overwhelming evidence for oxidative stress causing harm in reproduction. However, there is sparse evidence that supplementation with commonly used antioxidants (mostly vitamins C and E) makes any difference in overcoming oxidative stress or reversing disease processes. There may be potential for antioxidant therapy to ameliorate or prevent disease, but this requires a thorough understanding of the mechanism of action and specificity of currently used antioxidants.

Pre-eclampsia is a leading cause of maternal mortality, responsible annually for over 60,000 maternal deaths around the globe. Pre-eclampsia is a multisystem disease featuring hypertension, proteinuria, and renal, hepatic, and neurological involvement. Diagnosis is often elusive, as clinical presentation is highly variable. Even those with severe disease can remain asymptomatic. Angiogenic factors are emerging as having a role in the diagnosis of pre-eclampsia and in prognostication of established disease. In this article, we summarize new developments and focus on angiogenic biomarkers for prediction of disease onset. We also discuss recent advances in management strategies for patients with hypertensive disorders of pregnancy.

Objective To calculate the cost‐effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. Design Cost‐effectiveness analysis. Setting Eleven maternity units participating in the PARROT stepped‐wedge cluster‐randomised controlled trial. Population Women presenting with suspected pre‐eclampsia between 20+0 and 36+6 weeks’ gestation. Methods Monte Carlo simulation utilising resource use data and maternal adverse outcomes. Main outcome measures Cost per maternal adverse outcome prevented. Results Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost‐saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost‐saving of UK£2,891,196 each year across the NHS in England. Conclusions Clinical care with PlGF testing is associated with the potential for cost‐savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre‐eclampsia. Tweetable abstract Placental growth factor testing for suspected pre‐eclampsia is cost‐saving and improves maternal outcomes.

BackgroundObstetric haemorrhage, sepsis and pregnancy hypertension account for more than 50% of maternal deaths worldwide. Early detection and effective management of these conditions relies on vital signs. The Microlife® CRADLE Vital Sign Alert (VSA) is an easy-to-use, accurate device that measures blood pressure and pulse. It incorporates a traffic-light early warning system that alerts all levels of healthcare provider to the need for escalation of care in women with obstetric haemorrhage, sepsis or pregnancy hypertension, thereby aiding early recognition of haemodynamic instability and preventing maternal mortality and morbidity. The aim of the trial was to determine whether implementation of the CRADLE intervention (the Microlife® CRADLE VSA device and CRADLE training package) into routine maternity care in place of existing equipment will reduce a composite outcome of maternal mortality and morbidity in low- and middle-income country populations.MethodsThe CRADLE-3 trial was a stepped-wedge cluster-randomised controlled trial of the CRADLE intervention compared to routine maternity care. Each cluster crossed from routine maternity care to the intervention at 2-monthly intervals over the course of 20 months (April 2016 to November 2017). All women identified as pregnant or within 6 weeks postpartum, presenting for maternity care in cluster catchment areas were eligible to participate. Primary outcome data (composite of maternal death, eclampsia and emergency hysterectomy per 10,000 deliveries) were collected at 10 clusters (Gokak, Belgaum, India; Harare, Zimbabwe; Ndola, Zambia; Lusaka, Zambia; Free Town, Sierra Leone; Mbale, Uganda; Kampala, Uganda; Cap Haitien, Haiti; South West, Malawi; Addis Ababa, Ethiopia). This trial was informed by the Medical Research Council guidance for complex interventions. A process evaluation was undertaken to evaluate implementation in each site and a cost-effectiveness evaluation will be undertaken.DiscussionAll aspects of this protocol have been evaluated in a feasibility study, with subsequent optimisation of the intervention. This trial will demonstrate the potential impact of the CRADLE intervention on reducing maternal mortality and morbidity in low-resource settings. It is anticipated that the relatively low cost of the intervention and ease of integration into existing health systems will be of significant interest to local, national and international health policy-makers.Trial registrationISCRTN41244132. Registered on 2 February 2016.Prospective protocol modifications have been recorded and were communicated to the Ethics Committees and Trials Committees. The adapted Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Checklist and the SPIRIT Checklist are attached as Additional file 1.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2581-z) contains supplementary material, which is available to authorized users.

Key content Accurate blood pressure (BP) measurement is fundamental to early diagnosis of hypertensive disorders in pregnancy. Poor auscultatory technique and lack of training leads to inaccuracies in BP measurement using sphygmomanometry with mercury and aneroid devices. Automated devices limit user error but require validation of accuracy because they tend to underestimate BP in pre‐eclampsia. Systolic hypertension may better predict risk of adverse outcome (such as haemorrhagic stroke) than diastolic hypertension. Ambulatory/self‐monitoring increases the number of representative readings available on which to base management, limiting unnecessary intervention. Detection of hypotension in pregnancy is crucial to the diagnosis of shock secondary to haemorrhage and sepsis. Learning objectives To learn how to obtain accurate BP measurements in pregnancy. To understand the significance of hypertension in pregnancy. Ethical issues A large proportion of maternal deaths are associated with substandard care, often related to poor recognition of severity of hypertension or shock and need for treatment. Lack of cheap, accurate, easy‐to‐use BP devices in low‐ and middle‐income countries, where risk of maternal and perinatal mortality and morbidity secondary to pre‐eclampsia and shock is highest, continues to be a challenge.

Objective To assess the accuracy of fetal fibronectin (fFN) testing for prediction of preterm labour in asymptomatic high-risk women with a cervical cerclage.Design Retrospective observational study.Setting United Kingdom.Population Nine hundred and ten asymptomatic women at highrisk of Preterm birth referred to specialist antenatal clinics and undergoing fFN testing between November 1997 and December 2007.Methods Women had fFN tests taken between 23 +0 and 27 +6 weeks' gestation, on one or more occasions.Main outcome measures Sensitivity, specificity, positive predictive values and negative predictive values of fFN testing for predicting delivery <30 and <37 weeks were compared in those with and without cerclage.Results For delivery <30 weeks' gestation, the specificity of fFN testing was significantly lower in women with cervical cerclage (77% vs 90%; P £ 0.00001). The sensitivity of the test was similar between the groups (78.6 (no-cerclage) vs 60% (cerclage); P > 0.4). The negative predictive value of the fFN test for delivery <30 weeks was high in both groups (>98%).Conclusions Asymptomatic high-risk women with cerclage in situ are more likely to have a false positive fFN test. The negative predictive value is similar.Keywords Cerclage, fetal fibronectin, sensitivity and specificity, spontaneous preterm birth.Please cite this paper as: Duhig K, Chandiramani M, Seed P, Briley A, Kenyon A, Shennan A. Fetal fibronectin as a predictor of spontaneous preterm labour in asymptomatic women with a cervical cerclage. BJOG 2009;116:799-803.

Pre-eclampsia complicates around 5% of pregnancies and hypertensive disorders of pregnancy are responsible for over 60,000 maternal deaths worldwide annually. Pre-eclampsia is characterized by hypertension and features of multiple organ disease. Diagnosis remains a challenge as clinical presentation is highly variable and even with severe disease a woman can be asymptomatic. Pre-eclampsia is characterized by abnormal placentation with subsequent maternal inflammatory and vascular response. Improved understanding of the underlying pathophysiology relating to the role of angiogenic factors, has emerged and placed intense interest on their role in prognostic modelling or diagnosis of pre-eclampsia. This article summarizes new developments in diagnosis with a focus on angiogenic biomarkers for prediction of disease onset, and recent advances in management strategies for patients with pre-eclampsia.