Placental Growth Factor Testing Research Articles

A prospective study of placental growth factor in twin pregnancy and development of a dichorionic twin pregnancy specific reference range.

To develop a dichorionic twin pregnancy specific reference range for placental growth factor (PlGF), and to compare gestation-specific placental growth factor levels in twin pregnancies later complicated by pre-eclampsia, hypertensive disorder of pregnancy or fetal growth restriction with control pregnancies. Prospective observational study. Single large tertiary maternity unit in Ireland. Women with a twin pregnancy. Consenting pregnant women, across a variety of gestations, had a single blood sample taken at one time-point only during their pregnancy. The plasma was initially biobanked and PlGF was measured later in batches using the point of care Triage® PlGF test. Development of pre-eclampsia, hypertensive disorder of pregnancy or fetal growth restriction. Placental growth factor levels in uncomplicated dichorionic twin pregnancies were significantly lower in the women who later developed pre-eclampsia than in the controls at all gestational intervals. In those that later developed any hypertensive disorder of pregnancy, median PlGF was lower only in those recruited before 24weeks of gestation, whereas in infants with a customised birthweight below the third centile, PlGF was lower only in those sampled after 24weeks of gestation. Placental growth factor levels in twin pregnancy differ significantly between those women with a pregnancy that will later be complicated by pre-eclampsia and those that will not. This difference is present many weeks before clinical signs or symptoms of disease are present. Using cross-sectional values from uncomplicated twin pregnancies, we have developed a dichorionic twin pregnancy specific reference range for PlGF. Placental growth factor levels in twin pregnancy differ significantly between women that will later develop pre-eclampsia and those that will not.

Placental growth factor measurements in the assessment of women with suspected Preeclampsia: A stratified analysis of the PARROT trial.

Placental growth factor testing decreases time to recognition of preeclampsia and may reduce severe maternal adverse outcomes. This analysis aims to describe the clinical phenotype of women by PlGF concentration, and to determine the mechanism(s) underpinning the reduction in severe maternal adverse outcomes in the PARROT trial, in order to inform how PlGF testing may be optimally used within clinical management algorithms. This was a planned secondary analysis from the PARROT trial that compared revealed PlGF testing and management guidance with usual care in the assessment of women with suspected preterm preeclampsia. Maternal and perinatal outcomes following stratification of women by trial group, and measured PlGF concentration. 1006 women were included. PlGF<100pg/ml identified women with more marked hypertension, increased adverse maternal outcomes and preterm delivery rates, and higher rates of small for gestational age infants. There was a reduction in adverse maternal outcomes in women whose results were revealed when PlGF levels were 12-100pg/ml compared to usual care (3.8% vs 6.9%; aOR 0.15(95% CI 0.03-0.92). There was no significant difference in gestation at delivery between concealed or revealed groups in any PlGF categories. Low PlGF concentrations are associated with severe preeclampsia. The reduction in severe adverse maternal outcomes may be mediated through quicker diagnosis and intensive surveillance, as recommended by the management algorithm for those at increased risk. PlGF is particularly beneficial in those who test 12-100pg/ml, as these may be women with silent multi-organ disease who otherwise may go undetected.

Single-Tube Multimarker Assay for Estimating the Risk to Develop Preeclampsia.

Preeclampsia (PE) affects 2%-8% of all pregnancies worldwide. The predictive value of the currently used maternal serum fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) test is < 40% for PE onset within 4 weeks. We aimed to develop an innovative multiplex assay to improve PE prediction. The 6PLEX assay combining the measurements of ADAM12, sENG, leptin, PlGF, sFlt-1, and PTX3 was developed for the Luminex® xMAP platform. Assay performance was evaluated using 61 serum samples drawn from 53 pregnant women between 180 and 275 gestational days: diagnosed PE cases, n = 4; cases with PE onset within 4-62 days after sampling, n = 25; controls, n = 32. The B·R·A·H·M·S Kryptor sFlt-1/PlGF test (Thermo Fisher Scientific, Hennigsdorf, Germany) was applied as an external reference. Alternative PE prediction formulae combining 6PLEX measurements with clinical parameters were developed. There was a high correlation in sFlt-1/PlGF estimated for individual sera between the 6PLEX and B·R·A·H·M·S Kryptor immunoassays (Spearman's r = 0.93, P < 0.0001). The predictive power of the 6PLEX combined with gestational age and maternal weight at sampling reached AUC 0.99 (95% CI 0.97-1.00) with sensitivity 100.0% and specificity 96.9%. In all models, sFlt-1/PlGF derived from the B·R·A·H·M·S immunoassays exhibited the lowest AUC value (<0.87) and sensitivity (<80%) with broad confidence intervals (13%-92%). The estimated prognostic yield of the 6PLEX compared to the B·R·A·H·M·S assay was significantly higher (96.5% vs 73.7%; P = 0.0005). The developed single-tube multimarker assay for PE risk estimation in combination with clinical symptoms reached high prognostic yield (96.5%) and exhibited superior performance compared to the sFlt-1/PlGF test.

Rule-in thresholds for DELFIA Xpress PlGF 1-2-3 test for suspected pre-eclampsia.

We aimed to establish a rule-in threshold for the DELFIA Xpress placental growth factor (PlGF) 1-2-3 test. Plasma EDTA samples from 305 women presenting with suspected pre-eclampsia before 35weeks' gestation were analysed using three different PlGF-based tests: PlGF 1-2-3 test (Perkin Elmer); Triage PlGF test (Quidel); Elecsys immunoassay sFlt-1/PlGF ratio (Roche). The rule-in threshold for PlGF 1-2-3 test created with equivalent specificity of the Quidel and Roche tests was 50pg/ml. This can be used as a rule-in test for diagnosis of preterm pre-eclampsiarequiring delivery within 14days (specificity 95.0% (95% CI 91.7-97.2%), positive predictive value50 (95% CI 30.6-69.4%), positive likelihood ratio 10.7 (5.8-20).

Diagnostic accuracy of repeat placental growth factor measurements in women with suspected preeclampsia: A case series study.

IntroductionPreeclampsia affects about 3% of singleton pregnancies and is characterized by placental dysfunction. It is associated with significant maternal and perinatal morbidity and mortality. The diagnosis of preeclampsia remains a challenge, and the clinical course can develop for weeks before a diagnosis is confirmed. National guidelines have approved placental growth factor (PlGF) testing to rule out suspected preeclampsia, but the utility of repeated PlGF measurement is unknown. The aim of this case series analysis was to evaluate the test performance of repeated PlGF sampling in women presenting with suspected preeclampsia, and to describe relevant clinical outcomes.Material and methodsWomen who presented to maternity services with suspected preeclampsia between 20+0 and 36+6 weeks’ gestation who underwent repeat PlGF sampling with a minimum test interval of 7 days were assessed. The outcomes were delivery for preeclampsia within 14 days of sampling, the proportion changing PlGF categories, and time to delivery.ResultsIn total, 289 women with suspected preeclampsia undergoing repeat PlGF sampling were included. PlGF <100 pg/mL had a high sensitivity (87.5%, 95% confidence interval [CI] 67.6%‐97.3%) and a negative predictive value (97.7%, 95% CI 93.5%‐99.5%) at the initial test (receiver operating characteristic [ROC] area 0.79, 95% CI 0.68‐0.89). Similar test performance was seen for PlGF <100 pg/mL when undertaken as a repeat test (sensitivity 90.7%, 95% CI 85.2%‐95.9%, negative predictive value 92.2%, 95% CI 85.3‐96.6%). Overall, 25.6% of women changed PlGF category between the first and second PlGF tests. For each PlGF category, determination of time to delivery was similar for first and second tests.ConclusionsRepeat PlGF measurement demonstrates high negative predictive value for determining preeclampsia requiring delivery in 14 days. Repeat testing may be clinically useful to risk stratify women with ongoing symptoms of disease. Confirmation of the impact of these findings is required in further studies.

Placental Growth Factor Testing to Assess Women With Suspected Preeclampsia: A Multicentre, Pragmatic, Stepped-wedge Cluster-randomized Controlled Trial

(Lancet. 2019;393:1807–1818) Approximately 3% of singleton pregnancies are affected by preeclampsia, which can be difficult to diagnose as many women are asymptomatic. Hypertension and increased urinary protein excretion are common factors used to establish the diagnosis, but there are challenges in testing and observing both of these features. The pathophysiology of preeclampsia involves angiogenic factors, and low circulating maternal placental growth factor (PlGF) concentrations have been found to be useful in the diagnosis of preeclampsia with high sensitivity and negative predictive value. However, this potential tool for diagnosing preeclampsia should first be tested in a real-world setting to understand both its practical benefits and challenges. This study aimed to determine whether a preeclampsia diagnosis could be more quickly reached in women with suspected preeclampsia by incorporating measurement of the PlGF circulating concentration into an already established clinical management algorithm. The study also investigated the effect of using this diagnostic approach on maternal and perinatal outcomes.

Placental Growth Factor Testing in the Management of Non-Severe Late Preterm Preeclampsia (MAP): A Multicenter Randomised Controlled Trial

Placental Growth Factor Testing in the Management of Non-Severe Late Preterm Preeclampsia (MAP): A Multicenter Randomised Controlled Trial

Placental Growth Factor Testing to Assess Women With Suspected Preeclampsia: A Multicenter, Pragmatic, Stepped-Wedge Cluster-Randomized Controlled Trial

(Abstracted from Lancet 2019;393(10183):1807–1818) Hypertension affects 10% of pregnant women, and approximately 3% of singleton pregnancies are complicated by preeclampsia. Preeclampsia often presents ambiguously, and the risks for women with suspected preeclampsia are complex.

Contemporary Issues in Women's Health.

Placental growth factor testing for suspected pre‐eclampsia HPV Vaccination: A global public health priority Echo trial shows no increased risk of HIV acquisition with hormonal contraception

Generalisability of economic analyses.

As healthcare expenditures account for a greater share of the economy throughout the developed world, it has become increasingly recognised that economic analyses of healthcare interventions are important. Common economic analyses in healthcare include cost analyses, cost-benefit analyses, and cost-effectiveness analyses. A cost analysis examines the costs of the interventions and the downstream costs from the treatment as well, but does not include outcomes. A cost-benefit analysis assumes that the outcomes are similar, and converts all treatments and outcomes into costs. A cost-effectiveness analysis provides the results as an incremental cost-effectiveness ratio (ICER). The ICER has incremental costs in the numerator divided by incremental outcome differences in the denominator. The gold standard for a cost-effectiveness analysis is to utilise quality-adjusted life years in the denominator, which allows CEA ratios to be compared between different clinical settings. An ICER that has a reduction in costs in the numerator and improved outcomes in the denominator is deemed a dominant strategy. The authors describe an economic analysis that appears to be just such a dominant strategy, using placental growth factor (PlGF) as a way to augment the diagnosis of pre-eclampsia (Duhig et al. BJOG 2019;126:1390–8). The take home from the abstract is that there is a cost saving of £149. However, in the body of the manuscript, the use of PlGF is only cost saving in 56% of the iterations of the Monte Carlo simulation model that was run. This is akin to having a nonsignificant P-value when two clinical outcomes are compared. We usually say that such outcomes are not different with such a statistical test. I commend the authors for conducting Monte Carlo simulations, as too often they are not conducted for cost-effectiveness analyses, but it is important to incorporate the probabilistic results in the topline communication. Even though not statistically significant, why would PlGF lead to a reduction in costs? From the original trial, it appeared that the use of the test led to a more rapid diagnosis of pre-eclampsia (2 versus 4 days) and the test was used to triage whether women had their evaluation inpatient or outpatient. Therein lies the greatest source of cost saving from the test. However, for generalisability, would clinicians in different settings be willing to use the PlGF test in this fashion? For those who routinely evaluate most potential pre-eclampsia patients without severe features as outpatients already, there would seemingly be no potential for cost savings. When clinicians are unwilling to use the test to send patients out, given that those with a negative PlGF test still had a 12% chance of having pre-eclampsia, it may not lead to a savings either. Thus, when considering an economic analysis, the devil is in the detail; consideration of the costs included and how they apply to different clinical environments and practices is imperative. Honestly, in the end, for the majority of women, we have relatively inexpensive screening and diagnostic tests for pre-eclampsia (blood pressure checks and urinalysis). Thus, I am not exactly sure how this PlGF test would improve on the diagnostic approaches for most patients. However, there may be some sub-populations where we are more challenged (e.g. those with chronic hypertension) for which this test may lead to clearer diagnoses; at the very least it does not appear to lead to substantially greater costs. None declared. A completed disclosure of interests form is available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

SFlt-1/PlGF Ratio as a Predictive Marker in Women with Suspected Preeclampsia: An Economic Evaluation from a Swiss Perspective.

In Switzerland, 2.3% of pregnant women develop preeclampsia. Quantification of the soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) ratio has shown a diagnostic value in the second and third trimesters of pregnancy, in particular in ruling out preeclampsia within one week. We estimated the economic impact of implementing sFlt-1/PlGF ratio evaluation, in addition to the standard of care (SOC), for women with suspected preeclampsia from a Swiss healthcare system's perspective. A decision tree model was developed to estimate direct medical costs of diagnosis and management of a simulated cohort of Swiss pregnant women with suspected preeclampsia (median week of gestation: 32) until delivery. The model compared SOC vs. SOC plus sFlt-1/PlGF ratio, using clinical inputs from a large multicenter study (PROGNOSIS). Resource use data and unit costs were obtained from hospital records and public sources. The assumed cost for sFlt-1/PlGF evaluation was €141. Input parameters were validated by clinical experts in Switzerland. The model utilized a simulated cohort of 6084 pregnant women with suspected preeclampsia (representing 7% of all births in Switzerland in 2015, n = 86,919). In a SOC scenario, 36% of women were hospitalized, of whom 27% developed preeclampsia and remained hospitalized until birth. In a sFlt-1/PlGF test scenario, 76% of women had a sFlt-1/PlGF ratio of ≤38 (2% hospitalized), 11% had a sFlt-1/PlGF ratio of >38-<85 (55% hospitalized), and 13% had a sFlt-1/PlGF ratio of ≥85 (65% hospitalized). Total average costs/pregnant woman (including birth) were €10,925 vs. €10,579 (sFlt-1/PlGF), and total costs were €66,469,362 vs. €64,363,060 (sFlt-1/PlGF). Implementation of sFlt-1/PlGF evaluation would potentially achieve annual savings of €2,105,064 (€346/patient), mainly due to reduction in unnecessary hospitalization. sFlt-1/PlGF evaluation appears economically promising in predicting short-term absence of preeclampsia in Swiss practice. Improved diagnostic accuracy and reduction in unnecessary hospitalization could lead to significant cost savings in the Swiss healthcare system.

Placental growth factor testing for suspected pre-eclampsia: a cost-effectiveness analysis.

ObjectiveTo calculate the cost‐effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care.DesignCost‐effectiveness analysis.SettingEleven maternity units participating in the PARROT stepped‐wedge cluster‐randomised controlled trial.PopulationWomen presenting with suspected pre‐eclampsia between 20+0 and 36+6 weeks’ gestation.MethodsMonte Carlo simulation utilising resource use data and maternal adverse outcomes.Main outcome measuresCost per maternal adverse outcome prevented.ResultsClinical 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.ConclusionsClinical 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 abstractPlacental growth factor testing for suspected pre‐eclampsia is cost‐saving and improves maternal outcomes.

Placental growth factor testing cost effective in preeclampsia

Placental growth factor testing cost effective in preeclampsia

Placental growth factor testing for suspected pre-eclampsia

Placental growth factor testing for suspected pre-eclampsia

Placental growth factor testing to assess women with suspected pre-eclampsia: a multicentre, pragmatic, stepped-wedge cluster-randomised controlled trial

SummaryBackgroundPrevious 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.MethodsWe 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.FindingsBetween 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 concealed testing group withdrew consent to follow-up data collection, so 446 (>99%) women in this group were included in the analyses. The median time to pre-eclampsia diagnosis was 4·1 days with concealed testing versus 1·9 days with revealed testing (time ratio 0·36, 95% CI 0·15–0·87; p=0·027). Maternal severe adverse outcomes were reported in 24 (5%) of 447 women in the concealed testing group versus 22 (4%) of 573 women in the revealed testing group (adjusted odds ratio 0·32, 95% CI 0·11–0·96; p=0·043), but there was no evidence of a difference in perinatal adverse outcomes (15% vs 14%, 1·45, 0·73–2·90) or gestation at delivery (36·6 weeks vs 36·8 weeks; mean difference −0·52, 95% CI −0·63 to 0·73).InterpretationWe found that the availability of PlGF test results substantially reduced the time to clinical confirmation of pre-eclampsia. Where PlGF was implemented, we found a lower incidence of maternal adverse outcomes, consistent with adoption of targeted, enhanced surveillance, as recommended in the clinical management algorithm for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study.FundingNational Institute for Health Research.

145: A prospective comparative study of Placental Growth Factor in a multiple pregnancy cohort

To compare gestation specific placental growth factor (PlGF) levels in multiple pregnancies complicated by pre- eclampsia (PET) or any hypertensive disorder of pregnancy (HDP) to controls. Prospective study conducted in a single tertiary maternity hospital from July 2015-December 2017. Maternal plasma samples were collected at one time point across a cross section of gestations from consenting women with a multiple pregnancy without signs/symptoms or diagnosis of PET. Samples were analysed for PlGF using the Triage® PlGF Test (Alere). Clinical outcome data were gathered from medical notes following delivery. The cohort was divided into 2 groups based on gestational age at time of enrollment; <24 weeks and ≥ 24 weeks. Non parametric tests were conducted to compare the mean PlGF at each gestational interval using SPSS Version 23. Of the 275 women with a multiple pregnancy recruited, 15.3% (n=42) subsequently developed HDP and of those 11.3% (n=31) developed PET. Median time from sampling to diagnosis of HDP/PET was 97 days when recruited <24 weeks and 25 days when recruited at 24 weeks or beyond. A Mann-Whitney U Test revealed PlGF levels were significantly lower in the women who later developed PET than in the controls (153 pg/ml vs. 247 pg/ml, p = 0.04, 99.8 pg/ml vs. 304 pg/m, p = 0.01). However in those that later developed HDP, PlGF was lower <24 weeks only (150 pg/ml vs 250 pg/ml, p = 0.02). No differences in PlGF levels were noted when BMI >30, parity, assisted reproductive therapy or pregnancy through use of donor oocyte was compared between the two groups. PlGF levels in multiple pregnancy differs significantly between those pregnancies that will be complicated by PET and those that will not. This difference is present many weeks before clinical signs or symptoms of disease are present.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

138. Placental growth factor to assess and diagnose hypertensive pregnant women: A stepped wedge randomised controlled trial (PARROT)

Introduction Angiogenic factor measurements have shown potential for assisting in the diagnosis of pre-eclampsia in prospective cohort studies, but their diagnostic ability and clinical impact when revealed to clinicians remains uncertain. Hypothesis In women presenting with suspected pre-eclampsia, use of placental growth factor (PlGF) testing decreases time to clinician-recognised diagnosis of pre-eclampsia (primary outcome) and decreases maternal and perinatal morbidity, and has an impact on health resource use (secondary outcomes). Methods Design: Multi-centre, pragmatic, stepped-wedge cluster randomised controlled trial. Setting: Eleven UK maternity units (size range 3000–9000 deliveries per annum). Intervention: PlGF measurement with result revealed to clinical team and management guidance. Randomisation: Hospitals were randomly allocated to the order in which the intervention was implemented. Population: Women who presented to maternity services with suspected pre-eclampsia between 20 + 0 and 36 + 6 weeks’ gestation, providing individual-level consent. Results Between June 2016 and October 2017, 1023 women with suspected pre-eclampsia were recruited. The median time to diagnosis of pre-eclampsia was from 4.1 days (usual care) to 1.9 days with PlGF testing (time ratios 0.39 (95% CI 0.17–0.91) by parametric survival analysis). There was a reduction in maternal severe adverse outcomes (as defined in the fullPIERS consensus) from 5.4% (concealed PlGF group) to 3.8% (revealed PlGF group) adjusted OR 0.32 (95% CI 0.11–0.96) with no evidence of a significant difference in perinatal adverse outcomes. Discussion PlGF testing has been shown to be acceptable and clinically useful in substantially reducing the time to clinical recognition of pre-eclampsia. Where PlGF is implemented there is a reduction in maternal adverse outcomes, consistent with targeted enhanced surveillance as recommended in the trial management guidance for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study.

371. A comparative study of two immunoassays of placental growth factor

Objective To compare the results obtained from use of two commercially available immunoassays of maternal placental growth factor (PlGF) in a multiple pregnancy cohort. Methods Results obtained using the Triage® PlGF Test (Alere) were compared against those from the Quantikine® ELISA PlGF kit (RD p 0.001). Discussion Although the two assays correlate well, there is a significant difference in the actual PlGF values obtained. This is likely due to measurement of differing isoforms of PlGF in each assay. The ELISA kits may be detecting PIGF-2 & PIGF-3 while PIGF-4 remains untested. This highlights the importance of developing a unique reference range for any commercial PlGF test before introducing it into the clinical setting.

Placental Growth Factor Testing to Assess and Diagnose Preeclampsia: A Stepped Wedge Randomised Controlled Trial

Background Previous prospective cohort studies have demonstrated that angiogenic factor measurements have high diagnostic accuracy in women with suspected pre-eclampsia, but the clinical impact of these tests when revealed to clinicians remains uncertain. Methods We conducted a multi-centre, pragmatic, stepped-wedge cluster randomised controlled trial in eleven UK maternity units (3000-9000 deliveries per annum). Women who presented with suspected pre-eclampsia between 20 0 and 36 6 weeks' gestation were invited to participate. Maternity units were randomly assigned to the order of implementation of revealed PlGF measurement, incorporated within a clinical management algorithm; in the usual care arm, PlGF measurement remained concealed. The primary outcome was time from presentation with suspected pre-eclampsia to documented pre-eclampsia. Secondary outcomes included other maternal and perinatal adverse outcomes. Findings Between June 2016 and October 2017, 1,023 women with suspected pre-eclampsia were enrolled. Median time to preeclampsia diagnosis decreased from 4·1 days (usual care) to 1·9 days (intervention) (time ratio 0·39 (95% CI 0·17-0·91) by parametric survival analysis). Maternal severe adverse outcomes reduced from 5·4% (usual care group) to 3·8% ((intervention group) adjusted OR 0·32 (95% CI 0·11-0·96) with no evidence of a difference in perinatal adverse outcomes. Interpretation PlGF testing has been shown to substantially reduce the time to clinical confirmation of preeclampsia. Where PlGF was implemented there was a reduction in maternal adverse outcomes, consistent with targeted, enhanced surveillance as recommended in the trial management guidance for clinicians. Adoption of PlGF testing in women with suspected pre-eclampsia is supported by the results of this study. Trial Registration Number: ISRCTN 16842031 Funding: This trial was supported by grants from the National Institute for Health Research, Research for Patient Benefit Programme (PB-PG-0214-33054) and National Institute for Health Research Professorship (Chappell RP-2014-05-019). Declaration of Interest: KD, LCC, PS, JM and AS have no conflicts of interest. RH has received writing fees from Alere for previous work Ethical Approval: The trial was approved by the London South East Research Ethics Committee (ref. 15/LO/2058).

Economic evaluation of sFlt-1/PlGF ratio test in pre-eclampsia prediction and diagnosis in two Brazilian hospitals

To assess the economic impact of introducing the soluble FMS-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test into clinical practice in two Brazilian hospitals. An economic model estimating the incremental value of the information from a Brazilian public and private healthcare payer perspective generated by the sFlt-1/PlGF ratio test, compared with current diagnostic procedures, in guiding the management of women with suspected pre-eclampsia. A cohort of 1000 pregnant women between 24 weeks and 36 + 6 weeks of gestation were managed in either a 'test' scenario in which the sFlt-1/PlGF test is used in addition to current diagnostic procedures, or a 'no-test' scenario. Information on the costs associated with diagnosis, prediction and management were derived from the cost database of Hospital M'Boi Mirim (public) and Hospital Einstein (private). The probabilities used in the decision tree were derived from PROGNOSIS. The main outcome measure from the model was the cost per patient per episode of care (from first suspicion of pre-eclampsia to birth). Introduction of the sFlt-1/PlGF ratio test resulted in cost savings in both settings (M'Boi Mirim: R$185.06 and Einstein: R$635.84 per patient) compared with a 'no-test' scenario. Savings are generated primarily through an improvement in diagnostic accuracy and a reduction in unnecessary hospitalization. The sFlt-1/PlGF ratio test has the potential to improve clinical decision-making and allocation of scarce resources by reducing unnecessary hospitalization of women at low risk of developing pre-eclampsia, and ensuring that women at higher risk are identified and managed appropriately.