Screening Test For Preeclampsia Research Articles

Prospective Validation of First-Trimester Screening for Preterm Preeclampsia in Nulliparous Women (PREDICTION Study).

Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women. We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria. We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%. The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148.

Preterm preeclampsia screening using biomarkers: combining phenotypic classifiers into robust prediction models

Preeclampsia screening is a critical component of antenatal care worldwide. Currently, the most developed screening test for preeclampsia at 11 to 13 weeks' gestation integrates maternal demographic characteristics and medical history with 3 biomarkers-serum placental growth factor, mean arterial pressure, and uterine artery pulsatility index-to identify approximately 75% of women who develop preterm preeclampsia with delivery before 37 weeks of gestation. It is generally accepted that further improvements to preeclampsia screening require the use of additional biomarkers. We recently reported that the levels of specific metabolites and metabolite ratios are associated with preterm preeclampsia. Notably, for several of these markers, preterm preeclampsia prediction varied according to maternal body mass index class. These findings motivated us to study whether patient classification allowed for combining metabolites with the current biomarkers more effectively to improve prediction of preterm preeclampsia. This study aimed to investigate whether metabolite biomarkers can improve biomarker-based preterm preeclampsia prediction in 3 screening resource scenarios according to the availability of: (1) placental growth factor, (2) placental growth factor+mean arterial pressure, and (3) placental growth factor+mean arterial pressure+uterine artery pulsatility index. This was an observational case-control study, drawn from a large prospective screening study at 11 to 13 weeks' gestation on the prediction of pregnancy complications, conducted at King's College Hospital, London, United Kingdom. Maternal blood samples were also collected for subsequent research studies. We used liquid chromatography-mass spectrometry to quantify levels of 50 metabolites previously associated with pregnancy complications in plasma samples from singleton pregnancies. Biomarker data, normalized using multiples of medians, on 1635 control and 106 preterm preeclampsia pregnancies were available for model development. Modeling was performed using a methodology that generated a prediction model for preterm preeclampsia in 4 consecutive steps: (1) z-normalization of predictors, (2) combinatorial modeling of so-called (weak) classifiers in the unstratified patient set and in discrete patient strata based on body mass index and/or race, (3) selection of classifiers, and (4) aggregation of the selected classifiers (ie, bagging) into the final prediction model. The prediction performance of models was evaluated using the area under the receiver operating characteristic curve, and detection rate at 10% false-positive rate. First, the predictor development methodology itself was evaluated. The patient set was split into a training set (2/3) and a test set (1/3) for predictor model development and internal validation. A prediction model was developed for each of the 3 different predictor panels, that is, placental growth factor+metabolites, placental growth factor+mean arterial pressure+metabolites, and placental growth factor+mean arterial pressure+uterine artery pulsatility index+metabolites. For all 3 models, the area under the receiver operating characteristic curve in the test set did not differ significantly from that of the training set. Next, a prediction model was developed using the complete data set for the 3 predictor panels. Among the 50 metabolites available for modeling, 26 were selected across the 3 prediction models; 21 contributed to at least 2 out of the 3 prediction models developed. Each time, area under the receiver operating characteristic curve and detection rate were significantly higher with the new prediction model than with the reference model. Markedly, the estimated detection rate with the placental growth factor+mean arterial pressure+metabolites prediction model in all patients was 0.58 (95% confidence interval, 0.49-0.70), a 15% increase (P<.001) over the detection rate of 0.43 (95% confidence interval, 0.33-0.55) estimated for the reference placental growth factor+mean arterial pressure. The same prediction model significantly improved detection in Black (14%) and White (19%) patients, and in the normal-weight group (18.5≤body mass index<25) and the obese group (body mass index≥30), with respectively 19% and 20% more cases detected, but not in the overweight group, when compared with the reference model. Similar improvement patterns in detection rates were found in the other 2 scenarios, but with smaller improvement amplitudes. Metabolite biomarkers can be combined with the established biomarkers of placental growth factor, mean arterial pressure, and uterine artery pulsatility index to improve the biomarker component of early-pregnancy preterm preeclampsia prediction tests. Classification of the pregnant women according to the maternal characteristics of body mass index and/or race proved instrumental in achieving improved prediction. This suggests that maternal phenotyping can have a role in improving the prediction of obstetrical syndromes such as preeclampsia.

Validation of a preeclampsia early screening test in a Mexican population.

No preeclampsia screening test has been validated in our country. To assess the fit and performance of the FMF 4.0 Bayesian algorithm in a Mexican population. Cohort study in singleton pregnancies, according to the competing risks model for preeclampsia. A priori risk was calculated based on medical history. Mean blood pressure (MBP), uterine artery mean pulsatility index (UtAmPI) and pregnancy-associated plasma protein A (PAPP-A) were measured at 11-14 weeks of gestation using standardized methodology. The value of each marker was transformed into multiples of the median (MoM) by the originala algorithm and by population-correctionb. Multivariate normal distribution and Bayes theorem were applied to obtain post-test probabilities. There was 5.0% (40/807) of preeclampsia. Distributions in women without preeclampsia were MBP = 0.927a vs. 0.991b, UtAmPI = 0.895a vs. 1.030b and PAPP-A = 0.815a vs. 0.963b (p < 0.001). The AUC was 0.821a vs. 0.823b. For a detection rate of 69 %, cutoff points were 1 in 240a and 1 in 120b, with false positive rates of 31 %a and 29 %b. The model has to be adjusted to the target population.

Neutrophil-Lymphocyte Ratio as a Screening Test for Preeclampsia in the First and Early-Third Trimesters of Pregnancy: A Cohort Study

Background: Preeclampsia (PEC), affecting 5-10% of all pregnancies, is a multisystem disease diagnosed by hypertension (HTN) and protein in the urine or multi-organ problems without signs of proteinuria occurring after 20 weeks of gestation. PEC is the most common cause of maternal death and can lead to premature delivery. The current study aimed to investigate the accuracy of neutrophil-lymphocyte ratio (NLR) for predicting PEC in the first and early-third trimesters of pregnancy in a normal population in the south of Iran. Materials and Methods: A large-scale cohort study was performed from early pregnancy onward during November 2018-2019 in a normal population from Fars province, Southwest Iran. Four hundred forty-nine pregnant women were followed prospectively, and normal blood pressure (normotensive), gestational HTN, and PEC groups were compared in terms of white blood cells (WBC) count, neutrophil, lymphocyte, and NLR. Results: The serum levels of WBC count, neutrophil, and NLR significantly increased from the first to the early-third trimesters of pregnancy (P&lt;0.05); however, lymphocytes decreased (P&lt;0.05). The NLR cut-off points for predicting PEC were 2.79 (sensitivity=86.7% and specificity=92.6%) in the first and 3.2 (sensitivity=90.5% and specificity=79.4%) in the early-third trimesters. Conclusion: Our findings revealed that NLR could be an accurate predictive factor for PEC in the first and early-third trimesters of pregnancies; however, more studies are needed to investigate the immunomodulatory drugs for the prevention of PEC.

Early cost-effectiveness analysis of screening for preeclampsia in nulliparous women: A modelling approach in European high-income settings.

BackgroundPreeclampsia causes substantial maternal and perinatal morbidity and mortality and significant societal economic impact. Effective screening would facilitate timely and appropriate prevention and management of preeclampsia.ObjectivesTo develop an early cost-effectiveness analysis to assess both costs and health outcomes of a new screening test for preeclampsia from a healthcare payer perspective, in the United Kingdom (UK), Ireland, the Netherlands and Sweden.MethodsA decision tree over a 9-month time horizon was developed to explore the cost-effectiveness of the new screening test for preeclampsia compared to the current screening strategy. The new test strategy is being developed so that it can stratify healthy low risk nulliparous women early in pregnancy to either a high-risk group with a risk of 1 in 6 or more of developing preeclampsia, or a low-risk group with a risk of 1 in 100 or less. The model simulated 25 plausible scenarios in a hypothetical cohort of 100,000 pregnant women, in which the sensitivity and specificity of the new test were varied to set a benchmark for the minimum test performance that is needed for the test to become cost-effective. The input parameters and costs were mainly derived from published literature. The main outcome was incremental costs per preeclampsia case averted, expressed as an incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty.ResultsBase case results showed that the new test strategy would be more effective and less costly compared to the current situation in the UK. In the Netherlands, the majority of scenarios would be cost-effective from a threshold of €50,000 per preeclampsia case averted, while in Ireland and Sweden, the vast majority of scenarios would be considered cost-effective only when a threshold of €100,000 was used. In the best case analyses, ICERs were more favourable in all four participating countries. Aspirin effectiveness, prevalence of preeclampsia, accuracy of the new screening test and cost of regular antenatal care were identified as driving factors for the cost-effectiveness of screening for preeclampsia.ConclusionThe results indicate that the new screening test for preeclampsia has potential to be cost-effective. Further studies based on proven accuracy of the test will confirm whether the new screening test is a cost-effective additional option to the current situation.

Modified multiple marker aneuploidy screening as a primary screening test for preeclampsia

BackgroundAbnormal levels of maternal biochemical markers used in multiple marker aneuploidy screening have been associated with adverse pregnancy outcomes. This study aims to assess if a combination of maternal characteristics and biochemical markers in the first and second trimesters can be used to screen for preeclampsia (PE). The secondary aim was to assess this combination in identifying pregnancies at risk for gestational hypertension and preterm birth.MethodsThis case-control study used information on maternal characteristics and residual blood samples from pregnant women who have undergone multiple marker aneuploidy screening. The median multiple of the median (MoM) of first and second trimester biochemical markers in cases (women with PE, gestational hypertension and preterm birth) and controls were compared. Biochemical markers included pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), human chorionic gonadotropin (hCG), alpha feto-protein (AFP), unconjugated estriol (uE3) and Inhibin A. Logistic regression analysis was used to estimate screening performance using different marker combinations. Screening performance was defined as detection rate (DR) and false positive rate (FPR). Preterm and early-onset preeclampsia PE were defined as women with PE who delivered at < 37 and < 34 weeks of gestation, respectively.ResultsThere were 147 pregnancies with PE (81 term, 49 preterm and 17 early-onset), 295 with gestational hypertension, and 166 preterm birth. Compared to controls, PE cases had significantly lower median MoM of PAPP-A (0.77 vs 1.10, p < 0.0001), PlGF (0.76 vs 1.01, p < 0.0001) and free-β hCG (0.81 vs. 0.98, p < 0.001) in the first trimester along with PAPP-A (0.82 vs 0.99, p < 0.01) and PlGF (0.75 vs 1.02, p < 0.0001) in the second trimester. The lowest first trimester PAPP-A, PlGF and free β-hCG were seen in those with preterm and early-onset PE. At a 20% FPR, 67% of preterm and 76% of early-onset PE cases can be predicted using a combination of maternal characteristics with PAPP-A and PlGF in the first trimester. The corresponding DR was 58% for gestational hypertension and 36% for preterm birth cases.ConclusionsMaternal characteristics with first trimester PAPP-A and PlGF measured for aneuploidy screening provided reasonable accuracy in identifying women at risk of developing early onset PE, allowing triage of high-risk women for further investigation and risk-reducing therapy. This combination was less accurate in predicting women who have gestational hypertension or preterm birth.

440 Usage of low dosage aspirin to prevent preeclampsia – slovenian data

Introduction: The usage of anamnesis and first trimester test can reliably predict the development of pre-eclampsia and can select women who may benefit from low dose aspirin to prevent preterm preeclampsia. As important as the prediction of high-risk women is their compliance to really consume low dose aspirin every day. With our study we analysed how accurate the data in the National perinatal information system (NPIS) is and if it differs from our data. Material and methods: From 01. March to 30. June 2020 696 women filled out our anonymous questionary where we asked them about anamnestic reasons for taking aspirin, when they started with the therapy, how consistent they were and what the pregnancy outcome was. We compared the results with the NPIS, where the data are collected with interviewing the patient. In the 1457 births were recorded in this time. Results: From 696 women in our study 52 were taking low dosage aspirin (7,5%). 5 of them (0,7%) admitted, they were not taking aspirin regularly. 2 stopped aspirin before 20. week of pregnancy. 28 delivered before 34 weeks (4%). Only 3 of them were taking aspirin and delivered before 34 weeks because of chorioamnionitis. Only 5 women out of 52 (9,6%) were taking aspirin because they were screened with the FMF algorithm as high risk for preeclampsia. In the NPIS group there were 89 women taking aspirin (6,2%) and 44. delivered before 34 weeks (3%). 6 of them delivered because of preeclampsia. Conclusions: Based on our preliminary data, the data from the NPIS and the anonymous questionnaire are very similar. But we should encourage our doctors to use more reliable screening test for preeclampsia (for example the FMF algorithm for PE screening) as only the anamnesis.

Prenatal pre-eclampsia screening using maternal characteristics, maternal serum PAPP-A and PlGF in the first trimester

To assess the effectiveness of a combination of maternal characteristics, maternal serum pregnancy-associated plasma protein A (PAPP-A) and placental growth factor (PlGF) as a primary screening test for pre-eclampsia.

SY4-1. Reliable urinary screening tests for preeclampsia

Recent studies highlighted the link of schizophrenia risk with genetic variations in complement, which share the same pathogenesis with systemic lupus erythematosus (SLE). However, the coexistence of SLE and schizophrenia were rarely reported. We aimed to explore the autoantibody profiles, complement levels and prevalence of SLE in chronic schizophrenia patients.A prospective, cross-sectional study was conducted to recruit 481 long-term hospitalized schizophrenia spectrum disorder patients in Yuli hospital, Taiwan. Severity of schizophrenia was assessed by Positive and Negative Syndrome Scale (PANSS). Immunologic tests of autoantibodies and complement levels were measured. Genome-wide association analysis was conducted to compare genetic variants between schizophrenia with SLE and non-SLE schizophrenia.In total, 47 (9.8%) and 31 (6.4%) participants had positive anti-nuclear antibody (ANA) and anti-double stranded DNA (anti-dsDNA) antibodies, respectively. After rheumatologic exams, 30 (6.2%) patients were diagnosed schizophrenia with SLE, while 32 (6.7%) subjects were classified as schizophrenia with autoimmune features. Schizophrenia patients with SLE had more arthritis, serositis, homogenous ANA pattern, conceptual disorganization in PANSS and increased salivation due to psychotropics compared with their counterparts. ANA titers and complement levels were significantly correlated with PANSS scores and side effect of psychotropics. No significant genetic variation between schizophrenia with SLE and non-SLE schizophrenia were identified.SLE may coexist in chronic hospitalized schizophrenia. Complement levels could be a potential biomarker in schizophrenia patients. Considering the possible reversibility of psychotic features and adverse effects of antipsychotics, SLE with psychosis should be identified in patients with chronic hospitalized schizophrenia.

Clinical implementation of pre-eclampsia screening in the first trimester of pregnancy.

Early identification of preeclampia in the first trimester of pregnancy represents one of the major challenges of modern fetal medicine. The primary aim of our study was to evaluate the effectiveness of implementation of preeclampsia screening in Tuscany, Italy. The secondary aim was to evaluate pregnancy/neonatal outcome in the positive screening group compared with the negative screening group. Retrospective study including singleton pregnancies undergoing screening for preeclampsia. The screening test was a multiparametric algorithm based on maternal history, biochemical and biophysical parameters (Fetal Medicine Foundation algorithm). The overall performance of the test was calculated, in terms of sensitivity, specificity, positive and negative predictive value and in relation to gestational age at onset (primary aim). Pregnancy and neonatal outcomes were then compared between the positive and negative population at preeclampsia screening test (secondary aim). Of the 5719 patients enrolled, 4797 were included in the analysis. The sensitivity for early onset of preeclampsia (≤34weeks) was 0.75 (CI:0.41-0.93) and specificity 0.93 (CI:0.92-0.94) for a false positive rate of 7%. The population that tested positive for preeclampsia screening showed a higher incidence of deliveries at lower gestational ages (p<0.001), preeclampsia onset despite prophylaxis with aspirin (p<0.001), emergency caesarean section (p<0.001), low fetal birth weight (p<0.001) and neonatal admission in intensive care unit (p<0.001). Our data confirm the validity of first trimester screening test in identifying a category of patients at greatest risk for preeclampsia even in the presence of a post-test pharmacological prophylaxis.

Pravastatin suppresses inflammatory cytokines and endothelial activation in patients at risk of developing preeclampsia: INOVASIA study

Introduction The Indonesian INOVASIA study is an ongoing multicentre randomized, open controlled trial of pravastatin for the prevention of preeclampsia in patients deemed to be high risk. Here we evaluate the effects of pravastatin on circulating inflammatory and endothelial markers, i.e. Vascular Endothelial Growth Factor (VEGF), Interleukin-6 (IL-6), Endothelin-1 (ET-1), and Nitric Oxide (NO). Methods Pregnant women deemed to be at a high risk of developing preeclampsia women were recruited based on the Fetal Medicine Foundation preeclampsia screening test or a history of preterm preeclampsia, or clinical risk factors in combination with an abnormal uterine artery Doppler flow pattern at 11–20 week's gestation. This is a nested cohort study within the larger trial (INOVASIA); 38 patients were consecutively recruited and assigned to the pravastatin group and the control group. Participants in the pravastatin group received pravastatin (2 × 20 mg p.o) in addition to a standard regimen of aspirin (80 mg p.o) and calcium (1 g p.o), from 14 to 20 weeks until delivery. Blood samples to measure the various biomarkers were obtained in consecutive patients before starting the research medication and just before delivery (pre and post-test examination). Result The number of samples on the 2 time points for the various biomarkers was: VEGF: 38, IL-6: 30, ET-1: 38, and NO: 35. IL-6 levels decreased significantly in the pravastatin group (mean ± SD): (191.87 ± 82.99 vs. 151.85 + 48.46, p = .013), while levels in the control group did not change significantly (median (interquartile range)) (144.17 (53.91) vs. 140.82 (16.18), p = .177). ET-1 levels decreased significantly in the pravastatin group (3.64 ± 0.85 vs. 3.01 ± 0.74, p = .006) while the control group had more or less stable levels (3.57 ± 1.12 vs. 3.78 ± 0.73 p = .594). NO was the only serum marker that showed significant changes in both groups. NO levels increased in pravastatin group (11.30 (17.43) vs. 41.90 (53.18), p = .044) and decreased in control group (38.70 (34.80) vs. 10.03 (26.96), p = .002). VEGF levels appeared to follow opposite trends in the 2 groups (NS) (Pravastatin: 3.22 (0.62) vs. 3.28 (0.75), p = .402. Control: 3.38 (0.83) vs. 3.06 (0.74), p = .287). Conclusion Administration of 40 mg pravastatin resulted in an improvement in NO levels, and a decrease in IL-6 and endothelin (ET-1) levels. The direction of the effect of pravastatin on these biomarkers appears to underpin the potential for a beneficial effect of pravastatin in the prevention of preeclampsia.

Pregnancy outcomes in nulliparous women with positive first-trimester preterm preeclampsia screening test: the Great Obstetrical Syndromes cohort study

The Fetal Medicine Foundation proposed a competing risks model for early identification of women at a high risk of preterm preeclampsia, typically associated with deep placentation disorders. The Great Obstetrical Syndromes include a spectrum of pregnancy complications (preeclampsia, intrauterine growth restriction, preterm birth, late spontaneous abortion, and abruptio placentae) that are also associated with deep placentation disorders. This study aimed to estimate the rate of placenta-mediated pregnancy complications in nulliparous women with a positive first-trimester Fetal Medicine Foundation preterm preeclampsia screening test. We conducted a prospective cohort study of nulliparous women recruited at 11 to 14 weeks of gestation. Maternal characteristics, mean arterial blood pressure, levels of maternal serum biomarkers (pregnancy-associated plasma protein-A, placental growth factor, and soluble fms-like tyrosine kinase-1), and mean uterine artery pulsatility index were obtained to calculate the risk of preterm preeclampsia according to the Fetal Medicine Foundation algorithm. The predicted risks were dichotomized as a positive or negative test according to 2 risk cutoffs (1 in 70 and 1 in 100). The detection rate, false-positive rate, and positive and negative predictive values were calculated for placenta-mediated complications, including preeclampsia, small for gestational age (birthweight <10th percentile), fetal death, preterm birth, and a composite outcome, including any of the foregoing. The same analyses were computed for a composite of severe outcomes, including preterm preeclampsia, severe small for gestational age (less than third percentile), and fetal death. We included 4575 participants with complete observations, of whom 494 (10.8%) had an estimated risk of preterm preeclampsia of ≥1 in 70 and 728 (15.9%) had a risk of ≥1 in 100. The test based on a risk cutoff of 1 in 70 could have correctly predicted up to 27% of preeclampsia, 55% of preterm preeclampsia, 18% of small for gestational age, 24% of severe small for gestational age, and 37% of fetal deaths at a 10% false-positive rate. The test based on a cutoff of 1 in 100 could have predicted correctly up to 35% of preeclampsia, 69% of preterm preeclampsia, 25% of small for gestational age, 30% of severe small for gestational age, and 53% of fetal deaths at a 15% false-positive rate. The positive predictive value of a screening test for preterm preeclampsia of ≥1 in 70 was 3% for preterm preeclampsia, 32% for the composite outcome, and 9% for the severe composite outcome. Nulliparous women with a first-trimester positive preterm preeclampsia Fetal Medicine Foundation screening test are at a higher risk of both preterm preeclampsia and other severe placenta-mediated pregnancy complications. Approximately 1 woman of 10 identified as high risk by the Fetal Medicine Foundation algorithm developed at least 1 severe placenta-mediated pregnancy complication.

Research priorities for pregnancy hypertension: a UK priority setting partnership with the James Lind Alliance.

ObjectivesTo identify research priorities for hypertensive disorders of pregnancy from individuals with lived experience and healthcare professionals.DesignProspective surveys and consensus meetings using principles outlined by the James Lind Alliance.SettingUK.MethodsA steering group was established and ‘uncertainties’ were gathered using an online survey and literature search. An interim online survey ranked long-listed questions and the top 10 research questions were reached by consensus at a final prioritisation workshop.ParticipantsWomen, partners, relatives and friends of those with lived experience of pregnancy hypertension, researchers and healthcare professionals.ResultsThe initial online survey was answered by 278 participants (180 women with lived experience, 9 partners/relatives/friends, 71 healthcare professionals and 18 researchers). Together with a literature search, this identified 764 questions which were refined into 50 summary questions. All summary questions were presented in an interim prioritisation survey that was answered by 155 participants (87 women with lived experience, 4 partners/relatives/friends, 49 healthcare professionals and 15 researchers). The top 25 highest ranked questions were considered by the final prioritisation workshop. The top 10 uncertainties were identified by consensus and ranked as follows in order of priority: long-term consequences of pregnancy hypertension (for the woman and baby), short-term complications of pregnancy hypertension (for the woman and baby), screening tests for pre-eclampsia, prevention of long-term problems (for the woman and baby), causes of pregnancy hypertension, prevention of recurrent pregnancy hypertension, educational needs of healthcare professionals, diagnosis of pre-eclampsia, management of pregnancy hypertension, provision of support for women and families.ConclusionsResearch priorities shared by those with lived experience of pregnancy hypertension and healthcare professionals have been identified. Researchers should use these to inform the choice of future studies in this area.

Screening for Preeclampsia in the First Trimester and Aspirin Prophylaxis: Our First Year.

Preeclampsia is a major cause of perinatal and maternal morbidity and mortality. Our objective is to assess the performance of a combined screening test for preeclampsia in the first trimester and the prophylactic use of low-dose aspirin. Prospective study of all women attending our hospital for the first-trimester screening of aneuploidies, between March 2017 and February 2018 (n = 1,297). The exclusion criteria were multiple pregnancy and major fetal abnormalities. Preeclampsia screening was performed with an algorithm that includes maternal characteristics, and biophysical and biochemical biomarkers. High-risk was defined as a risk ≥ 1:50 of early-onset preeclampsia (before 34 weeks), in which cases low-dose aspirin (150 mg at night) was offered to these women from screening until 36 weeks. From the 1,272 enrolled participants, the majority were Caucasian (1,051; 82.6%) and multiparous (658, 51.7%). Fifty patients (3.9%) screened high-risk for preeclampsia, and all started a low-dose aspirin regimen, with good compliance (96%). Early-onset preeclampsia was found in 3 pregnant women (0.24%), and total preeclampsia was diagnosed in 25 (2.02%), compared with 28 (0.75%) cases of early preeclampsia (p = 0.0099) and 98 (2.62%) of total preeclampsia (p = 0.2904) before the implementation of screening. There was a lower incidence of both, early-onset and total preeclampsia, after the introduction of universal screening and prophylactic use of low-dose aspirin. This reduction was statistically significant in early-onset preeclampsia. The association of a first-trimester combined screening model and aspirin prophylaxis appears to be useful in predicting and reducing the incidence of early-onset preeclampsia, in a routine care setting.

Late pregnancy screening for preeclampsia with a urinary point-of-care test for misfolded proteins

The aim was to describe and assess a new late pregnancy point-of-care urinary preeclampsia screening test. Urine samples were collected from a consecutive series of 1,532 pregnant women hospitalized at 20–41 weeks gestation in a Chinese single obstetric unit. A simple disposable Congo red based device was newly developed and employed to prospectively test misfolded proteins in pregnant women’s urine. A total of 140 preeclampsia cases were clinically diagnosed, 101 severe and 87 pre-term. Detection and false positive rates were similar in the training and validation subsets with combined 74% and 3.0%. The detection rate was 83% in severe, 86% in pre-term, 49% and 50% in mild and term cases (P<0.0001) respectively. In conclusion, a simple point-of-care urinary test for misfolded proteins can be used to screen for preeclampsia in late pregnancy with very high screening performance. To the best of our knowledge, this is the first study to screen for preeclampsia using Congo red based device in Chinese pregnant population.

From first-trimester screening to risk stratification of evolving pre-eclampsia in second and third trimesters of pregnancy: comprehensive approach.

Preeclampsia and associated hypertensive disorders of pregnancy represent a leading cause of global maternal and neonatal morbidity and mortality. Identification of women at high risk for developing preterm-preeclampsia and prophylaxis with low-dose aspirin has the potential to significantly reduce the rate of preterm-preeclampsia. In addition, risk assessment and monitoring of women in the second and third trimester of pregnancy, to aid in early detection of evolving disease, timely referral to specialist care, and active monitoring of women with confirmed or suspected preeclampsia is essential for improving maternal and neonatal outcomes. The angiogenesis-related biomarkers sFlt-1 and PlGF have been shown to have clinical value to aid in the prediction, diagnosis, and risk stratification of preeclampsia when used either alone or in combination with other risk factors. However, currently there is no consensus on the optimum strategy to link first trimester screening for preterm-preeclampsia with appropriate second and third trimester risk assessment strategies. This opinion paper will outline the current evidence for first trimester preeclampsia screening and prevention, as well as the evidence for various risk stratification approaches for detection of evolving preeclampsia through the second and third trimesters of pregnancy, and proposes a potential model integrating these tools. This article is protected by copyright. All rights reserved.

Prediction of pre-eclampsia: review of reviews.

Primary studies and systematic reviews provide estimates of varying accuracy for different factors in the prediction of pre-eclampsia. The aim of this study was to review published systematic reviews to collate evidence on the ability of available tests to predict pre-eclampsia, to identify high-value avenues for future research and to minimize future research waste in this field. MEDLINE, EMBASE and The Cochrane Library including DARE (Database of Abstracts of Reviews of Effects) databases, from database inception to March 2017, and bibliographies of relevant articles were searched, without language restrictions, for systematic reviews and meta-analyses on the prediction of pre-eclampsia. The quality of the included reviews was assessed using the AMSTAR tool and a modified version of the QUIPS tool. We evaluated the comprehensiveness of search, sample size, tests and outcomes evaluated, data synthesis methods, predictive ability estimates, risk of bias related to the population studied, measurement of predictors and outcomes, study attrition and adjustment for confounding. From 2444 citations identified, 126 reviews were included, reporting on over 90 predictors and 52 prediction models for pre-eclampsia. Around a third (n = 37 (29.4%)) of all reviews investigated solely biochemical markers for predicting pre-eclampsia, 31 (24.6%) investigated genetic associations with pre-eclampsia, 46 (36.5%) reported on clinical characteristics, four (3.2%) evaluated only ultrasound markers and six (4.8%) studied a combination of tests; two (1.6%) additional reviews evaluated primary studies investigating any screening test for pre-eclampsia. Reviews included between two and 265 primary studies, including up to 25 356 688 women in the largest review. Only approximately half (n = 67 (53.2%)) of the reviews assessed the quality of the included studies. There was a high risk of bias in many of the included reviews, particularly in relation to population representativeness and study attrition. Over 80% (n = 106 (84.1%)) summarized the findings using meta-analysis. Thirty-two (25.4%) studies lacked a formal statement on funding. The predictors with the best test performance were body mass index (BMI) > 35 kg/m2 , with a specificity of 92% (95% CI, 89-95%) and a sensitivity of 21% (95% CI, 12-31%); BMI > 25 kg/m2 , with a specificity of 73% (95% CI, 64-83%) and a sensitivity of 47% (95% CI, 33-61%); first-trimester uterine artery pulsatility index or resistance index > 90th centile (specificity 93% (95% CI, 90-96%) and sensitivity 26% (95% CI, 23-31%)); placental growth factor (specificity 89% (95% CI, 89-89%) and sensitivity 65% (95% CI, 63-67%)); and placental protein 13 (specificity 88% (95% CI, 87-89%) and sensitivity 37% (95% CI, 33-41%)). No single marker had a test performance suitable for routine clinical use. Models combining markers showed promise, but none had undergone external validation. This review of reviews calls into question the need for further aggregate meta-analysis in this area given the large number of published reviews subject to the common limitations of primary predictive studies. Prospective, well-designed studies of predictive markers, preferably randomized intervention studies, and combined through individual-patient data meta-analysis are needed to develop and validate new prediction models to facilitate the prediction of pre-eclampsia and minimize further research waste in this field. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

332. The role of PlGF in the prediction of preeclampsia

Background Simple, accurate and non-invasive biomarker testing is needed to predict preeclampsia and stratify its risk to enable and appropriate management. Various biomarkers have been tested for their role. One of the commonly used biomarker is PlGF which is found to be decreased in patients with preeclampsia and on average heralds the onset of disease and antedates the appearance of clinical symptoms. Objective and study design The purpose of this meta-analysis was to test this concept using the available evidence in the literature. We explored the predictive accuracy of PlGF in pre-eclampsia. 18 studies with following criteria were included: (1) Using serum PlGF to predict preeclampsia. (2) Analysing after 18 weeks of gestation. (3) Excluding multiple and non-viable pregnancies. (3) Sufficient data to construct a 2 × 2 diagnostic table. Results • PlGF has high sensitivity and low negative likelihood ratio in predictive screening of preeclampsia. But, the sensitivity is not enough for it to be recommended as a screening test for preeclampsia. •It may help in making decision regarding hospitalization and follow-up in women at a high risk of preeclampsia. •The use of PlGF may also decrease the anxiety and health care costs in managing patients with a negative test. Conclusion • This points to the need for larger cohort studies with uniformity in study criteria and involving diverse patient population. • Studies disagree about cut-off, gestational age for screening, single or multiple testing, type of preeclampsia tested (early/late onset) and the eligible patient population. • This is the first meta-analysis studying the potential of PlGF as a biomarker in predicting preeclampsia.

Maternal serum Alpha-fetoprotein Level at 12, 22 and 32weeks’ gestation in screening for pre-eclampsia

Pre-eclampsia is a major cause of maternal and perinatal morbidity and mortality. Alpha_fetoprotein is measured in pregnant women, as a screening test for pre-eclampsia.This study aimed to examine the maternal serum alpha-fetoprotein at 12, 22 and 32 weeks ’gestation in singleton pregnancies and its performance as a screening test for Pre eclampsia. The study designed as prospective (Cohort) study, it was conducted in Obstetrics department in Salah AL Din Teaching Hospital, from the period of the 15th of December 2016 to the 1st of July 2017. Ninety six pregnant women at first trimester participated in the study, followed up prospectively sixty three of them was attended a second test in second trimester and seventy five of them was attended a third test in a third trimester. The mean age of the studied group was 27.1 ± 5.8 (range: 17-30) years .It had been observed that the mean level of Alphafetoprotein was increased and the mean Multi of Median( MoM) was significantly reduced with advanced gestational age., there are highly significant differences at the different check-points in both mean and MoM, of the maternal alpha-fetoprotein. The mean alpha-fetoprotein level was higher in pre-eclampsia group compared to non-preeclampsia in all of the three testing points. The Comparison of mean alpha-fetoprotein levels of pre-eclampsia vs. non-preeclampsia women revealed that the mean, alpha-fetoprotein level was higher in pre-eclampsia group compared to non-preeclampsia in all of the three testing points, alpha-fetoprotein level at the second test was the better than the first and third test.

A Systematic Review of First Trimester Biochemical and Molecular Predictive Tests for Preeclampsia.

Preeclampsia is a multisystem disorder affecting 5%-8% of pregnant women. Considering the ongoing debate over the predicting value of some commercial first trimester tests, the aim of this study was to compare the existing first-trimester screening tests for preeclampsia. In this systematic review, relevant articles published during 2000-2017 were extracted from PubMed, Science Direct, Scopus, Cochrane Library, ISI Web of Science, and ProQuest databases. After a thorough evaluation of the 412 potentially eligible papers, only 28 papers were selected based on the inclusion criteria. From a total of 412 retrieved studies, 28 papers were found eligible. Most studies had casecontrol or nested case-control designs. A total of 15164 pregnant women were evaluated in the reviewed studies. Various tests were applied in the first trimester of pregnancy to predict the development of preeclampsia. The most commonly used biomarkers were uterine artery pulsatility index, pregnancy-associated plasma protein A (PAPP-A), adiponectin, human chorionic gonadotropin (hCG) hormone and inhibin-A. Other tests were used in only one or two studies. Based on this review, a combination of markers should be evaluated for the identification of high-risk women. Novel methods measuring multiple markers will hopefully facilitate the development of clinically effective screening programs in the future.