***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE  Soluble endoglin ( sEng )  is increased dramatically in preeclampsia and acts synergistically with soluble fms-like tyrosine kinase 1 ( sFlt1 ) to promote the preeclamptic phenotype . The aim of this study was to investigate whether the  sEng  increase was present already in second-trimester pregnancies with abnormal uterine perfusion and whether the pregnancy was at risk for preeclampsia . STUDY DESIGN This prospect i ve study includes 77 second-trimester pregnant women with abnormal uterine perfusion .  sEng and sFlt1  were measured with an enzyme-linked immunosorbent assay . RESULTS Adverse pregnancy outcome was associated with higher  sEng levels in the second trimester . SEng was highest in those pregnancies with early-onset preeclampsia . Combined analysis of sEng and sFlt1 is able to predict early-onset preeclampsia with a sensitivity of 100 % and a specificity of 93.3 % . CONCLUSION Elevated sEng levels are detectable in second-trimester pregnancies with abnormal uterine perfusion and subsequent pregnancy complications . The concurrent measurement of uterine perfusion and angiogenic factors allows a highly efficient prediction of early-onset preeclampsia More than half of all cases of preeclampsia occur in healthy first-time pregnant women . Our aim was to develop a method to predict those at risk by combining clinical factors and measurements of biomarkers in women recruited to the Screening for Pregnancy Endpoints ( SCOPE ) study of low-risk nulliparous women . Forty-seven biomarkers identified on the basis of ( 1 ) association with preeclampsia , ( 2 ) a biological role in placentation , or ( 3 ) a role in cellular mechanisms involved in the pathogenesis of preeclampsia were measured in plasma sample d at 14 to 16 weeks ’ gestation from 5623 women . The cohort was r and omly divided into training ( n=3747 ) and validation ( n=1876 ) cohorts . Preeclampsia developed in 278 ( 4.9 % ) women , of whom 28 ( 0.5 % ) developed early-onset preeclampsia . The final model for the prediction of preeclampsia included placental growth factor , mean arterial pressure , and body mass index at 14 to 16 weeks ’ gestation , the consumption of ≥3 pieces of fruit per day , and mean uterine artery resistance index . The area under the receiver operator curve ( 95 % confidence interval ) for this model in training and validation cohorts was 0.73 ( 0.70–0.77 ) and 0.68 ( 0.63–0.74 ) , respectively . A predictive model of early-onset preeclampsia included angiogenin/placental growth factor as a ratio , mean arterial pressure , any pregnancy loss < 10 weeks , and mean uterine artery resistance index ( area under the receiver operator curve [ 95 % confidence interval ] in training and validation cohorts , 0.89 [ 0.78–1.0 ] and 0.78 [ 0.58–0.99 ] , respectively ) . Neither model included pregnancy-associated plasma protein A , previously reported to predict preeclampsia in population s of mixed parity and risk . In nulliparous women , combining multiple biomarkers and clinical data provided modest prediction of preeclampsia OBJECTIVE To evaluate the screening accuracy of pregnancy hypertensive disorders by maternal serum biomarkers and uterine artery Doppler in the first trimester . STUDY DESIGN Prospect ively enrolled nulliparous women had uterine artery Doppler and serum measured at 11 - 13 weeks .  Maternal characteristics , uterine artery Doppler , and serum placental biomarkers ( pregnancy-associated plasma protein-A , Inhibin-A , placental protein 13 , A disintegrin and metalloprotease 12 , free β-hCG , placental growth factor ) were recorded . RESULTS Among 893 women , 20 ( 2.2 % ) had gestational hypertension developed and 40 ( 4.5 % ) had preeclampsia developed , including 9 ( 1.0 % ) early-onset preeclampsia and 16 ( 1.8 % ) severe preeclampsia . A combined screening model with clinical characteristics , pregnancy-associated plasma protein-A , Inhibin-A , and placental growth factor could detect 75 % of early-onset preeclampsia at a 10 % false-positive rate . After adjustment for clinical variables , uterine artery Doppler , placental protein 13 , and A disintegrin and metalloprotease 12 did not improve the diagnostic accuracy . CONCLUSION A combination of clinical characteristics and first-trimester maternal serum biomarkers ( pregnancy-associated plasma protein-A , Inhibin-A , and placental growth factor ) provides an accurate screening for early-onset preeclampsia in nulliparous women Objectives To develop a predictive model for pre-eclampsia based on clinical risk factors for nulliparous women and to identify a subgroup at increased risk , in whom specialist referral might be indicated . Design Prospect i ve multicentre cohort . Setting Five centres in Auckl and , New Zeal and ; Adelaide , Australia ; Manchester and London , United Kingdom ; and Cork , Republic of Irel and . Participants 3572 “ healthy ” nulliparous women with a singleton pregnancy from a large international study ; data on pregnancy outcome were available for 3529 ( 99 % ) . Main outcome measure Pre-eclampsia defined as ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg , or both , on at least two occasions four hours apart after 20 weeks ’ gestation but before the onset of labour , or postpartum , with either proteinuria or any multisystem complication .  Preterm pre-eclampsia was defined as women with pre-eclampsia delivered before 37 + 0 weeks ’ gestation . In the stepwise logistic regression the comparison group was women without pre-eclampsia . Results Of the 3529 women , 186 ( 5.3 % ) developed pre-eclampsia , including 47 ( 1.3 % ) with preterm pre-eclampsia . Clinical risk factors at 14 - 16 weeks ’ gestation were age , mean arterial blood pressure , body mass index ( BMI ) , family history of pre-eclampsia , family history of coronary heart disease , maternal birth weight , and vaginal bleeding for at least five days . Factors associated with reduced risk were a previous single miscarriage with the same partner , taking at least 12 months to conceive , high intake of fruit , cigarette smoking , and alcohol use in the first trimester . The area under the receiver operating characteristics curve ( AUC ) , under internal validation , was 0.71 . Addition of uterine artery Doppler indices did not improve performance ( internal validation AUC 0.71 ) . A framework for specialist referral was developed based on a probability of pre-eclampsia generated by the model of at least 15 % or an abnormal uterine artery Doppler waveform in a subset of women with single risk factors . Nine per cent of nulliparous women would be referred for a specialist opinion , of whom 21 % would develop pre-eclampsia . The relative risk for developing pre-eclampsia and preterm pre-eclampsia in women referred to a specialist compared with st and ard care was 5.5 and 12.2 , respectively . Conclusions The ability to predict pre-eclampsia in healthy nulliparous women using clinical phenotype is modest and requires external validation in other population s. If vali date d , it could provide a personalised clinical risk profile for nulliparous women to which biomarkers could be added . Trial registration ACTRN12607000551493 OBJECTIVE To test the hypothesis that a combination of PP13 , PAPP-A and first-trimester uterine artery Doppler would improve the prediction of pre-eclampsia .  METHODS This is a prospect i ve cohort study of pregnant women followed from the first-trimester to delivery .  PP13 and PAPP-A were determined by immunoassay of maternal serum at 11 - 14 weeks ' , when uterine artery Doppler measurements were assessed . Cases identified with any form of pre-eclampsia were compared with a control group without pre-eclampsia . The sensitivity of each marker or their combinations in predicting pre-eclampsia for different fixed false positive rates was calculated from the ROC curves . RESULTS Forty two women were diagnosed with pre-eclampsia and 410 women with pregnancies not complicated by pre-eclampsia were used as controls . For a fixed false positive rate ( FPR ) of 20 % , PP13 , PAPP-A and mean uterine artery pulsatility index identified 49 % , 58 % and 62 % respectively , of women who developed any form of pre-eclampsia . PP13 was best in predicting early onset pre-eclampsia with a sensitivity of 79 % at a 20 % FPR . Combinations of the three first-trimester assessment s did not improve the prediction of pre-eclampsia in later pregnancy . CONCLUSION First-trimester PP13 , PAPP-A and uterine artery PI are reasonable , individual predictors of women at risk to develop pre-eclampsia . Combinations of these assessment s do not further improve the prediction of pre-eclampsia Objective . To evaluate the ability of endoglin , placental growth factor ( PlGF ) and the soluble form of vascular endothelial growth factor receptor ( sFlt‐1 ) measurements in gestational weeks 24–28 were used to predict pre‐eclampsia . Design . Observational , prospect i ve study . Setting . Department of Gynecological , Obstetrical Sciences and Reproductive Medicine , University of Messina . Sample . Fifty‐two pre‐eclamptic and 52 healthy pregnant women . Methods . A maternal serum sample was frozen and stored at 1‐h 50‐g glucose challenge test between 24 and 28 weeks ’ gestation . A second maternal serum sample was collected at admission for the onset of the disease in the pre‐eclamptic group and at admission for delivery in the control group . Levels of endoglin , sFlt‐1 and the PlGF  were measured in the stored serum . Pre‐eclamptic subjects were also divided into women with early‐onset ( < 37 weeks ) and women with late‐onset pre‐eclampsia ( ≥37 weeks ) .  Results . Levels of endoglin , sFlt‐1 , and sFlt‐1 : PlGF ratio were found to be higher in the pre‐eclamptic group in both trimesters . No differences were found between early‐ and late‐onset pre‐eclamptic . The Receiver Operating Characteristics curve , applied to the second trimester marker values , showed the best diagnostic profile for sFlt‐1 : PlGF ( area under the curve , AUC = 0.92 ) followed by endoglin ( AUC = 0.88 ) , sFlt‐1 ( AUC = 0.87 ) and PlGF ( AUC = 0.83 ) . This finding was confirmed by Bayesian analysis which highlighted a specificity , a sensitivity , a diagnostic accuracy , a positive predictive value and a negative predictive value of 88.5 % for sFlt‐1 : PlGF using a cut‐off of 38.47 . Conclusions . Endoglin , PlGF and sFlt‐1 might be used as markers for predicting pre‐eclampsia , but sFlt‐1 : PlGF seems to be more accurate OBJECTIVES To examine the performance of screening for hypertensive disorders in pregnancy by a combination of the maternal factor-derived a-priori risk with the uterine artery ( UtA ) pulsatility index ( PI ) and to determine whether it is best in such screening to use the mean PI of the two arteries , the highest PI or the lowest PI . METHODS This was a prospect i ve screening study for pre-eclampsia ( PE ) requiring delivery before 34 weeks ( early PE ) , late PE and gestational hypertension ( GH ) in women attending their routine first hospital visit in pregnancy at 11 + 0 to 13 + 6 weeks of gestation . Maternal history was recorded and color flow Doppler imaging was used to measure the left and right UtA-PI . The performance of screening for PE and GH by a combination of the maternal factor-derived a-priori risks determined in a previous study and the UtA-PI was assessed . RESULTS There were 8061 ( 96.4 % ) cases unaffected by PE or GH , 37 ( 0.4 % ) that developed early PE , 128 ( 1.5 % ) with late PE and 140 ( 1.7 % ) with GH . The lowest , mean and highest UtA-PI were significantly higher in early PE and late PE than in the controls ( P < 0.0001 ) and in early PE than late PE ( P < 0.0001 ) . The lowest UtA-PI was higher in GH than in controls ( P = 0.014 ) . The best performance in screening was provided by the lowest PI . The detection rate of early PE at a 10 % false-positive rate increased from 47 % in screening by maternal factors alone to 81 % in screening by maternal factors and the lowest UtA-PI . The respective detection rates for late PE increased from 41 % 
    Output:
    
Conclusion : Current evidence shows serum biomarkers such as PIGF , PP-13 and sFlt yielded the best results for a single biomarker with others having conflicting results .
However , a combination model with other diagnostic modalities performed better than a single biomarker .