***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 Angiogenic factors like placental growth factor and its antiangiogenic antagonist soluble fms-like tyrosine kinase 1 ( sFlt1 ) are closely related to the pathogenesis of preeclampsia and intrauterine growth restriction . Because it is known that altered maternal sFlt1 and placental growth factor levels are detectable weeks before the onset of these pregnancy complications , it was the aim of the study to investigate the predictive value of these markers in high-risk second trimester pregnancies characterized by abnormal uterine perfusion . This prospect i ve study includes 63 second trimester pregnant women with abnormal uterine perfusion . Twenty five of them developed a later complication ( 12 with preeclampsia , 11 with intrauterine growth restriction , and 2 with intrauterine death ) , whereas 38 had a normal course of pregnancy . Pregnancies with adverse pregnancy outcome showed in the second trimester significantly higher sFlt1 ( 1403.6±555 versus 451.8±42 pg/mL ; P<0.05 ) and lower placental growth factor ( 139.6±24 versus 184.1±21 pg/mL ) levels compared with those with normal outcome . These alterations were more pronounced in pregnancies with subsequent preeclampsia compared with intrauterine growth restriction and early onset diseases ( delivery < 34 weeks ) compared with late-onset diseases . The combination of Doppler and sFlt1  increases the sensitivity of Doppler alone for iatrogenic preterm delivery from 64 % up to 79 % and the specificity from 63 % up to 80 % . Using both factors , sFlt1 and placental growth factor , early onset preeclampsia can be predicted with 83 % sensitivity and 95 % specificity . We conclude that the concurrent measurement of uterine perfusion and angiogenic factors allows an efficient prediction of early onset pregnancy complications , particularly preeclampsia Summary Recent evidence suggests that the oxidative stress is an important factor in the pathophysiology of pre-eclampsia . The purpose of this study was to evaluate the possible relationship between increased resistance at the Doppler assessment of the uterine arteries between 20–23 gestational weeks and biochemical markers of oxidative stress , with the development of pre-eclampsia and /or growth restricted infants . This was a prospect i ve study of 34 pregnant women with normal uteroplacental flow and 30 women with abnormal uterine arteries Doppler analysis ( mean PI ≥ 1.60 ) during the transvaginal assessment of the uterine arteries at the routine anomaly scan . Blood sample s were obtained in order to assess the plasma oxidative stress , namely malondialdehyde ( MDA ) and uric acid levels . The MDA was significantly higher in the group of women with abnormal uterine arteries Dopplers . This group is at increased risk for the development of pre-eclampsia . The uric acid levels did not differ significantly between the two groups of women . There was no significant difference regarding the sensitivity or the specificity of the  uterine arteries Doppler examination in detecting pre-eclampsia in comparison to the combination of oxidative stress and Doppler 's . Our study provides additional evidence regarding the role of oxidative stress in the pathophysiology of pre-eclampsia . Whether antioxidant supplementation in the group of women with abnormal uterine Doppler 's is effective in reducing the incidence of the disease remains to be established Aim : To evaluate the efficacy of a combined 2nd-trimester maternal serum homocysteine and uterine artery Doppler screening  at 20 weeks of gestation for complications of pregnancy : preeclampsia , isolated intrauterine growth restriction ( IUGR ) , placental abruption , and stillbirths .  Methods : Consecutive singleton pregnancies without previous risk factors who had homocysteine measured as part of a serum-screening program for trisomy 21 had uterine artery Doppler performed .  Sensitivity , specificity , positive and negative predictive values , odds ratio , and positive and negative likelihood ratios for the subsequent development of preeclampsia , isolated IUGR , placental abruption , stillbirth , and preterm delivery were calculated for the following methods ( 1 ) homocysteine cutoff level 6.3 µmol/l ( 95th centile ) ; ( 2 ) on Doppler ultrasound bilateral notches with a mean resistance index ( RI ) > 0.55 ( 50th centile ) , all unilateral notches with a mean RI > 0.65 ( 80th centile ) , and absence of notches with a mean RI > 0.7 ( 95th centile ) , and ( 3 ) Doppler ultrasound notch evaluation ( bilateral , unilateral , absence as in method 2 ) combined with the homocysteine cutof level of 6.3 µmol/l . Results : By using a logistic regression model , methods 1 and 2 predicted preeclampsia ( p < 0.001 ) , isolated IUGR ( p < 0.01 ) , and ‘ any complication ’ ( p < 0.01 ) . The sensitivity for prediction of preeclampsia using the combined method ( 3 ) was 61.3 % for a false-positive rate of 2 % , better than that for isolated IUGR ( 54 % ) below the 5th centile and ‘ any complication’(56 % ) . Conclusion : This prospect i ve study confirms the potential of a combined method of elevated homocysteine and uterine artery Doppler screening for preeclampsia , isolated IUGR , and any obstetric complication Objective To evaluate whether the determination of maternal plasma Factor II : C ( FII : C ) and mean uterine artery resistance index may be useful to early predict pre-eclampsia in patients with gestational hypertension . Design Prospect i ve study . Setting Consecutive enrollment in a public tertiary clinical care centre . Patients A total of 65 women with gestational hypertension at 24–26 weeks . Intervention Measurements of maternal plasma FII : C activity levels , ultrasonographic biometrical parameters and Doppler velocimetry of maternal uterine arteries .  Main outcome measure(s ) The probability of developing pre-eclampsia was the main outcome of the study and it was computed by combining the FII : C and the mean uterine artery resistance index cut-off points , chosen by receiver operating characteristic ( ROC ) curve analysis . Results F-II : C activity levels and mean uterine artery resistance index were significantly ( both P < 0.01 ) higher in women who developed pre-eclampsia . A weak , but significant correlation ( r = 0.3 , P < 0.05 ) was found between these two parameters . FII : C activity levels at the cut-off value of 136.5 % achieved a sensitivity of 61.1 % and a specificity of 71.3 % , while mean uterine artery resistance index ( RI ) at the cut-off value of 0.57 showed a sensitivity of 85.7 % and a specificity of 90.2 % in predicting the onset of pre-eclampsia . When both FII : C and mean uterine RI were over the cut-off points the positive predictive value was of 89 % , with a 100 % negative predictive value when both were below the cut-off points . Conclusion  F-II : C activity levels and mean uterine artery resistance index determination at mid trimester may improve the prediction of superimposed pre-eclampsia on women with early onset gestational hypertension OBJECTIVE To evaluate the screening efficacy of  second-trimester maternal serum inhibin-A  combined with uterine artery Doppler studies performed at 20 weeks ' gestation for the prediction of pre-eclampsia . METHODS Six hundred and eighty-nine consecutive unselected women who had inhibin-A levels measured between 15 and 19 weeks ' gestation subsequently had color flow pulsed Doppler of both uterine arteries at the time of the anomaly scan ( mean 20.5 , range 18 - 22 weeks ' gestation ) . The main outcome measures were pre-eclampsia and pre-eclampsia requiring delivery before 37 weeks ' gestation . The presence or absence of notches in the flow velocity waveform was noted , and the resistance index measured . Receiver operator curves were created for inhibin-A and uterine artery Dopplers alone and in combination . Sensitivities for each method were compared at false-positive rates of 3 % and 7 % . RESULTS Thirty-five women developed pre-eclampsia , of whom 15 required delivery before 37 weeks ' gestation . For a false-positive rate of 7 % , the sensitivity using bilateral notches/mean resistance index > or = 0.65 was 60 % with a positive likelihood ratio of 8.6 ( confidence interval 5.7 - 12.6 ) . For the same false-positive rate , when bilateral notches/mean resistance index > or = 0.55 and unilateral notches/mean resistance index > or = 0.65 were combined with inhibin-A > or = 1.0 multiples of the median , the sensitivity improved to 71 % and the positive likelihood ratio to 10.8 ( confidence interval 7.4 - 15.4 ) . For pre-eclampsia requiring delivery before 37 weeks for a false-positive rate of 3 % , the sensitivity for bilateral notches improved from 27 % to 60 % and the positive likelihood ratio improved from 9.2 to 20.8 when uterine artery notch data was combined with inhibin-A. The improvement in sensitivity for the combined method , compared to either inhibin-A or uterine artery Dopplers alone , was statistically significant for both pre-eclampsia ( P < 0.05 ) and preterm pre-eclampsia ( P < 0.02 ) . CONCLUSION Combination of second-trimester serum inhibin-A and uterine artery Doppler at 20 weeks improves the screening efficacy for the prediction of pre-eclampsia especially when this necessitates early delivery . This combination might form the basis of an effective and practical early screening test for the condition OBJECTIVE To investigate the value of maternal serum placental protein 13 ( PP-13 ) measurement and uterine artery Doppler during first-trimester screening in the prediction of early pre-eclampsia . METHODS This was a nested case-control prospect i ve study of pregnancies at 11 + 0 to 13 + 6 weeks of gestation . The pulsatility index ( PI ) of blood flow in the uterine arteries and the maternal serum concentration of PP-13  were measured in 10 women who went on to develop pre-eclampsia that necessitated delivery before 34 weeks , and in 423 unaffected women . Results were expressed as multiples of the gestation-specific median in controls ( MoM ) . A logistic regression model was used to predict detection and false-positive rates . RESULTS In the cases that developed pre-eclampsia requiring delivery before 34 weeks , compared with the unaffected pregnancies , the median uterine artery PI was higher ( 1.43 MoM ) and the median serum PP-13 level was lower ( 0.07 MoM ; P < 0.001 , Wilcoxon rank sum test for both ) . Modeling predicted that for a 90 % detection rate of pre-eclampsia requiring delivery before 34 weeks , the false-positive rate of screening by PP-13 was 12 % , by uterine artery PI was 31 % and by a combination of the two methods was 9 % . A policy of contingency screening , whereby all women are screened by maternal serum PP-13 and only the 14 % at highest risk are then screened by Doppler , achieved a detection rate of 90 % with an overall false-positive rate of 6 % . CONCLUSION Effective screening for pre-eclampsia requiring delivery before 34 weeks can potentially be provided by assessment of a combination of maternal serum PP-13 and uterine artery Doppler in the first trimester of pregnancy BACKGROUND AND PURPOSE Women with unexplained elevation of serum alpha-fetoprotein ( AFP ) are at increased risk for adverse pregnancy outcomes , including small for gestational age neonate , preterm labor 
    Output:
    
Combinations of markers generally led to an increase in sensitivity and /or specificity compared with single markers .
SUMMARY Combinations of biochemical and ultrasonographic markers improved the performance of early prediction of preeclampsia .