Performance Of Screening For Pre-eclampsia Research Articles

Uterine artery pulsatility index at 12, 22, 32 and 36 weeks' gestation in screening for pre-eclampsia.

To examine the distribution of uterine artery pulsatility index (UtA-PI) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. UtA-PI was measured in 92 712 singleton pregnancies at 11-13 weeks, in 67 605 cases at 19-24 weeks, in 31 741 at 30-34 weeks and in 5523 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with UtA-PI. The performance of screening for PE requiring delivery < 32, at 32 + 0 to 36 + 6, < 37 and ≥ 37 weeks' gestation was estimated. The results of combined screening were compared to those of screening by UtA-PI and by maternal factors alone. In pregnancies that developed PE, UtA-PI was increased and the separation in multiples of the median (MoM) values from normal was greater with earlier, compared to later, gestational age at which delivery for PE became necessary. Additionally, the slope of regression lines of UtA-PI MoM with gestational age at delivery in pregnancies that developed PE increased with increasing gestational age at screening. The detection rate (DR), at a 10% false-positive rate (FPR), for PE delivering < 32 weeks was 71% and 88% with combined screening at 11-13 and 19-24 weeks, respectively, and the DR for PE delivering at 32 + 0 to 36 + 6 weeks was 52%, 63% and 71% with screening at 11-13, 19-24 and 30-34 weeks, respectively. However, the DR of PE delivering ≥ 37 weeks was only about 40%, irrespective of the gestational age at screening. The performance of screening by the approach utilizing Bayes' theorem was superior to that of using a percentile cut-off of UtA-PI for gestational age. The performance of combined screening with maternal factors and UtA-PI is superior for detection of early, compared to late, PE and, to a certain extent, improves with advancing gestational age at screening. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Mean arterial pressure at 12, 22, 32 and 36 weeks' gestation in screening for pre-eclampsia

To examine the distribution of mean arterial pressure (MAP) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. MAP was measured in 77 343 cases at 11-13 weeks, in 31 120 cases at 19-24 weeks, in 29 802 at 30-34 weeks and 5543 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with MAP. The performance of screening for PE requiring delivery < 32, at 32 + 0 to 36 + 6 and ≥ 37 weeks' gestation was estimated. In pregnancies that developed PE, MAP was increased and the separation in multiples of the median (MoM) values from normal was greater with an earlier, compared to later, gestational age at which delivery for PE became necessary. Additionally, the slope of the regression lines of MAP MoM with gestational age at delivery in pregnancies that developed PE increased with advancing gestational age at screening. The detection rate (DR), at a false-positive rate of 10%, for PE delivering < 32 weeks was 66% and 72% with screening at 12 and 22 weeks, respectively. The DR for PE delivering at 32 + 0 to 36 + 6 weeks was 54%, 56% and 81% with screening at 12, 22 and 32 weeks. The DR for PE delivering ≥ 37 weeks was 45%, 43%, 49% and 59% with screening at 12, 22, 32 and 36 weeks, respectively. The performance of combined screening with maternal factors and MAP is superior in screening for early, compared to late, PE and, to a certain extent, improves with advancing gestational age at screening. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Maternal serum soluble fms‐like tyrosine kinase‐1 at 12, 22, 32 and 36 weeks' gestation in screening for pre‐eclampsia

To examine the distribution of maternal serum soluble fms-like tyrosine kinase-1 (sFlt-1) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies that develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. Serum sFlt-1 was measured in 7066 cases at 11-13 weeks, 8079 cases at 19-24 weeks, 8472 at 30-34 weeks and 4043 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with serum levels of sFlt-1. The performance of screening for PE in women requiring delivery < 32, between 32 + 0 and 36 + 6 and ≥ 37 weeks' gestation was estimated. In pregnancies that developed PE, serum sFlt-1 was increased and the separation in multiples of the median (MoM) values from normal was greater with earlier, compared to later, gestational age at which delivery for PE became necessary. In pregnancies that developed PE, the slope of the regression lines of sFlt-1 MoM with gestational age at delivery increased with advancing gestational age at screening. Measurement of sFlt-1 at 11-13 weeks did not improve the prediction of PE achieved by maternal factors alone, sFlt-1 at 19-24 weeks improved the prediction of PE delivering < 37 weeks but not for PE delivering ≥ 37 weeks, sFlt-1 at 30-34 weeks improved the prediction of PE delivering < 37 and PE delivering ≥ 37 weeks and sFlt-1 at 35-37 weeks improved the prediction of PE delivering ≥ 37 weeks. The detection rates (DRs), at a false-positive rate (FPR) of 10%, of PE delivering < 32 weeks were 52% and 65% with screening at 12 and 22 weeks, respectively. The DRs for PE delivering between 32 + 0 and 36 + 6 weeks were 44%, 44% and 93% with screening at 12, 22 and 32 weeks. The DR for PE delivering ≥ 37 weeks were 37%, 37%, 52% and 69% with screening at 12, 22, 32 and 36 weeks, respectively. The performance of combined screening with maternal factors, medical history and serum sFlt-1 is superior for detection of early, compared to late, PE and improves with advancing gestational age at screening. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Maternal serum placental growth factor at 12, 22, 32 and 36 weeks' gestation in screening for pre-eclampsia.

To examine the distribution of maternal serum placental growth factor (PlGF) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. Serum PlGF was measured in 40 212 cases at 11-13 weeks, in 10 282 cases at 19-24 weeks, in 10 400 at 30-34 weeks and 4043 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with serum PlGF. The performance of screening for PE requiring delivery < 32, at 32 + 0 to 36 + 6 and ≥ 37 weeks' gestation was estimated. In pregnancies that developed PE, serum PlGF was decreased and the separation in multiples of the median (MoM) values from normal was greater with earlier, compared to later, gestational age at which delivery for PE became necessary. Additionally, the slope of the regression lines of PlGF MoM with gestational age at delivery in pregnancies that developed PE increased with advancing gestational age at screening. The detection rates (DRs), at a false-positive rate (FPR) of 10%, for PE delivering < 32 weeks were 79% and 97% with screening at 12 and 22 weeks, respectively. The DRs for PE delivering at 32 + 0 to 36 + 6 weeks were 57%, 65% and 90% with screening at 12, 22 and 32 weeks. The DRs for PE delivering ≥ 37 weeks were 40%, 37%, 54% and 64% with screening at 12, 22, 32 and 36 weeks, respectively. The performance of combined screening with maternal factors, medical history and PlGF is superior in screening for early, compared to late, PE and improves with advancing gestational age at screening. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30–34 weeks’ gestation

Preeclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. We have proposed a 2-stage strategy for the identification of pregnancies at high risk of developing PE. The objective of the first stage, at 11-13 weeks' gestation, is a reduction in the prevalence of the disease through pharmacological intervention in the high-risk group. The objective of the second stage, during the second and/or third trimesters, is to improve perinatal outcome through close monitoring of the high-risk group for earlier diagnosis of the clinical signs of the disease and selection of the appropriate, time, place, and method of delivery. The objective of the study was to examine the performance of screening for PE by a combination of maternal factors with early third-trimester biomarkers. This was a cohort study and data were derived from consecutive women with singleton pregnancies attending for their routine hospital visit at 30-34 weeks' gestation in 3 maternity hospitals in England between March 2011 and December 2014. In the first phase of the study, only uterine artery pulsatility index (UTPI) was measured and then measurement of mean arterial pressure (MAP) was added, and in the final phase, the serum concentration of placental growth factor (PLGF) was measured and then soluble fms-like tyrosine kinase-1 (SFLT) was added. We had data on UTPI, MAP, PLGF, and SFLT from 30,935, 29,042, 10,123, and 8,264 pregnancies, respectively. The Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of biomarker multiple of the median values. Ten-fold cross-validation was used to estimate the performance of screening for PE requiring delivery at < 37 weeks' gestation (preterm-PE) and those delivering at ≥ 37 weeks (term-PE). The empirical performance was compared with model predictions. In pregnancies that developed PE, the values of MAP, UTPI, and SFLT were increased and PLGF was decreased. For all biomarkers the deviation from normal was greater for preterm-PE than term-PE, and therefore, the performance of screening was inversely related to the gestational age at which delivery become necessary for maternal and/or fetal indications. Combined screening by maternal factors, MAP, UTPI, PLGF, and SFLT predicted 98% (95% confidence interval, 88-100%) of preterm-PE and 49% (95% confidence interval, 42-57%) of term-PE, at a false-positive rate of 5%. These empirical detection rates are compatible with the respective model-based rates of 98% and 54%, but the latter were optimistically biased. Combination of maternal factors and biomarkers in the early third trimester could predict nearly all cases of preterm-PE and half of those with term-PE, at 5% false-positive rate.

Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 19–24 weeks’ gestation

Preeclampsia (PE) affects 2-3% of all pregnancies and is a major cause of maternal and perinatal morbidity and mortality. The traditional approach to screening for PE is to use a risk-scoring system based on maternal demographic characteristics and medical history (maternal factors), but the performance of such an approach is very poor. To develop a model for PE based on a combination of maternal factors with second-trimester biomarkers. The data for this study were derived from prospective screening for adverse obstetric outcomes in women attending their routine hospital visit at 19-24 weeks' gestation in 3 maternity hospitals in England between January 2006 and July 2014. We had data from maternal factors, uterine artery pulsatility index (UTPI), mean arterial pressure (MAP), serum placental growth factor (PLGF), and serum soluble fms-like tyrosine kinase-1 (SFLT) from 123,406, 67,605, 31,120, 10,828, and 8079 pregnancies, respectively. Bayes' theorem was used to combine the a priori risk from maternal factors with various combinations of biomarker multiple of the median (MoM) values. The modeled performance of screening for PE requiring delivery at <32, <37, and ≥37 weeks' gestation was estimated. The modeled performance was compared to the empirical one, which was derived from 5-fold cross validation. We also examined the performance of screening based on risk factors from the medical history, as recommended by the American Congress of Obstetricians and Gynecologists (ACOG). In pregnancies that developed PE, the values of MAP, UTPI, and SFLT were increased and PLGF was decreased. For all biomarkers the deviation from normal was greater for early than for late PE, and therefore the performance of screening was inversely related to the gestational age at which delivery became necessary for maternal and/or fetal indications. Screening by maternal factors predicted 52%, 47%, and 37% of PE at <32, <37, and ≥37 weeks' gestation, respectively, at a false-positive rate of 10%. The respective values for combined screening with maternal factors and MAP, UTPI, and PLGF were 99%, 85%, and 46%; the performance was not improved by the addition of SFLT. In our population of 123,406 pregnancies, the DR of PE at <32, <37, and ≥37 weeks with the ACOG recommendations was 91%, 90%, and 91%, respectively, but at a screen positive rate of 67%. The performance of screening for PE by maternal factors and biomarkers in the middle trimester is superior to taking a medical history.

Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 11-13 weeks gestation

Preeclampsia affects approximately 3% of all pregnancies and is a major cause of maternal and perinatal morbidity and death. In the last decade, extensive research has been devoted to early screening for preeclampsia with the aim of reducing the prevalence of the disease through pharmacologic intervention in the high-risk group starting from the first trimester of pregnancy. The purpose of this study was to develop a model for preeclampsia based on maternal demographic characteristics and medical history (maternal factors) and biomarkers. The data for this study were derived from prospective screening for adverse obstetric outcomes in women who attended for their routine first hospital visit at 11-13 weeks gestation in 2 maternity hospitals in England. We screened 35,948 singleton pregnancies that included 1058 pregnancies (2.9%) that experienced preeclampsia. Bayes theorem was used to combine the a priori risk from maternal factors with various combinations of uterine artery pulsatility index, mean arterial pressure, serum pregnancy-associated plasma protein-A, and placental growth factor multiple of the median values. Five-fold cross validation was used to assess the performance of screening for preeclampsia that delivered at <37 weeks gestation (preterm-preeclampsia) and ≥37 weeks gestation (term-preeclampsia) by models that combined maternal factors with individual biomarkers and their combination with screening by maternal factors alone. In pregnancies that experienced preeclampsia, the values of uterine artery pulsatility index and mean arterial pressure were increased, and the values of serum pregnancy-associated plasma protein-A and placental growth factor were decreased. For all biomarkers, the deviation from normal was greater for early than late preeclampsia; therefore, the performance of screening was related inversely to the gestational age at which delivery became necessary for maternal and/or fetal indications. Combined screening by maternal factors, uterine artery pulsatility index, mean arterial pressure, and placental growth factor predicted 75% (95%confidence interval, 70-80%) of preterm-preeclampsia and 47% (95% confidence interval, 44-51%) of term-preeclampsia, at a false-positive rate of 10%; inclusion of pregnancy-associated plasma protein-A did not improve the performance of screening. Such detection rates are superior to the respective values of 49% (95% confidence interval, 43-55%) and 38% (34-41%) that were achieved by screening with maternal factors alone. Combination of maternal factors and biomarkers provides effective first-trimester screening for preterm-preeclampsia.

Prediction of Preeclampsia by Mean Arterial Pressure at 11-13 and 20-24 Weeks' Gestation

Objectives: To assess the performance of screening for preeclampsia (PE) by mean arterial pressure (MAP) at 11-13 and at 20-24 weeks' gestation. Methods: MAP was measured at 11-13 and 20-24 weeks in 17,383 singleton pregnancies, including 70 with early PE, requiring delivery <34 weeks' gestation, 143 with preterm PE, delivering <37 weeks and 537 with total PE. MAP was expressed as multiple of the median (MoM) after adjustment for maternal characteristics and corrected for adverse pregnancy outcomes. The performance of screening for PE by maternal characteristics and MAP MoM at 11-13 weeks (MAP-1), MAP MoM at 20-24 weeks (MAP-2) and their combination was evaluated. Results: In screening by maternal characteristics and MAP-1, at a false-positive rate (FPR) of 10%, the detection rates (DR) of early PE, preterm PE and total PE were 74.3, 62.9 and 49.3%, respectively; the DR at FPR of 5% were 52.9, 42.7 and 35.8%. In screening by MAP-1 and MAP-2 the DR at FPR of 10%, were 84.3, 65.7 and 52.5%; the DR at FPR of 5% were 60.0, 49.7 and 37.6%, respectively. Conclusions: Performance of screening for PE by MAP is best when measurements are taken at both 11-13 and 20-24 weeks' gestation than at only one of these gestational ranges.

Protocol for Measurement of Mean Arterial Pressure at 11-13 Weeks' Gestation

Objectives: To identify the best protocol for measurement of mean arterial pressure (MAP) in early pregnancy for the prediction of preeclampsia (PE). Methods: This was a prospective study in singleton pregnancies attending for a routine hospital visit at 11-13 weeks' gestation when a minimum of four recordings of MAP were taken from each arm. The performance of screening for PE by different combinations of MAP was compared to the protocol of the National Heart Foundation of Australia (NHFA). Results: The MAP was measured in 587 (2.4%) cases that developed PE and in 22,900 that were unaffected by hypertensive disorders in pregnancy. The area under the receiver operating characteristic curve (AUROC) for prediction of PE by MAP as recommended by the NHFA protocol was 0.773 (95% CI 0.768-0.778). This AUROC was not significantly different from the AUROC obtained by the average MAP of the first three measurements from one arm (0.765, 95% CI 0.760-0.771) or the average of the first (0.766, 95% CI 0.760-0.771), the first two (0.771, 95% CI 0.766-0.777), or the first three measurements from the two arms (0.773, 95% CI 0.768-0.778). Conclusion: Performance of screening for PE by taking the average of a minimum of two measurements from both arms is comparable to the NHFA protocol.

Maternal Serum Adiponectin at 11–13 Weeks of Gestation in Preeclampsia

Objective: To determine whether the maternal serum levels of adiponectin in the first trimester of pregnancy are altered in cases that develop preeclampsia (PE) and whether the levels are related to pregnancy-associated plasma protein-A (PAPP-A) and uterine artery pulsatility index (PI). Methods: Serum adiponectin, PAPP-A and uterine artery PI were measured at 11–13 weeks in 90 cases that developed PE, including 30 that required delivery before 34 weeks (early PE) and 300 unaffected controls. The median adiponectin, PAPP-A and uterine artery PI multiple of the unaffected median (MoM) in the outcome groups were compared. Results: In both early PE and late PE, compared to controls, uterine artery PI MoM was increased (1.32 and 1.05 vs. 1.02) and PAPP-A MoM was decreased (0.61 and 0.84 vs. 1.00), whereas adiponectin MoM was increased in early PE but not in late PE (1.32 and 1.05 vs. 1.02). In the PE group, there was no significant association between adiponectin and PAPP-A or uterine artery PI. Serum adiponectin did not improve the performance of screening for PE provided by a combination of the maternal factors, uterine artery PI and serum PAPP-A. Conclusion: Serum adiponectin levels at 11–13 weeks are increased in women that develop early PE by a mechanism unrelated to impaired placentation.

Hypertensive Disorders in Pregnancy: Screening by Systolic Diastolic and Mean Arterial Pressure at 11–13 Weeks

Objectives. To examine the performance of screening for hypertensive disorders in pregnancy and to compare systolic blood pressure (BP), diastolic BP, and mean arterial pressure (MAP) measured by validated automated devices in a large population of pregnant women at 11–13 weeks. Methods. We recorded maternal variables and measured BP by automated devices in 9149 women with singleton pregnancies. The performance of screening for preeclampsia (PE) and gestational hypertension (GH) by combinations of disease-specific maternal factor-derived a priori risk with systolic BP, diastolic BP, and MAP was determined. Results. There were 8061 cases that were unaffected by PE or GH, 37 that developed PE requiring delivery before 34 weeks (early-PE), 128 with late-PE, and 140 with GH. The systolic BP, diastolic BP, and MAP were significantly higher in early-PE, late-PE, and GH than in the controls (p < 0.0001). The systolic BP was significantly higher in early-PE than in late-PE (p = 0.008) and both systolic BP and MAP were significantly higher in early-PE than in GH (p < 0.01). The best performance in screening was provided by MAP. The detection rate of early-PE at a 10% false-positive rate increased from 47% in screening by maternal factor-derived a priori risk alone to 76% in screening by its combination with MAP. The respective detection rates for late-PE increased from 41 to 52% and for GH increased from 31 to 48%. Conclusion. The measurement of BP can be combined with the maternal factor-derived a priori risk to provide effective first-trimester screening for PE and GH.

Hypertensive disorders in pregnancy: screening by biophysical and biochemical markers at 11–13 weeks

To examine the performance of screening for pre-eclampsia (PE) and gestational hypertension (GH) by a combination of maternal factors and various biophysical and biochemical markers at 11-13 weeks' gestation. This was a case-control study of 26 cases of early PE, 90 of late PE, 85 of GH and 201 unaffected controls. Maternal history was recorded, the uterine artery with the lowest pulsatility index (L-PI) and mean arterial pressure (MAP) were measured and stored plasma and serum were analyzed for placental growth factor (PlGF), inhibin-A, activin-A, tumor necrosis factor receptor-1, matrix metalloproteinase-9, pentraxin-3 and P-selectin. Multivariate logistic regression analysis demonstrated that significant prediction for early PE was provided by maternal factors, MAP, uterine artery L-PI and serum PlGF. Significant prediction of late PE was provided by maternal factors, MAP, uterine artery L-PI, PlGF, activin-A and P-selectin. For GH significant prediction was provided by maternal factors, MAP, uterine artery L-PI and activin-A. In screening by a combination of maternal factors, biophysical and biochemical markers the estimated detection rates, at a 5% false-positive rate, were 88.5% (95% CI, 69.8-97.4%) for early PE, 46.7% (95% CI, 36.1-57.5%) for late PE and 35.3% (95% CI, 25.2-46.4%) for GH. Combined biophysical and biochemical testing at 11-13 weeks could effectively identify women at high risk for subsequent development of hypertensive disorders in pregnancy.

Maternal plasma soluble endoglin at 11–13 weeks' gestation in pre‐eclampsia

To examine the performance of screening for pre-eclampsia (PE) by a combination of maternal factors, soluble endoglin (sEng), pregnancy associated plasma protein-A (PAPP-A), placental growth factor (PlGF) and uterine artery lowest pulsatility index (L-PI) at 11-13 weeks' gestation. Uterine artery L-PI, sEng, PAPP-A and PlGF were measured at 11-13 weeks in 90 singleton pregnancies that subsequently developed PE, including 30 that required delivery before 34 weeks (early PE) and 60 with late PE, and 180 unaffected controls. Screening performance for PE by maternal factors, sEng, PAPP-A, PlGF and uterine artery L-PI and their combinations was determined. In early PE, compared to controls, plasma sEng and uterine L-PI were significantly increased and serum PAPP-A and PlGF were decreased. In late PE, compared to controls, serum PlGF was decreased and uterine L-PI was increased but plasma sEng and serum PAPP-A were not significantly different. In screening for early PE, the detection rate for a 10% false-positive rate was 46.7% for sEng alone and 96.3% for a combination of maternal factors, sEng, PlGF and uterine artery L-PI. Effective screening for early PE can be provided by a combination of maternal factors, sEng, PlGF and uterine artery L-PI at 11-13 weeks' gestation.

Hypertensive disorders in pregnancy: combined screening by uterine artery Doppler, blood pressure and serum PAPP‐A at 11–13 weeks

To explore if the addition of pregnancy-associated plasma protein-A (PAPP-A) to maternal factors and biophysical markers yields a significant improvement in the detection of hypertensive disorders before the clinical onset of disease. Prospective screening study for early preeclampsia (PE), late PE and gestational hypertension (GH) in women attending their first hospital visit at 11(+0)-13(+6) weeks of gestation. The performance of screening for PE and GH by combinations of maternal factors, uterine artery with the lowest pulsatility index (L-PI), mean arterial pressure (MAP) and serum PAPP-A was determined. There were 8061 unaffected controls, 37 of whom developed early PE, 128 with late PE and 140 with GH. Compared to the controls, in early PE and late PE MAP and uterine artery L-PI were increased and PAPP-A was decreased. In GH PAPP-A was not significantly different from controls. In screening for a combination of maternal factors, uterine artery L-PI, MAP and PAPP-A the detection rate of early PE was 83.8%, at a 5% false-positive rate. In the prediction of late PE and GH there was no significant improvement from the addition of PAPP-A to the combination of maternal factors, MAP and uterine artery L-PI. Measurement of PAPP-A improves the performance of screening for early PE provided by a combination of maternal factors and biophysical tests at 11-13 weeks.

Hypertensive disorders in pregnancy: screening by uterine artery Doppler imaging and blood pressure at 11–13 weeks

To examine the performance of screening for hypertensive disorders in pregnancy at 11-13 weeks by a combination of the maternal history, uterine artery Doppler imaging and blood pressure. This was a prospective screening study for pre-eclampsia (PE) requiring delivery before 34 weeks (early PE), late PE and gestational hypertension (GH) in women attending for their routine first hospital visit in pregnancy at 11 + 0 to 13 + 6 weeks of gestation. Maternal history was recorded, color flow Doppler imaging was used to identify the uterine artery with the lowest pulsatility index (L-PI) and automated devices were used to measure the mean arterial pressure (MAP). The performance of screening for PE and GH by a combination of the maternal factor-derived a-priori risk, the uterine artery L-PI and MAP was determined. There were 8061 (96.4%) cases unaffected by PE or GH, 165 (2.0%) that developed PE including 37 that required delivery before 34 weeks (early PE) and 128 with late PE, and 140 (1.7%) that developed GH. The MAP was higher in early PE, late PE and GH than in the unaffected group (P < 0.0001), and in early PE than in GH (P = 0.002). The uterine artery L-PI was significantly higher in early PE and late PE than in the unaffected group (P < 0.0001), in early PE than late PE or GH (P < 0.0001), and in GH than in the unaffected group (P = 0.014). In screening by a combination of the maternal factor-derived a-priori risk, uterine artery L-PI and MAP, the estimated detection rate at a 10% false-positive rate was 89.2% (95% CI, 74.6-96.9%) for early PE, 57.0% (95% CI, 48.0-65.7%) for late PE and 50.0% (95% CI, 41.4-58.6%) for GH. Effective screening for hypertensive disorders in pregnancy is provided by a combination of maternal history, uterine artery Doppler imaging and blood pressure at 11-13 weeks.

OP14.03: Longitudinal study of maternal insulin-like growth factor-I and uterine artery Doppler

Objective: To evaluate the performance of screening for preeclampsia (PET) in women who had both first and second trimester uterine artery (UtA) Doppler. Methods: This longitudinal study involved 3090 asymptomatic pregnant women who had UtA pulsatility index (PI) routinely at 11–14 and 20–25 weeks gestation. Demographic characteristics was also recorded contemporary. Multiple regression analysis was used to evaluate which of the maternal variables and Doppler findings were significant predictors of early-onset PET. Receiveroperating characteristics curves were used to evaluate the value as screening of different combined predictive models. Results: There were 93 (3.0%) women who later developed PET, including 30 women who delivered before 34 weeks gestation (early PET). Early and late PET differed substantially in their UtA PI findings during the first and second trimester of pregnancy. Multiple regression analysis showed that increased body mass index, previous PET, UtA PI at 11–14 and 20–25 weeks gestation, and the change in UtA resistance between the first and second trimester were significantly associated with the appearance of early PET. The detection rate of early PET for a 10% false positive rate in screening by maternal characteristics and first trimester UtA PI only and by a combination with a ratio between both UtA Dopplers was 50% and 82%, respectively. However, second trimester UtA PI alone was able to detect about 90% of women who subsequently developed early cases. Conclusion: This study has confirmed that the severe the PET the lower the magnitude of change in uterine artery dilatation between the first and second trimester of pregnancy. In addition, although the best methods to predict early PET is still the second trimester uterine artery Doppler, a combination between maternal findings, UtA Doppler at 11–14 weeks gestation and the ratio of changes between both trimesters should be also a good screening test for early PET. Supported by Fondecyt No 1090245

Hypertensive disorders in pregnancy: screening by uterine artery Doppler at 11–13 weeks

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. This was a prospective 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. 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% to 45% and those for GH increased from 31% to 35%. The patient-specific risk for PE and GH can be derived by combining the disease-specific maternal factor-derived a-priori risk with the measurement of the lowest UtA-PI in a multivariate regression model.

Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in the prediction of pre‐eclampsia

To evaluate the performance of screening for pre-eclampsia by uterine artery pulsatility index (PI) at 11 + 0 to 13 + 6 weeks' gestation and the change in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks. In 3107 singleton pregnancies attending for routine care at 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks' gestation we recorded maternal characteristics and medical and obstetric history, and measured uterine artery PI. The distributions of uterine artery PI were made Gaussian after logarithmic transformation and the log of the ratio of uterine artery PI at 21 + 0 to 24 + 6 weeks to that at 11 + 0 to 13 + 6 weeks was calculated. Multiple regression analysis was used to determine which of the maternal variables and Doppler findings were significant predictors of early and late pre-eclampsia. The performance of screening was described by receiver-operating characteristics curves. Pre-eclampsia developed in 93 (3.0%) pregnancies, including 22 (0.7%) in which delivery was before 34 weeks (early pre-eclampsia) and 71 (2.3%) with delivery at 34 weeks or more (late pre-eclampsia). Seventy-three (2.3%) women developed gestational hypertension, 346 (11.1%) delivered small-for-gestational-age (SGA) babies with no hypertensive disorders and 2595 (83.5%) were unaffected by pre-eclampsia, gestational hypertension or SGA. Multiple regression analysis demonstrated that maternal variables, uterine artery PI at 11 + 0 to 13 + 6 weeks and the change in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks' gestation provided significant independent contributions to the prediction of pre-eclampsia. For a false positive rate of 5% the predicted detection rates of early and late pre-eclampsia were 90.9 and 31.0%, respectively. The same performance of screening was achieved by reserving second-trimester testing for only the 20% of women at the highest risk after first-trimester screening. The decrease in uterine artery PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks is steeper in pregnancies with a normal outcome than in those developing pre-eclampsia. Effective screening for pre-eclampsia can be achieved by the Doppler measurement of uterine artery PI at 11 + 0 to 13 + 6 weeks and the change in PI between 11 + 0 to 13 + 6 and 21 + 0 to 24 + 6 weeks.

Urine albumin concentration and albumin‐to‐creatinine ratio at 11+0 to 13+6 weeks in the prediction of pre‐eclampsia

To determine the performance of screening for pre-eclampsia by maternal characteristics, urine albumin concentration and albumin-to-creatinine ratio (ACR) at 11(+0) to 13(+6) weeks. Prospective cross-sectional observational study. Routine antenatal visit. A total of 2679 pregnant women at 11(+0) to 13(+6) weeks of gestation. Maternal variables, urine albumin concentrations and ACR of 51 women who developed pre-eclampsia were compared with 2364 women who were unaffected by hypertensive disorders. Regression analysis was used first to determine which of the factors among the maternal characteristics were significant predictors of urine albumin concentration and ACR in the unaffected group and second to determine the contribution of urine albumin concentration and ACR in the prediction of pre-eclampsia. Development of pre-eclampsia. In the unaffected group, log urine albumin concentration and log ACR were influenced by ethnic origin, age, body mass index (BMI), parity and smoking. In the prediction of pre-eclampsia, significant contributions were provided by log urine albumin concentration, log ACR, ethnic origin, BMI, age, family and history of pre-eclampsia. The median urine albumin concentration and the median ACR in the pre-eclampsia group were significantly higher than those in the unaffected group. However, in screening for pre-eclampsia, the area under the receiver operating characteristic curve was not significantly improved by the combined models than with maternal variables alone. The value of urine albumin concentration was not improved by correcting for the creatinine concentration. In the prediction of pre-eclampsia, urine albumin concentration at 11(+0) to 13(+6) weeks does not provide additional value to maternal variables.

Mean Arterial Pressure at 11 +0 to 13 +6 Weeks in the Prediction of Preeclampsia

This study aimed to determine the performance of screening for preeclampsia (PE) by maternal medical history and mean arterial pressure (MAP) at 11(+0) to 13(+6) weeks. In 5590 women with singleton pregnancies attending for routine care at 11(+0) to 13(+6) week's gestation we recorded maternal variables and measured the MAP. We excluded 397 because they had missing outcome data or the pregnancies resulted in miscarriage or termination. In 104 patients there was subsequent development of PE, 97 developed gestational hypertension, 574 delivered small-for-gestational-age newborns, and 4418 were unaffected by PE, gestational hypertension, or small for gestational age. A multivariate Gaussian model was fitted to the distribution of log multiple of the median MAP in the PE and unaffected groups. Likelihood ratios for log multiple of the median MAP were computed and used together with maternal variables to produce patient-specific risks for each case. Detection rates and false-positive rates were calculated by taking the proportions with risks above a given risk threshold. In the unaffected group, log MAP was influenced by maternal age, ethnic origin, smoking, family and personal history of PE, and fetal crown-rump length. In the prediction of PE, significant contributions were provided by log multiple of the median MAP, ethnic origin, body mass index, and personal history of PE. The detection rate of PE by log multiple of the median MAP and maternal variables was 62.5% for a false-positive rate of 10%. Maternal variables, together with MAP, at 11(+0) to 13(+6) weeks identify a group at high risk for development of PE.