Suzy Duckworth

Diagnostic Accuracy of Placental Growth Factor in Women With Suspected Preeclampsia A Prospective Multicenter Study

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

Prediction of delivering a small for gestational age infant and adverse perinatal outcome in women with suspected pre-eclampsia

To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small‐for‐gestational‐age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre‐eclampsia.

Placental Growth Factor (PlGF) in Women with Suspected Pre-Eclampsia Prior to 35 Weeks’ Gestation: A Budget Impact Analysis

Objective To model the resource implications of placental growth factor (PlGF) testing in women with suspected pre-eclampsia prior to 35 weeks’ gestation as part of a management algorithm, compared with current practice. Methods Data on resource use from 132 women with suspected pre-eclampsia prior to 35 weeks’ gestation, enrolled in a prospective observational cohort study evaluating PlGF measurement within antenatal assessment units within two UK consultant-led maternity units was extracted by case note review. A decision analytic model was developed using these data to establish the budget impact of managing women with suspected pre-eclampsia for two weeks from the date of PlGF testing, using a clinical management algorithm and reference cost tariffs. The main outcome measures of resource use (numbers of outpatient appointments, ultrasound investigations and hospital admissions) were correlated to final diagnosis and used to calculate comparative management regimes. Results The mean cost saving associated with the PlGF test (in the PlGF plus management arm) was £35,087 (95% CI -£33,181 to -£36,992) per 1,000 women. This equated to a saving of £582 (95% CI -552 to -£613) per woman tested. In 94% of iterations, PlGF testing was associated with cost saving compared to current practice. Conclusions This analysis suggests PlGF used as part of a clinical management algorithm in women presenting with suspected pre-eclampsia prior to 35 weeks’ gestation could provide cost savings by reducing unnecessary resource use. Introduction of PlGF testing could be used to direct appropriate resource allocation and overall would be cost saving.

Diagnostic Accuracy of Placental Growth Factor in Women With Suspected Preeclampsia

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

Plasma Placental Growth Factor (PlGF) in the diagnosis of women with pre-eclampsia requiring delivery within 14 days: the PELICAN study

The following abstracts summarise 25 of the 27 top scoring papers presented at the annual meeting of the Blair Bell Research Society, now incorporated into the Annual Academic Meeting held at the Royal College of Obstetricians and Gynaecologists which was held on 6–7th December 2012. Two abstracts were withheld for publication. Dr Olivia Moran was awarded the oral presentation prize to present her paper at the Society for Gynecologic Investigation Annual Meeting in March 2013. More details of the Society and its meetings can be found at www.rcog.org.uk/our-profession/ academic-o-g/blair-bell-research-society

Effect of antioxidant supplementation on pre-labour rupture of the membranes

Background Previous research exists to suggest vitamin C and E supplementation reduces the incidence of PROM (pre-labour rupture of the membranes) and preterm PROM (PPROM), conditions that precede up to a third of premature births.1 Antioxidants have a theoretical membrane protective effect against reactive oxygen species and collagen degradation.2 Aim To assess whether supplementation with vitamin C and E influences occurrence of PROM and PPROM in high risk pregnancy. Methods Data were analysed from the VIP trial (1000 mg vitamin C and 400 IU E vs Placebo in women at risk for pre-eclampsia) involving high risk women between 14+0 and 21+6 weeks gestation, across 25 UK centres. Demographics and pregnancy outcome were recorded,3 including time of rupture of membranes prior to labour and gestational age at delivery. Results Of 2411 participants, 154 (6.4%) women experienced PROM (n=113) or PPROM (n=41). The risk ratio for antioxidant supplementation in these pregnancies was 0.95 (95% CI 0.66 to 1.3) for PROM and 0.87 (0.47 to 1.60) for PPROM. There was no significant effect of antioxidants on PROM or PPROM when analysed by singleton/multiple pregnancy sub-groups. Conclusion These results suggest that there is no proven benefit of antioxidant supplementation in the reduction of PROM and PPROM, in singleton or multiple pregnancies. Further research is required to determine the pathophysiology and prevention of this life-threatening condition.

PP051. Budget impact analysis of maternal plasma PIGF concentrations in women with suspected pre-eclampsia: The potential for improved health service usage.

INTRODUCTION Existing methods of assessing women with suspected pre-eclampsia are expensive and labour intensive, yet perform poorly. OBJECTIVES AND METHODS The PELICAN multi-centre observational cohort study demonstrated that PlGF predicts need for delivery for pre-eclampsia within 14 days. We constructed a decision analytical model using outcome data from 100 women comparing resource use by final diagnosis and PlGF level. Costs were obtained from 2012-2013 NHS tariffs. RESULTS Of the 100 women, 40 had a final diagnosis of pre-eclampsia and delivered within 14 days of the PlGF test; 10 were healthy pregnancies with normal PlGF levels. 82% of women with pre-eclampsia were admitted during the final 2 weeks of pregnancy, with a 5-day (SD=5) length of stay, compared with 30% of healthy pregnancies with normal PlGF (1 day; SD=0.58). Resource use for outpatient appointments, scans and day unit admissions was similar for the two groups although higher in the group with a final diagnosis of pre-eclampsia. Total costs, excluding delivery, were approximately a third higher in the pre-eclampsia group. CONCLUSIONS This interim analysis suggests pre-eclampsia is associated with significantly higher resource use, although there is some inappropriate resource use in healthy women. PlGF can assist diagnosis and identify women requiring increased care and could be used to direct appropriate resource allocation in women over 37 weeks.

Diagnostic Accuracy of Placental Growth Factor in Women With Suspected PreeclampsiaClinical Perspective: A Prospective Multicenter Study

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

Diagnostic Accuracy of Placental Growth Factor in Women With Suspected PreeclampsiaClinical Perspective

Background— Hypertensive disorders of pregnancy are a major contributor to death and disability for pregnant women and their infants. The diagnosis of preeclampsia by using blood pressure and proteinuria is of limited use because they are tertiary, downstream features of the disease. Placental growth factor (PlGF) is an angiogenic factor, a secondary marker of associated placental dysfunction in preeclampsia, with known low plasma concentrations in the disease. Methods and Results— In a prospective multicenter study, we studied the diagnostic accuracy of low plasma PlGF concentration (<5th centile for gestation, Alere Triage assay) in women presenting with suspected preeclampsia between 20 and 35 weeks’ gestation (and up to 41 weeks’ gestation as a secondary analysis). The outcome was delivery for confirmed preeclampsia within 14 days. Of 625 women, 346 (55%) developed confirmed preeclampsia. In 287 women enrolled before 35 weeks’ gestation, PlGF <5th centile had high sensitivity (0.96; 95% confidence interval, 0.89–0.99) and negative predictive value (0.98; 0.93–0.995) for preeclampsia within 14 days; specificity was lower (0.55; 0.48–0.61). Area under the receiver operating characteristic curve for low PlGF (0.87, standard error 0.03) for predicting preeclampsia within 14 days was greater than all other commonly used tests, singly or in combination (range, 0.58–0.76), in women presenting with suspected preeclampsia (P<0.001 for all comparisons). Conclusions— In women presenting before 35 weeks’ gestation with suspected preeclampsia, low PlGF has high sensitivity and negative predictive value for preeclampsia within 14 days, is better than other currently used tests, and presents an innovative adjunct to management of such women.

2.2 Plasma Placental Growth Factor (PlGF) in the Diagnosis of Women with Pre-Eclampsia Requiring Delivery Within 14 Days: The PELICAN Study

Introduction Evidence exists to suggest that the symptoms of pre-eclampsia are mediated by an imbalance of circulating angiogenic factors of placental origin; reduced concentrations of placental growth factor (PlGF) have been correlated with disease severity. Methods A prospective, observational, cohort study was undertaken in seven UK maternity units. Women presenting 20 + 0 to 40 + 6 weeks gestation with suspected pre-eclampsia had serum PlGF measurement. ISSHP definitions of hypertensive disease were assigned, blinded to PlGF values. Analysis of the enrolment sample was conducted to evaluate diagnostic accuracy for pre-eclampsia requiring delivery within 14 days for very low PlGF (<12 pg/ml) and low PlGF (>12 pg/ml < 5th centile) using PlGF high (>5th centile) as referent. Results Diagnosis of pre-eclampsia requiring delivery within 14 days using 5th centile as threshold. Conclusion In women presenting <35 weeks’ gestation with suspected pre-eclampsia, low PlGF level rules in women requiring delivery within 14 days and high PlGF rules out preterm delivery. Test performance falls off in women presenting over 35 weeks’ gestational. PlGF can assist diagnosis and identify women requiring increased care. Abstract 2.2 Table < 35+0 35+0 to 36+6 ≥37+0 N = 287 N = 137 N = 201 Sensitivity 0.95 (0.89–0.99)79/83 0.71 (0.59–0.82)47/66 0.59 (0.48–0.70)49/83 Specificity 0.56 (0.49–0.63)114/204 0.65 (0.53–0.76)46/71 0.77 (0.69–0.84)91/118 Positive Predictive Value 0.47 (0.39–0.55)79/169 0.65 (0.53–0.76)47/72 0.65 (0.53–0.75)49/76 Negative Predictive Value 0.97 (0.92–0.99)114/118 0.71 (0.58–0.81)46/65 0.73 (0.64–0.80)91/125 Positive Likelihood ratio 2.2 (1.8–2.5) 2.0 (1.4–2.9) 2.6 (1.8–3.8) Negative Likelihood ratio 0.09 (0.03–0.23) 0.4 (0.3–0.7) 0.5 (0.4–0.7)