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Angiogenic factors combined with clinical risk factors to predict preterm pre-eclampsia in nulliparous women: a
J E Myers1, L C Kenny, L M E McCowan
1Faculty of Medical and Human Sciences, Maternal & Fetal Heath Research Centre, Institute of Human Development, Manchester Academic Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, University of Manchester, UK. Jenny.myers@manchester.ac.uk
Objectives:
To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women.
Design:
Predictive test accuracy study.
Setting:
Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE).
Methods:
Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression.
Main Outcome Measure:
Preterm pre-eclampsia (delivered before 37(+0) weeks of gestation).
Results:
Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement.
Conclusions:
Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility.
