Abstract
To assess the diagnostic performance of angiogenic biomarkers in determining need for delivery in seven days in women with late preterm preeclampsia. In a prospective observational cohort study in 36 maternity units across England and Wales, we studied the diagnostic accuracy of placental growth factor (PlGF) and sFlt-1 in determining the risk of complications requiring delivery in late preterm (34+0 to 36+6 weeks' gestation) preeclampsia. Angiogenic biomarkers were measured using the Quidel (PlGF) and Roche (sFlt-1:PlGF ratio) assays. Additional clinical data was obtained for use within the established 'Prediction of complications in early-onset pre-eclampsia' (PREP)-S prognostic model. Biomarkers were assessed using standard methods (sensitivity, specificity, Receiver Operator Curve areas). Estimated probability of early delivery from PREP-S was compared to actual event rates. Clinically indicated need for delivery for pre-eclampsia within seven days. PlGF (Quidel) testing had high sensitivity (97.9%) for delivery within seven days, but negative predictive value was only 71.4%, with low specificity (8.4%), with similar results from sFlt-1/PlGF assay. The area under the curve for PlGF was 0.60 (SE 0.03), and 0.65 (0.03), and 0.64 (0.03) for PREP-S in combination with PlGF, and sFlt-1:PlGF, respectively. Angiogenic biomarkers do not add to clinical assessment to help determine need for delivery for women with late preterm pre-eclampsia. Existing models developed in women with early-onset pre-eclampsia to predict complications cannot be used to predict clinically indicated need for delivery in women with late preterm pre-eclampsia.
Highlights
Pre-eclampsia affects around 2–3% of all pregnancies [1], and is associated with potentially serious complications for the woman and baby, including multiple maternal organ dysfunction and fetal morbidity and mortality
Study design: In a prospective observational cohort study in 36 maternity units across England and Wales, we studied the diagnostic accuracy of placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1) in determining the risk of compli cations requiring delivery in late preterm (34+0 to 36+6 weeks’ gestation) preeclampsia
We have previously reported that a PlGF threshold of < 100 pg/mL predicted preeclampsia requiring delivery within 14 days or before 37 weeks’ gestation with sensitivity and negative predic tive values similar to diagnostic accuracy estimates obtained by using a < 5th centile cut-off [4]
Summary
Pre-eclampsia affects around 2–3% of all pregnancies [1], and is associated with potentially serious complications for the woman and baby, including multiple maternal organ dysfunction (severe hyperten sion, renal and liver impairment, abnormal clotting and stroke or sei zures) and fetal morbidity and mortality. We have recently completed the multicentre PHOENIX trial, in which we demonstrated that in women with late preterm pre-eclampsia, planned delivery reduces maternal morbidity, whilst increasing neonatal unit admissions (principally for prematurity as the indication), though with no difference in neonatal morbidity (including need for respiratory support), compared with expectant management [2]. Of women in this gestational age window (34 to 37 weeks of pregnancy) managed expectantly, over half required delivery for clinical indications before they reached 37 weeks’ gestation, and pregnancy was prolonged (compared to planned delivery) by three days only. The PREP-S model is a survival model censored at 34 weeks’ gestation to predict adverse maternal outcomes from early onset pre eclampsia at various timepoints
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