Cut-off values of angiogenic and antiangiogenic biomarkers in the assessment of preeclampsia in a high-risk population
06. April 2017 (online)
Aims and objectives:
Circulating differences in the antiangiogenic factor, soluble vascular endothelial growth factor receptor-1 (sFlt-1), and the pro-angiogenic placental growth factor (PlGF) seem to accurately predict preeclampsia (PE). The objective of this study was to investigate the recently proposed cut-off values of the sFlt-1:PlGF ratio in a high risk population.
Materials and Methods:
A prospective two centres cohort study was performed at the University Hospital of Basel and of Geneva after approval by the local CECs (EKBB 251/11 and GE 14 – 216) from 1/2012 until 3/2015. Pregnant women with singleton pregnancies and high risk to develop PE were asked to participate. The high risk group was followed regularly with clinical examinations and blood drawings for blinded biomarker analysis (sFlt-1, PlGF) every 2 – 4 weeks until delivery. Additionally, women who had symptoms, suspicious of PE (high blood pressure and/or proteinuria) were also approached and controlled clinically and biochemically from 1 to 7 days dependent on clinical condition until delivery. Only women with blood samples between 20+0 and 36+6 weeks of gestation (WOG) were included. Primary outcome was to assess the predicted absence (sFlt-1:PlGF ratio < 38) and presence of PE (sFlt-1:PlGF ratio of > 85 in < 34 weeks of gestation (WOG) or > 110 in > 35 WOG) within 4 weeks.
A total of 151 women with high risk or who were suspicious for PE were included for analysis, of whom 31 women finally developed PE. The difference in gestational age at blood collection was not significant with 28 (20 – 36) WOG in the high risk (54 d (0 – 142 d) before delivery) and 30 (21 – 36) WOG in the symptomatic group (3 d (0 – 27 d) before delivery). The negative predictive values (NPV) and positive predictive values (PPV) of the sFlt-1:PlGF ratio < 38 (rule out) were 99% (95% confidence interval (CI), 95 – 100%) and 61% (95% CI, 46 – 75%) with a sensitivity and a specificity of 97% (95% CI, 83 – 100%) and 84% (95% CI, 76 – 90%), retrospectively. The NPV and PPV of the sFlt-1:PlGF ratio > 85 or > 110 dependent on WOG (rule in) were 96% (95% CI, 90 – 99%) and 68% (95% CI, 51 – 82%) with a sensitivity and a specificity of 84% (95% CI, 66 – 95%) and 90% (95% CI, 83 – 95%).
The proposed cut-off value of 38 or lower can be used to rule out PE within 4 weeks in a high risk population.