Copeptin and mid‐regional pro‐atrial natriuretic peptide in women with suspected or confirmed pre‐eclampsia: comparison with sFlt‐1/PlGF ratio

ABSTRACT Objectives Arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) may contribute to the pathogenesis of pre‐eclampsia (PE), but their role remains to be elucidated. Our aims were to evaluate the surrogates of AVP and ANP, C‐terminal pro‐AVP (copeptin) and mid‐regional pro‐ANP (MR‐proANP), as biomarkers for the prediction of PE‐related pregnancy complications and whether they are associated with angiogenic markers and/or clinical manifestations of PE. Methods This was a retrospective analysis of a prospective cohort study that enrolled pregnant women with suspected or confirmed PE, between December 2013 and April 2016. From each patient, a blood sample was obtained at study entry and serum levels of copeptin, MR‐proANP, soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF) were measured. We evaluated the ability of sFlt‐1, PlGF, sFlt‐1/PlGF ratio, copeptin and MR‐proANP, assessed either alone or combined with traditional predictors (gestational age, parity, diastolic blood pressure and proteinuria), to predict maternal complications and fetal/neonatal complications. Models were compared using concordance statistic (C‐index). Results A total of 526 women were evaluated in the study. Women with confirmed PE displayed elevated serum copeptin and MR‐proANP levels in comparison to those with suspected PE but no hypertensive disease of pregnancy. When combined with traditional predictors, the sFlt‐1/PlGF ratio displayed a higher C‐index than copeptin and MR‐proANP (0.76, 0.63 and 0.67, respectively, vs 0.60 for the traditional predictors alone) for the prediction of maternal complications. Similarly, for the prediction of fetal/neonatal complications, the sFlt‐1/PlGF ratio displayed a higher C‐index than copeptin and MR‐proANP when added to the traditional model (0.83, 0.79 and 0.80, respectively, vs 0.79 for the traditional predictors alone). When subdividing women according to sFlt‐1/PlGF ratio (≥ 85 vs