Urinary placental growth factor in preeclampsia and fetal growth restriction: An alternative to circulating biomarkers?

Abstract

To correlate plasma and urinary soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PIGF) in preeclampsia (PE) and fetal growth restriction (FGR) and assess the performance in detecting established disease. A cross-sectional case-control study recruited 26-40 weeks gestation pregnancies into four clinical groups: normal pregnancy, PE, PE + FGR, and FGR. enzyme-linked immunosorbent assay (ELISA) measurements of urinary and plasma sFlt-1 and PlGF levels were performed. Urinary levels of sFlt-1 and PIGF were normalized to creatinine. Spearman's rank correlation was used to assess the association between plasma and urinary levels of sFlt-1 and PIGF, and receiver operating characteristic graphs were used to quantify the performance of each individual marker and their ratios in predicting normal versus pathological pregnancies affected by preeclampsia and/or FGR. There was a significant correlation between plasma PlGF and urinary PlGF (r = 0.718, P < 0.001) in all groups. In the pathological groups, plasma sFlt-1 and urinary sFlt-1 as well as plasma sFlt-1: PIGF ratio and urinary sFlt-1: PlGF ratio were higher, but plasma PIGF and urinary PlGF were lower when compared to normal pregnancy. Plasma PIGF and plasma sFlt-1: PlGF ratio was comparable in performance to urinary PlGF and urinary sFlt-1: PIGF ratio for the diagnosis of preeclampsia and/or FGR. Urinary PIGF can be used as an alternative to circulating biomarkers in preeclampsia and FGR. Plasma sFlt-1, PlGF and sFlt-1: PlGF ratio as well as urinary PIGF and sFlt-1: PlGF ratio can be used to differentiate between normal pregnancy and pregnancies complicated by preeclampsia and FGR.