Individual and Combined Diagnostic Accuracy of Biochemical Markers for Detecting Early On-Set Preeclampsia

Abstract

Background: Preeclampsia (PE) is one of the leading causes of maternal and neonatal mortality across the globe. Existing diagnostic parameters of PE have not proven to be sufficient in detecting the condition in its early stage. It is imperative to evaluate the biomarkers that are involve in the pathogenesis of PE, to identify which of them is specific and sensitive enough to detect early onset PE to prevent its associated adverse outcomes. This study evaluated the individual and combine diagnostic accuracy of angiogenic factors oxidative stress biomarkers, spot urine protein, creatinine and uric acid for detecting early onset PE. Methods: A total of 165 pregnant women comprising of 110 women with PE and 55 pregnant women without PE (controls) were recruited from the Obstetrics and Gynaecology department at the Komfo Anokye Teaching Hospital (KATH). Blood samples were collected and assayed for Placental Growth Factor (PIGF), soluble fms-like tyrosine kinase 1 (sFlt-1) and 8-epi-Prostaglandin F2alpha (8-epi-PGF2α) levels using ELISA kits whilst total antioxidant capacity (T-AOC), urea, creatinine and uric acid were measured spectrophotometrically. Results: Levels of PIGF, T-AOC, PIGF/sFlt-1 ratio, PIGF/8-epiPGF2α, and sFlt-1/8-epiPGF2α were significantly reduced in early onset PE whilst sFlt-1, 8-epi-PGF2α, sFlt-1/PIGF ratio, 8-epiPGF2α/PIGF, 8-epiPGF2α/sFlt-1, spot urine protein/creatinine (Cr) ratio and Uric Acid (UA) were significantly increased in early-onset PE compared to late-onset PE (p < 0.05). In descending order, the most specific and sensitive biomarker for early onset PE were PIGF/sFlt-1 ratio (0.81; 75.0% and 97.0%; p < 0.0001) followed by 8-epiPGF2α/PIGF (0.73; 60.0% and 81.0%; p = 0.0020), sFlt-1/PIGF ratio (0.79; 55.0% and 81.0%; p < 0.0001), PIGF/8-epiPGF2α (0.71; 60.0% and 78.0%; p = 0.0010) and UA (0.70; 50% and 79.0%; p = 0.0340). At the various diagnostic cut-off of the markers, levels of PIGF, PIGF/sFlt-1, and PIGF/8-epiPGF2α were reduced whilst elevated level of sFlt-1, sFlt-1/PIGF, and 8-epiPGF2α/PIGF were significant predictors of early onset preeclampsia.