Abstract

Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be identified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. We evaluate the performance of oxidative stress-associated potential biomarkers for FGR and PE, and their relationship with clinical characteristics. A prospective clinical pilot study was performed in healthy controls and women with pregnancies complicated by severe FGR with or without PE. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Placentas were examined microscopically. Descriptive statistics and receiver operating characteristics statistics were performed. Mothers with both severe FGR and PE had significantly reduced FT levels (p<0.001) and PlGF levels (p<0.001), and increased levels of plasma IMA (p<0.05), sFlt (p<0.001), leptin (p<0.05) and sRAGE (p<0.01) compared to women with FGR only. Systemic FT levels were significantly inversely associated with blood pressure (p<0.01) and plasma IMA (p<0.001), leptin (p=0.01) and sRAGE (p<0.001). Systemic FT and leptin showed significant discriminative ability to differentiate mothers with both FGR and PE from mothers with uncomplicated pregnancies or pregnancies complicated by FGR only. There is a significant discriminative capacity of FT, IMA, leptin and sRAGE that harbor potential as biomarkers of pregnancies complicated by combined FGR and PE.

Highlights

  • Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be iden­ tified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications

  • We evaluated maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), chorioamnionitis (CA), vil­ litis of unknown etiology (VUE), massive perivillous fibrin deposition (MPVFD), maternal floor infarction (MFI), chronic histiocytic inter­ villositis (CHIV), chorangiosis (CH) and fetal hypoxia (FH)

  • Serum FT levels are significantly reduced in mothers with combined FGR and PE, whereas plasma IMAR, leptin and soluble receptors for advanced glycation end products (sRAGE) levels are significantly higher compared to mothers with uncomplicated preg­ nancies

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Summary

Introduction

Oxidative stress as observed in fetal growth restriction (FGR) and preeclampsia (PE) can be iden­ tified by decreased levels of systemic free thiols (FT) and increased levels of plasma ischemia-modified albumin (IMA), which may serve as biomarkers in maternal blood for pregnancy complications. Blood samples were taken directly after inclusion and analyzed for FT; IMA; soluble FMS-like tyrosine kinase-1 (sFlt-1); placenta growth factor (PlGF); and biomarkers like leptin and soluble receptors for advanced glycation end products (sRAGE). Results: Mothers with both severe FGR and PE had significantly reduced FT levels (p < 0.001) and PlGF levels (p < 0.001), and increased levels of plasma IMA (p < 0.05), sFlt (p < 0.001), leptin (p < 0.05) and sRAGE (p < 0.01) compared to women with FGR only. Recent markers for pregnancies complicated with PE include plasma leptin and receptors for advanced glycation end products (sRAGE) [14,15,16,17]

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