Abstract
Abstract Fetal growth restriction (FGR) affects 3–5% of pregnancies and is associated with increased perinatal morbidity and mortality. Currently, there is no reliable biochemical test to differentiate a pathological FGR from a nonpathological one. The objective of this study was to screen whole maternal plasma to identify differentially expressed relatively abundant proteins associated with FGR. We analyzed maternal plasma from FGR (n=28) and healthy (n=22) pregnancies using two-dimensional gel electrophoresis (2D-GE) followed by software image analysis. Three spots with molecular weight (Mr) 18 kDa corresponding to haptoglobin (hp) α2, as identified by LC-MS/MS and immunoblotting, showed differential expression patterns in FGR. The distribution of hp α2 variants in maternal plasma samples showed the hp α2 variant 1 was low in 72% of FGR, medium in 16%, whereas high in 12%. In comparison, hp α2 variant 1 was high in (41%) of controls, medium in 41%, and low in 18% of cases. Based on the software image analysis, the mean spot volume for hp α2 variant 1 was 0.12 (SD=0.18) for FGR compared to 0.26 (SD=0.19) for control (p=0.006). Given that hp turnover is indicative of its maturation process and is traceable in plasma by its dominant/suppressed variants, we propose that hp α2 is an important potential target for evaluation of its clinical and pathophysiological role and as a diagnostic biomarker in FGR.
Highlights
Fetal growth restriction (FGR) is a pregnancy condition where estimated fetal weight is below the 10th percentile expected for gestational age (GA) [1,2]
Given that hp turnover is indicative of its maturation process and is traceable in plasma by its dominant/ suppressed variants, we propose that hp α2 is an important potential target for evaluation of its clinical and pathophysiological role and as a diagnostic biomarker in FGR
Based on the uterine artery Doppler velocimetry >50% of subjects were diagnosed with placental insufficiency, and the majority were in the ≥28 wk GA group
Summary
Fetal growth restriction (FGR) is a pregnancy condition where estimated fetal weight is below the 10th percentile expected for gestational age (GA) [1,2]. Fetal size is routinely ascertained using imaging technology; the differentiation of normal, constitutionally small fetuses from those with pathologic FGR remains a clinical challenge. Discovery of a candidate biomarker protein or a group of proteins that are associated with the pathophysiology of FGR, should lead to the development of rapid detection and quantification methods, for example immunoassays [6,7], for possible clinical screening. The measurement of biomarkers combined with advanced ultrasonographic (US) biometry and fetal Doppler technology in a temporal manner will provide the ability to more accurately and precisely detect the presence of FGR
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