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Open Access

Altered proteome profiles in maternal plasma in pregnancies with fetal growth restriction

Haptoglobin α2 isoform as a potential biomarker
  • Madhulika B. Gupta1, 2, 3Email author,
  • Maxim D. Seferovic1, 2, 3,
  • Suya Liu2,
  • Robert J. Gratton4, 3,
  • Amanda Doherty-Kirby2,
  • Gilles A. Lajoie2, 3 and
  • Victor K. M. Han1, 2, 4, 3
Clinical Proteomics2:BF02752499


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.


Retinol Binding ProteinFetal Growth RestrictionMaternal PlasmaHELLP SyndromePlacental Insufficiency