Proteomic Analysis of Maternal Urine for the Early Detection of Preeclampsia and Fetal Growth Restriction

Abstract

Background: To explore the use of maternal urine proteome for the identification of preeclampsia biomarkers. Methods: Maternal urine samples from women with and without preeclampsia were used for protein discovery followed by a validation study. The targeted proteins of interest were then measured in urine samples collected at 20–24 and 30–34 weeks among nine women who developed preeclampsia, one woman with fetal growth restriction, and 20 women with uncomplicated pregnancies from a longitudinal study. Protein identification and quantification was obtained using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Results: Among the 1108 urine proteins quantified in the discovery study, 21 were upregulated in preeclampsia and selected for validation. Nineteen (90%) proteins were confirmed as upregulated in preeclampsia cases. Among them, two proteins, ceruloplasmin and serpin A7, were upregulated at 20–24 weeks and 30–34 weeks of gestation (p < 0.05) in cases of preeclampsia, and could have served to identify 60% of women who subsequently developed preeclampsia and/or fetal growth restriction at 20–24 weeks of gestation, and 78% at 30–34 weeks, for a false-positive rate of 10%. Conclusions: Proteomic profiling of maternal urine can differentiate women with and without preeclampsia. Several proteins including ceruloplasmin and serpin A7 are upregulated in maternal urine before the diagnosis of preeclampsia and potentially fetal growth restriction.

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“…Recent proteomic studies have indicated that more than 130 urine proteins could improve timely detection of PE [34]. Patients suffering from PE have a different urine proteomic profile compared to healthy, pregnant patients.…”

“…Use of serpin A1 alongside albumin proved high accuracy for exposing patients at significant risk of developing PE up to 25 weeks before clinical diagnosis and, thus, indicating severe cases of PE that require immediate delivery [34]. Increased levels of serpin A1 in urine have been linked to the severity of PE [34]. Ceruloplasmin and serpin A7 were also significantly upregulated at 20-24 and 30-34 weeks of gestation in patients who subsequently developed PE.…”

“…Ceruloplasmin and serpin A7 were also significantly upregulated at 20-24 and 30-34 weeks of gestation in patients who subsequently developed PE. Ceruloplasmin is a copper-binding protein with antioxidant ferroxidase properties that is upregulated in PE secondary to placental ischemia [34]. The exact mechanism behind the upregulation of serpin A7 (or thyroxine-binding globulin, TBG) in PE remains unknown [34].…”

“…Ceruloplasmin is a copper-binding protein with antioxidant ferroxidase properties that is upregulated in PE secondary to placental ischemia [34]. The exact mechanism behind the upregulation of serpin A7 (or thyroxine-binding globulin, TBG) in PE remains unknown [34].…”

Diagnostic or Therapeutic Strategies for Pregnancy Complications

“…Advances in the early detection of women at risk of pregnancy complications have increased in the last decade, in part due to bioinformatic improvements, making it much easier to access and analyze large amounts of data and identify novel biomarkers. Indeed, proteomic biomarkers in maternal urine have proven promising as a non-invasive way of identifying women at risk of preeclampsia and fetal growth restriction [ 6 ]. Proteomic biomarkers, this time in maternal serum samples, were also investigated in a replication study looking at the ratio of IBP4/SHBG proteins as a predictive biomarker for spontaneous preterm birth [ 7 ].…”