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

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.