Proteomic Biomarkers in Second Trimester Amniotic Fluid That Identify Women Who Are Destined to Develop Preeclampsia

Abstract

Objectives: This study investigated whether proteomic analysis of amniotic fluid (AF) in the early second trimester can be used to predict the development of preeclampsia. Methods: Amniotic fluid samples were collected at the time of genetic amniocentesis (15-19 weeks of gestation) from women who subsequently developed preeclampsia and from gestational age-matched normotensive controls (n = 10 for each). Amniotic fluid samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, sodium dodecyl sulfate polyacrylamide gel coupled with in-gel tryptic digestion, electrospray ionization tandem mass spectrometry (MS/MS), immunodepletion assays, and enzyme-linke immunosorbent assay. Results: Five proteomic biomarkers were identified, which were differentially expressed in women who subsequently developed preeclampsia compared with those women who did not; four of these peaks were significantly upregulated (mass-to-charge ratio of 9080 [P = .006], 14 045 [P = .010], 14 345 [P = .049], and 28 087 [P = .006]) and one was significantly downregulated (mass-to-charge ratio of 4679 [P = .014]) in women who subsequently developed preeclampsia. Using electrospray ionization MS/MS and immunodepletion assays, two protein peaks were identified as albumin fragment and apolipoprotein A-I. Conclusions: Using proteomic technology, this study identified protein biomarkers that are differentially expressed in the early second trimester AF from women who subsequently develop preeclampsia compared with women who remained normotensive. Early identification of women at risk of developing preeclampsia will allow clinicians to better optimize maternal and perinatal outcomes.