title: Increased levels of copeptin before clinical diagnosis of preeclampsia.
abstract: Copeptin, a surrogate biomarker of vasopressin, has been associated with renal function decline and may serve as a useful early biomarker for preeclampsia. We measured serum copeptin using samples collected longitudinally during pregnancy among unaffected controls (n=136) and cases of preeclampsia (n=169), gestational diabetes mellitus (n=92), gestational hypertension (n=101), and preterm birth (n=86) in the Calcium for Preeclampsia Prevention trial (1992-1995). Preeclampsia and gestational hypertension were defined as having a diastolic blood pressure≥90 mm Hg on 2 occasions with and without proteinuria, respectively. The risk of pregnancy complications associated with copeptin was estimated by logistic regression adjusting for maternal age, race, body mass index, insurance status, marital status, current smoking, and clinical site. Baseline copeptin levels, at mean 16 weeks of gestation, were associated with increased preeclampsia risk (adjusted odds ratios and 95% confidence interval being 1.55 per log unit; 1.03-2.31) when compared with controls (P=0.03). The association was stronger among cases diagnosed before 37 weeks (1.86; 1.08-3.20) than those diagnosed later (1.45; 0.91-2.32). Copeptin levels rose with increasing gestational age in both cases and controls but remained significantly higher among those who were diagnosed with preeclampsia. Differences in levels of copeptin between cases and controls became more apparent closer to time of diagnosis. No significant associations were found for gestational hypertension without proteinuria, gestational diabetes mellitus, or preterm birth without preeclampsia. Copeptin levels are elevated in pregnant women before diagnosis of preeclampsia with elevation specific to this pregnancy complication rather than hypertension alone.
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.). yeungedw@mail.nih.gov.
authors.forename: Edwina H
authors.initials: EH
authors.lastname: Yeung
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.).
authors.forename: Aiyi
authors.initials: A
authors.lastname: Liu
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.).
authors.forename: James L
authors.initials: JL
authors.lastname: Mills
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.).
authors.forename: Cuilin
authors.initials: C
authors.lastname: Zhang
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.).
authors.forename: Tuija
authors.initials: T
authors.lastname: Männistö
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.).
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Lu
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.).
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
authors.affiliation: From the Epidemiology Branch (E.H.Y., J.L.M., C.Z., T.M., P.M.) and Biostatistics and Bioinformatics Branch (A.L.) in the Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD; Glotech, Inc, Rockville, MD (Z.L.); and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (M.Y.T.).
authors.forename: Pauline
authors.initials: P
authors.lastname: Mendola
mesh_terms: D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D003937:Diagnosis, Differential; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D016017:Odds Ratio; D011225:Pre-Eclampsia / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011498:Protein Precursors; D015203:Reproducibility of Results; D012307:Risk Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; D011498:Protein Precursors; C048197:copeptins
keywords: copeptin, human; diabetes; gestational; hypertension, pregnancy-induced; preeclampsia