title: Asymmetric dimethylarginine, arginine and homoarginine at 11-13 weeks' gestation and preeclampsia: a case-control study.
abstract: The aim of this study was to investigate whether the nitric oxide (NO) pathway is altered in pregnancies that develop preeclampsia (PE). This was a nested case-control study of screening for PE, in which plasma asymmetric dimethylarginine (ADMA), L-arginine and L-homoarginine were measured at 11(+0)-13(+6) weeks. In all, 75 pregnancies that developed PE, including 25 requiring delivery before 34 weeks (early PE), and 300 unaffected controls were included. L-arginine and L-homoarginine were measured by gas chromatography-mass spectrometry, whereas ADMA was measured by gas chromatography-tandem mass spectrometry. Multiple regression analysis was used to determine if any maternal characteristics or gestation were significant predictors. In the early-PE group, both L-arginine and L-homoarginine expected medians (MoMs) were significantly reduced (median, IQR: 0.85, 0.76-1.04 vs 0.98, 0.88-1.16, P=0.021 and 0.78, 0.65-0.96 vs 0.99, 0.77-1.31, P=0.006, respectively) but ADMA MoMs were not significantly different (P=0.599). In early PE, compared with controls, the ratios of ADMA to L-arginine MoMs and ADMA to L-homoarginine MoMs were increased (median, IQR: 1.19, 0.94-1.33 vs 1.01, 0.75-1.31, P=0.003 and 1.21, 0.93-1.61 vs 0.99, 0.87-1.16, P=0.012, respectively). There were no significant differences between late PE and controls in ADMA, L-arginine, L-homoarginine or their ratios. In conclusion, development of early PE is associated with altered NO metabolism and/or synthesis apparent from the first trimester.
authors.affiliation: Department of Fetal Medicine, Institute for Women's Health, University College London Hospitals, London, UK.
authors.forename: A A
authors.initials: AA
authors.lastname: Khalil
authors.forename: D
authors.initials: D
authors.lastname: Tsikas
authors.forename: R
authors.initials: R
authors.lastname: Akolekar
authors.forename: J
authors.initials: J
authors.lastname: Jordan
authors.forename: K H
authors.initials: KH
authors.lastname: Nicolaides
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D012044:Regression Analysis
chemical_list: D006709:Homoarginine; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine