Asymmetric dimethylarginine, arginine and homoarginine at 11-13 weeks' gestation and preeclampsia: a case-control study.

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.