Serial determinations of asymmetric dimethylarginine and homocysteine during pregnancy to predict pre-eclampsia: a longitudinal study

ObjectiveTo evaluate the usefulness of serial determinations of asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) concentrations during pregnancy to predict pre-eclampsia, taking into account maternal obesity and Bvitamin status. DesignLongitudinal study. SettingTwo obstetric referral hospitals. SampleTwo hundred and fifty-two of 411 women invited to participate in the study. MethodsThe women made monthly visits from 20weeks of gestation until delivery for measurements of plasma ADMA, Hcy, and vitamins B-6, B-12,B- and folic acid, and for the recording of clinical information. Main outcome measureEarly elevations in plasma ADMA and Hcy related to the development of pre-eclampsia. ResultsOf the 252 women who completed the study, 179 had no complications, 49 developed pre-eclampsia, and 24 presented with complications other than pre-eclampsia. ADMA and Hcy increased gradually throughout pregnancy in the pre-eclampsia group, independent of maternal B-vitamin status and obesity, but remained constant in women with no complications. Relative to the preceding month, ADMA and Hcy levels increased 1month prior to the onset of pre-eclampsia: 12427nmol (P<0.001) and 1177278nmol (P=0.001), respectively, in the pre-eclampsia group. The group of women with no complications did not show any significant changes. Increases of 80nmol ADMA and 1000nmol Hcy at 1month prior to the onset of pre-eclampsia demonstrated the best potential for prediction. ConclusionsIncreased ADMA and Hcy levels precede clinical manifestations of pre-eclampsia. Therefore, serial determinations of their concentrations may be helpful in identifying women at risk. Tweetable abstractIncreased ADMA and Hcy precede clinical pre-eclampsia and may identify women at risk. Tweetable abstract Increased ADMA and Hcy precede clinical pre-eclampsia and may identify women at risk.