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

Objective To 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 B vitamin status. Design Longitudinal study. Setting Two obstetric referral hospitals. Sample Two hundred and fifty-two of 411 women invited to participate in the study. Methods The women made monthly visits from ≤20 weeks of gestation until delivery for measurements of plasma ADMA, Hcy, and vitamins B6, B12, and folic acid, and for the recording of clinical information. Main outcome measure Early elevations in plasma ADMA and Hcy related to the development of pre-eclampsia. Results Of 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 1 month prior to the onset of pre-eclampsia: 124 ± 27 nmol (P < 0.001) and 1177 ± 278 nmol (P = 0.001), respectively, in the pre-eclampsia group. The group of women with no complications did not show any significant changes. Increases of 80 nmol ADMA and 1000 nmol Hcy at 1 month prior to the onset of pre-eclampsia demonstrated the best potential for prediction. Conclusions Increased 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 abstract Increased ADMA and Hcy precede clinical pre-eclampsia and may identify women at risk.