We sought to determine whether maternal plasma lipoprotein(a) [Lp(a)] levels are elevated in the second trimester, before the development of preeclampsia and other obstetrical complications, in women at risk. In the first part of the study (cross-sectional), plasma concentrations of Lp(a) were compared among 16 women with preeclampsia, 35 normotensive pregnant women and 18 healthy nonpregnant women. In the second part (nested case-control), blood samples were collected prospectively from 82 women at risk of preeclampsia, at 14-24 weeks of gestation, and Lp(a) levels were compared between those in whom preeclampsia or other obstetrical complications developed and those in whom they did not. In the cross-sectional study, plasma concentrations of Lp(a) were significantly higher in women with preeclampsia than in normotensive pregnant and healthy nonpregnant women (41 +/- 31 vs. 24 +/- 16 and 15 +/- 10 mg/dl, respectively; P=.001). Of the 82 women in the second part of the study, 9 (11%) developed preeclampsia and 19 (23%) had complications such as intrauterine growth restriction, preterm delivery and fetal or neonatal loss. There were no differences in plasma Lp(a) concentrations between the women with preeclampsia and those without complications, though Lp(a) levels were significantly higher in women with other complications than in those with either preeclampsia or uncomplicated pregnancies (40 +/- 29 vs. 17 +/- 13 or 28 +/- 18 mg/dl, respectively; P=.05). In conclusion, elevated plasma levels of Lp(a), associated with clinically established preeclampsia, are not detected before the appearance of the disorder in pregnant women at risk.