Elevated second-trimester serum homocyst(e)ine levels and subsequent risk of preeclampsia

Objective: Elevated plasma homocyst(e)ine is a risk factor for endothelial dysfunction and vascular disease. In late gestation, levels of homocyst(e)i ne are higher in preeclamptics, as compared with normotensive pregnant wome n. Our objective was to determine whether homocyst(e)ine elevations precede the development of preeclampsia. Study Design: We used a prospective neste d case-control study design to compare second trimester maternal serum homo cyst(e)ine concentrations in 52 patients who developed preeclampsia (pregna ncy-induced hypertension with proteinuria) compared with 56 women who remai ned normotensive throughout pregnancy. Study subjects were selected from a base population of 3,042 women who provided blood samples at an average ges tational age of 16 weeks and later delivered at our center. Serum homocyst( e)ine was measured by high-performance liquid chromatography and electroche mical detection. Results: Approximately 29% of preeclamptics, as compared t o 13% of controls had homocyst(e)ine levels greater than or equal to 5.5 mu mol/l (upper decile of distribution of control values). Adjusted for mater nal age, parity, and body mass-index, a second trimester elevation of homoc yst(e)ine was associated with a 3.2-fold increased risk of preeclampsia (ad justed OR = 3.2; 95% CI 1.1-9.2; p = 0.030). There was evidence of a intera ction between maternal adiposity (as indicated by her prepregnancy body mas s index) and parity with second trimester elevations in serum homocyst(e)in e. Nulliparous women with elevated homocyst(e)ine levels experienced a 9.7- fold increased risk of preeclampsia as compared with multiparous women with out homocyst(e)ine elevations (95% CI 2.1-14.1; p = 0.003). Women with a hi gher prepregnancy body mass index (greater than or equal to 21.4 kg/m(2), o r upper 50th percentile) and who also had elevated homocyst(e)ine levels, a s compared with leaner women without homocyst(e)ine elevations were 6.9 tim es more likely to later develop preeclampsia (95% CI 1.4-32.1; p = 0.016). Conclusion: Our findings are consistent with other indications of vascular endothelial dysfunction predating clinical preeclampsia. Studies designed t o examine the effect of dietary and/or pharmacological mediators of homocys t(e)ine metabolism in preeclampsia are warranted.