First-trimester lipoprotein(a) and longitudinal renal biomarker trajectories preceding preeclampsia: a pilot cohort study

PURPOSE: To evaluate whether early vascular susceptibility, reflected by first-trimester lipoprotein(a), together with longitudinal renal biomarker trajectories across pregnancy, is associated with the subsequent development of preeclampsia. METHODS: Retrospective analysis of prospectively collected data from a high-risk pregnancy cohort. Maternal serum inflammatory (interleukin-6, C-reactive protein), lipid (lipoprotein(a), triglycerides, total cholesterol), and renal (uric acid, cystatin C) biomarkers were measured at 11-13, 19-22, and 32 weeks of gestation. Longitudinal changes were assessed using population-averaged models including trimester, preeclampsia status, and their interaction, adjusted for maternal age and body mass index. First-trimester lipoprotein(a) was evaluated using adjusted logistic regression. RESULTS: Among 119 women, 20 developed preeclampsia. First-trimester lipoprotein(a) concentrations were higher in women who later developed preeclampsia and were independently associated with increased risk (OR 2.38; p < 0.001). Longitudinal analyses showed significant trimester-by-preeclampsia interactions for uric acid and cystatin C (both p = 0.03), indicating progressive divergence across pregnancy. Inflammatory biomarkers showed early between-group differences without significant longitudinal divergence. CONCLUSIONS: Our findings suggest that preeclampsia may be associated with both early maternal vascular susceptibility and progressive alterations in renal biomarkers during pregnancy. Elevated first-trimester lipoprotein(a) may reflect an underlying vascular phenotype, while divergent renal biomarker trajectories highlight the dynamic evolution of the disease before clinical onset, although these findings require validation in larger prospective studies.