Investigating the Associations Between Pre-pregnancy Lipoprotein(a) and Birth Outcomes: The Hispanic Community Health Study/Study of Latinos

Background Lipoprotein(a) [Lp(a)] is an atherosclerotic risk factor that may influence adverse pregnancy complications, although mechanisms remain poorly understood. Evidence linking Lp(a) with pregnancy outcomes relies on small cross-sectional studies, non-uniform Lp(a) measurement across pregnancy, and isoform-sensitive assays. Methods We identified 508 women with singleton live birth >43 weeks after baseline (2008–2011). Self-reported outcomes at second visit include: gestational diabetes mellitus (GDM, n=80 [16%]), hypertensive disorders of pregnancy (HDP, n=55 [11%]), preterm birth (PTB, n=55 [11%]), small for gestational age (SGA, n=37 [8%]), and Birth Weight Z-score (BWZ, n=483). Adverse pregnancy outcome (APO, n=179 [37%]) was defined as presence of GDM, HDP, PTB, or SGA. Confounder-adjusted (age, kidney function, Hispanic/Latino background) logistic regression examined linear, curvilinear, quartile-categorized, and binary risk-threshold (≥75 nmol/L) patterns. Results Baseline mean age was 26.4 (SD=5.8), almost half were of Mexican background, and the Lp(a) median=16.9 nmol/L (range: 2.8–415.1; IQR: 6.7–52.8 nmol/L; n=93 [18%] with Lp(a)>75 nmol/L). Lp(a) >75 nmol/L had an odds ratio of 0.77 for HDP (95%CI: 0.31–1.92) and 0.86 for PTB (95%CI: 0.32–2.32), both imprecise and did not reach statistical significance. The curvilinear model, though imprecise, suggested an inverted U-shaped dose–response pattern for odds of GDM and HDP, while PTB and BWZ showed downward and upward trends, respectively, across increasing Lp(a). Other associations showed no clear pattern. Conclusions Pre-pregnancy Lp(a) may exhibit a U-shaped dose-response with HDP and GDM, and a downward trend in PTB; however, there were no definite associations. Future work with larger samples is needed to understand the physiological implications of Lp(a) for pregnancy.