Association between preconception serum homocysteine levels and early pregnancy loss in women with recurrent pregnancy loss

BACKGROUND: Elevated homocysteine (HCY) levels have been implicated in early pregnancy loss (EPL) but evidence remains inconclusive. The aim of this study was to investigate the association between preconception serum HCY levels and EPL in women who have experienced recurrent pregnancy loss (RPL). METHODS: Using data from a prospective dynamic pregnancy loss cohort established by our group, we screened 812 eligible patients with RPL, collected their medical records, and followed them for subsequent pregnancy outcomes. Multivariable logistic regression was used to assess the relationship between preconception serum HCY levels and the risk of subsequent EPL. Generalized additive models were also used to examine nonlinear associations between serum HCY levels and EPL. Subgroup analyses were further performed according to age, body mass index (BMI), and the number of previous pregnancy losses. RESULTS: The proportion of subsequent EPL was 22.66% (184/812). Significant differences in the proportion of EPL were observed across HCY quartiles (Q1: 10.45%, Q2: 14.80%, Q3: 21.23%, Q4: 43.84%; P < 0.0001). After adjusting for confounders, elevated preconception serum HCY levels were found to be associated with an increased risk of EPL (adjusted OR = 1.27, 95% CI: 1.14-1.42). Participants in Q3 and Q4 had significantly higher odds of EPL than those in Q1, with adjusted ORs of 5.55 (95% CI: 1.01-30.49) for Q3 and 10.79 (95% CI: 1.87-62.37) for Q4. Additionally, the analyses demonstrated a nonlinear relationship between preconception serum HCY levels and EPL risk. In this cohort, when HCY levels were ≥ 10.71 μmol/L, the risk of EPL increased significantly (adjusted OR = 1.27; 95% CI: 1.03-1.58). CONCLUSIONS: Elevated preconception serum HCY levels were associated with an increased risk of EPL in women with RPL, and the data-derived threshold of 10.71 μmol/L supports preconception risk stratification in this high-risk population.