Abstract
BACKGROUND: Folate is essential for DNA synthesis and cell division, particularly during pregnancy, where insufficient levels can lead to adverse outcomes like neural tube defects and preterm birth. Tobacco smoke exposure, indicated by serum cotinine levels, is a known risk factor for reduced folate levels. However, the mechanisms underlying this relationship, especially the role of lymphocytes, are not well understood. OBJECTIVES: This study evaluates the relationship between serum cotinine levels and RBC folate concentrations in pregnant women, explores the mediating role of lymphocyte count, and identifies susceptibility factors that could guide targeted interventions. METHODS: We conducted a cross-sectional analysis using NHANES data from 1999 to 2018, including 1,021 pregnant women. Serum cotinine levels were used as a biomarker for tobacco exposure, while RBC folate levels indicated long-term folate status. Linear regression, restricted cubic spline, and mediation analyses were performed to assess these relationships. RESULTS: Serum cotinine levels were significantly negatively correlated with RBC folate concentrations (P < 0.001). A nonlinear relationship revealed more pronounced folate depletion at higher cotinine levels. Mediation analysis showed that elevated lymphocyte count mediated 19.3% of the cotinine-folate association. Factors such as smoking history, advanced maternal age, and heavy alcohol consumption exacerbated this negative effect. CONCLUSION: Tobacco exposure(as reflected by elevated cotinine levels) significantly reduces folate levels in pregnant women, with lymphocyte count playing a mediating role. These findings underscore the need for targeted public health interventions to mitigate tobacco-related risks during pregnancy.