Non‐Traditional Lipid Parameters and Risk of Adverse Pregnancy Outcomes in Gestational Diabetes Mellitus: Mediation by Maternal Metabolites

Aims To examine the association between non‐traditional lipid parameters and adverse pregnancy outcomes (APOs) in women with gestational diabetes mellitus (GDM) and the mediating role of maternal serum metabolites during pregnancy. Materials and Methods This prospective observational study enrolled 399 women with GDM. Multivariate logistic regression was used to examine the association between non‐traditional lipid parameters and APOs risk. Additionally, we assessed the mediating role of single and composite maternal serum metabolites during pregnancy using causal mediation analysis and high‐dimensional mediation analysis, respectively. Results APOs were observed in 12.0% ( N = 48) of participants. Seven non‐traditional lipid parameters, except for the RC/HDL‐C ratio, were associated with APOs risk, with the highest estimate for the atherogenic index of plasma (AIP) (OR = 3.873, 95% CI: 1.079–13.934, p = 0.037) after adjusting for confounders. Maternal metabolic markers mediated these associations, with mediation effect proportions of 21.9%–39.4%. Seven key metabolic markers were identified as potential mediators primarily involved in the biosynthesis of the unsaturated fatty acids pathway. Gene set variation analysis revealed significant differences in the positive regulation of this pathway between the APO and normal pregnancy outcome groups ( p = 0.015). Conclusions Non‐traditional lipid parameters were positively associated with APOs risk in women with GDM. Maternal serum metabolites, predominantly involved in the biosynthesis of unsaturated fatty acids, contribute to these associations.