Associations of early-pregnancy triiodothyronine and triglycerides with hypertensive disorders of pregnancy: a retrospective cohort study

Background Thyroid hormones are associated with hypertensive disorders of pregnancy (HDP), but the contribution of triiodothyronine (T3), the biologically active thyroid hormone, remains insufficiently understood. Given the established role of T3 in lipid homeostasis and the association of triglycerides (TG) with HDP, we aimed to examine the associations of early-pregnancy T3 and TG levels with HDP and evaluate the potential role of TG in the association between T3 and HDP. Methods This retrospective cohort study included 13,915 pregnant women who underwent prenatal screening between January 2020 and December 2021. Multivariable logistic regression was used to examine the associations of early-pregnancy free triiodothyronine (FT3), total triiodothyronine (TT3), and TG with HDP and its subtypes, while linear regression was used to assess the associations of FT3 and TT3 with TG. Mediation analysis assessed statistical indirect associations through TG, and multiplicative interaction analysis evaluated interactions between T3 and TG. Results Higher early-pregnancy FT3, TT3, and TG levels were associated with higher odds of HDP (all P < 0.05), and both FT3 and TT3 were positively associated with TG ( P < 0.05). Mediation analysis identified significant indirect associations through TG, representing an estimated 34.1% and 33.5% of the observed associations of FT3 and TT3 with HDP, respectively. Comparable indirect associations were observed for preeclampsia (PE), with estimated proportions of 18.6% and 28.3%, respectively. For gestational hypertension (GH), an indirect association through TG was observed for TT3 (estimated proportion, 42.0%), whereas the corresponding proportion for FT3 was not interpreted because the total association was not statistically significant. No evidence of multiplicative interaction between T3 and TG was observed in relation to HDP. Conclusion Higher early-pregnancy FT3 and TT3 levels were associated with higher odds of HDP, particularly PE. TG may represent a potential metabolic component involved in the observed associations between T3 and HDP.