Maternal TSH and FT4 changes during pregnancy as risk factors for preeclampsia in euthyroid women.

Objective: This large retrospective study aims to investigate the associations between FT4/TSH changes during pregnancy and the risk of preeclampsia among women with normal thyroid function in early and late pregnancy. Methods: We investigated the associations between changes in FT4 and TSH levels from early to late pregnancy and the risk of preeclampsia using restricted cubic spline and logistic regression models, both unadjusted and adjusted for potential confounders. Threshold effects were assessed via segmented regression to identify possible inflection points. Participants were categorized according to changes in thyroid function, and preeclampsia incidence was compared across the four groups. Sensitivity analyses were performed to evaluate the robustness of the findings. Statistical significance was set at two-sided P < 0.05. Results: TSH changes showed a J-shaped nonlinear association with preeclampsia risk (threshold 0.68 mIU/L), whereas FT4 changes were linearly and negatively associated. Participants were classified into four thyroid-function groups, with the Complete Decompensation group (ΔTSH > 0.68, ΔFT4 ≤ -3.30) showing the highest risk of preeclampsia (2.7%, aOR = 1.89, P < 0.001) and preeclampsia-related complications, including preterm birth (20.3%, aOR = 3.35, P = 0.016) and low birth weight (18.9%, aOR = 2.46, P = 0.046). Population-attributable risk analysis indicated that 21.6% of preeclampsia cases and 36.6% of severe cases were attributable to this pattern. Sensitivity analyses confirmed the robustness of these findings. Conclusion: Significant increases in TSH combined with decreases in FT4 during pregnancy are associated with higher risk of preeclampsia and related complications, even among women with normal thyroid function.