Maternal age-related thyroid changes during pregnancy: implications for isolated hypothyroxinemia patterns

Objective To investigate the associations between maternal age and thyroid function in early and late pregnancy, as well as their changes, with a focus on the impact of age on the longitudinal patterns of isolated hypothyroxinemia. Methods This retrospective cohort study included 43,545 women with singleton pregnancies. Serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were measured in early and late pregnancy, along with their changes. Linear regression, restricted cubic spline (RCS), and piecewise linear regression were used to assess non-linear associations and threshold effects. Isolated hypothyroxinemia was categorized into euthyroid, transient, and persistent patterns. Ordinal logistic regression was used to examine the association between maternal age and these patterns, as well as the relationships between the patterns and adverse pregnancy outcomes, including preeclampsia, preterm birth, macrosomia, and low birth weight (LBW). Results Maternal age showed significantly stronger negative associations with FT4 levels and their changes than with TSH. Maternal age was positively associated with the risk of isolated hypothyroxinemia in a dose–response manner. Compared with women aged 18–24 years, those aged 35–39 years (OR = 1.89) and 40–49 years (OR = 3.01) had higher risks of persistent isolated hypothyroxinemia. Risks of preeclampsia, macrosomia, and LBW increased progressively from transient to persistent patterns (all P for trend <0.01). Conclusion Maternal age is an important factor influencing FT4 during pregnancy . Increasing age is associated with a higher likelihood of persistent isolated hypothyroxinemia, which is linked to a broader range of adverse pregnancy outcomes.