Introduction Maternal thyroid hormone homeostasis during early gestation is fundamental for fetal growth and development, yet the specific clinical implications of the ratio between free triiodothyronine and free thyroxine, a marker of peripheral deiodinase activity and metabolic status, remain insufficiently explored regarding newborn health. Methods This retrospective cohort study investigated the association between the maternal free triiodothyronine to free thyroxine ratio measured during the first trimester and the risk of neonatal adverse outcomes. We analyzed data from 797 eligible mother–infant pairs, excluding those with pre-existing thyroid or immune disorders to isolate physiological variations. The primary endpoint was a composite of neonatal adverse outcomes, including respiratory, cardiovascular, and infectious complications. Multivariable logistic regression and restricted cubic spline modeling were employed to evaluate linear and non-linear associations. Results The results demonstrated that mothers in the highest quartile of the thyroid hormone ratio exhibited a significantly increased risk of adverse neonatal outcomes compared to those in the lowest quartile, an association that remained robust after adjusting for potential confounders such as maternal age, body mass index, and gestational age. The relationship followed a non-linear J-shaped pattern, with risks escalating sharply beyond a specific threshold. Specifically, a higher ratio was strongly associated with neonatal anemia, patent ductus arteriosus, jaundice, and myocardial injury. Subgroup analyses revealed that this risk was particularly pronounced in nulliparous women, mothers with a normal body mass index, and female neonates. Discussion These findings suggest that an elevated free triiodothyronine to free thyroxine ratio in early pregnancy serves as a sensitive indicator of neonatal risk, potentially reflecting maladaptive maternal metabolic demands that impact fetal health independent of traditional obstetric risk factors.
Chen et al. (2026) studied this question.