Association between early pregnancy thyroid function and placental-to-fetal weight ratio (PWR): A large-scale retrospective cohort study

This large retrospective study aimed to investigate the association between first-trimester thyroid function and the placental-to-fetal weight ratio (PWR), as well as the relationship between PWR and adverse pregnancy outcomes. A total of 34,193 singleton pregnancies were included. Univariate and multivariate logistic regression models examined associations between free thyroxine (FT4), thyroid-stimulating hormone (TSH), and abnormal PWR. Stratified analyses assessed effect modifications, and likelihood ratio tests evaluated nonlinear relationships among thyroid hormones, PWR, and adverse outcomes. FT4 showed a bidirectional association with PWR. Higher FT4 levels were linked to a reduced risk of low PWR (OR = 0.98 [CI 0.96–1.00], P = 0.021) and an increased risk of high PWR (OR = 1.02 [CI 1.00–1.04], P = 0.025). In women ≥35 years, the protective association was stronger (OR = 0.91 [CI 0.86–0.97], P = 0.002). TSH exhibited a J-shaped nonlinear association with PWR, increasing the risk of low PWR (OR = 1.07 [CI 1.02–1.11], P = 0.002), with a significant interaction in the IVF subgroup (P = 0.036). PWR showed nonlinear associations with outcomes including macrosomia, preterm birth, SGA, emergency cesarean delivery, and fetal distress, with an optimal range of 0.18–0.20. Preeclampsia and GDM were linearly associated with higher PWR. Mediation analyses showed minimal mediation by PWR in the associations between maternal thyroid hormones and adverse pregnancy outcomes. This study found that thyroid function in early pregnancy is associated with late-pregnancy placental efficiency marker PWR, which is also linked to multiple adverse pregnancy outcomes. • A large retrospective cohort of 34,193 singleton pregnancies examined associations between early pregnancy thyroid function and PWR. • FT4 showed a bidirectional association with abnormal PWR , with modified by maternal age. • TSH showed a J-shaped association with PWR , with modified by IVF pregnancies. • Both high and low PWR were linked to adverse outcomes ; the optimal PWR range was approximately 0.18–0.20. • Early pregnancy thyroid function independently affected multiple outcomes , including macrosomia, SGA, GDM, and emergency cesarean delivery.