Dose-response relationships between maternal thyroid hormone levels and infant BMI trajectories: a prospective cohort study

Background Maternal thyroid hormones are key regulators of fetal metabolic programming, with gestational disruption potentially altering long-term offspring growth and adiposity. However, most evidence is restricted to single time-point outcomes like birth weight, and trimester-specific nonlinear dose-response relationships between maternal thyroid function and longitudinal infant BMI trajectories remain unclear. This study investigated these associations across all three trimesters in a large prospective birth cohort. Methods We enrolled 3461 mother-infant pairs from a prospective birth cohort. Serum TSH, FT3, and FT4 concentrations were measured each trimester, and gestational week-adjusted Z-scores were calculated to reduce timing bias. Latent class growth modeling (LCGM) identified distinct BMI trajectories from birth to 24 months. Multivariable logistic regression and restricted cubic spline (RCS) models evaluated associations, adjusted for maternal age, education, pre-pregnancy BMI, parity and other confounders. Results Four infant BMI trajectories were identified: normal growth (46.1%), slow growth (16.8%), catch-up growth (14.3%), and accelerated growth (22.8%). Associations showed significant trimester-specific, hormone-dependent nonlinear patterns. In the first trimester, lower TSH and higher FT3/FT4 correlated with reduced accelerated growth risk (all P < 0.05). In the second trimester, the highest TSH group increased accelerated growth risk ( OR = 1.99, 95% CI 1.01–3.89, P = 0.045), although the RCS analysis did not show a significant overall association ( P for overall > 0.05). In the third trimester, elevated FT3 was associated with higher risks of all three abnormal growth patterns (Slow growth: OR = 2.08, 95% CI 1.14–3.71, P = 0.014; Catch-up growth: OR = 1.89, 95% CI 1.03–3.38, P = 0.035; Accelerated growth: OR = 1.78, 95% CI 1.03–3.06, P = 0.038), with a U-shaped nonlinear link to slow growth risk (overall P = 0.031, P for nonlinearity = 0.013). Conclusions Maternal thyroid hormones were associated with infant BMI trajectories in a trimester- and hormone-specific manner, with a U-shaped nonlinear association observed for late-pregnancy FT3 and slow growth. These findings suggest a potential gestational window for thyroid hormone influence on infant growth, but further studies are needed to determine whether targeted thyroid monitoring or intervention could improve infant growth outcomes.