Early-to-mid-pregnancy maternal free thyroxine and fetal growth velocity trajectories: evidence from a large prospective cohort

Early pregnancy is a critical period for fetal development. Isolated hypothyroxinemia has been reported in 4.2–8.8% of women in Chinese early-pregnancy cohorts, yet population-level evidence linking maternal thyroid hormone status to longitudinal fetal growth trajectories remains limited. We analysed 69,675 singleton pregnancies from a prospective cohort. Maternal free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibody (TPOAb) were assessed in the first or second trimester. Fetal growth velocities were derived from 324,886 ultrasound observations obtained between 13 and 41 gestational weeks, including head circumference (HC), abdominal circumference (AC), femur length (FL), biparietal diameter (BPD), and estimated fetal weight (EFW). Growth restriction patterns (cephalic, head-sparing, selective, symmetrical) were defined using population-based 10th percentiles. Linear mixed-effects models assessed velocity associations, while mixed-effects multinomial logistic regression evaluated pattern associations. Higher maternal FT4 was associated with modestly higher fetal growth velocities across all biometric parameters, with estimated EFW velocity differences of 3.07 (95% CI 2.88, 3.26) g/week between the 10th and 90th percentiles of FT4, and with lower odds of cephalic, head-sparing, and symmetrical restriction patterns (all P < 0.001). Hypothyroxinemia was associated with slower fetal growth velocities (all P < 0.001) and increased odds of symmetrical restriction (OR 1.76, 95% CI 1.37, 2.26). Exploratory interaction analyses suggested heterogeneity in the associations of hypothyroxinemia with HC, AC, FL, and BPD velocities according to TPOAb status. Maternal FT4 and hypothyroxinemia were associated with fetal growth velocities and selected growth restriction phenotypes in this large longitudinal cohort. These findings indicate modest population-level associations between maternal thyroid hormone status and fetal growth trajectories, while the clinical relevance of these differences requires further investigation.