Maternal thyroxine associated with fetal growth velocity in 69,675 pregnancies

In a prospective analysis of 69,675 singleton pregnancies, higher maternal free thyroxine during the first or second trimester was associated with modestly faster fetal growth across several ultrasound measurements, while hypothyroxinemia was associated with slower growth and increased odds of symmetrical growth restriction. The observational study does not establish that changes in maternal thyroid hormone status cause differences in fetal development, and the clinical relevance of the estimated associations remains uncertain. The researchers combined maternal blood-test results with 324,886 ultrasound observations recorded between 13 and 41 gestational weeks.

The ultrasound series included head circumference, abdominal circumference, femur length, biparietal diameter and estimated fetal weight. Free thyroxine, thyroid-stimulating hormone and thyroid peroxidase antibodies were measured in maternal samples collected during the first or second trimester. Linear mixed-effects models were used to assess associations between maternal thyroid measures and fetal growth velocities, while mixed-effects multinomial logistic regression examined associations with fetal growth-restriction patterns.

Higher maternal free thyroxine was associated with modestly higher velocities for all five fetal biometric parameters. For estimated fetal weight, the model estimated a difference of 3.07 grams per week between pregnancies at the 10th and 90th percentiles of maternal free thyroxine, with a 95% confidence interval of 2.88 to 3.26 grams per week. These figures describe population-level associations in the cohort; they do not show that altering thyroid hormone levels would produce a corresponding change in fetal growth.

Maternal free thyroxine was also associated with lower odds of cephalic, head-sparing and symmetrical fetal growth-restriction patterns, with all reported P values below 0.001. These phenotypes were defined using population-based 10th-percentile thresholds. Hypothyroxinemia was associated with slower velocities across all measured biometrics and with increased odds of symmetrical restriction: the reported odds ratio was 1.76, with a 95% confidence interval of 1.37 to 2.26.

The odds ratio represents increased odds rather than a directly measured difference in the frequency of symmetrical restriction, and the prospective design cannot determine whether maternal thyroid status caused the observed outcomes. Exploratory interaction analyses suggested that associations between hypothyroxinemia and the velocities of head circumference, abdominal circumference, femur length and biparietal diameter varied according to thyroid peroxidase antibody status. The investigators characterized these results as evidence of possible heterogeneity rather than a definitive clinical subdivision.

Although the large prospective cohort and repeated ultrasound measurements provide an extensive basis for estimating associations, the study did not test a screening or treatment intervention. The authors concluded that the findings show modest population-level relationships between maternal thyroid hormone status and fetal growth trajectories and that further investigation is needed to establish their clinical relevance.

Subject of Research: Maternal thyroid hormone status and longitudinal fetal growth trajectories in a prospective pregnancy cohort

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

Article References: Jiang, H., Mu, Z., Liang, Y., Zhou, H., Ying, H., & Hua, J. (2026). Early-to-mid-pregnancy maternal free thyroxine and fetal growth velocity trajectories: evidence from a large prospective cohort. BMC Medicine. https://doi.org/10.1186/s12916-026-05342-5

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05342-5

Keywords: maternal thyroid health, free thyroxine, hypothyroxinemia, fetal growth, growth restriction, ultrasound biometrics, pregnancy cohort, longitudinal study, thyroid peroxidase antibodies, Early-to-mid-pregnancy, maternal, free