Maternal Third-Trimester TRAb Is Associated with Neonatal Thyroid Dysfunction and 24-Month Offspring Neurodevelopment: A Bidirectional Cohort Study.

BACKGROUND

Maternal Graves' disease (GD) has been linked to neonatal thyroid dysfunction, but its relationship with offspring neurodevelopment remains unclear. We examined the associations of maternal GD-related thyroid factors with neonatal thyroid function and neurodevelopment at 24 months. We also explored whether neonatal thyroid function might partly explain this association.

METHODS

This single-center bidirectional cohort study included pregnant women with GD and their offspring delivered between January 1, 2019, and December 31, 2023. Maternal thyroid-related variables, including thyrotropin (TSH), free T4, thyrotropin receptor antibodies (TRAbs), and antithyroid drug exposure, were collected across pregnancy. Neonatal thyroid function was assessed at 7-14 days after birth, and neurodevelopmental screening at a corrected age of 24 months was performed using the Ages and Stages Questionnaire, Third Edition. Logistic regression was used to identify factors associated with neonatal thyroid dysfunction and abnormal neurodevelopmental screening results. Covariates were selected with guidance from a directed acyclic graph, and exploratory mediation analysis was performed using PROCESS Model 4.

RESULTS

Among 159 neonates, 60 (37.7%) had thyroid dysfunction, with hyperthyrotropinemia as the most common abnormality (28.9%). Higher maternal third-trimester TRAb was independently associated with neonatal thyroid dysfunction (odds ratio [OR] = 1.59 [confidence interval or CI: 1.29-1.97], p < 0.001). Of the 143 offspring with follow-up data, 23 (16.1%) had abnormal neurodevelopmental screening results at 24 months. Higher maternal third-trimester TRAb (OR = 1.15 [CI: 1.04-1.27], p = 0.005) and higher neonatal TSH (OR = 1.11 [CI: 1.02-1.20], p = 0.016) were independently associated with abnormal neurodevelopmental screening results. Exploratory mediation analysis did not support a significant mediating role of neonatal TSH.

CONCLUSIONS

Higher maternal third-trimester TRAb levels were associated with both neonatal thyroid dysfunction and abnormal neurodevelopmental screening results at 24 months in offspring of mothers with GD. This association with neurodevelopmental screening results may not be explained primarily by neonatal thyroid function alone.