Maternal TSH-receptor antibodies predict fetal/neonatal hyperthyroidism in pregnancies with a history of Graves' disease.
prospective_cohort · Level II
Where this comes from
- Record sourced from PubMed, PMID 41846542.
- Also identified by DOI 10.1210/clinem/dgag118.
- No licence information is recorded for this record.
- Because redistribution is not established, this page shows the abstract only. Follow the links below for the full text.
Abstract
Transplacental transfer of Thyroid-Stimulating Hormone Receptor antibodies (TRAb) during pregnancy may cause fetal/neonatal thyroid dysfunction. Current guidelines recommend a universal TRAb titer threshold, irrespective of gestational age or assay platform. However, evidence supporting trimester-specific and assay-specific thresholds is lacking. 1) To determine whether trimester-specific TRAb levels predict fetal/neonatal thyroid dysfunction. 2) to establish assay-specific cutoff values for clinical risk stratification. Prospective multicenter observational cohort study (2010-2023), in which maternal TRAb titers were measured using the TRAK human assay on the BRAHMS Kryptor Compact Plus analyzer. Tertiary and secondary care centers (n=44) across the Netherlands. Women with a history of (n=500) or active (n=178) Graves' disease. Biochemically confirmed fetal/neonatal hyperthyroidism or hypothyroidism. Trimester-specific TRAb titer thresholds predicted risk with high accuracy. In women with a history of Graves' disease (n=500), trimester-specific cut-offs of 25-, 19-, and 6-fold the upper limit of normal (ULN) showed a negative predictive value of 100%. In women with active Graves (n=178), cut-offs of 10-, 12-, and 10-fold the ULN showed sensitivities of 89%, 86%, and 83%. Neonatal hyperthyroidism occurred despite low or declining maternal TRAb levels in mothers treated with antithyroid drugs. Trimester-specific TRAb thresholds were higher than the universal ULN multipliers commonly applied in clinical practice, and differed by gestational age and disease status. Application of a single ULN-based threshold titer across different TRAb assays may result in misclassification (i.e. overestimation of fetal and neonatal Graves' disease) and consequently in unnecessary and resource-intensive fetal surveillance. This indicates that TRAb thresholds are assay-specific and require platform-specific clinical validation, even when assays are calibrated against a common international standard.