Development of Gestational Age-Specific Thyroid Function Test Reference Intervals in Four Analytic Platforms Through Multilevel Modeling.

Background: A population-based reference interval (RI) of thyroid hormones in pregnancy using a standardized methodology is crucial for clinicians to make accurate diagnoses and important for the comparison of test results obtained from different analytic platforms. Methods: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation, after exclusion of subjects with antibodies to thyroid peroxidase, thyroglobulin or thyrotropin receptor. Gestational age-specific RIs were constructed by using polynomial regression equations with MLwiN. Results: Free thyroxine (fT4) levels rose to a peak at the 7th-8th gestational weeks and then declined gradually till 28th week, while thyrotropin (TSH) level decreased from early pregnancy to a nadir at the 9th week. The data support the recent notion by the American Thyroid Association to raise the TSH upper RI to 4.0 mIU/L. We also demonstrate that thyroid hormone reference ranges are not affected in a mildly iodine-deficient population and by including women with the presence of antibodies against thyroid peroxidase and thyroglobulin who are otherwise healthy. Conclusions: The study highlights a methodology in constructing gestational age-specific thyroid function test RIs on different analytic platforms to provide a better interpretation and comparison of results obtained across different platforms.