Standardization of TSH and FT4 to gestational age in early pregnancy and associations with clinical outcomes.

Background: To account for pregnancy-specific changes in thyroid physiology, international guidelines recommend the use of trimester-specific reference intervals. However, the pragmatic division in trimesters does not necessarily align with the changes in thyroid physiology. While the goal of treating gestational thyroid dysfunction is to prevent thyroid hormone-mediated adverse events, it remains unclear which method of standardizing to gestational age, if any, is most effective in identifying individuals at higher risk of adverse pregnancy events.

Methods: We included 5,675 women participating in a population-based prospective cohort with data on thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroperoxidase antibodies (TPOAbs) during early pregnancy (median: 13.2 weeks, 95% range: 9.8-17.6). We studied the association of TSH and FT4 with pre-eclampsia, premature delivery, birth weight and offspring IQ with or without full gestational age standardization of TSH and FT4 using multivariable regression models.

Results: There was a positive association of gestational age at blood sampling with TSH (difference in mean TSH: +9.6%; P < 0.001) and a negative association with FT4 (difference in mean FT4: -20.2%; P < 0.001). Standardizing TSH to gestational age led to reclassification of 36 women as having normal TSH (9.9%) and 27 as having abnormal TSH (0.5%). For FT4, 62 women were reclassified as having normal FT4 (20.3%) and 57 as having abnormal FT4 (1.1%). Standardization of TSH and FT4 concentrations led to an attenuation of the associations with any outcome of up to 71% as compared to non-standardized TSH or FT4.

Conclusions: Full standardization of TSH and FT4 to gestational age either does not affect or weakens their associations with clinical outcomes, suggesting that accounting for gestational age offers no benefit with regard to identifying high-risk thyroid dysfunction during early pregnancy.