Establishment of the Trimester-Specific Reference Range for Free Thyroxine Index

Background: Accurate assessment of thyroid status during pregnancy is vital for maternal and fetal health. Because free thyroxine (FT4) values in pregnancy vary widely between methods, assessment of total T4 (TT4) and FT4 index (FT4I) may be superior to FT4 in pregnant women. However, trimester-specific reference intervals for FT4I have not yet been established. In this longitudinal self-sequential survey, we aimed at determining the trimester-specific reference range for FT4I in healthy Iranian women with singleton pregnancies. Methods: A total of 466 healthy pregnant women were evaluated. After exclusion of women with history, ultrasonographic, or laboratory evidence of any thyroid disorder or iodine deficiency and those who were positive for thyroid autoantibodies, 152 women entered the study. Serum thyrotropin (TSH), TT4, and triiodothyronine-resine uptake were measured by an immunoassay method. Reference intervals were defined as 5th and 95th percentiles, using the bootstrap-based procedure. Results: Mean values in the first, second, and third trimesters were 1.7±1.5, 1.9±1.8, and 1.9±1.8 mIU/L for TSH; 12.9±3, 14.4±3.1, and 13.6±3.3 μg/dL for TT4; and 12.8±3.5, 14.2±3.3, and 13.5±3.8 for FT4I, respectively. Reference intervals in the first, second, and third trimesters were as follows (respectively): TSH—0.2–3.9, 0.5–4.1, and 0.6–4.1 mIU/L; TT4—8.2–18.5, 10.1–20.6, and 9–19.4 μg/dL; and FT4I—8.5–19, 9.7–21, and 8.7–20.4. Serum TSH had no significant correlation with TT4. Serum TSH had a significant but weak correlation with FT4I only in the first trimester ( r =−0.24, p =0.006). Conclusion: This study, for the first time, establishes the trimester-specific reference intervals for FT4I in a reference population of normal iodine-sufficient pregnant Iranian women.