Pregnancy Week-Specific Reference Ranges for Thyrotropin and Free Thyroxine in the North Denmark Region Pregnancy Cohort

Background: Physiological changes in maternal thyroid function during pregnancy necessitate the use of pregnancy-specific reference ranges. Dynamic changes in thyrotropin (TSH) within the first trimester of pregnancy have been reported, but more evidence is needed to substantiate the findings. The objective of this study was to estimate pregnancy week-specific reference ranges for maternal TSH and free thyroxine (fT4) in early pregnancy. Methods: The study consecutively recruited serum residues from blood samples collected as part of the prenatal screening in the North Denmark Region, 2011–2015. TSH, fT4, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured using an ADVIA Centaur XPT immunoassay. The reference cohort included 10,337 pregnant women who had no thyroid disease or other autoimmune diseases and were TPOAb- and TgAb negative. The main outcome measures were lower and upper reference limits (2.5th and 97.5th percentiles) for TSH and fT4 stratified by week of pregnancy. Results: Blood samples were drawn in pregnancy weeks 4–20 (median week 10), and 92% of the pregnancies ended with a live birth. TSH varied considerably in the first trimester of pregnancy, and the levels were highest in early pregnancy (weeks 4–6: 0.6–3.7 mIU/L) followed by a gradual decline to lower levels in weeks 9–11 (0.1–2.8 mIU/L) and 12–14 (0.03–2.8 mIU/L). Maternal fT4 showed less variation (weeks 4–6: 12–20 pmol/L; weeks 9–11: 13–21 pmol/L; weeks 12–14: 13–20 pmol/L). Conclusions: The results corroborate dynamic week-specific changes in maternal TSH in early pregnancy. The use of uniform lower and upper reference limits for TSH in early pregnancy may be too simple.