Pregnancy week specific reference ranges for TSH and free T4 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 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 T4 (fT4) in the early pregnancy.

METHODS: We 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 (TPO-Ab) and thyroglobulin antibodies (Tg-Ab) 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 TPO-Ab and Tg-Ab negative. The main outcome measures were lower and upper reference limits (2.5 and 97.5 percentiles) for TSH and fT4 stratified by week of pregnancy.

RESULTS: Blood samples were drawn in pregnancy week 4-20 (median week 10), and 92% of the pregnancies ended with live birth. TSH varied considerably in the first trimester of pregnancy, and the levels were highest in the early pregnancy (week 4-6: 0.6-3.7 mIU/l) followed by a gradual decline to lower levels in week 9-11 (0.1-2.8 mIU/l) and 12-14 (0.03-2.8 mIU/l). Maternal fT4 showed less variation (week 4-6: 12-20 pmol/l; week 9-11: 13-21 pmol/l; week 12-14: 13-20 pmol/l).

CONCLUSIONS: Results corroborate dynamic week specific changes in maternal TSH in early pregnancy. The use of uniform lower and upper reference range for TSH in early pregnancy may be too simple.