Establishment of trimester-specific reference range for thyroid hormones during pregnancy

Objective: Physiological gestational changes are associated with alterations in thyroid function which require different biochemical interpretation from that of non-pregnant women and necessitate established pregnancy-specific reference ranges. We aimed to identify the trimester-specific ranges of thyroid markers in a healthy population of pregnant Iranian women. Methods: In this self-sequential study, data were extracted from The Tehran Thyroid and Pregnancy Study; a total of 314 women were tested during the 1st, 2nd and 3rd trimesters for serum levels of thyrotropin (TSH), thyroxine (T4), free thyroxine index (FT4I) and thyroid peroxidase antibody (TPOAb). Trimester-specific reference intervals for TSH, T4 and FT4I and first trimester reference range for TPOAb were estimated. The normal and modulus exponential-normal models were fitted by maximum likelihood using STATA software. The 2.5th and 97.5th percentiles of thyroid parameters were determined and used as reference intervals. Results: Mean +/- SD age of participants was 26.8 +/- 5.2 years. Estimated reference intervals for TSH, T4 and FT4I in the 1st, 2nd and 3rd trimesters corresponding to the 2.5th and 97.5th percentiles were 0.14-6.14, 0.43-4.64, 0.63-3.9 mu IU/ml; 78.01-215.19, 93.23-243.87, 89.61-211.37 nmol/L; and 1.73-4.53, 1.96-5.64, 1.72-4.30, respectively. Reference interval for TPOAb in the 1st trimester was 1.40-38.02 IU/mL. Median of TSH was low in the 1st trimester, and gradually increased until 2nd trimester, followed by a slight decrease onward. A decreasing trend in TSH levels was observed in higher centiles with advancing gestational age. Conclusion: This study provides trimester-specific reference ranges for some common thyroid markers among healthy Iranian women in an iodine sufficient area, to prevent biochemical misinterpretations during pregnancy.