Endocrine Abstracts

Objective: Defining thyroid function test abnormalities in pregnancy is complicated by changes in maternal physiology. Ideally, reference intervals (RIs) should be population-based and pregnancy-specific. Large methodological differences between published reports limit the adoption of such RIs into clinical practice.

Methods: The study was performed in the Consortium on Thyroid and Pregnancy. In line with current consensus and the 2017 American Thyroid Association guidelines, cohort-specific RIs based on the 2.5th and 97.5th percentiles were calculated after exclusion of participants with pre-pregnancy thyroid disease, thyroid medication use and TPOAb positivity. To evaluate current recommendations and methodological variations, RIs were also calculated using the above mentioned methods and eight different methodologies often encountered in literature; 1) using the 5th to 95th percentiles, 2) without excluding TPOAb positivity, and using additional exclusion criteria defined as 3) exclusion of TgAb-positivity 4) pre-pregnancy diabetes mellitus, 5) essential hypertension, 6) obesity 7) active smoking, or 8) any pregnancy complications.

Results: The final study population comprised of n=63,198 participants from 22 cohorts. Between cohorts, the upper limit for TSH calculated according to the current consensus ranged from 2.24 to 6.02 mU/l in the first trimester, from 2.67 to 6.15 mU/l in the second trimester and from 3.03 to 6.13 mU/l in the third trimester. Not excluding TPOAb positive participants led to a rise of the upper limits of TSH in all cohorts, especially in the first (+17.4% average, range +1.6 to +30.3%) and second (+9.8% average, range +0.6 to +32.3%) trimester. The use of the 95th percentile led to considerable changes in upper limits, varying from -10.8% to -21.8% for TSH and -1.2% to -13.2% for FT4 across all trimesters. All other additional exclusion criteria led to less than 3.5% variability around the 97.5th percentile, without a trend towards increase or decrease.

Conclusion: The large variability in reference limits between cohorts stress the importance of hospital- and pregnancy specific RIs. Furthermore, our data emphasize the importance of excluding TPOAb-positive participants and the use of appropriate percentiles cut-offs. Additional exclusions frequently encountered in literature did not affect TSH or FT4 reference intervals during pregnancy, indicating that the majority of published studies can be implemented into clinical practice despite methodological differences and future studies can adapt simplified study setups to define valid RIs.