Method-dependent variation in TSH and FT4 reference intervals in pregnancy: A systematic review.

Background: Gestational TSH and FT4 reference intervals may differ according to assay method, but the extent of variation is unclear and has not been systematically evaluated. We conducted a systematic review of published studies on TSH and FT4 reference intervals in pregnancy. Our aim was to quantify method-related differences in gestation reference intervals, across four commonly used assay methods, Abbott, Beckman, Roche and Siemens.

Methods: We searched the literature for relevant studies, published between January 2000 and December 2020, in healthy pregnant women without thyroid antibodies or disease. For each study, we extracted trimester-specific reference intervals (2.5-97.5 percentiles) for TSH and FT4 as well as the manufacturer-provided reference interval for the corresponding non-pregnant population.

Results: TSH reference intervals showed a wide range of study-to-study differences with upper limits ranging from 2.33 to 8.30 mU/L. FT4 lower limits ranged from 4.40 to 13.93 pmol/L, with consistently lower reference intervals observed with the Beckman method. Differences between non-pregnant and first trimester reference intervals were highly variable, and for most studies, the TSH upper limit in the first trimester could not be predicted or extrapolated from non-pregnant values.

Conclusions: Our study confirms significant intra- and intermethod disparities in gestational thyroid hormone reference intervals. The relationship between pregnant and non-pregnant values is inconsistent and does not support the existing practice in many laboratories of extrapolating gestation references from non-pregnant values. Laboratories should invest in deriving method-specific gestation reference intervals for their population.