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

Abstract

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 4.40–13.93 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 inter-method 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 some laboratories of extrapolating gestation references from non-pregnant values. Laboratories should invest in deriving method-specific gestation reference intervals for their population.

Pregnancy disrupts the accuracy of automated fT4 immunoassays

“…However, different fT4 IAs have varying techniques and reagent composition in measuring fT4 concentrations, meaning pregnancy does not influence all different IAs to the same extent as was shown in our study. Therefore, reference intervals for pregnant women need to be established for every IA separately and cannot be used from or recalculated based on other IAs, which has also been highlighted previously by Bliddal et al 52 and Okosieme et al 53 . Furthermore, patient populations highly differ between countries or regions which could lead to altered reference ranges of thyroid hormone parameters 54 .…”

A Positive Newborn Screen for Congenital Hypothyroidism in a Clinically Euthyroid Neonate—Avoiding Unnecessary Treatment

“…The presence of maternal thyroid antibodies is an alternative explanation for a transient neonatal increase in TSH, although this invokes a second unproven pathology. Furthermore, reference intervals for TSH levels during pregnancy are unclear and assay dependent [ 11 ], and we acknowledge that the mother’s first trimester TSH level was not definitively elevated.…”

Trimester-specific reference intervals for thyroid function parameters in pregnant Caucasian women using Roche platforms: a prospective study

“…In 2021 a systematic review of published studies on TSH and FT4 reference intervals in pregnancy obtained using Abbott, Beckman, Roche and Siemens assay methods, including 139,734 pregnant women, was conducted [31]. It is noteworthy that, in the first trimester, TSH upper limits obtained with the Abbott system ranged from 2.33 to 8.30 mU/L, those obtained with Siemens from 2.83 to 4.65 mU/L, whereas FT4 higher limits ranged from 13.2 to 18.7 pmol/L with the Beckman system, and from 16.7 to 26.5 pmol/L with the Siemens method.…”