Tsh and Ft4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis Publisher Pubmed



Osinga JAJ^{1, 2} ; Derakhshan A^{1, 2} ; Palomaki GE³ ; Ashoor G⁴ ; Mannisto T⁵ ; Maraka S^{6, 7, 8} ; Chen L⁹ ; Bliddal S¹⁰ ; Lu X⁹ ; Taylor PN¹¹ ; Vrijkotte TGM¹² ; Tao FB¹³ ; Brown SJ¹⁴ ; Ghafoor F¹⁵ Show All Authors
Source: Journal of Clinical Endocrinology and Metabolism Published:2022

Abstract

Context: Interpretation of thyroid function tests during pregnancy is limited by the generalizability of reference intervals between cohorts due to inconsistent methodology. Objective: (1) To provide an overview of published reference intervals for thyrotropin (TSH) and free thyroxine (FT4) in pregnancy, (2) to assess the consequences of common methodological between-study differences by combining raw data from different cohorts. Methods: (1) Ovid MEDLINE, EMBASE, and Web of Science were searched until December 12, 2021. Studies were assessed in duplicate. (2) The individual participant data (IPD) meta-analysis was performed in participating cohorts in the Consortium on Thyroid and Pregnancy. Results: (1) Large between-study methodological differences were identified, 11 of 102 included studies were in accordance with current guidelines; (2) 22 cohorts involving 63 198 participants were included in the meta-analysis. Not excluding thyroid peroxidase antibody-positive participants led to a rise in the upper limits of TSH in all cohorts, especially in the first (mean +17.4%; range +1.6 to +30.3%) and second trimester (mean +9.8%; range +0.6 to +32.3%). 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. All other additional exclusion criteria changed reference interval cut-offs by a maximum of 3.5%. Applying these findings to the 102 studies included in the systematic review, 48 studies could be used in a clinical setting. Conclusion: We provide an overview of clinically relevant reference intervals for TSH and FT4 in pregnancy. The results of the meta-analysis indicate that future studies can adopt a simplified study setup without additional exclusion criteria. © 2022 The Author(s). Published by Oxford University Press on behalf of the Endocrine Society.