TSH and FT4 reference intervals in pregnancy: a systematic review and individual participant data meta-analysis

Osinga, J. A. J. et al. (2022) TSH and FT4 reference intervals in pregnancy: a systematic review and individual participant data meta-analysis. Journal of Clinical Endocrinology and Metabolism, 107(10), pp. 2925-2933. (doi: 10.1210/clinem/dgac425) (PMID:35861700) (PMCID:PMC9516198)

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.

• Item Type: Articles
• Additional Information: Funding: Netherlands Organization for Scientific Research (grant 401.16.020).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nelson, Professor Scott
• Authors: Osinga, J. A. J., Derakhshan, A., Palomaki, G. E., Ashoor, G., Männistö, T., Maraka, S., Chen, L., Bliddal, S., Lu, X., Taylor, P. N., Vrijkotte, T. G. M., Tao, F.-B., Brown, S. J., Ghafoor, F., Poppe, K., Veltri, F., Chatzi, L., Vaidya, B., Broeren, M. A. C., Shields, B. M., Itoh, S., Mosso, L., Popova, P. V., Anopova, A. D., Kishi, R., Aminorroaya, A., Kianpour, M., López-Bermejo, A., Oken, E., Pirzada, A., Vafeiadi, M., Bramer, W. M., Suvanto, E., Yoshinaga, J., Huang, K., Bassols, J., Boucai, L., Feldt-Rasmussen, U., Grineva, E. N., Pearce, E. N., Alexander, E. K., Pop, V. J. M., Nelson, S. M., Walsh, J. P., Peeters, R. P., Chaker, L., Nicolaides, K. H., D’Alton, M. E., and Korevaar, T. I. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Clinical Endocrinology and Metabolism
• Publisher: Oxford University Press
• ISSN: 0021-972X
• ISSN (Online): 1945-7197
• Published Online: 21 July 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Journal of Clinical Endocrinology and Metabolism 107(10): 2925-2933
• Publisher Policy: Reproduced under a Creative Commons License