Defining gestational thyroid dysfunction through modified non-pregnancy reference intervals: an individual participant meta-analysis

Osinga, Joris A. J., Nelson, Scott M., Walsh, John P., Ashoor, Ghalia, Palomaki, Glenn E., López-Bermejo, Abel, Bassols, Judit, Aminorroaya, Ashraf, Broeren, Maarten A. C., Chen, Liangmiao, Lu, Xuemian, Brown, Suzanne J., Veltri, Flora, Huang, Kun, Männistö, Tuija, Vafeiadi, Marina, Taylor, Peter N. ORCID: https://orcid.org/0000-0002-3436-422X, Tao, Fang-Biao, Chatzi, Lida, Kianpour, Maryam, Suvanto, Eila, Grineva, Elena N., Nicolaides, Kypros H., D'Alton, Mary E., Poppe, Kris G., Alexander, Erik, Feldt-Rasmussen, Ulla, Bliddal, Sofie, Popova, Polina V., Chaker, Layal, Visser, W Edward, Peeters, Robin P., Derakhshan, Arash, Vrijkotte, Tanja G. M., Pop, Victor J. M. and Korevaar, Tim I. M. 2024. Defining gestational thyroid dysfunction through modified non-pregnancy reference intervals: an individual participant meta-analysis. The Journal of Clinical Endocrinology & Metabolism , dgae528. 10.1210/clinem/dgae528

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Abstract

Background: Establishing local trimester-specific reference intervals for gestational TSH and FT4 is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific non-pregnancy reference intervals as compared to trimester-specific reference intervals. Methods: We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the non-pregnancy reference intervals included an absolute modification (per 0.1 mU/L TSH or 1 pmol/L FT4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 to 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity and positive predictive value (PPV) of aforementioned methodologies with population-based trimester-specific reference intervals. Results: The final study population comprised 52,496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity 0.70, confidence interval [CI] 0.47-0.86; PPV 0.64, CI 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity 0.91, CI 0.67-0.98; PPV 0.71, CI 0.58-0.80). Absolute and fixed modifications yielded similar results. Confidence intervals were wide, limiting generalizability. Conclusion: We could not identify modifications of non-pregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned towards studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Medicine
Publisher:	Oxford University Press
ISSN:	0021-972X
Date of First Compliant Deposit:	15 August 2024
Date of Acceptance:	29 July 2024
Last Modified:	20 Aug 2024 07:14
URI:	https://orca.cardiff.ac.uk/id/eprint/171424

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