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

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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 TSH and 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 the 12th of December 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 TPOAb-positive participants led to a rise of 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.

CONCLUSIONS

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.

Investigators
Abbreviation
J Clin Endocrinol Metab
Publication Date
2022-07-21
Pubmed ID
35861700
Medium
Print-Electronic
Full Title
TSH and FT4 reference intervals in pregnancy: a systematic review and individual participant data meta-analysis.
Authors
Osinga JAJ, Derakhshan A, Palomaki GE, Ashoor G, Männistö T, Maraka S, Chen L, Bliddal S, Lu X, Taylor PN, Vrijkotte TGM, Tao FB, Brown SJ, Ghafoor F, Poppe K, Veltri F, Chatzi L, Vaidya B, Broeren MAC, Shields BM, Itoh S, Mosso L, Popova PV, Anopova AD, Kishi R, Aminorroaya A, Kianpour M, López-Bermejo A, Oken E, Pirzada A, Vafeiadi M, Bramer WM, Suvanto E, Yoshinaga J, Huang K, Bassols J, Boucai L, Feldt-Rasmussen U, Grineva EN, Pearce EN, Alexander EK, Pop VJM, Nelson SM, Walsh JP, Peeters RP, Chaker L, Nicolaides KH, D'Alton ME, Korevaar TIM