TY - JOUR

T1 - TSH and FT4 Reference Intervals in Pregnancy

T2 - A Systematic Review and Individual Participant Data Meta-Analysis

AU - Osinga, Joris A.J.

AU - Derakhshan, Arash

AU - Palomaki, Glenn E.

AU - Ashoor, Ghalia

AU - Männistö, Tuija

AU - Maraka, Spyridoula

AU - Chen, Liangmiao

AU - Bliddal, Sofie

AU - Lu, Xuemian

AU - Taylor, Peter N.

AU - Vrijkotte, Tanja G.M.

AU - Tao, Fang Biao

AU - Brown, Suzanne J.

AU - Ghafoor, Farkhanda

AU - Poppe, Kris

AU - Veltri, Flora

AU - Chatzi, Lida

AU - Vaidya, Bijay

AU - Broeren, Maarten A.C.

AU - Shields, Beverley M.

AU - Itoh, Sachiko

AU - Mosso, Lorena

AU - Popova, Polina V.

AU - Anopova, Anna D.

AU - Kishi, Reiko

AU - Aminorroaya, Ashraf

AU - Kianpour, Maryam

AU - López-Bermejo, Abel

AU - Oken, Emily

AU - Pirzada, Amna

AU - Vafeiadi, Marina

AU - Bramer, Wichor M.

AU - Suvanto, Eila

AU - Yoshinaga, Jun

AU - Huang, Kun

AU - Bassols, Judit

AU - Boucai, Laura

AU - Feldt-Rasmussen, Ulla

AU - Grineva, Elena N.

AU - Pearce, Elizabeth N.

AU - Alexander, Erik K.

AU - Pop, Victor J.M.

AU - Nelson, Scott M.

AU - Walsh, John P.

AU - Peeters, Robin P.

AU - Chaker, Layal

AU - Nicolaides, Kypros H.

AU - D'Alton, Mary E.

AU - Korevaar, Tim I.M.

N1 - Publisher Copyright: © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - free thyroxine (FT4)

KW - pregnancy

KW - reference values

KW - thyroid

KW - thyrotropin (TSH)

U2 - 10.1210/clinem/dgac425

DO - 10.1210/clinem/dgac425

M3 - Journal article

C2 - 35861700

AN - SCOPUS:85139375230

VL - 107

SP - 2925

EP - 2933

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 10

ER -