TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis
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TSH and FT4 Reference Intervals in Pregnancy : A Systematic Review and Individual Participant Data Meta-Analysis. / Osinga, Joris A.J.; Derakhshan, Arash; Palomaki, Glenn E.; Ashoor, Ghalia; Männistö, Tuija; Maraka, Spyridoula; Chen, Liangmiao; Bliddal, Sofie; Lu, Xuemian; Taylor, Peter N.; Vrijkotte, Tanja G.M.; Tao, Fang Biao; Brown, Suzanne J.; Ghafoor, Farkhanda; Poppe, Kris; Veltri, Flora; Chatzi, Lida; Vaidya, Bijay; Broeren, Maarten A.C.; Shields, Beverley M.; Itoh, Sachiko; Mosso, Lorena; Popova, Polina V.; Anopova, Anna D.; Kishi, Reiko; Aminorroaya, Ashraf; Kianpour, Maryam; López-Bermejo, Abel; Oken, Emily; Pirzada, Amna; Vafeiadi, Marina; Bramer, Wichor M.; Suvanto, Eila; Yoshinaga, Jun; Huang, Kun; Bassols, Judit; Boucai, Laura; Feldt-Rasmussen, Ulla; Grineva, Elena N.; Pearce, Elizabeth N.; Alexander, Erik K.; Pop, Victor J.M.; Nelson, Scott M.; Walsh, John P.; Peeters, Robin P.; Chaker, Layal; Nicolaides, Kypros H.; D'Alton, Mary E.; Korevaar, Tim I.M.
In: The Journal of clinical endocrinology and metabolism, Vol. 107, No. 10, 2022, p. 2925-2933.Research output: Contribution to journal › Journal article › Research › peer-review
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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 -
ID: 323997823