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

Joris A J Osinga; Arash Derakhshan; Glenn E Palomaki; Ghalia Ashoor; Tuija Männistö; Spyridoula Maraka; Liangmiao Chen; Sofie Bliddal; Xuemian Lu; Peter N Taylor; Tanja G M Vrijkotte; Fang-Biao Tao; Suzanne J Brown; Farkhanda Ghafoor; Kris Poppe; Flora Veltri; Lida Chatzi; Bijay Vaidya; Maarten A C Broeren; Beverley M Shields; Sachiko Itoh; Lorena Mosso; Polina V Popova; Anna D Anopova; Reiko Kishi; Ashraf Aminorroaya; Maryam Kianpour; Abel López-Bermejo; Emily Oken; Amna Pirzada; Marina Vafeiadi; Wichor M Bramer; Eila Suvanto; Jun Yoshinaga; Kun Huang; Judit Bassols; Laura Boucai; Ulla Feldt-Rasmussen; Elena N Grineva; Elizabeth N Pearce; Erik K Alexander; Victor J M Pop; Scott M Nelson; John P Walsh; Robin P Peeters; Layal Chaker; Kypros H Nicolaides; Mary E D'Alton; Tim I M Korevaar

doi:10.1210/clinem/dgac425

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

Joris A J Osinga, Arash Derakhshan, Glenn E Palomaki, Ghalia Ashoor, Tuija Männistö, Spyridoula Maraka, Liangmiao Chen, Sofie Bliddal, Xuemian Lu, Peter N Taylor, Tanja G M Vrijkotte, Fang-Biao Tao, Suzanne J Brown, Farkhanda Ghafoor, Kris Poppe, Flora Veltri, Lida Chatzi, Bijay Vaidya, Maarten A C Broeren, Beverley M ShieldsSachiko Itoh, Lorena Mosso, Polina V Popova, Anna D Anopova, Reiko Kishi, Ashraf Aminorroaya, Maryam Kianpour, Abel López-Bermejo, Emily Oken, Amna Pirzada, Marina Vafeiadi, Wichor M Bramer, Eila Suvanto, Jun Yoshinaga, Kun Huang, Judit Bassols, Laura Boucai, Ulla Feldt-Rasmussen, Elena N Grineva, Elizabeth N Pearce, Erik K Alexander, Victor J M Pop, Scott M Nelson, John P Walsh, Robin P Peeters, Layal Chaker, Kypros H Nicolaides, Mary E D'Alton, Tim I M Korevaar

23 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	The Journal of clinical endocrinology and metabolism
Vol/bind	107
Udgave nummer	10
Sider (fra-til)	2925-2933
Antal sider	9
ISSN	0021-972X
DOI	https://doi.org/10.1210/clinem/dgac425
Status	Udgivet - 28 sep. 2022

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10.1210/clinem/dgac425

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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., ... Korevaar, T. I. M. (2022). TSH and FT4 reference intervals in pregnancy: a systematic review and individual participant data meta-analysis. The Journal of clinical endocrinology and metabolism, 107(10), 2925-2933. https://doi.org/10.1210/clinem/dgac425

Osinga, JAJ, Derakhshan, A, Palomaki, GE, Ashoor, G, Männistö, T, Maraka, S, Chen, L, Bliddal, S, Lu, X, Taylor, PN, Vrijkotte, TGM, Tao, F-B, 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 2022, 'TSH and FT4 reference intervals in pregnancy: a systematic review and individual participant data meta-analysis', The Journal of clinical endocrinology and metabolism, bind 107, nr. 10, s. 2925-2933. https://doi.org/10.1210/clinem/dgac425

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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.",

keywords = "Female, Humans, Iodide Peroxidase, Pregnancy, Reference Values, Thyroid Function Tests, Thyroid Gland, Thyrotropin, Thyroxine, reference values, free thyroxine (FT4), pregnancy, thyrotropin (TSH), thyroid",

author = "Osinga, {Joris A J} and Arash Derakhshan and Palomaki, {Glenn E} and Ghalia Ashoor and Tuija M{\"a}nnist{\"o} and Spyridoula Maraka and Liangmiao Chen and Sofie Bliddal and Xuemian Lu and Taylor, {Peter N} and Vrijkotte, {Tanja G M} and Fang-Biao Tao and Brown, {Suzanne J} and Farkhanda Ghafoor and Kris Poppe and Flora Veltri and Lida Chatzi and Bijay Vaidya and Broeren, {Maarten A C} and Shields, {Beverley M} and Sachiko Itoh and Lorena Mosso and Popova, {Polina V} and Anopova, {Anna D} and Reiko Kishi and Ashraf Aminorroaya and Maryam Kianpour and Abel L{\'o}pez-Bermejo and Emily Oken and Amna Pirzada and Marina Vafeiadi and Bramer, {Wichor M} and Eila Suvanto and Jun Yoshinaga and Kun Huang and Judit Bassols and Laura Boucai and Ulla Feldt-Rasmussen and Grineva, {Elena N} and Pearce, {Elizabeth N} and Alexander, {Erik K} and Pop, {Victor J M} and Nelson, {Scott M} and Walsh, {John P} and Peeters, {Robin P} and Layal Chaker and Nicolaides, {Kypros H} and D'Alton, {Mary E} and Korevaar, {Tim I M}",

note = "{\textcopyright} The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.",

year = "2022",

month = sep,

day = "28",

doi = "10.1210/clinem/dgac425",

language = "English",

volume = "107",

pages = "2925--2933",

journal = "The Journal of clinical endocrinology and metabolism",

issn = "0021-972X",

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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

PY - 2022/9/28

Y1 - 2022/9/28

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 - Female

KW - Humans

KW - Iodide Peroxidase

KW - Pregnancy

KW - Reference Values

KW - Thyroid Function Tests

KW - Thyroid Gland

KW - Thyrotropin

KW - Thyroxine

KW - reference values

KW - free thyroxine (FT4)

KW - pregnancy

KW - thyrotropin (TSH)

KW - thyroid

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U2 - 10.1210/clinem/dgac425

DO - 10.1210/clinem/dgac425

M3 - Review

C2 - 35861700

SN - 0021-972X

VL - 107

SP - 2925

EP - 2933

JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

IS - 10

ER -

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

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