TSH and FT4 Reference Intervals in Pregnancy: A Systematic Review and Individual Participant Data Meta-Analysis

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  • 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
  • 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

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.

Original languageEnglish
JournalThe Journal of clinical endocrinology and metabolism
Volume107
Issue number10
Pages (from-to)2925-2933
Number of pages9
ISSN0021-972X
DOIs
Publication statusPublished - 2022

Bibliographical note

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

    Research areas

  • free thyroxine (FT4), pregnancy, reference values, thyroid, thyrotropin (TSH)

ID: 323997823