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Association of thyroid peroxidase antibodies and thyroglobulin antibodies with thyroid function in pregnancy - an individual participant data meta-analysis

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  • Sofie Bliddal
  • Arash Derakhshan
  • Yi Xiao
  • Liangmiao Chen
  • Tuija Männistö
  • Ghalia Ashoor
  • Fangbiao Tao
  • Suzanne J Brown
  • Marina Vafeida
  • Sachiko Itoh
  • Elena Nikolaevna Grineva
  • Peter Taylor
  • Farkhanda Ghafoor
  • Bijay Vaidya
  • Andrew Hattersley
  • Lorena Mosso
  • Emily Oken
  • Reiko Kishi
  • Erik K Alexander
  • Spyridoula Maraka
  • Kun Huang
  • Layal Chaker
  • Judit Bassols
  • Amna Pirzada
  • Abel López-Bermejo
  • Laura Boucai
  • Robin P Peeters
  • Elizabeth N Pearce
  • Scott McGill Nelson
  • Leda Chatzi
  • Tanja G Vrijkotte
  • Polina Popova
  • John Walsh
  • Kypros H Nicolaides
  • Eila Suvanto
  • Xuemian Lu
  • Victor J M Pop
  • Julie Lyng Forman
  • Tim I M Korevaar
  • Ulla Feldt-Rasmussen
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Objectives: Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase antibodies (TPOAbs) assessed by a negative-positive dichotomy and rarely take into account thyroglobulin antibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively, and interdependently, with maternal thyroid function. Methods: This was a meta-analysis of individual participant cross-sectional data from 20 cohorts in the Consortium on Thyroid and Pregnancy. Women with multiple pregnancy, pregnancy by assisted reproductive technology, history of thyroid disease, or use of thyroid interfering medication were excluded. Associations of (log2) TPOAbs and TgAbs (with/without mutual adjustment) with cohort-specific z-scores of (log2) thyrotropin (TSH), free triiodothyronine (fT3), total triiodothyronine (TT3), free thyroxine (fT4), total thyroxine (TT4), or triiodothyronine:thyroxine (T3:T4) ratio were evaluated in a linear mixed model. Results: In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 had TgAb-data). Isolated TPOAb positivity was present in 4.1% [95% confidence interval, CI: 3.0 to 5.2], isolated TgAb positivity in 4.8% [CI: 2.9 to 6.6], and positivity for both antibodies in 4.7% [CI: 3.1 to 6.3]. Compared with antibody-negative women, TSH was higher in women with isolated TPOAb positivity (z-score increment 0.40, CI: 0.16 to 0.64) and TgAb positivity (0.21, CI: 0.10 to 0.32), but highest in those positive for both antibodies (0.54, CI: 0.36 to 0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12, CI: 0.09 to 0.15, TgAbs 0.08, CI: 0.02 to 0.15). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. A higher TPOAb concentration was associated with lower fT4 (p < 0.001) and higher T3:T4 ratio (0.09, CI: 0.03 to 0.14), however, the association with fT4 was not significant when adjusting for TgAbs (p = 0.16). Conclusions: This individual participant data meta-analysis demonstrated an increase in TSH with isolated TPOAb positivity and TgAb positivity, respectively, which was amplified for individuals positive for both antibodies. There was a dose-dependent association of TPOAbs, but not TgAbs, with TSH when adjusting for the other antibody. This supports current practice of using TPOAbs in initial laboratory testing of pregnant women suspected of autoimmune thyroid disease. However, studies on the differences between TPOAb- and TgAb-positive women are needed to fully understand the spectrum of phenotypes.

Original languageEnglish
JournalThyroid : official journal of the American Thyroid Association
Issue number7
Pages (from-to)828-840
Number of pages13
Publication statusPublished - Jul 2022

    Research areas

  • Autoantibodies, Cross-Sectional Studies, Female, Humans, Iodide Peroxidase, Pregnancy, Thyroglobulin, Thyroid Diseases, Thyrotropin, Thyroxine, Triiodothyronine, meta-Analysis, thyroglobulin antibodies, pregnancy, thyroid autoimmunity, thyroid peroxidase antibodies, thyroid

ID: 78227368