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

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Thyroid autoimmunity is common in pregnant women and associated with thyroid dysfunction and adverse obstetric outcomes. Most studies focus on thyroid peroxidase autoantibodies (TPOAbs) assessed by negative-positive dichotomy and rarely take into account thyroglobulin autoantibodies (TgAbs). This study aimed at determining the association of TPOAbs and TgAbs, respectively and interdependently, with maternal thyroid function.


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) thyroid stimulating hormone (TSH), free triiodothyronine (FT3), total triiodothyronine (TT3), free thyroxine (FT4), total thyroxine (TT4) or T3:T4 ratio were evaluated in a linear mixed model.


In total, 51,138 women participated (51,094 had TPOAb-data and 27,874 TgAb-data). Isolated TPOAb-positivity was present in 4.1% (95% confidence interval(CI):3.0-5.2), isolated TgAb-positivity in 4.8% (95%CI:2.9-6.6), and positivity for both antibodies in 4.7% (95%CI:3.1-6.3). Compared to antibody-negative women, TSH was higher in women with isolated TPOAb-positivity (z-score increment 0.40, 95% confidence interval(CI):0.16-0.64) and TgAb-positivity (0.21,95%CI:0.10-0.32), but highest in those positive for both antibodies (0.54,95%CI:0.36-0.71). There was a dose-response effect of higher TPOAb and TgAb concentrations with higher TSH (TSH z-score increment for TPOAbs 0.12,95%CI:0.09-0.15, TgAbs 0.08,95%CI:0.02-0.15)). When adjusting analyses for the other antibody, only the association of TPOAbs remained statistically significant. Higher TPOAb concentration was associated with lower FT4 (p<0.001) and higher T3:T4 ratio (0.09, 95%CI:0.03-0.14), however, the association with FT4 was not significant when adjusting for TgAbs (p=0.16).


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.

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Association of thyroid peroxidase antibodies and thyroglobulin antibodies with thyroid function in pregnancy - an individual participant data meta-analysis.
Bliddal S, Derakhshan A, Xiao Y, Chen L, Männistö T, Ashoor G, Tao F, Brown SJ, Vafeida M, Itoh S, Grineva EN, Taylor P, Ghafoor F, Vaidya B, Hattersley A, Mosso L, Oken E, Kishi R, Alexander EK, Maraka S, Huang K, Chaker L, Bassols J, Pirzada A, López-Bermejo A, Boucai L, Peeters RP, Pearce EN, Nelson SM, Chatzi L, Vrijkotte TG, Popova P, Walsh J, Nicolaides KH, Suvanto E, Lu X, Pop VJM, Forman JL, Korevaar TIM, Feldt-Rasmussen U