TY - JOUR

T1 - Association of Thyroid Peroxidase Antibodies and Thyroglobulin Antibodies with Thyroid Function in Pregnancy

T2 - An Individual Participant Data Meta-Analysis

AU - Bliddal, Sofie

AU - Derakhshan, Arash

AU - Xiao, Yi

AU - Chen, Liang-Miao

AU - Mannisto, Tuija

AU - Ashoor, Ghalia

AU - Tao, Fangbiao

AU - Brown, Suzanne J.

AU - Vafeiadi, Marina

AU - Itoh, Sachiko

AU - Grineva, Elena Nikolaevna

AU - Taylor, Peter

AU - Ghafoor, Farkhanda

AU - Vaidya, Bijay

AU - Hattersley, Andrew

AU - Mosso, Lorena

AU - Oken, Emily

AU - Kishi, Reiko

AU - Alexander, Erik K.

AU - Maraka, Spyridoula

AU - Huang, Kun

AU - Chaker, Layal

AU - Bassols, Judit

AU - Pirzada, Amna

AU - Lopez-Bermejo, Abel

AU - Boucai, Laura

AU - Peeters, Robin P.

AU - Pearce, Elizabeth N.

AU - Nelson, Scott McGill

AU - Chatzi, Leda

AU - Vrijkotte, Tanja G.

AU - Popova, Polina V.

AU - Walsh, John P.

AU - Nicolaides, Kypros H.

AU - Suvanto, Eila

AU - Lu, Xuemian

AU - Pop, Victor J. M.

AU - Forman, Julie Lyng

AU - Korevaar, Tim I. M.

AU - Feldt-Rasmussen, Ulla

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - meta-analysis

KW - pregnancy

KW - thyroglobulin antibodies

KW - thyroid

KW - thyroid autoimmunity

KW - thyroid peroxidase antibodies

KW - AUTOANTIBODIES

KW - AUTOIMMUNITY

KW - DISEASE

KW - WOMEN

KW - PREVALENCE

KW - DIAGNOSIS

KW - PROGRAM

KW - RANGES

KW - RISK

U2 - 10.1089/thy.2022.0083

DO - 10.1089/thy.2022.0083

M3 - Journal article

C2 - 35596568

VL - 32

SP - 828

EP - 840

JO - Thyroid

JF - Thyroid

SN - 1050-7256

IS - 7

ER -