TY - JOUR

T1 - Risk Factors for Thyroid Dysfunction in Pregnancy

T2 - An Individual Participant Data Meta-Analysis

AU - Osinga, Joris A. J.

AU - Liu, Yindi

AU - Männistö, Tuija

AU - Vafeiadi, Marina

AU - Tao, Fang-Biao

AU - Vaidya, Bijay

AU - Vrijkotte, Tanja G. M.

AU - Mosso, Lorena

AU - Bassols, Judit

AU - López-Bermejo, Abel

AU - Boucai, Laura

AU - Aminorroaya, Ashraf

AU - Feldt-Rasmussen, Ulla

AU - Hisada, Aya

AU - Yoshinaga, Jun

AU - Broeren, Maarten A. C.

AU - Itoh, Sachiko

AU - Kishi, Reiko

AU - Ashoor, Ghalia

AU - Chen, Liangmiao

AU - Veltri, Flora

AU - Lu, Xuemian

AU - Taylor, Peter N.

AU - Brown, Suzanne J.

AU - Chatzi, Leda

AU - Popova, Polina V.

AU - Grineva, Elena N.

AU - Ghafoor, Farkhanda

AU - Pirzada, Amna

AU - Kianpour, Maryam

AU - Oken, Emily

AU - Suvanto, Eila

AU - Hattersley, Andrew

AU - Rebagliato, Marisa

AU - Riaño-Galán, Isolina

AU - Irizar, Amaia

AU - Vrijheid, Martine

AU - Delgado-Saborit, Juana Maria

AU - Fernández-Somoano, Ana

AU - Santa-Marina, Loreto

AU - Boelaert, Kristien

AU - Brenta, Gabriela

AU - Dhillon-Smith, Rima

AU - Dosiou, Chrysoula

AU - Eaton, Jennifer L.

AU - Guan, Haixia

AU - Lee, Sun Y.

AU - Maraka, Spyridoula

AU - Morris-Wiseman, Lilah F.

AU - Nguyen, Caroline T.

AU - Shan, Zhongyan

AU - Guxens, Mònica

AU - Pop, Victor J. M.

AU - Walsh, John P.

AU - Nicolaides, Kypros H.

AU - D'Alton, Mary E.

AU - Visser, W. Edward

AU - Carty, David M.

AU - Delles, Christian

AU - Nelson, Scott M.

AU - Alexander, Erik K.

AU - Chaker, Layal

AU - Palomaki, Glenn E.

AU - Peeters, Robin P.

AU - Bliddal, Sofie

AU - Huang, Kun

AU - Poppe, Kris G.

AU - Pearce, Elizabeth N.

AU - Derakhshan, Arash

AU - Korevaar, Tim I. M.

PY - 2024

Y1 - 2024

N2 - Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

AB - Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

U2 - 10.1089/thy.2023.0646

DO - 10.1089/thy.2023.0646

M3 - Journal article

C2 - 38546971

VL - 34

SP - 646

EP - 658

JO - Thyroid

JF - Thyroid

SN - 1050-7256

IS - 5

ER -