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Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis

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@article{24af81991c6a4be29395a7c2dcd3ba30,
title = "Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis",
abstract = "Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models.Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age).Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1{\%}) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2{\%}) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5{\%}) were TPO antibody positive; 2357 (5.0{\%}) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1{\%} vs 5.0{\%}, respectively; absolute risk difference, 1.4{\%} [95{\%} CI, 0{\%}-3.2{\%}]; odds ratio [OR], 1.29 [95{\%} CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1{\%} vs 5.0{\%} in euthyroid women (absolute risk difference, 2.3{\%} [95{\%} CI, 0.6{\%}-4.5{\%}]; OR, 1.46 [95{\%} CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2{\%} [95{\%} CI, 0{\%}-0.4{\%}] per 1 SD; OR, 1.04 [95{\%} CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6{\%} vs 4.9{\%}, respectively; absolute risk difference, 1.6{\%} [95{\%} CI, 0.7{\%}-2.8{\%}]; OR, 1.33 [95{\%} CI, 1.15-1.56]).Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.",
keywords = "Adult, Autoantibodies/blood, Autoimmune Diseases/blood, Female, Gestational Age, Humans, Hypothyroidism/complications, Infant, Newborn, Iodide Peroxidase/immunology, Pregnancy, Pregnancy Complications/blood, Premature Birth/etiology, Thyroid Diseases/blood, Thyroid Function Tests, Thyrotropin/blood, Thyroxine/blood",
author = "Korevaar, {T I M} and Arash Derakhshan and Taylor, {Peter N} and Marcel Meima and Liangmiao Chen and Sofie Bliddal and Carty, {David M} and Margreet Meems and Bijay Vaidya and Beverley Shields and Farkhanda Ghafoor and Popova, {Polina V} and Lorena Mosso and Emily Oken and Eila Suvanto and Aya Hisada and Jun Yoshinaga and Brown, {Suzanne J} and Judit Bassols and Juha Auvinen and Bramer, {Wichor M} and Abel L{\'o}pez-Bermejo and Colin Dayan and Laura Boucai and Marina Vafeiadi and Grineva, {Elena N} and Tkachuck, {Alexandra S} and Pop, {Victor J M} and Vrijkotte, {T G} and M Guxens and L Chatzi and J Sunyer and A Jim{\'e}nez-Zabala and I Ria{\~n}o and M Murcia and X Lu and S Mukhtar and C Delles and U Feldt-Rasmussen and Nelson, {S M} and Alexander, {E K} and L Chaker and T M{\"a}nnist{\"o} and Walsh, {J P} and Pearce, {E N} and Steegers, {E A P} and Peeters, {R P} and {Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth}",
year = "2019",
month = "8",
day = "20",
doi = "10.1001/jama.2019.10931",
language = "English",
volume = "322",
pages = "632--641",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "7",

}

RIS

TY - JOUR

T1 - Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth

T2 - A Systematic Review and Meta-analysis

AU - Korevaar, T I M

AU - Derakhshan, Arash

AU - Taylor, Peter N

AU - Meima, Marcel

AU - Chen, Liangmiao

AU - Bliddal, Sofie

AU - Carty, David M

AU - Meems, Margreet

AU - Vaidya, Bijay

AU - Shields, Beverley

AU - Ghafoor, Farkhanda

AU - Popova, Polina V

AU - Mosso, Lorena

AU - Oken, Emily

AU - Suvanto, Eila

AU - Hisada, Aya

AU - Yoshinaga, Jun

AU - Brown, Suzanne J

AU - Bassols, Judit

AU - Auvinen, Juha

AU - Bramer, Wichor M

AU - López-Bermejo, Abel

AU - Dayan, Colin

AU - Boucai, Laura

AU - Vafeiadi, Marina

AU - Grineva, Elena N

AU - Tkachuck, Alexandra S

AU - Pop, Victor J M

AU - Vrijkotte, T G

AU - Guxens, M

AU - Chatzi, L

AU - Sunyer, J

AU - Jiménez-Zabala, A

AU - Riaño, I

AU - Murcia, M

AU - Lu, X

AU - Mukhtar, S

AU - Delles, C

AU - Feldt-Rasmussen, U

AU - Nelson, S M

AU - Alexander, E K

AU - Chaker, L

AU - Männistö, T

AU - Walsh, J P

AU - Pearce, E N

AU - Steegers, E A P

AU - Peeters, R P

AU - Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth

PY - 2019/8/20

Y1 - 2019/8/20

N2 - Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models.Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age).Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

AB - Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth.Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth.Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded.Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models.Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age).Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]).Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

KW - Adult

KW - Autoantibodies/blood

KW - Autoimmune Diseases/blood

KW - Female

KW - Gestational Age

KW - Humans

KW - Hypothyroidism/complications

KW - Infant, Newborn

KW - Iodide Peroxidase/immunology

KW - Pregnancy

KW - Pregnancy Complications/blood

KW - Premature Birth/etiology

KW - Thyroid Diseases/blood

KW - Thyroid Function Tests

KW - Thyrotropin/blood

KW - Thyroxine/blood

U2 - 10.1001/jama.2019.10931

DO - 10.1001/jama.2019.10931

M3 - Journal article

VL - 322

SP - 632

EP - 641

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 7

ER -

ID: 59064454