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Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.
JAMA 2019; 322(7):632-641JAMA

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 Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4]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 After the addition of 5 unpublished data sets, a total of 19 cohorts were included.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.

Authors+Show Affiliations

No affiliation info availableDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.Thyroid Research Group, Systems Immunity Research Institute, School of Medicine, Cardiff University, Cardiff, England.Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.Department of Endocrinology and Rui'an Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.Department of Diabetes, Endocrinology, and Clinical Pharmacology, Glasgow Royal Infirmary, Glasgow, Scotland. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.Departments of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.Department of Endocrinology, Royal Devon and Exeter Hospital NHS Foundation Trust, University of Exeter Medical School, Exeter, England.Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, England.National Health Research Complex, Shaikh Zayed Medical Complex, Lahore, Pakistan.Almazov National Medical Research Centre, St Petersburg, Russia. Department of Internal Diseases and Endocrinology, St Petersburg Pavlov State Medical University, St Petersburg, Russia.Department of Endocrinology, Pontificia Universidad Catolica de Chile, Santiago.Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School, Boston, Massachusetts. Harvard Pilgrim Health Care Institute, Boston, Massachusetts. Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.Department of Obstetrics and Gynecology and Medical Research Center Oulu, University of Oulu, Oulu, Finland.Center for Preventive Medical Science, Chiba University, Chiba, Japan.Faculty of Life Sciences, Toyo University, Gunma, Japan.Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Australia.Maternal-Fetal Metabolic Research Group, Girona Biomedical Research Institute, Dr Josep Trueta Hospital, Girona, Spain.Medical Research Center Oulu, Oulu University Hospital, Center for Life Course Health Research, University of Oulu, Oulu, Finland.Medical Library, Erasmus University Medical Center, Rotterdam, the Netherlands.Pediatric Endocrinology Research Group, Girona Biomedical Research Institute, Dr Josep Trueta Hospital, Girona, Spain.Thyroid Research Group, Institute of Molecular and Experimental Medicine, School of Medicine, Cardiff University, Cardiff, England.Division of Endocrinology, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell University, New York, New York.Department of Social Medicine, University of Crete, Heraklion, Greece.Almazov National Medical Research Centre, St Petersburg, Russia. Department of Internal Diseases and Endocrinology, St Petersburg Pavlov State Medical University, St Petersburg, Russia.Almazov National Medical Research Centre, St Petersburg, Russia. Department of Internal Diseases and Endocrinology, St Petersburg Pavlov State Medical University, St Petersburg, Russia.Departments of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands.Department of Public Health, Amsterdam University Medical Center, University of Amsterdam, Amsterdam Public Health Research Institute, Amsterdam, the Netherlands.ISGlobal, Centre for Research in Environmental Epidemiology, Barcelona, Spain. Pompeu Fabra University, Barcelona, Spain. Spanish Consortium for Research on Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain. Department of Child and Adolescent Psychiatry/Psychology, Erasmus University Medical Center, Sophia Children's Hospital, Rotterdam, the Netherlands.Keck School of Medicine, Department of Preventive Medicine, University of Southern California, Los Angeles.ISGlobal, Centre for Research in Environmental Epidemiology, Barcelona, Spain. Pompeu Fabra University, Barcelona, Spain. Spanish Consortium for Research on Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain. Hospital del Mar Medical Research Institute, Barcelona, Spain.Biodonostia Health Research Institute, San Sebastian, Spain. Public Health Division of Gipuzkoa, Basque Government, San Sebastian, Spain.Spanish Consortium for Research on Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain. AGC Pediatrics, Hospital Universitario Central de Asturias, Oviedo, Spain.Spanish Consortium for Research on Epidemiology and Public Health, Instituto de Salud Carlos III, Madrid, Spain. Epidemiology and Environmental Health Joint Research Unit, FISABIO-Universitat Jaume I-Universitat de València, Valencia, Spain.Department of Endocrinology and Rui'an Center of the Chinese-American Research Institute for Diabetic Complications, Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.Department of Gynecology and Obstetrics, Shaikh Zayed Medical Complex, Lahore, Pakistan.Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, Scotland.Department of Medical Endocrinology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.School of Medicine, University of Glasgow, Glasgow, Scotland. National Institute for Health Research, Bristol Biomedical Research Centre, Bristol, England.Division of Endocrinology, Hypertension, and Diabetes, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.Northern Finland Laboratory Center Nordlab and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.Maternal-Fetal Metabolic Research Group, Girona Biomedical Research Institute, Dr Josep Trueta Hospital, Girona, Spain. Medical School, University of Western Australia, Crawley.Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts.Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands.Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. Academic Center for Thyroid Diseases, Erasmus University Medical Center, Rotterdam, the Netherlands.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

31429897

Citation

Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth, et al. "Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: a Systematic Review and Meta-analysis." JAMA, vol. 322, no. 7, 2019, pp. 632-641.
Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth, Korevaar TIM, Derakhshan A, et al. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis. JAMA. 2019;322(7):632-641.
Korevaar, T. I. M., Derakhshan, A., Taylor, P. N., Meima, M., Chen, L., Bliddal, S., ... Peeters, R. P. (2019). Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis. JAMA, 322(7), pp. 632-641. doi:10.1001/jama.2019.10931.
Consortium on Thyroid and Pregnancy—Study Group on Preterm Birth, et al. Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: a Systematic Review and Meta-analysis. JAMA. 2019 08 20;322(7):632-641. PubMed PMID: 31429897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis. AU - ,, AU - Korevaar,Tim 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,Judith, 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,Tanja G, AU - Guxens,Mònica, AU - Chatzi,Leda, AU - Sunyer,Jordi, AU - Jiménez-Zabala,Ana, AU - Riaño,Isolina, AU - Murcia,Mario, AU - Lu,Xuemian, AU - Mukhtar,Shafqat, AU - Delles,Christian, AU - Feldt-Rasmussen,Ulla, AU - Nelson,Scott M, AU - Alexander,Erik K, AU - Chaker,Layal, AU - Männistö,Tuija, AU - Walsh,John P, AU - Pearce,Elizabeth N, AU - Steegers,Eric A P, AU - Peeters,Robin P, PY - 2020/02/20/pmc-release PY - 2019/8/21/entrez PY - 2019/8/21/pubmed PY - 2019/9/7/medline SP - 632 EP - 641 JF - JAMA JO - JAMA VL - 322 IS - 7 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/31429897/Association_of_Thyroid_Function_Test_Abnormalities_and_Thyroid_Autoimmunity_With_Preterm_Birth:_A_Systematic_Review_and_Meta-analysis L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2019.10931 DB - PRIME DP - Unbound Medicine ER -