Gi Hyeon Seo, MD *; Tae Hyuk Kim, MD, PhD *; Jae Hoon Chung, MD, PhD
Disclaimer: The authors take full responsibility for data collection, data interpretation, and writing of the manuscript. Dr. Chung had full access to the data and was responsible for submitting the manuscript for publication.
Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-1398.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer and Johnson & Johnson.
Reproducible Research Statement:Study protocol and statistical code: Available from Dr. Chung (e-mail, firstname.lastname@example.org). Data set: Not available.
Requests for Single Reprints: Jae Hoon Chung, MD, PhD, Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea; e-mail, email@example.com.
Current Author Addresses: Dr. Seo: Health Insurance Review and Assessment Service, 60 Hyeoksin-ro(Bangok-dong), Wonju-si, Gangwon-do 26465, Korea.
Drs. Kim and Chung: Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea.
Author Contributions: Conception and design: G.H. Seo, T.H. Kim, J.H. Chung.
Analysis and interpretation of the data: G.H. Seo, T.H. Kim, J.H. Chung.
Drafting of the article: G.H. Seo, T.H. Kim, J.H. Chung.
Critical revision of the article for important intellectual content: G.H. Seo, T.H. Kim, J.H. Chung.
Final approval of the article: G.H. Seo, T.H. Kim, J.H. Chung.
Statistical expertise: G.H. Seo.
Administrative, technical, or logistic support: G.H. Seo, J.H. Chung.
Collection and assembly of data: G.H. Seo.
Untreated or insufficiently treated Graves disease in pregnancy may pose risks to both mother and fetus. Antithyroid drugs (ATDs) are the treatment mainstay, but the potential teratogenic effect of these drugs has prompted clinicians to question the safe management of this vulnerable population.
To examine the association between maternal prescriptions for ATDs and congenital malformations in live births.
Nationwide cohort study.
Korean National Health Insurance database.
A cohort of 2 886 970 completed pregnancies linked to live-born infants in 2 210 253 women between 2008 and 2014.
Maternal prescriptions for ATDs in the first trimester.
The risk for overall and organ-specific congenital malformations in offspring, with logistic regression models used to control for potential confounders.
12 891 pregnancies (0.45%) were exposed to ATDs during the first trimester. The prevalence of malformations in exposed offspring was 7.27%, compared with 5.94% in offspring of women who were not prescribed ATDs during pregnancy (P < 0.001) (adjusted odds ratio, 1.19 [95% CI, 1.12 to 1.28]). Absolute increases in the prevalence of congenital malformations per 1000 live births were 8.81 cases (CI, 3.92 to 13.70 cases) for propylthiouracil alone, 17.05 cases (CI, 1.94 to 32.15 cases) for methimazole (MMI) alone, and 16.53 cases (CI, 4.73 to 28.32 cases) for propylthiouracil and MMI, compared with pregnancies without ATD prescriptions. In the MMI group, a high cumulative dose (>495 mg) during the first trimester was associated with an increased risk for malformations compared with a low dose (1 to 126 mg) (adjusted odds ratio, 1.87 [CI, 1.06 to 3.30]).
The study used a prescription claims database to assess ATD exposure.
Exposure to ATDs during the first trimester was associated with increased risk for congenital malformations, particularly for pregnancies in which women received prescriptions for MMI or both ATDs.
Seo GH, Kim TH, Chung JH. Antithyroid Drugs and Congenital Malformations: A Nationwide Korean Cohort Study. Ann Intern Med. 2018;168:405–413. doi: 10.7326/M17-1398
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Published: Ann Intern Med. 2018;168(6):405-413.
Published at www.annals.org on 23 January 2018
Endocrine and Metabolism, Healthcare Delivery and Policy, Thyroid Disorders.
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