Treatment of Graves' Disease with Antithyroid Drugs in the First Trimester of Pregnancy and the Prevalence of Congenital Malformation
Abstract
BACKGROUND: Several reports have suggested that propylthiouracil (PTU) may be safer than methimazole (MMI) for treating thyrotoxicosis during pregnancy because congenital malformations have been associated with the use of MMI during pregnancy. OBJECTIVES: We investigated whether in utero exposure to antithyroid drugs resulted in a higher rate of major malformations than among the infants born to a control group of pregnant women. METHODS: We reviewed the cases of women with Graves' disease who became pregnant. The pregnancy outcomes of 6744 women were known, and there were 5967 live births. MMI alone had been used to treat 1426 of the women, and 1578 women had been treated with PTU alone. The 2065 women who had received no medication for the treatment of Graves' disease during the first trimester served as the control group. The remaining women had been treated with potassium iodide, levothyroxine, or more than one drug during the first trimester. The antithyroid drugs were evaluated for associations with congenital malformations. RESULTS: The overall rate of major anomalies in the MMI group was 4.1% (50 of 1231), and it was significantly higher than the 2.1% (40 of 1906) in the control group (P = 0.002), but there was no increase in the overall rate of major anomalies in the PTU group in comparison with the control group (1.9%; 21 of 1399; P = 0.709). Seven of the 1231 newborns in the MMI group had aplasia cutis congenita, six had an omphalocele, seven had a symptomatic omphalomesenteric duct anomaly, and one had esophageal atresia. Hyperthyroidism in the first trimester of pregnancy did not increase the rate of congenital malformation. CONCLUSIONS: In utero exposure to MMI during the first trimester of pregnancy increased the rate of congenital malformations, and it significantly increased the rate of aplasia cutis congenita, omphalocele, and a symptomatic omphalomesenteric duct anomaly.
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MMI-associated birth defects may be observed in 2%-4% of exposed children and include aplasia cutis; choanal atresia, esophageal, and other gut atresias; abdominal wall abnormalities including omphalocale; and eye, heart, and urinary tract malformations.
“Defects that may be observed in 2%-4% of exposed children (462,463) have included aplasia cutis; choanal atresia, esophageal, and other types of gut atresias; abdominal wall abnormalities including omphalocale; and eye, heart, and urinary tract malformations.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [462]
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References 34 · Cited by 231
- Authors
- Yoshihara, A., Noh, J., Yamaguchi, T., Ohye, H., Sato, S., Sekiya, K., Kosuga, Y., Suzuki, M., Matsumoto, M., Kunii, Y., Watanabe, N., Mukasa, K., Ito, K., & Ito, K.
- Affiliations
- Tohoku University (JP)
- Ito Hospital (JP)
- Corresponding author
- Yoshihara, Ai
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-07
- Volume
- 97
- Issue
- 7
- Pages
- 2396-2403
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2147913311
- Cited by
- 231
- References
- 34
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 6 · 2023: 11 · 2022: 16 · 2021: 21 · 2020: 21 · 2019: 19 · 2018: 17 · 2017: 24 · 2016: 21 · 2015: 21 · 2014: 20 · 2013: 17 · 2012: 6
- FWCI
- 16.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- Graves' disease, antithyroid drugs, propylthiouracil, methimazole, first trimester, congenital malformations, prenatal drug exposure, hyperthyroidism in pregnancy, aplasia cutis congenita, omphalocele, esophageal atresia, drug safety in pregnancy
- MeSH terms
- Abnormalities, Drug-Induced, Adult, Female, Graves Disease, Humans, Infant, Newborn, Methimazole, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Pregnancy Trimester, First, Prenatal Exposure Delayed Effects, Propylthiouracil, Antithyroid Agents, Prevalence, Case-Control Studies, Live Birth, Young Adult
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