The DOI matches its Crossref record; 43 of the 44 references it cites were found in a registry or an index.
Birth Defects After Early Pregnancy Use of Antithyroid Drugs: A Danish Nationwide Study
Abstract
INTRODUCTION: Hyperthyroidism in pregnant women should be adequately treated to prevent maternal and fetal complications, but teratogenic effects of antithyroid drug (ATD) treatment have been described. Evidence is still lacking in regard to the safety and choice of ATD in early pregnancy. OBJECTIVE: Our objective was to determine to which degree the use of methimazole (MMI)/carbimazole (CMZ) and propylthiouracil (PTU) in early pregnancy is associated with an increased prevalence of birth defects. METHODS: This Danish nationwide register-based cohort study included 817 093 children live-born from 1996 to 2008. Exposure groups were assigned according to maternal ATD use in early pregnancy: PTU (n = 564); MMI/CMZ (n = 1097); MMI/CMZ and PTU (shifted in early pregnancy [n = 159]); no ATD (ATD use, but not in pregnancy [n = 3543]); and nonexposed (never ATD use [n = 811 730]). Multivariate logistic regression was used to estimate adjusted odds ratio (OR) with 95% confidence interval (95% CI) for diagnosis of a birth defect before 2 years of age in exposed versus nonexposed children. RESULTS: The prevalence of birth defects was high in children exposed to ATD in early pregnancy (PTU, 8.0%; MMI/CMZ, 9.1%; MMI/CMZ and PTU, 10.1%; no ATD, 5.4%; nonexposed, 5.7%; P < .001). Both maternal use of MMI/CMZ (adjusted OR = 1.66 [95% CI 1.35-2.04]) and PTU (1.41 [1.03-1.92]) and maternal shift between MMI/CMZ and PTU in early pregnancy (1.82 [1.08-3.07]) were associated with an increased OR of birth defects. MMI/CMZ and PTU were associated with urinary system malformation, and PTU with malformations in the face and neck region. Choanal atresia, esophageal atresia, omphalocele, omphalomesenteric duct anomalies, and aplasia cutis were common in MMI/CMZ-exposed children (combined, adjusted OR = 21.8 [13.4-35.4]). CONCLUSIONS: Both MMI/CMZ and PTU were associated with birth defects, but the spectrum of malformations differed. More studies are needed to corroborate results in regard to early pregnancy shift from MMI/CMZ to PTU. New ATD with fewer side effects should be developed.
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“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 [463]
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Cites
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Wallach‐Kildemoes, H., Sørensen, H. T., & Hallas, J. (2011) · Scandinavian Journal of Public Health · doi:10.1177/1403494810394717 · Cited by 2,490
The Danish National Hospital Register. A valuable source of data for modern health sciences.
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Self-citationThe Danish Civil Registration System. A cohort of eight million persons.
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Fetal and Neonatal Hyperthyroidism
Zimmerman, D. (1999) · Thyroid · doi:10.1089/thy.1999.9.727 · Cited by 288
MATERNAL HYPERTHYROIDISM AND CONGENITAL MALFORMATION IN THE OFFSPRING
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A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy
Wing, D. A., Millar, L. K., Koonings, P. P., Montoro, M. N., & Mestman, J. H. (1994) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(94)70390-6 · Cited by 218
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Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938
“3% above the background rate) was also observed after PTU exposure in early pregnancy (463), but these defects tended to be less severe than with MMI and included preauricular sinuses and cysts and urinary tract abnormalities (466).”
BackgroundInfluentialSelf-citationAlexander, E. K., Pearce, E. N., Brent, G. A., Brown, R. S., Chen, H., Dosiou, C., Grobman, W. A., Laurberg, P., Lazarus, J. H., Mandel, S. J., et al. (2017) · Thyroid® · doi:10.1089/thy.2016.0457 · Cited by 2,731
Self-citation2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism
Kahaly, G. J., Bartalena, L., Hegedüs, L., Leenhardt, L., Poppe, K. G., & Pearce, S. H. S. (2018) · European Thyroid Journal · doi:10.1159/000490384 · Cited by 1,025
De Leo, S., Lee, S. Y., & Braverman, L. E. (2016) · The Lancet · doi:10.1016/s0140-6736(16)00278-6 · Cited by 883
Patel, K. N., Yip, L., Lubitz, C. C., Grubbs, E. G., Miller, B. S., Shen, W. T., Angelos, P., Chen, H., Doherty, G. M., Fahey, T. J., et al. (2020) · Annals of Surgery · doi:10.1097/sla.0000000000003580 · Cited by 567
Metadata
- Authors
- Andersen, S. L., Olsen, J., Wu, C. S., & Laurberg, P.
- Affiliations
- Aalborg University Hospital (DK)
- Aarhus University (DK)
- Corresponding author
- Andersen, Stine Linding
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2013-11
- Volume
- 98
- Issue
- 11
- Pages
- 4373-4381
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2102423760
- Cited by
- 267
- References
- 44
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 8 · 2023: 15 · 2022: 23 · 2021: 22 · 2020: 29 · 2019: 23 · 2018: 27 · 2017: 24 · 2016: 29 · 2015: 23 · 2014: 22 · 2013: 1
- FWCI
- 19.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- 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
- antithyroid drugs, congenital malformations, early pregnancy, hyperthyroidism in pregnancy, methimazole, carbimazole, propylthiouracil, teratogenicity, choanal atresia, esophageal atresia, omphalocele, drug safety
- MeSH terms
- Abnormalities, Drug-Induced, Adult, Carbimazole, Denmark, Female, Humans, Hyperthyroidism, Infant, Newborn, Male, Methimazole, Pregnancy, Pregnancy Complications, Pregnancy Trimester, First, Propylthiouracil, Antithyroid Agents, Prevalence
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