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Cited by 267Thyroid Disorders and TreatmentsPregnancy and Medication ImpactPharmacological Effects and Toxicity Studies

Birth Defects After Early Pregnancy Use of Antithyroid Drugs: A Danish Nationwide Study

Andersen, Stine Linding, Olsen, Jørn, Wu, Chun Sen, Laurberg, Peter·2013·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2013-2831
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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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  • 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 [463]

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1 of the 44 references couldn’t be matched to a known paper.

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  1. Cooper DS. Antithyroid drugs. N Engl J Med. 2005;352:905-917.

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Authors
Andersen, S. L., Olsen, J., Wu, C. S., & Laurberg, P.
Affiliations
  • Aalborg University Hospital (DK)
  • Aarhus University (DK)
Corresponding author
Andersen, Stine Linding
ORCID
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
DOI
10.1210/jc.2013-2831
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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