title: Birth defects after early pregnancy use of antithyroid drugs: a Danish nationwide study.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Endocrinology, Aalborg University Hospital, Søndre Skovvej 15, DK-9000 Aalborg, Denmark. stine.a@rn.dk.
authors.forename: Stine Linding
authors.initials: SL
authors.lastname: Andersen
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
authors.forename: Chun Sen
authors.initials: CS
authors.lastname: Wu
authors.forename: Peter
authors.initials: P
authors.lastname: Laurberg
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000328:Adult; D013956:Antithyroid Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002231:Carbimazole / Q000008:administration & dosage / Q000009:adverse effects*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000188:drug therapy*; D007231:Infant, Newborn; D008297:Male; D008713:Methimazole / Q000008:administration & dosage / Q000009:adverse effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011261:Pregnancy Trimester, First; D015995:Prevalence; D011441:Propylthiouracil / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil; D002231:Carbimazole