title: Therapy of endocrine disease: antithyroid drug use in early pregnancy and birth defects: time windows of relative safety and high risk?
abstract: BACKGROUND
  Antithyroid drugs (ATDs) may have teratogenic effects when used in early pregnancy.
  
  
  OBJECTIVE
  To review the association between the time period of ATD exposure in early pregnancy and the development of birth defects.
  
  
  METHODS
  We identified publications on birth defects after early pregnancy exposure to the ATDs methimazole (MMI; and its prodrug carbimazole (CMZ)) and propylthiouracil (PTU). Cases of birth defects after ATD treatment had been initiated or terminated within the first 10 weeks of pregnancy were identified and studied in detail.
  
  
  RESULTS
  A total of 92 publications were read in detail. Two recent large controlled studies showed ATD-associated birth defects in 2-3% of exposed children, and MMI/CMZ-associated defects were often severe. Out of the total number of publications, 17 included cases of birth defects with early pregnancy stop/start of ATD treatment, and these cases suggested that the high risk was confined to gestational weeks 6-10, which is the major period of organogenesis. Thus, the cases reported suggest that the risk of birth defects could be minimized if pregnant women terminate ATD intake before gestational week 6.
  
  
  CONCLUSIONS
  Both MMI and PTU use in early pregnancy may lead to birth defects in 2-3% of the exposed children. MMI-associated defects are often severe. Proposals are given on how to minimize the risk of birth defects in fertile women treated for hyperthyroidism with ATDs.
authors.affiliation: Department of EndocrinologyAalborg University Hospital, DK-9000 Aalborg, DenmarkDepartment of Clinical MedicineAalborg University, Aalborg, DenmarkDepartment of EndocrinologyAalborg University Hospital, DK-9000 Aalborg, DenmarkDepartment of Clinical MedicineAalborg University, Aalborg, Denmark peter.laurberg@rn.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Laurberg
authors.affiliation: Department of EndocrinologyAalborg University Hospital, DK-9000 Aalborg, DenmarkDepartment of Clinical MedicineAalborg University, Aalborg, DenmarkDepartment of EndocrinologyAalborg University Hospital, DK-9000 Aalborg, DenmarkDepartment of Clinical MedicineAalborg University, Aalborg, Denmark.
authors.forename: Stine Linding
authors.initials: SL
authors.lastname: Andersen
mesh_terms: D013956:Antithyroid Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002231:Carbimazole / Q000009:adverse effects / Q000627:therapeutic use; D000013:Congenital Abnormalities / Q000209:etiology / Q000517:prevention & control*; D004700:Endocrine System Diseases / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy; D011441:Propylthiouracil / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D013956:Antithyroid Agents; D011441:Propylthiouracil; D002231:Carbimazole