title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Ito Hospital, Tohoku University Graduate School of Medicine, Miyagi, 980-8574, Japan. a-yoshihara@ito-hospital.jp
authors.forename: Ai
authors.initials: A
authors.lastname: Yoshihara
authors.forename: JaedukYoshimura
authors.initials: J
authors.lastname: Noh
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ohye
authors.forename: Shiori
authors.initials: S
authors.lastname: Sato
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sekiya
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kosuga
authors.forename: Miho
authors.initials: M
authors.lastname: Suzuki
authors.forename: Masako
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Yo
authors.initials: Y
authors.lastname: Kunii
authors.forename: Natsuko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Koji
authors.initials: K
authors.lastname: Mukasa
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Ito
authors.forename: Koichi
authors.initials: K
authors.lastname: Ito
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000328:Adult; D013956:Antithyroid Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D016022:Case-Control Studies; D005260:Female; D006111:Graves Disease / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D050498:Live Birth / Q000453:epidemiology; D008713:Methimazole / Q000009:adverse effects / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy / Q000453:epidemiology*; D011256:Pregnancy Outcome / Q000453:epidemiology; D011261:Pregnancy Trimester, First / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology; D015995:Prevalence; D011441:Propylthiouracil / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil