Ito Hospital, Tohoku University Graduate School of Medicine, Miyagi, 980-8574, Japan.
J Clin Endocrinol Metab. 2012 Jul;97(7):2396-403. doi: 10.1210/jc.2011-2860. Epub 2012 Apr 30.
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.
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.
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.
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.
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.
有几项报告表明，丙硫氧嘧啶（PTU）在治疗妊娠期间甲状腺毒症时可能比甲巯咪唑（MMI）更安全，因为先天性畸形与妊娠期间使用 MMI 有关。
我们研究了胎儿暴露于抗甲状腺药物是否会导致畸形发生率高于对照组孕妇所生婴儿。
我们回顾了患有格雷夫斯病的孕妇的病例。已知 6744 名妇女的妊娠结局，有 5967 例活产。单独使用 MMI 治疗了 1426 名妇女，单独使用 PTU 治疗了 1578 名妇女。2065 名在妊娠早期未接受任何治疗格雷夫斯病的药物的妇女作为对照组。其余妇女在妊娠早期接受了碘化钾、左甲状腺素或多种药物治疗。评估了抗甲状腺药物与先天性畸形的关系。
MMI 组的整体严重畸形发生率为 4.1%（50/1231），明显高于对照组的 2.1%（40/1906）（P=0.002），但 PTU 组与对照组相比，严重畸形发生率没有增加（1.9%；1399 例中有 21 例；P=0.709）。MMI 组的 1231 名新生儿中，有 7 名患有先天性表皮发育不全，6 名患有脐膨出，7 名患有症状性脐肠系膜导管异常，1 名患有食管闭锁。妊娠早期的甲状腺功能亢进并未增加先天性畸形的发生率。
妊娠早期胎儿暴露于 MMI 增加了先天性畸形的发生率，显著增加了先天性表皮发育不全、脐膨出和症状性脐肠系膜导管异常的发生率。
