Department of Endocrinology, Aalborg University Hospital, Søndre Skovvej 15, DK-9000 Aalborg, Denmark.
J Clin Endocrinol Metab. 2013 Nov;98(11):4373-81. doi: 10.1210/jc.2013-2831. Epub 2013 Oct 22.
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.
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.
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.
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]).
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.
甲状腺功能亢进症孕妇应进行充分治疗以预防母婴并发症，但抗甲状腺药物（ATD）治疗的致畸作用已有描述。关于早期妊娠 ATD 的安全性和选择，仍缺乏证据。
我们的目的是确定在早期妊娠中使用甲巯咪唑（MMI）/卡比马唑（CMZ）和丙基硫氧嘧啶（PTU）与增加出生缺陷的患病率之间的关联程度。
这项丹麦全国范围内基于登记的队列研究纳入了 1996 年至 2008 年期间出生的 817 093 名活产儿。根据母亲在早期妊娠中使用 ATD 进行暴露组分组：PTU（n=564）；MMI/CMZ（n=1097）；MMI/CMZ 和 PTU（在早期妊娠中转换[ n=159]）；无 ATD（在妊娠期间使用 ATD，但未在妊娠期间使用[ n=3543]）；未暴露（从未使用过 ATD[n=811730]）。使用多变量逻辑回归来估计调整后的比值比（OR）及其 95%置信区间（95%CI），用于比较暴露于 ATD 与未暴露的儿童在 2 岁前诊断出出生缺陷的情况。
在早期妊娠中暴露于 ATD 的儿童中，出生缺陷的患病率较高（PTU，8.0%；MMI/CMZ，9.1%；MMI/CMZ 和 PTU，10.1%；无 ATD，5.4%；未暴露，5.7%；P<0.001）。母亲使用 MMI/CMZ（调整后的 OR=1.66[95%CI 1.35-2.04]）和 PTU（1.41[1.03-1.92]）以及母亲在早期妊娠中从 MMI/CMZ 转换为 PTU（1.82[1.08-3.07]）均与出生缺陷的 OR 增加相关。MMI/CMZ 和 PTU 与泌尿系统畸形有关，PTU 与面颈部畸形有关。MMI/CMZ 暴露的儿童中常见的是后鼻孔闭锁、食管闭锁、脐膨出、卵黄管异常和先天性皮肤缺失（联合时，调整后的 OR=21.8[13.4-35.4]）。
MMI/CMZ 和 PTU 均与出生缺陷相关，但畸形谱不同。需要更多的研究来证实早期妊娠中从 MMI/CMZ 转换为 PTU 的结果。应开发具有较少副作用的新型 ATD。
