Andersen Stine Linding, Olsen Jørn, Wu Chun Sen, Laurberg Peter
1 Department of Endocrinology, Aalborg University Hospital , Aalborg, Denmark .
Thyroid. 2014 Oct;24(10):1533-40. doi: 10.1089/thy.2014.0150. Epub 2014 Jun 25.
Propylthiouracil (PTU) used in the treatment of maternal hyperthyroidism in early pregnancy may be associated with a higher prevalence of birth defects in the face and neck region and in the urinary system but the severity of these complications remains to be elucidated.
Review of hospital-registered cases of birth defects in the face and neck region and in the urinary system after PTU exposure in early pregnancy. We obtained information on maternal redeemed prescription of PTU and child diagnosis of birth defect from nationwide registers for all children born in Denmark between 1996 and 2008 (n=817,093). The children were followed until December 31, 2010 (median age, 8.3 years) and the Cox proportional hazards model was used to estimate adjusted hazard ratio (HR) with 95% confidence interval (CI) for having a birth defect after PTU exposure versus nonexposed children (n=811,730).
Fourteen cases of birth defects were identified in the face and neck region and in the urinary system after PTU exposure in early pregnancy; 11 children were exposed to PTU only (n=564), whereas 3 children were born to mothers who switched from methimazole (MMI)/carbimazole (CMZ) to PTU in early pregnancy (n=159). Among children exposed to PTU only, the adjusted HR for having a birth defect in the face and neck region was 4.92 (95% CI 2.04-11.86) and in the urinary system 2.73 (1.22-6.07). Looking into details of the 14 cases, 7 children were diagnosed with a birth defect in the face and neck region (preauricular and branchial sinus/fistula/cyst) and 7 children had a birth defect in the urinary system (single cyst of kidney and hydronephrosis). Surgical treatment was registered in 6 of the cases with a birth defect in the face and neck region and 3 of the cases with a birth defect in the urinary system. Two of the children with a birth defect in the urinary system also had other birth defects (genital organs).
We report details on possible PTU-associated birth defects. They tend to be less severe than the defects observed after MMI/CMZ exposure. Yet, the majority of affected children had to undergo surgery.
在妊娠早期用于治疗孕妇甲状腺功能亢进的丙硫氧嘧啶（PTU）可能与面部和颈部区域以及泌尿系统出生缺陷的较高患病率相关，但这些并发症的严重程度仍有待阐明。
回顾妊娠早期暴露于PTU后医院登记的面部和颈部区域以及泌尿系统出生缺陷病例。我们从丹麦1996年至2008年出生的所有儿童（n = 817,093）的全国登记册中获取了母亲PTU赎回处方和儿童出生缺陷诊断的信息。对这些儿童进行随访至2010年12月31日（中位年龄8.3岁），并使用Cox比例风险模型估计暴露于PTU的儿童与未暴露儿童（n = 811,730）相比出现出生缺陷的调整风险比（HR）及95%置信区间（CI）。
在妊娠早期暴露于PTU后，在面部和颈部区域以及泌尿系统中发现了14例出生缺陷；11名儿童仅暴露于PTU（n = 564），而3名儿童的母亲在妊娠早期从甲巯咪唑（MMI）/卡比马唑（CMZ）改用PTU（n = 159）。在仅暴露于PTU的儿童中，面部和颈部区域出现出生缺陷的调整HR为4.92（95%CI 2.04 - 11.86），泌尿系统为2.73（1.22 - 6.07）。深入研究这14例病例的细节，7名儿童被诊断为面部和颈部区域出生缺陷（耳前及鳃窦/瘘管/囊肿），7名儿童有泌尿系统出生缺陷（肾囊肿和肾积水）。6例面部和颈部区域出生缺陷病例及3例泌尿系统出生缺陷病例登记了手术治疗情况。2例泌尿系统出生缺陷儿童还伴有其他出生缺陷（生殖器官）。
我们报告了与PTU可能相关的出生缺陷细节。它们往往比MMI/CMZ暴露后观察到的缺陷症状较轻。然而，大多数受影响的儿童都必须接受手术。
