Maternal Thyroid Function, Use of Antithyroid Drugs in Early Pregnancy, and Birth Defects
Maternal Thyroid Function, Use of Antithyroid Drugs in Early Pregnancy, and Birth Defects
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DOI：
10.1210/jc.2019-01343
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发表时间：
2019-12-01
影响因子：
5.8
通讯作者：
Andersen, Stig
中科院分区：
文献类型：
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作者：
Andersen, Stine Linding;Knosgaard, Louise;Andersen, Stig
背景：妊娠早期的抗甲状腺药物(ATD)治疗与出生缺陷有关，但需要更多的数据来证实与不同类型ATD相关的风险。此外，母亲甲状腺功能异常本身的作用仍不清楚。目的：评估在全国范围内扩大的队列中与使用ATD相关的出生缺陷的风险以及母亲甲状腺功能异常在出生队列中的作用，包括从怀孕早期储存的母亲血液样本。参与者：丹麦孕妇及其活产儿童，包括1997年至2016年全国登记队列(NRBC)的1,243,353名儿童；1997年至2003年丹麦国家出生队列(DNBC)的8830名儿童；结果：在北丹麦地区妊娠队列(NDRPC)中，共有2718名(0.2%)儿童在怀孕早期暴露于ATD。非接触组出生缺陷发生率为6.7%(95%CI，6.7%~6.8%)，暴露于他巴唑/卡比唑(9.6%；95%CI，8.2%~11.2%)和丙基硫氧嘧啶(8.3%；95%CI，6.7%~10.3%)后，出生缺陷发生率较高。DNBC组和NDRPC组孕妇早期妊娠甲状腺功能异常的发生率分别为12.4%和15.4%(P=0.8)，DNBC组和NDRPC组的发生率分别为12.4%和15.4%(P=0.8)。结论：研究结果证实了妊娠早期使用ATD可增加出生缺陷的风险，提示孕妇甲状腺功能异常不是出生缺陷的主要危险因素。
Context: Antithyroid drug (ATD) therapy in early pregnancy is associated with birth defects, but more data are needed to substantiate the risk associated with different types of ATD. Furthermore, the role of abnormal maternal thyroid function per se remains unclarified.Objective: To evaluate the risk of birth defects associated with the use of ATD in an extended nationwide cohort and the role of abnormal maternal thyroid function in birth cohorts including stored maternal blood samples from early pregnancy.Participants: Danish pregnant women and their live-born children, including 1,243,353 children from a Nationwide Register-Based Cohort (NRBC), 1997 to 2016; 8830 children from the Danish National Birth Cohort (DNBC), 1997 to 2003; and 14,483 children from the North Denmark Region Pregnancy Cohort (NDRPC), 2011 to 2015.Main Outcome Measures: Birth defects diagnosed before 2 years of age.Results: In the NRBC, altogether 2718 (0.2%) children had been exposed to ATD in early pregnancy. The overall frequency of birth defects was 6.7% (95% CI, 6.7% to 6.8%) in nonexposed children and higher after exposure to methimazole/carbimazole (9.6%; 95% CI, 8.2% to 11.2%) and propylthiouracil (8.3%; 95% CI, 6.7% to 10.3%). On the other hand, the frequency of maternal thyroid dysfunction in early pregnancy was similar in the random cohort and in cases of birth defect in the DNBC (12.4 vs 12.6%, P = 0.8) and the NDRPC (15.1 vs 15.4%, P = 0.8).Conclusions: Results corroborate an increased risk of birth defects associated with the use of ATD in early pregnancy and suggest that abnormal maternal thyroid function is not a major risk factor for birth defects.