Nervous system drugs taken by future fathers and birth defects in offspring: a prospective registry-based cohort study.
Nervous system drugs taken by future fathers and birth defects in offspring: a prospective registry-based cohort study.
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未来父亲服用神经系统药物与后代出生缺陷：一项基于登记的前瞻性队列研究。
DOI：
10.1136/bmjopen-2021-053946
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发表时间：
2022-03-30
期刊：
影响因子：
2.9
通讯作者：
Eisenberg M
中科院分区：
文献类型：
--
作者：
Wensink M;Lu Y;Tian L;Jensen TK;Skakkebæk NE;Lindahl-Jacobsen R;Eisenberg M
评价在受精精子发育过程中父亲摄入抗精神病药、抗焦虑药、催眠药和镇静药、抗抑郁药、选择性5-羟色胺再摄取抑制剂（SSRIs）和（苯并）二氮卓类药物与后代出生缺陷的相关性。基于登记的前瞻性队列研究。使用丹麦国家登记处的1997-2016年丹麦出生队列总数。1997年至2016年出生的所有1，201，119名丹麦活产独生子女均符合资格，其中39，803人（3.3%）至少患有一种重大出生缺陷。如果后代的父亲在受精精子发育期间（受孕前3个月）服用了至少一种相关药物类别的处方，则认为后代暴露。主要结局是在出生后第一年内诊断出至少一种EUROCAT指南中分类的重大出生缺陷。次要结局是在出生后第一年内，在EUROCAT的任何子类别中至少诊断出一种重大出生缺陷。计算调整后的OR（AOR），沿着计算其95% CI，调整了母亲的年龄、教育程度、吸烟状况和年龄，以及父亲的教育程度、可支配收入和年龄。这项研究发现，出生缺陷和选定的药物之间的联系很弱或没有联系。具体而言，抗抑郁药（17827例暴露的出生）导致3.5%的出生缺陷（AOR 0.97（0.89至1.05））。二氮卓类、氧氮卓类、硫氮卓类和氧杂卓类（抗精神病药）1633例子代的出生缺陷发生率为4.7%（AOR 1.22（0.97 ~ 1.54）），排除母亲处方后下降为1.13。假设100%的治疗依从性，该研究具有良好的把握度，而假设50%的治疗依从性，该研究在最大组（SSRI和抗抑郁药总体）中仍具有良好的把握度。抗精神病药、抗焦虑药、催眠药和镇静药、抗抑郁药、SSRI和苯二氮卓类抗焦虑药，当父亲在受精精子发育期间服用时，通常对出生缺陷是安全的。
To evaluate the association of paternal intake of antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, selective serotonin reuptake inhibitors (SSRIs) and (benzo)diazepines during the development of fertilising sperm with birth defects in offspring. Prospective registry-based cohort study. Total Danish birth cohort 1997–2016 using Danish national registries. All 1 201 119 Danish liveborn singletons born 1997–2016 were eligible, 39 803 (3.3%) of whom had at least one major birth defect. Offspring were considered exposed if their father had filled at least one prescription in the relevant drug category during development of fertilising sperm (the 3 months prior to conception). Primary outcome was the diagnosis, in the first year of life, of at least one major birth defect as categorised in the EUROCAT guidelines. Secondary outcome was the diagnosis, in the first year of life, of at least one major birth defect in any of the EUROCAT subcategories. Adjusted ORs (AORs) were calculated, along with their 95% CIs, adjusted for year, education, smoking status and age of the mother, and education, disposable income and age of the father. This study found weak or null associations between birth defects and selected drugs. Specifically, antidepressants (17 827 exposed births) gave 3.5% birth defects (AOR 0.97 (0.89 to 1.05)). Diazepines, oxazepines, thiazepines and oxepines (as antipsychotics, 1633 offspring) gave 4.7% birth defects (AOR 1.22 (0.97 to 1.54)), attenuated to 1.13 when excluding by mothers’ prescriptions. The study was well powered assuming 100% therapy adherence, while assuming 50% therapy adherence, the study remained well powered for the largest groups (SSRIs and antidepressants overall). Antipsychotics, anxiolytics, hypnotics and sedatives, antidepressants, SSRIs and benzodiazepine-derived anxiolytics, when taken by the father during development of fertilising sperm, are generally safe with regard to birth defects.
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