父方在受孕前 3 个月内使用硫唑嘌呤/6-巯基嘌呤或甲氨蝶呤与后代的长期健康结局：一项全国性队列研究。
Paternal use of azathioprine/6-mercaptopurine or methotrexate within 3 months before conception and long-term health outcomes in the offspring-A nationwide cohort study.
机构信息
Center for Crohn's and Colitis, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.
Center for Clinical Epidemiology, Odense University Hospital, and Research Unit of Clinical Epidemiology, University of Southern Denmark, Odense, Denmark.
出版信息
Reprod Toxicol. 2017 Oct;73:196-200. doi: 10.1016/j.reprotox.2017.08.013. Epub 2017 Aug 24.
PURPOSE
We examined the effect of preconception paternal use of azathioprine (AZA)/6-mercaptopurine (6-MP) or methotrexate (MTX) and the risk of adverse long-term outcomes in the offspring.
METHODS
This study included all children born in Denmark from 1 January 1997 through 2013. Exposed cohort: children fathered by men who used AZA/6-MP (N=735) or MTX (N=209) within three months before conception; unexposed cohort: children fathered by men who did not use AZA/6-MP/MTX (N=1,056,524).
OUTCOMES
malignancies, autism spectrum disorders (ASD)/schizophrenia/psychosis, and attention deficit hyperactivity disorder (ADHD).
RESULTS
Outcomes: of children: AZA/6-MP exposure: one with leukemia (0.14%), one with ASD/schizophrenia (0.14%) and three with ADHD (0.41%); MTX exposure: three with ADHD (1.4%). Unexposed: 1710 with malignancies (0.16%), 2107 with ASD/schizophrenia (0.20%), 2799 with ADHD (0.26%). Median follow up times were 6.7 [IQR:3.6-11.3] and 9.9 [IQR:5.7-14.3] years respectively.
CONCLUSIONS
There was no negative impact of paternal preconception use of AZA/6-MP/MTX on selected childhood health outcomes.
目的
我们研究了准父亲在受孕前使用硫唑嘌呤（AZA）/6-巯基嘌呤（6-MP）或甲氨蝶呤（MTX）的情况及其对子代不良长期结局的风险。
方法
本研究纳入了 1997 年 1 月 1 日至 2013 年期间在丹麦出生的所有儿童。暴露队列：父亲在受孕前三个月内使用 AZA/6-MP（N=735）或 MTX（N=209）的儿童；未暴露队列：父亲未使用 AZA/6-MP/MTX 的儿童（N=1,056,524）。
结局
恶性肿瘤、自闭症谱系障碍（ASD）/精神分裂症/精神病、注意力缺陷多动障碍（ADHD）。
结果
结局：AZA/6-MP 暴露组的儿童：1 例白血病（0.14%）、1 例 ASD/精神分裂症（0.14%）和 3 例 ADHD（0.41%）；MTX 暴露组：3 例 ADHD（1.4%）。未暴露组：1710 例恶性肿瘤（0.16%）、2107 例 ASD/精神分裂症（0.20%）、2799 例 ADHD（0.26%）。中位随访时间分别为 6.7[IQR：3.6-11.3]和 9.9[IQR：5.7-14.3]年。
结论
父亲在受孕前使用 AZA/6-MP/MTX 并未对选定的儿童健康结局产生负面影响。
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