Paternal medications and congenital malformations in offspring

在美国，先天性出生缺陷会影响3%的新生儿。有几个父母因素被证明是 修改关联。吸烟、年龄增长和某些职业暴露对母亲和 父亲会增加孩子出生缺陷的风险。然而，考虑到一个更长期和更明显的影响 母亲已经怀孕，大多数出生缺陷的危险因素都集中在女性身上。然而，随着年龄的增长， 在发达国家，怀孕时的父子关系增加，父亲的共生症也增加。有了这些，就会有更多 未来的父亲在精子发生周期中暴露在处方药中，这将导致生命 出生。我们就父亲的药物暴露向患者提供充分咨询的能力受到以下因素的限制 稀疏数据。研究人员对有限数量的患者进行了研究，这些患者接触了某些 极有可能影响精子DNA的药物(如抗肿瘤药物)。然而，研究的局限性 设计使得向患者提出明确建议的能力具有挑战性。此外，到目前为止， 尽管精子在受精过程中起着关键作用，但对各种药物的研究却很少 几天的开发时间。在男性中，在检查 药物的安全性在于精液质量。因此，男性会被建议服用哪些药物可能会降低精子 注意力集中、能动性或形态。然而，这可能是不够的，因为一些常见的药物可能会影响 在批量精液参数(如抗抑郁剂)几乎没有变化的情况下，精子的DNA完整性。不足为奇的是， 许多潜在的父母担心父亲的药物对胎儿的风险。这个项目探索了 父亲用药与包括先天出生缺陷在内的不良分娩结局之间的关系。 使用唯一的国家识别码，我们将把丹麦的人口、出生、健康和用药联系起来 1995年至2015年约130万人的出生登记。接下来，我们将确定个人是否 父亲在服用前服用的具有已知生精作用的药物或药物类别 怀孕与先天出生缺陷的风险更高有关。这样的发现可能会有广泛的影响 对试图怀孕并为药物安全性提供指导的夫妇的影响 生殖努力。

Congenital birth defects affect 3% of births in the United States. Several parental factors been shown to modify the incidence. Smoking, increasing age, and certain occupational exposures in both mothers and fathers increase the risk of birth defects in children. However, given the longer and more obvious influence a mother has on gestation, most risk factors for birth defects have focused on women. However, as the age of paternity at conception increases around the developed world, paternal comorbidities increase. With that, more prospective fathers are exposed to prescription medications during spermatogenesis cycles, which lead to live births. Our ability to adequately counsel patients regarding paternal exposures to medicines is limited by sparse data. Investigators have performed studies on limited numbers of patients exposed to certain medications strongly suspected of impacting sperm DNA (e.g. anti-neoplastics). However, limitations of study design make the ability to make definitive recommendations to patients challenging. Moreover, to date large studies of diverse medications are rare despite the crucial role the sperm contributes to fertilization and the first few days of development. In men, the most common reproductive endpoint assessed when examining the safety of a medication is semen quality. As such, men are counseled which medications may lower sperm concentration, motility, or morphology. Yet this may be inadequate, as some common medications may affect the DNA integrity of sperm with little change in bulk semen parameters (e.g. antidepressants). Not surprisingly, many potential parents are concerned about fetal risks from the father's medications. This project explores the association between paternal medication use and adverse birth outcomes, including congenital birth defects. Using unique national identification numbers, we will link Danish demographic, birth, health, and medication registries for the approximately 1.3 million births from 1995 to 2015. Next, we will determine if individual medications or classes of medications with known spermatogenic effects taken by fathers just before conception are associated with a higher risk of congenital birth defects. Such findings are likely to have wide implications for couples attempting to conceive and provide guidance for the safety of medications during reproductive efforts.