Paternal medications and congenital malformations in offspring

父亲用药与后代先天性畸形

• 批准号: 9755241
• 负责人: MICHAEL L EISENBERG
• 金额: $ 17.02万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-06 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9755241
• 关键词: Acute; Affect; Age; Anatomy; Anti-Anxiety Agents; Antidepressive Agents; Antihypertensive Agents; Antineoplastic Agents; Birth; Birth Order; Birth Weight; Characteristics; Chemicals; Child; Chromosome abnormality; Chronic Disease; Classification; Comorbidity; Conceptions; Congenital Abnormality; Counseling; Couples; DNA; Data; Denmark; Development; Exposure to; Fathers; Fertilization; Gestational Age; Health; Impairment; Incidence; Individual; Lead; Link; Live Birth; Marital Status; Medical; Medicine; Modeling; Morphology; Mothers; Occupational Exposure; Outcome; Parents; Paternal Exposure; Patients; Pharmaceutical Preparations; Pregnancy; Pregnant Women; Production; Recommendation; Registries; Research Design; Research Personnel; Risk; Risk Factors; Role; Safety; Seminal fluid; Smoking; Sperm Count Procedure; Sperm Motility; Spermatogenesis; System; Therapeutic; Time trend; United States; Woman; antimicrobial; base; cell motility; dosage; electronic registry; father role; fetal; high risk; interest; medication safety; men; offspring; parity; primary outcome; prospective; reproductive; sperm cell; trend

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.

在美国，先天性出生缺陷影响了3%的出生。有几个父母因素被证明 改变发病率。吸烟、年龄增长以及母亲和母亲的某些职业暴露 父亲会增加孩子出生缺陷的风险。然而，考虑到更长和更明显的影响， 在母亲怀孕期间，大多数出生缺陷的危险因素都集中在妇女身上。然而，随着年龄的 在发达国家，受孕时的父亲身份增加，父亲合并症增加。与此同时，更多 准父亲在精子发生周期中暴露于处方药，这导致了生活质量的下降。 出生我们就父亲暴露于药物方面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暴露于某些药物的患者进行了研究。 强烈怀疑影响精子DNA的药物（例如抗肿瘤药物）。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，迄今为止， 尽管精子在受精中起着至关重要的作用， 几天的发展。在男性中，当检查生殖系统时， 药物的安全性在于精液质量。因此，男性被告知哪些药物可能会降低精子 浓度、运动性或形态学。然而，这可能是不够的，因为一些常见的药物可能会影响 精子的DNA完整性，大量精液参数变化不大（例如抗抑郁药）。毫不奇怪的是， 许多准父母担心父亲的药物对胎儿的风险。这个项目探讨了 父亲用药与不良出生结果之间的关联，包括先天性出生缺陷。 使用唯一的国家识别号码，我们将把丹麦人口统计、出生、健康和药物联系起来， 从1995年到2015年，大约有130万名新生儿登记。接下来，我们将确定个人 父亲在怀孕前服用的具有已知生精作用的药物或药物类别 怀孕与先天性出生缺陷的风险较高有关。这些发现可能会有广泛的 对试图怀孕的夫妇的影响，并为怀孕期间的药物安全性提供指导。 生殖努力。

项目成果

Balsalazide Exposure During the Development of Fertilizing Sperm May Be Associated With Offspring Birth Defects.

受精精子发育过程中接触巴柳氮可能与后代出生缺陷有关。

• DOI: 10.1093/ibd/izac038
• 发表时间: 2022
• 期刊: Inflammatory bowel diseases
• 影响因子: 4.9
• 作者: Wensink,MaartenJ;Streett,SarahE;Damkier,Per;Lindahl-Jacobsen,Rune;Kjeldsen,Jens;Eisenberg,MichaelL
• 通讯作者: Eisenberg,MichaelL

Impaired fecundity as a marker of health and survival: a Danish twin cohort study.

• DOI: 10.1093/humrep/deab077
• 发表时间: 2021-07-19
• 期刊: Human reproduction (Oxford, England)
• 作者: Ahrenfeldt LJ;Möller S;Wensink MJ;Eisenberg ML;Christensen K;Jensen TK;Lindahl-Jacobsen R
• 通讯作者: Lindahl-Jacobsen R

Nervous system drugs taken by future fathers and birth defects in offspring: a prospective registry-based cohort study.

• DOI: 10.1136/bmjopen-2021-053946
• 发表时间: 2022-03-30
• 期刊: BMJ open
• 影响因子: 2.9
• 作者: Wensink M;Lu Y;Tian L;Jensen TK;Skakkebæk NE;Lindahl-Jacobsen R;Eisenberg M
• 通讯作者: Eisenberg M

Paternal prescription medication before conception: A retrospective cohort study of all births in Denmark 1997-2017.

• DOI: 10.1177/1403494820987468
• 发表时间: 2021-12
• 期刊: Scandinavian journal of public health
• 影响因子: 3.4
• 作者: Wensink MJ;Rizzi S;Jensen TK;Skakkebaek NE;Lu Y;Lindahl-Jacobsen R;Eisenberg ML
• 通讯作者: Eisenberg ML