Paternal medications and congenital malformations in offspring

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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.