Linking reproduction and ageing

Medication and malformations

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.

Yet, 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. The ability to adequately counsel patients regarding paternal exposures to medicines is limited due to 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 plays in 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 about which medications that 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 Danish 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. Our findings are likely to have wide implications for couples attempting to conceive and will provide guidance for the safety of medications during reproductive efforts.

People:
Maarten Wensink
Rune Lindahl-Jacobsen

Fecundity, health and survival

Fecundity may be declining in many Western countries. Up to 15% of all couples in the world are unable to conceive after 12 months. We have demonstrated that male fecundity is a strong biomarker for health and survival. In males, semen quality is a good proxy for fecundity. In females, there is no readily available similar individual measure. Instead, women’s fecundity is often represented by the female part of a couple’s time to pregnancy. Studies in causes and consequences of female fecundity on health and survival have so far been limited. The current project will extend the frontier on the subject through the collaboration between Stanford University and SDU. Taking advantage of the combined excellent resources and opportunities presented by the in-house Danish Twin Registry and a large population-based data set on female fecundity, combined with unique Danish registries, the aim of this study is to: 1) explore the genetic, shared environmental (e.g., shared in foetal life) and non-shared environmental components (e.g., lifestyle) of women’s fecundity, for both the women and their children, and to report potential consequences for their health and survival. We hypothesize that a reduced fecundity could reflect a life in poor health and that this is also reflected in the health of offspring.

Specific aims:

1) To examine possible causes influencing female fecundity in twins and singletons, by investigating: a) Correlations between genes, environment and twin mothers’ fecundity using the Danish Twin Registry, b) Health and fertility among children of monozygotic twins, dizygotic twins and singletons associated with their fecundity, combining data with the Danish health registries 1968-2015.

2) Shed light on potential health consequences of female fecundity in twins and singletons by studying: a) Health of a large cohort of Danish singleton and twin women and their male partners following up for hospitalization and cancer risk in Danish health registries (1943-2016), b) Mortality and specific causes of death for the same study cohorts by means of Danish population registries.

Elucidating possible causes that contribute to reduced fecundity will bring insight into why some have low fecundity, and thus potentially increase the awareness of the individual’s possibility of influencing their fecundity. After revealing possible causal components, we add to the well-known consequences of a couple’s reduced fecundity by implications related to individual health and survival – our preliminary results suggest an important public health perspective.

People:
Rune Lindahl-Jacobsen
Linda Ahrenfeldt

Fertility, family, and health in Nordic countries: A combined genetic-demographic-epidemiological perspective

Reproductive factors and other aspects of people’s family situation likely affect their health, through biological or social pathways, but there is much uncertainty about these effects, not least because the observed relationships may be confounded by genetic and other joint determinants of fertility/family behaviour and health that are hard to control. This project aims to add to the knowledge about these health effects of reproductive and family behavior by combining insights and experiences from genetics, demography and epidemiology. Such knowledge may be helpful to individuals making family decisions, and also serve as important underpinning for political discussions about how to meet the health care needs of a population with increasingly unstable intimate relationships, fewer children and siblings, and later entry into parenthood.

People:
Rune Lindahl-Jacobsen