Reproductive Epidemiology

Shortly after conception and throughout the period until a baby is delivered, vulnerabilities may develop that can lead to diseases that are either present at birth or manifest themselves later in life.

We are therefore mapping to what extent gestation – the time from conception to birth – influences foetal damage and disease, and are also seeking to identify some of the factors causing health conditions. The main focus is on prevention, which means our findings aim to help improve public health. Our research also covers factors that can lead to chronic illnesses – illnesses which may only become evident much later.

Examples of the diseases we study  include birth defects, asthma, diabetes, reduced fertility, and obesity. Investigations look at a wide range of lifestyle factors, such as the pregnant woman’s exposure to coffee, stress, and smoking, and exposure to occupational factors, illness, and medications.

 

Improving child health

Epidemiological studies of reproductive damage require access to data from large populations. In that respect we are very fortunate: In 1996, mainly with funding from the Danish National Research Foundation, we set up a database and began to recruit 100,000 pregnant women and their children and to register information about their state of health and other topics. This database is quite unique, and each year it supplies factual information to about 80 research groups around the world. Its fields of use are wide-ranging, from genetics and occupational medicine to studies of diet, medication use, and smoking and eating habits.

The research done using this database has provided many international contacts, one of which led the Centers for Disease Control and Prevention (CDC) to invest in expanding the database. We also use the registered data when providing expert advice to the National Board of Health and other public authorities that issue specific guidelines for pregnant women.

In addition to epidemiologists, this research group consists of biostatisticians, clinical specialists, neurologists, and IT professionals to handle the large amounts of data involved, as well as geneticists. This last group will become more strongly epresented as the focus on gene–environment interaction intensifies in the future.

 

Projects

  • Exposure to serious stress as a factor in prenatal programming. Women who lose a child or another close family member immediately prior to or during a pregnancy are in a state of elevated stress, which may affect the child’s risk of disease or illness later in life. Animal experiments suggest that such a programming effect does exist; an effect that could potentially lead to obesity, diabetes, or mental problems during the child’s adolescence or adult life.
  • The use of pharmaceuticals during pregnancy. Illnesses occurring during pregnancy must sometimes be treated with medication that could have unknown side effects on the unborn child. We know that certain pharmaceuticals can seriously affect the foetus, but we also know that untreated illness can do damage as well. The data resources we have at our disposal enable us to broaden and deepen our knowledge in this area.
  • Is maternal obesity and alcohol consumption during pregnancy associated with poor semen quality in sons? In order to investigate possible connections, we will be collecting blood and semen samples from about 500 young men. They are sons of mothers who, during their pregnancies, were included in the “Healthy Habits for Two” cohort (1984–87) and answered questions about alcohol consumption and other habits before and during pregnancy, and about their height and weight prior to conceiving. This study is expected to yield valuable information about the causes of impaired semen quality.
  • Age of sexual maturity: Causes and consequences. A study among selected children in the “Better Health for Mother and Child” cohort. We will be collecting information about pubertal development from a group of approximately 14,000 children of mothers who, during their pregnancies in 1999–2002, agreed to participate in the “Better Health for Mother and Child” project (the DNBC), answering questions about a wide range of health and lifestyle factors. The resulting data, collected from the children every six months from the age of 11 and throughout puberty, will undergird numerous studies investigating the causes and consequences of changes in the age of puberty onset.
  • Caffeine metabolites and the risk of miscarriage. The primary aim of this project is to examine the link between the plasma concentration of coffee and its metabolites and the risk of miscarriage. More specifically we will also study whether genotypes for metabolizing caffeine (CYP1A2 and NAT2) are associated with spontaneous abortion, and we will apply the principles of Mendelian randomization to approximate whether such an association (if evidenced) is causal.

 

Milestones

Apgar score predicts ADHD (Li J, et al. J Pediatrics 2011:158(5):775-779).

Pregnant women should adapt their weight increased during pregnancy to their pre-pregnancy weight (Nohr EA, et al. Am J Clin Nutr 2008;87:1750-1759).

The structure and history of the Danish National Birth Cohort (Olsen J et al. Scand J Public Health. 2001 Dec;29(4):300-307).

Antidepressants given to pregnant women (Pedersen LH et al. BMJ. 2009 Sep 23;339:b3569. doi: 10.1136/bmj.b3569).

Alcohol and semen quality(Ramlau-Hansen CH et al. Hum Reprod 2010 Sep;25(9):2340-2345. Epub 2010 Jun 29).

Methods

  • In our work we apply both experimental and observational epidemiological methods. Much of our research is based on longitudinal studies, but we also use case-control studies, particularly for projects that rely on biological data.
  • We use existing population data as well as data gathered by our own unit. The various public registers and databases that exist in Denmark, and which hold information about the entire nation, can provide us with up to 30 years’ follow -up time. Our own follow-up studies cover up to 25 years, in some cases with data collection still ongoing.