Currently, thousands of pregnant women in the EU and worldwide are being prescribed medications for which we do not have sufficient information on fetal safety. We believe that our current understanding of safety pharmacology is oversimplified and that medication prescribed during pregnancy may play an unrecognized role in the development of neurodevelopmental disorders.
About the project
The lack of knowledge stands in disturbing contrast to the frequent use of analgesics and psychotropic medications, and the public demand for information about the long-term safety on the child’s developing brain. As pregnant women cannot be included in randomized controlled trials due to ethical considerations, we need to find alternative methods to establish fetal safety. As learned from the thalidomide catastrophe, results from animal studies cannot be directly extrapolated to humans and the structure or activity of the drug is generally not predictive of teratogenesis. Therefore, prospective, long-term pharmacoepidemiological studies among pregnant women offer the only real solution to fill the gap of knowledge concerning safety of pharmaceuticals in pregnancy.
The precise molecular mechanisms of most teratogenic processes are unknown but altered patterns of DNA methylation, which result in aberrant gene expression, are thought to play a vital role. With the recent juncture between availability/affordability of genome-wide mapping of DNA methylation, our research proposal has just come within reach.
The size and richness of the available human data in this project - including epidemiological data of more than 100,000 pregnancies in combination with DNA samples (>90,000) and three nation-wide registries - makes this project unique worldwide.
Objectives
The research proposal is divided into two parts, Work Part 1 (WP1) and Work Part 2 (WP2) (Fig 1).
Work Part 1. Pharmacoepidemiological
This part will use an analytical strategy to narrow down the most relevant psychotropic groups and neurodevelopmental outcomes during using a series of different epidemiological designs and biostatistical approaches to strengthen causal inference.
Work Part 2. Pharmacoepigenetics
This part will make use of the most significant findings from to perform epigenetic analyses, such as global DNA methylation (Figure 2).
Together, the two parts will determine whether changes in epigenetic modifications increase the risks of neurodevelopmental disorders in childhood. This opens a new research field and creates a paradigm shift in the field of drug safety, reaching far beyond today’s knowledge of how pharmaceuticals work.
In conclusion, this advance could potentially provide us with the missing links in our understanding of pharmacology and toxicology in pregnancy and fetal origins of neurodevelopmental disorders. The implications will not only be for how we treat pregnant women, but how we use pharmaceuticals in any patient population.
Full name of this project: Effects of Medication Use in Pregnancy on Infant Neurodevelopment
ERC Starting grant
Project period:
2015 - 2020
This project is funded by the European Union