Abstract
Paracetamol is the most used painkiller in pregnancy and is generally considered safe. However, in the last decade, several large studies demonstrated a connection between long-term use of paracetamol during pregnancy with an increased risk of developing attention-deficit hyperactivity disorder (ADHD).
This thesis presents a protocol for a 20-day conversion of human embryonic stem cells to immature brain cells. Cell changes were analyzed with single-cell whole-genome sequencing technology. The protocol was designed for investigating potential effects that common medications might have on human brain development.
In the second part of this thesis, this protocol is used to investigate paracetamol’s effects on neuronal cell development. After paracetamol-exposure, the cells were delayed in their development. These subtle changes caused by paracetamol might offer a mechanistic explanation of the observed risk for ADHD after embryonal/fetal exposure. Discovering subtle damaging effects of a “safe” drug, like paracetamol, might be difficult in currently used safety-testing. Therefore, it is reasonable to take extra precautions when classifying drugs as safe to use in pregnancy.