Paving ways for personalizing drug therapy during pregnancy: A focus on the risk of drug teratogenicity

Medication use during pregnancy is very common, but can potentially harm the unborn child. Many studies have evaluated the safety of certain medications, but data are still lacking. The level of medication exposure of the unborn child also differs because of differences between individual mothers and fetuses. In this thesis, we explore the parameters that can be associated with a higher risk of birth defects following the use of certain medications.

In the first section, we focus on the role of placental transporter proteins in fetal exposure to medication. The transporter protein P-glycoprotein (P-gp) was found to play a significant role in limiting fetal exposure to certain medications. The use of P-gp inhibitors together with these medications was shown to increase the risk of birth defects. Furthermore, genetic variations of transporter proteins may affect their role in fetal protection.

In the second section, we explore genetic variations that might affect the risk of birth defects caused by medication use. We focus on the use of serotonin reuptake inhibitors (SRIs), a group of antidepressants, and the risk of heart defects. Several genetic differences are involved in the body’s reaction to SRIs and the development of heart defects. A study was performed to identify genetic differences that affect the risk of heart defects among children whose mothers had used SRIs during the first trimester of pregnancy. We found indications for a role of genetic differences and anticipate further exploration in this field to promote personalized medication use among pregnant women.