Prenatal Medication Exposure, DNA Methylation and Child Neurodevelopment

Abstract

Approximately 4 in 5 women use medication(s) during pregnancy. Yet, women also report concerns about the fetal safety of medications, as studies find associations between medication exposure before birth (i.e., prenatally) and abnormal brain development in the child. Understanding the mechanisms underlying these associations is important: it may guide the development of novel therapeutics and identify prognostic markers of brain developmental conditions. One suggested mechanism includes DNA methylation (DNAm), whereby small molecules attach to our DNA, and may turn genes on or off. To this end, this thesis explored the relationship between prenatal exposure to paracetamol or the antidepressant escitalopram, DNAm in umbilical cord blood and brain development. We found no association of exposure to medications with DNAm. However, DNAm at birth was associated with delayed child language and motor development, suggesting that DNAm may support early risk detection of developmental conditions. When we systematically reviewed the literature, we identified no overlapping findings between studies, albeit methodological differences made comparisons challenging. Additionally, we uncovered discrepancies in measured DNAm levels between technologies, potentially impacting findings. In conclusion, the research field faces challenges, but improvements of methodologies and technologies hold promise for more robust results of clinical value in the near future.