Mechanisms of Teratogenic ADRs

Teratogenesis is the process that results in structural and/or functional defects in a fetus. ^1,7 A teratogen is any agent that can induce teratogenesis. While drugs are most frequently implicated, other potential teratogens include: radiation exposure, Zika virus, and lead exposure. Overall, an estimated 5% of birth defects are believed to be caused by a known teratogen.⁷ Drug teratogenicity depends on the ability of the teratogen to diffuse from the maternal circulation across the placenta. The extent of diffusion depends on the chemical nature of the agent (molecular weight, protein binding capacity, lipid solubility, and pKa) and maternal pharmacokinetic factors.

Teratogens present the greatest risk to the embryo during periods of intense mitotic activity. Exposure to a teratogen from the time of conception to day seventeen results in spontaneous abortion. Exposure to a teratogen during organogenesis, i.e., from day 18 to day 55 results in developmental abnormalities (Figure 5). The period from day 55 through the 3^rd trimester is a period of fetal growth, during which exposure to a teratogen affects organ function.

Figure 5. Periods of Increased Organ-specific Sensitivity of Fetal Tissues to Teratogens.

Figure 5. Periods of Increased Organ-specific Sensitivity of Fetal Tissues to Teratogens.