Background Serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants for Major Depressive Disorder (MDD), and prenatal exposure to SSRIs has been associated with brain changes in newborns. Although few human studies have reported these changes, they may explain the increased risk for depression after in-utero exposure to SSRIs. This review analyzes findings from a small number of studies to explore SSRI-induced changes in the developing hippocampus and other regions associated with depression. Methods A literature search using key phrases such as “perinatal SSRIs,” “hippocampal changes,” and “fetal brain development” between April-July 2024 yielded six human and 17 rodent studies exploring the potential effects of prenatal exposure to SSRIs on fetal brain areas linked to depression vulnerability. Results Four of the six reviewed studies in human subjects revealed significant changes in corticofugal and corticothalamic tracts after prenatal SSRI exposure. Two human studies showed increased amygdala volume and one preliminary study found decreased hippocampal volume. One study reported global brain changes, which contradicted another. Compared to only one study in human subjects, fifteen of seventeen rodent studies revealed hippocampal changes after SSRI exposure, with reduced BDNF exon mRNA. Two of the studies also reported decreased serotonin and dendritic density. Some inconsistent findings regarding hippocampal DNA methylation, cell proliferation, and synaptic density were reported. Conclusion This review reinforces the connection between in-utero exposure to SSRIs and an increased risk for depression. More research is required to confirm the findings from the reviewed studies, including the risk of increased vulnerability to depression and decreased treatment response.