Metabolomic insights: LC–MS profiling of human placental tissue from SSRI-treated pregnancies

Antenatal depression, a common pregnancy complication, poses significant risks if untreated. Consequently, pregnant mothers are prescribed selective serotonin reuptake inhibitors (SSRIs). Based on their pharmacological action, SSRIs have the potential to disrupt serotonin signaling, which is crucial for placental function and fetal development. SSRIs are associated with adverse effects on both placenta and fetus. Understanding placental metabolism is essential for assessing fetal exposure to SSRIs. However, the association between maternal SSRI use and placental metabolism remains understudied. We performed a comprehensive determination of the placental metabolome by nontargeted liquid chromatography-mass spectrometry metabolomics approach to determine whether SSRIs alter placental metabolic functions. A total of 48 placental samples from individuals using SSRI medication throughout the pregnancy (n = 24) and non-depressive controls without antidepressant medication (n = 24) were included. We observed significant alterations in placental metabolic profiles among individuals using SSRIs, potentially indicating a response to changes in placental redox homeostasis and energy metabolism. Furthermore, four of the altered metabolites were positively correlated with the 1- and 5-min Apgar score in SSRI-treated pregnancies, indicating that higher metabolite levels may correlate with better birth outcomes. Given the limited research on placental metabolomics, our exploratory study provides new insights into SSRI-associated alterations in the placenta.