Introduction Antenatal depression, a common pregnancy complication, poses significant risks if untreated. Consequently, pregnant mothers are prescribed selective serotonin reuptake inhibitors (SSRIs).

Methods We performed a comprehensive determination of the placental metabolome by nontargeted liquid chromatography-mass spectrometry (LC-MS) 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.

Results We found significant alterations in glutathione, amino acid, and lipid metabolism, potentially indicating a response to changes in placental redox homeostasis and energy metabolism. Furthermore, four of the altered metabolites were positively associated with the 5-minute Apgar score in SSRI-treated pregnancies, indicating that higher metabolite levels may correlate with better birth outcomes.

Discussion Given the limited research on placental metabolomics, our exploratory study provides new insights into SSRI-induced changes in the placenta.

O.K. is the co-founder of Afekta Technologies Ltd., a company that provides metabolomics analysis services (not used here). A.I., M.L., H.S., L.K-N., and J.R report no competing interests.

This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 825762

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All participants in the KuBiCo study provided a written informed consent. The study was conducted in accordance with the guidelines outlined in the Declaration of Helsinki. Ethical approval was obtained from the Research Ethics Committee of the Hospital District of Central Finland in Jyvaskyla, Finland on November 15, 2011 (18U/2011). The study was conducted in accordance with the Strengthening the reporting of observational studies in epidemiology (STROBE) guidelines.

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