Introduction Selective serotonin reuptake inhibitors (SSRIs) are the most prescribed antidepressants for pregnant women. While SSRIs are known to alter the circulating metabolic profile in non-pregnant individuals, the association between SSRIs and the changes in circulating metabolome during pregnancy remains unstudied. Pregnancy itself induces significant metabolic adjustments to meet the increased nutritional demands, and these maternal metabolic changes are crucial for the normal development and growth of the fetus.

Objectives To study the impact of SSRI usage on circulating maternal metabolome during pregnancy.

Methods A targeted nuclear magnetic resonance (NMR) spectroscopy method was used to analyze maternal serum samples obtained from the 1st trimester of pregnancy and at the time of the delivery from both SSRI users (n =122) and non-depressive controls without antidepressants (n =117) for concentrations of metabolites and lipoproteins.

Results During the 1st trimester of pregnancy, SSRI usage was associated with increased lipid content in sixteen very low-density lipoprotein (VLDL) and chylomicron subtypes. At delivery, SSRI users exhibited alterations in lipoprotein lipid and fatty acid ratios. Similarly, while investigating the influence of SSRI usage on the pregnancy-driven changes in the metabolome, the interplay between pregnancy progression and SSRI usage lowered the lipoprotein lipid ratios.

Conclusion Our analysis revealed a significant association between SSRIs and lipid metabolism. However, the observed changes were minor, suggesting a limited clinical impact. The findings enhance our understanding of the safe usage of SSRI medication during pregnancy.

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

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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Ethics approval was obtained from the Research Ethics Committee of the Hospital District of Central Finland in Jyvaskyla, Finland on November 15, 2011 (18U/2011).

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