Introduction: Maternal depressive symptoms during pregnancy are associated with a range of adverse neurodevelopmental outcomes in offspring. DNA methylation, influenced by both genetic and environmental factors, has been identified as a potential mechanism mediating these associations. Because the placenta serves as an interface between mother and fetus, epigenetic marks in this tissue may provide insights into how the intrauterine environment influences child outcomes. The present study aimed to determine whether maternal Edinburgh Postnatal Depression Scale (EPDS) scores in mid-pregnancy (20 + 6 to 30 + 0 gestational weeks) are associated with placental DNA methylation marks and whether these marks differ from those associated with EPDS scores in early pregnancy.

Methods: In this descriptive analysis, the DNA methylomes of placental samples collected at birth from 91 women in the FinnBrain cohort were analyzed using reduced representation bisulfite sequencing. The association of EPDS with DNA methylation of each CpG site was examined using the PQLseq.

Results: A total of 1345 CpG sites in 381 genes were identified with FDR ≤0.05, suggesting a potential association with mid-pregnancy EPDS scores. The most significant methylation marks were found in the following genes: PTPRO, RPTOR, TBX1, SLC7A4, FBRSL1, and ADAMTS17. When accounting for early pregnancy EPDS scores, 272 methylation marks remained significant. The genes were functionally enriched in biological pathways such as cell adhesion, nervous system development, and anatomical structure development. Compared with methylation marks associated with early pregnancy EPDS scores, similar methylation marks were found in 29 distinct genic regions. Further studies are needed to determine whether these methylation marks mediate the effects of maternal depressive symptoms on the fetus.