Abstract

Background Depression is common during pregnancy and increasing numbers of women are being prescribed antidepressant medications during pregnancy - especially Selective Serotonin Reuptake Inhibitors (SSRIs). There is emerging evidence suggesting that maternal use of SSRIs may be associated with an increased risk of congenital defects and adverse neurodevelopmental outcomes. One suggestion is that prenatal exposure to maternal depression or SSRIs might influence offspring health through a mechanism involving DNA methylation. The aim of this study was to investigate the association between SSRI exposure during pregnancy and methylation changes in the cord blood of the newborn. Methods We measured DNA methylation at over 850,000 CpG sites in cord blood from 176 newborns in the Aarhus Birth Cohort, selected according to maternal depression or SSRI use status. We carried out epigenome-wide association studies to compare DNA methylation between three groups: (1) SSRI use during pregnancy (n=88); (2) non-medicated depression during pregnancy (n=44); (3) unexposed=no depression or SSRI use during pregnancy (n=44). We performed a single-site regression analysis and a regional analysis adjusting the results for the following covariates: Maternal smoking, parity, maternal age at delivery, the use of other types of medication and Socio-Economic Status (SES), batch effects, and estimated cell composition. Results We found 99 unique Differentially Methylated Regions (DMRs) when comparing the three exposure groups. 18 DMRs were specific to the SSRI exposed compared to the unexposed, and 53 DMRs were specific to the depressed, non-medicated group vs. the unexposed. 27 DMRs were specific to the SSRI exposed compared to the non-medicated, depressed group. Finally, 1 DMR was found in both the SSRI exposed group and the depressed, non-medicated group. Discussion Prenatal exposure to untreated depression was associated with more DNA methylation differences in the newborn than prenatal exposure to SSRIs. Further research is warranted to confirm these findings and investigate causality.

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