Epigenetic trajectories in early childhood following perinatal parental stress – insights from the DREAM study

• Applicants: Professorin Nina Alexander, Ph.D.; Professorin Susan Garthus-Niegel, Ph.D.; Dr. Susann Schmiedgen
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 495984244

Accumulating evidence suggests that a mother’s stress level during pregnancy has lasting effects on the development of her child. In this regard, epigenetic signatures such as DNA methylation have emerged as central mechanisms explaining how prenatal maternal stress (PNMS) may get under the skin. Importantly, the few epigenetic studies in this field so far mostly rely on broad retrospective measures of PNMS or assess the epigenetic state at or shortly after birth. To address this gap, the Dresden Study on Parenting, Work, and Mental Health (DREAM; “DResdner Studie zu Elternschaft, Arbeit und Mentaler Gesundheit”) is ideally suited to delineate biological pathways by which prenatal and early postnatal parental stress exposures longitudinally impact on child development. Launched in June 2017, the DREAM study is a prospective cohort study including a total of N = 3,865 individuals expecting a child to assess perinatal stress on a psychological, social, clinical, and biological level during the course from late pregnancy to 4.5 years postpartum, with planned extension into middle childhood. While most prior epigenetic studies focused on severe forms of PNMS an explicit aim of the DREAM study is to investigate a widely neglected source of PNMS, namely the role of work-related stress of the (expectant) mothers. In addition, the DREAM study will further allow to evaluate combined effects of multiple PNMS exposures on the fetal epigenome. While the role of the (becoming) father has been widely neglected in PNMS studies, the assessment of stress exposure in both parents posits a significant strength, e.g., in order to disentangle the effects of PNMS from those of the shared genetic susceptibility. In summary, this project aims to test the hypothesis that cumulative PNMS in general and work-related stress in specific provoke a longitudinal trajectory of epigenetic changes in young children (∼4.5 years) that, in turn, predict early health outcomes. To this end, we will estimate stress-related epigenetic risk scores (ERS) derived from summary statistics of prior epigenome-wide association studies on PNMS, internalizing symptoms, cortisol output, and epigenetic aging. Use of such ERS reflects a powerful strategy to aggregate small effects of single loci, which can then serve to robustly predict health phenotypes. As a secondary goal, we seek to evaluate independent and combined effects of PNMS and early postnatal parental stress during the first years of life on respective ERS. A third goal of the proposed project is to investigate whether ERS mediate changes in stress-related health outcomes (e.g., acute and long-term cortisol output, internalizing symptoms) following exposure to PNMS. Providing an in-depth understanding of the molecular pathways underlying fetal origins of health and disease has now become a public health concern of high priority with the long-term goal of delivering evidence-based prevention strategies.

• DFG Programme: Research Grants