The transgenerational impact of maternal early life adversity on infant development
Description
The biological embedding of maternal adversity, both preconception and prenatal, can alter health trajectories of the next generation. Alterations in biological processes, including inflammation and accelerated aging, are proposed mechanisms through which adverse environmental and experiential exposures alter disease risk over the life-course. To identify biological pathways of transgenerational risk, we describe how maternal preconception adversity, assessed by adverse childhood experience score (ACEs), influences the development of her infant’s psychopathology risk and autonomic nervous system (ANS) by examining genomic and epigenomic alterations in both the infant and the placenta. Maternal ACEs elevated her infant’s externalizing behaviors at 18-months of age. Cellular aging, indexed by telomere length (TL) erosion, modified this relation; in infants with greater TL erosion from 4- to 18-months of age, higher maternal ACEs predicted higher externalizing behaviors. At 4-months of age, we examined infant ANS stress physiology and found that higher maternal ACEs predicted lower ANS stress response. Next, we examined TL in the placenta as a pathway conferring transgenerational risk. Higher maternal ACEs predicted shorter placental TL and placental TL modified the impact of maternal ACEs on her infant’s ANS; in placentas with shorter placental TL, higher maternal ACEs predicted greater ANS stress responsivity. To understand the molecular pathways impacted by maternal ACEs and related to TL, we examined placental mRNA expression of an inflammatory gene (CCL2), a gene linked to apoptosis (BCL2), and a gene tied to cellular senescence (GLB1). CCL2 expression modified the relation between higher maternal ACEs and shorter placental TL and CCL2 expression also contributed to the relation between shorter placental TL and decreased BCL2 expression. Lastly, shorter TL moderated the relation between CCL2 expression and both BCL2 and GLB1. The demonstration of the effects of maternal ACE exposure across generations highlights the need to further define the underlying mechanisms contributing to disease risk in the next generation. Maternal ACE exposure effects the placenta, the infant’s ANS, and the infant’s behavior through the first 18-months of life, which highlights the powerful impact of maternal early life adversity across generations and compliments the known lasting health risks found within the individual.