Intergenerational Transmission of Maternal Childhood Maltreatment Exposure: Implications for Fetal Brain Development

Abstract

Objective Growing evidence suggests the deleterious consequences of exposure to childhood maltreatment (CM) may not only endure over the exposed individual’s life span, but also may be transmitted across generations. The time windows, mechanisms, and targets of such intergenerational transmission are, however, poorly understood. The prevailing paradigm posits that mother-to-child transmission of the effects of maternal CM likely occurs after her child’s birth. We seek to extend this paradigm, and we advance here a trans-disciplinary framework that integrates the concepts of biological embedding of life experiences and fetal origins of health and disease risk. Method We posit that the period of embryonic and fetal life represents a particularly sensitive time for intergenerational transmission; that the developing brain represents a target of particular interest; and that stress-sensitive maternal-placental-fetal biological (endocrine, immune) pathways represent leading candidate mechanisms of interest. Results The plausibility of our model is supported by theoretical considerations and empirical findings in humans and animals. We synthesize several research areas and identify important knowledge gaps that may warrant further study. Conclusion The scientific and public health relevance of this effort relates to achieving a better understanding of the “when,” “what,” and “how” of intergenerational transmission of CM, with implications for early identification of risk, prevention, and intervention.

Research Review: Intergenerational transmission of disadvantage: epigenetics and parents' childhoods as the first exposure

“…Buss et al. () note that epigenetic inheritance (i.e., transmission of epigenetic marks) is often confused with de novo production of stable epigenetic alterations in the offspring. While not technically intergenerational epigenetic inheritance, such prenatal de novo epigenetic changes in offspring of parents who experienced early life adversity could constitute an epigenetic mechanism by which the effects of adversity might be propagated in the subsequent generation if the epigenetic reprogramming in utero is dependent on biological factors in the mother caused by early life adversity.…”

“…Early life stress in the mother appears to alter the placental environment regardless of a women's health and experiences during pregnancy, affecting fetal development or even causing de novo epigenetic changes in the developing embryo that could mimic the epigenetic changes identified in the mother. One way this could happen is that maternal early life adversity might produce alterations in her egg cell cytoplasm (such as mitochondria, proteins, and RNA molecules) that, after conception, exerts an influence on the developing embryo or fetus (Buss et al., ). Another possibility is that increased placental concentrations of endocrine and immune stress mediators (caused by early life adversity in the mother) could cause alterations in the expression of miRNA and DNA methylation in the fetal brain, which could result in changes in fetal cell proliferation, neuronal differentiation, gliogenesis, availability of neurotrophic growth factors, cell survival, synaptogenesis, neurotransmitter levels, myelination, and adult neurogenesis (Babenko, Kovalchuk, & Metz, ; Buss, Entringer, Swanson, & Wadhwa, ).…”

Exposure to traumatic events in childhood predicts cortisol production among high risk pregnant women

“…Offspring of mothers who experienced early life trauma and post-traumatic stress are at greater risk for adverse mental health outcomes, (Collishaw, Dunn, O’Connor, & Golding, 2007; Yehuda, Halligan, & Bierer, 2001) reduced intracranial volume (Moog et al, 2018), and altered stress physiology, including lower levels of cortisol (a key stress hormone and glucocorticoid) at baseline and over a 24 hour period in comparison to non-exposed controls (Brand et al, 2011; Yehuda, Halligan, & Grossman, 2001). Pathways proposed to underlie this transfer of risk from mother to offspring include shared environmental risk factors, parenting behaviors, and epigenetic inheritance (Buss et al, 2017; Bowers & Yehuda, 2016; Yehuda & Meany, 2018). Another complimentary but less frequently considered pathway is the biological embedding of mothers’ early traumatic experiences on her stress physiology and the resulting impact on the prenatal environment (Buss et al, 2017; Bowers & Yehuda, 2016; Moog et al, 2016).…”

“…Pathways proposed to underlie this transfer of risk from mother to offspring include shared environmental risk factors, parenting behaviors, and epigenetic inheritance (Buss et al, 2017; Bowers & Yehuda, 2016; Yehuda & Meany, 2018). Another complimentary but less frequently considered pathway is the biological embedding of mothers’ early traumatic experiences on her stress physiology and the resulting impact on the prenatal environment (Buss et al, 2017; Bowers & Yehuda, 2016; Moog et al, 2016). This is a plausible pathway, because childhood traumatic experiences exert a lasting biological imprint that persists into adulthood (Heim et al, 2000; Heim et al, 2002).…”

Thinking Across Generations: Unique Contributions of Maternal Early Life and Prenatal Stress to Infant Physiology

“…7 These findings are consistent with life course theory, which posits that health trajectories are influenced by recent events and reflect cumulative exposure, suggesting that consideration of both current stressors and experiences across a mother’s lifespan are needed to understand intergenerational health disparities. 8,9 An infant’s developing ANS, and therefore future self-regulation and mental health risk, are likely influenced by a combination of a mother’s experience of prenatal stress and her own earlier exposures to adversity. 2,10 No previous study has examined concurrently maternal ACE exposure and prenatal stress on her child’s ANS regulation.…”