Prenatal Maternal Stress
Allostatic load is the physiological and psychological wear and tear that comes from a person’s cumulative experiences of stress over their lifetime. During times of stress, the body changes physiologically to adapt and respond appropriately to the stressor. Once the stressor is gone, the body usually returns to the normal set point, known as homeostasis. Chronic stress responses, however, result in a new set point and can be damaging. Evidence suggests that a high allostatic load can lead to adverse pregnancy outcomes, low birth rates, perinatal mortality, and lifelong disease in offspring (e.g., diabetes, obesity, neurological changes.) Some stressors we know contribute to adverse pregnancy outcomes include adverse childhood experiences, racial disparities, a prenatal history of abuse, and so on. Unfortunately, a person’s allostatic load is not limited to the here and now but is transmitted and amplified through multiple generations by genetic and epigenetic mechanisms.
Figure 1: Allostatic Load Leads to Multiple Disease States
An allostatic load that exceeds a person’s psychological and physiological resilience increases their risk for many disease states, including preterm birth. This allostatic load can also be passed down to offspring increasing their risk for lifelong disease. Taken from Olson, DM et al. International Journal of Molecular Sciences 2015).
We study the physiological and behavioural effects of maternal and paternal prenatal stress on parents and offspring in rats with Prof. Gerlinde Metz. We expose these rats to several stressors, including psychological (e.g., social isolation, restraint, or forced swimming) and immune stress (injection of IL-1β). We measure how these stressors influence gestation length, maternal and offspring weights, hormone levels (e.g., cortisol), inflammatory factors (e.g., cytokines, prostaglandins), brain morphology, metabolic factors (e.g., glucose), anxiety, and behaviours. From this work, we’ve learned that single stressors have different outcomes on mothers and offspring compared with multiple stressors, and these outcomes vary based on the species, time of exposure, duration of stress, and the sex of the offspring.
We also look at the transgenerational effects of a stressor on offspring up to the F3 generation in these animals. Through these studies, we determined that parental stressors influence the offspring’s risk for preterm birth. Understanding the transgenerational influences of events and environmental factors is critical for the evolution of precision medicine.
Sudden and Acute Stressors:
Pregnant or postpartum women and babies are highly vulnerable during a natural disaster or other acutely stressful events. As climate change progresses, we expect an increase in the frequency and severity of natural disasters, famines, military conflicts, and migration. Previous studies of prenatal maternal stress during natural disasters demonstrate that it can lead to preterm birth and/or long-term cognitive and physiological consequences in the offspring. We need to understand how these events affect both mother and baby to develop inexpensive and easy-to-implement therapies to improve maternal resilience and health outcomes.
Our team studied the effectiveness of expressive writing in women who were pregnant during or soon after the Fort McMurray wildfires of 2016. There, we developed methods that we have shared with other teams worldwide, studying other traumatized groups such as women who lived through Hurricane Harvey or migrants in Europe.
The Olson Lab is developing tools to diagnose and provide interventions to women at risk for preterm birth. Part of that process is understanding who is at risk. Together with our collaborators, we hope to harness the power of data and artificial intelligence to identify the combination of risk factors that best predict preterm birth. Allostatic load, and the resultant biomarkers of stress, are an essential part of that equation.
Our animal models provide critical information revealing the biological pathways that connect stress to preterm birth. Using “omics” techniques, we delineate the full spectrum of physiological changes in mothers in their response to stress. Our studies aim to understand these connections well enough to develop strategies to diminish the effects of stress on mothers and their offspring.
Figure 2: Allostatic Load and Preterm Birth Conceptual Framework: This framework demonstrates how an individual’s allostatic load includes the generational inheritance of stressors, lived experiences, and the individual’s physiological and psychological capacity to respond. Once this allostatic load exceeds their capacity to adapt, it leads to physiological responses that reflect risks for preterm birth (See Pathway to Preterm Birth). Maternal allostatic load and the experience of preterm birth are then passed to the next generation by genetic and epigenetic mechanisms.