Weathering the storm; a review of pre-pregnancy stress and risk of spontaneous abortion.

The Weathering Effect is a theory that links stress exposure, over the life-course, with racial disparities in reproductive outcomes, through the effects of social adversity on a woman's body. The concept of maternal "weathering" captures cumulative somatic and psychological adversities that can exacerbate the effects of aging. Much of the evidence for weathering comes from observational studies linking self-report measures with reproductive outcomes. The purpose of this review is to explore biological mechanisms that underlie these observations. We focus on spontaneous abortion because this event is understudied despite evidence of racial disparities in this outcome. Spontaneous abortion is the most common pregnancy failure, and it happens early in pregnancy. Early pregnancy is a time most susceptible to the harmful effects of immune dysregulation that may, in part, result from adversities experienced before pregnancy begins. In exploring these mechanisms, we draw on well-defined signaling processes observed in the stressor-depression relationship. Pro-inflammatory dysregulation, for example, has particular relevance to immunological control occurring early in pregnancy. Early pregnancy immunologic changes affect the trajectories of pregnancy via control of trophoblastic invasion. Within the first few weeks of pregnancy, uterine derived cytokines operate within cytokine networks and play a critical role in this invasion. Programming for pro-inflammatory dysregulation can occur before conception. This dysregulation, brought into early pregnancy, has implications for viability and success of the index pregnancy. These patterns suggest early pregnancy health is susceptible to stress processing pathways that influence this immunologic control in the first six to eight weeks of pregnancy. In this review, we discuss the known mediating role of immune factors in the stressor-depression relationship. We also discuss how adversity experienced before the index pregnancy, or "pre-pregnancy" may influence these pathways, and subsequently influence early pregnancy health. There is a need to understand adversity, experienced before pregnancy, and mechanisms driving the effects of these experiences on pregnancy outcomes. This approach is a useful entry point for understanding racial inequities in pregnancy health through an understanding of differences in exposures to adversity. We hypothesize that spontaneous abortion involves cyclical changes within a woman's reproductive tract in response to stressors that are established well before a woman enters into pregnancy. Furthermore, we propose mechanisms that potentially drive weathering processes relevant to reproductive disparities. We also examine what is known about pre-pregnancy stress exposures associated with race, inequity, and adversity, and their potential impact on neuroendocrine and immune changes affecting early pregnancy risk.