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

•This conceptual review proposes mechanisms driving the Weathering Effect.•Danger signaling may mediate psychosocial effects on spontaneous abortion risk.•Stress effects on early pregnancy neuroendocrine and immune regulation are reviewed. 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