Preterm birth is a universal health problem that is one of the largest unmet medical needs contributing to the global burden of disease. Adding to its complexity is that there are no means to predict who is at risk when pregnancy begins or when women will actually deliver. Until these problems are addressed, there will be no interventions to reduce the risk because those who should be treated will not be known. Considerable evidence now exists that chronic life, generational or accumulated stress is a risk factor for preterm delivery in animal models and in women. This wear and tear on the body and mind is called allostatic load. This review explores the evidence that chronic stress contributes to preterm birth and other adverse pregnancy outcomes in animal and human studies. It explores how allostatic load can be used to, firstly, model stress and preterm birth in animal models and, secondly, how it can be used to develop a predictive model to assess relative risk among women in early pregnancy. Once care providers know who is in the highest risk group, interventions can be developed and applied to mitigate their risk.

Complex cellular and physiological interactions are required to prepare the uterus for birth. The change from the state of pregnancy to the state of parturition, which we call uterine transitioning, requires the actions of inflammatory mediators and results in an activated uterus capable of performing the physiology of labor. Interleukin (IL)-1β and prostaglandin (PG)F2α are two key mediators implicated in preparing the uterus for labor by regulating the expression of uterine activation proteins (UAPs) and pro-inflammatory cytokines and chemokines. To investigate this process, primary human myometrial smooth muscle cells (HMSMC) isolated from the lower segment of women undergoing elective cesarean sections at term (not in labor) were used to test the inflammatory cytokine and UAP outputs induced by PGF2α and IL-1β alone or in sequential combinations. PGF2α and IL-1β regulate mRNA abundance of the PGF2α receptor FP, the IL-1 receptor system, interleukin 6, and other UAPs (OXTR, COX2), driving positive feedback interactions to further amplify their own pro-inflammatory effects. Sequential stimulation of HMSMC by PGF2α and IL-1β in either order results in amplified upregulation of IL-6 and COX-2 mRNA and protein, compared to their effects individually. These profound increases were unique to myometrium and not observed with stimulation of human fetal membrane (hFM) explants. These results suggest that PGF2α and IL-1β act cooperatively upstream in the birth cascade to maximize amplification of IL-6 and COX-2, to build inflammatory load and thereby promote uterine transition. Targeting PGF2α or IL-1β, their actions, or intermediates (e.g. IL-6) would be an effective therapeutic intervention for preterm birth prevention or delay.

Maternal stress and inflammation excesses can lead to adverse pregnancy outcomes and offspring development. We evaluated whether distinct prenatal stressors affect pregnancy, maternal and offspring outcomes and uterine gene expression differently when combined than either alone. Long-Evans dams were exposed to psychological or/and (two-hit) immune stress (interleukin-1 beta [IL-1β]), on gestational days 12–18 and 17-delivery respectively. Gestational length, maternal weight gain, glycaemia and corticosterone levels, offspring weight and gender effects were recorded. Maternal and offspring uteri were collected at weaning and on postnatal day 160 correspondingly. Uterine expression of genes involved in local progesterone metabolism, neuroendocrine and immune systems were analyzed using qRT-PCR. Maternal two-hit stress increased gestational length variation and the occurrence of adverse pregnancy outcomes while reducing gestational weight gain. Pup weight was negatively affected by prenatal stressors in a gender-specific way. In dams, IL-1β upregulated gene expression of neuroendocrine (Crh, Crhr1) and cytokine genes (Il1b, Il1rn, Il6 and Il10). Conversely, transcriptional patterns in offspring uteri were more variable with gene-specific up- or downregulation by each stressor separately, while exposure to both extensively reduced the expression of neuroendocrine (Hsd11b1), cytokine (Il1a, Il1rn, Il6) and IL-1 receptor genes. In conclusion, maternal stress affects physiological and molecular processes in dams and their offspring; two hits have different effects than single stressors. Outcomes appear generation-, gender- and stressor-specific. Dampening of offspring uterine gene expression after exposure to multiple stressors could fit within the match/mismatch hypothesis of perinatal programming, with offspring preparing for a stressful life.

Following disasters, perinatal women are vulnerable to developing post-traumatic stress disorder (PTSD)-like symptoms. Little is known about protective factors. We hypothesized that peritraumatic stress would predict PTSD-like symptoms in pregnant and postpartum women and would be moderated by social support and resilience. Women (n = 200) who experienced the 2016 Fort McMurray Wood Buffalo wildfire during or shortly before pregnancy completed the Peritraumatic Distress Inventory (PDI), Peritraumatic Dissociative Experiences Questionnaire, and the Impact of Event Scale-Revised for current PTSD-like symptoms. They also completed scales of social support (Social Support Questionnaire-Short Form) and resilience (Connor-Davidson Resilience Scale). Greater peritraumatic distress (r = 0.56) and dissociative experiences (r = 0.56) correlated with more severe PTSD-like symptoms. Greater social support satisfaction was associated with less severe post-traumatic stress symptoms but only when peritraumatic distress was below average; at more severe levels of PDI, this psychosocial variable was not protective. Maternal PTSD-like symptoms after a wildfire depend on peritraumatic distress and dissociation. Higher social support satisfaction buffers the association with peritraumatic distress, although not when peritraumatic reactions are severe. Early psychosocial interventions may protect perinatal women from PTSD-like symptoms after a wildfire.

Purpose: Canada's perinatal, infant and maternal mortality rates were examined and compared with other Organization for Economic Cooperation and Development (OECD) countries. The type and the quality of the available data and best practices in several OECD countries were evaluated. Source: A literature search was performed in PubMed and the Cochrane Library. Vital statistics data were obtained from the OECD Health Database and Statistics Canada and subjected to secondary analysis. Principal Findings: Overall, Canadian pregnancy mortality rates have fallen dramatically since the early 1960's. Perinatal and infant mortality rates remain low and stable, but the maternal mortality rate has increased slightly and both mortality rates have declined in their relative OECD rankings over the last 20 years. Data quality and coverage across Canada and internationally, especially for Indigenous peoples, is inconsistent and registration practices differ greatly, making comparisons difficult. Available data do show that Indigenous people's perinatal and infant mortality rates are nearly twice those of the general population. Best practices in other OECD countries include Australia's National Maternity Services plan to improve Aboriginal perinatal health, the Netherlands' midwifery services and National Perinatal Registry and Japan's national pregnancy registration and Maternal Handbook. Conclusion: To diminish Canadian disparities in perinatal health rates and improve health outcomes we recommend a) uniform registration practices across Canada, b) better data quality and coverage especially among Indigenous communities, c) adoption of a national pregnancy registration and a maternal handbook along with d) improved midwifery and primary practice services to rural and remote communities. At a time when Canada is focusing upon improving pregnancy health in developing nations, it also needs to address its own challenges in improving pregnancy outcomes.