Stress is deined as a condition or adverse circumstance that disturbs the normal physiological or psychological functioning of an individual. Examples of stressors are nutrient restriction, obesity, infection, and diabetes. Psychological duress can include racial discrimination, childhood stress, depression, or posttraumatic stress syndrome (Gillespie, 2017; Goldstein, 2017; Shaw, 2017). A quantitative measure of "stress" is difficult. Yet, considerable evidence shows a correlation between some degree of maternal stress and adverse birth outcomes that include stillbirth, preterm birth, and abnormal fetal development (Hobel, 2003; Ruiz, 2003). Factors that activate this cascade likely are broad and inluence the stress response.
One potential mechanism for stress-induced preterm birth is premature activation of the placental-adrenal endocrine axis. One trigger may be elevations in cortisol from maternal psychological stress (Lockwood, 1999; Petraglia, 2010; Wadhwa, 2001). Activation of this axis yields rising maternal serum levels of placentalderived corticotropin-releasing hormone (CRH). This raises adult and fetal adrenal steroid hormone production and promotes early loss of uterine quiescence (Fig. 21-10, p. 410).
If preterm delivery is associated with early activation of the fetal adrenal-placental endocrine axis, maternal estrogen levels would likely be prematurely elevated. Indeed, an early rise in serum estriol concentrations is noted in women with subsequent preterm labor (Heine, 2000; McGregor, 1995). Physiologically, this premature rise in estrogen levels may alter myometrial quiescence and accelerate cervical ripening.
Another mechanism by which stress may translate to preterm birth is premature cellular senescence. As part of normal physiology, aging of fetal and decidual cells precipitates the release of uterotonic signals for uterine activation at term (Menon, 20 14a). Animal studies supported by correlative studies in women demonstrate that accelerated senescence of the decidua results in preterm birth (Cha, 2013; Hirota, 2010). In addition, premature cellular senescence may contribute to PPROM (Menon, 2016).
In most cases, premature cervical remodeling precedes premature labor onset. In some instances, cervical dysfunction of either the epithelia or stromal extracellular matrix is the underlying cause. For example, an intact cervical epithelial barrier is critical to prevent ascending infection. Disruption of this barrier, such as that in mice lacking the glycosaminoglycan hyaluronan, predisposes mice to ascending infection and preterm birth (Akgul, 2014). Interestingly, the enhanced risk of preterm birth from group B streptococcal colonization may be in part due to the bacteria's ability to secrete hyaluronidase. his enzyme degrades hyaluronic acid in the cervicovaginal epithelia to aid bacterial ascension (V ornhagen, 2017).
Second, the mechanical competence of the cervix can be reduced. For example, genetic mutations in components of collagen and elastic fibers or proteins required for their assembly are risk factors for cervical insuiciency, PPROM, and preterm birth (Anum, 2009; Nallasamy, 2017; Pyeritz, 2000).