Analogous to other complex disease processes, multiple coexistent genetic alterations and environmental factors may lead to preterm birth (Esplin, 2005; Velez, 2008; Ward, 2008). For example, inherited mutations in genes regulating collagen assembly may predispose to cervical insuiciency or prematurely ruptured membranes (Anum, 2009; Wang, 2006; Warren, 2007). And, whole blood gene expression and proteonomic biomarkers are now being used to help identiy predictors of preterm birth (Cantonwine, 2016; Heng, 2016).
For both clinical and research purposes, pregnancies with spontaneous preterm labor yet intact fetal membranes must be distinguished from those complicated by preterm prematurely ruptured membranes. Even so, those with spontaneous preterm labor do not constitute a homogeneous group. Among the more common associated findings are multi fetal pregnancy, intrauterine infection, bleeding, placental infarction, premature cervical dilation, cervical insuiciency, hydramnios, uterine fundal abnormalities, and fetal anomalies. Severe maternal illness from infections, autoimmune diseases, and gestational hypertension also raises preterm labor risks.
Despite their diversity, these processes culminate in a common end point-premature cervical dilation and efacement and premature activation of uterine contractions. Importantly, the actual process of preterm labor should be considered a final step stemming from progressive or acute changes that could be initiated days or even weeks before labor onset. Indeed, many forms of spontaneous preterm labor that result from premature initiation of phase 2 of parturition may be viewed in this light (Chap. 21, p. 408). Although the end result in preterm birth is the same as at term with cervical ripening and myometrial activation, recent studies in animal models support the idea that preterm birth is not always an acceleration of the normal process. Diverse pathways to instigate parturition exist and are dependent on the etiology of preterm birth. Four major causes include uterine distention, maternal-fetal stress, premature cervical changes, and infection.
Multifetal pregnancy and hydramnios are well-recognized risks for preterm birth. Early uterine distention likely acts to initiate expression of contraction-associated proteins (CAPs) in the myometrium. he CAP genes that are influenced by stretch include those coding for gap-junction proteins such as connexin 43, for oxytocin receptors, and for prostaglandin synthase (Korita, 2002; Lyall, 2002; Sooranna, 2004). More recent reports suggest that levels of gastrin-releasing pep tides (GRPs) are increased with stretch to promote myometrial contractility. GRP antagonists can inhibit uterine contractility (Tattershell, 2012). Also, a stretch-induced potassium channel-TREK-1is up regulated during gestation and downregulated in labor. his suggests a potential role in uterine relaxation during pregnancy (Buxton, 2010).
Excessive uterine stretch also leads to early activation of the placental-fetal endocrine cascade shown in Figure 21-10 (p. 410). The resultant early rise in maternal corticotropinreleasing hormone and estrogen levels can further enhance the expression of myometrial CAP genes (Warren, 1990; Wolfe, 1988). Finally, the influence of uterine stretch should be considered with regard to the cervix. Prematurely increased stretch and endocrine activity may initiate events that shift the timing of uterine activation, including premature cervical ripening.