The last few hours of human pregnancy are characterized by uterine contractions that effect cervical dilatation and cause the fetus to descend through the birth canal. Long before these forceful, painful contractions, there are extensive preparations in both the uterus and cervix, and these progress throughout gestation. During the first 36 to 38 weeks of normal gestation, the myometrium is in a preparatory yet unresponsive state. Concurrently, the cervix begins an early stage of remodeling termed softening, yet maintains structural integrity. Following this prolonged uterine quiescence, there is a transitional phase during which myometrial unresponsiveness is suspended, and the cervix undergoes ripening, effacement, and loss of structural integrity.
The physiological processes that regulate parturition and the onset of labor continue to be defined. It is clear, however, that labor onset represents the culmination of a series of biochemical changes in the uterus and cervix. These result from endocrine and paracrine signals emanating from both mother and fetus. Their relative contributions vary between species, and it is these differences that complicate elucidation of the exact factors that regulate human parturition. When parturition is abnormal, preterm labor, dystocia, or postterm pregnancy may result. Of these, preterm labor remains the major contributor to neonatal mortality and morbidity in developed countries (see Chap. 36, Mortality Rates of Preterm Infants).
Parturition, the bringing forth of young, requires multiple transformations in both uterine and cervical function. As shown in Figure 6-1, parturition can be arbitrarily divided into four overlapping phases that correspond to the major physiological transitions of the myometrium and cervix during pregnancy (Casey and MacDonald, 1993, 1997; Challis and associates, 2000; Word and colleagues, 2007). These phases of parturition include: (1) a prelude to—first phase; (2) the preparation for—second phase; (3) the process of—third phase; and (4) recovery from—fourth phase. Importantly, the phases of parturition should not be confused with the clinical stages of labor, that is, the first, second, and third stages—which comprise the third phase of parturition (Fig. 6-2).
The phases of parturition.
Composite of the average dilatation curve for labor in nulliparous women. The curve is based on analysis of data derived from a large, nearly consecutive series of women. The first stage is divided into a relatively flat latent phase and a rapidly progressive active phase. In the active phase, there are three identifiable component parts: an acceleration phase, a linear phase of maximum slope, and a deceleration phase. (Redrawn from Friedman, 1978.)
Phase 1 of Parturition: Uterine Quiescence and Cervical Softening
Beginning even before implantation, a remarkably effective period of myometrial quiescence is imposed. This phase normally comprises 95 percent of pregnancy and is characterized by uterine smooth muscle tranquility with maintenance of cervical structural integrity. The inherent propensity of the myometrium to contract is held in abeyance, and uterine muscle is rendered unresponsive to natural stimuli. Concurrently, the uterus must initiate extensive changes in its size and vascularity to accommodate the pregnancy and prepare for uterine contractions in phase 3 of parturition. The myometrial unresponsiveness of phase 1 continues until near the end of pregnancy.
Although some myometrial contractions are noted during the quiescent phase, they do not normally cause cervical dilatation. They are characterized by their unpredictability, low intensity, and brief duration. Any discomfort that they produce usually is confined to the lower abdomen and groin. Near the end of pregnancy, contractions of this type become more common, especially in multiparous women. They are sometimes referred to as Braxton Hicks contractions or false labor (see Chap. 17, Identification of Labor).
The cervix has multiple functions during pregnancy that include: (1) maintenance of barrier function to protect the reproductive tract from infection, (2) maintenance of cervical competence despite the increasing gravitational forces imposed by the expanding uterus, and (3) orchestrating extracellular matrix changes that allow progressive increases in tissue compliance in preparation for birth.
In nonpregnant women, the cervix is closed and firm, and its consistency is similar to nasal cartilage. By the end of pregnancy, the cervix is easily distensible, and its consistency is similar to the lips of the oral cavity. Thus, the first stage of this remodeling—termed softening—is characterized by an increase in tissue compliance, yet the cervix remains firm and unyielding. Hegar (1895) first described palpable softening of the lower uterine segment at 4 to 6 weeks' gestation, and this sign was once used to diagnose pregnancy.
Clinically, the maintenance of cervical anatomical and structural integrity is essential for continuation of pregnancy to term. Preterm cervical dilatation, structural incompetence, or both may forecast an unfavorable pregnancy outcome that ends most often in preterm delivery (see Chap. 36, Cervical Changes). Indeed, cervical shortening between 16 and 24 weeks has been associated with an increased risk of preterm delivery (Hibbard and associates, 2000; Iams and colleagues, 1996).
Structural Changes with Softening
Cervical softening results from increased vascularity, stromal hypertrophy, glandular hypertrophy and hyperplasia, and compositional or structural changes of the extracellular matrix (Danforth and colleagues, 1974; Leppert, 1995; Liggins, 1978; Word and associates, 2007). Specifically, during phase 1 of parturition, the cervix begins a slow, progressive increase in turnover of matrix components. For example, in mouse models with deficiency of the extracellular matrix protein, thrombospondin 2, collagen fibril morphology is altered and there is premature cervical softening (Kokenyesi and co-workers, 2004).
Another change found in animal models is that physiological softening is preceded by an increase in collagen solubility ...