Normal and Pathological Facilitation of Parturition by a Feedforward Endocrine Mechanism

The emergence of mammals is tied to evolved brains, evolving placental function, and lactation (Easteal, 1999). The placenta is unique in its vast storehouse of biochemical information molecules that are vital to the developing fetus. Nature conserved, extended, and utilized the diverse myriad of information molecules that are well represented in the brain and the placenta and that are fundamental for normal development (Petraglia et al., 1990). Moreover, nature selected a number of endocrine mechanisms to facilitate the viability of fetal development and the progression of a healthy baby; one is an endocrine mechanism that is feedforward. It also provided mechanisms to insure reproductive fitness; for example, extreme nausea during pregnancy may, under some conditions, be a reaction to teratogens (Profet, 1991).

Let me begin with a question: Why the study of preterm delivery of babies in a book on allostatic regulation? There are several reasons. First, placental CRH is elevated during adverse events in pregnancy. It may be a predictor of preterm labor when there are conditions of adversity (see, e.g., Wolfe et al., 1988; Goland et al., 1993; Wadhwa et al., 2001). Second, a positive feedback loop underlies parturition, providing an allostatic mechanism; namely, cortisol increases CRH gene expression in the placenta under normal conditions. And third, this feedback loop may be exaggerated during adverse conditions (allostatic overload ). In the case of adverse events in pregnancy such as infections, metabolic stress, and social stress, CRH may be overexpressed in the placenta. Similarly, in the case of fear and anxiety, CRH may be altered in the brain (Gold et al., 1984; Nemeroff et al., 1984; Nemeroff, 1992) or with a sense of potential harm (Kalin et al.,

1989; Koob, 1993a; Schulkin et al., 1994). In other words, similar mechanisms that are feedforward (allostatic) endocrine systems underlie the expression of CRH in the brain and CRH in the placenta. This chapter is therefore consistent with the preceding chapters—particularly chapter 3 on fear—with regard to positive feedback endocrine systems. Moreover, these events in utero are known to have long-term physiological and behavioral consequences, including changes in the central nucleus of the amygdala and vulnerability to perceive events as fearful in the infant (Welberg and Seckl, 2001).

Preterm Low-Birth-Weight Babies

Consider the real-world consequences of preterm delivery of babies. Preterm delivery accounts for up to 10 percent of all births and is a leading factor in neonatal morbidity. Consequences of preterm birth include low birth weight and decreased respiratory function (Center for Disease Control, 1997). It accounts for up to 70 percent of newborn deaths (Goldenberg et al., 2000). The rate of preterm delivery has not declined in this country over the past 20 years, but survival of preterm infants has increased.

There are a number of biological and demographic predictors of risk for preterm birth. For example, there are significant differences in the rate of preterm and low-birth-weight infants born to African American women when compared to other racial/ ethnic groups. Babies born to African American women are nearly twice as likely as those of any other group to be preterm and have a low birth weight (National Vital Statistics Report, 2000). This difference tends to hold even when one controls for demographic characteristics and the link between infectious diseases and preterm delivery. More generally, a number of infectious diseases (e.g., bacterial vaginosis) increase a woman's vulnerability to preterm delivery (Goldenberg et al., 2000). Levels of CRH, as we will see below, are significantly linked to preterm delivery (Holzman et al., 2001; Wadhwa et al., 2001; figure 4.1).

Feedforward Mechanism

Figure 4.1

Potential sites of bacterial infection within the uterus (Goldenberg et al., 2000).

Figure 4.1

Potential sites of bacterial infection within the uterus (Goldenberg et al., 2000).

Placenta and Chemical Messages

Several physiological systems linked to the placenta may play a role in preterm delivery (see, e.g., Goland et al., 1988,1992a, b, 1995; MacGregor et al., 1994, 1995; Pepe and Albrecht, 1995; Goldenberg et al., 1998). A large number of hormones are produced in the placenta (see, e.g., Ahmed et al., 1992; Lefebvre et al., 1992; Bramley et al., 1994; Petraglia et al., 1990, 1995a, b):

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Getting to Know Anxiety

Getting to Know Anxiety

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