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Preterm Birth: Causes, Consequences, and Prevention (2007)
Board on Health Sciences Policy (HSP)

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. "6 Biological Pathways Leading to Preterm Birth ." Preterm Birth: Causes, Consequences, and Prevention. Washington, DC: The National Academies Press, 2007.

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Preterm Birth: Causes, Consequences, and Prevention

MECHANISMS OF PARTURITION

Parturition

The process of normal spontaneous parturition can be divided into four stages (see the reviews of Challis [2000] and Challis et al. [2000]). During most of pregnancy, the uterus remains relatively quiescent, and this corresponds to Phase 0 (quiescence) of parturition. Phase 1 (activation) involves uterine stretch and fetal hypothalamic-pituitary-adrenal (HPA) activation. Phase 2 (stimulation) refers to stimulation of the activated uterus by various substances, including corticotropin-releasing hormone (CRH), oxytocin, and prostaglandins. These different processes lead to a common pathway to parturition involving increased uterine contractility, cervical ripening, and decidual and fetal membrane activation (Romero et al., 2004a). Phase 3 (involution) corresponds to postpartum involution of the uterus. These unique phases are described below and are summarized in Figure 6-1.

FIGURE 6-1 The stages of parturition. Following implantation, more than 95 percent of gestation is spent in Phase 0, uterine quiescence. During quiescence, myometrial contractility is inhibited by a variety of biological substances, including progesterone. Phase 1, myometrial activation, is characterized by increased expression of contraction-associated proteins, receptors for oxytocin, and prostaglandins, and increased placental estrogen biosynthesis. The signal for myometrial activation is controlled by the fetal HPA axis, which, in turn, is up-regulated by endogenous placental CRH production. Phase 2, myometrial stimulation, involves a progressive cascade of events, beginning with myometrial activation, which results in myometrial contractility, cervical ripening, and decidua and membrane activation. It is likely initiated by the same events of fetal HPA activation that initiate Phase 1. Phase 3, involution, involves placental separation and contraction of the uterus. It is primarily effected by maternal oxytocin. Implantation

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170
Front Matter (R1-R18)
Summary (1-30)
1 Introduction (31-52)
SECTION I Measurement : 2 Measurement of Fetal and Infant Maturity (53-83)
Section I Recommendations (84-86)
SECTION II Causes of Preterm Birth: 3 Behavioral and Psychosocial Contributors to Preterm Birth (87-123)
4 Sociodemographic and Community Factors Contributing to Preterm Birth (124-147)
5 Medical and Pregnancy Conditions Associated with Preterm Birth (148-168)
6 Biological Pathways Leading to Preterm Birth (169-206)
7 Role of Gene-Environment Interactions in Preterm Birth (207-228)
8 Role of Environmental Toxicants in Preterm Birth (229-254)
Section II Recommendations (255-258)
SECTION III Diagnosis and Treatment of Preterm Labor: 9 Diagnosis and Treatment of Conditions Leading to Spontaneous Preterm Birth (259-307)
Section III Recommendations (308-310)
SECTION IV Consequences of Preterm Birth: 10 Mortality and Acute Complications in Preterm Infants (311-345)
11 Neurodevelopmental, Health, and Family Outcomes for Infants Born Preterm (346-397)
12 Societal Costs of Preterm Birth (398-429)
Section IV Recommendations (430-432)
SECTION V Research and Policy: 13 Barriers to Clinical Research on Preterm Birth and Outcomes of Preterm Infants (433-454)
14 Public Policies Affected by Preterm Birth (455-472)
Section V Recommendations (473-476)
15 A Research Agenda to Investigate Preterm Birth (477-492)
References (493-590)
Appendix A Data Sources and Methods (591-603)
Appendix B Prematurity at Birth: Determinents, Consequences, and Geographic Variation (604-643)
Appendix C A Review of Ethical Issues involved in Premature Birth (644-687)
Appendix D A Systematic Review of Costs Associated with Preterm Birth (688-724)
Appendix E Selected Programs Funding Preterm Birth Research (725-731)
Appendix F Committee and Staff Biographies (732-740)
Index (741-772)