The Preterm Parturition Syndrome

Indeed, suspension of progesterone action through the administration of progesterone receptor inhibitors and progesterone receptor antagonists can induce activation of the components of the common pathway of parturition in animals and humans.

The progesterone/estradiol and progesterone/estriol ratios in amniotic fluid are lower in laboring than in nonlaboring subjects, and the progesterone/estriol ratio is lower in preterm labor followed by preterm delivery compared with preterm labor followed by term delivery, suggesting that these hormones are important in determining the duration of pregnancy.

Trials of progesterone administration to prevent preterm delivery have shown interesting results. Specifically, two recent randomized clinical trials demonstrated that vaginal suppositories containing natural progesterone, or injections of a progesterone, 17 α-hydroxyprogesterone caproate, to women at risk for preterm delivery seem to reduce the rate of spontaneous preterm delivery. Moreover, in the trial using 17 α-hydroxyprogesterone caproate, infants of mothers treated with this compound had a lower rate of necrotizing enterocolitis, intraventricular hemorrhage, and the need for supplemental oxygen. Further research is needed to identify the ideal progesterone regimen and the patients who may benefit from this intervention.

EAR: What about stress as a cause of premature labor?

RR: Epidemiologic studies have indicated that women exposed to stressful conditions during pregnancy have a mild increase in the rate of spontaneous preterm labor. The work of Dr. Pathik Wadhwa and Dr. Cal Hobel has been seminal in this area.

The precise mechanisms whereby stress causes premature labor implicate corticotropin-releasing hormone (CRH), which is produced by the hypothalamus and—importantly—by the placenta. Dr. Roger Smith's work in Australia has proposed that CRH is the regulator of a placental clock. Dr. Felice Petraglia in Italy has also contributed significantly to establish a link between CRH and premature labor.

The clinical implications of this work are related to the epidemiologic observations reported by Dr. Emile Papiernik in France, noting that women who are prescribed rest during pregnancy had a lower frequency of preterm delivery. This interesting experience has not been explored in the United States.

However, a targeted intervention to the patient at risk—such as the woman who must stand or do significant physical work during pregnancy—may be beneficial. However, bed rest per se is not an effective treatment to prevent all causes of premature labor. It is easy to understand that if the cause of preterm parturition is infection, then bed rest will not cure it.

EAR: What is the final message that you would like the readers of OB.GYN. NEWS take with them?

RR: Preterm labor is not just labor before its time, but is the result of a pathologic process. The challenge for health care providers is to try to identify why a women is in premature labor, what specific mechanism of disease may be involved, how sick the fetus is, and whether the benefits of pregnancy prolongation outweigh the risk of prematurity. The administration of steroids has been demonstrated to reduce the rate of adverse neonatal outcomes, and it is indicated when the patient is at risk for preterm delivery.

Preterm Labor Has Multiple Causes

In July's Master Class, the specific role of infection in preterm labor was discussed at length by Dr. Roberto Romero, chief of the Perinatology Research Branch at the National Institute of Child Health and Human Development, and professor of obstetrics and gynecology at Wayne State University in Detroit.

Although infection is a leading—and perhaps the best understood—cause of spontaneous preterm labor and delivery, it is not the only cause. Research from Dr. Romero's group and others increasingly point to several disease mechanisms with genetic and environmental components that can be responsible for what we now know as the preterm parturition syndrome.

I am pleased to welcome back Dr. Romero, an international authority on the syndrome.

In this month's discussion, Dr. Romero provides an overview of evolving knowledge about the syndrome and details current scientific progress in the understanding of the noninfectious causes that may be important in the process of preterm labor.