The Role of Infection
EAR: If most intrauterine infections are subclinical, how can an obstetrician determine whether or not a neonate had intrauterine infection after birth?
RR: One possibility is to look at the placenta. Inflammation in the placenta can be of maternal origin or of fetal origin. Histologic chorioamnionitis is inflammation of the chorioamniotic membranes caused by maternal cells and is, therefore, a maternal inflammatory response. By contrast, funisitis—inflammation of the umbilical cord—is a fetal inflammatory response. Therefore, the presence of funisitis, diagnosed by examination of the placenta, indicates that the fetus was exposed to microorganisms before birth, or that the fetus mounted a FIRS. This is the reason why we call funisitis the hallmark of FIRS. The practical implication of this is that the examination of the placenta may be helpful in understanding what happened before birth. This is particularly important, given that funisitis has been associated with the subsequent development of cerebral palsy. The medicolegal implications of this are apparent. Because there is no known treatment for funisitis, there is no evidence that any intervention by obstetricians can prevent cerebral palsy associated with or induced by intrauterine infection.
EAR: Do systemic infections cause premature labor?
RR: Systemic clinical infections—such as pyelonephritis, pneumonia, malaria, and appendicitis—have been associated with premature labor and delivery. However, there is recent evidence that subclinical distant infections may also be a cause of premature labor and delivery. Specifically, periodontal disease, which is a chronic inflammatory process, has been associated with the subsequent development of preterm labor as well as with small-for-gestational-age infants.
The Changing Approach to Preterm Labor
Preterm delivery accounts for a significant component of infant mortality in the world. In this, the United States has not been spared; in fact, our country ranks a dismal 21st internationally in infant mortality, with prematurity as a major contributor.
Historically, obstetrics has approached this problem from a therapeutic perspective: If you see a contraction, try to stop it. In large measure, we have been unsuccessful, staving off delivery by a mean of approximately 2 days despite our best efforts. Although this window can allow for the stabilization of patients, arranging for their transfer to appropriate delivery sites, and initiating required medications, it does not solve the problem of prematurity.
By focusing on the symptoms of premature labor, we have not paused sufficiently to ask basic questions about potential causes and triggers that could help us to develop preventive strategies and targeted treatments for what is clearly a multifactorial syndrome.
This is all changing. The National Institutes of Health saw this as such a priority that it formed a Perinatology Research Branch within the National Institute of Child Health and Development and chose international authority Dr. Roberto Romero to lead it. The Centers for Disease Control and Prevention and the March of Dimes have similarly launched research initiatives and made the prevention of prematurity a priority.
Much progress has been made, with Dr. Romero's team taking a role in the forefront. I am very pleased to welcome Dr. Romero, professor of ob.gyn. at Wayne State University in Detroit and chief of the Perinatology Research Branch at NIH, as this month's guest professor. We will review advances in our understanding of the biology of prematurity as a syndrome and offer potential treatment implications, beginning with a focus on infection.
In September, we will similarly review the other contributors to the prematurity syndrome.
