The University of Rochester has filed a patent on several ideas to help prevent early labor and the premature delivery of low-birth-weight babies. The discovery is an incremental step in an area of obstetrics that has seen little improvement in 20 years.
Mark Plessinger, Ph.D., assistant professor of Obstetrics and Gynecology at the University of Rochester Medical Center, discovered that certain proteins known as toll-like receptors (TLRs), located in the amniotic membranes of pregnant women, sometimes fuel a harmful inflammatory response. The inflammation, in turn, may cause the fetal membranes to rupture and lead to preterm labor.
The pending University patent protects the development of a chemical test to ascertain the effectiveness of drugs that could be used to treat women at greater risk of preterm delivery. Other claims of the patent protect the idea that once these agents are identified, a drug might be developed to block the TLRs and stop early labor.
Plessinger is showcasing the research this week in Toronto at the annual meeting of the Society for Gynecological Investigation. Although doctors today can treat women in early labor with antibiotics and other drugs designed to slow contractions, studies have demonstrated that this approach is often ineffective.
"I am optimistic that we have landed on a novel idea," Plessinger said, "although it is far from therapeutic intervention."
Premature delivery is when an infant is born before 37 weeks of pregnancy. It occurs in about 12 percent of pregnancies in the United States and is the leading cause of infant death, according to the National Vital Statistics Report for 2004. When premature babies do survive they often face many health problems.
To better understand what brings on preterm labor, Plessinger started by isolating the cells within the amniotic membranes. The membranes are balloon-like, wrapping around the fetus and the amniotic fluid in which the fetus is bathed. The cells within the membranes (both fibroblasts and epithelial) are critical to the chemical process that causes the premature rupture of the fetal membranes. This is known as when a woman's "water breaks," and once that happens it is difficult to stop the ensuing delivery.
Meanwhile, in related investigations, researchers discovered that in nearly 80 percent of the cases of preterm labor, bacteria are present in the amniotic fluid. Plessinger's lab has been focusing on the association between the infectious organisms and the amniotic fibroblasts, zeroing in on E. coli as a potential culprit. (Many premature babies test positive for E. coli.)
Plessinger hypothesizes that when the mother's body tries to fight off the offending bacteria, the TLRs activate and cause inflammation. The inflammatory cells brought in to kill off the infectious microbes may pump naturally occurring hypochlorous acids and enzymes from the body into the fetal membranes, causing them to break apart and rupture.
Plessinger and colleagues Melanie O'Bara and Dongdong Guo, discovered the existence of the toll-like receptors and their role in fueling an inflammatory response after they had isolated amniotic cells from women who experienced normal, full-term delivery and cells from women who went into early labor.
"The big question is: What is it about the inflammatory process that impacts the fetal membranes and starts the entire chain of events that leads to early labor?" Plessinger said. "We are on a path to discovering that answer, and we hope it will lead us to the development of a new class of drugs that can shut down the process of premature delivery."