Developing treatments to prevent premature birth

The U.S. premature birth rate has dropped for the sixth consecutive year to 11.5 percent in 2012. However, more than 450,000 babies are still born too soon each year. Studies show that various strategies to prevent premature delivery, including bedrest, intensive prenatal care for high-risk women, antibiotics and medications to stop uterine contractions are not effective. New approaches are needed to prevent preterm births.

Preterm premature rupture of the fetal membranes (bag of waters) may contribute to as many as 40 percent of preterm births. John J. Moore, MD, a PRI grantee at MetroHealth Medical Center in Cleveland, Ohio, is examining factors that may contribute to membrane weakening, in order to develop treatments to prevent it and the resulting preterm births.

What triggers uterine contractions to begin at term or preterm is not understood. A number of grantees are seeking to unravel this mystery. A number of factors may help regulate the timing of labor. For example, Sarah K. England, PhD, a PRI grantee at Washington University in St. Louis, Missouri, believes the key may lie in tiny openings in cell membranes (called SK3 channels) that allow potassium to flow out of uterine muscle cells. When potassium exits the cells, the uterus relaxes, allowing the pregnancy to continue to term. At term, the channels may close, prompting labor to begin. If this proves correct, it could lead to the development of drugs that open the channels and prevent or halt preterm labor.

Jennifer Condon, PhD, a PRI grantee at the University of Pittsburgh, believes that an enzyme (protein) called caspase-3 may play a similar role. The enzyme may help prevent contractions until term, when levels drop sharply, possibly helping to trigger labor. Dr. Condon is investigating whether an early drop in caspase-3 levels also trigger preterm labor. If so, it may be possible to develop drugs to regulate enzyme levels and prevent preterm labor.

Although Dr. England and Dr. Condon’s studies hold promise for the future, another PRI grantee is exploring a novel approach that could be used right away. Nazeeh N. Hanna, MD, a PRI grantee at Winthrop University Hospital in Mineola, New York, is investigating whether inhaling low doses of carbon monoxide may help prevent preterm labor in women with uterine infections, possibly by suppressing inflammation.

These and other March of Dimes research grantees are exploring diverse ways to prevent or halt preterm labor, based on an improved understanding of the biology of labor and delivery. What they learn could lead to novel drugs and other treatments to reduce the risk of prematurity.