Developing treatments to prevent premature birth

Over the years, health care providers have tried various strategies to prevent premature delivery, including bedrest, intensive prenatal care for high-risk women, antibiotics and medications to stop uterine contractions. There is no evidence that any of these measures were effective and the rates of prematurity have continued to rise. Clearly, new approaches to preventing premature birth are needed.

One of the efforts shows promise, but only for a minority of high-risk women. Treatment with the hormone progesterone helps in women who had previously delivered a premature baby. However, many questions remain about how progesterone treatment helps prevent preterm labor and which forms of progesterone may be most effective. A study by PRI grantee Michal Elovitz, MD, of the University of Pennsylvania, suggests that it may delay labor by preventing cervical ripening (softening of the cervix). It may do so by regulating the action of genes involved in preparing the cervix for labor. This information may help to identify those women who will  benefit from this treatment.

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 are known to help regulate the timing of labor. For example, Sarah K. England, PhD, a PRI grantee at the University of Iowa, 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 triggers preterm labor. If so, it may be possible to develop drugs to regulate enzyme levels and prevent preterm labor.

Although Dr. England's and Dr. Condon's studies hold promise for the future, another PRI grantee is investigating a simple approach that could be used right away. Martin Hewison, PhD, of the University of California at Los Angeles, is looking at whether vitamin D supplements will 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.

Courtesy of the March of Dimes