Progesterone Cuts Preterm Births by One-Third

A form of the hormone progesterone called hydroxyprogesterone caproate, or 17P, can reduce preterm births by up to one-third, according to a study due out in the June 12 New England Journal of Medicine.

The finding comes after a two-and-a-half-year trial by the Maternal Fetal Medicine Units (MFMU), a National Institutes of Health (NIH)-funded network of 13 major medical research centers that includes the University of Utah.

Michael W. Varner, M.D., professor of maternal-fetal medicine in the Department of Obstetrics and Gynecology at the University of Utah medical school, served as principal investigator for the Utah portion of the study. Utah medical centers involved included the University of Utah Hospitals & Clinics, LDS Hospital, McKay-Dee Hospital, and Utah Valley Regional Medical Center.

"I'm optimistic that we may be able to decrease the risk of recurrent preterm birth," Varner said.

The trial began in October 1999, with 463 women nationwide who previously had spontaneous preterm births and who were between 16 and 20 weeks pregnant. Participants were randomly assigned, at a 2-to-1 ratio, to receive weekly injections of 17P or a placebo.

The reduction in preterm deliveries was significant:

In women taking 17P, 36.3 percent delivered babies before 37 weeks, compared with 54.9 percent of the women taking the placebo. The results were as dramatic in women delivering before 35 weeks and before 32 weeks.

In fact, 17P was so effective that enrollment in the trial was halted in February 2002 before the target number of 500 subjects had been reached.

How 17P prolongs gestation is not entirely known.

Progesterone relaxes the smooth muscle wall of the uterus, blocks the action of oxytocin, a hormone that makes the uterus contract, and inhibits the formation of gap junctions. Gap junctions are connections that allow the muscle cells in the uterus to communicate with each other so they can contract at the same time. The researchers studied 17P because its effectiveness had been reported in previous, smaller trials.

As for babies born to mothers who received 17P, their immediate newborn outcomes improved, too. Fewer needed help breathing, and fewer suffered inflammation of the small intestine and colon than those whose mothers received the placebo.

Utahn Katie Howard enrolled in the study after losing her first baby to a preterm birth. Her second baby was born only two weeks early, while she was participating in the trial. "I stopped the study medication a week before she was born," said Howard, who now has a second daughter, born just nine days early, this time without progesterone.

Howard, who lives in Syracuse, Utah, was referred to Varner by her mother's neighbor, a midwife at LDS Hospital in Salt Lake City. Once a week she traveled to Salt Lake City to receive an injection of 17P.

"It was totally worth it to me to go down to Salt Lake to see him (Varner)," Howard said. "I'm a huge advocate of the studies they do at the U."

Preterm deliveries are more common in the U.S. than in many other developed countries and are on the rise here. They are considered the principal reason for the high U.S. infant mortality rate.

A high frequency of preterm birth is associated with such factors as multiple fetuses, infection, poverty, previous preterm birth, and ethnic status, with a higher rate among African-Americans than whites.

The lowest frequency of preterm birth is found in highly socialized northern Europe where women don't work beyond 20 weeks of pregnancy and have paid leave afterward, according to Varner.

Although more than half the women in the study were African-American and less than a quarter Caucasian, there was no significant statistical difference in outcomes for the two groups.

Although the study findings are encouraging, Varner said, some cautions are necessary.

Since 17P presumably works by preventing preterm labor, this treatment doesn't address the major problem of spontaneous preterm birth in women without a previous history. Researchers also have no information on potential long-term effects of fetus exposure to 17P. Further studies are being developed at the U of U and the IHC Perinatal Centers to define the precise role of 17P in preventing spontaneous preterm birth.

Paul J. Meis, M.D., professor of obstetrics and gynecology at Wake Forest University, is first author of the study.