Drug Found to Prevent Many Premature Births

Obstetricians have identified the first medical treatment that can prevent premature births in large numbers of high-risk pregnant women, a discovery that could halt the spiraling increase in early deliveries in this country.

A nationwide team of researchers has found that administering a form of the hormone progesterone weekly during the mid to late stages of pregnancy can reduce premature births by a third.

The drug, which is now available as a treatment for infertility and to prevent early miscarriage, proved so effective that the clinical trial was halted early to provide the treatment to all participants, Dr. Paul J. Meis of Wake Forest University Baptist Medical Center told a San Francisco meeting of the Society for Maternal-Fetal Medicine on Thursday. He and his associates have already begun using the drug for high-risk women in their regular practice, Meis said.

“This is an exciting breakthrough,” said Dr. Nancy S. Green, medical director of the March of Dimes Birth Defects Foundation, which just last week announced a new program aimed at reducing premature births. “This appears to be the most effective treatment to reduce the risk of pre-term delivery for any one woman.”

Doctors were particularly excited because the treatment worked as well for blacks, who are 50% more likely to have premature births, as for whites.

“Pre-term labor and prematurity and the racial disparity have been plaguing us throughout my entire career,” said Dr. Fredric Frigoletto of Massachusetts General Hospital in Boston. “Every so often, there has been a new cure on the horizon, and it has amounted to nothing. But this appears to be a very effective intervention.”

One in 8 babies in the United States, or about 476,000 per year, is born prematurely -- before the 37th week of gestation -- a proportion that has grown 27% over the last two decades. The increase, in part, is because of the increasing age of mothers and the increasing use of in vitro fertilization, which often leads to multiple births, a major risk factor for premature deliveries. In most other cases, the cause is still unknown.

Whatever the cause, premature birth can have a devastating effect on infants. It is the leading cause of death in the first month of life. Those who survive have lifelong aftereffects, including lower IQs, learning disabilities and neurological problems, as well as a higher risk of blindness, retardation, lung diseases and cerebral palsy.

The problem can also have profound economic effects. The hospital bill for a premature birth averaged $58,000 in 2000, compared with $4,300 for a routine birth of a full-term baby, according to the March of Dimes.

Women who are at high risk of giving birth prematurely, especially those who have already delivered one premature infant, often undergo intensive monitoring during pregnancy. But unless there is a specific cause of early delivery, such as an infection or unusual stress, there is often little that can be done to prevent an early birth, Green said.

The researchers studied a drug called 17-alpha-hydroxyprogesterone caproate, commonly known simply as 17P. Physicians had studied the drug previously in a couple of small clinical studies, but the results were not definitive. They were promising enough, however, that the National Institute of Child Health and Human Development organized the new trial.

The study has so far enrolled 463 women who had previously had a premature delivery. Beginning between the 16th and 20th weeks of gestation, two-thirds of the women received a weekly injection of 17P, while the rest received a dummy injection or placebo.

Meis reported Thursday that, among the women receiving 17P, the risk of birth before 32 weeks was reduced by 42% and the risk before 37 weeks by 34%.

“This is the first well-documented demonstration of a successful treatment to reduce pre-term births in women at risk,” Meis said.

Researchers were particularly pleased with the effectiveness among African American women. “This is a group of women who have not been easy to treat,” Green said. “They had marked improvement. It is really remarkable.”

Meis also noted that the drug, which is licensed in the United States, is very safe. “We found no evidence of any harmful effects for women and the babies who have been treated,” he said. He also noted that only this particular form of the natural hormone progesterone seems to work. “It is uniquely effective,” he said.

Theoretically, high-risk women could go to their doctors tomorrow and begin treatment with 17P, but researchers are discouraging such individual treatments in favor of further trials.

“We are discouraging the cowboy approach” by individual doctors, Green said. “This will move fairly promptly through clinical research steps” and then will become widely available, she added.

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Premature births

The percentage of premature births has increased steadily in the last 20 years.

Percentage of live births that were premature

1981: 9.4

1991: 10.8

2003: 11.9

Rates by state

States with the highest percentages of live births that were premature in 2001:

District of Columbia: 16.0

Alabama: 15.4

Louisiana: 15.2

Tennessee: 14.0

South Carolina: 13.9

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Source: March of Dimes