Low birth weight and serious, sometimes-deadly complications also occurred
less often in babies whose mothers got the weekly injections, according to the
study in Thursday's New England Journal of Medicine.
"This is really the first innovation that's clearly been shown to prevent or
reduce the incidence of premature delivery," said Dr. Charles J. Lockwood,
director of obstetrics and gynecology at Yale University School of Medicine and
former chairman of obstetrical practices of the American College of
Obstetricians and Gynecologists.
The study involved women at very high risk of premature delivery. The women
previously had at least one baby very early — at about 31 weeks on average. Full
term is considered 37 weeks to 40 weeks. Some of the women received
progesterone; a comparison group got shots of an inert oil.
The progesterone proved so effective that the study was halted early because
it would have been unethical to keep giving some women a placebo.
"This is a start at finally having some successful treatments to prevent the
biggest problem we have in caring for pregnant women," said lead researcher Dr.
Paul J. Meis, professor of obstetrics and gynecology at Wake Forest University
School of Medicine. "We have tried so many treatments to prevent premature
birth, and they have not been successful."
Meis said giving just a half-dozen women progesterone would prevent one
premature birth.
Compounds of progesterone, a natural hormone that helps maintain pregnancy,
were used in the 1960s and '70s to prevent premature birth. But Meis said they
fell out of favor because the few, small tests of effectiveness had mixed
results.
His study, conducted at a network of 19 clinical centers run by the National
Institute of Child Health and Human Development, followed 459 women, mostly in
their 20s, who had high-risk pregnancies from 1999 to 2002.
Among the two-thirds who got progesterone, about 36 percent gave birth before
37 weeks, compared with 55 percent of women in the comparison group. About 11
percent of mothers who had progesterone shots delivered before 32 weeks,
compared with about 20 percent in the other group.
The babies of mothers given progesterone also fared better, with only 27
percent weighing less than 5 1/2 pounds at birth, compared with 41 percent in
the comparison group. Babies of mothers in the progesterone group also were less
likely than the others to be stillborn, die soon after birth or have breathing
problems or other serious complications, although the numbers with such problems
were too small for firm proof.
Seventeen babies died — 6 percent in the comparison group and 3 percent in
the progesterone group.
Lockwood said many doctors now are starting to give progesterone in high-risk
pregnancies, because results of this study were reported at a February
conference and because a similar study in Brazil published in February found
daily vaginal suppositories of progesterone cut premature births by half.
But Dr. Michael Varner, principal investigator for the portion of the study
conducted by the University of Utah, urged caution. He said the study's findings
need to be replicated and follow-up done "that shows we're not trading one
problem for another."
The form of progesterone used in the study — hydroxyprogesterone caproate —
isn't available commercially in the United States, and it's unknown whether
other forms of progesterone would be as effective, he said.
In 2001, 11.9 percent of American babies were born before 37 weeks'
gestation, a 27 percent increase over 1981 that was partly fueled by more
multiple births, according to the National Center for Health Statistics.
Premature birth is the country's No. 2 cause of infant mortality. But with
better medical care for preemies, the death rate in the first year dropped from
12.6 deaths for each 1,000 births in 1980 to 6.9 deaths in 2000.
Dr. Joseph Apuzzio, director of maternal-fetal medicine at University of
Medicine and Dentistry of New Jersey in Newark, said researchers now must see if
progesterone has any long-term effects on babies. He noted mothers getting
progesterone had five miscarriages, but the comparison group had none, raising a
"yellow flag."
Apuzzio said scientists still must nail the cause of the many unexplained
premature deliveries — those not triggered by complications such as uterine
infection or bleeding, overactive thyroid or drug abuse — to find the best
prevention method.
