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The surprise was just how unhealthy some of these women giving birth to preterm infants really were. Nearly one-fourth of the mothers were sick when the program began. They had severe hypertension, sickle-cell disease or uncontrolled heart problems. Even though they would have automatically become eligible for Medicaid once they were pregnant, for these most at-risk women, "pregnancy is too late," Brann says.
With Brann's guidance, a larger version of the Atlanta trial is recruiting volunteers in Mississippi which has the highest infant-mortality rate in the U.S. Two other studies have been proposed, one in another Georgia health district and one in Alabama.
Of course, plenty of women appear to be perfectly healthy and still give birth preterm. But the idea that an infant's and a mother's health are related in some complex way that factors not just during pregnancy but also before conception can have an impact may help explain why preterm birth has remained a mystery for so long. Many of the things that researchers associated with preterm birth in the field have not seemed to matter when tested rigorously in randomized controlled trials. "[Of] all these things we take for granted prenatal care, nutrition," says the CDC's Lackritz, almost none have proved effective by themselves in preventing preterm delivery. Only one intervention weekly shots of a synthetic progesterone has been shown to reduce preterm birth in high-risk pregnancies. But no other measure, such as bed rest or home uterine monitoring, has proved consistently effective.
It is possible that the reason doctors cannot pinpoint a single cause of preterm birth is that there are simply too many, involving a vast range of genetic, medical and social factors. "It's almost like cancer," Lackritz says. "There are so many different kinds of cancer, and that's probably going to be our [research] model too."
Search and Rescue
Like cancer researchers, the network of scientists who study prematurity has cast a wide net. "We know what's associated with preterm birth, and we know some of the pathophysiology," says Alan Fleischman, medical director of the March of Dimes, the nonprofit foundation best known for its role in ridding the U.S. of paralytic polio in the 20th century and now at the forefront of the charge against prematurity. "But we still have a long way to go in truly understanding what initiates labor or initiates the rupture of membranes that results in preterm birth."
In 2005 the March of Dimes began issuing grants as part of a new Prematurity Research Initiative, dedicated to rooting out the underlying causes of preterm labor. Last year the initiative had $11.5 million pledged to active studies. Some researchers are hunting for microorganisms that live in the womb to determine their possible role in preterm labor. Others are looking at uterine-muscle function, disruptions in circadian rhythm and weight gain during pregnancy. But perhaps most intriguing of all is the search for genes in mother and child that may affect inflammation the body's first-line immune response to injury and infection.
Researchers think it's possible that the mother's inflammatory response could be revved up by disease (bacterial vaginosis, for instance), physical stress (working long hours in a physically demanding job like waitressing) or even social stress. Researchers have long wondered why unmarried women and those with low education have higher preterm-birth rates than their married, college-educated counterparts; social stress could play a role.
Perhaps more troubling is the pronounced racial disparity in infant mortality. African-American babies die more than twice as often as non-Hispanic white babies. (But taken alone, even white Americans would rank just 26th in infant survival globally, behind most of the world's high-income populations; black Americans would fall about 10 places lower.) This divergence is driven largely by blacks' higher rates of preterm birth. Since the death-rate gap persists even among highly educated and high-income Americans well-educated blacks have higher preterm-birth rates than poorly educated whites some researchers think there could be greater stress among blacks at all social strata or a genetic predisposition to certain inflammatory responses among some African Americans.
That's because inflammation, researchers believe, may trigger early labor. Labor itself appears to be an inflammatory process. In biopsies of women undergoing cesarean sections, Scottish researchers found large numbers of pro-inflammatory white blood cells in the cervixes of women who had begun labor. Other studies found these cells in fetal membranes during labor, as well as gene expression in the mother consistent with localized inflammation. If such a far-reaching mechanism is to blame, it might explain why discrete treatments, like treating a single infection, don't always help.
The answer is by no means clear. Progress on prematurity, Lackritz says, will probably spring from innovations that combine social, clinical and genetic research. But she is optimistic. "We've seen it over and over," she says. When the nation's resources and will are behind a common goal, "then we have impact," she says and thousands of babies' lives could be saved in the process.