Study Points to Genetics in Disparities in Preterm Births
By NICHOLAS BAKALAR
Published: February 27, 2007
Black women have significantly higher rates of premature birth than white women, and a new study suggests there may be underlying genetic factors even when other known risks are taken into account.
The researchers, who published their findings this month in The American Journal of Obstetrics & Gynecology, say that even though preterm birth is not a desirable outcome, it may provide some advantage, perhaps protection against diseases -- in somewhat the same way the gene for sickle cell confers protection against malaria.
''We have to think of everything in the context of what's been evolutionarily advantageous,'' said Dr. Louis J. Muglia, a professor of pediatrics at Washington University in St. Louis, who was the senior author of the study.
Dr. Muglia noted that during a normal pregnancy, certain immune responses are suppressed, and that cytokines, the molecules involved in healthy immune response, are heavily involved in preterm birth.
''The same things that select for a robust immune response,'' he said, ''may also confer a risk for giving birth early.''
Some experts remain skeptical. Neil J. Risch, director of the Institute for Human Genetics at the University of California, San Francisco, said he was not impressed with the quality of the evidence.
''They're inferring something is genetic by elimination of other factors,'' he said. ''But geneticists believe that to implicate something as genetic requires direct evidence, as opposed to evidence by absence. One should use high standards of evidence before trying to directly implicate genetics in group differences. There could be a genetic contribution, but they haven't shown it.''
That black women give birth prematurely more often than white women has been demonstrated in numerous studies, and there is wide agreement on many of the risks. The mother's age, prenatal care, socioeconomic status, education level, body-mass index, smoking and maternal diabetes have all been shown to affect the likelihood of preterm birth.
But the new study found that black women still had higher rates of preterm birth even after accounting for all these variables.
The researchers used the Missouri Department of Health and Senior Services' database of more than 711,000 live births from 1989 to 1997. They found that compared with white women, black women were twice as likely to give birth from 20 to 34 weeks; that their rate of recurrent preterm birth is higher; and that the median time for recurrence is two weeks earlier -- 31 weeks for black mothers, compared with 33 for whites. (Normal gestation is 37 to 41 weeks.)
The researchers found that race was an even more powerful predictor than lack of prenatal care, which is itself one of the strongest risk factors for prematurity. For black women, the risk of recurrent preterm delivery is four times as great as it is for white women.
The study also found that for both blacks and whites, the most likely time for the birth of a second preterm child is the same week as the first preterm delivery. These findings suggest, but do not prove, that there is a genetic contribution to premature birth.
A co-author of the paper, Dr. F. Sessions Cole, also a professor of pediatrics at Washington University, acknowledged that the study was not a genetic analysis. But he said that should be the next step.
''There is no specific candidate gene or pathway identified here,'' Dr. Cole said, ''but this is a sufficiently large and robust cohort that inferences about genetic contribution can be made. The study provides momentum for a genomic approach to understanding the racial disparity between blacks and whites in rates of prematurity.''
Dr. Muglia acknowledges that because many people are genetically mixed, critics say it is impossible to associate race with any specific genes. But he added, ''There have been enough studies to show that when you look at people's self-reported race, it does track with specific markers of ethnicity.''
Previous studies have shown that the tendency to give birth prematurely is inherited, and that women who were themselves born prematurely are significantly more likely to give birth to preterm infants. One study found that women born at 30 weeks of gestation or less are more than twice as likely as women born after 36 weeks to have their own babies prematurely.
Dr. Muglia said that genes and environment interact. ''There are likely genetic variations that will require certain environmental exposures to result in preterm birth,'' he said, ''and those environmental contributors vary as a function of race as well. This complicates the overall analysis of ascribing risk to specific variables.''
Dr. Jerome F. Strauss, dean of the Virginia Commonwealth University School of Medicine, said that the findings were ''new and significant'' and that ''they add support to the idea that genetic factors contribute to the disparity between African-Americans and Americans of European descent'' in rates of prematurity. Dr. Strauss was not involved in the study.
Although no one has identified a specific gene for prematurity, Dr. Strauss and his colleagues have identified a gene variant, much more common in people of African descent, that confers an increased risk of premature rupture of the fetal membranes. Still, Dr. Muglia said, even that finding gives no indication of the overall contribution of genetics to the likelihood of giving birth prematurely.
The authors emphasize that their analysis does not prove that the disparity in preterm births has a genetic component, because unknown variables that go along with black race may also contribute.
''Many moms feel they've done something wrong if they have a preterm infant,'' Dr. Muglia said. ''But there are still other risk factors that aren't in their control, like their genetic makeup, that we need to know more about -- for both whites and blacks.''
Photo: YOUNG AND FRAGILE -- A girl who was born at 27 weeks being fed through a tube. (Photo by Dilip Vishwanat for The New York Times)