Mothers' genes important in preterm birth risk
NEW YORK (Reuters Health) - A mother's genes may be an important factor in the risk of preterm birth, two new studies suggest.
Past research has shown that genes likely play a role in a pregnant woman's odds of delivering prematurely -- before the 37th week of pregnancy.
The risk is increased, for example, among women who were themselves born prematurely or have a sister who ever gave birth preterm. And findings from twin studies suggest that up to 40 percent of preterm deliveries involve some genetic susceptibility.
But little is known about the specifics of how genes influence preterm labor.
The two new studies, reported in the American Journal of Epidemiology, suggest that the mother's genes -- rather than genes affecting fetal development that are inherited from both parents -- are key.
In one study, Danish researchers analyzed national database information on more than 1 million singleton births in Denmark between 1978 and 2004. They found that, not surprisingly, women with a history of preterm delivery were at increased risk of having a subsequent early birth.
But the risk was also elevated among women with a mother, sister or half-sister (born to the same mother) who had delivered prematurely. Compared with women without such a family history, these women were 60 percent more likely to have a preterm birth.
In contrast, preterm births among female members of the father's side of the family, or among the female partners of a woman's male relatives, had no bearing on a woman's own risk of premature delivery.
The findings were similar in the second study -- this one of more than 989,000 births in Sweden between 1992 and 2004. Researchers found that sisters of women who had delivered preterm had an 80 percent higher risk of early delivery, versus women without that family history.
There was no evidence of an increased risk, however, when a brother's partner had delivered prematurely. Nor was there evidence that the increased risk shared by sisters was explained by non-genetic factors that could influence the chances of preterm delivery, like smoking or lower education levels.
Overall, the researchers estimate that mothers' genes account for one-quarter of the variation in preterm delivery risk across the population. In contrast, fetal genes -- which are inherited from both parents -- showed little influence.
"Our results suggest that maternal genes are important for the risk of preterm birth," Dr. Anna C. Svensson, the lead investigator on the Swedish study and a researcher at the Karolinska Institute in Stockholm noted in an email to Reuters Health.
It's possible, she said, that genes that regulate the womb environment during pregnancy are involved, but further studies are needed to pinpoint the exact molecular pathways.
Svensson also stressed that while these studies highlight a role for maternal genes in preterm delivery, that does not mean that the risk is high for any one woman with a mother or sister who gave birth prematurely.
"Our study estimates the relative importance of genes and environment for the variation in preterm birth on the population level," the researcher explained, "On the individual level, the extent to which genes and environment actually determine the risk of preterm birth varies."
In fact, the vast majority of women in the studies did not deliver early, regardless of family history. In the Danish study, for example, about 7 percent of women with a sister who had delivered prematurely had a preterm birth themselves; that compared with 4.5 percent of women whose sisters had no history of preterm delivery.
The main significance of the findings is that they point to directions for future studies on the genetic underpinnings of preterm birth, according to Dr. Heather A. Boyd and colleagues at the Statens Serum Institute in Copenhagen.
They speculate that so-called imprinted genes may be important.
Imprinted genes, which play a key role in fetal development, differ from other genes in that their expression -- whether they are "turned on" or not -- depends on whether they came from the father or mother.
It's also possible, according to Boyd's team, that mitochondrial genes are at work. Unlike most genes, mitochondrial genes exist in the fluid that surrounds a body cell's nucleus, and they are inherited only from the mother.
SOURCE: American Journal of Epidemiology, December 1, 2009.
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