Women who get the flu while pregnant have a much higher risk of hospitalization and death and are four times more likely to deliver a premature baby. During the 1918 epidemic, in fact, the death rate among pregnant women was at least 28 times that of the general population.

Medical science has assumed this vulnerability was an unfortunate result of a suppressed immunity that keeps a woman’s body from rejecting the fetus.

A Stanford study now disputes that central assumption, and suggests the immune system kicks into high gear in response to the pandemic “swine flu” virus, H1N1, and a seasonal H3N2 influenza virus. The results, published online Monday in the journal Proceedings of the National Academy of Sciences, could lead to additional ways to combat influenza infection among pregnant women.

It’s still true that women’s immune systems are strongly suppressed, overall, during pregnancy — a result the study reaffirmed. But researchers suspected this alone could not explain pregnant women’s increased vulnerability to influenza. It seemed to contradict chemistry and common sense.

Recent studies had shown there was a complicated mix of chemicals promoting and combating inflammation among the white blood cells of pregnant women infected with the virus. And pregnant women with the flu frequently suffer from severe congestion, a symptom that is typical of an inflammatory response on overdrive.

“Nobody bothered to look at the direct viral response before,” said Dr. Catherine Blish, an immunologist at Stanford University School of Medicine and principal investigator of the study. “The only person on the research team who was not surprised by this result is our obstetrician, who takes care of all these flu patients.”

Researchers looked at the proportion and behavior of “natural killer” and T cells, which are crucial in fighting viral infection. Both were suppressed by the standard test of immunity. But in the presence of influenza virus, these cells increased in number and changed in function, producing more chemicals that heighten the body’s inflammatory response, the study found.

“Too much inflammation in the lung is a disaster if it gets out of control,” Blish said. “You can get such thick air walls that you can’t exchange air.”

The inflammatory response also appeared to grow slightly stronger as pregnancy progressed. Whether that implies a different immunity regime later in pregnancy or other factors remains to be seen.

And physiology might explain complications in the last six months of pregnancy. It’s harder to breathe deeply because of the growing fetus. So women in late stages of pregnancy may not be able to muster the power to clear the inflammation, which set the stage for the more perilous bacterial pneumonia.

Responses to the two strains also were slightly different, Blish added.

“I wish we knew what that meant, but I think we need to study more,” she said.

If the findings hold up, however, it could mean that another treatment path may be open – tinkering with the inflammatory response, not just fighting the replication of the virus. Such a treatment would be years away, though.

“Right now I think the most important thing a pregnant woman can do – or someone thinking about pregnancy can do – is protect themselves against getting flu in the first place,” Blish said. “We’ve got years of safety data showing the vaccine is safe and decreases hospitalization and death in pregnant women, and decreases the risk of hospitalization of their babies born during flu season.”