Doctors trying to find some of the causes of autism put another piece into the puzzle on Monday: They found women who had flu while they were pregnant were twice as likely to have a child later diagnosed with autism. Those who had a fever lasting a week or longer -- perhaps caused by flu or maybe by something else -- were three times as likely to have an autistic child.
The study of 96,000 children in Denmark raises as many questions as it answers. But it fits in with a growing body of evidence that suggests that, in at least some cases, something is going on with a mother’s immune system during pregnancy that affects the developing child’s brain. Health officials said the finding reinforces their recommendations that pregnant women should make sure to get flu shots.
Autism seems to be a growing problem in the United States. According to the U.S. Centers for Disease Control and Prevention, autism spectrum disorder affects one in 88 children, including about one in 54 boys. The autism spectrum refers to a broad range of symptoms, from the relatively mild social awkwardness of Asperger’s syndrome to profound mental retardation, debilitating repetitive behaviors and an inability to communicate.
Scientists agree that it’s not just a matter of better diagnosis; the numbers seem to be growing because more children are indeed developing autism. But no one is sure why. Genetics are a large factor -- if one twin has autism the other twin is very likely to -- but genes don’t explain it all.
Some studies have pointed towards inflammation -- the mother’s immune response somehow affecting the brain of the developing fetus. So a team including Dr. Hjördis Ósk Atladóttir of the University of Aarhus in Denmark, Diana Schendel of the U.S. Centers for Disease Control and Prevention and colleagues studied a big database of children born in Denmark.
The 96,000 children were born between 1997 and 2003, to about 30 percent of all the women in Denmark who had children during those years. The women were interviewed twice while they were pregnant and then again when their babies were six months old. They were specifically asked about sicknesses they had, and about drugs they took to treat them.
Overall, 976 of the children were later diagnosed with an autism spectrum disorder -- about 1 percent of them.
Moms who said they had influenza while pregnant were more likely to have children later diagnosed with autism, the researchers report in Monday’s issue of the journal Pediatrics.
“We found almost a twofold increased risk of infantile autism in the child after self-reported infection with influenza virus during pregnancy,” the researchers wrote. Children whose mothers said they had a fever lasting more than a week during pregnancy had triple the risk of autism.
Women who reported other infections, such as a cold, a urinary tract infection or herpes, were not more likely to have a child with autism.
That doesn’t mean the infection caused autism and women should not panic if they become ill while pregnant, said Dr. Coleen Boyle, Director of the National Center on Birth Defects and Developmental Disabilities at the Centers for Disease Control and Prevention.
“We want to reassure women. In this study, most women who experienced flu or prolonged fever or who were taking antibiotics did not have children with an autism spectrum disorder,” Boyle told NBC News.
"It is important to bear in mind that when you look at the absolute numbers, we see that around 99 percent of women reporting to have had influenza or fever during pregnancy, do not have children with ASD (autism spectrum disorder)," Atladottir said by email "We do not want pregnant women to worry."
The researchers are not sure what may be going on. They also found that women who took certain antibiotics were more likely to have a child with autism, but it’s not clear if it’s the drug itself, or if women who took antibiotics were perhaps sicker than the other women.
“Animal studies suggest that when the mother’s immune system is triggered during pregnancy, such as when she is fighting off an infection… that immune response might affect a child’s developing brain,” Boyle said. Vaccines do not stimulate a similar immune response, doctors note.
It’s also not clear if there is something special about the influenza virus. “Misreporting of influenza is likely to be considerable; any episode of fever may be mistaken for influenza, and not all women infected with influenza virus might have been aware of this,” the researchers wrote. They did not cross-check what the women said against medical records to see who may have been diagnosed with flu.
Another study done in Sweden earlier this year found no association between flu or any other infection and autism. But a study published in May in the Journal of Autism and Developmental Disorders did find a connection. That study, done in the United States, found that women who had fevers while pregnant were twice as likely to have a child with autism or a developmental disorder.
"Growing evidence suggests inflammatory processes may be interfering with brain development at critical stages, leading to changes in behaviors such as those associated with autism, as well as cognitive deficits," Dr. Irva Hertz-Picciotto of the University of California-Davis MIND Institute, who conducted that study, told NBC News by email.
Each study adds a piece to the puzzle but none of them can answer the questions on their own. “We just need more research,” Boyle said.
So what can women do if they are worried?
Pregnant women are already strongly urged to get flu shots. The immunization protects them -- because a pregnant woman’s immune system is suppressed -- and it protects the baby for the first six months after birth. Pregnant women are much more likely to become severely ill with flu than other women. In Denmark, women are not routinely vaccinated against influenza.
“All women need to get their flu shots regardless of whether they are pregnant,” Boyle said. “And if a woman is pregnant and experiencing flu-like symptoms, she should call her doctor right away. If she has a fever, that fever can be treated with Tylenol. We know from other studies that fever (during pregnancy) can lead to other serious health problems in a child, such as a birth defect.”
Some people have been wary of vaccines since a study published in the 1980s linked autism to the combined measles, mumps and rubella vaccine. But that study has been debunked and the doctor who wrote it stripped of his license. Many researchers have tried hard since to find any possible evidence that vaccines could cause autism and they have been unable to.
“We don’t know what causes autism,” said Dr. Marshalyn Yeargin-Allsopp, chief of the Developmental Disabilities Branch at CDC.
“We know that genetic factors are extremely important. If a woman had flu and she has a child with autism, even with the results of this study, it doesn’t mean that the child’s autism is due to the fact that the mother had flu. There are a lot of factors that may be responsible for autism.”
(This story corrects Dr. Irva Hertz-Picciotto's affiliation. She is at the University of California-Davis MIND Institute)