Running a fever during pregnancy—particularly during the second trimester—is linked to an increased risk of autism in children, according to a new study. Treating fevers with acetaminophen (best known as Tylenol) may be somewhat protective, say the authors, although they stress that more research is needed in this area.
Autism has previously been tied to prenatal exposure to a wide range of infections, researchers at Columbia University wrote in the journal Molecular Psychiatry. Because fever is such a common response to infections and illness, they wanted to see whether high temperatures during pregnancy—and attempts to lower those temperatures with medication—seemed to play a role in a child’s likelihood of being diagnosed years later.
So the researchers studied nearly 100,000 mothers and their children born between 1999 and 2009 in Norway. About 16% of the women reported having at least one fever during their pregnancies, a rate that’s similar to estimates in the United States. Between ages 3 and 7, the children were screened for autism spectrum disorder, and 583 were diagnosed.
After adjusting for factors such as maternal age, smoking status, and previous pregnancies, the researchers found that children whose mothers reported fever at any time during pregnancy had a 34% increased risk of developing autism compared to those whose moms reported no fevers. Much of that increased risk seemed to originate in the second trimester: Kids whose moms had fevers during this period had a 40% increased risk of autism, compared to those whose moms didn’t.
When women reported only one or two fever episodes after 12 weeks, their children’s increased risk for autism was only about 30%. But with three or more fever episodes, it jumped to more than 300%.
That may sound scary to mothers-to-be. But first author Mady Hornig, MD, associate professor of epidemiology at Columbia University’s Center for Infection and Immunity, says it’s important to remember that the overall risk is still very low. Even among mothers who had three or more fevers after the 12-week mark, only 5 out of 308 children (or about 1 in 62) developed autism. That’s compared to 376 out of the 65,502 children whose moms never had fever, or about 1 in 178.
Doctors don’t know why, exactly, a mother’s fever might boost her child’s autism risk. But Dr. Hornig points out that the second trimester is a time of key brain development; it’s also a time when the mother’s immune system is somewhat “turned down,” so her body won’t reject the growing fetus. Together, she says, these factors could make her offspring more vulnerable to developmental disruption.
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Because the study was observational, it was unable to prove a cause-and-effect relationship between prenatal fever exposure and the development of autism. As a follow-up, the researchers are now analyzing blood samples from mothers and babies to determine what types of infections—or what types of immune responses from the mother—may be associated with greater risks than others.
“If we can figure that out, we can think more about how to prevent those specific infections during pregnancy,” Dr. Hornig says. But it’s equally important, she adds, to know how to treat fever in pregnant women when it does occur.
The study did find that children whose mothers took acetaminophen to lower fevers during their pregnancies had a slightly lower risk of autism than those who had fevers but didn’t take anything. But the difference between groups was much smaller than the researchers expected.
“We were surprised there was not a more robust effect,” says Dr. Hornig. “At this point it’s hard to tell whether it really has a meaningful effect at all.”
The researchers wanted to know if taking ibuprofen would have protective effects, as well, but not enough women in the sample used the drug during pregnancy to make any meaningful conclusions. (None of the moms who took ibuprofen had children who developed autism, but Dr. Hornig says this finding should be interpreted with “extreme caution.”)
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While acetaminophen and ibuprofen both reduce fever, only ibuprofen has anti-inflammatory properties—which could potentially offer additional safeguards against the risks associated with fever and infection, the authors say. But some studies have suggested a link between ibuprofen and miscarriages, and doctors don’t usually recommend the drug to pregnant patients.
Dr. Hornig says that it’s important to weigh the pros and cons of any medication considered during pregnancy—including acetaminophen—and she stresses that the new study doesn’t change current recommendations for how moms-to-be should manage pain or fever. (If you’re unsure of what’s safe, she says, ask your obstetrician.)
But she does say women can take simple precautions to reduce their risk of developing infections that can trigger a fever—like the flu, for example. “I think that being healthy, washing your hands, and avoiding contact with sick individuals are all fairly easy to do," she says, "and it’s a good idea for this and a lot of other reasons."
The U.S. Centers for Disease Control and Prevention recommend that pregnant women get a flu shot in any trimester to protect themselves and their newborns from the flu (protective antibodies can be passed from mom to baby).