Fever in pregnancy linked to autism

Spiking a fever in pregnancy may contribute to autism risk in the offspring. Researchers report that women who run a high temperature while pregnant — and don’t treat it — appear twice as likely to have a child with autism as women who don’t report any untreated fevers.

Other studies have suggested a link between infectious diseases during gestation and a heightened risk of having a child with an autism spectrum disorder. But the new study didn’t find a specific connection between influenza and the behavioral disorders, the researchers report in an upcoming issue of the Journal of Autism and Developmental Disorders.

“I think this is the largest and most careful study that’s been done on the topic of fever and influenza in autism development,” says Paul Patterson, a developmental neurobiologist at Caltech, who wasn’t part of this study.

Researchers at the University of California, Davis identified 538 children with an autism spectrum disorder, 163 others with developmental delays and 421 who were developing without any apparent problems. The children’s mothers provided health information on their pregnancies. After accounting for differences in race, child’s age, insurance, smoking, mother’s education and residence at the time of birth, the scientists found that women who had suffered an uncontrolled fever during pregnancy were roughly twice as likely to have an autistic child as mothers with no untreated fevers. Fever in gestation was also associated with a more than doubled risk of developmental delays, report the researchers, who recently also linked autism risk with obesity in pregnancy (SN: 5/19/12, p. 16).

 “I think pregnancy is the key for autism,” Patterson says. Several other research groups have also zeroed in on gestation as a critical time, he notes.

Inflammation accompanies fever in the body, and inflammatory proteins called cytokines can pass through the placenta into the fetus during pregnancy, says study coauthor Ousseny Zerbo, an epidemiologist at the Kaiser Permanente Northern California Division of Research in Oakland, who worked on the study while at UC Davis. This transfer would pose a risk if it alters brain development in the fetus at a crucial time, he says. “Elevated pro-inflammatory cytokines [in utero] lead to behavioral problems in animals,” he says.

What’s more, Patterson says, the heat of fever can overactivate neurons, inducing them to fire more and damage fetal brain growth, tests in animals show. 

Patterson cautions that while the new study is better than previous work on fever and autism, much of the data are based on the mothers’ memories of events that occurred years earlier. “Recall bias is always an issue in this area,” he says. “If you have an autistic child, you’re always searching for why that happened.”