Fever during pregnancy boosts autism risk

UC DAVIS (US) — Mothers who had a fever while pregnant were more than twice as likely to have a child with autism than mothers who did not have a fever or who took medication to counter its effect.

Published online in the Journal of Autism and Developmental Disorders, a new study is believed to be the first to consider how fever from any cause, including the flu, and its treatment during pregnancy can affect an unborn child’s chances of autism or developmental delay.

“Our study provides strong evidence that controlling fevers while pregnant may be effective in modifying the risk of having a child with autism or developmental delay,” says Ousseny Zerbo, lead author of the study, who was a Ph.D. candidate at the University of California, Davis when the study was conducted and is now a postdoctoral researcher with the Kaiser Permanente Northern California Division of Research.

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“We recommend that pregnant women who develop fever take anti-pyretic medications and seek medical attention if their fever persists.”

The results are based on data from a large, case-control investigation known as the Childhood Autism Risk from Genetics and the Environment (CHARGE) Study led by the UC Davis MIND Institute. Another recent study based on CHARGE data found that mothers who were obese or diabetic had a higher likelihood of having children with autism.

Fever is produced by acute inflammation—the short-term, natural immune system reaction to infection or injury—and chronic inflammation, which no longer serves a beneficial purpose and can damage healthy tissue, may be present in mothers with metabolic abnormalities like diabetes and obesity, says Irva Hertz-Picciotto, a professor of public health sciences at UC Davis and principal investigator of CHARGE.

Role of inflammatory factors

“Since an inflammatory state in the body accompanies obesity and diabetes as well as fever, the natural question is: Could inflammatory factors play a role in autism?”

When people are infected by bacteria or viruses, the body generally reacts by mounting a healing response that involves the release of pro-inflammatory cytokines from white blood cells into the bloodstream. Some cytokines are able to cross the placenta, and therefore could reach the fetal central nervous system, potentially altering levels of neurotransmitters and brain development.

“We definitely think more research is necessary to pinpoint the ways that inflammation could alter brain development,” says Hertz-Picciotto.

CHARGE includes an ethnically diverse population of children aged 2 to 5 years born in California and living in Northern California. The current study included 538 children with autism, 163 children with developmental delay but not autism, and 421 typically developing children whose mothers answered standardized questionnaires about whether they had the flu and/or fever during pregnancy and if they took medications to treat their illnesses.

The results show that flu during pregnancy is not associated with greater risks of having a child with autism or developmental delay. Fever from any cause during pregnancy, however, is far more likely to be reported by mothers of children with autism (2.12 times higher odds) or developmental delay (2.5 times higher odds), as compared with mothers of children who were developing typically. For children of mothers who took anti-fever medication, the risk of autism was not different from the risk in children whose mothers reported no fever.

Results based on CHARGE data are noteworthy because of the study’s large population-based sample and detailed information on participants, Irva Hertz-Picciotto says. Other CHARGE evaluations have found that taking prenatal vitamins prior to and during the first month of pregnancy may help prevent autism and that living near a freeway or in areas with high regional air pollution is associated with higher risk of autism in children.

“CHARGE has obtained a wealth of environmental, demographic and medical information on young children and their parents and provides a solid basis for a variety of epidemiologic studies,” says Hertz-Picciotto. “Those studies are helping us find ways to protect childhood neurodevelopment.”

The study was funded by the National Institute of Environmental Health Science.

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