Prenatal fever linked to autism risk

(Reuters Health) - Children born to mothers who experienced fever, especially multiple fevers, during the second trimester of pregnancy are at increased risk for developing autism spectrum disorder (ASD), a new study suggests.

Researchers found that mothers who experienced a fever over 99 degrees F (37.22 C) during the second trimester of pregnancy had a 40 percent increased risk of having a child with ASD compared to women who had no fevers.

But none of the women who used ibuprofen to treat a fever during pregnancy gave birth to children later diagnosed with autism, the researchers note.

“What is particularly important about our findings is that it not only strengthens the evidence for a particular pathway for ASD, but it also suggests that we may be very close to understanding how to safely mitigate or prevent some outcomes by directing prevention or intervention strategies toward this pathway,” said lead author Dr. Mady Hornig of Columbia University’s Mailman School of Public Health in New York.

An increased risk of ASD among women with prenatal fevers has been reported before, the authors write in the journal Molecular Psychiatry. What’s new about this study is that it is the first large, prospective investigation showing a so-called dose-response effect.

The chances of ASD rose with the number of maternal fevers, increasing by more than 300 percent if a mother had three or more fevers after the first trimester.

Since fever is caused by acute inflammation, the profound difference in risk of ASD is consistent with the idea that a longer exposure of the fetus to an inflammatory environment in the womb can cause a greater disruption of brain development, said Hornig. A crosstalk of immune molecules called cytokines can reach the fetus across the placenta to affect the developing brain.

The findings also provide clues to suggest women are using the wrong drug during pregnancy to bring down fever, according to Hornig. While none of the mothers who took the nonsteroidal anti-inflammatory (NSAID) ibuprofen to treat fever during the second trimester had a child who developed ASD, mothers who took acetaminophen during this time made very little difference in their child’s fever-related risk for ASD.

The study analyzed data on 95,754 women participating in the Norwegian Mother and Child Cohort Study, which is following pregnant Norwegian women and their children born between 1999 and 2009.

Among its limitations is that small numbers of women used ibuprofen during pregnancy so researchers can’t be confident that ibuprofen had mitigating effects.

In addition, the study did not address the causes of fever, such as microbial infections. “An ongoing study is testing blood samples collected at mid-pregnancy and at birth to explore the possible role of specific infectious agents and the contribution of distinctive patterns of immune response among mothers and children to understand the mechanisms creating vulnerability,” the researchers note in a statement.

“This is a really important study that sheds light on risk factors for ASD because of its size and it looked at how the use of different medications, as well as how the timing of a fever affects the risk of ASD. I don’t think previous studies have done that well enough. However, the studies have not been entirely consistent so we need to conduct more of them to sort out these effects,” said Dr. Geraldine Dawson, who wasn’t involved in the study.

Dawson, who directs the Duke Center for Autism and Brain Development in Durham, North Carolina, said she thinks it’s very important that fever and the medications used to treat it not be considered to be the causes of autism, but rather potential risk factors, just as cholesterol and high blood pressure are risk factors for heart disease.

“Fever may contribute to risk of ASD, but likely doesn’t operate in isolation,” she told Reuters Health.

Dr. Nathaniel DeNicola, an obstetrician at George Washington University in Washington, DC, told Reuters Health it is premature to recommend any changes in medical practice based on the study.

“In general, obstetrical practice won’t change with one study. We’ll need a large meta-analysis or systematic review to change our policy,” he said.

There has been an increase in ASD, he added, and “maternal fevers may be along for the ride.”

SOURCE: Molecular Psychiatry, online June 13, 2017.