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 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.
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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: http://go.nature.com/2sx1tEl Molecular Psychiatry, online
June 13, 2017.
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