Does Autism risk climbs with number of fevers during pregnancy?

Sun Jul 3, 2022

Pregnancy fever increases the chance for having children diagnosed with autism, as per the study of more than 95,000 women.

The connection is most evident in the second trimester where a single fever can lead to an increase of 40 percent in the risk of autism. Three or more fevers following the first trimester can triple the likelihood for having children diagnosed with autism, as per the study, published on the 13th of June Molecular Psychiatry.

The research supports the notion that the immune system of a pregnant woman, which can include fever, could cause brain damage in the fetus. the principal investigator Mady Hornig Associate Professor of Epidemiology at Columbia University.

The study has not concluded whether medications that lower fever reduce the risk of developing autism but the results suggest that they may, according to Sarkis Mazmanian who is a professor of biology in the California Institute of Technology. Mazmanian did not participate in the study, but studies the role of maternal infections as an important risk factor for autism. "I'm being very optimistic here, but I think there's value in more research in this space," Mazmanian declares.

In another study, researchers have asked mothers of children diagnosed with autism to tell them if they experienced a fever while they had babies. In this new study the women were asked questions regarding fevers at least every four weeks during the course of pregnancy. The ability to recall a fever for years after the event is a challenge for mothers of children who have autism might be more likely to falsely remember having the fever. Therefore, the study's method may yield more precise findings than the previous study.

"This is a major strength, since the questions were asked at a time relatively close to the fever episodes and long before the mothers knew their child's neurodevelopmental status," says Irva Hertz-Picciotto Professor of Epidemiology of the University of California, Davis and not part of the study.


Temperature Monitoring

Hornig together with colleagues examined the data of the study of 95,754 mother-child pairs from Norway. Of them, 15,701 of mothers had reported on an assessment of their health that they'd suffered at least one fever during their time pregnant. The team monitored all of their children's children up until they reached the age of 9, on average, and discovered that 583 had an Autism diagnosis.

The time of the fever's onset is important in determining the risk of autism, researchers discovered. In comparison to the 40 percent increase during the second trimester, that is, having a fever during the first trimester is associated with a 34 percent increase in risk of having autism; however, this isn't statistically significant. The presence of a fever during the third semester does not have an influence on the risk of developing autism.

Researchers also discovered the dose-response connection for fever The risk increase can range from 30 percent through pregnancy for a single or two instances of fever up to three times greater for more than three episodes during the second trimester , and even beyond.

However, most women that experience an illness during pregnancy don't have an autistic child and the increase in risk is minimal. For mothers who have three or more fevers only 5 thirty-eight children (about 1.6 per cent) have autism, as compared with 376 children out of 65502 (about 0.6 per cent) with mothers who reported no fevers.


The Effect

Another study by the same group, which was published in last week's issue of mSphere and discovered that women who have been confirmed with laboratory tests for flu during pregnancy aren't less likely than women without the illness to be blessed with a baby who has autism 2.. However, women who had symptoms of influenza, such as fever, almost doubled their chances for having children diagnosed with autism, which supports the notion that inflammatory processes are the main cause of the risks, Hornig says. The rise isn't statistically significant, however it should not be overlooked as the team suggests.

"Although chance may explain our findings, the magnitude of the potential association may be of biological importance," researchers write in the study.

It also increases the creation of white blood cells which release certain molecules called cytokines to fight off infections. Research in mice suggests that the cytokines can enter the bloodstreams of the foetus via the placenta, and then change the expression of genes linked with autism in the brain's development.

Chronic fevers can cause cytokines to accumulate, increasing the risk of autism, Hornig states.

"A transient fever that comes and goes quickly perhaps doesn't have as much risk as something that is happening frequently and causing these molecules to increase or perhaps accumulate over many weeks," she states.

The severity of the fever could be influenced by the genetic nature of the mother's body, Hornig says. "Some women have an immune response that fails to come back down again after it's done its work," she states. "There may be genetic factors on the fetus side as well."

Hornig's team looked into whether medicines that reduce body temperature could lower the chance of developing a complication. Over 5,600 women used Acetaminophen for fever during the second trimester. The researchers found a link between acetaminophen usage and a reduction in autism risk, however it wasn't statistically significant. There were only 161 women who took ibuprofen during the second trimester but none has children with autism. (About 50% of women who are pregnant utilize acetaminophen on a regular basis but doctors typically recommend against using ibuprofen in pregnancy.)

"Because the numbers were small, we need huge caution," when considering the findings about ibuprofen Hornig states. However, she adds that the link requires further study.

A 2013 study , led by Hertz-Picciotto discovered that the use of drugs that reduce fever can mitigate the risk of developing autism that is associated with the fever.

Hornig is planning to investigate whether certain women are more likely to gain from these medications during pregnancy. "We want to look at the genetic component, to help us provide precision medicine for management of a common phenomenon during pregnancy," she states. She plans to also measure the levels of cytokines present in pregnant women in order to determine the role played by the molecules within the development process.


Ashutosh Bhardwaj, MBBS, DCH, PGDUS, PGPN
He is a Pediatrician and Neonatologist with passion of teaching on pregnancy diet and nutrition, scientific womb talk trainer, and baby brain development trainer.

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