The cold and flu season is beginning amid conflicting guidance on vaccination and the use of acetaminophen - a common fever-reducing drug sold under brand names such as Tylenol - during pregnancy. Adrienne Antonson is a professor of animal sciences at the University of Illinois Urbana-Champaign who studies the immune response during pregnancy and prenatal neurodevelopment. She discussed what her research has found about infection during pregnancy, how it affects development and effective ways to treat and prevent it in an interview with Lauren Quinn, the assistant director of research communications for the College of Agricultural, Consumer and Environmental Sciences at the U. of I.
We are heading into flu season here in the U.S. How can maternal infection affect fetal development?
My lab's primary focus is to understand the cellular and molecular pathways by which maternal flu infection during pregnancy impacts the developing fetal brain. To do this work, we utilize mice, as this allows us to collect and examine fetal brains at different time points following maternal infection, something we cannot do with humans.
When designing these experiments, we intentionally selected two doses of flu infection that are relevant to seasonal outbreaks in humans: one that is moderate - approximating the average infection during flu season, when patients experience fever and cough or sore throat but are able to manage these on their own - and one that is more severe - approximating the subset of bad flu cases with symptoms that require patients to see a clinician.
When we examine these two infection severities side-by-side, we find that the moderate infection leads to very few adverse outcomes in the fetus. Overall, the brain develops relatively normally. However, with the severe maternal infection, we find that fetal growth is restricted, there are more myeloid immune cells in the brain, and cortical development is disrupted - the brain cortex is thinner than expected, and the neurons are not expressing the appropriate markers.
These outcomes mirror what we see in the human data: only a subset of severe flu cases during pregnancy are linked to later diagnosis of mental health disorders or developmental delays in those children. Our lab calls this an "infection severity threshold."
But the flu is a respiratory virus. How can that cause changes in the fetal brain?
This is an important aspect of my research: The flu virus is very good at infecting the lungs, but not very good at infecting other organs. Thus, our studies and others have shown that it is the maternal inflammatory response to the infection that subsequently leads to problems in the fetal brain.
The virus itself does not infect the placenta nor the fetus. Instead, it is the immune signaling molecules produced by the pregnant mom - primarily pro-inflammatory cytokines - that are believed to directly and indirectly regulate adverse outcomes in the fetal brain. These signaling responses are part of the natural, and necessary, immune response against the virus, and they help mom fight off and clear the infection.
You can think of it this way: In the case of a moderate flu infection, the levels of antiviral inflammatory signaling molecules that mom produces to fight and clear the infection are still within a "less or nonharmful" range, and the fetus is relatively protected. But in the case of a severe infection, these signaling molecules may rise above this threshold, leading to adverse fetal outcomes. In some cases, severe infections can lead to miscarriage, stillbirth or preterm birth.
What about fever? Is that also a factor?
It is important to note that a fever is part of the natural antiviral immune reaction and aids the immune system inhibit viral replication, clear damaged cells and build up protective antibodies. Think of a fever as setting your oven to the correct baking temperature for a certain recipe; you want the temperature to be high enough for baking, but not too high and not too long.
However, there are many studies that link fever during pregnancy with increased offspring risk for neurodevelopmental disorders. Further evidence demonstrates that use of antifever medications reduces this risk. In the case of a severe infection, when a fever spikes to very high levels - over 103 degrees F - or lasts longer than expected, taking acetaminophen can be beneficial, as it helps to bring down the harmful temperature.
There's a lot of concern right now about correlation between the fever reduction medicine acetaminophen and neurodevelopmental disorders. If fever also is linked with those disorders, what is a pregnant person to do?
Because of numerous safety studies conducted around the world over many decades, acetaminophen is considered the safest option for pregnant people compared to nonsteroidal anti-inflammatory drugs or other pain relievers, which can have adverse effects on development. For example, ibuprofen can damage the heart and kidneys and increase the risk of other birth defects.
While it is always a good idea to consult your doctor, the risks of not taking Tylenol when experiencing a high or prolonged fever far outweigh the risks of taking it. The American College of Obstetricians and Gynecologists issued a statement affirming acetaminophen's safety.
It's safe to say severe infections of any kind aren't desirable in pregnancy. Are there measures people can take during pregnancy to reduce their risk?
If a pregnant woman has a confirmed infection with flu, she may be prescribed an antiviral medication like Tamiflu or Relenza. They prevent the spread of the virus within the body. Again, the benefits of taking this oral antiviral drug far outweigh the potential risks, and multiple studies have shown that Tamiflu and Relenza are safe to take during pregnancy.
Pregnant women should also ensure that they are up-to-date on their vaccinations, especially seasonal vaccines that protect against circulating viruses like the flu. These vaccines induce the body to generate protective antibodies, which means a pregnant person is far less likely to have a severe infection if they are exposed. The additional benefit of vaccination during or immediately preceding pregnancy is the phenomenon of passive immunity: In humans, the placenta facilitates the beneficial transfer of mom's protective antibodies to the developing child. Thus, the child can obtain this additional blanket of protection even before it is born.
As with all of these recommendations, it's always best to consult your physician before taking any medications or scheduling vaccinations. However, the biggest take-home message is this: The benefits of preventative measures like vaccination and mitigating strategies like the use of antifever or antiviral medications far outweigh the risks to both mom and baby in the case of an infection during pregnancy.
