New insights into flu risk during pregnancy

Researchers in Australia and Ireland may have discovered why influenza affects pregnant women so severely, sometimes leading to life-threatening complications.

A pre-clinical study in mice suggests the virus spreads from the lungs through the blood vessels into the circulatory system, triggering a damaging hyperactive immune response.

“Conventional thinking has blamed the suppressed immune system that occurs in pregnancy, but what we see is the opposite effect: flu infection leads to a drastically heightened immune response,” says Stella Liong, from Australia’s RMIT University.

“The inflammation we found in the circulatory system is so overwhelming, it’s like a vascular storm wreaking havoc throughout the body.

“We need further research to clinically validate our findings, but the discovery of this new mechanism is a crucial step towards the development of flu therapies designed specifically for pregnant women.”

Liong is the lead author of a paper in the journal Proceedings of the National Academy of Sciences. The research was a collaboration between RMIT, University of South Australia, Trinity College Dublin, La Trobe University and Monash University.

200922 flu aorta
An immunofluorescence microscopy image shows how activated immune cells (red) stick to the inside of the aorta (green) during flu infection in pregnancy. Credit: RMIT University

Pregnant women who develop influenza are considered at higher risk of hospitalisation with pneumonia and other complications, while babies of mothers severely affected by flu are at increased risk of foetal growth restriction, miscarriage and preterm births.

Liong and colleagues found that pregnant mice with flu had severe inflammation in the large blood vessels and the aorta – the major conduit from the heart. While a healthy blood vessel dilates 90-100% to let blood flow freely, the flu-infected blood vessels functioned at only 20-30% of capacity.

“We found a dramatic difference in these inflamed blood vessels, which can seriously affect how much blood makes it to the placenta and all the organs that help support the growing baby,” says RMIT’s Stavros Selemidis.

While the researchers did not directly measure blood flow, the study found an increase in biomarkers for oxygen starvation in the foetuses of the flu-infected mice.

Pregnancy makes a difference, they say, because the placenta secretes proteins and releases foetal DNA into the mother’s blood, which can cause underlying inflammation.

The study suggests the influenza infection may tip that underlying inflammation in the mother’s body over the edge, into a full-blown systemic inflammatory event.

The research also reveals a new connection to pre-eclampsia, a dangerous pregnancy complication characterised by high blood pressure, Selemidis says. “We found the same protein that is elevated in pre-eclampsia is also significantly elevated with flu.

“While it will take further research to unpack this link, it could mean drugs targeting vascular inflammation that are currently being tested could potentially be repurposed in future for flu infection in pregnancy.”

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