‘Fascinating’ pregnancy research reinforces importance of flu shot

Matt Woodley

22/09/2020 3:30:48 PM

A ‘drastically heightened’ immune response, not immunosuppression, leads to complications during pregnancy, a new study has found.

Pregnant woman with flu-like symptoms
The research suggests the vascular system is central to complications caused by influenza during pregnancy.

The research, led by RMIT, suggests influenza does not stay in the lungs but spreads throughout the mother’s body – impacting current scientific thinking on why flu infections affect pregnant women and their babies so severely.
The research, conducted in animal models, shows flu spreads through the blood vessels during pregnancy into the circulatory system, triggering a damaging hyperactive immune response.
Lead author Dr Stella Liong said the research suggests the vascular system is at the heart of the potentially devastating complications.
‘We’ve known for a long time that flu can cause serious maternal and fetal complications, but how this happens has not been clearly understood,’ she said.
‘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.
‘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.’
Dr Wendy Burton is Chair of the RACGP Specific Interests Antenatal/Postnatal Care network. She told newsGP that while she has always advised pregnant women to receive a flu shot, the ‘fascinating’ new research could take the strength of her recommendation to a ‘whole other level’.
‘The take-away points for me were that [severe complications] may not represent immunosuppression in pregnant women, but a heightened immune response with cardiovascular consequences and a possible link to preeclampsia,’ she said.
‘This paper reinforces the importance of asking “why” and then following up promising leads from animal studies with human equivalents.’
Despite the known risks associated with contracting the flu during pregnancy – including pneumonia and other complications, increased risk of fetal growth restriction, miscarriage and preterm births – only around 39% of pregnant Australian women get immunised against the virus. 
However, general practice is well placed to help; previous research has shown GPs are critical to improving influenza immunisation rates among pregnant women, with a strong recommendation found to be the most important factor in increasing vaccine uptake.
‘It raises the importance of having an influenza vaccine in pregnancy from [being] “this is a really important preventative step for you to take” to [adding] “and it may affect you and your baby in profound ways that we are still actively researching”,’ Dr Burton said.
‘Anything we can do to reduce preeclampsia and to limit the number of pregnant women who end up in ICU is a really good idea.’
The research
Scientists had previously thought the reason flu has such serious health impacts during pregnancy is because the immune system is suppressed to enable the fetus to thrive, making it harder to fight infections.
But the new research on influenza A shows the virus behaves very differently in the bodies of pregnant and non-pregnant mice.
Study co-author Professor John O’Leary from Trinity College, Dublin, said the findings represent a landmark advance in the understanding of viral infections and pregnancy.
‘The discovery of an influenza-induced “vascular storm” is one of the most significant developments in inflammatory infectious diseases over the last 30 years,’ he said. ‘[It also] has significant implications for other viral infections, including COVID-19.’

Dr Wendy Burton says anything that reduces preeclampsia is ‘a really good idea’.
The spread of infection in pregnant mice into the circulatory system via the blood vessels led to intense inflammation, which drastically affected the function of large blood vessels and severely affected the health of the mother.
It was also shown to restrict blood flow to the growing fetus, as pregnant mice with flu had severe inflammation in the large blood vessels and the aorta, allowing them to function at only 20–30% capacity.
According to lead investigator Associate Professor Stavros Selemidis, even a small change in the diameter of a blood vessel can result in profound changes to blood flow.
‘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,’ he said.
‘We’ve known that flu infection in pregnancy results in an increased risk of babies being smaller and suffering oxygen starvation.
‘Our research shows the critical role that the vascular system could be playing in this, with inflammation in the blood vessels reducing blood flow and nutrient transfer from mum to baby.’
While the researchers did not directly measure blood flow, the study found an increase in biomarkers for oxygen starvation in the fetuses of the flu-infected mice.
Pregnancy is believed to affect influenza severity, as the placenta secretes proteins and releases fetal DNA into the mother’s blood that can cause underlying inflammation; influenza infection may tip that underlying inflammation in the mother’s body into a full-blown systemic inflammatory event.
As noted by Dr Burton, Associate Professor Selemidis said the research also revealed a new connection to preeclampsia. 
‘We found the same protein that is elevated in preeclampsia is also significantly elevated with flu,’ he said.
‘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.’
Aside from providing insights into how influenza affects pregnant women, Dr Liong said the research also contributes to the understanding of how COVID-19 may be affecting the vascular system.
‘Flu and coronavirus are different but there are parallels and we do know that COVID-19 causes vascular dysfunction, which can lead to strokes and other cardiovascular problems,’ she said.
‘Our studies in pregnancy offer new insights into the fundamental biology of how respiratory viruses can drive dysfunction in the vascular system.
‘This could be valuable knowledge for those scientists working directly on treatments and vaccines for COVID-19.’
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