Severe Flu During Pregnancy Can Break Fetal Barriers in Mice, Allowing Harmful Molecules to Enter the Brain

A groundbreaking study from the University of Illinois Urbana-Champaign has revealed that severe influenza infections during pregnancy can compromise the protective barriers in the fetus, specifically the placental and brain barriers. This breakdown allows potentially harmful molecules, such as fibrinogen—a blood clotting protein linked to neuroinflammatory diseases like multiple sclerosis and Alzheimer’s— to pass into the developing fetal brain.

The research involved infecting pregnant mice with live influenza A virus at moderate and severe levels to mimic typical and extreme human flu cases. During pregnancy, fluorescent tracers of various sizes were injected into the mice, enabling scientists to track the movement of molecules analogous to blood proteins into fetal tissues. The findings showed that in cases of severe infection, even large molecules that normally cannot cross the blood-brain barrier accumulated in the fetal brain. They also found high levels of fibrinogen in the fetal brains, particularly in regions critical for neurodevelopment, such as the subventricular zone and choroid plexus.

"Our results suggest that influenza infection can make the placental and brain barriers 'leaky,' which may have long-term effects on neural development and mental health outcomes," explained senior author Adrienne Antonson. This leaky barrier could expose the fetal brain to inflammatory molecules, potentially impacting neurodevelopmental processes.

The study highlights that the severity of the infection plays a crucial role, with more severe infections increasing the likelihood of these molecules breaching fetal defenses. By including doses that resemble mild and severe human flu, the findings are highly relevant to human health. It underscores the importance of influenza vaccination during pregnancy to prevent severe infections that could disrupt fetal development.

While this research was conducted in mice, it offers important insights that may translate to humans. It points to the need for further studies to understand how infections during pregnancy can influence long-term neurodevelopmental health. The findings emphasize the critical role of maternal health and infection severity in safeguarding fetal brain development.