Infections During Pregnancy May Increase Autism Risk

Every day our brains help us make sense of the world around us, interpreting the experiences we see, hear, taste, touch and smell. But if someone’s brain has trouble processing this incoming information, it can be hard to communicate, understand or learn.

Autism spectrum disorders (ASD) are characterized by difficulties in social interaction, verbal and nonverbal communication and repetitive behaviors. These disorders include autism, Asperger syndrome and pervasive developmental disorder-not otherwise specified (PDD-NOS).

About one in 88 children have been identified with an autism spectrum disorder, and over 2 million people are affected in the United States, according to the Centers for Disease Control and Prevention. Government statistics also suggest that the proportion of people with autism spectrum disorders have increased 10 to 17 percent annually in recent years. This is in part due to wider awareness and better screening, but the continued increase is not fully understood.

The cause of ASD is also not fully known, but current research indicates that it is likely due to a complex combination of genetic predisposition and environmental risk factors that influence early brain development. Significant environmental risk factors include the advance age of either parent at the time of conception, maternal illness during pregnancy, extreme prematurity and very low birth weight.

Over 40 years ago, epidemiological studies determined that the risk of having a child with ASD is increased when the mother has an infection early in the pregnancy. Since a wide range of bacterial and viral infections can increase the risk, studies suggest that activation of the mother’s general immune system is responsible. However, scientists do not completely understand how the activated immune system can disrupt normal brain development to cause ASD.

Research at the UC Davis’ Center for Neuroscience provides new insight. Recently published in the Journal of Neuroscience, their studies identify a new biological mechanism that links maternal immune activation to neurodevelopmental disorders.

Kimberley McAllister, a senior author of the study, explained in a press release, “This is the first evidence that neurons in the developing brain of newborn offspring are altered by maternal immune activation. Until now, very little has been known about how maternal immune activation leads to autism spectrum disorder and schizophrenia-like pathophysiology and behaviors in the offspring.”

The researchers studied pregnant mice with immune systems that were activated halfway through gestation compared to pregnant control mice without activated immune systems. They found that the mice exposed to a viral infection had offspring with dramatically elevated levels of immune molecules called major histocompatibility complex 1 (MHC1) on their brain surface.

In the affected newborn mice, these high levels of MCH1 disrupted the development of neural cells in the brain. Specifically, the increase in MCH1 interfered with the neurons’ ability to form the synapses that allow neurons to pass electrical or chemical signals to other cells; consequently, these offspring had less than half as many synapses than the control offspring. When MCH1 were returned to normal levels in the neurons of maternal immune-activated offspring, the synapses density returned to normal.

However, MCH1 doesn’t work alone. In a series of additional experiments, the researchers identified the new biological signaling pathway that regulates synapses development caused by maternal immune activation. This signaling pathway requires calcineurin, myocyte enhancer factor-2 and MCH1 to limit synapses density.

A better understanding of the underlying biological mechanisms will hopefully lead to the development of improved prenatal health screening, diagnostic tests and eventually therapies for neurodevelopmental disorders.

Of course, not every child of a bacterially or virally infected mother develops a neurodevelopmental disorder like autism. The effect of maternal immune activation depends on a complex interaction involving the strength of the infection and genetic predisposition.