Brain development linked to inflammation

Increased inflammation during pregnancy is associated with subtle changes in brain organisation in newborns and a decrease in working memory at age two, new research shows.

The study, published in Nature Neuroscience, improves our understanding of the complex interplay between prenatal environment and development, and could lead to early interventions that reduce the impact of inflammation during pregnancy. 

Inflammation doesn’t just arise from infection or injury, but can also arise as a result of multiple environmental factors, such as poverty, obesity, famine, diet, as well as physical and emotional stress. 

Such stresses, when prolonged, can alter the way immune cells respond to hormonal cues, and disrupt the body’s ability to regulate inflammation.  

Growing evidence supports a link between chronic inflammation during pregnancy and poor neurological outcomes for offspring, including an increased likelihood of a number of cognitive and psychiatric conditions such as ADHD, major depression and schizophrenia. 

Moreover, it is known that certain markers of inflammation, like the protein interleukin-6, are expressed throughout the developing brain. But precisely how inflammation influences foetal brain development is unclear.

In an effort to learn more, researchers at the Oregon Health and Science University, in collaboration with researchers in Berlin and California, collected blood samples from 84 expectant mothers during each trimester of their pregnancies, and then tested the blood samples for levels interleukin-6. 

When the infants were four weeks old, they underwent MRI scans to determine their brain connectivity patterns. 

The researchers discovered that variations in levels of interleukin-6 during pregnancy were directly associated with small differences in neural connectivity patterns in the infants’ brains, suggesting that inflammation levels during pregnancy are linked with changes in neural communication in newborns.  

They were then able to use machine learning to develop a computer model that can analyse neural connectivity patterns in newborns, and then accurately estimate how much interleukin-6 must have been present during development. 

“Now, we have an approach that can utilize MRI brain scans of a newborn to accurately estimate the mother’s overall levels of inflammation during the time of her pregnancy,” says Alice Graham, one of the paper’s authors. 

The researchers also hypothesised that the inflammation-linked changes in infants’ brains could have implications for working memory skills later on.

Working memory relates to the ability to hold “chunks” of information in the mind for short periods of time while using that information, and is important for cognitive development.

When the children were two years old, they were given a simple test to assess working memory. Several pots were arranged on a spinning tray and each child was asked to place stickers inside six of the eight pots. After each time the tray was spun, the child had to remember which pots contained stickers and was asked to choose one.

It was found that infants whose mothers had higher levels of interleukin-6 during pregnancy had more difficulty with this task.   {%recommended 6558%}

Graham points out that the findings do not suggest that every exposure to inflammation in pregnancy will have a negative impact on the child. 

Moreover, she and her colleagues clarify that their findings do not show that inflammation directly causes individual differences in brain connectivity and working memory. Teasing out that relationship will require further research. 

However, the current results highlight an important connection between maternal inflammation and the developing architecture of the newborn brain and later cognitive function.   

“These findings provide new avenues for research, and can help health care providers think about how, and when, inflammation might impact a child’s long-term learning development and mental health,” says Graham.

This, in turn, could reveal opportunities for early clinical intervention where needed.

Associate Professor Seth Masters of the Walter and Eliza Hall Research Institute, who was not involved in the study, says that there has been speculation for a while that chronic low-grade inflammation could affect neural development, but “the changes are likely to be subtle and difficult to measure”. 

“The advance here is using sophisticated machine learning to examine connections in the brains of newborns, and finding that this can predict the prior level of inflammation during pregnancy,” he says.

“Neural differences associated with inflammation in pregnancy are so small that they can only be found by machine learning,” he cautions, “but this work provides more evidence that they are relevant for cognition later in life.”