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Inflammation in pregnant women strongly linked to baby’s brain development

A mother’s inflammation during pregnancy, whether caused by infection, injury or stress, may have an impact on the brain development of her child, a new study has found.

US and German researchers studied 84 families and found mothers with higher levels of an inflammatory protein called interleukin-6 (IL-6) during pregnancy had children with poorer working memories at age 2.

“This doesn’t mean that every exposure to inflammation will result in a negative impact to the child,” co-author Alice Graham from Oregon Health and Science University (OHSU) said.

“However, 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.”

A growing number of epidemiological and animal studies have shown that in pregnant women, the immune system’s inflammatory response to an injury or illness can increase the risk of mental illness or brain development problems in the child.

For the first time, researchers from OHSU, University of California, Irvine, and Charité – Universitätsmedizin Berlin have established a strong link between maternal inflammation, altered brain function and working memory through a human study.

First, they measured the levels of IL-6, an inflammatory marker known to play a role in foetal brain development, in each pregnant woman.

After birth, they measured each infant’s brain activity at rest with functional magnetic resonance imaging to determine the pattern of the newborn’s brain network organisation.

Later, when each child turned two, they invited them to the lab to play games. They focused on a game that tested working memory called ‘spin-the-pots’. Scores ranged from a high of 16 (no errors) to a low of 0 (16 incorrect guesses).

Higher levels of IL-6 tended to result in less working memory capacity in the child.

“Findings highlight the association of maternal inflammation during pregnancy with the developing functional architecture of the brain and emerging executive function,” they wrote in the latest Nature Neuroscience.

In another first, the researchers created a model using artificial intelligence that could accurately predict a mother’s inflammatory response during pregnancy based on her baby’s brain connectivity patterns.

In turn, they were also able to predict a child’s future working memory based on a mother’s levels of IL-6 during pregnancy.

“Increased stress and poor diet are considered normal by today’s standards, but greatly impact inflammation rates in all humans, not just expectant mothers,” co-author Associate Professor Damien Fair from OHSU said.

“Just as important to understanding how the immune system and inflammation affect early brain development, we also need to understand what common factors contribute to heightened inflammation so that we may target therapies to help reduce the rates of inflammation and overall impact on the developing brain.”

Associate Professor Tim Moss, a developmental physiologist at Monash University, raised concerns about the narrow focus on a single type of protein, saying there were countless other inflammatory markers.

“I’d like to see if the associations the researchers describe can be replicated using some of these other indicators,” he said.

Michael Berk, professor of psychiatry at Deakin University, said the study was concordant with previous work that showed environmental factors in pregnancy – infections, smoking and diet – may impact brain development.

“It would have been nice to know of maternal exposure to poor or good quality diet, smoking, major stressors and illnesses, to explain where the inflammation is coming from,” he said.

“That persistent inflammation is deleterious to the brain is well understood, but the links to functional connectivity and later cognition are important findings.”

Associate Professor Seth Masters from the Walter and Eliza Hall Institute said the new models to predict IL-6 levels in pregnancy women and future working memories of children were an important advance.

“Remarkably, this also had predictive power for behaviour of the children when they became toddlers,” he said.

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

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