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There is growing evidence to support a link between maternal inflammation during pregnancy and brain development in offspring, but a full understanding is lacking. In a longitudinal study, Rudolph et al. found that differences in maternal interleukin-6 (IL-6) levels during pregnancy correlate with changes in functional brain connectivity in newborns, and with reductions in working memory performance in these children when they reached 2 years of age.

Cytokines and their receptors are expressed throughout the fetal brain and play roles in various developmental processes, including cell survival, axon growth and synaptogenesis. Systemic inflammation results in increased production of pro-inflammatory cytokines, and it is conceivable that cytokines in the maternal circulation could impact the developing fetus via the maternal–placental–fetal route. Maternally derived pro-inflammatory cytokine signalling could thus alter neurodevelopmental processes throughout the fetal brain and affect brain function later in life.

Research in animal models has suggested that the pro-inflammatory cytokine IL-6, in particular, is a key factor communicating maternal inflammation to the developing fetus, and has been associated with an increased risk of disrupted neurodevelopment. The authors used this cytokine as a marker of maternal inflammation during pregnancy.

First, the authors measured maternal IL-6 levels in early, middle and late pregnancy. Then, in the newborn offspring, they measured functional connectivity within and between key large-scale brain networks, and used a machine-learning approach to generate a multivariate model of the relationship between brain connectivity and mean maternal IL-6 levels. Certain patterns of alterations in connectivity between several large-scale networks (particularly salience, dorsal attention and subcortical networks) were significantly associated with higher maternal IL-6 levels. Importantly, many of these networks comprised brain areas that had been determined by a meta-analysis to be involved in working memory. When working memory was tested in these children at 2 years of age, the authors found a negative correlation between working memory performance and maternal IL-6 levels.

Overall, these data indicate that, in humans, elevated inflammation during pregnancy alters the functional connectivity of and between large-scale brain networks and may be associated with reduced working memory performance in early childhood.