Systemic inflammation during the first year of life is associated with brain functional connectivity and future
Ashley M Bach1, Wanze Xie2, Laura Piazzoli3
1Labs of Cognitive Neuroscience, Division of Developmental Medicine, Boston Children's Hospital, USA; Harvard T.H. Chan School of Public Health, USA.
Insights
Early life systemic inflammation negatively impacts child cognitive development. Inflammation in the first year is linked to poorer cognitive scores later, despite not directly affecting brain connectivity pathways.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Early childhood is a critical period for neural and immune system development.
- Adverse experiences can trigger systemic inflammation, potentially impacting developmental trajectories.
- The precise mechanisms linking inflammation to brain development and cognitive outcomes are not fully understood.
Purpose of the Study:
- To investigate the association between recurrent systemic inflammation in infancy, brain functional connectivity, and cognitive outcomes in early childhood.
- To explore the role of electroencephalography (EEG) functional connectivity (FC) in mediating the relationship between inflammation and cognition.
Main Methods:
- Longitudinal cohort study of 122 children in a limited-resource setting (Dhaka, Bangladesh).
- Systemic inflammation assessed via C-reactive protein (CRP) levels at multiple time points in the first year.
- EEG functional connectivity (FC) measured at 36 months.
- Composite cognitive outcomes assessed at 3, 4, and 5 years.
Main Results:
- Recurrent systemic inflammation in the first year was significantly associated with lower cognitive scores at ages 3, 4, and 5, even after controlling for stunting and home environment.
- Systemic inflammation was positively associated with parietal-occipital FC in the Beta band at 36 months.
- This altered FC was negatively associated with cognitive scores at 3 and 4 years, but did not mediate the inflammation-cognition link.
Conclusions:
- Early life recurrent systemic inflammation poses a risk to cognitive development.
- While altered brain functional connectivity is associated with inflammation, it does not appear to be the sole mediator of cognitive deficits.
- Further research is needed to elucidate the complex pathways between inflammation, brain development, and long-term cognitive function.
Abstract:
The first years of life are a sensitive period of rapid neural and immune system development vulnerable to the impact of adverse experiences. Several studies support inflammation as a consequence of various adversities and an exposure negatively associated with developmental outcomes. The mechanism by which systemic inflammation may affect brain development and later cognitive outcomes remains unclear. In this longitudinal cohort study, we examine the associations between recurrent systemic inflammation, defined as C-reactive protein elevation on ≥ 2 of 4 measurements across the first year of life, electroencephalography (EEG) functional connectivity (FC) at 36 months, and composite cognitive outcomes at 3, 4, and 5 years among 122 children living in a limited-resource setting in Dhaka, Bangladesh. Recurrent systemic inflammation during the first year of life is significantly negatively associated with cognitive outcomes at 3, 4, and 5 years, after accounting for stunting and family care indicators (a measure of stimulation in the home environment). Recurrent systemic inflammation is significantly positively associated with parietal-occipital FC in the Beta band at 36 months, which in turn is significantly negatively associated with composite cognitive scores at 3 and 4 years. However, FC does not mediate the relationship between recurrent systemic inflammation and cognitive outcomes.
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