Gestational cytokine concentrations and neurocognitive development at 7 years

Area of Science:

• Neuroscience
• Immunology
• Developmental Psychology

Background:

• Gestational inflammation is a suspected contributor to childhood brain abnormalities and neuropsychiatric disorders.
• The relationship between maternal cytokine levels during pregnancy and offspring neurocognitive development requires further investigation.

Purpose of the Study:

• To examine the association between maternal cytokine concentrations during the second and third trimesters of pregnancy and neurocognitive development in offspring at age 7.
• To investigate the cumulative effects of specific pro-inflammatory and anti-inflammatory cytokines on intelligence, academic achievement, and neuropsychological functioning.

Main Methods:

• Maternal serum samples from 1366 women in the New England Family Study were assayed for five cytokines (IL-6, IL-1β, IL-8, TNF-α, IL-10) up to four times during pregnancy.
• Offspring neurocognitive outcomes, including IQ, academic achievement, and neuropsychological tests, were assessed at age 7.
• Linear mixed-effects models were used to estimate cumulative cytokine exposure and its association with neurocognitive outcomes.

Main Results:

• Higher gestational levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α) were associated with lower offspring IQ, higher visual-motor maturity scores, and lower Draw-a-Person test scores.
• Elevated gestational levels of the pro-inflammatory cytokine interleukin-8 (IL-8) were linked to better performance on the Draw-a-Person test and tactile finger recognition.
• Other investigated cytokines (IL-6, IL-1β, IL-10) did not show significant associations with the studied neurocognitive outcomes.

Conclusions:

• Gestational exposure to specific pro-inflammatory cytokines, particularly TNF-α and IL-8, may differentially influence various domains of childhood neurocognitive development.
• The opposing associations of TNF-α and IL-8 suggest complex, potentially pleiotropic effects of maternal immune activation on fetal brain development.
• Immune system processes during pregnancy may play a role in shaping neurocognitive trajectories, contributing to the multifactorial etiology of childhood neurodevelopmental outcomes.