Maternal pathways linking sociocognitive resources and immune balance to infant neurodevelopment: from cytokines to education.

BACKGROUND

The COVID-19 pandemic renewed interest in prenatal immune exposures and offspring neurodevelopment. While maternal immune activation (MIA) is associated with neurodevelopmental disorders (NDD), emerging evidence suggests that immune balance-particularly within the IL-6/IL-10 axis-may be more informative than absolute inflammatory levels.

METHODS

In the COGESTCOV-19 cohort, 95 children (50 prenatally exposed to maternal SARS-CoV-2 infection; 45 controls) were reassessed at 26 months using the Bayley-III (cognitive, language, and motor domains). Group comparisons (ANOVA/ANCOVA) and linear and nonlinear regressions (GAMs) examined associations between Bayley-III scores and the maternal baseline IL-6/IL-10 ratio, focusing on samples obtained within 0-4 weeks post-infection/vaccination; sensitivity analyses extended this window to 9 weeks.

RESULTS

No overall differences in Bayley-III outcomes were observed between exposed and control groups after covariate adjustment. However, time-sensitive nonlinear associations emerged. Among non-vaccinated mothers infected during pregnancy and sampled within 0-4 weeks post-infection, higher IL-6/IL-10 ratios were associated with lower model-estimated offspring expressive-language and fine-motor scores in specific analytical subsets. Vaccination was associated with higher IL-10 levels in controls, not cases, and longer post-vaccination intervals corresponded to declining IL-10 in controls. Independently, higher maternal education predicted better communication outcomes, while advanced maternal age showed nonlinear associations with poorer fine motor performance.

CONCLUSIONS

Variation in maternal immune balance during infection may be associated with subtle, domain-specific differences in early neurodevelopment. These exploratory findings do not establish causal immune pathways, a clinical IL-6/IL-10 threshold, or a protective effect of vaccination and require independent replication.