Maternal and neonatal cytokine profiles in a twin cohort: evidence from an exploratory pilot study of perinatal immune dysregulation in autism

Abstract Background Autism spectrum disorder (ASD) has been linked to immune dysregulation during early development, yet few studies jointly examine maternal pregnancy and cord blood (CB) cytokines in relation to later diagnosis. Methods In a nested case–control design within the Peri/Postnatal Epigenetic Twins Study, we measured 19 cytokines in maternal pregnancy serum (~28 weeks) and CB at birth. Participants included autism cases ( n = 15), controls ( n = 72), mothers of autism cases ( n = 11), and control mothers ( n = 36). In this exploratory pilot study, CB cytokine–autism associations were analyzed using generalized estimating equations, maternal cytokines using logistic regression, and maternal–cord associations using linear mixed-effects models. False discovery rate (FDR) correction was applied. Results Elevated CB IL-1α ( p = 0.038), IL-5 ( p = 0.036), IL-12p40 ( p = 0.016), and GM-CSF ( p = 0.016) were significantly associated with autism following FDR correction. Combined, these cytokines demonstrated apparent discriminatory ability (AUC = 0.93; 95% CI 0.85–1.0) within the study sample. No maternal pregnancy cytokines were independently associated with autism. Maternal–cord analyses revealed cytokine‑specific coupling differences, particularly for IL-1α and IL-5 (both p = 0.008, FDR corrected). Conclusion Selective CB cytokine differences at birth are associated with later ASD diagnosis, supporting a role for perinatal immune signaling in neurodevelopment. Replication in larger cohorts is recommended for further validation. Impact In twins, cord blood cytokine signatures at birth are associated with autism diagnosis at 6 years. Elevated IL‑1α, IL‑5, IL‑12p40 and GM‑CSF characterize autism cases and show strong individual‑level discriminative performance. Combined cord blood cytokines can discriminate autism from controls, highlighting potential biomarker utility. Different maternal-cord cytokine coupling suggests disrupted late‑gestation immune signaling relevant to neurodevelopment.