Altered maternal immune networks are associated with adverse child Check for neurodevelopment: Impact of alcohol consumption during pregnancy

• Authors: Tamara S. Bodnar, University of British Columbia; Charlis Raineki, University of British Columbia; Wladimir Wertelecki, University of California, San Diego; Lyubov Yevtushok, Rivne Oblast Medical Diagnostic Center; Larisa Plotka, Rivne Oblast Medical Diagnostic Center; Natalya Zymak-Zakutnya, Khmelnytsky Perinatal Center; Gordon Honerkamp-Smith, University of California, San Diego; Alan Wells, University of California, San Diego; Matthieu Rolland, University of California, San Diego; Todd S. Woodward, University of British Columbia; Claire Coles, Emory University; Julie Kable, Emory University; Christina D. Chambers, University of California, San Diego; Joanne Weinberg, University of British Columbia
• Journal Title: Brain, Behavior, and Immunity
• Volume: Volume 73
• Publisher: Elsevier: 12 months | 2018-10-01, Pages 205-215
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.bbi.2018.05.004
• Subjects: Health Sciences, Medicine and Surgery; Health Sciences, Immunology; Biology, Neuroscience
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Neurosciences; Psychiatry; Neurosciences & Neurology; Cytokines; Neurodevelopment; Pregnancy; Immune; Alcohol; Fetal alcohol spectrum disorders; TUMOR-NECROSIS-FACTOR; PRINCIPAL COMPONENT ANALYSIS; AUTISM SPECTRUM DISORDERS; ENDOTHELIAL GROWTH-FACTOR; EARLY-LIFE ADVERSITY; INFLAMMATORY CYTOKINES; AMNIOTIC-FLUID; NEURONAL DEVELOPMENT; NEONATAL BRAIN; FACTOR-ALPHA

Abstract

Cytokines and chemokines are potent modulators of brain development and as such, dysregulation of the maternal immune system can result in deviations in the fetal cytokine balance, altering the course of typical brain development, and putting the individual on a “pathway to pathology”. In the current study, we used a multi-variate approach to evaluate networks of interacting cytokines and investigated whether alterations in the maternal immune milieu could be linked to alcohol-related and alcohol-independent child neurodevelopmental delay. This was achieved through the measurement of 40 cytokines/chemokines from maternal blood samples collected during the second and third trimesters of pregnancy. Importantly, during the second trimester we identified network enrichment in levels of cytokines including IFN-ɣ IL-10, TNF-β TNF-α and CRP associated with offspring neurodevelopmental delay. However, as elevations in levels of these cytokines have previously been reported in a wide range of neurodevelopmental disorders including autism spectrum disorder and schizophrenia, we suggest that this cytokine profile is likely not disorder specific, but rather may be an indicator of neurodevelopmental delay in general. By contrast, distinct clusters of activated/inhibited cytokines were identified based on maternal alcohol consumption and child neurodevelopmental outcome. Specifically, cytokines including IL-15, IL-10, MDC, and members of the VEGF sub-family were highest in alcohol-consuming mothers of children with neurodevelopmental delay and were identified in both network analyses and examination of individual cytokines, whereas a differential and unique cytokine profile was identified in the case of alcohol-independent child neurodevelopmental delay. We propose that the current findings could provide a critical step towards the development of early biomarkers and possibly interventions for alcohol-related neurodevelopmental delay. Importantly, the current approach could be informative for understanding mechanisms linking maternal immune system dysfunction and adverse child outcomes in a range of other neurodevelopmental disorders.