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Author Notes:

Tamara S. Bodnar, Ph.D., Department of Cellular and Physiological Sciences, University of British Columbia, 3307 – 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada, Phone: +1 (604) 822-4554,FAX: +1 (604) 822-2316, tamara.bodnar@ubc.ca.

The authors wish to thank Dr. Timothy Kieffer for generously providing access to the QuickPlex and; Travis Webber for his assistance, as well as the families and children in Ukraine who generously participated in this study.

Subjects:

Research Funding:

This work was done in conjunction with the CIFASD, which is funded by grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Specific funding for this study was provided by a Developmental Project grant from the CIFASD (NIH/NIAAA U24AA014811) as well as NIH/NIAAA R37 AA007789 and RO1 AA022460 to JW.

Funding was also provided by NIH U01AA014835; and a grant from the U.S. Office of Dietary Supplements to CC.

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

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

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Journal Title:

Brain, Behavior, and Immunity

Volume:

Volume 73

Publisher:

, Pages 205-215

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2018 Elsevier Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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