Molecular Neurobiology

, Volume 56, Issue 7, pp 5000–5008 | Cite as

Maternal Gestational Immune Response and Autism Spectrum Disorder Phenotypes at 7 Years of Age in the Seychelles Child Development Study

  • Jessica L. Irwin
  • Alison J. Yeates
  • Maria S. Mulhern
  • Emeir M. McSorley
  • J. J. Strain
  • Gene E. Watson
  • Katherine Grzesik
  • Sally W. Thurston
  • Tanzy M. Love
  • Tristram H. Smith
  • Daniel W. Mruzek
  • Conrad F. Shamlaye
  • Catriona Monthy
  • Gary J. Myers
  • Philip W. Davidson
  • Edwin van WijngaardenEmail author


Findings from observational and experimental studies suggest that maternal inflammation during pregnancy is associated with autism spectrum disorder (ASD). We report the first study in humans to examine this association in a large prospective birth cohort. We studied 788 mother-child pairs from the Seychelles Child Development Study Nutrition Cohort 2. Thirteen inflammatory markers were measured in mothers’ serum at 28 weeks’ gestation, along with the sum of T-helper 1 (Th1) and 2 (Th2) cytokines. The Social Communication Questionnaire (SCQ) and Social Responsiveness Scale (SRS) were administered at age 7 years to obtain information on ASD phenotype. We evaluated associations between maternal inflammatory markers and ASD phenotype using multivariable linear regression. For the SCQ, increased MCP-1 (a chemokine that is upregulated in response to pro-inflammatory cytokines) was associated with fewer ASD symptoms (B = − 0.40; 95% CI = − 0.72, − 0.09). Increased IL-4 (a cytokine that is typically associated with an enhanced anti-inflammatory response) was associated with more ASD symptoms (B = 2.10; 95% CI = 0.78, 3.43). For the SRS, higher concentrations of the anti-inflammatory cytokine IL-10 were associated with fewer ASD symptoms (B = − 0.18; 95% CI = − 0.35, − 0.01), but only after removal of outliers. No associations were observed for other markers. These findings suggest that a shift in the maternal immune balance during pregnancy may be associated with ASD symptomatology. While the use of well-established measures that capture ASD phenotypic variability is a strength of the study, measurement of peripheral immune markers only once during gestation is a limitation. Our results should be confirmed using maternal immune markers measured throughout gestation.


Pregnancy Immune response Inflammation Autism Spectrum disorder Cytokines Chemokines 



We acknowledge with thanks the contribution of the nursing and laboratory teams in Seychelles. The study sponsors had no role in the design, collection, analysis, or interpretation of the data; in the writing of the report; or in the decision to submit the article for publication.

Funding information

This research was supported by grants R01-ES010219, P30-ES01247, R03-ES027514, T32-ES007271, and T32-ES007026 from the US National Institute of Environmental Health Sciences (National Institutes of Health) and in-kind by the Government of the Republic of Seychelles.

Compliance with ethical standards

The study was reviewed and approved by the Seychelles Ethics Board and the Research Subjects Review Board at the University of Rochester.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jessica L. Irwin
    • 1
  • Alison J. Yeates
    • 2
  • Maria S. Mulhern
    • 2
  • Emeir M. McSorley
    • 2
  • J. J. Strain
    • 2
  • Gene E. Watson
    • 1
  • Katherine Grzesik
    • 1
  • Sally W. Thurston
    • 1
  • Tanzy M. Love
    • 1
  • Tristram H. Smith
    • 1
  • Daniel W. Mruzek
    • 1
  • Conrad F. Shamlaye
    • 3
  • Catriona Monthy
    • 4
  • Gary J. Myers
    • 1
  • Philip W. Davidson
    • 1
  • Edwin van Wijngaarden
    • 1
    Email author
  1. 1.Department of Public Health SciencesUniversity of Rochester School of Medicine and DentistryRochesterUSA
  2. 2.Nutrition Innovation Centre for Food and Health (NICHE)Ulster UniversityCo. LondonderryUK
  3. 3.Ministry of HealthMahéRepublic of Seychelles
  4. 4.Ministry of Education & Human Resource DevelopmentMahéRepublic of Seychelles

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