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

Abstract:

: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.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Irwin JL,Yeates AJ,Mulhern MS,McSorley EM,Strain JJ,Watson GE,Grzesik K,Thurston SW,Love TM,Smith TH,Mruzek DW,Shamlaye CF,Monthy C,Myers GJ,Davidson PW,van Wijngaarden E

doi

10.1007/s12035-018-1424-y

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

5000-5008

issue

7

eissn

0893-7648

issn

1559-1182

pii

10.1007/s12035-018-1424-y

journal_volume

56

pub_type

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