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 Mc Sorley, 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 Wijngaarden

Research output: Contribution to journalArticle

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.
LanguageEnglish
Number of pages9
JournalMolecular Neurobiology
Early online date14 Nov 2018
DOIs
Publication statusE-pub ahead of print - 14 Nov 2018

Fingerprint

Seychelles
Child Development
Mothers
Phenotype
Pregnancy
Cytokines
Anti-Inflammatory Agents
Biomarkers
Communication
Autism Spectrum Disorder
Chemokines
Interleukin-4
Interleukin-10
Observational Studies
Linear Models
Cohort Studies
Parturition
Inflammation

Keywords

  • pregnancy (MeSH)
  • Immune Response
  • Inflammation
  • Autism Spectrum Disorders (ASD)
  • Cytokines
  • Chemokines

Cite this

Irwin, Jessica L ; Yeates, Alison J. ; Mulhern, Maria S ; Mc Sorley, Emeir M ; Strain, J J ; Watson, Gene E ; Grzesik, Katherine ; Thurston, Sally W ; Love, Tanzy M ; Smith, Tristram H ; Mruzek, Daniel W ; Shamlaye, Conrad F ; Monthy, Catriona ; Myers, Gary J ; Davidson, Philip W ; van Wijngaarden, Edwin. / Maternal Gestational Immune Response and Autism Spectrum Disorder Phenotypes at 7 Years of Age in the Seychelles Child Development Study. 2018.
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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.",
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Irwin, JL, Yeates, AJ, Mulhern, MS, Mc Sorley, 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 2018, 'Maternal Gestational Immune Response and Autism Spectrum Disorder Phenotypes at 7 Years of Age in the Seychelles Child Development Study'. https://doi.org/10.1007/s12035-018-1424-y

Maternal Gestational Immune Response and Autism Spectrum Disorder Phenotypes at 7 Years of Age in the Seychelles Child Development Study. / Irwin, Jessica L; Yeates, Alison J.; Mulhern, Maria S; Mc Sorley, Emeir M; Strain, J J; Watson, Gene E; Grzesik, Katherine; Thurston, Sally W; Love, Tanzy M; Smith, Tristram H; Mruzek, Daniel W; Shamlaye, Conrad F; Monthy, Catriona; Myers, Gary J; Davidson, Philip W; van Wijngaarden, Edwin.

14.11.2018.

Research output: Contribution to journalArticle

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T1 - Maternal Gestational Immune Response and Autism Spectrum Disorder Phenotypes at 7 Years of Age in the Seychelles Child Development Study

AU - Irwin, Jessica L

AU - Yeates, Alison J.

AU - Mulhern, Maria S

AU - Mc Sorley, Emeir M

AU - Strain, J J

AU - Watson, Gene E

AU - Grzesik, Katherine

AU - Thurston, Sally W

AU - Love, Tanzy M

AU - Smith, Tristram H

AU - Mruzek, Daniel W

AU - Shamlaye, Conrad F

AU - Monthy, Catriona

AU - Myers, Gary J

AU - Davidson, Philip W

AU - van Wijngaarden, Edwin

PY - 2018/11/14

Y1 - 2018/11/14

N2 - 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.

AB - 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.

KW - pregnancy (MeSH)

KW - Immune Response

KW - Inflammation

KW - Autism Spectrum Disorders (ASD)

KW - Cytokines

KW - Chemokines

U2 - 10.1007/s12035-018-1424-y

DO - 10.1007/s12035-018-1424-y

M3 - Article

ER -