Polychlorinated biphenyls influence on autism spectrum disorder risk in the MARBLES cohort

Lauren Granillo, Sunjay Sethi, Kimberly P. Keil, Yanping Lin, Sally J Ozonoff, Ana-Maria Iosif, Birgit Puschner, Rebecca Jean Schmidt

Research output: Contribution to journalArticle

Abstract

Background: Autism spectrum disorder (ASD) is suspected to have environmental and genetic contributions. Polychlorinated biphenyls (PCBs) are environmental risk factors of interest due to their potential as neurodevelopmental toxicants and environmental persistence despite a US production ban in the 1970s. Methods: Participants were mother-child pairs from MARBLES, a high-risk pregnancy cohort that enrolls families who have one child diagnosed with ASD and are planning to have another child. PCB concentrations were measured in maternal blood at each trimester of pregnancy using gas chromatography coupled with triple quadruple mass spectrometry. Concentrations were summed into total PCB and two categories based on function/mechanisms of action: dioxin-like (DL), and ryanodine receptor (RyR)-activating PCBs. Multinomial logistic regression assessed risk of clinical outcome classification of ASD and non-typical development (Non-TD) compared to typically developing (TD) in the children at 3 years old. Results: A total of 104 mother-child pairs were included. There were no significant associations for total PCB; however, there were borderline significant associations between DL-PCBs and decreased risk for Non-TD outcome classification (adjusted OR: 0.41 (95% CI 0.15–1.14)) and between RyR-activating PCBs and increased risk for ASD outcome classification (adjusted OR: 2.63 (95% CI 0.87–7.97)). Conclusion: This study does not provide strong supporting evidence that PCBs are risk factors for ASD or Non-TD. However, these analyses suggest the need to explore more deeply into subsets of PCBs as risk factors based on their function and structure in larger cohort studies where non-monotonic dose-response patterns can be better evaluated.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalEnvironmental Research
Volume171
DOIs
StatePublished - Apr 1 2019

Fingerprint

Polychlorinated Biphenyls
PCB
risk factor
Ryanodine Receptor Calcium Release Channel
Dioxins
Mothers
pregnancy
dioxin
Pregnancy Trimesters
Autism Spectrum Disorder
Aryl Hydrocarbon Receptors
High-Risk Pregnancy
Set theory
environmental risk
Gas chromatography
Gas Chromatography
Mass spectrometry
Logistics
logistics
Mass Spectrometry

Keywords

  • Autism
  • Polychlorinated biphenyls
  • Pregnancy
  • Prospective study
  • Ryanodine receptor

ASJC Scopus subject areas

  • Biochemistry
  • Environmental Science(all)

Cite this

Polychlorinated biphenyls influence on autism spectrum disorder risk in the MARBLES cohort. / Granillo, Lauren; Sethi, Sunjay; Keil, Kimberly P.; Lin, Yanping; Ozonoff, Sally J; Iosif, Ana-Maria; Puschner, Birgit; Schmidt, Rebecca Jean.

In: Environmental Research, Vol. 171, 01.04.2019, p. 177-184.

Research output: Contribution to journalArticle

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abstract = "Background: Autism spectrum disorder (ASD) is suspected to have environmental and genetic contributions. Polychlorinated biphenyls (PCBs) are environmental risk factors of interest due to their potential as neurodevelopmental toxicants and environmental persistence despite a US production ban in the 1970s. Methods: Participants were mother-child pairs from MARBLES, a high-risk pregnancy cohort that enrolls families who have one child diagnosed with ASD and are planning to have another child. PCB concentrations were measured in maternal blood at each trimester of pregnancy using gas chromatography coupled with triple quadruple mass spectrometry. Concentrations were summed into total PCB and two categories based on function/mechanisms of action: dioxin-like (DL), and ryanodine receptor (RyR)-activating PCBs. Multinomial logistic regression assessed risk of clinical outcome classification of ASD and non-typical development (Non-TD) compared to typically developing (TD) in the children at 3 years old. Results: A total of 104 mother-child pairs were included. There were no significant associations for total PCB; however, there were borderline significant associations between DL-PCBs and decreased risk for Non-TD outcome classification (adjusted OR: 0.41 (95{\%} CI 0.15–1.14)) and between RyR-activating PCBs and increased risk for ASD outcome classification (adjusted OR: 2.63 (95{\%} CI 0.87–7.97)). Conclusion: This study does not provide strong supporting evidence that PCBs are risk factors for ASD or Non-TD. However, these analyses suggest the need to explore more deeply into subsets of PCBs as risk factors based on their function and structure in larger cohort studies where non-monotonic dose-response patterns can be better evaluated.",
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