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Scholarly Works (167 results)

  • Thesis
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UC Davis Electronic Theses and Dissertations (2023)

The California Department of Developmental Services (DDS) (2003) reported that children with Autism Spectrum Disorder (ASD) are being recognized at accelerated rates. These increases in prevalence cannot be fully attributed to changes in diagnostic criteria, improvements in detection, or population increases. Maternal substance use is one area of environmental risk under study. Of these substances, cannabis remains one of the most used by pregnant mothers. Cannabis, referring to the component of the plant cannabis sativa that contains >0.3% delta-9-tetrahydrocannabinol (THC), has been identified as a developmental toxicant. The psychoactive cannabinoid–THC–can be passed from mother to fetus via the placenta or to the child through breastfeeding. THC has been implicated in affecting a child’s developing endocannabinoid system, and ultimately affects a child’s neurodevelopment. This is concerning as the THC content of cannabis products has increased with increased legalization and evolving markets. This study sought to examine the association between maternal cannabis use before or during pregnancy and the odds of ASD diagnosis in 1,152 children from the Childhood Autism Risk from Genetics and the Environment (CHARGE) study, a large population-based case-control study with data from over 20 counties. The crude model indicated an association in the direction of increased risk with low precision (OR=1.28; 95%CI=0.81-2.01). After adjustment for mother’s age at delivery, maternal experience of stress, family history of ADHD, maternal intake of folic acid supplements during pregnancy, presence of any smokers in the house before or during pregnancy, protective socioeconomic factors, maternal use of non-cannabis recreational drugs and tobacco products, and year of birth, the effect was moved toward the null (OR=1.20; 95%CI=0.68, 2.12). However, the lack of significant results does not confirm that maternal cannabis use does not increase odds of ASD. Further studies are needed on more recent cohorts given the increased THC potency, accessibility of cannabis products, and changing attitudes toward use during pregnancy.

    Cover page: Maternal cannabis use and associations with Autism Spectrum Disorder diagnosis in Californian children using data from CHARGE
    • Article
    • Peer Reviewed
    UC Davis Previously Published Works (2014)
    Despite the emerging role of mitochondria in immunity, a link between bioenergetics and the immune response in autism has not been explored. Mitochondrial outcomes and phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst were evaluated in granulocytes from age-, race-, and gender-matched children with autism with severity scores of ≥7 (n = 10) and in typically developing (TD) children (n = 10). The oxidative phosphorylation capacity of granulocytes was 3-fold lower in children with autism than in TD children, with multiple deficits encompassing ≥1 Complexes. Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions. Mitochondrial dysfunction in children with autism was accompanied by a lower (26% of TD children) oxidative burst by PMA-stimulated reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and by a lower gene expression (45% of TD children's mean values) of the nuclear factor erythroid 2-related factor 2 transcription factor involved in the antioxidant response. Given that the majority of granulocytes of children with autism exhibited defects in oxidative phosphorylation, immune response, and antioxidant defense, our results support the concept that immunity and response to oxidative stress may be regulated by basic mitochondrial functions as part of an integrated metabolic network.
      Cover page: Deficits in bioenergetics and impaired immune response in granulocytes from children with autism.
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2014)

      Background

      Over the past 10 years, research into environmental risk factors for autism has grown dramatically, bringing evidence that an array of non-genetic factors acting during the prenatal period may influence neurodevelopment.

      Methods

      This paper reviews the evidence on modifiable preconception and/or prenatal factors that have been associated, in some studies, with autism spectrum disorder (ASD), including nutrition, substance use and exposure to environmental agents. This review is restricted to human studies with at least 50 cases of ASD, having a valid comparison group, conducted within the past decade and focusing on maternal lifestyle or environmental chemicals.

      Results

      Higher maternal intake of certain nutrients and supplements has been associated with reduction in ASD risk, with the strongest evidence for periconceptional folic acid supplements. Although many investigations have suggested no impact of maternal smoking and alcohol use on ASD, more rigorous exposure assessment is needed. A number of studies have demonstrated significant increases in ASD risk with estimated exposure to air pollution during the prenatal period, particularly for heavy metals and particulate matter. Little research has assessed other persistent and non-persistent organic pollutants in association with ASD specifically.

      Conclusions

      More work is needed to examine fats, vitamins and other maternal nutrients, as well as endocrine-disrupting chemicals and pesticides, in association with ASD, given sound biological plausibility and evidence regarding other neurodevelopmental deficits. The field can be advanced by large-scale epidemiological studies, attention to critical aetiological windows and how these vary by exposure, and use of biomarkers and other means to understand underlying mechanisms.
        Cover page: Maternal lifestyle and environmental risk factors for autism spectrum disorders
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2014)

        Background

        The environmental contribution to autism spectrum disorders (ASD) is largely unknown, but household pesticides are receiving increased attention. We examined associations between ASD and maternally-reported use of imidacloprid, a common flea and tick treatment for pets.

        Methods

        Bayesian logistic models were used to estimate the association between ASD and imidacloprid and to correct for potential differential exposure misclassification due to recall in a case control study of ASD.

        Results

        Our analytic dataset included complete information for 262 typically developing controls and 407 children with ASD. Compared with exposure among controls, the odds of prenatal imidacloprid exposure among children with ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for exposures during pregnancy than for early life exposures, whereas limiting to frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9).

        Conclusions

        Within plausible estimates of sensitivity and specificity, the association could result from exposure misclassification alone. The association between imidacloprid exposure and ASD warrants further investigation, and this work highlights the need for validation studies regarding prenatal exposures in ASD.
          Cover page: Autism spectrum disorder, flea and tick medication, and adjustments for exposure misclassification: the CHARGE (CHildhood Autism Risks from Genetics and Environment) case–control study
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2014)
          To compare gastrointestinal (GI) problems among children with: (1) autism spectrum disorder (ASD), (2) developmental delay (DD) and (3) typical development (TD), GI symptom frequencies were obtained for 960 children from the CHildhood Autism Risks from Genetics and Environment (CHARGE) study. We also examined scores on five Aberrant Behavior Checklist (ABC) subscales comparing ASD children with high versus low frequency GI symptoms. Compared to TD children, those with ASD [aOR 7.92 (4.89-12.85)] and DD [aOR 4.55 (2.51-8.24)] were more likely to have at least one frequent GI symptom. Restricting to ASD children, those with frequent abdominal pain, gaseousness, diarrhea, constipation or pain on stooling scored worse on irritability, social withdrawal, stereotypy, and hyperactivity compared with children having no frequent GI symptoms. Frequent GI problems affect young children with ASD and DD more commonly than those with TD. Maladaptive behaviors correlate with GI problems, suggesting these comorbidities require attention.
            Cover page: Gastrointestinal Problems in Children with Autism, Developmental Delays or Typical Development
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2014)
            Research into environmental risk factors for autism has grown dramatically over the past 10 years, providing evidence that non-genetic factors acting during the prenatal period may influence the underlying neurodevelopmental processes. This paper reviews the evidence on modifiable preconception and/or prenatal factors that have been associated with autism spectrum disorder (ASD), including only human studies with at least 50 cases of ASD, having a valid comparison group, conducted within the past decade, and focusing on maternal lifestyle or environmental chemicals. Consistent results have been reported for an association of higher maternal intake of certain nutrients and supplements with reduction in ASD risk, with the strongest evidence for folic acid supplements. A number of studies have demonstrated significant increases in ASD risk with estimated exposure to air pollution during the prenatal period, particularly for heavy metals and particulate matter. A few studies suggest a link with organophosphate pesticides. More rigorous ascertainment of exposure is needed for studies of substance use; most investigations adjusting for potential confounders, but relying on self-reported use, have shown no links between maternal smoking or alcohol consumption and ASD. Little research has assessed other persistent and non-persistent organic chemical pollutants, such as are found in common household or personal care products, in association with ASD specifically. More work is needed to examine fats, vitamins, and other maternal nutrients, as well as endocrine-disrupting chemicals and pesticides, in association with ASD, given sound biological plausibility and evidence regarding other neurodevelopmental outcomes. In addition, the field could be advanced by the use of large-scale epidemiologic studies, attention to critical etiologic windows and how these vary by exposure, interactions with genetic susceptibility, and a focus on underlying mechanisms.
              Cover page: Environment and Autism: Current State of the Science.
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2013)
              Previous findings on relationships between infertility, infertility therapies, and autism spectrum disorders (ASD) have been inconsistent. The goals of this study are first, to briefly review this evidence and second, to examine infertility and its treatments in association with having a child with ASD in newly analyzed data. In review, we identified 14 studies published as of May 2013 investigating infertility and/or its treatments and ASD. Overall, prior results showed little support for a strong association, though some increases in risk with specific treatments were found; many limitations were noted. In new analyses of the CHildhood Autism Risk from Genetics and the Environment (CHARGE) population-based study, cases with autism spectrum disorder (ASD, n = 513) and controls confirmed to have typical development (n = 388) were compared with regard to frequencies of infertility diagnoses and treatments overall and by type. Infertility diagnoses and treatments were also grouped to explore potential underlying pathways. Logistic regression was used to obtain crude and adjusted odds ratios overall and, in secondary analyses, stratified by maternal age (≥35 years) and diagnostic subgroups. No differences in infertility, infertility treatments, or hypothesized underlying pathways were found between cases and controls in crude or adjusted analyses. Numbers were small for rarer therapies and in subgroup analyses; thus the potential for modest associations in specific subsets cannot be ruled out. However, converging evidence from this and other studies suggests that assisted reproductive technology is not a strong independent risk factor for ASD. Recommendations for future studies of this topic are provided.
                Cover page: Infertility and Its Treatments in Association with Autism Spectrum Disorders: A Review and Results from the CHARGE Study
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2014)
                Despite the emerging role of mitochondria in immunity, a link between bioenergetics and the immune response in autism has not been explored. Mitochondrial outcomes and phorbol 12-myristate 13-acetate (PMA)-induced oxidative burst were evaluated in granulocytes from age-, race-, and gender-matched children with autism with severity scores of ≥7 (n = 10) and in typically developing (TD) children (n = 10). The oxidative phosphorylation capacity of granulocytes was 3-fold lower in children with autism than in TD children, with multiple deficits encompassing ≥1 Complexes. Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions. Mitochondrial dysfunction in children with autism was accompanied by a lower (26% of TD children) oxidative burst by PMA-stimulated reduced nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase and by a lower gene expression (45% of TD children's mean values) of the nuclear factor erythroid 2-related factor 2 transcription factor involved in the antioxidant response. Given that the majority of granulocytes of children with autism exhibited defects in oxidative phosphorylation, immune response, and antioxidant defense, our results support the concept that immunity and response to oxidative stress may be regulated by basic mitochondrial functions as part of an integrated metabolic network.
                  Cover page: Deficits in Bioenergetics and Impaired Immune Response in Granulocytes From Children With Autism
                  • Article
                  • Peer Reviewed
                  UC Davis Previously Published Works (2012)

                  Background

                  Autism spectrum disorders (ASDs) have been increasing in many parts of the world and a portion of cases are attributable to environmental exposures. Conclusive replicated findings have yet to appear on any specific exposure; however, mounting evidence suggests gestational pesticides exposures are strong candidates. Because multiple developmental processes are implicated in ASDs during gestation and early life, biological plausibility is more likely if these agents can be shown to affect core pathophysiological features.

                  Objectives

                  Our objectives were to examine shared mechanisms between autism pathophysiology and the effects of pesticide exposures, focusing on neuroexcitability, oxidative stress, and immune functions and to outline the biological correlates between pesticide exposure and autism risk.

                  Methods

                  We review and discuss previous research related to autism risk, developmental effects of early pesticide exposure, and basic biological mechanisms by which pesticides may induce or exacerbate pathophysiological features of autism.

                  Discussion

                  On the basis of experimental and observational research, certain pesticides may be capable of inducing core features of autism, but little is known about the timing or dose, or which of various mechanisms is sufficient to induce this condition.

                  Conclusions

                  In animal studies, we encourage more research on gene × environment interactions, as well as experimental exposure to mixtures of compounds. Similarly, epidemiologic studies in humans with exceptionally high exposures can identify which pesticide classes are of greatest concern, and studies focused on gene × environment are needed to determine if there are susceptible subpopulations at greater risk from pesticide exposures.
                    Cover page: Tipping the Balance of Autism Risk: Potential Mechanisms Linking Pesticides and Autism
                    • Article
                    • Peer Reviewed
                    UC Davis Previously Published Works (2016)
                    This study investigates whether sociodemographic factors are associated with utilization of intervention services for children with autism spectrum disorder (ASD) enrolled in the Childhood Autism Risks from Genetics and the Environment Study. Maternal ethnicity, insurance status, and education for 696 families of children with ASD were available. Children of Black mothers entered intervention earlier compared to White mothers (2 vs. 2.6 years; p = 0.001). Having public insurance was associated with receiving <15 h/week of individual services, while having a Bachelor degree was associated with receiving <15 h/week of classroom-based services. These differences suggest that SES may be a factor in utilization of services. Efforts should be made to ensure that interventions offered are culturally and linguistically accessible.
                      Cover page: Sociodemographic Disparities in Intervention Service Utilization in Families of Children with Autism Spectrum Disorder
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