Irva Hertz-Picciotto

Polybrominated diphenyl ethers in relation to autism and developmental delay: A case-control study

BackgroundPolybrominated diphenyl ethers (PBDEs) are flame retardants used widely and in increasing amounts in the U.S. over the last few decades. PBDEs and their metabolites cross the placenta and studies in rodents demonstrate neurodevelopmental toxicity from prenatal exposures. PBDE exposures occur both via breastfeeding and hand-to-mouth activities in small children.MethodsParticipants were 100 children from the CHARGE (CH ildhood A utism R isk from G enetics and the E nvironment) Study, a case-control epidemiologic investigation of children with autism/autism spectrum disorder, with developmental delay and from the general population. Diagnoses of autism were confirmed by the Autism Diagnostic Observation Schedule and Autism Diagnostic Inventory-Revised, and of developmental delay using the Mullens Scales of Early Learning and the Vineland Adaptive Behavior Scales. Typically developing controls were those with no evidence of delay, autism, or autism spectrum disorder. Eleven PBDE congeners were measured by gas chromatography/mass spectrometry from serum specimens collected after children were assessed. Logistic regression was used to evaluate the association between plasma PBDEs and autism.ResultsChildren with autism/autism spectrum disorder and developmental delay were similar to typically developing controls for all PBDE congeners, but levels were high for all three groups.ConclusionsPlasma samples collected post-diagnosis in this study may not represent early life exposures due to changes in diet and introduction of new household products containing PBDEs. Studies with direct measurements of prenatal or infant exposures are needed to assess the possible causal role for these compounds in autism spectrum disorders.

Neonatal Cytokine Profiles Associated With Autism Spectrum Disorder

BACKGROUND Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that can be reliably diagnosed at age 24 months. Immunological phenomena, including skewed cytokine production, have been observed among children with ASD. Little is known about whether immune dysregulation is present before diagnosis of ASD. METHODS We examined neonatal blood spots from 214 children with ASD (141 severe, 73 mild/moderate), 62 children with typical development, and 27 children with developmental delay as control subjects who participated in the Childhood Autism Risks from Genetics and the Environment study, a population-based case-control study. Levels of 17 cytokines and chemokines were compared across groups and in relation to developmental and behavioral domains. RESULTS Interleukin (IL)-1β and IL-4 were independently associated with ASD compared with typical development, although these relationships varied by ASD symptom intensity. Elevated IL-4 was associated with increased odds of severe ASD (odds ratio [OR] = 1.40, 95% confidence interval [CI], 1.03, 1.91), whereas IL-1β was associated with increased odds of mild/moderate ASD (OR = 3.02, 95% CI, 1.43, 6.38). Additionally, IL-4 was associated with a higher likelihood of severe ASD versus mild/moderate ASD (OR = 1.35, 95% CI, 1.04, 1.75). In male subjects with ASD, IL-4 was negatively associated with nonverbal cognitive ability (β = -3.63, SE = 1.33, p = .04). CONCLUSIONS This study is part of a growing effort to identify early biological markers for ASD. We demonstrate that peripheral cytokine profiles at birth are associated with ASD later in childhood and that cytokine profiles vary depending on ASD severity. Cytokines have complex roles in neurodevelopment, and dysregulated levels may be indicative of genetic differences and environmental exposures or their interactions that relate to ASD.

Asthma and Allergies in Children With Autism Spectrum Disorders: Results From the CHARGE Study.

Immune aberrations are often noted in children with autism spectrum disorder (ASD), but whether asthma and allergy are related to ASD is not well defined. This study examined asthma and allergies in association with ASD and phenotypic subsets. Participants were 560 children with confirmed ASD and 391 typically developing children from the CHildhood Autism Risks from Genetics and the Environment study. Maternally reported child asthma and allergy was compared between cases and controls, and in association with cognitive and behavioral test scores. Prevalence of asthma and overall allergies did not differ between cases and controls, but overall allergy in children with ASD was associated with higher stereotypy scores as measured by the Aberrant Behavior Checklist. In addition, reported food allergies were significantly associated with ASD (adjusted odds ratio = 2.23, 95% confidence interval 1.28, 3.89). Our results suggest food allergies and sensitivities may be more common in children with ASD, and that these issues may correlate with other behaviors. Autism Res 2015, 8: 567–574.

Increased production of IL-17 in children with autism spectrum disorders and co-morbid asthma.

Inflammation and asthma have both been reported in some children with autism spectrum disorder (ASD). To further assess this connection, peripheral immune cells isolated from young children with ASD and typically developing (TD) controls and the production of cytokines IL-17, -13, and -4 assessed following ex vivo mitogen stimulation. Notably, IL-17 production was significantly higher following stimulation in ASD children compared to controls. Moreover, IL-17 was increased in ASD children with co-morbid asthma compared to controls with the same condition. In conclusion, children with ASD exhibited a differential response to T cell stimulation with elevated IL-17 production compared to controls.

Autism-specific maternal anti-fetal brain autoantibodies are associated with metabolic conditions.

Approximately 23% of mothers of children with autism spectrum disorder (ASD) produce specific patterns of autoantibodies to fetal brain proteins that have been detected in only 1% of mothers of typically developing children. The biological mechanisms underlying the development of ASD‐specific maternal autoantibodies are poorly understood. We sought to determine whether ASD‐specific maternal autoantibodies identified postnatally were associated with metabolic conditions (MCs) during gestation. Participants were 227 mothers of 2–5 year old children with confirmed ASD, enrolled in CHARGE (Childhood Autism Risk from Genetics and the Environment) between January 2003 and April 2008, and from whom blood samples were collected and analyzed for anti‐fetal brain autoantibodies (Ab+). MCs included diabetes, hypertensive disorders, and prepregnancy obesity or overweight, ascertained from medical records or structured telephone interviews. Log‐linear regression models were performed to estimate prevalence ratios and 95% confidence intervals (CI) based on robust standard errors. Fifty‐six (25%) mothers were Ab+. Ab+ prevalence was higher among mothers with diabetes, hypertensive disorders, or overweight compared to healthy mothers, but differences were not statistically significant. In a subset of 145 mothers whose children exhibited severe ASD (31 Ab+), those diagnosed with type 2 or gestational diabetes were 2.7‐fold more likely to be Ab+ (95% CI 1.1, 6.6), controlling for delivery payer and smoking. Gestational diabetes specifically was associated with a 3.2‐fold increased Ab+ prevalence (95% CI 1.2, 8.6). In this exploratory study, mothers whose children had severe ASD and who experienced diabetes were more likely to have anti‐fetal brain autoantibodies 2–5 years later. Autism Res 2017, 10: 89–98.