Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder.

BACKGROUND: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. OBJECTIVE: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). METHODS: Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800µg (median). Mothers' addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. RESULTS: High FA intake (≥800µg) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800µg FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (≥6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. CONCLUSIONS: In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604.

The clinician's guide to autism.

On the basis of the most recent epidemiologic research, Autism Spectrum Disorder (ASD) affects approximately 1% to 2% of all children. (1)(2) On the basis of some research evidence and consensus, the Modified Checklist for Autism in Toddlers isa helpful tool to screen for autism in children between ages 16 and 30 months. (11) The Diagnostic Statistical Manual of Mental Disorders, Fourth Edition, changes to a 2-symptom category from a 3-symptom category in the Diagnostic Statistical Manual of Mental Disorders, Fifth Edition(DSM-5): deficits in social communication and social interaction are combined with repetitive and restrictive behaviors, and more criteria are required per category. The DSM-5 subsumes all the previous diagnoses of autism (classic autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified) into just ASDs. On the basis of moderate to strong evidence, the use of applied behavioral analysis and intensive behavioral programs has a beneficial effect on language and the core deficits of children with autism. (16) Currently, minimal or no evidence is available to endorse most complementary and alternative medicine therapies used by parents, such as dietary changes (gluten free), vitamins, chelation, and hyperbaric oxygen. (16) On the basis of consensus and some studies, pediatric clinicians should improve their capacity to provide children with ASD a medical home that is accessible and provides family-centered, continuous, comprehensive and coordinated, compassionate, and culturally sensitive care. (20)

Efficacy of a sound-based intervention with a child with an autism spectrum disorder and auditory sensory over-responsivity.

Sound-based interventions (SBIs) are being used by paediatric occupational therapists to help children with autism spectrum disorders and co-morbid sensory processing disorders. A limited yet growing body of evidence is emerging related to the efficacy of SBIs in reducing sensory processing deficits among paediatric clients with co-morbid conditions. The current study employed an ABA single-subject case-controlled design, implementing The Listening Program® with a 7-year-old child diagnosed with autism spectrum disorder who demonstrated auditory sensory over-responsivity (SOR). The intervention consisted of 10 weeks of psycho-acoustically modified classical music that was delivered using specialized headphones and amplifier and a standard CD player. Repeated measures were conducted during the A(1), B and A(2) phases of the study using the Sensory Processing Measure, a subjective caregiver questionnaire, and the Sensory Over-Responsivity Scales, an examiner-based assessment measure to track changes of the participant's auditory SOR-related behaviours. The results indicated that the participant exhibited a decrease in the number of negative (avoidant, verbal and physical negative) and self-stimulatory behaviours. The decreases in negative and self-stimulatory behaviour may have been due to the therapeutic effect of the repeated exposure to the Sensory Over-Responsivity Scales or The Listening Program SBI.

Utilization patterns of conventional and complementary/alternative treatments in children with autism spectrum disorders and developmental disabilities in a population-based study.

OBJECTIVE: To compare the utilization of conventional treatments and utilization of complementary and alternative medicine in preschoolers with autism spectrum disorders (ASD) and other developmental disabilities (DD). METHODS: Participants were 578 children who were part of an ongoing population-based, case-control study of 2- to 5-year olds with ASD, DD, and the general population. Parents completed an interview on past and current services. RESULTS: Four hundred fifty-three children with ASD and 125 DD children were included. ASD families received more hours of conventional services compared with DD families (17.8 vs 11; p < .001). The use of psychotropic medications was low in both groups (approximately 3%). Overall, complementary and alternative medicine (CAM) use was not significantly different in ASD (39%) versus DD (30%). Hispanic families in both groups used CAM less often than non-Hispanic families. Variables such as level of function, immunization status, and the presence of an identified neurogenetic disorder were not predictive of CAM use. A higher level of parental education was associated with an increased CAM use in ASD and DD. Families who used >20 hours per week of conventional services were more likely to use CAM, including potentially unsafe or disproven CAM. Underimmunized children were marginally more likely to use CAM but not more likely to have received potentially unsafe or disproven CAM. CONCLUSION: Use of CAM is common in families of young children with neurodevelopmental disorders, and it is predicted by higher parental education and non-Hispanic ethnicity but not developmental characteristics. Further research should address how health care providers can support families in making decisions about CAM use.

Quality of life in children and adolescents with autism spectrum disorders: what is known about the effects of pharmacotherapy?

A diagnosis of autistic spectrum disorder (ASD), now estimated to affect one in 88 children, requires deficits in social communication and interactions, and restricted interests and/or repetitive behaviors. Almost all children with ASD have deficits in adaptive skills, many have intellectual disability, and others have co-occurring psychiatric disorders or symptoms. Thus, this complex disorder has shown to have a substantial impact on patients' quality of life (QoL) and that of their families. Medication treatment is considered by clinicians and families to address problems with functioning due to psychiatric problems, and, as such, one-third of children and adolescents with ASD take at least one psychotropic medication and many use complementary and alternative medicine. This paper reviews what is known about the benefits and risks of psychotropic medications on the QoL of children with ASD. Although scarce, there are studies of psychiatric medications in autistic patients that include QoL measures, such as the pediatric studies of aripiprazole for irritability and one adult study of oxytocin. The aripiprazole study showed a positive effect on QoL in treated patients, as did the oxytocin study. Several other psychotropic medications are used in the treatment of children with ASD, and although information is available on the risks and benefits of each, we do not have specific data on the QoL impact of these medications. The aripiprazole and oxytocin studies exemplify how researchers can include QoL measures and use this information to guide clinicians. Additionally, we will recommend areas of further study in pharmacotherapy and QoL research in the context of treating children with ASD.

Sensory hypersensitivity in children with high-functioning pervasive developmental disorder.

BACKGROUND: Studies have shown that children with pervasive developmental disorder (PDD) have high rates of sensory hypersensitivity. In addition, a few recent studies suggested that sensory hypersensitivity was related to anxiety or depression. However, most studies had methodological limitations because they included children with mental retardation and did not examine broadband psychopathology. Therefore, the purpose of this study was to examine the prevalence of sensory hypersensitivity in children with high-functioning PDD (HFPDD) and the correlation among sensory hypersensitivity, various characteristics, and broadband psychopathology. METHODS: We assessed 132 children with HFPDD (aged 6-15 years, 75% male) that were divided into sensory hypersensitivity (HS) and sensory non-hypersensitivity (non-HS) groups. A logistic regression model was used to examine correlations among sensory hypersensitivity, age, gender, PDD subtypes, socioeconomic status, and broadband psychopathology, including symptoms of anxiety and depression. RESULTS: Of the 132 children with HFPDD, 65.9% (n = 87) were categorized as HS and 34.1% (n = 45) as non-HS. The most common sensory hypersensitivity was auditory. Logistic regression analyses revealed that sensory hypersensitivity in HFPDD was significantly associated with autistic disorder and symptoms of anxiety and depression. CONCLUSIONS: Majority of children with HFPDD exhibited sensory hypersensitivity. Our findings suggested that sensory hypersensitivity may be a core feature of HFPDD and is possibly correlated to symptoms of anxiety and depression. We propose that sensory hypersensitivity in children with PDD should be aggressively assessed.

Analysis of self-selection bias in a population-based cohort study of autism spectrum disorders.

BACKGROUND: This study examined potential self-selection bias in a large pregnancy cohort by comparing exposure-outcome associations from the cohort to similar associations obtained from nationwide registry data. The outcome under study was specialist-confirmed diagnosis of autism spectrum disorders (ASDs). METHODS: The cohort sample (n = 89 836) was derived from the population-based prospective Norwegian Mother and Child Cohort Study and its substudy of ASDs, the Autism Birth Cohort (ABC) study. The nationwide registry data were derived from the Medical Birth Registry of Norway (n = 507 856). The children were born in 1999­2007, and seven prenatal and perinatal exposures were selected for analyses. RESULTS: ASDs were reported for 234 (0.26%) children in the cohort and 2072 (0.41%) in the nationwide population. Compared with the nationwide population, the cohort had an under-representation of the youngest women (<25 years), those who had single status, mothers who smoked during pregnancy, and non-users of prenatal folic acid supplements. The ratios of the adjusted odds ratios (ORs) in the cohort over the adjusted ORs in the nationwide population were as follows; primipara pregnancy: 1.39/1.22, prenatal folic acid use: 0.85/0.86, prenatal smoking: 1.20/1.17, preterm birth (<37 weeks): 1.48/1.42, low birthweight (<2500 g): 1.60/1.58, male sex: 4.39/4.59 (unadjusted only); and caesarean section history: 1.03/1.04. CONCLUSIONS: Associations estimated between ASDs and perinatal and prenatal exposures in the cohort are close to those estimated in the nationwide population. Self-selection does not appear to compromise validity of exposure-outcome associations in the ABC study.

Video game use in boys with autism spectrum disorder, ADHD, or typical development.

OBJECTIVES: The study objectives were to examine video game use in boys with autism spectrum disorder (ASD) compared with those with ADHD or typical development (TD) and to examine how specific symptoms and game features relate to problematic video game use across groups. METHODS: Participants included parents of boys (aged 8-18) with ASD (n = 56), ADHD (n = 44), or TD (n = 41). Questionnaires assessed daily hours of video game use, in-room video game access, video game genres, problematic video game use, ASD symptoms, and ADHD symptoms. RESULTS: Boys with ASD spent more time than did boys with TD playing video games (2.1 vs 1.2 h/d). Both the ASD and ADHD groups had greater in-room video game access and greater problematic video game use than the TD group. Multivariate models showed that inattentive symptoms predicted problematic game use for both the ASD and ADHD groups; and preferences for role-playing games predicted problematic game use in the ASD group only. CONCLUSIONS: Boys with ASD spend much more time playing video games than do boys with TD, and boys with ASD and ADHD are at greater risk for problematic video game use than are boys with TD. Inattentive symptoms, in particular, were strongly associated with problematic video game use for both groups, and role-playing game preferences may be an additional risk factor for problematic video game use among children with ASD. These findings suggest a need for longitudinal research to better understand predictors and outcomes of video game use in children with ASD and ADHD.

How nutritional status, diet and dietary supplements can affect autism. A review.

Autism is a neurodevelopmental disorder with symptoms arising that are apparent throughout the patient's lifespan. Autism Spectrum Disorders (ASD) are characterised by impaired social and communication interactions as well as restricted, repetitive interests and behaviour. Currently in Poland, about 50 000 people suffer from autism, of which 1/5 are children. Epidemiological studies show that the incidence of autism is increasing, which may be due to the diagnostic category of ASD having been developed. Of vital importance in the treatment of autism, is early diagnosis which is conducive to more rapidly improving the quality of patients' health. It is believed that both genetic and environmental factors may affect the development of the disease. Moreover, expert opinion emphasises the importance of making an adequate diagnosis when the first symptoms of autism start appearing which can be both psychological, gastro-intestinal and metabolic ones. Conventional treatment is based on the combination of behavioural and dietary therapy together with pharmacotherapy. For example, adapting an appropriate diet could help alleviate the disease severity, as well as the psychological and gastrointestinal symptoms. Much scientific research has indicated that pathogenesis of autism may have a beginning already in foetal life. During pregnancy, specialists should take special heed of metabolic disorders, which can increase the risk ofASD in children. One of the dietician's tasks are to properly assess the nutritional status of mothers before and during pregnancy, thereby allowing changes in nutrition to be made wherever necessary in order that metabolic indicators be improved. Thus an important part of autism therapy is the improving patient's nutritional status to prevent the onset of gastrointestinal symptoms. Adopting diets and tailored to individual disease symptoms, is linked to the nutritional requirements and food preferences of the patient. Specialists also emphasise that continual monitoring of the diet and nutritional status of children with ASD is required. It is also essential to start adequate dietary management in autistic patients with overweight, obesity or wasting, caused by improper nutrition. Frequently only a dietary therapy is insufficient to effectively treat autism. Many studies demonstrate the need to supplement the nutritional deficiencies of autistic patients with fatty acids omega-3, probiotics, vitamins and minerals in combination with medical and psychological interventions. A properly designed elimination diet adapted to the patient's individual may also lead to relief of the autism symptoms and the occurrence of gastrointestinal disorders. Parents and caregivers should therefore be aware of the benefits of nutritional therapy and need for proper monitoring the treatment of patients with ASD. A review of nutritional factors, dietary treatments and diet supplementation in patients with ASD is presented.

Autism and social cognition in epilepsy: implications for comprehensive epilepsy care.

PURPOSE OF REVIEW: The association of epilepsy, autism spectrum disorders (ASD) and social cognition is now well recognized. The overlap of these disorders is generating increasing scientific and clinical interest as the comprehensive management of epilepsy has expanded to include the cognitive and social consequences commonly being recognized as an integral part of epilepsy disorders. RECENT FINDINGS: Recent studies have shown that in individuals with ASD and intellectual disability the rate of epilepsy is as high as 20%. In those with ASD and no intellectual disability the rates of epilepsy are approximately 8%. In epilepsy those most likely to have ASD are those with intellectual disability. There is limited information regarding how often ASD impacts epilepsy and less data on the effect of epilepsy on social cognition. There is a convergence of evidence that when epilepsy coexists with ASD and intellectual disability they share etiopathogenic mechanisms. SUMMARY: There is a significant and important overlap between epilepsy and ASD and this has important implications for comprehensive care of all individuals with epilepsy. Early recognition of social deficits is essential. Treating the seizures in individuals with epilepsy and ASD is not enough. Clinicians need to be aware of and implement interventions that address the social-cognitive deficits.

Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children.

IMPORTANCE: Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. OBJECTIVE: To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder-not otherwise specified [PDD-NOS]) in children. DESIGN, SETTING, AND PATIENTS: The study sample of 85,176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. MAIN OUTCOME MEASURE: Specialist-confirmed diagnosis of ASDs. RESULTS: At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61,042) had autistic disorder, compared with 0.21% (50/24,134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use. CONCLUSIONS AND RELEVANCE: Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.

Autism spectrum disorders: a pediatric overview and update.

PURPOSE OF REVIEW: To provide an updated overview of autism spectrum disorders (ASDs), with particular attention to the pediatrician's role in assessing and managing patients with ASDs. RECENT FINDINGS: Clinical perspectives on ASDs continue to evolve. The prevalence of ASDs in the United States continues to rise, and pediatricians are being tasked with the responsibility for universal screening. Further changes in its epidemiology will undoubtedly result from anticipated changes in the diagnostic criteria put forth in the upcoming revision to the Diagnostic and Statistical Manual (5th edition). Although there have been considerable advances in identifying a genetic cause in many more cases, the cause remains elusive in most cases. Recent studies of concordant twins suggest there is a stronger environmental component than previously believed. Research suggests earlier diagnosis may be feasible in some cases, and a new treatment approach has been shown to be effective in very young children. Although there have not been any large-scale advances in the medical treatment, some isolated successes have been reported and other promising therapies are now being investigated. SUMMARY: Clinical guidelines for ASDs are evolving, with updated diagnostic criteria expected and revised recommendations for evaluation also imminent. This article provides pediatricians with a clinical overview of ASD - with an emphasis on the clinical considerations relating to screening, evaluation, and management.

Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study.

BACKGROUND: Periconceptional folate is essential for proper neurodevelopment. OBJECTIVE: Maternal folic acid intake was examined in relation to the risk of autism spectrum disorder (ASD) and developmental delay (DD). DESIGN: Families enrolled in the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study from 2003 to 2009 were included if their child had a diagnosis of ASD (n = 429), DD (n = 130), or typical development (TD; n = 278) confirmed at the University of California Davis Medical Investigation of Neurodevelopmental Disorders Institute by using standardized clinical assessments. Average daily folic acid was quantified for each mother on the basis of dose, brands, and intake frequency of vitamins, supplements, and breakfast cereals reported through structured telephone interviews. RESULTS: Mean (±SEM) folic acid intake was significantly greater for mothers of TD children than for mothers of children with ASD in the first month of pregnancy (P1; 779.0 ± 36.1 and 655.0 ± 28.7 µg, respectively; P < 0.01). A mean daily folic acid intake of ≥600 µg (compared with <600 µg) during P1 was associated with reduced ASD risk (adjusted OR: 0.62; 95% CI: 0.42, 0.92; P = 0.02), and risk estimates decreased with increased folic acid (P-trend = 0.001). The association between folic acid and reduced ASD risk was strongest for mothers and children with MTHFR 677 C>T variant genotypes. A trend toward an association between lower maternal folic acid intake during the 3 mo before pregnancy and DD was observed, but not after adjustment for confounders. CONCLUSIONS: Periconceptional folic acid may reduce ASD risk in those with inefficient folate metabolism. The replication of these findings and investigations of mechanisms involved are warranted.

Effect of suboptimal breast-feeding on occurrence of autism: a case-control study.

OBJECTIVE: To evaluate the association between suboptimal breast-feeding practices and autism spectrum disorders (ASDs). METHODS: A case-control study was conducted in 102 ASD cases and 102 matched healthy controls. RESULTS: Based on adjusted odds ratios from logistic regression models, ASD was found to be associated with the late initiation of breast-feeding (odds ratio 1.48, 95% confidence interval 1.01-3.1), a non-intake of colostrum (odds ratio 1.7, 95% confidence interval 1.03-4.3), prelacteal feeding, and bottle-feeding. The risk of ASD was found to decrease in a dose-response fashion over increasing periods of exclusive breast-feeding (P for trend = 0.04) and continued breast-feeding (P for trend = 0.001). CONCLUSION: The study indicates that increased ASD risk is generally associated with suboptimal breast-feeding practices.

Caracterización de niños y adolescentes con trastornos del espectro autista en una institución de Bogotá, Colombia / Profile of children and adolescents with autism spectrum disorders in an institution in Bogota, Colombia

Objetivo: Caracterizar la población de niños y adolescentes con diagnóstico de trastornos del espectro autista (TEA) en un centro de atención integral en Bogotá Colombia. Material y métodos: Estudio descriptivo-correlacional, de la población de pacientes que han asistido al centro desde el año 2003 hasta el 2009. Se evaluaron los aspectos demográficos y clínicos, y se realizó una correlación entre las variables con el diagnóstico y la severidad para la búsqueda de factores de riesgo.Resultados: Se estudió a 138 pacientes. La edad promedio de inicio fue a los 21 meses y el diagnóstico a los 45. Hubo predominancia masculina (6,15:1). El diagnóstico mas frecuente fue síndrome autista (83%), seguido por trastorno generalizado del desarrollo no determinado (17%). No se encontraron antecedentes importantes en la familia, durante el embarazo ni en el periodo neonatal. El desarrollo motor durante el primer año fue normal mientras que el desarrollo de la comunicación verbal se encontró comprometido. Los signos específicos de TEA como el trastorno en referencia a sí mismo, comunicación, habla espontánea, comprensión verbal, atención, imitación, utilización de objetos, autocuidado y juego simbólico se relacionaron significativamente con la severidad del cuadro.Conclusiones: El diagnostico de los TEA continúa siendo tardío en nuestra población y generalmente luego de la remisión de personal ajeno a la salud. Las alteraciones más importantes se encuentran en la comunicación y en la relación con los pares. En el estudio no se evidenciaron factores de riesgo que pudieran estar asociados (AU)

To determine the profile of children and adolescents diagnosed with autism spectrum disorder (ASD) in a comprehensive care centre in Bogota, Colombia. Material and methods: A descriptive-correlational study with a sample of patients who had attended the institution from 2003 to 2009. Demographic and clinical aspects were evaluated and a correlation between the diagnosis and severity being analysed in search for risk factors. Results: A total of138 patients were studied. The average age of onset was 21 months, and diagnosis had been made at 45 months. There was a male predominance (6.15:1). The predominant diagnosis was autistic syndrome (83%), followed by pervasive developmental disorder not otherwise specified (17%). There was no pathological background in the family history, during pregnancy or during the neonatal period. Motor development during the first year was normal but acquisition of language skills was compromised. The specific signs of ASD as regards the disorder in itself, communication skills, spontaneous speech, verbal comprehension, attention, imitation, use of objects, self-care and symbolic play were significantly related to the severity of the disease. Conclusions: Diagnosis of ASD is still delayed in our population and usually after referral from someone other than a health professional. The most important problems were found in communication skills and relationships with peers. The study did not show significant associated risk factors (AU)