Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic.

Lead, mercury, and arsenic are neurotoxicants with known effects on neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder apparent by early childhood. Using data on 4486 children with ASD residing in 2489 census tracts in five sites of the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring (ADDM) Network, we used multi-level negative binomial models to investigate if ambient lead, mercury, and arsenic concentrations, as measured by the US Environmental Protection Agency National-Scale Air Toxics Assessment (EPA-NATA), were associated with ASD prevalence. In unadjusted analyses, ambient metal concentrations were negatively associated with ASD prevalence. After adjusting for confounding factors, tracts with air concentrations of lead in the highest quartile had significantly higher ASD prevalence than tracts with lead concentrations in the lowest quartile (prevalence ratio (PR) = 1.36; 95 '% CI: 1.18, 1.57). In addition, tracts with mercury concentrations above the 75th percentile (>1.7 ng/m(3)) and arsenic concentrations below the 75th percentile (≤0.13 ng/m(3)) had a significantly higher ASD prevalence (adjusted RR = 1.20; 95 % CI: 1.03, 1.40) compared to tracts with arsenic, lead, and mercury concentrations below the 75th percentile. Our results suggest a possible association between ambient lead concentrations and ASD prevalence and demonstrate that exposure to multiple metals may have synergistic effects on ASD prevalence.

Prevalence of intellectual disability among eight-year-old children from selected communities in the United States, 2014.

BACKGROUND: Children with intellectual disability (ID), characterized by impairments in intellectual functioning and adaptive behavior, benefit from early identification and access to services. Previous U.S. estimates used administrative data or parent report with limited information for demographic subgroups. OBJECTIVE: Using empiric measures we examined ID characteristics among 8-year-old children and estimated prevalence by sex, race/ethnicity, geographic area and socioeconomic status (SES) area indicators. METHODS: We analyzed data for 8-year-old children in 9 geographic areas participating in the 2014 Autism and Developmental Disabilities Monitoring Network. Children with ID were identified through record review of IQ test data. Census and American Community Survey data were used to estimate the denominator. RESULTS: Overall, 11.8 per 1,000 (1.2%) had ID (IQ ≤ 70), of whom 39% (n = 998) also had autism spectrum disorder. Among children with ID, 1,823 had adaptive behavior test scores for which 64% were characterized as impaired. ID prevalence per 1,000 was 15.8 (95% confidence interval [95% CI], 15.0-16.5) among males and 7.7 (95% CI, 7.2-8.2) among females. ID prevalence was 17.7 (95% CI, 16.6-18.9) among children who were non-Hispanic black; 12.0 (95% CI, 11.1-13.0), among Hispanic; 8.6 (95% CI, 7.1-10.4), among non-Hispanic Asian; and 8.0 (95% CI, 7.5-8.6), among non-Hispanic white. Prevalence varied across geographic areas and was inversely associated with SES. CONCLUSIONS: ID prevalence varied substantively among racial, ethnic, geographic, and SES groups. Results can inform strategies to enhance identification and improve access to services particularly for children who are minorities or living in areas with lower SES.

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2016.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance program that provides estimates of the prevalence of ASD among children aged 8 years whose parents or guardians live in 11 ADDM Network sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by medical and educational service providers in the community. In the second phase, experienced clinicians who systematically review all abstracted information determine ASD case status. The case definition is based on ASD criteria described in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: For 2016, across all 11 sites, ASD prevalence was 18.5 per 1,000 (one in 54) children aged 8 years, and ASD was 4.3 times as prevalent among boys as among girls. ASD prevalence varied by site, ranging from 13.1 (Colorado) to 31.4 (New Jersey). Prevalence estimates were approximately identical for non-Hispanic white (white), non-Hispanic black (black), and Asian/Pacific Islander children (18.5, 18.3, and 17.9, respectively) but lower for Hispanic children (15.4). Among children with ASD for whom data on intellectual or cognitive functioning were available, 33% were classified as having intellectual disability (intelligence quotient [IQ] ≤70); this percentage was higher among girls than boys (39% versus 32%) and among black and Hispanic than white children (47%, 36%, and 27%, respectively) [corrected]. Black children with ASD were less likely to have a first evaluation by age 36 months than were white children with ASD (40% versus 45%). The overall median age at earliest known ASD diagnosis (51 months) was similar by sex and racial and ethnic groups; however, black children with IQ ≤70 had a later median age at ASD diagnosis than white children with IQ ≤70 (48 months versus 42 months). INTERPRETATION: The prevalence of ASD varied considerably across sites and was higher than previous estimates since 2014. Although no overall difference in ASD prevalence between black and white children aged 8 years was observed, the disparities for black children persisted in early evaluation and diagnosis of ASD. Hispanic children also continue to be identified as having ASD less frequently than white or black children. PUBLIC HEALTH ACTION: These findings highlight the variability in the evaluation and detection of ASD across communities and between sociodemographic groups. Continued efforts are needed for early and equitable identification of ASD and timely enrollment in services.

Children with autism: quality of life and parental concerns.

Past research has shown that children with autism and their families have compromised quality of life (QOL) in several domains. This study examined QOL and parental concerns in children with autism during early childhood, childhood, and adolescence compared to children with Attention Deficit Disorder/Attention Deficit Hyperactivity Disorder (ADD/ADHD) and to typical controls from a US national sample. Families with children diagnosed with autism reported more profound QOL effects than families of children with ADD/ADHD or unaffected controls. Children with autism were significantly less likely to attend religious services, more likely to miss school, and less likely to participate in organized activities. Parental concerns over learning difficulty, being bullied, stress-coping, and achievement were overwhelming in the autism group relative to the comparison groups.

Increased risk of injury in children with developmental disabilities.

The objective of this study was to examine injury risk in children with autism, ADD/ADHD, learning disability, psychopathology, or other medical conditions. Children aged 3-5 years who participated in the National Survey of Children's Health were included. Six study groups were analyzed in this report: autism (n=82), ADD/ADHD (n=191), learning disability (n=307), psychopathology (n=210), other medical conditions (n=1802), and unaffected controls (n=13,398). The weighted prevalence of injury in each group was 24.2% (autism), 26.5% (ADD/ADHD), 9.3% (learning disability), 20.5% (psychopathology), 14.6% (other medical conditions), and 11.9% (unaffected controls). Compared to unaffected controls, the risk of injury was 2.15 (95% confidence interval (CI): 1.00-4.60), 2.74 (95% CI: 1.63-4.59), 2.06 (95% CI: 1.24-3.42), and 1.26 (95% CI: 1.00-1.58) in children with autism, ADD/ADHD, psychopathology, and other medical conditions, respectively, after adjusting for child sex, child age, number of children in the household, child race, and family poverty level. Children with autism, ADD/ADHD, and other psychopathology were about 2-3 times more likely to experience an injury that needs medical attention than unaffected controls. Future studies need to clarify the extent to which injuries in young children with autism, ADD/ADHD, and psychopathology are related to core symptoms, comorbid conditions, associated behaviors, or unintentional injuries due to lack of additional supervision from caregivers.

Relationship Between Advanced Maternal Age and Timing of First Developmental Evaluation in Children with Autism.

OBJECTIVE: Mothers of advanced maternal age (AMA) at childbirth (age ≥35 years) may have different perceptions of autism spectrum disorder (ASD) risk, independent of sociodemographic factors, that may affect ASD identification. We aimed to estimate associations between AMA and both age of a child's first evaluation noting developmental concerns and time from first evaluation to first ASD diagnosis. METHODS: We used data for 8-year-olds identified with ASD in the 2008 to 2012 Autism and Developmental Disabilities Monitoring Network. We estimated differences in age at first evaluation noting developmental concerns and time to first ASD diagnosis by AMA using quantile and Cox regression. RESULTS: Of 10,358 children with ASD, 19.7% had mothers of AMA. AMA was associated with higher educational attainment and previous live births compared with younger mothers. In unadjusted analyses, AMA was associated with earlier first evaluation noting developmental concerns (median 37 vs 40 mo) and patterns in time to first evaluation (hazard ratio: 1.12, 95% confidence interval: 1.06-1.18). Associations between AMA and evaluation timing diminished and were no longer significant after adjustment for socioeconomic and demographic characteristics. Children's intellectual disability did not modify associations between AMA and timing of evaluations. CONCLUSION: Advanced maternal age is a sociodemographic factor associated with younger age of first evaluation noting developmental concerns in children with ASD, but AMA was not independently associated likely, because it is a consequence or cofactor of maternal education and other sociodemographic characteristics. AMA may be a demographic factor to consider when aiming to screen and evaluate children at risk for ASD.

Disparity in report of autism-related behaviors by social demographic characteristics: Findings from a community-based study in Taiwan.

The Social Communication Questionnaire is one of the most commonly used screening tools for autism spectrum disorder. The Social Communication Questionnaire is a caregiver-reported questionnaire with 40 items based on questions from the Autism Diagnostic Interview-Revised. This study collected Social Communication Questionnaire data from a community-based, multi-stage case identification design epidemiologic study in one socioeconomically disadvantaged county in Taiwan. The Social Communication Questionnaire was distributed to 3034 school children, aged 6-8 years. Item prevalence results indicate males were reported to have more autism-related behaviors than females (higher prevalence on most items), in the whole study sample as well as in children meeting Social Communication Questionnaire clinical cut-offs (⩾15). Children whose biological fathers completed the Social Communication Questionnaire were reported to have more behavioral issues than children whose biological mothers were the respondent. Lower respondent education levels were associated with reports of clinically concerning autism-related behaviors. However, males were not at higher risk of meeting Social Communication Questionnaire clinical cut-offs than females in this study population. Findings from this study help to better understand reporting patterns on children's autism-related behaviors potentially due to social demographic characteristics and child sex, which may lead to improved identification of these behaviors.

Autism spectrum disorder reporting in lower socioeconomic neighborhoods.

Utilizing surveillance data from five sites participating in the Autism and Developmental Disabilities Monitoring Network, we investigated contributions of surveillance subject and census tract population sociodemographic characteristics on variation in autism spectrum disorder ascertainment and prevalence estimates from 2000 to 2008 using ordinal hierarchical models for 2489 tracts. Multivariable analyses showed a significant increase in ascertainment of autism spectrum disorder cases through both school and health sources, the optimal ascertainment scenario, for cases with college-educated mothers (adjusted odds ratio = 1.06, 95% confidence interval = 1.02-1.09). Results from our examination of sociodemographic factors of tract populations from which cases were drawn also showed that after controlling for other covariates, statistical significance remained for associations between optimal ascertainment and percentage of Hispanic residents (adjusted odds ratio = 0.93, 95% confidence interval = 0.88-0.99) and percentage of residents with at least a bachelor's degree (adjusted odds ratio = 1.06, 95% confidence interval = 1.01-1.11). We identified sociodemographic factors associated with autism spectrum disorder prevalence estimates including race, ethnicity, education, and income. Determining which specific factors influence disparities is complicated; however, it appears that even in the presence of education, racial and ethnic disparities are still apparent. These results suggest disparities in access to autism spectrum disorder assessments and special education for autism spectrum disorder among ethnic groups may impact subsequent surveillance.

Autism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury.

Prenatal and perinatal exposures to air pollutants have been shown to adversely affect birth outcomes in offspring and may contribute to prevalence of autism spectrum disorder (ASD). For this ecologic study, we evaluated the association between ASD prevalence, at the census tract level, and proximity of tract centroids to the closest industrial facilities releasing arsenic, lead or mercury during the 1990s. We used 2000 to 2008 surveillance data from five sites of the Autism and Developmental Disabilities Monitoring (ADDM) network and 2000 census data to estimate prevalence. Multi-level negative binomial regression models were used to test associations between ASD prevalence and proximity to industrial facilities in existence from 1991 to 1999 according to the US Environmental Protection Agency Toxics Release Inventory (USEPA-TRI). Data for 2489 census tracts showed that after adjustment for demographic and socio-economic area-based characteristics, ASD prevalence was higher in census tracts located in the closest 10th percentile compared of distance to those in the furthest 50th percentile (adjusted RR=1.27, 95% CI: (1.00, 1.61), P=0.049). The findings observed in this study are suggestive of the association between urban residential proximity to industrial facilities emitting air pollutants and higher ASD prevalence.

Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay.

OBJECTIVE: To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs). METHODS: A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information. RESULTS: Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07-7.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17-8.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98-11.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20-20.62). Findings were similar among mothers with an anxiety or mood disorder history. CONCLUSIONS: In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms.

Serotonin hypothesis of autism: implications for selective serotonin reuptake inhibitor use during pregnancy.

Serotonin, a neurotransmitter found throughout the brain and body, has long been of interest in autism. Repeated findings of elevated platelet serotonin levels in approximately one third of children with autism has led some to believe that dysfunctional serotonin signaling may be a causal mechanism for the disorder. Because serotonin is critical to fetal brain development, concerns have arisen regarding prenatal exposure to substances that manipulate serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs). This review examines evidence regarding the serotonin system and autism spectrum disorders (ASD), as well as what the literature has reported thus far on developmental effects of prenatal exposure to SSRIs. Possible mechanisms by which SSRIs could affect the fetus during pregnancy and clinical implications are also discussed. Though the majority of studies conducted in infants and children suggest prenatal exposure to SSRIs does not affect neurodevelopment, interpretation must be tempered given small sample sizes. The only published study that focused on prenatal SSRI exposure and ASD found an increased risk with exposure to SSRIs, especially during the first trimester. Obstacles that will be faced in future research are isolating medication effects from maternal depression and, given the infrequent occurrence of exposure and outcome, obtaining an adequate sample size. Whether serotonin is an etiologic factor in ASD, and what it points to as a marker for subgrouping, remains unclear. Understanding how the development of ASD might be affected by prenatal factors that influence serotonin levels, such as SSRIs, could identify modifiable targets for prevention.

Effects of hippocampal lesions on the monkey's ability to learn large sets of object-place associations.

Earlier studies found that recognition memory for object-place associations was impaired in patients with relatively selective hippocampal damage (Vargha-Khadem et al., Science 1997; 277:376-380), but was unaffected after selective hippocampal lesions in monkeys (Malkova and Mishkin, J Neurosci 2003; 23:1956-1965). A potentially important methodological difference between the two studies is that the patients were required to remember a set of 20 object-place associations for several minutes, whereas the monkeys had to remember only two such associations at a time, and only for a few seconds. To approximate more closely the task given to the patients, we trained monkeys on several successive sets of 10 object-place pairs each, with each set requiring learning across days. Despite the increased associative memory demands, monkeys given hippocampal lesions were unimpaired relative to their unoperated controls, suggesting that differences other than set size and memory duration underlie the different outcomes in the human and animal studies.