Community testing practices for autism within the autism and developmental disabilities monitoring network.

BACKGROUND: No data exist at the population level on what tests are used to aid in the diagnosis of autism spectrum disorder in community practice. OBJECTIVES: To describe autism spectrum disorder testing practices to inform autism spectrum disorder identification efforts. METHODS: Data are from the Autism and Developmental Disabilities Monitoring Network, a multi-site surveillance system reporting prevalence estimates and characteristics of 8-year-old children with autism spectrum disorder. Percentages of children with autism spectrum disorder who received any autism spectrum disorder test or a 'gold standard' test were calculated by site, sex, race, median household income, and intellectual ability status. Risk ratios were calculated to compare group differences. RESULTS: Of 5058 8-year-old children with autism spectrum disorder across 11 sites, 3236 (64.0%) had a record of any autism spectrum disorder test and 2136 (42.2%) had a 'gold standard' ADOS or ADI-R test. Overall, 115 children (2.3%) had both the ADOS and ADI-R in their records. Differences persisted across race, median household income, and intellectual ability status. Asian/Pacific Islander children had the highest percent receiving any ASD test (71.8%; other groups range: 57.4-66.0%) and White children had the highest percent receiving 'gold standard' tests (46.4%; other groups range: 35.6-43.2%). Children in low-income neighbourhoods had a lower percent of any test (62.5%) and 'gold standard' tests (39.4%) compared to medium (70.2% and 47.5%, respectively) and high (69.6% and 46.8%, respectively) income neighbourhoods. Children with intellectual disability had a lower percent of any ASD test (81.7%) and 'gold standard' tests (52.6%) compared to children without intellectual disability (84.0% and 57.6%, respectively). CONCLUSIONS: Autism spectrum disorder testing practices vary widely by site and differ by race and presence of co-occurring intellectual disability, suggesting opportunities to standardise and/or improve autism spectrum disorder identification practices.

Prevalence and Characteristics of Adolescents with Autism Spectrum Disorder in the New York-New Jersey Metropolitan Area.

PURPOSE: Almost all epidemiologic studies estimating autism spectrum disorder (ASD) prevalence have focused on school-age children. This study provides the first population-based data on the prevalence and expression of ASD among adolescents in a large US metropolitan region. METHODS: Active multiple source ASD surveillance of adolescents aged 16-years was conducted according to the Autism and Developmental Disabilities Monitoring (ADDM) Network method in a four-county New Jersey metropolitan region. Prevalence estimates are provided, characteristics are described and comparison of the distribution and characteristics of ASD is offered for this cohort, at 8 and 16-years. RESULTS: ASD prevalence was 17.7 per 1000 (95% CI: 16.3-19.2)]. One-in-55 males and one in 172 females were identified with ASD. High-SES was positively associated with ASD and White adolescents had higher ASD prevalence (22.2 per 1000) than Hispanic adolescents (13.1 per 1000). One in four study-confirmed individuals with ASD did not have an ASD diagnosis. A majority of ASD adolescents (58.8%) had a co-occurring neuropsychiatric disorder. White and High-SES individuals had greater likelihood of co-occurring disorder. The demographic distribution and functional profile of ASD was similar in this cohort at 8 and 16-years. CONCLUSION: Approximately one-in-55 adolescents in our area had ASD, in 2014, and one-in-4 16-year-olds with ASD was not diagnosed. A majority (3-in-5) of the adolescents with ASD had a co-occurring neuropsychiatric disorder. ASD under-identification and the high frequency of co-disorders in adolescents with ASD pose significant challenges to care and support.

Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020.

Problem/Condition: Autism spectrum disorder (ASD). Period Covered: 2020. 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. In 2020, there were 11 ADDM Network sites across the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. A child met the case definition if their record documented 1) an ASD diagnostic statement in an evaluation, 2) a classification of ASD in special education, or 3) an ASD International Classification of Diseases (ICD) code. Results: For 2020, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 23.1 in Maryland to 44.9 in California. The overall ASD prevalence was 27.6 per 1,000 (one in 36) children aged 8 years and was 3.8 times as prevalent among boys as among girls (43.0 versus 11.4). Overall, ASD prevalence was lower among non-Hispanic White children (24.3) and children of two or more races (22.9) than among non-Hispanic Black or African American (Black), Hispanic, and non-Hispanic Asian or Pacific Islander (A/PI) children (29.3, 31.6, and 33.4 respectively). ASD prevalence among non-Hispanic American Indian or Alaska Native (AI/AN) children (26.5) was similar to that of other racial and ethnic groups. ASD prevalence was associated with lower household income at three sites, with no association at the other sites.Across sites, the ASD prevalence per 1,000 children aged 8 years based exclusively on documented ASD diagnostic statements was 20.6 (range = 17.1 in Wisconsin to 35.4 in California). Of the 6,245 children who met the ASD case definition, 74.7% had a documented diagnostic statement of ASD, 65.2% had a documented ASD special education classification, 71.6% had a documented ASD ICD code, and 37.4% had all three types of ASD indicators. The median age of earliest known ASD diagnosis was 49 months and ranged from 36 months in California to 59 months in Minnesota.Among the 4,165 (66.7%) children with ASD with information on cognitive ability, 37.9% were classified as having an intellectual disability. Intellectual disability was present among 50.8% of Black, 41.5% of A/PI, 37.8% of two or more races, 34.9% of Hispanic, 34.8% of AI/AN, and 31.8% of White children with ASD. Overall, children with intellectual disability had earlier median ages of ASD diagnosis (43 months) than those without intellectual disability (53 months). Interpretation: For 2020, one in 36 children aged 8 years (approximately 4% of boys and 1% of girls) was estimated to have ASD. These estimates are higher than previous ADDM Network estimates during 2000-2018. For the first time among children aged 8 years, the prevalence of ASD was lower among White children than among other racial and ethnic groups, reversing the direction of racial and ethnic differences in ASD prevalence observed in the past. Black children with ASD were still more likely than White children with ASD to have a co-occurring intellectual disability. Public Health Action: The continued increase among children identified with ASD, particularly among non-White children and girls, highlights the need for enhanced infrastructure to provide equitable diagnostic, treatment, and support services for all children with ASD. Similar to previous reporting periods, findings varied considerably across network sites, indicating the need for additional research to understand the nature of such differences and potentially apply successful identification strategies across states.

Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2020.

Problem/Condition: Autism spectrum disorder (ASD). Period Covered: 2020. Description of System: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates prevalence and characteristics of ASD and monitors timing of ASD identification among children aged 4 and 8 years. In 2020, a total of 11 sites (located in Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) conducted surveillance of ASD among children aged 4 and 8 years and suspected ASD among children aged 4 years. Surveillance included children who lived in the surveillance area at any time during 2020. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement in an evaluation, 2) a special education classification of autism (eligibility), or 3) an ASD International Classification of Diseases (ICD) code (revisions 9 or 10). Children aged 4 years were classified as having suspected ASD if they did not meet the case definition for ASD but had a documented qualified professional's statement indicating a suspicion of ASD. This report focuses on children aged 4 years in 2020 compared with children aged 8 years in 2020. Results: For 2020, ASD prevalence among children aged 4 years varied across sites, from 12.7 per 1,000 children in Utah to 46.4 in California. The overall prevalence was 21.5 and was higher among boys than girls at every site. Compared with non-Hispanic White children, ASD prevalence was 1.8 times as high among Hispanic, 1.6 times as high among non-Hispanic Black, 1.4 times as high among Asian or Pacific Islander, and 1.2 times as high among multiracial children. Among the 58.3% of children aged 4 years with ASD and information on intellectual ability, 48.5% had an IQ score of ≤70 on their most recent IQ test or an examiner's statement of intellectual disability. Among children with a documented developmental evaluation, 78.0% were evaluated by age 36 months. Children aged 4 years had a higher cumulative incidence of ASD diagnosis or eligibility by age 48 months compared with children aged 8 years at all sites; risk ratios ranged from 1.3 in New Jersey and Utah to 2.0 in Tennessee. In the 6 months before the March 2020 COVID-19 pandemic declaration by the World Health Organization, there were 1,593 more evaluations and 1.89 more ASD identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. After the COVID-19 pandemic declaration, this pattern reversed: in the 6 months after pandemic onset, there were 217 fewer evaluations and 0.26 fewer identifications per 1,000 children aged 4 years than children aged 8 years received 4 years earlier. Patterns of evaluation and identification varied among sites, but there was not recovery to pre-COVID-19 pandemic levels by the end of 2020 at most sites or overall. For 2020, prevalence of suspected ASD ranged from 0.5 (California) to 10.4 (Arkansas) per 1,000 children aged 4 years, with an increase from 2018 at five sites (Arizona, Arkansas, Maryland, New Jersey, and Utah). Demographic and cognitive characteristics of children aged 4 years with suspected ASD were similar to children aged 4 years with ASD. Interpretation: A wide range of prevalence of ASD by age 4 years was observed, suggesting differences in early ASD identification practices among communities. At all sites, cumulative incidence of ASD by age 48 months among children aged 4 years was higher compared with children aged 8 years in 2020, indicating improvements in early identification of ASD. Higher numbers of evaluations and rates of identification were evident among children aged 4 years until the COVID-19 pandemic onset in 2020. Sustained lower levels of ASD evaluations and identification seen at a majority of sites after the pandemic onset could indicate disruptions in typical practices in evaluations and identification for health service providers and schools through the end of 2020. Sites with more recovery could indicate successful strategies to mitigate service interruption, such as pivoting to telehealth approaches for evaluation. Public Health Action: From 2016 through February of 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing ASD evaluation and identification 4 years earlier (from 2012 until March 2016) among the cohort of children aged 8 years in 2020 . From 2016 to March 2020, ASD evaluation and identification among the cohort of children aged 4 years was outpacing that among children aged 8 years in 2020 from 2012 until March 2016. The disruptions in evaluation that coincided with the start of the COVID-19 pandemic and the increase in prevalence of suspected ASD in 2020 could have led to delays in ASD identification and interventions. Communities could evaluate the impact of these disruptions as children in affected cohorts age and consider strategies to mitigate service disruptions caused by future public health emergencies.

Statewide county-level autism spectrum disorder prevalence estimates-seven U.S. states, 2018.

PURPOSE: Autism spectrum disorder (ASD) prevalence information is necessary for identifying community needs such as addressing disparities in identification and services. METHODS: Seven Autism and Developmental Disabilities Monitoring (ADDM) Network sites participated in a pilot project to link statewide health and education data to generate statewide and county-level prevalence estimates for a broader age range for their states for the first time. RESULTS: Statewide prevalence of ASD for ages 3-21 years in 2018 ranged from 1.5% in Tennessee and Wisconsin to 2.3% in Arizona. The median county-level prevalence of ASD was 1.4% of residents ages 3-21 years. More boys than girls had ASD at all sites, and prevalence was lower among non-Hispanic Black, Hispanic, Asian/Pacific Islander, and American Indian/Alaska Native residents compared to non-Hispanic White residents at most sites. ASD prevalence estimates for children aged 8 years were similar to 2018 ADDM Network estimates that used record review to provide more in-depth information, but showed greater variation for children aged 4 years. CONCLUSIONS: Linkage of statewide data sets provides less detailed but actionable local information when more resource-intensive methods are not possible.

Prevalence and Disparities in the Detection of Autism Without Intellectual Disability.

BACKGROUND: Intellectual ability predicts functional outcomes for children with autism spectrum disorder (ASD). It is essential to classify ASD children with and without intellectual disability (ID) to aid etiological research, provide services, and inform evidence-based educational and health planning. METHODS: Using a cross-sectional study design, data from 2000 to 2016 active ASD surveillance among 8-year-olds residing in the New York-New Jersey Metropolitan Area were analyzed to determine ASD prevalence with and without ID. Multivariable Poisson regression models were used to identify trends for ASD with ID (ASD-I) and without ID (ASD-N). RESULTS: Overall, 4661 8-year-olds were identified with ASD. Those that were ASI-I were 1505 (32.3%) and 2764 (59.3%) were ASD-N. Males were 3794 (81.4%), 946 (20.3%) were non-Hispanic Black (Black), 1230 (26.4%) were Hispanic, and 2114 (45.4%) were non-Hispanic white (white). We observed 2-fold and 5-fold increases in the prevalence of ASD-I and ASD-N, respectively, from 2000-2016. Black children were 30% less likely to be identified with ASD-N compared with white children. Children residing in affluent areas were 80% more likely to be identified with ASD-N compared with children in underserved areas. A greater proportion of children with ASD-I resided in vulnerable areas compared with children with ASD-N. Males had higher prevalence compared with females regardless of ID status; however, male-to-female ratios were slightly lower among ASD-I compared with ASD-N cases. CONCLUSIONS: One-in-3 children with ASD had ID. Disparities in the identification of ASD without ID were observed among Black and Hispanic children as well as among children residing in underserved areas.

Disparities in Early Intervention Program Participation by Children With Autism Spectrum Disorder in a US Metropolitan Area, 2006 to 2016.

Importance: Multiple studies have shown the value of early interventions for autism spectrum disorder (ASD). In the US, the Early Intervention Program (EIP) is mandated by law (Part C of the Individuals With Disabilities Education Act [IDEA]) to provide services to all young children with delays or disabilities. However, the extent to which children with ASD participate in this key service system is unknown. Objectives: To evaluate EIP use by children with ASD from 2006 to 2016 and to describe the factors associated with EIP participation. Design, Setting, and Participants: This cross-sectional study used repeated data collected from 2006 to 2016 by active ASD surveillance of the New York-New Jersey metropolitan area as reported in the New Jersey Autism Study. The New Jersey Autism Study identified 4050 children aged 8 years with ASD from 2006 to 2016. Demographic and clinical data were collected and participation in an EIP was assessed through active surveillance. Data were analyzed from June to December 2021. Exposure: Sociodemographic factors associated with the outcome of EIP participation. Main Outcomes and Measures: Participation in an EIP assessed at age 8 years. Demographic, ecological, and clinical factors, as well as temporal patterns, were examined by using standard and multilevel logistic regression models. Results: Among 4050 children aged 8 years with ASD by active surveillance, 1887 (46.6%) received EIP services. Of these children, 3303 (81.6%) were boys; 1105 (27.3%) were Hispanic, 801 (19.8%) were non-Hispanic Black, 1816 (44.8%) were non-Hispanic White, and 328 (8.1%) were non-Hispanic other (included Alaska Native or American Indian and Asian or Pacific Islander). In adjusted regression models, non-Hispanic Black children with ASD had lower odds of EIP participation (adjusted odds ratio [AOR], 0.67; 95% CI, 0.54-0.84) compared with their non-Hispanic White peers, and children residing in affluent areas had higher odds of receiving EIP services (AOR, 1.71; 95% CI, 1.36-2.15) compared with children residing in underserved areas. Children with ASD born in 2008 had higher odds of EIP participation than children born in 1998 (AOR, 2.64; 95% CI, 2.07-3.36). Conclusions and Relevance: Early identification of ASD is an important public health priority and receipt of EIP services may improve ASD outcomes. Approximately half of the population of children aged 8 years with ASD received EIP services between 2006 and 2016, and EIP participation by children with ASD increased during the 10-year period. However, receipt of EIP services was marked by strong socioeconomic status- and race and ethnicity-based disparities. Universal ASD screening and additional strategies are needed to address disparities and to increase access to EIP services.

Prevalence of autism spectrum disorder in a large, diverse metropolitan area: Variation by sociodemographic factors.

Autism spectrum disorder (ASD) prevalence estimates have varied by region. In this study, ASD prevalence, based on active case finding from multiple sources, was determined at the county and school district levels in the New Jersey metropolitan area. Among children born in 2008, residing in a four-county area and enrolled in public school in 2016, ASD prevalence was estimated to be 36 per 1000, but was significantly higher in one region-54 per 1000 and greater than 70 per 1000, in multiple school districts. Significant variation in ASD prevalence by race/ethnicity, socioeconomic status (SES), and school district size was identified. Highest prevalence was in mid-SES communities, contrary to expectation. Prevalence among Hispanic children was lower than expected, indicating a disparity in identification. Comprehensive surveillance should provide estimates at the county and town levels to appreciate ASD trends, identify disparities in detection or treatment, and explore factors influencing change in prevalence. LAY SUMMARY: We found autism prevalence to be 3.6% in New Jersey overall, but higher in one region (5.4%) and in multiple areas approaching 7.0%. We identified significant variation in autism spectrum disorder (ASD) prevalence by race/ethnicity, socioeconomic status (SES) and school district size. Mapping prevalence in smaller, well-specified, regions may be useful to better understand the true scope of ASD, disparities in ASD detection and the factors impacting ASD prevalence estimation.

Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring Network is an active surveillance program that estimates ASD prevalence and monitors timing of ASD identification among children aged 4 and 8 years. This report focuses on children aged 4 years in 2018, who were born in 2014 and had a parent or guardian who lived in the surveillance area in one of 11 sites (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin) at any time during 2018. Children were classified as having ASD if they ever received 1) an ASD diagnostic statement (diagnosis) in an evaluation, 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. Suspected ASD also was tracked among children aged 4 years. Children who did not meet the case definition for ASD were classified as having suspected ASD if their records contained a qualified professional's statement indicating a suspicion of ASD. RESULTS: For 2018, the overall ASD prevalence was 17.0 per 1,000 (one in 59) children aged 4 years. Prevalence varied from 9.1 per 1,000 in Utah to 41.6 per 1,000 in California. At every site, prevalence was higher among boys than girls, with an overall male-to-female prevalence ratio of 3.4. Prevalence of ASD among children aged 4 years was lower among non-Hispanic White (White) children (12.9 per 1,000) than among non-Hispanic Black (Black) children (16.6 per 1,000), Hispanic children (21.1 per 1,000), and Asian/Pacific Islander (A/PI) children (22.7 per 1,000). Among children aged 4 years with ASD and information on intellectual ability, 52% met the surveillance case definition of co-occurring intellectual disability (intelligence quotient ≤70 or an examiner's statement of intellectual disability documented in an evaluation). Of children aged 4 years with ASD, 72% had a first evaluation at age ≤36 months. Stratified by census-tract-level median household income (MHI) tertile, a lower percentage of children with ASD and intellectual disability was evaluated by age 36 months in the low MHI tertile (72%) than in the high MHI tertile (84%). Cumulative incidence of ASD diagnosis or eligibility received by age 48 months was 1.5 times as high among children aged 4 years (13.6 per 1,000 children born in 2014) as among those aged 8 years (8.9 per 1,000 children born in 2010). Across MHI tertiles, higher cumulative incidence of ASD diagnosis or eligibility received by age 48 months was associated with lower MHI. Suspected ASD prevalence was 2.6 per 1,000 children aged 4 years, meaning for every six children with ASD, one child had suspected ASD. The combined prevalence of ASD and suspected ASD (19.7 per 1,000 children aged 4 years) was lower than ASD prevalence among children aged 8 years (23.0 per 1,000 children aged 8 years). INTERPRETATION: Groups with historically lower prevalence of ASD (non-White and lower MHI) had higher prevalence and cumulative incidence of ASD among children aged 4 years in 2018, suggesting progress in identification among these groups. However, a lower percentage of children with ASD and intellectual disability in the low MHI tertile were evaluated by age 36 months than in the high MHI group, indicating disparity in timely evaluation. Children aged 4 years had a higher cumulative incidence of diagnosis or eligibility by age 48 months compared with children aged 8 years, indicating improvement in early identification of ASD. The overall prevalence for children aged 4 years was less than children aged 8 years, even when prevalence of children suspected of having ASD by age 4 years is included. This finding suggests that many children identified after age 4 years do not have suspected ASD documented by age 48 months. PUBLIC HEALTH ACTION: Children born in 2014 were more likely to be identified with ASD by age 48 months than children born in 2010, indicating increased early identification. However, ASD identification among children aged 4 years varied by site, suggesting opportunities to examine developmental screening and diagnostic practices that promote earlier identification. Children aged 4 years also were more likely to have co-occurring intellectual disability than children aged 8 years, suggesting that improvement in the early identification and evaluation of developmental concerns outside of cognitive impairments is still needed. Improving early identification of ASD could lead to earlier receipt of evidence-based interventions and potentially improve developmental outcomes.

Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2018. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network conducts active surveillance of ASD. This report focuses on the prevalence and characteristics of ASD among children aged 8 years in 2018 whose parents or guardians lived in 11 ADDM Network sites in the United States (Arizona, Arkansas, California, Georgia, Maryland, Minnesota, Missouri, New Jersey, Tennessee, Utah, and Wisconsin). To ascertain ASD among children aged 8 years, ADDM Network staff review and abstract developmental evaluations and records from community medical and educational service providers. In 2018, children met the case definition if their records documented 1) an ASD diagnostic statement in an evaluation (diagnosis), 2) a special education classification of ASD (eligibility), or 3) an ASD International Classification of Diseases (ICD) code. RESULTS: For 2018, across all 11 ADDM sites, ASD prevalence per 1,000 children aged 8 years ranged from 16.5 in Missouri to 38.9 in California. The overall ASD prevalence was 23.0 per 1,000 (one in 44) children aged 8 years, and ASD was 4.2 times as prevalent among boys as among girls. Overall ASD prevalence was similar across racial and ethnic groups, except American Indian/Alaska Native children had higher ASD prevalence than non-Hispanic White (White) children (29.0 versus 21.2 per 1,000 children aged 8 years). At multiple sites, Hispanic children had lower ASD prevalence than White children (Arizona, Arkansas, Georgia, and Utah), and non-Hispanic Black (Black) children (Georgia and Minnesota). The associations between ASD prevalence and neighborhood-level median household income varied by site. Among the 5,058 children who met the ASD case definition, 75.8% had a diagnostic statement of ASD in an evaluation, 18.8% had an ASD special education classification or eligibility and no ASD diagnostic statement, and 5.4% had an ASD ICD code only. ASD prevalence per 1,000 children aged 8 years that was based exclusively on documented ASD diagnostic statements was 17.4 overall (range: 11.2 in Maryland to 29.9 in California). The median age of earliest known ASD diagnosis ranged from 36 months in California to 63 months in Minnesota. Among the 3,007 children with ASD and data on cognitive ability, 35.2% were classified as having an intelligence quotient (IQ) score ≤70. The percentages of children with ASD with IQ scores ≤70 were 49.8%, 33.1%, and 29.7% among Black, Hispanic, and White children, respectively. Overall, children with ASD and IQ scores ≤70 had earlier median ages of ASD diagnosis than children with ASD and IQ scores >70 (44 versus 53 months). INTERPRETATION: In 2018, one in 44 children aged 8 years was estimated to have ASD, and prevalence and median age of identification varied widely across sites. Whereas overall ASD prevalence was similar by race and ethnicity, at certain sites Hispanic children were less likely to be identified as having ASD than White or Black children. The higher proportion of Black children compared with White and Hispanic children classified as having intellectual disability was consistent with previous findings. PUBLIC HEALTH ACTION: The variability in ASD prevalence and community ASD identification practices among children with different racial, ethnic, and geographical characteristics highlights the importance of research into the causes of that variability and strategies to provide equitable access to developmental evaluations and services. These findings also underscore the need for enhanced infrastructure for diagnostic, treatment, and support services to meet the needs of all children.

Early Identification of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Six Sites, United States, 2016.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2016. DESCRIPTION OF SYSTEM: The Early Autism and Developmental Disabilities Monitoring (Early ADDM) Network, a subset of the overall ADDM Network, is an active surveillance program that estimates ASD prevalence and monitors early identification of ASD among children aged 4 years. Children included in surveillance year 2016 were born in 2012 and had a parent or guardian who lived in the surveillance area in Arizona, Colorado, Missouri, New Jersey, North Carolina, or Wisconsin, at any time during 2016. Children were identified from records of community sources including general pediatric health clinics, special education programs, and early intervention programs. Data from comprehensive evaluations performed by community professionals were abstracted and reviewed by trained clinicians using a standardized ASD surveillance case definition with criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). RESULTS: In 2016, the overall ASD prevalence was 15.6 per 1,000 (one in 64) children aged 4 years for Early ADDM Network sites. Prevalence varied from 8.8 per 1,000 in Missouri to 25.3 per 1,000 in New Jersey. At every site, prevalence was higher among boys than among girls, with an overall male-to-female prevalence ratio of 3.5 (95% confidence interval [CI] = 3.1-4.1). Prevalence of ASD between non-Hispanic white (white) and non-Hispanic black (black) children was similar at each site (overall prevalence ratio: 0.9; 95% CI = 0.8-1.1). The prevalence of ASD using DSM-5 criteria was lower than the prevalence using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria at one of four sites that used criteria from both editions. Among sites where ≥60% of children aged 4 years had information about intellectual disability (intelligence quotient ≤70 or examiner's statement of intellectual disability documented in an evaluation), 53% of children with ASD had co-occurring intellectual disability. Of all children aged 4 years with ASD, 84% had a first evaluation at age ≤36 months and 71% of children who met the surveillance case definition had a previous ASD diagnosis from a community provider. Median age at first evaluation and diagnosis for this age group was 26 months and 33 months, respectively. Cumulative incidence of autism diagnoses received by age 48 months was higher for children aged 4 years than for those aged 8 years identified in Early ADDM Network surveillance areas in 2016. INTERPRETATION: In 2016, the overall prevalence of ASD in the Early ADDM Network using DSM-5 criteria (15.6 per 1,000 children aged 4 years) was higher than the 2014 estimate using DSM-5 criteria (14.1 per 1,000). Children born in 2012 had a higher cumulative incidence of ASD diagnoses by age 48 months compared with children born in 2008, which indicates more early identification of ASD in the younger group. The disparity in ASD prevalence has decreased between white and black children. Prevalence of co-occurring intellectual disability was higher than in 2014, suggesting children with intellectual disability continue to be identified at younger ages. More children received evaluations by age 36 months in 2016 than in 2014, which is consistent with Healthy People 2020 goals. Median age at earliest ASD diagnosis has not changed considerably since 2014. PUBLIC HEALTH ACTION: More children aged 4 years with ASD are being evaluated by age 36 months and diagnosed by age 48 months, but there is still room for improvement in early identification. Timely evaluation of children by community providers as soon as developmental concerns have been identified might result in earlier ASD diagnoses, earlier receipt of evidence-based interventions, and improved developmental outcomes.

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.

Disparities in Documented Diagnoses of Autism Spectrum Disorder Based on Demographic, Individual, and Service Factors.

The objectives of our study were to (a) report how many children met an autism spectrum disorder (ASD) surveillance definition but had no clinical diagnosis of ASD in health or education records and (b) evaluate differences in demographic, individual, and service factors between children with and without a documented ASD diagnosis. ASD surveillance was conducted in selected areas of Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin. Children were defined as having ASD if sufficient social and behavioral deficits and/or an ASD diagnosis were noted in health and/or education records. Among 4,498 children, 1,135 (25%) had ASD indicators without having an ASD diagnosis. Of those 1,135 children without a documented ASD diagnosis, 628 (55%) were not known to receive ASD services in public school. Factors associated with not having a clinical diagnosis of ASD were non-White race, no intellectual disability, older age at first developmental concern, older age at first developmental evaluation, special education eligibility other than ASD, and need for fewer supports. These results highlight the importance of reducing disparities in the diagnosis of children with ASD characteristics so that appropriate interventions can be promoted across communities. Autism Res 2020, 13: 464-473. © 2019 International Society for AutismResearch,Wiley Periodicals, Inc. LAY SUMMARY: Children who did not have a clinical diagnosis of autism spectrum disorder (ASD) documented in health or education records were more likely to be non-White and have fewer developmental problems than children with a clinical diagnosis of ASD. They were brought to the attention of healthcare providers at older ages and needed fewer supports than children with a clinical diagnosis of ASD. All children with ASD symptoms who meet diagnostic criteria should be given a clinical diagnosis so they can receive treatment specific to their needs.

Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 4 Years - Early Autism and Developmental Disabilities Monitoring Network, Seven Sites, United States, 2010, 2012, and 2014.

PROBLEM/CONDITION: Autism spectrum disorder (ASD) is estimated to affect up to 3% of children in the United States. Public health surveillance for ASD among children aged 4 years provides information about trends in prevalence, characteristics of children with ASD, and progress made toward decreasing the age of identification of ASD so that evidence-based interventions can begin as early as possible. PERIOD COVERED: 2010, 2012, and 2014. DESCRIPTION OF SYSTEM: The Early Autism and Developmental Disabilities Monitoring (Early ADDM) Network is an active surveillance system that provides biennial estimates of the prevalence and characteristics of ASD among children aged 4 years whose parents or guardians lived within designated sites. During surveillance years 2010, 2012, or 2014, data were collected in seven sites: Arizona, Colorado, Missouri, New Jersey, North Carolina, Utah, and Wisconsin. The Early ADDM Network is a subset of the broader ADDM Network (which included 13 total sites over the same period) that has been conducting ASD surveillance among children aged 8 years since 2000. Each Early ADDM site covers a smaller geographic area than the broader ADDM Network. Early ADDM ASD surveillance is conducted in two phases using the same methods and project staff members as the ADDM Network. The first phase consists of reviewing and abstracting data from children's records, including comprehensive evaluations performed by community professionals. Sources for these evaluations include general pediatric health clinics and specialized programs for children with developmental disabilities. In addition, special education records (for children aged ≥3 years) were reviewed for Arizona, Colorado, New Jersey, North Carolina, and Utah, and early intervention records (for children aged 0 to <3 years) were reviewed for New Jersey, North Carolina, Utah, and Wisconsin; in Wisconsin, early intervention records were reviewed for 2014 only. The second phase involves a review of the abstracted evaluations by trained clinicians using a standardized case definition and method. A child is considered to meet the surveillance case definition for ASD if one or more comprehensive evaluations of that child completed by a qualified professional describes behaviors consistent with the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnostic criteria for any of the following conditions: autistic disorder, pervasive developmental disorder-not otherwise specified (PDD-NOS, including atypical autism), or Asperger disorder (2010, 2012, and 2014). For 2014 only, prevalence estimates based on surveillance case definitions according to DSM-IV-TR and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) were compared. This report provides estimates of overall ASD prevalence and prevalence by sex and race/ethnicity; characteristics of children aged 4 years with ASD, including age at first developmental evaluation, age at ASD diagnosis, and cognitive function; and trends in ASD prevalence and characteristics among Early ADDM sites with data for all 3 surveillance years (2010, 2012, and 2014), including comparisons with children aged 8 years living in the same geographic area. Analyses of time trends in ASD prevalence are restricted to the three sites that contributed data for all 3 surveillance years with consistent data sources (Arizona, Missouri, and New Jersey). RESULTS: The overall ASD prevalence was 13.4 per 1,000 children aged 4 years in 2010, 15.3 in 2012, and 17.0 in 2014 for Early ADDM sites with data for the specific years. ASD prevalence was determined using a surveillance case definition based on DSM-IV-TR. Within each surveillance year, ASD prevalence among children aged 4 years varied across surveillance sites and was lowest each year for Missouri (8.5, 8.1, and 9.6 per 1,000, for 2010, 2012, and 2014, respectively) and highest each year for New Jersey (19.7, 22.1, and 28.4 per 1,000, for the same years, respectively). Aggregated prevalence estimates were higher for sites that reviewed education and health care records than for sites that reviewed only health care records. Among all participating sites and years, ASD prevalence among children aged 4 years was consistently higher among boys than girls; prevalence ratios ranged from 2.6 (Arizona and Wisconsin in 2010) to 5.2 boys per one girl (Colorado in 2014). In 2010, ASD prevalence was higher among non-Hispanic white children than among Hispanic children in Arizona and non-Hispanic black children in Missouri; no other differences were observed by race/ethnicity. Among four sites with ≥60% data on cognitive test scores (Arizona, New Jersey, North Carolina, and Utah), the frequency of co-occurring intellectual disabilities was significantly higher among children aged 4 years than among those aged 8 years for each site in each surveillance year except Arizona in 2010. The percentage of children with ASD who had a first evaluation by age 36 months ranged from 48.8% in Missouri in 2012 to 88.9% in Wisconsin in 2014. The percentage of children with a previous ASD diagnosis from a community provider varied by site, ranging from 43.0% for Arizona in 2012 to 86.5% for Missouri in 2012. The median age at earliest known ASD diagnosis varied from 28 months in North Carolina in 2014 to 39.0 months in Missouri and Wisconsin in 2012. In 2014, the ASD prevalence based on the DSM-IV-TR case definition was 20% higher than the prevalence based on the DSM-5 (17.0 versus 14.1 per 1,000, respectively). Trends in ASD prevalence and characteristics among children aged 4 years during the study period were assessed for the three sites with data for all 3 years and consistent data sources (Arizona, Missouri, and New Jersey) using the DSM-IV-TR case definition; prevalence was higher in 2014 than in 2010 among children aged 4 years in New Jersey and was stable in Arizona and Missouri. In Missouri, ASD prevalence was higher among children aged 8 years than among children aged 4 years. The percentage of children with ASD who had a comprehensive evaluation by age 36 months was stable in Arizona and Missouri and decreased in New Jersey. In the three sites, no change occurred in the age at earliest known ASD diagnosis during 2010-2014. INTERPRETATION: The findings suggest that ASD prevalence among children aged 4 years was higher in 2014 than in 2010 in one site and remained stable in others. Among children with ASD, the frequency of cognitive impairment was higher among children aged 4 years than among those aged 8 years and suggests that surveillance at age 4 years might more often include children with more severe symptoms or those with co-occurring conditions such as intellectual disability. In the sites with data for all years and consistent data sources, no change in the age at earliest known ASD diagnosis was found, and children received their first developmental evaluation at the same or a later age in 2014 compared with 2010. Delays in the initiation of a first developmental evaluation might adversely affect children by delaying access to treatment and special services that can improve outcomes for children with ASD. PUBLIC HEALTH ACTION: Efforts to increase awareness of ASD and improve the identification of ASD by community providers can facilitate early diagnosis of children with ASD. Heterogeneity of results across sites suggests that community-level differences in evaluation and diagnostic services as well as access to data sources might affect estimates of ASD prevalence and age of identification. Continuing improvements in providing developmental evaluations to children as soon as developmental concerns are identified might result in earlier ASD diagnoses and earlier receipt of services, which might improve developmental outcomes.

Prevalence of Autism Spectrum Disorder Among Children Aged 8 Years - Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2014.

PROBLEM/CONDITION: Autism spectrum disorder (ASD). PERIOD COVERED: 2014. DESCRIPTION OF SYSTEM: The Autism and Developmental Disabilities Monitoring (ADDM) Network is an active surveillance system that provides estimates of the prevalence of autism spectrum disorder (ASD) among children aged 8 years whose parents or guardians reside within 11 ADDM sites in the United States (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). ADDM surveillance is conducted in two phases. The first phase involves review and abstraction of comprehensive evaluations that were completed by professional service providers in the community. Staff completing record review and abstraction receive extensive training and supervision and are evaluated according to strict reliability standards to certify effective initial training, identify ongoing training needs, and ensure adherence to the prescribed methodology. Record review and abstraction occurs in a variety of data sources ranging from general pediatric health clinics to specialized programs serving children with developmental disabilities. In addition, most of the ADDM sites also review records for children who have received special education services in public schools. In the second phase of the study, all abstracted information is reviewed systematically by experienced clinicians to determine ASD case status. A child is considered to meet the surveillance case definition for ASD if he or she displays behaviors, as described on one or more comprehensive evaluations completed by community-based professional providers, consistent with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnostic criteria for autistic disorder; pervasive developmental disorder-not otherwise specified (PDD-NOS, including atypical autism); or Asperger disorder. This report provides updated ASD prevalence estimates for children aged 8 years during the 2014 surveillance year, on the basis of DSM-IV-TR criteria, and describes characteristics of the population of children with ASD. In 2013, the American Psychiatric Association published the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which made considerable changes to ASD diagnostic criteria. The change in ASD diagnostic criteria might influence ADDM ASD prevalence estimates; therefore, most (85%) of the records used to determine prevalence estimates based on DSM-IV-TR criteria underwent additional review under a newly operationalized surveillance case definition for ASD consistent with the DSM-5 diagnostic criteria. Children meeting this new surveillance case definition could qualify on the basis of one or both of the following criteria, as documented in abstracted comprehensive evaluations: 1) behaviors consistent with the DSM-5 diagnostic features; and/or 2) an ASD diagnosis, whether based on DSM-IV-TR or DSM-5 diagnostic criteria. Stratified comparisons of the number of children meeting either of these two case definitions also are reported. RESULTS: For 2014, the overall prevalence of ASD among the 11 ADDM sites was 16.8 per 1,000 (one in 59) children aged 8 years. Overall ASD prevalence estimates varied among sites, from 13.1-29.3 per 1,000 children aged 8 years. ASD prevalence estimates also varied by sex and race/ethnicity. Males were four times more likely than females to be identified with ASD. Prevalence estimates were higher for non-Hispanic white (henceforth, white) children compared with non-Hispanic black (henceforth, black) children, and both groups were more likely to be identified with ASD compared with Hispanic children. Among the nine sites with sufficient data on intellectual ability, 31% of children with ASD were classified in the range of intellectual disability (intelligence quotient [IQ] <70), 25% were in the borderline range (IQ 71-85), and 44% had IQ scores in the average to above average range (i.e., IQ >85). The distribution of intellectual ability varied by sex and race/ethnicity. Although mention of developmental concerns by age 36 months was documented for 85% of children with ASD, only 42% had a comprehensive evaluation on record by age 36 months. The median age of earliest known ASD diagnosis was 52 months and did not differ significantly by sex or race/ethnicity. For the targeted comparison of DSM-IV-TR and DSM-5 results, the number and characteristics of children meeting the newly operationalized DSM-5 case definition for ASD were similar to those meeting the DSM-IV-TR case definition, with DSM-IV-TR case counts exceeding DSM-5 counts by less than 5% and approximately 86% overlap between the two case definitions (kappa = 0.85). INTERPRETATION: Findings from the ADDM Network, on the basis of 2014 data reported from 11 sites, provide updated population-based estimates of the prevalence of ASD among children aged 8 years in multiple communities in the United States. The overall ASD prevalence estimate of 16.8 per 1,000 children aged 8 years in 2014 is higher than previously reported estimates from the ADDM Network. Because the ADDM sites do not provide a representative sample of the entire United States, the combined prevalence estimates presented in this report cannot be generalized to all children aged 8 years in the United States. Consistent with reports from previous ADDM surveillance years, findings from 2014 were marked by variation in ASD prevalence when stratified by geographic area, sex, and level of intellectual ability. Differences in prevalence estimates between black and white children have diminished in most sites, but remained notable for Hispanic children. For 2014, results from application of the DSM-IV-TR and DSM-5 case definitions were similar, overall and when stratified by sex, race/ethnicity, DSM-IV-TR diagnostic subtype, or level of intellectual ability. PUBLIC HEALTH ACTION: Beginning with surveillance year 2016, the DSM-5 case definition will serve as the basis for ADDM estimates of ASD prevalence in future surveillance reports. Although the DSM-IV-TR case definition will eventually be phased out, it will be applied in a limited geographic area to offer additional data for comparison. Future analyses will examine trends in the continued use of DSM-IV-TR diagnoses, such as autistic disorder, PDD-NOS, and Asperger disorder in health and education records, documentation of symptoms consistent with DSM-5 terminology, and how these trends might influence estimates of ASD prevalence over time. The latest findings from the ADDM Network provide evidence that the prevalence of ASD is higher than previously reported estimates and continues to vary among certain racial/ethnic groups and communities. With prevalence of ASD ranging from 13.1 to 29.3 per 1,000 children aged 8 years in different communities throughout the United States, the need for behavioral, educational, residential, and occupational services remains high, as does the need for increased research on both genetic and nongenetic risk factors for ASD.

Preliminary Evaluation of a Brief Autism Screener for Young Children.

OBJECTIVE: Our objective was to assess the operating characteristics of the Psychological Development Questionnaire-1 (PDQ-1), an autism screener for use with young children. METHODS: In Phase 1, we evaluated the concordance of the PDQ-1 with established autism scales, determined test-retest reliability, and identified a risk threshold score. In Phase 2, a population of 1959 toddler-age children was prospectively screened through multiple pediatric practices in a diverse metropolitan region, using the new instrument. Screen-positive children were referred for diagnostic evaluation. Screened children received follow-up at age 4 years to identify autism cases missed by screening and to specify the scale's psychometric properties. RESULTS: By screening a diverse population of low risk children, age 18 to 36 months, with the PDQ-1, we detected individuals with autism who had not come to professional attention. Overall, the PDQ-1 showed a positive predictive value (PPV) of 88%, with a sensitivity of 85% and specificity of 99% in a low risk population. High specificity, good sensitivity, and PPV were observed across the 18 to 36 month age-range. CONCLUSION: The findings provide preliminary empirical support for this parent report-based indicator of toddler psychological development and suggest that the PDQ-1 may be a useful supplement to developmental surveillance of autism. Additional research is needed with high risk samples and large, unselected populations under real-world conditions.

Increasing autism prevalence in metropolitan New Jersey.

High baseline autism spectrum disorder prevalence estimates in New Jersey led to a follow-up surveillance. The objectives were to determine autism spectrum disorder prevalence in the year 2006 in New Jersey and to identify changes in the prevalence of autism spectrum disorder or in the characteristics of the children with autism spectrum disorder, between 2002 and 2006. The cohorts included 30,570 children, born in 1998 and 28,936 children, born in 1994, residing in Hudson, Union, and Ocean counties, New Jersey. Point prevalence estimates by sex, ethnicity, autism spectrum disorder subtype, and previous autism spectrum disorder diagnosis were determined. For 2006, a total of 533 children with autism spectrum disorder were identified, consistent with prevalence of 17.4 per 1000 (95% confidence interval = 15.9-18.9), indicating a significant increase in the autism spectrum disorder prevalence (p < 0.001), between 2002 (10.6 per 1000) and 2006. The rise in autism spectrum disorder was broad, affecting major demographic groups and subtypes. Boys with autism spectrum disorder outnumbered girls by nearly 5:1. Autism spectrum disorder prevalence was higher among White children than children of other ethnicities. Additional studies are needed to specify the influence of better awareness of autism spectrum disorder prevalence estimates and to identify possible autism spectrum disorder risk factors. More resources are necessary to address the needs of individuals affected by autism spectrum disorder.

An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon.

Acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) are enzymes that belong to the superfamily of alpha/beta-hydrolase fold proteins. While they share many characteristics, they also possess many important differences. For example, whereas they have about 54% amino acid sequence identity, the active site gorge of acetylcholinesterase is considerably smaller than that of butyrylcholinesterase. Moreover, both have been shown to display simple and complex kinetic mechanisms, depending on the particular substrate examined, the substrate concentration, and incubation conditions. In the current study, incubation of butyrylthiocholine in a concentration range of 0.005-3.0 mM, with 317 pM human butyrylcholinesterase in vitro, resulted in rates of production of thiocholine that were accurately described by simple Michaelis-Menten kinetics, with a K(m) of 0.10 mM. Similarly, the inhibition of butyrylcholinesterase in vitro by the organophosphate chlorpyrifos oxon was described by simple Michaelis-Menten kinetics, with a k(i) of 3048 nM(-1) h(-1), and a K(D) of 2.02 nM. In contrast to inhibition of butyrylcholinesterase, inhibition of human acetylcholinesterase by chlorpyrifos oxon in vitro followed concentration-dependent inhibition kinetics, with the k(i) increasing as the inhibitor concentration decreased. Chlorpyrifos oxon concentrations of 10 and 0.3 nM gave k(i)s of 1.2 and 19.3 nM(-1) h(-1), respectively. Although the mechanism of concentration-dependent inhibition kinetics is not known, the much smaller, more restrictive active site gorge of acetylcholinesterase almost certainly plays a role. Similarly, the much larger active site gorge of butyrylcholinesterase likely contributes to its much greater reactivity towards chlorpyrifos oxon, compared to acetylcholinesterase.