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Seizures occur in up to 59% of boys with creatine transporter deficiency (CTD). While seizure phenotypes have been previously described, electroencephalogram (EEG) findings have only been reported in several case reports. In this prospective observational study, we report seizure characteristics and EEG findings in combination with neurobehavioral and SLC6A8 pathogenic variants in twenty males with CTD. Eighteen study participants (SP) underwent video-EEG, and seven had follow-up EEG recordings. Seizures typically occurred by age of 2 years. Thirteen (65%) had non-febrile seizures, requiring anti-seizure medications in nine. Four had febrile seizures. Seizures were bilateral tonic-clonic in 7 SP and focal impaired awareness in 5 SP; often responding to 1 to 2 antiseizure medications. EEG showed slowing in 5 SP, beta activity in 6 SP, and focal/multifocal, and/or generalized epileptiform activity in 9 SP. Follow-up EEGs in 7 SP showed emergence of epileptiform activity in 1 SP, and increased activity in 2 SP. In conclusion, seizures were frequent in our cohort but tended to respond to antiseizure medications. Longitudinal follow up provided further insight into emergence of seizures and EEG abnormalities soliciting future studies with long term follow up. Biomarkers of epileptogenicity in CTD are needed to predict seizures in this population.
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Encefalopatías Metabólicas Innatas , Creatina/deficiencia , Electroencefalografía , Discapacidad Intelectual Ligada al Cromosoma X , Masculino , Humanos , Preescolar , Mutación , Convulsiones/diagnóstico , Convulsiones/tratamiento farmacológico , Convulsiones/genética , Proteínas del Tejido Nervioso , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/genéticaRESUMEN
Our study characterized the neurodevelopmental spectrum of individuals with PTEN Hamartoma Tumor Syndrome (PHTS), a syndrome that predisposes to both neurodevelopmental phenotypes and cancer risk. We aim to better understand life-impacting neurodevelopmental features of PHTS. Our study recruited 20 children/adolescents with PHTS, who were then administered assessments for autism spectrum disorder (ASD) and other neurocognitive measures, including assessment of IQ, executive and adaptive functioning, and health-related quality of life. Thirteen individuals (65%) were identified as having ASD, of which five were newly diagnosed during the study. Of those, ASD symptom severity was in the mild-moderate range for 77%. Overall, IQ was in the average range, with a mean of 92.61 (SD 24.45, p = 0.5), though there was a non-statistically significant trend toward individuals without ASD having a higher mean IQ (102.7 vs 82.3; p = 0.1). Subjects had significant impairment in processing speed (mean 75.38, SD 24.75, p < 0.05), decreased adaptive functioning skills across all domains, and a trend toward having more executive functioning problems. Individuals with PHTS are at increased risk of neurodevelopmental disorders, including ASD and impaired executive and adaptive functioning. Although clear guidelines exist for cancer surveillance for individuals with PHTS, additional guidelines and screening for neurodevelopmental disorders are warranted.
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Trastorno del Espectro Autista , Síndrome de Hamartoma Múltiple , Fosfohidrolasa PTEN , Fenotipo , Humanos , Masculino , Femenino , Niño , Adolescente , Síndrome de Hamartoma Múltiple/genética , Síndrome de Hamartoma Múltiple/patología , Síndrome de Hamartoma Múltiple/diagnóstico , Trastorno del Espectro Autista/genética , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/diagnóstico , Fosfohidrolasa PTEN/genética , Preescolar , Calidad de VidaRESUMEN
PURPOSE: Quality of life (QoL) is identified as a clinical and research priority by the autistic community. Researchers have the responsibility to ensure that instruments used to measure QoL do so reliably and accurately among autistic participants. METHODS: Our study evaluated measurement invariance of Emotional Distress (Depression, Anxiety, Anger, Psychological Stress) and Subjective Well-Being (Life Satisfaction, Positive Affect, and Meaning & Purpose) scales of the Patient-Reported Outcomes Measurement Information System (PROMIS) among groups of autistic (N=140, n per scale=132-140) and general population (N=1,224, n per scale=406-411) teenagers (14-17 years). These scales were included in the PROMIS Autism Battery-Lifespan, which uses PROMIS scales to measure QoL domains most relevant for autistic people. RESULTS: Multi-group confirmatory factor analyses using permutation tests demonstrated that Depression and Positive Affect scales exhibited scalar invariance between groups, indicating that scores can be meaningfully compared across autistic and general population teens. Anger and Psychological Stress scales demonstrated metric invariance between groups, indicating that these scales measure the same latent trait in both groups, but group comparisons are not supported. CONCLUSION: We provide guidance as to how these scales can be used in psychometrically supported ways to capture constructs relevant for understanding QoL among autistic teens.
Quality of life is an important outcome for autistic people and their families. However, many quality of life scales have not been tested to make sure they accurately measure quality of life among autistic people. It is important to make sure that quality of life measures works similarly among the autistic population. The goal of our study is to test whether scales on a common quality of life measure the Patient-Reported Outcomes Measurement Information System (PROMIS) measures quality of life in the same way between autistic and general population adolescents. We found that some of the PROMIS scales worked the same way for autistic and general population adolescents and others did not. These results help researchers confidently use the PROMIS scales to measure different aspects of quality of life among autistic youth.
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Early identification is a goal for creatine transporter deficiency and will be critical for future treatment. Before their first birthday, one-half of this sample showed both a significant feeding/weight gain issue and delayed sitting or crawling. Combined, these early indicators could have alerted providers to conduct a urine screen.
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Encefalopatías Metabólicas Innatas/diagnóstico , Creatina/deficiencia , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/deficiencia , Adolescente , Factores de Edad , Encefalopatías Metabólicas Innatas/complicaciones , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Discapacidad Intelectual Ligada al Cromosoma X/complicaciones , Estudios Retrospectivos , Factores de Riesgo , Evaluación de Síntomas , Urinálisis , Adulto JovenRESUMEN
PURPOSE OF REVIEW: This article discusses common issues surrounding transition to adulthood in youth with autism spectrum disorder (ASD). We review recent evidence on co-occurring medical and mental health conditions and topics of education and employment, sexuality and relationships, independent living, and financial support. RECENT FINDINGS: Transitioning individuals with ASD have increased risk for several medical and behavioral health comorbidities and should be routinely screened for co-occurring conditions. Evidence on interventions for mental health disorders is limited but emerging, particularly with respect to mindfulness training and cognitive behavioral therapy. Many autistic adults or their families express a desire for independent living, participation in education/employment, and intimacy and social relationships, but they often lack skills and/or resources to successfully achieve these outcomes. The time of transition to adulthood for adolescents with ASD is an opportunity for physicians to provide anticipatory guidance and necessary supports around issues of community participation. To allow time for planning, these discussions should occur well before the child reaches adulthood. Clinicians should also routinely screen for and address medical and/or behavioral health comorbidities.
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Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/psicología , Adolescente , Niño , Comorbilidad , Humanos , Adulto JovenRESUMEN
The electronic health record (EHR) should contain information to support culturally responsive care and research; however, the widely used default "Asian" demographic variable in most US social systems (including EHRs) lacks information to describe the diverse experience within the Asian diaspora (e.g., ethnicities, languages). This has a downstream effect on research, identifying disparities, and addressing health equity. We were particularly interested in EHRs of autistic patients from the Asian diaspora, since the presence of a developmental diagnosis might call for culturally responsive care around understanding causes, treatments, and services to support good outcomes. The aim of this study is to determine the degree to which information about Asian ethnicity, languages, and culture is documented and accessible in the EHR, and whether it is differentially available for patients with or without autism. Using electronic and manual medical chart review, all autistic and "Asian" children (group 1; n = 52) were compared to a randomly selected comparison sample of non-autistic and "Asian" children (group 2; n = 50). Across both groups, manual chart review identified more specific approximations of racial/ethnic backgrounds in 54.5% of patients, 56% for languages spoken, and that interpretation service use was underestimated by 13 percentage points. Our preliminary results highlight that culturally responsive information was inconsistent, missing, or located in progress notes rather than a central location where it could be accessed by providers. Recommendations about the inclusion of Asian ethnicity and language data are provided to potentially enhance cultural responsiveness and support better outcomes for families with an autistic child.
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The lives of caregivers can be deeply impacted by having a child with a developmental disability (DD). To offset those impacts, caregivers may engage in accommodations, or strategies to bolster everyday functioning. The nature and extent of these accommodations can provide insight into how the family is doing and what supports are needed from a family-centered perspective. This paper presents the development and preliminary validation of the Accommodations & Impact Scale for Developmental Disabilities (AISDD). The AISDD is a rating scale that measures day-to-day accommodations and impacts of raising a child with a DD. A sample of 407 caregivers of youth with DDs (Mage = 11.7 years; 63% males) completed the AISDD, along with measures of caregiver strain, daily challenges, child adaptive behavior, and behavior and emotional regulation. The AISDD is a unidimensional, 19-item scale with excellent internal consistency (ordinal alpha = .93) and test-retest (ICC = .95) reliability. Scores were normally distributed and sensitive to age (r = - .19), diagnosis (ASD + ID > ASD > ID), adaptive functioning (r = - .35), and challenging behaviors (r = .57). Finally, the AISDD showed excellent convergent validity with similar measures of accommodations and impacts. These findings support the use of the AISDD as a valid and reliable tool for measuring accommodations among caregivers of individuals with DDs. This measure shows promise in its ability to identify which families may need additional support for their children.
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LAY ABSTRACT: Historically, children from non-Hispanic Black and Hispanic backgrounds, those from lower-income families, and girls are less likely to be diagnosed with autism spectrum disorder. Under-identification among these historically and contemporaneously marginalized groups can limit their access to early, autism spectrum disorder-specific interventions, which can have long-term negative impacts. Recent data suggest that some of these trends may be narrowing, or even reversing. Using electronic health record data, we calculated autism spectrum disorder prevalence rates and age of first documented diagnosis across socio-demographic groups. Our cohort included children seen at young ages (when eligible for screening in early childhood) and again at least after 4 years of age in a large primary care network. We found that autism spectrum disorder prevalence was unexpectedly higher among Asian children, non-Hispanic Black children, children with higher Social Vulnerability Index scores (a measure of socio-economic risk at the neighborhood level), and children who received care in urban primary care sites. We did not find differences in the age at which autism spectrum disorder diagnoses were documented in children's records across these groups. Receiving primary care at an urban site (regardless of location of specialty care) appeared to account for most other socio-demographic differences in autism spectrum disorder prevalence rates, except among Asian children, who remained more likely to be diagnosed with autism spectrum disorder after controlling for other factors. We must continue to better understand the process by which children with autism spectrum disorder from traditionally under-identified and under-served backgrounds come to be recognized, to continue to improve the equity of care.
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Trastorno del Espectro Autista , Trastornos Generalizados del Desarrollo Infantil , Niño , Preescolar , Femenino , Humanos , Trastorno del Espectro Autista/diagnóstico , Prevalencia , Atención Primaria de Salud , Asiático , Negro o Afroamericano , Poblaciones Vulnerables , PediatríaRESUMEN
Introduction: The M50 electrophysiological auditory evoked response time can be measured at the superior temporal gyrus with magnetoencephalography (MEG) and its latency is related to the conduction velocity of auditory input passing from ear to auditory cortex. In children with autism spectrum disorder (ASD) and certain genetic disorders such as XYY syndrome, the auditory M50 latency has been observed to be elongated (slowed). Methods: The goal of this study is to use neuroimaging (diffusion MR and GABA MRS) measures to predict auditory conduction velocity in typically developing (TD) children and children with autism ASD and XYY syndrome. Results: Non-linear TD support vector regression modeling methods accounted for considerably more M50 latency variance than linear models, likely due to the non-linear dependence on neuroimaging factors such as GABA MRS. While SVR models accounted for ~80% of the M50 latency variance in TD and the genetically homogenous XYY syndrome, a similar approach only accounted for ~20% of the M50 latency variance in ASD, implicating the insufficiency of diffusion MR, GABA MRS, and age factors alone. Biologically based stratification of ASD was performed by assessing the conformance of the ASD population to the TD SVR model and identifying a sub-population of children with unexpectedly long M50 latency. Discussion: Multimodal integration of neuroimaging data can help build a mechanistic understanding of brain connectivity. The unexplained M50 latency variance in ASD motivates future hypothesis generation and testing of other contributing biological factors.
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[This corrects the article DOI: 10.1016/j.ymgmr.2023.101001.].
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Background: Creatine transporter deficiency (CTD) is a rare X-linked disorder of creatine transport caused by pathogenic variants in SLC6A8 (Xq28). The disorder is marked by developmental delay, especially speech delay. The biomarkers Aß40, Aß42 and total tau are abnormal in Alzheimer disease (AD), a common neurodegenerative disorder pathologically characterized by Aß peptide containing amyloid plaques and tau neurofibrillary tangles. Although CTD results in neuronal energy deficiency, the pathological processes underlying the CTD phenotype are not fully characterized. Methods: Cerebral spinal fluid (CSF) was collected as an optional part of a natural history study of CTD. Aß40, Aß42 and total tau levels were quantified in CSF from individuals with CTD and from age-appropriate comparison samples. Neuro3-Plex enzyme-linked immunoassay was performed on a Quanterix SR-X instrument. The Vineland Adaptive Behavior Scale, 3rd Edition was used to determine an overall Adaptive Behavior Composite (ABC) standard score. Results: CSF from 12 individuals with CTD and 23 age appropriate non-CTD comparison samples were analyzed. We found that levels of total tau [t(32) = 4.05, p = 0.0003], Aß40 [t(31) = 6.11, p < 0.0001], and Aß42 [t(32) = 3.20, p = 0.003] were elevated in the participants with CTD relative to the comparison group. Additionally, except for one individual that we considered an outlier, all three biomarkers correlated inversely with the adaptive behavior score (total tau: ρ = -0.60 [-0.88, 0.005]; Aß40: ρ = -0.67 [-0.91, -0.12]; Aß42: ρ = -0.62 [-0.89, -0.02]). Conclusion: We describe here the novel finding of elevated protein biomarkers in the CSF of individuals with CTD. Aß40, Aß42 and total tau are markedly elevated in individuals with CTD compared to comparison samples, and increased levels of these biomarkers inversely correlated with ABC scores. We hypothesize that elevated CSF levels of Aß40 and Aß42 are due to cellular energy deficiency. Elevated CSF total tau levels may indicate ongoing neuronal damage. The observed inverse correlation of Vineland ABC scores with increased biomarker levels needs to be confirmed in a larger CTD cohort; however, our observation of increased Aß40, Aß42 and total tau levels in CSF from individuals with CTD may provide insight into pathological mechanisms contributing to the CTD phenotype and may prove useful as supportive data in future therapeutic trials.
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The objectives of this study were to (1) demonstrate the application of percentiles to advance the interpretation of patient-reported outcomes and (2) establish autism-specific percentiles for four Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROMIS measures were completed by parents of autistic children and adolescents ages 5-17 years as part of two studies (n = 939 parents in the first study and n = 406 parents in the second study). Data from the first study were used to develop autism-specific percentiles for PROMIS parent-proxy sleep disturbance, sleep-related impairment, fatigue, and anxiety. Previously established United States general population percentiles were applied to interpret PROMIS scores in both studies. Results of logistic regression models showed that parent-reported material hardship was associated with scoring in the moderate-severe range (defined as ≥75th percentile in the general population) on all four PROMIS measures (odds ratios 1.7-2.2). In the second study, the percentage of children with severe scores (defined as ≥95th percentile in the general population) was 30% for anxiety, 25% for sleep disturbance, and 17% for sleep-related impairment, indicating a high burden of these problems among autistic children. Few children had scores at or above the autism-specific 95th percentile on these measures (3%-4%), indicating that their scores were similar to other autistic children. The general population and condition-specific percentiles provide two complementary reference points to aid interpretation of PROMIS scores, including corresponding severity categories that are comparable across different PROMIS measures.
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Trastorno del Espectro Autista , Trastorno Autístico , Trastornos del Sueño-Vigilia , Niño , Adolescente , Humanos , Estados Unidos , Preescolar , Trastorno Autístico/complicaciones , Trastorno Autístico/diagnóstico , Encuestas y Cuestionarios , Calidad de Vida , Medición de Resultados Informados por el Paciente , Trastornos del Sueño-Vigilia/diagnóstico , Trastornos del Sueño-Vigilia/epidemiología , Sistemas de InformaciónRESUMEN
OBJECTIVE: To assess the impact of the COVID-19 pandemic on screening for autism spectrum disorder (ASD) and screening equity among eligible children presenting for well-child care in a large primary care pediatric network, we compared rates of ASD screening completion and positivity during the pandemic to the year prior, stratified by sociodemographic factors. METHODS: Patients who presented for in-person well-child care at 16 to 26 months between March 1, 2020 and February 28, 2021 (COVID-19 cohort, n = 24,549) were compared to those who presented between March 1, 2019 and February 29, 2020 (pre-COVID-19 cohort, n = 26,779). Demographics and rates of completion and positivity of the Modified Checklist for Autism in Toddlers with Follow-up (M-CHAT/F) were calculated from the electronic health record and compared by cohort using logistic regression models. RESULTS: Total eligible visits decreased by 8.3% between cohorts, with a greater decline in Black and publicly insured children. In the pre-COVID-19 cohort, 89.0% of eligible children were screened at least once, compared to 86.4% during the pandemic (P < 0.001). Significant declines in screening completion were observed across all sociodemographic groups except among Asian children, with the sharpest declines among non-Hispanic White children. Sociodemographic differences were not observed in screen-positive rates by cohort. CONCLUSIONS: Well-child visits and ASD screenings declined across groups, but with different patterns by race and ethnicity during the COVID-19 pandemic. Findings regarding screen-completion rates should not be interpreted as a decline in screening disparities, given differences in who presented for care. Strategies for catch-up screening for all children should be considered.
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Trastorno del Espectro Autista , COVID-19 , Humanos , Niño , Lactante , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/epidemiología , COVID-19/diagnóstico , Pandemias , Tamizaje Masivo , Atención Primaria de SaludRESUMEN
Aim: To describe healthcare utilization patterns among children with autism (n = 1821), and compare these patterns to children with other developmental delays (DD; n = 12,336) and a population comparison (PC; n = 18,210) cohort. Materials & methods: Retrospective study of administrative billing data. Results: Children with autism had roughly six-times more annual outpatient visits as PC children and twice as many as children with DD. Children with autism were more likely than PC children to use nearly all services, but comparisons between the autism and DD cohorts were mixed. Children with autism were more likely to have psychiatry/psychology visits, 'other' specialty care visits and psychotropic prescriptions, but less likely to have pediatric specialty care visits, immunizations and some prescriptions. Conclusion: Findings reveal opportunities to streamline, coordinate or improve care for young children with autism, particularly for outpatient services, and to give caregivers appropriate anticipatory guidance about what to expect after an autism diagnosis.
Lay abstract We compared how young children with autism use healthcare services versus children with other developmental delays (DDs) and a population comparison (PC) group. We examined medical billing records of children with private health insurance from across the USA. Children with autism were more likely than PC children to use nearly all healthcare services. Children with autism had about six-times as many annual outpatient visits as PC children and twice as many as children with DD. Children with autism were more likely to use some services and less likely to use other services compared with children with DD. For example, children with autism were more likely to have mental health visits and medications, but less likely to have pediatric specialty care visits or allergy medications. Outpatient visits and other healthcare services may need to be streamlined, coordinated or improved for young children with autism.
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Trastorno Autístico , Trastorno Autístico/diagnóstico , Trastorno Autístico/epidemiología , Trastorno Autístico/terapia , Cuidadores , Niño , Preescolar , Estudios de Cohortes , Humanos , Aceptación de la Atención de Salud , Estudios RetrospectivosRESUMEN
BACKGROUND: 47,XYY syndrome (XYY) is a male sex chromosome disorder where subjects have one X chromosome and two copies of the Y chromosome. XYY is associated with a physical phenotype and carries increased risk of neurodevelopmental disorders such as autism spectrum disorder (ASD). Imbalance of excitation and inhibition has been proposed as a putative biological basis of disorders such as ASD [1-3] and several studies have reported atypical brain γ-aminobutyric acid (GABA) levels in this population. Given the male preponderance in the prevalence of ASD, the unique presence of the Y chromosome in males leads to the intriguing possibility of investigating boys with XYY syndrome as a model of excess Y-chromosome genes. METHOD: In this study, we investigated the associations of genotype and clinical phenotype with levels of GABA, estimated by regionally localized edited magnetic resonance spectroscopy in boys with 47, XYY syndrome compared to age-matched typically developing (XY) peers. RESULTS: Overall, we observed a decrease in GABA levels in XYY vs. XY, which appeared more significant in the left compared to the right hemisphere. There was no additional significant modulation of GABA levels in XYY according to presence/absence of ASD diagnosis. Interestingly, a positive correlation between bilateral GABA levels and testosterone levels was observed in pubescent XY boys that was not observed in XYY. CONCLUSION: The inhibitory neurotransmitter GABA appears to be reduced in boys with 47,XYY, especially in the left hemisphere. Further, the typical association between GABA and testosterone levels, observed in older typically developing control boys was not evident in boys with 47,XYY.
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Trastornos de los Cromosomas Sexuales/metabolismo , Lóbulo Temporal/metabolismo , Cariotipo XYY/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Adolescente , Niño , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Trastornos de los Cromosomas Sexuales/diagnóstico por imagen , Lóbulo Temporal/diagnóstico por imagen , Cariotipo XYY/diagnóstico por imagenRESUMEN
OBJECTIVES: Guidelines recommend universal screening for developmental concerns in young children in pediatric primary care, with referral to early intervention (EI) as early as possible for children with a positive screen. However, participation in EI differs by child race, ethnicity, language, and sex. This study evaluated disparities in rates of referral to EI and estimated the factors associated with referral before and immediately after a positive developmental screen. METHODS: Children seen in a large primary care network that has implemented universal developmental screening were included if they screened positive on the Survey of Well-being of Young Children (SWYC) Milestones during a 16- to 30-month well-child visit (n = 7358). Demographics, screening results, and referrals were extracted from the electronic health record. RESULTS: Among children who screened positive, 17.5% were already in EI, and 39.9% were referred to EI during the visit with positive screen; 42.5% were not referred. In adjusted regression, the following factors were associated with being in EI before the positive screen: lower SWYC score and being male, older, and White. The following factors were associated with new referral to EI during a visit with positive SWYC: having lower SWYC score or lower income and being male, older, and Black race. CONCLUSION: The finding that White children were more likely referred before developmental screening and non-White children more likely referred at the time of positive screen suggests that screening decreases disparities by increasing referral for children with developmental delays from traditionally underserved backgrounds.
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Discapacidades del Desarrollo , Derivación y Consulta , Niño , Preescolar , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/epidemiología , Intervención Educativa Precoz , Humanos , Lactante , Masculino , Tamizaje Masivo , Atención Primaria de SaludRESUMEN
Both anxiety and autism spectrum disorder (ASD) are associated with atypical physiological activity. Few studies have systematically assessed the resting physiological activity in ASD with co-occurring anxiety disorders. We tested 75 participants divided in four groups: youth with ASD, with (ASD + Anxiety = 22, 6F, 12.29 ± 2.83 years old) and without co-occurring anxiety (ASD Alone = 15, 6F, 11.59 ± 2.85 years old) and compared their physiological profile with that of matched typically developing controls (TDC) with (Anxiety Alone = 16, 6F, 11.24 ± 3.36 years old) and without co-occurring anxiety disorders (TDC = 22, 8F, 11.88 ± 2.88 years old). Results indicated reduced sympathetic and parasympathetic activity at rest in ASD as compared to TDC youth. ASD + Anxiety and Anxiety Alone groups showed different sympathetic, but similar parasympathetic activity. These findings suggest that autonomic profile-based approaches may advance research, diagnosis, and treatment of ASD and anxiety.
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Trastorno del Espectro Autista , Adolescente , Ansiedad , Trastornos de Ansiedad/epidemiología , Sistema Nervioso Autónomo , Niño , HumanosRESUMEN
Importance: Early identification of autism spectrum disorder (ASD) is associated with improved cognitive and behavioral outcomes. Targeted strategies are needed to support equitable access to diagnostic services to ensure that children from low-income and racial/ethnic minority families receive the benefits of early ASD identification and treatment. Objective: To test the efficacy of family navigation (FN), an individually tailored, culturally informed care management strategy, to increase the likelihood of achieving diagnostic ascertainment among young children at risk for ASD. Design, Setting, and Participants: This randomized clinical trial of 249 families of children aged 15 to 27 months who had positive screening results for possible ASD was conducted in 11 urban primary care sites in 3 cities. Data collection occurred from February 24, 2015, through November 5, 2018. Statistical analysis was performed on an intent-to-treat basis from November 5, 2018, to July 27, 2020. Interventions: Families were randomized to FN or conventional care management (CCM). Families receiving FN were assigned a navigator who conducted community-based outreach to families to address structural barriers to care and support engagement in recommended services. Families receiving CCM were assigned to a care manager, who did limited telephone outreach. Families received FN or CCM after positive initial screening results and for 100 days after diagnostic ascertainment. Main Outcomes and Measures: The primary outcome, diagnostic ascertainment, was measured as the number of days from randomization to completion of the child's clinical developmental evaluation, when a diagnosis of ASD or other developmental disorder was determined. Results: Among 250 families randomized, 249 were included in the primary analysis (174 boys [69.9%]; mean [SD] age, 22.0 [3.5] months; 205 [82.3%] publicly insured; 233 [93.6%] non-White). Children who received FN had a greater likelihood of reaching diagnostic ascertainment over the course of 1 year (FN, 108 of 126 [85.7%]; CCM, 94 of 123 [76.4%]; unadjusted hazard ratio [HR], 1.39 [95% CI, 1.05-1.84]). Site (Boston, New Haven, and Philadelphia) and ethnicity (Hispanic vs non-Hispanic) moderated the effect of FN (treatment × site interaction; P = .03; Boston: HR, 2.07 [95% CI, 1.31-3.26]; New Haven: HR, 1.91 [95% CI, 0.94-3.89]; and Philadelphia: HR, 0.91 [95% CI, 0.60-1.37]) (treatment × ethnicity interaction; P < .001; Hispanic families: HR, 2.81 [95% CI, 2.23-3.54] vs non-Hispanic families: HR, 1.49 [95% CI, 1.45-1.53]). The magnitude of FN's effect was significantly greater among Hispanic families than among non-Hispanic families (diagnostic ascertainment among Hispanic families: FN, 90.9% [30 of 33], and CCM, 53.3% [16 of 30]; vs non-Hispanic families: FN, 89.7% [35 of 39], and CCM, 77.5% [31 of 40]). Conclusions and Relevance: Family navigation improved the likelihood of diagnostic ascertainment among children from racial/ethnic minority, low-income families who were detected as at risk for ASD in primary care. Results suggest differential effects of FN by site and ethnicity. Trial Registration: ClinicalTrials.gov Identifier: NCT02359084.
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Trastorno Autístico/diagnóstico , Técnicas y Procedimientos Diagnósticos/psicología , Relaciones Familiares/psicología , Aceptación de la Atención de Salud/psicología , Navegación de Pacientes/normas , Trastorno Autístico/psicología , Preescolar , Técnicas y Procedimientos Diagnósticos/normas , Femenino , Humanos , Lactante , Masculino , Aceptación de la Atención de Salud/estadística & datos numéricos , Navegación de Pacientes/métodos , Navegación de Pacientes/estadística & datos numéricosRESUMEN
OBJECTIVE: Certain copy number variants (CNVs) greatly increase the risk of autism. The authors conducted a genetics-first study to investigate whether heterogeneity in the clinical presentation of autism is underpinned by specific genotype-phenotype relationships. METHODS: This international study included 547 individuals (mean age, 12.3 years [SD=4.2], 54% male) who were ascertained on the basis of having a genetic diagnosis of a rare CNV associated with high risk of autism (82 16p11.2 deletion carriers, 50 16p11.2 duplication carriers, 370 22q11.2 deletion carriers, and 45 22q11.2 duplication carriers), as well as 2,027 individuals (mean age, 9.1 years [SD=4.9], 86% male) with autism of heterogeneous etiology. Assessments included the Autism Diagnostic Interview-Revised and IQ testing. RESULTS: The four genetic variant groups differed in autism symptom severity, autism subdomain profile, and IQ profile. However, substantial variability was observed in phenotypic outcome in individual genetic variant groups (74%-97% of the variance, depending on the trait), whereas variability between groups was low (1%-21%, depending on the trait). CNV carriers who met autism criteria were compared with individuals with heterogeneous autism, and a range of profile differences were identified. When clinical cutoff scores were applied, 54% of individuals with one of the four CNVs who did not meet full autism diagnostic criteria had elevated levels of autistic traits. CONCLUSIONS: Many CNV carriers do not meet full diagnostic criteria for autism but nevertheless meet clinical cutoffs for autistic traits. Although profile differences between variants were observed, there is considerable variability in clinical symptoms in the same variant.
Asunto(s)
Trastorno Autístico/genética , Variaciones en el Número de Copia de ADN/genética , Predisposición Genética a la Enfermedad/genética , Trastorno Autístico/diagnóstico , Trastorno Autístico/epidemiología , Niño , Eliminación de Gen , Estudios de Asociación Genética , Heterocigoto , Humanos , Entrevista Psicológica , Masculino , Prevalencia , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
OBJECTIVES: Although the American Academy of Pediatrics recommends screening for autism spectrum disorder (ASD) for all young children, disparities in ASD diagnosis and intervention in minority children persist. One potential contributor to disparities could be whether physicians take different actions after an initial positive screen based on patient demographics. This study estimated factors associated with physicians completing the follow-up interview for the Modified Checklist for Autism in Toddlers with Follow-up (M-CHAT-F), and referring children to diagnostic services, audiology, and Early Intervention (EI) immediately after a positive screen. METHODS: Children seen in a large primary care network that has implemented universal ASD screening were included if they screened positive on the M-CHAT parent questionnaire during a 16-30 month well child visit (N = 2882). Demographics, screening results, and referrals were extracted from the electronic health record. RESULTS: Children from lower-income families or on public insurance were more likely to have been administered the follow-up interview. Among children who screened positive, 26% were already in EI, 31% were newly referred to EI, 11% were referred each to audiology and for comprehensive ASD evaluation. 40.2% received at least one recommended referral; 3.7% received all recommended referrals. In adjusted multivariable models, male sex, white versus black race, living in an English-speaking household, and having public insurance were associated with new EI referral. Male sex, black versus white race, and lower household income were associated with referral to audiology. Being from an English-speaking family, white versus Asian race, and lower household income were associated with referral for ASD evaluation. A concurrent positive screen for general developmental concerns was associated with each referral. CONCLUSIONS: We found low rates of follow-up interview completion and referral after positive ASD screen, with variations in referral by sex, language, socio-economic status, and race. Understanding pediatrician decision-making about ASD screening is critical to improving care and reducing disparities.