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Down syndrome (DS) is the most common cause of intellectual disability, yet little is known about the neurobiological pathways leading to cognitive impairments. Electroencephalographic (EEG) measures are commonly used to study neurodevelopmental disorders, but few studies have focused on young children with DS. Here we assess resting state EEG data collected from toddlers/preschoolers with DS (n = 29, age 13-48 months old) and compare their aperiodic and periodic EEG features with both age-matched (n = 29) and developmental-matched (n = 58) comparison groups. DS participants exhibited significantly reduced aperiodic slope, increased periodic theta power, and decreased alpha peak amplitude. A majority of DS participants displayed a prominent peak in the theta range, whereas a theta peak was not present in age-matched participants. Overall, similar findings were also observed when comparing DS and developmental-matched groups, suggesting that EEG differences are not explained by delayed cognitive ability.
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BACKGROUND: Children with Down syndrome (DS) often need support building language, socialization, and regulation, yet few receive behavioral intervention for this. The Joint Attention, Symbolic Play, Engagement and Regulation (JASPER) intervention holds promise as a clinician-caregiver-mediated approach. AIMS: The aims of this pilot study were to (1) describe the behavioral phenotype of children with DS (2) quantify change in child engagement following JASPER receipt, (3) measure caregiver adoption of JASPER strategies, and (4) generate hypotheses and directions for future research. METHODS AND PROCEDURES: Sixteen toddlers with DS and their caregivers enrolled in the study. Dyads were randomly assigned to one of two conditions: immediate intervention or waitlist control. During the COVID-19 pandemic, intervention was delivered remotely. OUTCOMES AND RESULTS: Caregivers learned to implement JASPER strategies and pilot data suggest improvements in joint engagement and regulation during play. Case series data show individual heterogeneity of intervention response. Remote intervention delivery may be associated with greater participant retention. CONCLUSIONS AND IMPLICATIONS: JASPER may be a viable treatment option to improve joint engagement and emotion regulation in young children with DS. Parents appear receptive to learning and implementing JASPER strategies at home. Remote JASPER delivery may improve participation in research or treatment programs.
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Síndrome de Down , Humanos , Síndrome de Down/psicología , Proyectos Piloto , Masculino , Femenino , Preescolar , COVID-19/psicología , Atención , Regulación Emocional , Cuidadores/psicología , Lactante , Juego e Implementos de Juego/psicología , Terapia Conductista/métodos , SARS-CoV-2 , SocializaciónRESUMEN
Down syndrome is the most common cause of intellectual disability, yet little is known about the neurobiological pathways leading to cognitive impairments. Electroencephalographic (EEG) measures are commonly used to study neurodevelopmental disorders, but few studies have focused on young children with DS. Here we assess resting state EEG data collected from toddlers/preschoolers with DS (n=29, age 13-48 months old) and compare their aperiodic and periodic EEG features with both age-matched (n=29) and cognitive-matched (n=58) comparison groups. DS participants exhibited significantly reduced aperiodic slope, increased periodic theta power, and decreased alpha peak amplitude. A majority of DS participants displayed a prominent peak in the theta range, whereas a theta peak was not present in age-matched participants. Overall, similar findings were also observed when comparing DS and cognitive-matched groups, suggesting that EEG differences are not explained by delayed cognitive ability.
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Developmental changes that occur before birth are thought to be associated with the development of autism spectrum disorders. Identifying anatomical predictors of early brain development may contribute to our understanding of the neurobiology of autism spectrum disorders and allow for earlier and more effective identification and treatment of autism spectrum disorders. In this study, we used retrospective clinical brain magnetic resonance imaging data from fetuses who were diagnosed with autism spectrum disorders later in life (prospective autism spectrum disorders) in order to identify the earliest magnetic resonance imaging-based regional volumetric biomarkers. Our results showed that magnetic resonance imaging-based autism spectrum disorder biomarkers can be found as early as in the fetal period and suggested that the increased volume of the insular cortex may be the most promising magnetic resonance imaging-based fetal biomarker for the future emergence of autism spectrum disorders, along with some additional, potentially useful changes in regional volumes and hemispheric asymmetries.
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Trastorno del Espectro Autista , Trastorno Autístico , Humanos , Trastorno Autístico/diagnóstico por imagen , Trastorno del Espectro Autista/diagnóstico por imagen , Estudios Prospectivos , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , BiomarcadoresRESUMEN
Introduction: The Neurodevelopmental Parent Report for Outcome Monitoring (ND-PROM), initially developed to monitor developmental and behavioral functions in children with autism spectrum disorder (ASD), assesses symptoms across a wide range of domains relevant in Down syndrome (DS). Methods: Psychometric properties of ND-PROM were assessed in 385 individuals with DS and 52 with a combined diagnosis of DS and ASD (DS+ASD), whose caregivers completed the ND-PROM questionnaire for a clinical visit in a specialized Down syndrome program at a tertiary pediatric hospital. Confirmatory factor analysis was conducted to evaluate the internal structure validity of the ND-PROM. Measurement invariance was assessed, with a comparison group of 246 individuals with ASD, and latent mean differences between the DS and ASD-only groups, as well as the combined DS+ASD groups, were assessed. Results: Findings support the existence of the 12 clinically-derived factors in the DS population: Expressive Language, Receptive Language, Adaptive skills/Toileting, Social Emotional Understanding, Social Interaction, Independent Play, Sensory Processes, Challenging Behaviors, Impulse/ADHD, and Mental Health. Differences in response patterns of development and behaviors were observed between those with DS and those with ASD, including those with DS having higher abilities in nonverbal communication, social emotional understanding, and social interaction, and fewer restricted and repetitive behaviors and interests, impulsivity or ADHD symptoms, and mental health concerns compared to those with ASD. Individuals in the DS+ASD group had more difficulties with expressive and receptive language, nonverbal and social communication, social interaction, independent play, and adaptive skills than either the DS-only group or the ASD-only groups. Discussion: The ND-PROM has a desirable factor structure and is a valid and clinically useful tool that captures a range of distinct and independent areas of developmental and behavioral functioning in DS, for individuals with and without an ASD diagnosis.
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OBJECTIVE: To determine the prevalence of neuroimaging abnormalities in individuals with Down syndrome regression disorder (DSRD) and evaluate if neuroimaging abnormalities were predictive of therapeutic responses. METHODS: A multicenter, retrospective, case-control study which reviewed neuroimaging studies of individuals with DSRD and compared them to a control cohort of individuals with Down syndrome (DS) alone was performed. Individuals aged 10-30 years and meeting international consensus criteria for DSRD were included. The presence of T1, T2/FLAIR, and SWI signal abnormalities was reviewed. Response rates to various therapies, including immunotherapy, were evaluated in the presence of neuroimaging abnormalities. RESULTS: In total, 74 individuals (35%) had either T2/FLAIR and/or SWI signal abnormality compared to 14 individuals (12%) without DSRD (p < 0.001, 95%CI: 2.18-7.63). T2/FLAIR signal abnormalities were not appreciated more frequently in individuals with DSRD (14%, 30/210) than in the control cohort (9%, 11/119) (p = 0.18, OR: 1.63, 95%CI: 0.79-3.40). SWI signal abnormalities were appreciated at a higher frequency in individuals with DSRD (24%, 51/210) compared to the control cohort (4%, 5/119) (p < 0.001, OR: 7.31, 95%CI: 2.83-18.90). T2/FLAIR signal abnormalities were localized to the frontal (40%, 12/30) and parietal lobes (37%, 11/30). SWI signal abnormalities were predominantly in the bilateral basal ganglia (94%, 49/52). Individuals with DSRD and the presence of T2/FLAIR and/or SWI signal abnormalities were much more likely to respond to immunotherapy (p < 0.001, OR: 8.42. 95%CI: 3.78-18.76) and less likely to respond to benzodiazepines (p = 0.01, OR: 0.45, 95%CI: 0.25-0.83), antipsychotics (p < 0.001, OR: 0.28, 95%CI: 0.11-0.55), or electroconvulsive therapy (p < 0.001, OR: 0.12; 95%CI: 0.02-0.78) compared to individuals without these neuroimaging abnormalities. INTERPRETATION: This study indicates that in individuals diagnosed with DSRD, T2/FLAIR, and SWI signal abnormalities are more common than previously thought and predict response to immunotherapy.
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Síndrome de Down , Humanos , Síndrome de Down/terapia , Estudios Retrospectivos , Estudios de Casos y Controles , Neuroimagen/métodos , InmunoterapiaRESUMEN
Individuals with Down syndrome (DS) or Autism Spectrum Disorder (ASD), and especially those with both DS and co-occurring ASD (DS + ASD) commonly display behavioral and psychiatric symptoms that can impact quality of life and places increased burden on caregivers. While the mainstay of treatment in DS and ASD is focused on educational and behavioral therapies, pharmacological treatments can be used to reduce symptom burden. There is a paucity of evidence and limited clinical trials in DS and DS + ASD. Some scientific evidence is available, primarily in open label studies and case series that can guide treatment choices. Additionally, clinical decisions are often extrapolated from evidence and experience from those with ASD, or intellectual disability in those without DS. This article reviews current research in pharmacological treatment in DS, ASD, and DS + ASD, reviews co-occurring neurodevelopmental and mental health diagnoses in individuals with DS + ASD across the lifespan, and describes practical approaches to psychopharmacological management.
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Trastorno del Espectro Autista , Síndrome de Down , Discapacidad Intelectual , Humanos , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/diagnóstico , Síndrome de Down/complicaciones , Síndrome de Down/tratamiento farmacológico , Síndrome de Down/diagnóstico , Calidad de VidaRESUMEN
Individuals with Down syndrome (DS) experience a range of medical and neurodevelopmental conditions, necessitating systematic study of their occurrence and impact on neurodevelopmental outcomes. We describe the prevalence and relationships of medical, neurodevelopmental (ND), and mental health (MH) conditions in children with DS. We created a prospective clinical database of individuals with DS, integrated into the workflow of a specialty Down Syndrome Program at a specialty pediatric referral hospital. Conditions were collected through caregiver- and clinician report at clinical visits (N = 599). We calculated frequencies of medical, ND, and MH conditions and then assessed the relationship between medical, ND, and MH conditions using frequencies and comparative statistics. The most frequent co-occurring conditions were vision (72.5%), ear/hearing (71.0%), gastrointestinal (61.3%), respiratory (45.6%), and feeding (33.6%) problems, with variation in frequency by age. ND and MH conditions were reported in one quarter, most commonly autism spectrum disorder and attention-deficit/hyperactivity disorder. Those with ND and MH conditions had greater frequency of medical conditions, with highest rates of vision, ear/hearing, and gastrointestinal issues, and CHD. Systematically collected clinical data in a large cohort of children with DS reveals high prevalence of several co-occurring medical, ND, and MH conditions. Clinical care requires an understanding of the complex relationship between medical conditions and neurodevelopment.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno del Espectro Autista , Síndrome de Down , Trastornos del Neurodesarrollo , Niño , Humanos , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Trastorno del Espectro Autista/epidemiología , Estudios ProspectivosRESUMEN
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social communication and social interaction impairments accompanied by restrictive and repetitive behaviors or interests. Co-occurring conditions may greatly impact overall functioning and intervention needs, and contribute to individual variability and etiologic subtypes. Clinical care of individuals with ASD requires gathering a breadth of information across multiple domains. The neurodevelopmental parent report for outcome monitoring (ND-PROM) was developed to assess symptoms across core features of ASD as well as frequent concerns and comorbidities. The current study expands upon the initially reported psychometric properties of the ND-PROM and evaluates a proposed a clinically derived 12-factor structure of the ND-PROM. Methods and procedures: The ND-PROM was completed for 246 children with ASD ands tested using confirmatory factor analysis (CFA) and measurement invariance based on sex. Outcomes and results: A 12-factor correlated structure was found (expressive language, receptive language, nonverbal communication, social emotional understanding, social interaction, independent play, adaptive/toileting skills, restrictive and repetitive behaviors and interests, sensory processes, challenging behaviors, impulse/ADHD, and mental health), which did not vary by sex. Conclusions and implications: The ND-PROM captures a range of distinct aspects of developmental and behavioral functioning in ASD that can be used to track independent functioning across domains.
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BACKGROUND: Down syndrome (DS) is one of the most common genetic causes of intellectual disability, and it is associated with an increased incidence of numerous co-occurring conditions. Autism spectrum disorder (ASD) is common in persons with DS, with rates reported as high as 39%. However, little is known regarding co-occurring conditions in children with both DS and ASD. METHODS: A single-center retrospective review of prospective longitudinally collected clinical data was performed. Any patient with a confirmed diagnosis of DS evaluated at a large, specialized Down Syndrome Program in a tertiary pediatric medical center between March 2018 and March 2022 was included. A standardized survey which included demographic and clinical questions was administered during each clinical evaluation. RESULTS: In total, 562 individuals with DS were included. The median age was 10 years (IQR: 6.18-13.92). Of this group, 72 (13%) had a co-occurring diagnosis of ASD (DS+ASD). Individuals with DS+ASD were more likely to be male (OR 2.23, CI 1.29-3.84) and had higher odds of a current or prior diagnosis of constipation (OR 2.19, CI 1.31-3.65), gastroesophageal reflux (OR 1.91, CI 1.14-3.21), behavioral feeding difficulties (OR 2.71, CI 1.02-7.19), infantile spasms (OR 6.03, CI 1.79-20.34) and scoliosis (OR 2.73, CI 1.16-6.40). There were lower odds of congenital heart disease in the DS+ASD group (OR 0.56, CI 0.34-0.93). There was no observed difference in prematurity or Neonatal Intensive Care Unit complications between groups. Individuals with DS+ASD had similar odds of having a history of congenital heart defect requiring surgery to those with DS only. Furthermore, there was no difference in rates of autoimmune thyroiditis or celiac disease. There was also no difference in rates of diagnosed co-occurring neurodevelopmental or mental health conditions in this cohort, including anxiety disorders and attention-deficit/hyperactivity disorder. CONCLUSIONS: This study identifies a variety of medical conditions which are more frequent in children with DS+ASD than DS alone, providing important information for the clinical management of these patients. Future research should investigate the role of some of these medical conditions in the development of ASD phenotypes, and whether there may be distinct genetic and metabolic contributions towards these conditions.
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Trastorno del Espectro Autista , Trastorno Autístico , Síndrome de Down , Masculino , Humanos , Femenino , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/epidemiología , Estudios Retrospectivos , Estudios ProspectivosRESUMEN
PURPOSE OF REVIEW: Down syndrome regression disorder (DSRD) is a symptom cluster consisting of neuropsychiatric regression without cause. Although knowledge of this condition has accelerated over the last decade, prior studies have been limited by heterogenous nomenclature, diagnostic approaches and therapeutic interventions. This review highlights recent advances in the diagnosis and clinical approach to DSRD and reviews the most up-to-date literature on therapeutic interventions for this condition. RECENT FINDINGS: Several multicentre studies have reported exciting findings on the presence of neurodiagnostic study abnormalities and responses to a variety of therapeutics, including psychotropics (including benzodiazepines), electroconvulsive therapy and immunotherapy. Differential response rates have been observed in the presence and absence of a variety of clinical and diagnostic factors. SUMMARY: Individuals with DSRD are responsive to a variety of psychiatric pharmacotherapy and immunotherapy underscoring this phenotype may have multiple causes. Multidisciplinary care is helpful in the evaluation and management of individuals with this condition.
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Síndrome de Down , Terapia Electroconvulsiva , Humanos , Síndrome de Down/terapia , Psicotrópicos , Benzodiazepinas/uso terapéuticoRESUMEN
Individuals with Down syndrome (DS) are at increased risk for being overweight/obese, but the associated cardiometabolic risk (CR) is not clear. Cross-sectional anthropometric and clinical laboratory data from a multi-site, international cohort of individuals with DS were analyzed to determine cardiometabolic risk by reporting observed distributions of cardiometabolic biomarkers in overweight/obese individuals with DS throughout the lifespan. Descriptive statistics and regression analyses by age categories determined the distributive percentiles for cardiometabolic biomarkers and tested for adiposity as a predictor of CR. Across seven DS clinics, data were collected on 240 patients between the ages of 3 and 63 years, with one quarter overweight and three quarters obese among children and nearly all adults being obese. In children and adults, most cardiometabolic biomarker profiles showed distributive values within normal ranges. Blood lipids were positively associated with body mass index (BMI) in children (high density lipid-cholesterol, p = 0.01; low density lipid-cholesterol, p = 0.02). Levels of hs-CRP were elevated in both children and adults, with BMI positively associated with hs-CRP in adults with DS (p = 0.04). Liver enzyme values were positively associated with BMI in children and adults. The data suggest that in contrast to the general population, in individuals with Down syndrome, being overweight and obese does not appear to confer a significantly increased risk for cardiometabolic disease by biomarker profile. Individuals with DS who are overweight/obese appear to have unique cardiometabolic profiles unrelated to adiposity, notable for increased hs-CRP and normal HA1c levels.
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Enfermedades Cardiovasculares , Síndrome de Down , Enfermedades Metabólicas , Humanos , Niño , Adulto , Preescolar , Adolescente , Adulto Joven , Persona de Mediana Edad , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Proteína C-Reactiva/análisis , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Estudios Transversales , Factores de Riesgo , Obesidad/complicaciones , Índice de Masa Corporal , Biomarcadores , Lípidos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiologíaRESUMEN
Down syndrome (DS) is a complex condition associated with multiple medical, developmental, and behavioral concerns. A prospective, longitudinal clinical database was integrated into a specialty Down Syndrome Program, with the goals of better understanding the incidence, course, and impact of co-occurring medical, neurodevelopmental, and mental health conditions in DS. We describe the process of developing the database, including a systematic approach to data collection and database infrastructure, and report on feasibility, challenges, and solutions of initial implementation. Between March 2018 and November 2021, data from 842 patients (ages 4.8 months to 26 years) was collected. Challenges included caregiver form completion as well as time and personnel required for successful implementation. With full integration into clinical visit flow, the database proved to be feasible. The database enables identification of patterns of development and health throughout the lifespan and it facilitates future data sharing and collaborative research to advance care.
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Research to guide clinicians in the management of the devastating regression which can affect adolescents and young adults with Down syndrome is limited. A multi-site, international, longitudinal cohort of individuals with a clinical diagnosis of Unexplained Regression in Down syndrome (URDS) was collated through seven Down syndrome clinics. Tiered medical evaluation, a 28-item core symptom list, and interim management are described naturalistically. Improvement-defined by the percentage of baseline function on a Parent-reported Functional Score, overall improvement in symptoms on a Clinician-administered Functional Assessment, or report of management type being associated with improvement-was analyzed. Improvement rates using ECT, IVIG, and others were compared. Across seven clinics, 51 patients with URDS had regression at age 17.6 years, on average, and showed an average 14.1 out of 28 symptoms. Longitudinal improvement in function was achieved in many patients and the medical management, types of treatment, and their impact on function are described. Management with intravenous immunoglobulin (IVIG) was significantly associated with higher rate of improvement in symptoms at the next visit (p = 0.001). Our longitudinal data demonstrates that URDS is treatable, with various forms of clinical management and has a variable course. The data suggests that IVIG may be an effective treatment in some individuals. Our description of the management approaches used in this cohort lays the groundwork for future research, such as development of standardized objective outcome measure and creation of a clinical practice guideline for URDS.
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Síndrome de Down , Adolescente , Síndrome de Down/complicaciones , Síndrome de Down/epidemiología , Síndrome de Down/terapia , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Evaluación de Resultado en la Atención de Salud , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Unexplained regression in Down syndrome (URDS) involves a loss of acquired skills resulting in functional deterioration. Despite extensive workup and treatment, few individuals regain baseline function. This study aimed to understand the role of psychosocial stressors in URDS. METHODS: We describe psychosocial stressors in 14 cases of URDS. Specifically, we examined psychosocial stressors in the context of presentation and clinical symptoms. We also examined co-occurring neurodevelopmental disorders and medical and mental health conditions. RESULTS: All individuals experienced psychosocial stressors within one year of diagnosis of URDS. The most common psychosocial stressors were moving to a new home or school. CONCLUSION: Psychosocial stressors are commonly reported preceding URDS. Knowledge about psychosocial stressors' impact may lead to preventive interventions, improved monitoring, and earlier diagnosis. Future research should focus on understanding psychosocial stressors to help identify individuals at risk for URDS and contribute to treatment.
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Síndrome de Down , Trastornos Mentales , Humanos , Estrés Psicológico/psicologíaRESUMEN
Individuals with Down syndrome (DS) are among the groups with the highest risk for severe COVID-19. Better understanding of the efficacy and risks of COVID-19 vaccines for individuals with DS may help improve uptake of vaccination. The T21RS COVID-19 Initiative launched an international survey to obtain information on safety and efficacy of COVID-19 vaccines for individuals with DS. De-identified survey data collected between March and December 2021 were analyzed. Of 2172 individuals with DS, 1973 (91%) had received at least one vaccine dose (57% BNT162b2), 107 (5%) were unvaccinated by choice, and 92 (4%) were unvaccinated for other reasons. Most participants had either no side effects (54%) or mild ones such as pain at the injection site (29%), fatigue (12%), and fever (7%). Severe side effects occurred in <0.5% of participants. About 1% of the vaccinated individuals with DS contracted COVID-19 after vaccination, and all recovered. Individuals with DS who were unvaccinated by choice were more likely to be younger, previously recovered from COVID-19, and also unvaccinated against other recommended vaccines. COVID-19 vaccines have been shown to be safe for individuals with DS and effective in terms of resulting in minimal breakthrough infections and milder disease outcomes among fully vaccinated individuals with DS.
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The recent National Institute of Health (NIH) INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) initiative has bolstered capacity for the current increase in clinical trials involving individuals with Down syndrome (DS). This new NIH funding mechanism offers new opportunities to expand and develop novel approaches in engaging and effectively enrolling a broader representation of clinical trials participants addressing current medical issues faced by individuals with DS. To address this opportunity, the NIH assembled leading clinicians, scientists, and representatives of advocacy groups to review existing methods and to identify those areas where new approaches are needed to engage and prepare DS populations for participation in clinical trial research. This paper summarizes the results of the Clinical Trial Readiness Working Group that was part of the INCLUDE Project Workshop: Planning a Virtual Down Syndrome Cohort Across the Lifespan Workshop held virtually September 23 and 24, 2019.
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Síndrome de Down , Estudios de Cohortes , Síndrome de Down/complicaciones , Síndrome de Down/terapia , HumanosRESUMEN
OBJECTIVE: As understanding of the neurobiological basis of cognitive impairment in Down syndrome (DS) advances and new pharmaceutical interventions targeting neurodevelopment become available, an in-depth understanding of the family perspective is essential to inform research efforts. A mixed methods study was conducted with parents of individuals with DS to learn about attitudes toward pharmacological interventions to enhance cognition, participation in clinical research trials in DS, and the relationship between child/family-specific factors and parent attitudes. METHOD: Parents completed an online survey (N = 37) assessing family/child sociodemographic factors and to capture thoughts on cognitive enhancement and participation in clinical drug trials. A subset of interested parents participated in a follow-up phone interview (N = 21) or focus group (N = 3; 1 FG). Double-blind thematic analysis was used to analyze qualitative data. RESULTS: Parents' attitudes toward improving cognition, reversing intellectual disability, and participation in clinical trials correlated with each other and were informed by specific parent and child factors (e.g., child attention-deficit hyperactivity disorder/behavioral diagnosis and parent education). Qualitative themes included advantages, disadvantages, and ethical implications of enhancing cognition. In addition, themes emerged regarding the need to understand the mechanism and potential side effects of experimental drugs, logistical factors relating to willingness to participate in clinical trials, and the evolution of parents' attitudes over time. CONCLUSION: The findings highlight the complexity of issues and implications of clinical trials for enhancing cognition in DS. Child-specific factors, logistical and safety considerations, and personal belief systems all inform parent attitudes and decision making. The findings reflect the importance of incorporating parent perspectives and values in research direction and design.