Adults with neurodevelopmental disorders (NDD) are at high risk of developing obesity, yet systematic evaluations of their eating behavior profiles remain scarce. In this study, participants were adults with overweight or obesity associated with a genetically confirmed NDD with intellectual disability (ID). We characterized multidimensional eating behavior phenotypes across three groups: Prader-Willi syndrome (PWS) and Bardet-Biedl syndrome (BBS), the two most frequent syndromic forms of obesity, and other neurodevelopmental genetic conditions associated with obesity (“other NDD”). We then evaluated the glucagon-like peptide-1 receptor agonist (GLP1-RA) semaglutide-associated changes in real-world conditions. We assessed eating behavior in 149 adults with NDD (PWS, n = 90; BBS, n = 13; other NDD, n = 46) using the Dykens Hyperphagia Questionnaire (HQ), the Children’s Eating Behavior Questionnaire (CEBQ), and the Parental–Developmental Disorders Quality of Life questionnaire (Par-DD-QoL). In a subgroup with longitudinal follow-up (PWS, n = 8; other NDD, n = 12), changes in body weight and eating behavior were evaluated after 12 months of semaglutide treatment (2.4 mg/week). Given the limited sample size, these subgroup analyses were considered hypothesis-generating and were not adjusted for multiple comparisons. Groups exhibited marked hyperphagic traits, with earlier onset of food interest in PWS and BBS (mean 6.6 and 2.7 years, respectively) compared with other NDD group (10.5 years). Distinct profiles emerged: PWS was characterized by lower food fussiness and desire to drink, whereas BBS tended to show higher satiety responsiveness. Nearly half of caregivers (46.4
There is significant heterogeneity in clinical presentations, brain-imaging findings, and genetic underpinnings of autism. Autism traits, particularly social affect and joint attention, and related domains of adaptive functioning and cognitive development, are key characteristics in determining autism “profiles”. This study aimed to understand such baseline profiles in preschool autistic children receiving early intervention (age range, 2–7 years old; sample size N = 67). We also examined the association between phenotypic pre-intervention characteristics and response to intervention using Early Start Denver Model (ESDM). Baseline characteristics prior to receiving early intervention demonstrated a link between eye tracking measure of joint attention, namely better gaze accuracy, and clinical profile of autism traits, particularly better social affect/social overtures and adaptive functioning. Further, better receptive and expressive language, visual reception and fine motor skills, and higher development quotients on a visual processing task, were found to be associated with more accurate eye movements on a joint attention task. Predictors of improvement in autistic traits post-intervention included higher age at entry to intervention and baseline developmental functioning. Specifically, social affect was found to change in the same direction as cognitive functioning post-ESDM intervention, especially with regard to visual reception, fine motor and receptive language skills. The findings also suggest that better social affect and joint attention, characterised by better social overtures and maintenance of attention, are predictive of more accurate eye gaze in a social exercise, thereby making these potential intervention targets in early intervention.
Up to a third of autistic children do not develop functional speech and remain minimally verbal (MV) beyond the age of 5, yet little is known about the clinical characteristics of this group. Less still is known about the prevalence or impact of MV status in children with intellectual disability. Our objective was to provide further insights into the clinical phenotype of MV children with ID. To do so, we investigated the prevalence of MV status in children with intellectual disability (ID) and genetic conditions, with and without a co-occurring autism diagnosis. We also investigated the association between communication ability (MV status) and outcomes known to be associated with MV status, including adaptive function, motor abilities and emotional and behavioural difficulties. A pre-registered secondary data analysis using cross-sectional parent-reported data from children with ID of genetic origin (IMAGINE-ID https://imagine-id.org/): We (1) compared the prevalence of MV status in children with ID with and without co-occurring autism and (2) quantified associations between MV status and adaptive function, motor abilities and emotional and behavioural difficulties while controlling for autism diagnoses. One in five children with ID of genetic aetiology were ascertained to be MV. Of those who were MV, 31
ADHD is often accompanied by motor difficulties in childhood, yet little is known about how these traits emerge in early life or the genetic pathways that contribute to their development. Studying infants with an elevated familial likelihood of ADHD (EL-ADHD) alongside those with a monogenic condition associated with ADHD, such as Neurofibromatosis type 1 (NF1), provides a unique opportunity to compare polygenic and monogenic influences on early motor development and its relationship to later ADHD traits. Accordingly, this study examined motor profiles in EL-ADHD, NF1, and typically developing (TD) infants, and investigated how early motor behaviour relates to emerging ADHD characteristics. The motor behaviour of infants with EL-ADHD, NF1, and TD were assessed at 10 and 14 months using a multimodal approach that included standardized motor assessments, parent reports of activity levels, behavioural coding of movements during free play, and accelerometery. Early ADHD traits were subsequently evaluated at follow-up visits at ages 2 and 3 years using the Child Behaviour Checklist (CBCL). Across infancy, EL-ADHD infants exhibited higher gross motor scores on standardised assessments compared to TD and NF1 infants, although they did not differ from either group in their fine motor scores. In contrast, NF1 infants showed both lower gross and fine motor scores relative to TD and EL-ADHD peers. During free play, EL-ADHD infants displayed more mature motor behaviours and marginially higher mean acceleration levels compared to TD and NF1 infants, whereas only minimal free play differences were observed between TD and NF1. Additionally, group-specific relationships emerged between motor behaviour and later ADHD traits. In the EL-ADHD group only, 14-month gross motor skills showed a trend-level positive association with ADHD traits at 36 months, and 14-month parent-reported activity levels significantly predicted ADHD traits at both 24 and 36 months. This study is the first to examine the relationship between motor development and ADHD traits in both polygenic and monogenic contexts. Our findings show that motor difficulties emerge early in infants with NF1, whereas such difficulties are not evident in those at elevated likelihood of ADHD in the general population. Moreover, early motor behaviour predicts later ADHD traits in ways that are specific to both developmental context and population. These results suggest that ADHD phenotypes can arise through distinct neurodevelopmental trajectories across different atypically developing populations.
Sensory differences constitute core diagnostic features of autism. The cascading effect model posits that early sensory differences may be prospectively associated with subsequent autistic traits, whereas empirical evidence in infancy remains scarce. This study aims to characterize trajectory differences of early sensory profiles and examine the cascading effect on subsequent autistic traits in infants later diagnosed with autism. In this prospective longitudinal study, 134 Chinese infants were followed from 12 to 36 months of age. Trajectory differences in four sensory profiles (sensitivity, avoiding, registration, and seeking) were compared between diagnostic groups using the Toddler Sensory Profile-2. The cascading effect were examined through Structural Equation Modeling and temporally ordered path analysis to test direct and indirect effects of early sensory differences on subsequent autistic traits via the mediation of social skills in autism. Compared to typical development, infants later diagnosed with autism exhibited significantly elevated sensory sensitivity and sensory avoiding, along with elevated sensory registration scores at 12 months, with sensory sensitivity showing differential trajectories over time (F = 3.25, p = 0.004). Elevated sensory avoiding at 18 months exerted an indirect effect on social-communication at 36 months via the mediating role of social skills at 24 months (B = 0.08, p = 0.007). Additionally, temporally ordered path analysis revealed that elevated sensory avoiding at 18 months negatively predicted social skills at 24 months (β = -0.19, p = 0.030). Notably, in an exploratory analysis, increased sensory seeking at 18 months positively predicted adaptive skills at 36 months (B = 0.97, p = 0.031). Sensory differences emerge as early as 12 months in infants who later receive an autistic diagnosis, with sensory sensitivity demonstrating distinct developmental trajectories. These findings provide prospective evidence to support the cascading effect model in autism, identifying early sensory avoiding as an important early correlate of subsequent social-communicative development. Furthermore, early sensory seeking behaviors may facilitate subsequent adaptive functioning, highlighting the heterogeneous developmental pathways within autism. www.chictr.org.cn; Trial No: ChiCTR2100049811; Trial Date:2021.08.10.
Infants with familial autism are at elevated likelihood for future neurodevelopmental needs, including autism spectrum disorder, attention deficit hyperactivity disorder, and clinically significant cognitive and behavioral challenges. Science is advancing the near-future ability to determine presymptomatic and prodromal periods of neurodevelopmental disabilities in infancy. To meet the needs of these infants and their families, proactive intervention and support models must advance in tandem. The present study investigated a novel, telehealth-based approach to caregiver coaching within a naturalistic and developmental behavioral intervention framework to address behavioral priors of attention and sensorimotor responding with nine infants at elevated likelihood of autism due to family history. We sought to answer a primary research question on the functional relation of the NDBI intervention on proximal infant behaviors related to sensorimotor and attentional responding during three, concurrent multiple baseline designs across infant/caregiver dyads. Secondary questions on the feasibility of the study and pre/post characterization of distal measures of infant development were also included. Based on descriptive analysis of attendance data and visual analysis of SCED data, there was promising feasibility and initial single case experimental design evidence on the idiographic efficacy particularly on motor imitation, although results were variable across participants and targeted responses. Following iterations on the study design, the final procedures in the third multiple baseline design led to the most consistent changes across dyads. Given the known importance on earlier identification of autism spectrum disorder/neurodevelopmental disabilities (ASD/NDD) coupled with the nascent stage of intervention research at prodromal or presymptomatic periods, intervention research needs to develop in lockstep with earlier identification. Flexibility appears to be an important component of the present intervention and other emerging models of infant intervention for families with young children and with multiple children with or at elevated likelihood of ASD/NDD. This study was retrospectively registered at OSF. https://osf.io/6tuyx/overview?view_only=2c85f33fd60b496f86ecb09625e6e4b7, Clinical Trial Registration: not applicable.
MECP2 Duplication Syndrome (MDS) is a rare, X-linked neurodevelopmental disorder characterized by severe-to-profound intellectual disability, epilepsy, limited-to-absent speech and global functional dependence. Caregivers consistently identify developmental and adaptive functioning as a chief concern. To support investigational therapies entering the clinic, the developmental and behavioral outcomes in MDS, changes over time, and clinical modifiers of functional progression must be defined using standardized, trial-ready instruments. Data were aggregated from prospective studies at a single center. The analysis included 62 males with genetically confirmed MDS who were < 18 years old. Assessments included the Vineland Adaptive Behavior Scales, Second Edition (VABS-II), Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III), and Aberrant Behavior Checklist, Community version (ABC-C). Analyses examined developmental profiles, trajectories across age bins, longitudinal changes, and impacts of epilepsy on functioning and behavior. Cross-sectional analysis demonstrated significant developmental delays across all domains, with median age-equivalent scores not exceeding 20 months despite chronological age up to 15 years. Receptive communication emerged as a relative strength, whereas expressive language, interpersonal relationships, and gross motor skills were weaknesses. No child achieved gross motor function beyond a 24-month level. Longitudinal data showed modest gains in adaptive skills in the pre-epileptic population and mostly during early childhood. Epilepsy was associated with markedly lower functioning (e.g., 9 months reduced gross motor ability) and increased lethargy. VABS-II scores were well-correlated with BSID-III performance measures, suggesting caregiver report is a reliable proxy. ABC-C scores revealed higher levels of social withdrawal and modest repetitive behaviors. Relatively higher functioning levels may be correlated with higher levels of externalizing behaviors. This study provides one of the largest standardized characterizations of adaptive and developmental functioning in MDS. Measurements quantify an eventual plateau in skill acquisition and substantial impact of epilepsy. In clinical trials, a group-mean change of 3 or more raw score points on any VABS-II subdomain would be largely unexpected over 12-to-18 months of follow-up. In individuals who have MDS and epilepsy, even halting progression or stabilization of VABS-II scores could reflect clinical benefit within the same period. Implications for supportive and adjunctive therapies are discussed.
Autistic traits in the general population share the genetic liability with autism and distribute as a quantitative continuum. In addition, the risk for co-occurring psychotic and emotional symptoms, physical health conditions, and the associated functional impairment may increase along with the level of autistic traits. This study aimed to examine the potential clinical relevance of subdiagnostic autistic traits in adults, focusing on co-occurring mental health and neurodevelopmental problems and low adaptive dysfunctioning. A total of 659 adult participants (age range 20 to 83 years, mean age 34.49 ± 11.08 years, 53.3
Sleep problems and sensory over-responsivity (SOR) are common, co-occurring, and early emerging features of Autism Spectrum Disorder (ASD). Yet, the early neural mechanisms underlying these symptoms remain unclear. Here, we used resting-state fMRI data from the Infant Brain Imaging Study (IBIS) to examine how functional brain connectivity at 6 months may relate to parent-reported measures of sleep-onset problems and SOR in infants at varying familial likelihood for ASD. The right anterior insula (rAI) – a key hub of the salience network – was used in ROI-ROI analyses to investigate functional connectivity to cortical and cerebellar regions previously implicated in sleep disruption, sensory processing challenges, and ASD. Infants at high (HL) and low (LL) likelihood for ASD displayed divergent patterns of rAI connectivity with sensorimotor cortex, as well as cerebellar regions involved in sensorimotor processing and higher-order functions. Furthermore, stronger rAI connectivity with sensorimotor cortices and cerebellar regions was associated with worse sleep-onset problems and SOR in HL infants. In contrast, stronger rAI-cerebellar connectivity was related to fewer sleep-onset problems and SOR in LL infants. Our findings indicate that altered rAI connectivity may result in over-attribution of attention to sensory stimuli and highlight aberrant sensory prediction learning, which may underlie worse sleep problems and higher SOR in HL infants.
Self-determination, or the degree to which an individual perceives they have “causal agency” over their life plans, is an important predictor of quality of life, employment, and education for autistic people. However, little research has explored predictors of self-determination in autism. Limited research links executive function (EF) to self-determination, but tends to focus on EF globally and fails to address specific EF subdomains. Report of cross-rater links between EF and self-determination (e.g., parent-report EF and self-report self-determination) is also missing. As such, the current study evaluates the relation between real-world EF subdomains and self-determination, both within and between raters. 226 autistic teens ages 14–22 years (M = 16.17; 73
Angelman Syndrome (AS, MIM #105,830) is a rare neurodevelopmental disorder caused by imprinting defects, and it is marked by motor impairment, intellectual disability, speech limitations, and seizures. The condition arises due to the loss of function in neurons of the maternally-inherited UBE3A gene, mapping in the imprinted chromosomal region 15q11.2-q13, through a variety of genetic and epigenetic mechanisms. UBE3A encodes a ubiquitin E3 ligase, which is essential for synaptic plasticity. Most studies of AS have been performed on animal models, while induced pluripotent stem cells (IPSCs), mainly generated from patients with deletion, remain limited in number. Here we report on the generation and characterization of human cortical neurons derived from IPSCs obtained from children representative of the main AS genotypes: 3 with 15q11–13 deletion, 3 with UBE3A mutations, 3 with uniparental disomy, and 2 with imprinting defects. During early neuronal differentiation, morphological analyses highlighted a reduced dendritic branching and an increased number of thin filopodia, while migration assays revealed reduced neurite mobility in AS human neurons with the most severe genetic defect, namely the 15q11-13 deletion. At a later differentiation time point, electrophysiological analyses revealed impaired neuronal activity in AS patient-derived neurons. To investigate pathways potentially involved in synaptic dysfunction, we examined the JNK (c-Jun N-terminal kinase) signalling pathway, which plays key roles in neuroinflammation and synaptic development. We found increased JNK activation and, importantly, treatment with a JNK-inhibitor, D-JNKI1, partially rescued the neuronal morphological defects, significantly reducing the number of immature protrusions, as well as defects in electrophysiological properties. Our patient-specific models contribute elucidate how loss of UBE3A leads to aberrant neuronal maturation and function in the precocious stages of neuronal development and how treatment with D-JNKI1 may pave the way for new therapeutic possibilities.
Among neurotypical children working memory and language development are closely related, but the longitudinal relationship between these factors is unknown in autism. This study had the goal of evaluating potential bidirectional relationships between these domains. A longitudinal design included language and visuospatial working memory assessments across three time points with 160 autistic preschoolers. Time points were one year apart. A cross-lagged panel model (CLPM) using Full-Information Maximum Likelihood (FIML) was used to evaluate longitudinal associations between performance on a working memory task (i.e., the Hide and Seek Task) and language scores (i.e., verbal development quotient). Cross-lagged associations were significant for paths from working memory at the first time point to language at the second time point (β = .31, p = .01) and from language at first time point to working memory at the second time point (β = .40, p < .001). Cross-lagged paths from the second to third time point were not statistically significant in either direction. This study provides evidence of a bidirectional relationship between working memory and language in autistic toddlers and preschoolers among younger autistic preschoolers. These results highlight working memory as a potential early assessment and intervention domain for improving language outcomes in autism as well as the role of language delays as a factor related to reduced working memory skills later in development.
Pharmacotherapy is recommended as the first-line treatment for adult attention-deficit/hyperactivity disorder (ADHD), yet some individuals show partial or inadequate response associated with adverse effects. These limitations have prompted interest in adjunctive or alternative interventions. Electroencephalography (EEG) neurofeedback is a non-pharmacological intervention for ADHD, which enables self-regulation of neural activity. This systematic review synthesised clinical, cognitive, and electrophysiological outcomes of EEG neurofeedback in adult ADHD, and examined standard versus personalised training protocols. Following PRISMA guidelines, four databases (PubMed, ScienceDirect, Ovid, Web of Science) were searched from 1960 to October 2025 for this PROSPERO-registered review (ID: CRD420251020898). Eligible studies included adults (≥ 18 years) with a formal ADHD diagnosis undergoing EEG neurofeedback. Outcomes comprised symptom severity, cognitive performance, electrophysiology, and adverse events. Risk of bias was assessed using RoB 2 and ROBINS-I V2. Seven studies (three RCTs, four non-randomised; n = 390) met inclusion criteria. Protocols included theta/beta (n = 1), slow cortical potential (n = 1), alpha downregulation training (n = 1) and personalised approaches guided by individual alpha peak frequency (n = 3) or QEEG profiles (n = 1). Naturalistic and personalised studies reported large symptom reductions, whereas RCTs revealed small, generally non-significant effects relative to controls. Cognitive improvements were inconsistently reported and largely attributable to practice effects. Electrophysiological changes were protocol-specific without convergence across studies. No treatment-related adverse events were observed. Evidence remains limited by methodological heterogeneity, small samples, variable controls, inconsistent learning metrics, and risk of bias. Current RCTs do not demonstrate evidence of efficacy over placebo. Blinded, adequately powered trials using standardised learning measures are needed to clarify mechanisms of neurofeedback.
Establishing evidence of content validity, or how well a measure reflects the intended outcome, is essential for developing or selecting assessment tools that support individualized care and research in clinical populations like Down syndrome (DS). This study aimed to examine caregiver-reported relevance of a widely used measure of executive function in school-aged youth with DS, the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2), Parent Form. Specifically, this study focused on one aspect of content validity, relevance to the target population, which has yet to be systematically evaluated in DS. This study integrated data from two online studies of youth with DS. After completing the BRIEF-2, caregivers were asked forced-choice questions about the relevance of the measure to their child with DS, as well as an open-text question about their response strategy for items they deemed not relevant. Caregivers of 281 youth with DS between the ages of 6–18 years (M = 12.7, SD = 3.4) reported on the relevance of the BRIEF-2 for their child. Just under half (46.3
Cerebral palsy (CP) is a neurodevelopmental disorder with a significant male predisposition, yet the underlying genetic mechanisms driving this sex-specific risk remain poorly understood. Given the hemizygous state of X-linked variants in males, we hypothesized that X-chromosomal genetic variations may contribute to CP susceptibility in male patients. We performed an X-chromosome-wide association study (XWAS) using whole-exome sequencing (WES) data from 1,076 male CP patients and 1,057 healthy male controls of Chinese ancestry. Quality control, principal component analysis (PCA), and logistic regression were applied to identify risk loci for CP. Six candidate single nucleotide variants (SNVs) in UTP14A were genotyped via MassARRAY, and haplotype analysis was conducted using SHEsis. We identified a significant association between the intronic variant rs2281277 in UTP14A and CP (P = 1.38E-05, FDR q-value = 0.0465, OR = 0.644). In addition to the lead SNV rs2281277, five other SNVs in UTP14A also showed a suggestive association with CP, including rs141750783, rs61318448, rs2273021, rs2281278, and rs111975985. Haplotype analysis further revealed a risk haplotype (CGTATC) defined by these six SNVs, which was associated with a 53.1
Auditory processing (AP) is a fundamental function in speech signal processing. The ability to process speech signals in noisy environments is commonly used to assess AP capabilities. Research on the AP characteristics in Chinese children remains scarce, and the relationship between AP and language/cognitive development has not been explored. This study investigated the AP performance of children with developmental language disorder (DLD) in daily life and under the standardized speech-in-noise (SIN) comprehension paradigm. Using functional Near-Infrared Spectroscopy (fNIRS) to monitor brain activation in real-time during noisy environments, the study analyzed the functional modes of targeted brain regions in Chinese DLD children under noisy environments, while also exploring the relationships between AP behaviors, brain activation patterns, and cognition. This cross-sectional study enrolled 34 Chinese preschool children with DLD and 43 age- and gender-matched typically developing (TD) children. Parents completed basic demographic information, the Preschool Auditory Processing Assessment Scale (PAPAS), and the Behavior Rating Scale of Executive Function-Preschool Version (BRIEF-P). A self-developed SIN comprehension paradigm adapted for Chinese preschool children with DLD was utilized, and fNIRS was employed to record brain activation patterns while the children performed the SIN comprehension task. 1) AP Behavior: The DLD group scored higher than TD group on all dimensions of the PAPAS (P < 0.05); main effects of the group (F = 54.303, P < 0.001) and listening condition (F = 11.83, P = 0.001) were significant for the accuracy (ACC). 2) Brain activation characteristics during the SIN comprehension task: The DLD group showed significantly lower activation than the TD group in the left dorsolateral prefrontal cortex (DLPFC), left Broca’s area, bilateral superior temporal gyrus and middle temporal gyrus (STG and MTG), and right Wernicke’s area (P-corrected < 0.05). 3) The AP total scores, auditory decoding scores, and hyperactivity impulse dimension scores of both groups of children were negatively correlated with the scores on each dimension of the DREAM-C and the WPPSI-IV/WISC-IV (P-corrected < 0.05); the scores on each PAPAS dimension were positively correlated with the scores on each dimension of BRIEF-P (P-corrected < 0.05). 4) The activation levels in the left DLPFC, left Broca’s area, right Wernicke’s area, and bilateral STG and MTG in both groups of children were positively correlated with all dimensions of the DREAM-C (P-corrected < 0.05). The activation levels in the left DLPFC, left Broca’s area, right Wernicke’s area, and right STG and MTG were positively correlated with the full-scale intelligence quotient and verbal comprehension index scores (P-corrected < 0.05). Children with DLD may exhibit AP abnormalities as early as the preschool years, as reflected by poorer performance on AP tasks and atypical cortical activation patterns.
With the advent of exome sequencing, a growing number of children are being identified with de novo loss-of-function mutations in the dynamin 1-like (DNM1L) gene, which encodes the large GTPase essential for mitochondrial fission, dynamin-related protein 1 (DRP1). Mutations in DRP1 result in severe neurodevelopmental phenotypes, such as developmental delay, optic atrophy, and epileptic encephalopathies. Though it is established that mitochondrial fission is an essential precursor to the rapidly changing metabolic needs of the developing cortex, it is not understood how identified mutations in different domains of DRP1 uniquely disrupt cortical development and synaptic maturation. We leveraged the power of human induced pluripotent stem cells (iPSCs) harboring DRP1 mutations in either the GTPase or stalk domains to model early stages of cortical development in vitro. High-resolution time-lapse imaging of transport in neuronal projections revealed mutation-specific changes in mitochondrial motility of severely hyperfused mitochondrial structures. Transcriptional profiling of mutant DRP1 cortical neurons during maturation also implicated mutation-dependent alterations in synaptic development and gene expression of calcium-regulatory genes. Disruptions in calcium dynamics were confirmed using live functional recordings of 65–200 days in vitro (DIV) mutant DRP1 cortical neurons. These findings strongly suggest that altered mitochondrial morphology in DRP1 mutant neurons leads to pathogenic dysregulation of synaptic development and activity.
Abstract Background Epilepsy and Autism Spectrum Disorder (ASD) frequently co-occur, yet the prevalence and factors associated with epilepsy within autistic individuals remain insufficiently defined. This study aimed to determine the prevalence of epilepsy and examine demographic, developmental, and medical correlates in a large cohort of autistic individuals in Qatar. Methods We conducted a cross-sectional analysis of 1,257 autistic individuals recruited through clinical and research channels in Qatar. Bivariate and multivariable logistic regression analyses were used to identify factors associated with epilepsy, with false discovery rate correction applied for multiple comparisons. Results Epilepsy was identified in 10.7% of the cohort, with affected individuals being significantly older (7.33 years) than those without epilepsy (6.59 years, p = 0.003). Factors associated with epilepsy included developmental delays—particularly in motor milestones such as delayed sitting (aOR = 2.954, p < 0.001) and walking (aOR = 3.289, p < 0.001)—and perinatal complications such as hypoxia (aOR = 3.188, p = 0.015). Behavioral features, including sleep disturbances (aOR = 5.167, p < 0.001) and anxiety (aOR = 2.334, p < 0.001), were also significantly associated. Conclusion These findings highlight the complex interplay between developmental, behavioral, and perinatal factors associated with epilepsy within this cohort of autistic individuals and underscore the importance of systematic monitoring and multidisciplinary management to optimize outcomes in this cohort.
Abstract Background The Early Start Denver Model (ESDM) is a naturalistic developmental behavioral intervention (NDBI) widely used to support early development in young autistic children. This study examines early developmental trajectories associated with different styles and intensities of ESDM-based intervention compared with community Therapy as Usual (TAU) over a 6-month period. It also explores predictors of individual language development based on the intervention style. Methods A total of 112 autistic children participated in the study and were assessed longitudinally while receiving either higher (6 h a week) or lower (3 h a week) intensity ESDM, or TAU at higher (6 h a week) intensity ( N = 29, 32, and 51 participants in each group, respectively). Results The primary findings show that children receiving higher-intensity ESDM exhibited steeper developmental trajectories than children receiving TAU in all the developmental areas such as Language, Personal-Social skills, Performance, Eye-Hand coordination and the General score. Notably, lower-intensity ESDM was associated with steeper developmental gains in individual general development, language, personal social skills, and performance when compared to TAU at double the intensity. Additionally, secondary results indicate that language developmental trajectories are influenced by different factors in the ESDM and TAU groups, with social domain and adaptive behaviors predicting language progress in the ESDM group and baseline cognitive skills predicting language development in the TAU group. Conclusions This study provides observational evidence that different intervention models and intensities may be associated with different short-term developmental trajectories in community settings, particularly where only limited weekly intervention hours are feasible. These findings may help inform service planning in low-resource contexts, while requiring replication in more controlled designs. Trial registration Clinical Trial ID: NCT06494605.
Abstract Background Children born very preterm (VPT) have greater executive function (EF) challenges and internalizing, inattention, and social communication-interaction differences (the Preterm Behavioral Phenotype [PBP]) than full-term (FT) children. EF and PBP outcomes for VPT children with white matter injury (WMI) are less well understood. Furthermore, the extent that EF challenges serve as a neurocognitive mechanism for the PBP is unknown. Methods As part of a longitudinal study, 123 VPT infants (≤ 30 weeks gestation) were recruited from a level-III neonatal intensive care unit and underwent developmental follow-up at ages 5 and 9–10 years. Forty-four VPT infants had high-grade WMI. Seventy-nine FT control children were also included. At the 5 and 9–10 year follow-up, children completed EF tasks tapping short-term/working memory, inhibitory control, and flexibility/shifting, which were combined into an EF composite at each timepoint. Parents and children also completed measures assessing children’s attention-deficit/ hyperactivity, internalizing/anxiety, and social communication-interaction outcomes to generate parent- and child-informant PBP composites at age 9–10 years. Serial mediation analysis examined EF at ages 5 and 9–10 years as serial mediators linking VPT birth and WMI with the PBP, adjusted for covariate factors. Results VPT and WMI children demonstrated lower EF abilities at both timepoints compared to FT children ( p ≤.02). VPT and WMI children obtained higher child-informant PBP composite scores ( p <.001) as well as parent- and child-informant social communication-interaction and ADHD-inattentive problem ratings ( p ≤.03) at age 9–10 years. Lower EF at both timepoints correlated with higher parent- and child-informant PBP ratings ( r -0.2 to -0.45, p <.05). Serial mediation analysis showed that EF development from age 5 to 9–10 years (proportion mediated 3–5%) as well as EF at age 9–10 years (proportion mediated 16–43%) partially mediated associations linking VPT birth and WMI with PBP outcomes. Conclusions VPT and WMI children had greater EF and PBP challenges compared to FT children, with WMI children at greatest risk. Disrupted EF development, at least in part, contributed to the PBP. Findings suggest that VPT and WMI children are in need of early and ongoing EF supports, and that EF training interventions may improve mental health outcomes in this population.
