ABSTRACT Introduction Down syndrome (DS), arising from Trisomy 21, is the most common genetic condition associated with intellectual disability. While smaller total brain volumes have been consistently observed in DS, no longitudinal neuroimaging studies have examined volumetric brain development in DS during infancy, a period of rapid neural growth when interventions may have the greatest impact. Method High-resolution T1- and T2-weighted images were acquired during natural sleep in a multisite longitudinal cohort of 44 infants with DS and 39 control infants without DS at ages 6 and 12 months. Neuroimaging data were harmonized to reduce batch effects, and a novel deep-learning, repeated-measures segmentation approach was applied to optimize neuroanatomical segmentations. Total intracranial volume (ICV) and bilateral absolute subcortical volumes (amygdala, caudate, hippocampus, pallidum, putamen, thalamus) were first directly compared in infants with and without DS at 6 and 12 months. Hierarchical linear modeling (HLM) evaluated longitudinal group differences for each structure, accounting for sex, gestational age, and laterality. Subcortical group differences estimated by HLM were also compared to group differences in total ICV. Results ICV in infants with DS was lower than controls at 6 months (12.6%; p< .001) and 12 months (16.3%; p< .001). Subcortical structures displayed a range of lower volumes (6.9%-13.1%; p’s ≤.003) in infants with DS, although the caudate and putamen were exceptions. Caudate volumes were on average lower in DS but not significantly different from controls, while putamen volumes were on average higher in DS but not significantly different from controls, except for the right putamen, which was significantly larger (5.3%; p =.018) at 6 months. In HLM, ICV and all subcortical structures showed slower growth in DS from 6 to 12 months, except for the amygdala and putamen, which displayed similar growth rates to controls. DS-associated reductions in subcortical volumes were similar in magnitude to ICV, although 12-month caudate and 6- and 12-month putamen volumes were enlarged relative to ICV. Conclusion Infants with DS exhibited substantially reduced ICV and widespread reductions in subcortical volumes and growth from 6-12 months. Across a range of volumetric differences, findings were most distinct in the basal ganglia, for which volume reductions were attenuated in the caudate, while the putamen was uniquely enlarged with comparable growth to controls. These observations support early regional specificity in the neural impact of Trisomy 21 and underscore the utility of infant neuroimaging to inform biologically based interventions and clinical trial readiness in DS.

Visual processing undergoes rapid development in the first year of life, supporting the emergence of higher-order cognitive, language, and motor functions. Visual evoked potentials (VEPs) provide a noninvasive measure of visual system maturation that may shed light on heterogeneous developmental trajectories among infants at high familial likelihood for autism. Infants with an older sibling with autism spectrum disorder (N = 177 at 6 months; N = 132 at 12 months) participated in the Infant Brain Imaging Study-Early Prediction (IBIS-EP) study. Pattern-reversal VEPs were recorded at 6 and 12 months, and developmental skills were assessed at 24 months using the Bayley Scales of Infant and Toddler Development (Bayley-4). VEP components (P1 and N1) were characterized by their amplitude and latency, as well as trial-to-trial variability in these measures. Associations with 24-month cognitive, language, and motor scores were examined using general linear models controlling for age, site, sex, and trial count. Robust VEPs were observed at both time points, with age-appropriate morphology and expected developmental changes, including decreases in P1 latency and amplitude from 6 to 12 months. Greater trial-to-trial variability in P1 latency at both time points was associated with higher cognitive and language scores at 24 months. In contrast, conventional measures of mean P1 latency and amplitude were not associated with developmental outcomes. These findings suggest that temporal variability in early visual responses may index adaptive sensory-circuit flexibility during a period of rapid experience-dependent development. VEP response-timing variability may therefore provide an early mechanistic marker of sensory-circuit organization relevant to later developmental trajectories.

Language development, a core pillar of social communication, has variable trajectories in autism that include a regression or loss of skills in roughly 20% of autistic individuals. Language regression is most frequently identified through parent report but can also be observed as a decrease in raw scores on a repeated language assessment (measure-defined). Later language outcomes after regression have been observed to be highly variable, but not lower than children without a language regression. The current study explores rates of parent-reported and measure-defined language regression in a large sample of infants at high familial likelihood of autism due to having an older autistic sibling. Among all participants at high familial likelihood for autism ( n =428), parent-reported regression was observed in 2.8% ( n =12) and was associated with 2.77 times higher odds of receiving an autism diagnosis. Measure-defined regression was observed in 8% ( n =36) and was associated with 1.21 times higher odds of autism diagnosis. These rates of regression are expectedly lower than estimates collected in autistic samples. Neither of these elevated odds was statistically significant and there was low concordance between these groups with only one participant present in both. Nearest-neighbor comparison samples of non-autistic infants at high and low likelihood for autism without language regression were selected to assess differences in language growth trajectories associated with regression. Infants with parent-reported language regression showed comparable language development to a matched high-likelihood sample while infants with measure-defined language regression showed slower overall language development than matched peers. Taken together, our results show that parent-report and direct measurement of regression capture unique aspects of child language development that may not be predictive of an autism diagnosis but may indicate delayed language growth in early toddlerhood. These language outcomes support previous findings of wide heterogeneity among those with regression and continued language growth after loss of skills. Key Points:Language regression can be captured through parent-report or decrease in raw scores on repeated language assessment and is reported in approximately 20% of autistic toddlers.Most research on language regression uses retrospective report of regression in autistic children, but this study prospectively examines regression in toddlers at high familial likelihood for autism who do and do not receive later diagnoses.Parent-reported and measure-defined regression in this high-likelihood sample have low concordance indicating that these may be different events in language development.The presence of language regression was not associated with significantly higher odds of receiving an autism diagnosis.Children who exhibit language regression continue growing and developing language and those with parent-reported regression display comparable language skills to children without language regression at three years of age.

Human induced pluripotent stem cell (iPSC) derived cortical organoids (hCOs) model neurogenesis on an individual's genetic background. The degree to which hCO phenotypes recapitulate the brain growth of the participants from which they were derived is not well established. We generated up to 3 iPSC clones from each of 18 participants in the Infant Brain Imaging Study, who have undergone longitudinal brain imaging during infancy. We identified consistent hCO morphology and cortical cell types across clones from the same participant. hCO cross-sectional area and production of cortical hem cells were associated with in vivo cortical growth rates. Cell cycle associated genes expression in early progenitors at the crux of fate decision trajectories were correlated with cortical growth rate from 6-12 months of age, and were enriched in microcephaly and neurodevelopmental disorder genes. Our data suggest the hCOs capture inter-individual variation in cortical cell types influencing infant cortical surface area expansion.

The ability to selectively attend to one talker in the presence of competing talkers is crucial to communication in noisy, real-world environments. In this study, we investigated the relationship between intellectual ability and speech perception under multitalker conditions. Since neurodivergent individuals show a wide range of intellectual ability, from above average IQ to intellectual disability, intellectual ability may be an important individual characteristic that impacts multitalker speech perception, but this is not currently well understood. We tested individuals with autism, fetal alcohol spectrum disorder, and an age- and sex-matched comparison group, all with typical hearing. We found a strong positive correlation between IQ and multitalker speech perception thresholds. This demonstrates that deficits in intellectual ability, despite intact peripheral encoding of sound, are associated with difficulty listening under complex conditions for individuals with autism and fetal alcohol spectrum disorder. Future research is needed to investigate specific cognitive control mechanisms that contribute to difficulty listening under complex conditions. These findings suggest that audiological services to improve communication in real-world environments for neurodivergent individuals should be considered during clinical evaluations.

Canonical babbling (CB) is a critical developmental milestone that typically occurs in the second half of the first year of life. Studies focusing on CB in infants at elevated familial likelihood for autism spectrum disorder (ASD) or who later receive an ASD diagnosis are limited and the evidence is mixed. CB comprises a series of canonical syllables (CS) which are defined as the rapid transitions between consonant-like sounds paired with vowel-like sounds (e.g., [gugugu]). One way of measuring CB is by computing canonical babbling ratio (CBR) i.e. total number of CS divided by the total number of syllables. If the child has reached the criterion of 0.15 CBR it is said that they have achieved the CB stage. For several years now, CB has been measured using short lab based or home-based video recordings which may not represent a child's natural vocalization pattern since child vocalizations fluctuate throughout the day. Day long audio recordings, that capture a child's vocalizations throughout the day, has the potential to overcome this limitation. Therefore, the current study aimed to answer whether CBRs computed from day-long audio recordings using the language environment analysis (LENA®) were different among infants at elevated familial likelihood for ASD who receive an ASD diagnosis (EL-ASD; n = 11), who did not receive an ASD diagnosis (EL-Neg; n = 32) and infants at low likelihood for ASD (LL-Neg; n = 25) at 9 and 15 months. The study also aimed to evaluate if there are group differences in reaching the canonical babbling stage at 9 and 15 months and are CBRs at 9 and 15 months associated with later language abilities at 24 months. Findings indicated no group differences in mean CBRs at 9 and 15 months and no association with later language abilities. However, we found that children in the EL-ASD group were less likely to reach the 0.15 CBR threshold for being in the canonical babbling stage by 9 months of age. Thus, suggesting that a diagnosis of ASD is associated with delays in CB for some children. Future work in this area must include a larger sample and more standardized annotation protocols to harmonize results across studies and ensure replication.

Down syndrome (DS) is the most common genetic cause of intellectual disability, but our understanding of white matter microstructure in children with DS remains limited. Previous studies have reported reductions in white matter integrity, but nearly all studies to date have been conducted in adults or relied solely on diffusion tensor imaging (DTI), which lacks the ability to disentangle underlying properties of white matter organization. This study examined white matter microstructural differences in 7- to 12-year-old children with DS (n = 23), autism (n = 27), and typical development (n = 50) using DTI as well as High Angular Resolution Diffusion Imaging, and Neurite Orientation and Dispersion Imaging. There was a spatially specific pattern of results that showed a dissociation between intra- and inter-hemispheric pathways. Intra-hemispheric pathways (e.g., inferior fronto-occipital fasciculus, superior longitudinal fasciculus) exhibited reduced organization and structural integrity. Inter-hemispheric pathways (e.g., corpus callosum projections) and motor pathways (e.g., corticospinal tract) showed denser neurite packing and lower neurite dispersion. The current findings provide early insight into white matter development in school-aged children with DS and have the potential to further elucidate microstructural differences and inform more targeted clinical trials than what has previously been observed through DTI models alone.

Early intervention has the potential to improve the outcomes of children with autism. As more evidence-based early intervention approaches become available, data generated from studies testing their efficacy provide the unique opportunity to examine whether specific interventions differentially benefit children based on their demographic and behavioral characteristics. In this study, we retrospectively applied a probability-of-intervention-benefit framework to data from a randomized controlled trial comparing the outcomes of children with autism receiving community intervention as usual to those receiving the Early Start Denver Model (ESDM) delivered by university-based clinicians. Data from 85 children, randomized to one of the two intervention groups were analyzed. The primary outcome was the Brief Observation of Social Communication Change, a video coded measure of autism related social communication and repetitive behaviors. Children were classified as making reliable change or not on this outcome based on their reliable change index. 73% of children in the ESDM group and 57% in the community group made reliable improvements over the 24 months of intervention. The probability of intervention benefit in the community group depended on children's baseline characteristics. Those with more significant cognitive delays and greater autism severity were less likely to make reliable change in the community group, but not the ESDM group. Overall, the data highlight the variability of change that individual children make in early interventions, the role of various factors contributing to change, and finally, the importance of analyzing change at both the group and the individual levels.

Naturalistic developmental behavioral interventions target developmentally appropriate skills in young children with autism spectrum disorders using behavioral techniques in naturalistic interactions. Naturalistic developmental behavioral interventions demonstrate strong empirical support and frequently utilize caregiver training of intervention strategies. However, our understanding of the mechanisms of change linked to naturalistic developmental behavioral interventions remains limited. Based on retrospective, secondary data analyses from three previously conducted randomized controlled trials of caregiver-mediated naturalistic developmental behavioral interventions, this study examined the direct effect of intervention on caregiver naturalistic developmental behavioral intervention strategy use and how caregiver changes mediate intervention effects on children's social communication. A total of 419 videos from 229 dyads consisting of autistic children (M = 32.5 months/ages 1-5 years) and caregivers were included in analyses using the masked ratings of the measure of naturalistic developmental behavioral intervention strategy implementation-caregiver changes (MONSI-CC) and brief observation of social communication change (BOSCC-SC). Using longitudinal mediation analyses, we examined the mediation effect of caregiver behavioral changes on children's outcomes. Results demonstrated a significant intervention effect on changes of caregiver naturalistic developmental behavioral intervention strategy use (MONSI-CC) and of changeds of caregiver strategy use (MONSI-CC) on child social communication change (BOSCC-SC) scores, but no overall total effect of intervention on changes of child social communication (BOSCC-SC). This study demonstrates the mediating role of caregiver behavior on the child intervention response, a first step toward better understanding underlying mechanisms in naturalistic developmental behavioral interventions.Lay AbstractNaturalistic developmental behavioral interventions use behavioral techniques in naturalistic interactions and settings. Naturalistic developmental behavioral interventions also teach caregivers to use strategies to enhance social communication in their children with autism spectrum disorder. Naturalistic developmental behavioral interventions are effective in supporting young autistic children but how naturalistic developmental behavioral interventions work ("underlying mechanisms") is not known yet. Therefore, by applying new instruments to videos already collected from the three previously conducted randomized controlled trials of caregiver-mediated naturalistic developmental behavioral interventions, we examined how caregivers change in their strategy use over the course of intervention and how that relates to changes in social communication in their autistic children. A total of 419 videos from 229 dyads consisting of autistic children (M = 32.5 months/ages 1-5 years) and caregivers were included in analyses using two measures, one for the caregiver behavioral changes (the measure of naturalistic developmental behavioral intervention strategy implementation-caregiver changes [MONSI-CC]), and another for the children's social communication (the brief observation of social communication change [BOSCC-SC]). We found that naturalistic developmental behavioral interventions were effective in leading to increased mastery of caregiver naturalistic developmental behavioral intervention strategy use, which then affected the changes in child's social communication skills. However, we found no direct effect of treatment for child social communication skills. This study highlights the mediating role of caregiver behavior on the child intervention response, supporting the importance of involving caregivers as partners in the intervention for young autistic children.

Sleep problems have been associated with atypical development, but there is limited understanding of when sleep problems arise and how they differ across clinical populations. We aimed to evaluate sleep characteristics of infants with Down syndrome (DS), higher familial likelihood of autism (HL) and lower familial likelihood of autism (LL) at 6 and 12 months of age. Participants were from two longitudinal, multi-site, studies. Sleep was estimated by parent report on the Brief Infant Sleep Questionnaire at 6 months (59 DS, 173 HL, 54 LL); 12 months (58 DS, 129 HL, 30 LL); and in a longitudinal subset at both 6 and 12 months (100 HL; 23 LL; 33 DS). At 6-months, DS parents reported less concern about infant sleep and less night wakefulness than LL parents; HL parents reported longer sleep onset latency (SOL). At 12 months DS parents reported less night sleep and more night wakefulness; HL parents reported less night sleep, more night wakefulness and longer SOL compared to LL. Night wakefulness increased significantly in the DS and HL groups from 6 to 12 months of age. A higher proportion of DS and HL infants decreased Night Sleep and increased Night Wakefulness compared with the LL group. A higher proportion of DS infants increased SOL compared with the LL group. Sleep alterations are present in the first year of life and may differ in DS and HL infants. The mechanisms behind these sleep alterations may be an important early intervention target.

Sleep problems occur at a higher rate in autism spectrum disorder (ASD) than in typical development (TD). Polysomnography (PSG) is the gold-standard for collecting objective sleep data, but it is labor-intensive, intrusive, requires patients to stay overnight in an unfamiliar environment, and typically limited to one night of recording decreasing its validity and scalability to larger cohorts of ASD individuals. We tested a non-contact biomotion sensor, the SleepScore Max (SSM) to determine the acceptability of longitudinal use and feasibility of estimating sleep characteristics in ASD and TD youth in the home. 7 ASD (M=13.0y, SD=2.2y, with community ASD diagnosis) and 6 TD (M=13.3y, SD=2.3 y) individuals completed 2 weeks of at-home sleep monitoring using the device. Participants were between age 8-15 years, living with a caregiver, sleeping alone, and >80lbs. Caregivers completed an acceptability questionnaire at the end of the study. Sleep metrics were analyzed using repeated-measures ANOVA with fixed effects of group (ASD vs TD), day, and their interaction. Pairwise comparisons of standard deviations determined differences in night-to-night variability between groups. The ASD group exhibited more deep sleep (F=21.52, p< 0.001), longer sleep onset latency (F=5.13, p=0.025), and increased total wake time (F=4.56, p=0.034), whereas the TD group had more light sleep (F=5.58, p=0.019), and total interruptions (F=12.79, p< 0.001). Pairwise comparisons determined that the ASD group had greater night-to-night variability in REM sleep (t=-2.7, p=0.021). Caregivers reported the device to be highly acceptable (M=6.44; SD=1), reasonable to use (M=6.31; SD=1) and causing little to no discomfort (M=1.7; SD=1.2) on a 1-7 Likert scale. Our results agree with previous PSG studies showing an increase in sleep onset latency and an increase in deep sleep in autistic individuals. These results provide preliminary evidence that a non-contact biomotion sensor can accurately measure and differentiate sleep between ASD and NT individuals in a naturalistic and sensory friendly manner with high levels of acceptability and low participant burden. Non-contact sensors show great promise for long-term longitudinal characterization of sleep in the home to evaluate outcomes of sleep focused interventions.

Induced pluripotent stem cell (iPSC)-derived human cortical organoids (hCOs) model neurogenesis on an individual’s genetic background. The degree to which hCO phenotypes recapitulate the brain growth of the participants from whom they were derived is not well established. We generated up to 3 iPSC clones from each of 18 participants in the Infant Brain Imaging Study, who underwent longitudinal brain imaging during infancy. We identified consistent hCO morphology and cortical cell types across clones from the same participant. hCO cross-sectional area and production of hem/choroid plexus were associated with in vivo cortical growth rates. Cell-cycle-associated gene expression in early progenitors at the crux of fate-decision trajectories was correlated with cortical growth rates from 6 to 12 months of age and was enriched for microcephaly and neurodevelopmental disorder genes. Our data suggest the hCOs capture inter-individual variation in cortical cell types that influences infant cortical surface area expansion.

Mass univariate testing on functional connectivity MRI (fcMRI) data is limited by difficulties achieving experiment-wide significance. Recent work addressing this problem has used enrichment analysis, which aggregates univariate screening statistics for a set of variables into a single enrichment statistic. There have been promising results using this method to explore fcMRI-behavior associations. However, there has not yet been a rigorous examination of the statistical properties of enrichment analysis when applied to fcMRI data. Establishing power for fcMRI enrichment analysis will be important for future neuropsychiatric and cognitive neuroscience study designs that plan to include this method. Here, we use realistic simulation methods, which mimic the covariance structure of fcMRI data, to examine the false positive rate and statistical power of one technique for enrichment analysis, over-representation analysis. We find it can attain high power even for moderate effects and sample sizes, and it strongly outperforms univariate analysis. The false positive rate associated with permutation testing is robust.

Gestures serve as both a communication and a word-learning tool, with typically developing children consistently showing that early gestures are positively associated with later vocabulary skills. However, many autistic children experience delays and challenges in both gesture and vocabulary skills, and studies also show mixed gesture-vocabulary associations; thus, it is unclear whether gestures in autistic children support emerging vocabulary skills. To address previous conflicting findings, the current conceptual replication study uses linear models with a large sample (N = 451) of 12- to 24-month-old English-raised infants to investigate whether gestures are associated with expressive and receptive vocabulary. Using the infant-sibling design, gesture-vocabulary associations and group moderation were investigated in three groups: infant-siblings of autistic children who later meet the criteria for autism themselves (HL-ASD, n = 73), infant-siblings who did not meet criteria for autism (HL-Neg, n = 238), and a control group without a family history of autism (LL-Neg, n = 140). Both LL-Neg and HL-ASD groups showed positive associations between 12-month gestures and 18-month receptive vocabulary; however, only the LL-Neg group showed a positive association between 12-month gestures and 18-month expressive vocabulary. For 12-month gestures and 24-month receptive and expressive vocabulary, the LL-Neg and HL-Neg groups showed positive association, whereas the HL-ASD group did not. Similarly, the LL-Neg and HL-Neg groups showed positive associations between 18-month gestures and 24-month vocabulary, but the HL-ASD did not. Overall, the LL-Neg group showed significant gesture-vocabulary associations across all tested models, while the HL-ASD only showed one significant positive association.

Intrinsic connectivity of the fusiform face area (FFA) was assessed using resting-state functional magnetic resonance imaging (fMRI) to compare adults with autism spectrum disorder (ASD; n = 17) and age-, sex-, and IQ-matched typically developing controls (TD; n = 22). The FFA seed region was delineated in each participant using a functional localizer task. Whole brain analyses of FFA connectivity revealed increased connectivity between the right FFA and the vermis, sensorimotor cortex, and extended face-processing network in individuals with ASD compared to TD participants; the TD group did not demonstrate increased functional connectivity. No group differences were observed from the left FFA. The relationship between FFA connectivity and the ability to remember faces significantly differed between the groups. Better face memory performance was positively correlated with increased connectivity within general visual processing areas in the ASD participants; whereas for the TD group, better face memory performance was associated with increased connectivity with brain regions related to face encoding, recognition, and retrieval. FFA overconnectivity with face, emotion, and memory processing areas, along with atypical relationships between FFA–occipito-temporal connections and face memory performance highlights a possible mechanism underlying social dysfunction in individuals with ASD.

Abstract Background Empirical evidence regarding the development of sensory responsivity in young children at high likelihood to develop autism spectrum disorder (ASD) remains relatively limited. It is unclear how sensory responsivity behaviors may change over time and impact later developmental outcomes. The goals of this study were to (a) characterize developmental trajectories of sensory responsivity across infancy (∼12 months), toddlerhood (∼24 months), and school age (6–11 years) in children at high and low familial likelihood for ASD; and (b) determine if sensory responsivity in infancy predicts adaptive and cognitive functioning at school age among children with ASD. Methods Generalized linear mixed effects models were used to examine scores from the Sensory Experiences Questionnaire in three groups of children including high‐likelihood children later diagnosed with ASD (HL‐ASD; n = 30), high‐likelihood children without ASD (HL‐Neg; n = 150), and low‐likelihood control children not meeting ASD diagnostic criteria (LL‐Neg; n = 94). Hierarchical linear regression was then used to examine the association between sensory responsivity scores in infancy and functional adaptive and cognitive outcomes at school age for children at high likelihood of ASD. Results Development of sensory responsivity from infancy to later childhood is best estimated by the effects of chronological age and Group for Sensory Seeking and Hypo responsivity and the additional effect of the interaction of Group and chronological age for Total and Hyper responsivity. Early elevated Hypo responsivity and Sensory Seeking scores are negatively associated with later adaptive behavior but not cognitive level. Conclusion Overall, higher degrees of Sensory Seeking and Hypo sensory responsivity are detectable in autistic children's behavioral repertoires by 12 months of age and associate with reduced adaptive functioning in middle childhood. These results point to the potential importance of early detection and treatment implications of early sensory behaviors.

Autism spectrum disorder is associated with a high rate of sleep problems, affecting over 80% of autistic individuals. Sleep problems have pervasive negative effects on health, behavior, mood, and cognition but are underrecognized in autistic children. Problems initiating and maintaining sleep-hallmarks of insomnia-are common. Sleep-disordered breathing and restless legs syndrome have also been described in autism at a higher prevalence than in community populations. The authors describe current research on sleep in autistic children and potential pathophysiologic mechanisms. They describe practical approaches to sleep assessment and synthesize approaches to addressing sleep problems in autistic children.

Many neurodiverse individuals experience auditory processing differences including hyper- or hyposensitivity to sound, attraction or aversions to sound, and difficulty listening under noisy conditions. However, the origins of these auditory symptoms are not well understood. In this study, we tested 7-to-10-year-old autistic children and age and sex-matched neurotypical comparison participants. To simulate a realistic classroom situation where many people are often speaking simultaneously, we obtained neural and behavioral measures of speech perception in both quiet and noise conditions. Using electroencephalography, we recorded neural responses to naturalistic, continuous speech to assess the cortical encoding of the speech envelope. We also obtained behavioral multitalker speech perception thresholds and estimates of spatial release from masking, a binaural hearing phenomenon in which speech perception improves when distracting speakers are spatially separated from the target speaker. Our preliminary results from both neural and behavioral measures suggest that the autistic group shows worse speech perception in noise and less spatial release from masking than the neurotypical group. These findings suggest that autistic children may benefit from environments with reduced noise to facilitate speech perception. These findings also warrant further investigation into speech perception under real-world conditions and the neural mechanisms underlying sound processing in autistic children.

BACKGROUND:Naturalistic Developmental Behavioral Interventions (NDBIs) for young children with autism spectrum disorder commonly involve caregiver-mediated approaches. However, to date, there is limited research on how caregivers' skills change, and, in turn, impact child outcomes. METHODS:We evaluated the NDBI strategy use of 191 caregivers prior to participation in NDBIs (or control groups) across multiple randomized controlled trials, using the Measure of NDBI Strategy Implementation, Caregiver Change (MONSI-CC). Clustering analyses were used to examine caregiver variability in NDBI strategy use at intervention entry. Generalized Linear Mixed Models were used to examine changes in caregiver strategy use over the course of intervention and its impact on changes in children's social communication. RESULTS:Using clustering analysis, we found that caregivers' baseline skills fit four profiles: limited, emerging, variable, and consistent/high, with few demographic factors distinguishing these groups. Caregivers starting with limited or emerging skills improved in their strategy use with intervention. Caregivers starting with more skills (consistent/high or variable) maintained higher skills over intervention. Children of caregivers in these groups who received target NDBIs improved in their social communication skills. CONCLUSIONS:Results suggested that caregiver skills improve through participation in NDBIs and may directly contribute to their children's outcomes, although more research on mediating factors is needed. Individualized approaches for caregivers and their children starting with differing skill profiles at intervention entry may be warranted.