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Children from economically distressed families and neighborhoods are at risk for stress and pollution exposure and potential neurotoxic sequelae. We examine dimensions of early-life stress affecting hippocampal volumes, how prenatal exposure to air pollution might magnify these effects, and associations between hippocampal volumes and visuospatial reasoning.Fifty-three Hispanic/Latinx and/or Black children of ages 7 to 9 years were recruited from a longitudinal birth cohort for magnetic resonance imaging and cognitive assessment. Exposure to airborne polycyclic aromatic hydrocarbons was measured during the third trimester of pregnancy. Maternal report of psychosocial stress was collected at child age 5 and served as measures of early-life stress. Whole hippocampus and subfield volumes were extracted using FreeSurfer. Wechsler performance IQ measured visuospatial reasoning.Maternal perceived stress associated with smaller right hippocampal volume among their children (B = -0.57,Prenatal and early-life exposures to chemical and social stressors are likely compounding. Socioeconomic deprivation and disparities increase risk of these exposures that exert critical neurobiological effects. Developing deeper understandings of these complex interactions will facilitate more focused public health strategies to protect and foster the development of children at greatest risk of mental and physical effects associated with poverty.

Socioeconomic status (SES) has been linked to differences in brain structure and psychiatric risk across the lifespan. Despite many neuropsychiatric disorders emerging in childhood, few studies have examined the influence of SES on brain aging and psychopathology in youth.We re-analyzed relative brain age (RBA) data from the Healthy Brain Network to examine the influence of SES components (parent education, occupation, household income-to-needs ratio (INR), public assistance enrollment) on RBA. RBA was previously determined using covariation patterns for cortical morphology, white, and subcortical gray matter volumes without SES in predictive models. We also examined associations between RBA and psychiatric symptoms (child behavior checklist). Full case analysis included 470 youth (5-17 years; 61.3% male), self-identifying as White (55%), African American (15%), Hispanic (9%), or multiracial (17.2%). Mean household income was 3.95±2.33 (Mean±SD) times the federal poverty threshold. Multiple linear regression examined if 1) SES components associated with RBA, and 2) RBA associated with psychiatric symptoms. Models covaried for sex, scan location, and parent psychiatric diagnoses.RBA associated with public assistance (p = 0.03), parent occupation (p = 0.01), and parent psychiatric diagnosis (p = 0.01), but not with INR and parent education. Parent occupation (p = 0.02) and RBA (p = 0.04) associated with CBCL anxiety/depression scores.Components of SES associated with brain aging, underscoring the risk of omitting these factors in developmental brain research. Further, delayed brain aging was associated with low parental occupational prestige and child anxiety/depression scores, suggesting a possible biological pathway from SES to mental health risk.

BACKGROUND: Emerging evidence suggests that the cerebellum may contribute to variety of cognitive capacities, including social cognition. Nonverbal learning disability (NVLD) is characterized by visual-spatial and social impairment. Recent functional neuroimaging studies have shown that children with NVLD have altered cerebellar resting state functional connectivity, which is associated with various symptom domains. However, little is known about cerebellar white matter microstructure in NVLD and whether it contribute to social deficits. METHODS: Twenty-seven children (12 with NVLD; 15 typically developing (TD)) contributed useable diffusion tensor imaging data. Tract-based spatial statistics (TBSS) were used to quantify fractional anisotropy (FA) in the cerebellar peduncles. Parents completed the Child Behavior Checklist, providing a measure of social difficulty. RESULTS: Children with NVLD had greater fractional anisotropy in the left and right inferior cerebellar peduncle. Furthermore, right inferior cerebellar peduncle FA was associated with social impairment as measured by the Child Behavior Checklist Social Problems subscale. Finally, the association between NVLD diagnoses and greater social impairment was mediated by right inferior cerebellar peduncle FA. CONCLUSIONS: These findings provide additional evidence that the cerebellum contributes both to social cognition and to the pathophysiology of NVLD.

ImportanceMillions of rental evictions occur in the United States each year, disproportionately affecting households with children. Increasing attention has been paid to the impact of evictions on child health outcomes.ObjectiveTo synthesize and assess studies examining the associations of eviction exposure with infant and child health outcomes.Evidence ReviewFor this systematic review without meta-analysis, a database search was performed using PubMed, Web of Science, and PsycINFO, through September 25, 2022. Included studies were peer-reviewed quantitative studies examining an association between exposure to eviction and at least 1 health outcome, both before age 18 years, including prenatal exposures and perinatal outcomes. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from March 3 to December 7, 2022.FindingsDatabase searches identified 266 studies, and 11 studies met inclusion criteria. Six studies examined associations between prenatal eviction and birth outcomes, such as gestational age, and each found that eviction was significantly associated with at least 1 adverse birth outcome. Five studies investigated other childhood outcomes, including neuropsychological test scores, parent-rated child health, lead testing rates, and body mass index, and among these 5 studies, 4 reported an association between eviction and adverse child health outcomes. Direct experience of eviction or residence in a neighborhood with more evictions was associated with adverse perinatal outcomes in 6 studies, higher neurodevelopmental risk in 2 studies, worse parent-rated child health in 2 studies, and less lead testing in 1 study. Study designs and methods were largely robust.Conclusions and RelevanceIn this systematic review without meta-analysis of the association between evictions and child health outcomes, evidence demonstrated the deleterious associations of eviction with a range of developmental periods and domains. In the context of a rental housing affordability crisis, ongoing racial disparities in evictions, and continuing harm to millions of families, health care practitioners and policy makers have an integral role to play in supporting safe, stable housing for all.

Nonverbal Learning Disability (NVLD) is characterized by deficits in visual-spatial, but not verbal, reasoning. Nevertheless, the functioning of the neural circuits supporting spatial processing have yet to be assessed in children with NVLD. We compared the resting state functional connectivity of a spatial brain network among children with NVLD, children with reading disorder (RD), and typically developing (TD) children. Seventy-five participants (7–15 years old) were included in the study (20 TD, 24 NVLD, and 31 RD). Group differences in global efficiency and functional connectivity among 12 regions comprising a previously defined spatial network were evaluated. Associations with behavior were explored. Global efficiency of the spatial network associated positively with spatial ability and inversely with socioemotional problems. Within the spatial network, associations between left posterior cingulate (PCC) and right retrosplenial cortical activity were reduced in children with NVLD relative to those without spatial deficits (RD and TD). Connectivity between left PCC and right posterior cerebellum (Crus I and II) was reduced in both groups of children with learning disabilities (NVLD and RD) relative to TD children. Functional connectivity of the spatial network was atypically associated with cognitive and socioemotional performance in children with NVLD. Identifying a neurobiological substrate for NVLD provides evidence that it is a discrete clinical entity and suggests targets for treatment.

© 2022 Elsevier Ltd. All rights reserved., Humans are ubiquitously exposed to neurotoxicants in air pollution, causing increased risk for psychiatric outcomes. Effects of prenatal exposure to air pollution on early emerging behavioral phenotypes that increase risk of psychopathology remain understudied. We review animal models that represent analogues of human behavioral phenotypes that are risk markers for internalizing and externalizing problems (behavioral inhibition, behavioral exuberance, irritability), and identify commonalities among the neural mechanisms underlying these behavioral phenotypes and the neural targets of three types of air pollutants (polycyclic aromatic hydrocarbons, traffic-related air pollutants, fine particulate matter < 2.5 µm). We conclude that prenatal exposure to air pollutants increases risk for behavioral inhibition and irritability through distinct mechanisms, including altered dopaminergic signaling and hippocampal morphology, neuroinflammation, and decreased brain-derived neurotrophic factor expression. Future studies should investigate these effects in human longitudinal studies incorporating complex exposure measurement methods, neuroimaging, and behavioral characterization of temperament phenotypes and neurocognitive processing to facilitate efforts aimed at improving long-lasting developmental benefits for children, particularly those living in areas with high levels of exposure., This work was supported by the National Institutes of Environmental Health Sciences R01ES030950, R01ES032296 and K23026239 to A.E.M. and Whole Communities Whole Health, a University of Texas at Austin Grand Challenge Initiative (OVPR) to F.A.C.

Background Autism spectrum disorder (ASD) is a common neurodevelopmental diagnosis showing substantial phenotypic heterogeneity. A leading example can be found in verbal and nonverbal cognitive skills, which vary from elevated to impaired compared with neurotypical individuals. Moreover, deficits in verbal profiles often coexist with normal or superior performance in the nonverbal domain. Methods To study brain substrates underlying cognitive imbalance in ASD, we capitalized categorical and dimensional IQ profiling as well as multimodal neuroimaging. Results IQ analyses revealed a marked verbal to nonverbal IQ imbalance in ASD across 2 datasets (Dataset-1: 155 ASD, 151 controls; Dataset-2: 270 ASD, 490 controls). Neuroimaging analysis in Dataset-1 revealed a structure–function substrate of cognitive imbalance, characterized by atypical cortical thickening and altered functional integration of language networks alongside sensory and higher cognitive areas. Conclusion Although verbal and nonverbal intelligence have been considered as specifiers unrelated to autism diagnosis, our results indicate that intelligence disparities are accentuated in ASD and reflected by a consistent structure–function substrate affecting multiple brain networks. Our findings motivate the incorporation of cognitive imbalances in future autism research, which may help to parse the phenotypic heterogeneity and inform intervention-oriented subtyping in ASD.

It is well known that financial disadvantage is associated with alterations in brain development in regions critical to socioemotional well-being such as the hippocampus and the amygdala. Yet little is known about whether family income at different points in development is differentially associated with these structures. Furthermore, little is known about which environmental factors statistically mediate associations between income and subcortical structure. Using a longitudinal birth cohort and linear mixed-effects models, we identified associations between income-to-needs ratio (INR) at 6 timepoints throughout childhood and hippocampal and amygdala volumes at age 7-9 years (n = 41; 236 INR measurements; 41 brain measurements). Mediation analysis identified environmental sequelae of income that statistically accounted for INR-brain associations. Lower INR prior to age 4 was associated with smaller hippocampal volumes, whereas lower INR prior to age 2 was associated with smaller right amygdala volume. These associations were mediated by unmet basic needs (e.g., food, housing). These findings delineate the temporal specificity of associations between income and hippocampal and amygdala structures.

Background and Objectives: Prenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children’s brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children’s cognitive control circuitry and behavior. Methods: Forty-one children (7–9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist. Results: Compared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR

ImportanceThe primary outcomes of the COVID-19 pandemic on the mental health of women with children remain largely unknown.ObjectivesTo identify and describe clusters of mothers of children participating in the Environmental influences on Child Health Outcomes (ECHO) Program that characterize pandemic-associated hardships, coping mechanisms, and behaviors, and to evaluate associations between pandemic-associated hardships, coping strategies, and behavior changes with pandemic-associated traumatic stress symptoms.Design, Setting, and ParticipantsThis multicenter cohort study investigated experiences during the COVID-19 pandemic between April 2020 and August 2021 among maternal caregivers of children participating in the ECHO Program. Data from self-identified mothers of ECHO-enrolled children from 62 US cohorts were included in analyses. Data were analyzed from November 2021 to July 2022.ExposuresThe primary exposures were pandemic-associated changes in mothers’ health, health care utilization, work and finances, coping strategies, and health-associated behaviors. Exposures were assessed via a self-reported questionnaire designed by ECHO investigators.Main Outcomes and MeasuresThe primary outcome was the total symptoms score of pandemic-associated traumatic stress (PTS), defined as the number of items endorsed at least sometimes or more frequently, from a 10-item self-report measure.ResultsThe study surveyed 11 473 mothers (mean [SD] age, 37.8 [7.4] years; 342 American Indian [2.98%], 378 Asian [3.29%], 1701 Black [14.83%], and 7195 White [62.71%]; 2184 with Hispanic/Latina ethnicity [19.04%]) and identified 2 clusters that best characterized their COVID-19 pandemic experiences—one characterized by higher life disruptions (eg, to work and health care), higher social isolation, more coping behaviors to mitigate the outcomes of the pandemic, and more changes to their health behavior routines (high change [1031 mothers]) and the other characterized by lower changes (low change [3061 mothers]). The high change cluster was more socioeconomically advantaged and reported higher PTS (mean [SD] number of symptoms, 3.72 [2.44] vs 2.51 [2.47]). Across both clusters, higher pandemic-associated hardships, coping mechanisms, and behavior changes were associated with higher PTS, and these associations were greater in the low change cluster.Conclusions and RelevanceIn this study of more than 11 000 US mothers, associations between socioeconomic factors, stressful life events, and mental health sequelae were complex. Accordingly, programs, policies, and practices targeting mental health during public health crises such as the COVID-19 pandemic should consider the range and configuration of hardships in designing the most effective interventions to mitigate long-term outcomes.

Due to the diverse behavioral presentation of autism spectrum disorder (ASD), identifying ASD subtypes using patterns of cognitive abilities has become an important point of research. Some previous studies on cognitive profiles in ASD suggest that the discrepancy between verbal intelligence quotient (VIQ) and performance IQ (PIQ) is associated with ASD symptoms, while others have pointed to VIQ as the critical predictor. Given that VIQ is a component of the VIQ-PIQ discrepancy, it was unclear which was most driving these associations. This study tested whether VIQ, PIQ, or the VIQ-PIQ discrepancy was most associated with ASD symptoms in children and adults with ASD (N = 527). Using data from the Autism Brain Imaging Data Exchange (ABIDE), we tested the independent contribution of each IQ index and their discrepancy to ASD symptom severity using multiple linear regressions predicting ASD symptoms. VIQ was most associated with lower symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS) total score, and when VIQ was included in models predicting ASD symptoms, associations with PIQ and IQ discrepancy were not significant. An association between VIQ and ASD communication symptoms drove the association with ASD symptom severity. These results suggest that associations between ASD communication symptoms and IQ discrepancy or PIQ reported in prior studies likely resulted from variance shared with VIQ. Subtyping ASD on the basis of VIQ should be a point of future research, as it may allow for the development of more personalized approaches to intervention. LAY SUMMARY: Previous research on links between autism severity and verbal and nonverbal intelligence has produced mixed results. Our study examined whether verbal intelligence, nonverbal intelligence, or the discrepancy between the two was most related to autism symptoms. We found that higher verbal intelligence was most associated with less severe autism communication symptoms. Given the relevance of verbal intelligence in predicting autism symptom severity, subtyping autism on the basis of verbal intelligence could lead to more personalized treatments.

BACKGROUND: Excessive environmental noise exposure and noise annoyance have been linked to adverse physical and mental health outcomes. Although socioeconomic disparities in acoustically measured and geospatially estimated noise have been established, less is known about disparities in noise complaints, one of the most common sources of distress reported to local municipalities. Furthermore, although some studies have posited urban quieting during the COVID-19 pandemic, little empirical work has probed this and probed noise complaints during the pandemic. OBJECTIVES: Using over 4 million noise complaints from the New York City (NYC) 311 database, we quantified census tract-level socioeconomic disparities in noise complaints since 2010 and examined how such disparities changed during the COVID-19 pandemic. METHODS: Using data from January 2010 through February 2020, we fit linear mixed-effects models, estimating monthly tract-level noise complaints by the proportion of residents who were low-income, time in months since January 2010, categorical month, their interactions, and potential confounds, such as total population and population density. To estimate COVID-19 pandemic effects, we included additional data from March 2020 through February 2021 and additional interactions between proportion low-income, month of year, and an indicator variable for COVID-19 pandemic onset in March 2020. RESULTS: Census tracts with a higher proportion of low-income residents reported more monthly noise complaints and this increased over time (time×month×proportion low-income interaction p-values < .0001 for all months), particularly in warmer months. Socioeconomic disparities in noise complaints were exacerbated during the COVID-19 pandemic (month×proportion low-income×pandemic era interaction p-values < .0001 for March through November), also in a seasonal manner. DISCUSSION: Since 2010, noise complaints have increased the most in the most economically distressed communities, particularly in warmer seasons. This disparity was particularly exacerbated during the COVID-19 pandemic, contrary to some theories of urban quieting. Community-based interventions to ameliorate noise and noise annoyance, both public health hazards, are needed in underserved communities.

Autism is a common neurodevelopmental condition characterized by substantial phenotypic heterogeneity, which hinders diagnosis, research, and intervention. A leading example can be found in marked imbalances in language and perceptual skills, where deficits in one domain often co-exist with normal or even superior performance in the other domain. The current work capitalized on multiple data analytics including data-driven subtyping and dimensional approaches to quantify cognitive imbalances in multi-site datasets of individuals diagnosed with autism spectrum disorder (ASD) and neurotypical controls, and assessed structural and functional brain network substrates. Studying cognitive dimensions as well as multimodal neuroimaging signatures in 155 ASD and 151 neurotypical individuals, we observed robust evidence for a structure-function substrate of cognitive imbalances in ASD. Specifically, ASD presented with marked imbalances in cognitive profiles relative to neurotypical controls, characterized by verbal to non-verbal intelligence discrepancy. Different analytical approaches including subtyping and dimensional regression methods converged in showing that these imbalances were reflected in atypical cortical thickening and functional integration of language networks, alongside with sensory and higher cognitive networks. Phenotypic findings could be replicated in an independent sample of 325 ASD and 569 neurotypical controls. Although verbal and non-verbal intelligence are currently considered as specifiers unrelated to the categorical diagnosis of autism, our results show that intelligence disparities are accentuated in ASD and relate to a consistent structure-function substrate affecting multiple brain networks. Our findings motivate the incorporation of cognitive imbalances in future autism research, which may help to parse the phenotypic heterogeneity of autism and potentially inform intervention-oriented subtyping.

Although severe early life stress has been shown to accelerate the development of frontolimbic resting-state functional connectivity (RSFC), less is known about the effects of socioeconomic disadvantage, a prolonged and multifaceted stressor. In a cross-sectional study of 127 participants aged 5–25, we examined whether lower neighborhood socioeconomic status (SES; measured by Area Deprivation Index and neighborhood poverty and educational attainment) was associated with prematurely reduced amygdala-ventromedial prefrontal cortex (vmPFC) RSFC. We further tested whether neighborhood SES was more predictive than household SES and whether SES effects on connectivity were associated with anxiety symptoms. We found reduced basolateral amygdala-vmPFC RSFC at earlier ages in participants from more disadvantaged neighborhoods; this effect was unique to neighborhood SES and absent for household SES. Furthermore, this reduced connectivity in more disadvantaged youth and increased connectivity in more advantaged youth were associated with less anxiety; children who deviated from the connectivity pattern associated with their neighborhood SES had more anxiety. These results demonstrate that neighborhood socioeconomic disadvantage is associated with accelerated maturation of amygdala-vmPFC RSFC and suggest that the pathophysiology of pediatric anxiety depends on a child’s neighborhood socioeconomic characteristics. Our findings also underscore the importance of examining SES effects in studies of brain development.

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD.

BACKGROUND: Prenatal air pollution exposure is associated with reductions in self-regulation and academic achievement. Self-regulation has been separately linked with academic achievement. Understudied, however, are the contributions of pollution exposure to inhibitory control, a facet of self-regulation, and whether pollution-related inhibitory control deficits are associated with impairment in academic achievement. METHODS: Participants were recruited from a prospective birth cohort. Measures of prenatal airborne polycyclic aromatic hydrocarbons (PAH) during the third trimester of pregnancy, inhibitory control (NEPSY Inhibition) at mean age = 10.4 years, and Woodcock-Johnson Tests of Achievement-III at mean age = 13.7 were available for N = 200 participants. Multiple linear regression examined sex-dependent and sex independent associations among prenatal PAH, childhood inhibitory control, and academic achievement during adolescence, and whether childhood inhibitory control mediated associations between prenatal PAH and academic achievement during adolescence, controlling for ethnicity, maternal country of birth, language of prenatal interview, maternal marital status, maternal years of education, material hardship, quality of home caregiving environment, and early life stress. RESULTS: Across all participants, higher prenatal PAH was significantly associated with worse spelling skills (WJ-III Spelling, β = −0.16, 95%Confidence Interval [CI]: 0.30, −0.02, p = .02). Trend level associations between higher prenatal PAH and worse reading comprehension (WJ-III Passage Comprehension, β = −0.13, 95%CI: 0.28, 0.01, p = .07) and math skills (WJ-III Broad Math, β = −0.11, 95%CI: 0.25, 0.03, p = .11) were detected. Across all participants, higher PAH was significantly associated with worse inhibitory control (β = −0.15, 95%CI: 0.29, −0.01 p = .03). Better inhibitory control was significantly associated with better reading comprehension (WJ-III Passage Comprehension, β = 0.22, 95%CI: 0.09, 0.36, p < .002) and math skills (WJ-III Broad Math Index, β = 0.32, 95%CI: 0.19, 0.45, p < .001), and trend level associations with better spelling skills (WJ-III Spelling, β = 0.12, 95%CI: 0.02, 0.26, p = .10). Inhibitory control significantly mediated PAH-related achievement effects for Passage Comprehension (β = −0.61, 95%CI: 1.49, −0.01) and Broad Math Index (β = −1.09, 95%CI: 2.36, −0.03). CONCLUSIONS: Higher prenatal PAH exposure and lower childhood inhibitory control were associated with worse spelling, passage comprehension, and math in adolescence. Notably, childhood inhibitory control mediated PAH exposure-related effects on achievement in adolescents. Identifying these potential exposure-related phenotypes of learning problems may promote interventions that target inhibitory control deficits rather than content specific deficits.

Low childhood socioeconomic status (SES) predisposes individuals to altered trajectories of brain development and increased rates of mental illness. Brain connectivity at birth is associated with psychiatric outcomes. We sought to investigate whether SES at birth is associated with neonatal brain connectivity and if these differences account for socioeconomic disparities in infant symptoms at age 2 years that are predictive of psychopathology. Resting state functional MRI was performed on 75 full-term and 37 term-equivalent preterm newborns (n = 112). SES was characterized by insurance type, the Area Deprivation Index, and a composite score. Seed-based voxelwise linear regression related SES to whole-brain functional connectivity of five brain regions representing functional networks implicated in psychiatric illnesses and affected by socioeconomic disadvantage: striatum, medial prefrontal cortex (mPFC), ventrolateral prefrontal cortex (vlPFC), and dorsal anterior cingulate cortex. Lower SES was associated with differences in striatum and vlPFC connectivity. Striatum connectivity with frontopolar and medial PFC mediated the relationship between SES and behavioral inhibition at age 2 measured by the Infant-Toddler Social Emotional Assessment (n = 46). Striatum-frontopolar connectivity mediated the relationship between SES and externalizing symptoms. These results, convergent across three SES metrics, suggest that neurodevelopmental trajectories linking SES and mental illness may begin as early as birth.

This secondary analysis of a cross-sectional study estimates the prevalence of the nonverbal learning disability cognitive profile in children and adolescents from studies centered around brain imaging in the US and Canada., Key Points Question What is the prevalence of nonverbal learning disability among children and adolescents in North America? Findings In this secondary analysis of a cross-sectional study of 2596 children and adolescents in North America, the population prevalence of nonverbal learning disability ranged from 3% to 4%. Meaning This study showed that 2.2 million to 2.9 million children and adolescents may have nonverbal learning disability; further studies appear to be needed to develop and test interventions for treatment of this disorder., Importance Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial processing but not in reading or verbal ability; in addition, problems in math calculation, visual executive functioning, fine-motor skills, and social skills are often present. To our knowledge, there are no population-based estimates of the prevalence of NVLD in community samples. Objective To estimate the prevalence of the NVLD cognitive profile in 3 independent samples of children and adolescents from studies centered around brain imaging in the US and Canada. Design, Setting, and Participants This cross-sectional study used data from 2 samples recruited from the community and overselected for children with psychiatric disorders (Healthy Brain Network [HBN], January 1, 2015, to December 31, 2019, and Nathan Kline Institute–Rockland Sample [NKI], January 1, 2011, to December 31, 2018) and 1 community-ascertained population sample (Saguenay Youth Study [SYS], January 1, 2003, to December 31, 2012) overselected for active maternal smoking during pregnancy. Main Outcomes and Measures Prevalence of NVLD. Criteria for NVLD were based on clinical records of deficits in visual-spatial reasoning and impairment in 2 of 4 domains of function (fine-motor skills, math calculation, visual executive functioning, and social skills). Sample weighting procedures adjusted for demographic differences in sample frequencies compared with underlying target populations. Inflation factor weights accounted for overrepresentation of psychiatric disorders (HBN and NKI samples). Results Across 3 independent samples, the prevalence of NVLD was estimated among 2596 children and adolescents aged 6 to 19 years (mean [SD] age, 12.5 [3.4] years; 1449 male [55.8%]). After sample and inflation weights were applied, the prevalence of NVLD was 2.78% (95% CI, 2.03%-3.52%) in the HBN sample and 3.9% (95% CI, 1.96%-5.78%) in the NKI sample. In the SYS sample, the prevalence of NVLD was 3.10% (95% CI, 1.93%-4.27%) after applying the sample weight. Across samples and estimation strategies, the population prevalence of NVLD was estimated to range from 3% to 4%. When applied to the US population younger than 18 years, 2.2 million to 2.9 million children and adolescents were estimated to have NVLD. Conclusions and Relevance The findings suggest that the prevalence of NVLD in children and adolescents may be 3% to 4%. Given that few youths are diagnosed with NVLD and receive treatment, increased awareness, identification of the underlying neurobiological mechanisms, and development and testing interventions for the disorder are needed.