Faculty Bibliography

Individuals with DS develop Alzheimer's disease (AD) neuropathology, including endosomal-lysosomal system abnormalities and degeneration of basal forebrain cholinergic neurons (BFCNs). We investigated whether maternal choline supplementation (MCS) affects early endosome pathology within BFCNs using the Ts65Dn mouse model of DS/AD. Ts65Dn and disomic (2N) offspring from dams administered MCS were analyzed for endosomal pathology at 3-4 months or 10-12 months. Morphometric analysis of early endosome phenotype was performed on individual BFCNs using Imaris. The effects of MCS on the endosomal interactome were interrogated by relative co-expression (RCE) analysis. MCS effectively reduced age- and genotype-associated increases in early endosome number in Ts65Dn and 2N offspring, and prevented increases in early endosome size in Ts65Dn offspring. RCE revealed a loss of interactome cooperativity among endosome genes in Ts65Dn offspring that was restored by MCS. These findings demonstrate MCS rescues early endosome pathology, a driver of septohippocampal circuit dysfunction. The genotype-independent benefits of MCS on endosomal phenotype indicate translational applicability as an early-life therapy for DS as well as other neurodevelopmental/neurodegenerative disorders involving endosomal pathology.

Autistic youth are more likely to experience maltreatment, victimization, and other traumatic events. However, it can be difficult to identify trauma-related symptoms in autistic youth, especially in those with limited verbal communication. In this study, we compared the prevalence of trauma-related diagnoses given to youth with autism spectrum disorder (ASD) to those given to youth without ASD who presented to a specialized pediatric psychiatric emergency department. We found that youth with ASD were 42% less likely to receive trauma-related diagnoses than youth without ASD. As there is evidence that youth with ASD are no less likely to experience traumatic events compared with youth without ASD, one possible explanation for this result is that trauma-related symptoms are missed during emergency psychiatric evaluations. Developing trauma screening instruments specifically designed for the needs of youth with ASD is an outstanding need.

The goal of our study was to describe the availability of community child and adolescent mental health services, trauma-informed care, and the geographic accessibility of these services for juvenile justice-involved (JJ) youth who received mental health services while in secure detention. Data collection occurred through direct contact with the child and adolescent outpatient clinics listed on the New York State Office of Mental Health website. Zip codes were collected from the juvenile secure detention census. Of the clinics contacted, 88.5 percent accepted JJ youth; however, 43.5 percent accepted them on a conditional basis. Only 62.1 percent offered trauma-informed care, including evidence-based interventions and unspecified care. Although 84.5 percent of the clinics that would accept this population reported currently accepting new patients, reported wait times were as high as six or more months. When JJ residents' home zip codes and those of the clinics were geographically mapped, there were few clinics in the zip codes where most residents lived. The clinics that accepted youth on a conditional basis often refused high-risk patients, essentially ruling out a large majority of this population. The geographical inaccessibility of these clinics limits their ability to provide care for this vulnerable population.

IMPORTANCE/UNASSIGNED:Stress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown. OBJECTIVE/UNASSIGNED:To examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Data for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024. EXPOSURES/UNASSIGNED:Prenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed. RESULTS/UNASSIGNED:The COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.

IMPORTANCE/UNASSIGNED:Neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) are increasingly common. Individuals with NDDs have heightened obesity risks, but long-term data on body mass index (BMI) trends over time in this population are lacking. OBJECTIVE/UNASSIGNED:To assess secular BMI changes from 2004 to 2020 among children with NDDs compared with those without NDDs. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This repeated cross-sectional study used data from the Child and Adolescent Twin Study in Sweden. Children born between January 1, 1992, and December 31, 2010, were screened for neurodevelopmental symptoms using the Autism-Tics, ADHD, and Other Comorbidities inventory between July 2004 and April 2020 when they were 9 or 12 years of age. Data analysis was conducted between September 27, 2023, and January 30, 2024. MAIN OUTCOMES AND MEASURES/UNASSIGNED:BMI percentiles (15th, 50th, and 85th) were modeled using quantile regression and compared between youths with and without NDDs. Secular changes in BMI percentiles over time spanning 2004 to 2020 were evaluated and stratified by NDD subtype. RESULTS/UNASSIGNED:The cohort included 24 969 Swedish twins (12 681 [51%] boys) born between 1992 and 2010, with mean (SD) age of 9 (0.6) years. Of these, 1103 (4%) screened positive for 1 or more NDDs, including ADHD, ASD, and/or learning disability. Results indicated that at the 85th BMI percentile, there was a greater increase in BMI from 2004 to 2020 among youths with NDDs compared with those without NDDs (β for interaction [βint] between NDD status and time, 1.67; 95% CI, 0.39-2.90). The greatest divergence was seen for ASD (βint, 2.12; 95% CI, 1.26-3.70) and learning disability (βint, 1.92; 95% CI, 0.65-3.82). Within the latest cohort (2016-2020), the 85th BMI percentile was 1.99 (95% CI, 1.08-2.89) points higher among children with NDDs compared with those without NDDs. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this repeated cross-sectional study, at the higher end of the BMI distribution, children with NDDs had significantly greater increases in BMI compared with peers without NDDs over a 16-year period, highlighting an increasing risk of overweight over time in youths with NDDs compared with those without NDDs. Targeted obesity prevention efforts for this high-risk population are needed.

IMPORTANCE/UNASSIGNED:Increasing numbers of unaffected individuals could benefit from genetic evaluation for inherited cancer susceptibility. Automated conversational agents (ie, chatbots) are being developed for cancer genetics contexts; however, randomized comparisons with standard of care (SOC) are needed. OBJECTIVE/UNASSIGNED:To examine whether chatbot and SOC approaches are equivalent in completion of pretest cancer genetic services and genetic testing. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This equivalence trial (Broadening the Reach, Impact, and Delivery of Genetic Services [BRIDGE] randomized clinical trial) was conducted between August 15, 2020, and August 31, 2023, at 2 US health care systems (University of Utah Health and NYU Langone Health). Participants were aged 25 to 60 years, had had a primary care visit in the previous 3 years, were eligible for cancer genetic evaluation, were English or Spanish speaking, had no prior cancer diagnosis other than nonmelanoma skin cancer, had no prior cancer genetic counseling or testing, and had an electronic patient portal account. INTERVENTION/UNASSIGNED:Participants were randomized 1:1 at the patient level to the study groups at each site. In the chatbot intervention group, patients were invited in a patient portal outreach message to complete a pretest genetics education chat. In the enhanced SOC control group, patients were invited to complete an SOC pretest appointment with a certified genetic counselor. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were completion of pretest cancer genetic services (ie, pretest genetics education chat or pretest genetic counseling appointment) and completion of genetic testing. Equivalence hypothesis testing was used to compare the study groups. RESULTS/UNASSIGNED:This study included 3073 patients (1554 in the chatbot group and 1519 in the enhanced SOC control group). Their mean (SD) age at outreach was 43.8 (9.9) years, and most (2233 of 3063 [72.9%]) were women. A total of 204 patients (7.3%) were Black, 317 (11.4%) were Latinx, and 2094 (75.0%) were White. The estimated percentage point difference for completion of pretest cancer genetic services between groups was 2.0 (95% CI, -1.1 to 5.0). The estimated percentage point difference for completion of genetic testing was -1.3 (95% CI, -3.7 to 1.1). Analyses suggested equivalence in the primary outcomes. CONCLUSIONS AND RELEVANCE/UNASSIGNED:The findings of the BRIDGE equivalence trial support the use of chatbot approaches to offer cancer genetic services. Chatbot tools can be a key component of sustainable and scalable population health management strategies to enhance access to cancer genetic services. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT03985852.

Efforts to bolster the school readiness of Latinx children from low-income homes in the United States have focused on fostering parent engagement in children"™s education. Measurement of parent engagement in early childhood however, has been critiqued for having too narrow a focus on school-based involvement and missing other aspects of Latinx parent engagement. Using a recently developed culturally sensitive assessment of Latinx parent engagement, we test for associations between dimensions of Latinx parent engagement in learning and indicators of school readiness in a diverse sample of Latinx families (n = 114). We find significant associations between multiple dimensions of Latinx parent engagement and indicators of child school readiness. In addition to promoting parent-teacher connections, efforts to support Latinx school readiness equitably are encouraged to attend to various culturally relevant aspects of Latinx parent engagement in early childhood. In particular, investing in programing that supports parents"™ well-being and capacity for home-based engagement in learning may be a promising way to support the school readiness of Latinx children living in historically disinvested neighborhoods.

BACKGROUND/UNASSIGNED:Preterm birth (birth at <37 completed weeks gestation) is a significant public heatlh concern worldwide. Important health, and developmental consequences of preterm birth include altered temperament development, with greater dysregulation and distress proneness. AIMS/UNASSIGNED:The present study leveraged advanced quantitative techniques, namely machine learning approaches, to discern the contribution of narrowly defined and broadband temperament dimensions to birth status classification (full-term vs. preterm). Along with contributing to the literature addressing temperament of infants born preterm, the present study serves as a methodological demonstration of these innovative statistical techniques. STUDY DESIGN/UNASSIGNED:= 402) born at term, with data combined across investigations to perform classification analyses. SUBJECTS/UNASSIGNED:Participants included infants born preterm and term-born comparison children, either matched on chronological age or age adjusted for prematurity. OUTCOME MEASURES/UNASSIGNED:Infant Behavior Questionnaire-Revised Very Short Form (IBQ-R VSF) was completed by mothers, with factor and item-level data considered herein. RESULTS AND CONCLUSIONS/UNASSIGNED:Accuracy estimates were generally similar regardless of the comparison groups. Results indicated a slightly higher accuracy and efficiency for IBQR-VSF item-based models vs. factor-level models. Divergent patterns of feature importance (i.e., the extent to which a factor/item contributed to classification) were observed for the two comparison groups (chronological age vs. adjusted age) using factor-level scores; however, itemized models indicated that the two most critical items were associated with effortful control and negative emotionality regardless of comparison group.

BACKGROUND:The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS:3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS:Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION/CONCLUSIONS:The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT/CONCLUSIONS:Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.