Faculty Bibliography

BACKGROUND:HIV status disclosure remains a major challenge among children living with perinatally acquired HIV with many taking treatment up to adolescence without knowing their serostatus. This non-disclosure is influenced by factors like fear of the negative consequences of disclosure. Since HIV status disclosure has been found to have good effects including improving treatment adherence and better mental health outcomes, there is a need to design interventions aimed at improving disclosure rates among children living with HIV. This study aims at adapting a clinic-based pediatric HIV status disclosure intervention and tasking shifting from healthcare workers to caregiver peer supporters in Eastern Uganda. METHODS:The adaptation process involved consultations with caregivers, healthcare workers involved in the care of children living with HIV, researchers in this field, intervention developers, and other experts and stakeholders. This was done through conducting FGDs with HCWs, caregivers, and peer supporters and consultations with researchers in the field of HIV. The original intervention manual was translated to Lusoga which is the commonly spoken dialect in this region. Collected qualitative data were analyzed using an inductive approach to develop themes and subthemes. Written informed consent will be obtained from all participants before participation in the study. RESULTS:A total of 28 participants were involved in the FGDs, while two pediatricians and two HIV researchers/specialists were consulted. Six themes were generated in relation to all suggested changes to the original manual which were related to: (1) sociocultural beliefs/norms/perceptions (5 FGDs), (2) boosting caregiver's confidence for disclosure (5FGDs), (3) disclosure mode, environment, and person (4 FGDs), (4) health facility/system related changes (3 FGDs), (5) reorganization/paraphrasing (3FGDs) and (6) age appropriateness (2FGDs). CONCLUSION/CONCLUSIONS:This study emphasized that whereas some aspects of intervention can apply to various contexts, there is a need for cross-cultural adaptation of interventions before being implemented in settings where they were not developed.

Toddler visual attention development correlates with subsequent language, cognitive, and social developmental outcomes. This study investigates the association of maternal trauma on toddler looking behaviors in 39 mother-child dyads from the Western Cape Province, South Africa. At 15 months postpartum, maternal trauma was assessed using the Life Events Checklist and toddler multisensory attention skills were measured using the Multisensory Attention Assessment Protocol (MAAP) during eye-tracking. We used two-way mixed ANOVA to analyze the association of maternal trauma and MAAP condition with attention maintenance, intersensory matching, and attention shifting. This study provides support for the MAAP's reliability with a sample of 15-month-old toddlers from a low-income setting. We observed a significant interaction between MAAP condition and maternal trauma group on attention maintenance, but pairwise comparisons did not meet the threshold for statistical significance. In a stratified analysis, toddlers of mothers in the low trauma exposure group demonstrated significant differences in attention maintenance, intersensory matching, and attention shifting by condition. Unexpectedly, toddlers of mothers in the high trauma exposure group did not exhibit significant differences in these attentional skills, potentially indicating attentional adaptations. Further research is needed to explore the relationship between the intergenerational transmission of trauma on infant and toddler multisensory attention skills in low-income settings.

BACKGROUND:Concerns about the cardiovascular safety of medications used for the treatment of attention-deficit hyperactivity disorder (ADHD) remain. We aimed to compare the effects of pharmacological treatments for ADHD on haemodynamic values and electrocardiogram (ECG) parameters in children, adolescents, and adults. METHODS:For this systematic review and network meta-analysis, we searched 12 electronic databases, including Cochrane CENTRAL, Embase, PubMed, and the WHO International Clinical Trials Registry Platform, from database inception to Jan 18, 2024, for published and unpublished randomised controlled trials comparing amphetamines, atomoxetine, bupropion, clonidine, guanfacine, lisdexamfetamine, methylphenidate, modafinil, or viloxazine against each other or placebo. Primary outcomes were change in systolic blood pressure (SBP) and diastolic blood pressure (DBP), measured in mm Hg, and pulse, measured in beats per minute, at timepoints closest to 12 weeks, 26 weeks, and 52 weeks. Summary data were extracted and pooled in random-effects network meta-analyses. Certainty of evidence was assessed with the Confidence in Network Meta-Analysis (CINeMA) framework. This study was registered with PROSPERO, CRD42021295352. Before study initiation, we contacted representatives of a UK-based charity of people with lived experience of ADHD-the ADHD Foundation-regarding the relevance of the topic and the appropriateness of the outcomes chosen. FINDINGS/RESULTS:102 randomised controlled trials with short-term follow-up (median 7 weeks [IQR 5-9]) were included, encompassing 13 315 children and adolescents (aged ≥5 years and <18 years; mean age 11 years [SD 3]; of available data, 9635 [73%] were male and 3646 [27%] were female; of available data, 289 [2%] were Asian, 1719 [15%] were Black, and 8303 [71%] were White) and 9387 adults (≥18 years, mean age 35 years [11]; of available data, 5064 [57%] were male and 3809 [43%] were female; of available data, 488 [6%] were Asian, 457 [6%] were Black, and 6372 [79%] were White). Amphetamines, atomoxetine, lisdexamfetamine, methylphenidate, and viloxazine led to increments in haemodynamic values in children and adolescents, adults, or both. In children and adolescents, mean increase against placebo ranged from 1·07 (95% CI 0·36-1·79; moderate CINeMA confidence) with atomoxetine to 1·81 (1·05-2·57; moderate) with methylphenidate for SBP; from 1·93 (0·74-3·11; high) with amphetamines to 2·42 (1·69-3·15; low) with methylphenidate for DBP; and from 2·79 (1·05-4·53; moderate) with viloxazine to 5·58 (4·67-6·49; high) with atomoxetine for pulse. In adults, mean increase against placebo ranged from 1·66 (95% CI 0·38-2·93; very low) with methylphenidate to 2·3 (0·66-3·94; very low) with amphetamines for SBP; from 1·60 (0·29-2·91; very low) with methylphenidate to 3·07 (0·69-5·45; very low) with lisdexamfetamine for DBP; and from 4·37 (3·16-5·59; very low) with methylphenidate to 5·8 (2·3-9·3; very low) with viloxazine for pulse. Amphetamines, lisdexamfetamine, or methylphenidate were not associated with larger increments in haemodynamic values compared with atomoxetine or viloxazine in either children and adolescents or adults. Guanfacine was associated with decrements in haemodynamic values in children and adolescents (mean decrease against placebo of -2·83 [95% CI -3·8 to -1·85; low CINeMA confidence] in SBP, -2·08 [-3 to -1·17; low] in DBP, and -4·06 [-5·45 -2·68; moderate] in pulse) and adults (mean decrease against placebo of -10·1 [-13·76 to -6·44; very low] in SBP, -7·73 [-11·88 to -3·58; very low] in DBP, and -6·83 [-10·85 to -2·81; very low] in pulse). Only four RCTs informed on effects in the medium term and none on the long term. INTERPRETATION/CONCLUSIONS:Practitioners should monitor blood pressure and pulse in patients with ADHD treated with any pharmacological intervention, and not stimulants only. Given the short duration of available randomised controlled trials, new research providing insights on the causal effects of ADHD medications on cardiovascular parameters in the longer term should be funded. FUNDING/BACKGROUND:National Institute for Health and Care Research.

BACKGROUND:Children born very preterm (VPT) are at high risk for attention problems. This study's purpose was to describe the Conners Kiddie Continuous Performance Test (K-CPT) assessment in children born VPT, including rates of clinically elevated scores, change over time, and associations between K-CPT scores and parent reported attention problems. METHODS:We studied 305 children from a multi-site study of children born VPT who completed at least one K-CPT assessment at age 5, 6, and/or 7 years. Parent-reported ADHD symptoms and diagnosis were also collected. We calculated K-CPT completion rates, mean scores, and rates of clinically elevated scores at each timepoint. Linear mixed models examined change over time in K-CPT scores. Correlations and generalized linear models investigated associations between K-CPT scores and ADHD symptoms and diagnoses. RESULTS:K-CPT scores showed expected age-related improvements from age 5-7, with significant intra- and inter-individual variability. Up to 1/3 of children had clinically elevated attention problems and another 1/3 had subclinical elevations. K-CPT scores were modestly correlated with parent-rated ADHD symptoms and children with a parent-reported ADHD diagnosis performed worse on nearly all K-CPT metrics. CONCLUSION/CONCLUSIONS:Performance-based measures like the K-CPT can be useful for research and clinical practice in VPT populations. IMPACT/CONCLUSIONS:Attention problems are a specific area of weakness for children born very preterm. Performance-based tests of attention have benefits and drawbacks compared to parent report measures yet are understudied in this population. We examined one performance-based measure (the Conners Kiddie Continuous Performance Test [K-CPT]) in 305 children born very preterm. We observed improving task scores from age 5-7 years with significant intra- and inter-individual variability, a sizable proportion of children with clinically and subclinically elevated scores, and modest associations between K-CPT scores and parent reported attention problems. The K-CPT could be a useful clinical and research tool in this population.

BACKGROUND/UNASSIGNED:Attention Deficit Hyperactivity Disorder (ADHD) among children younger than 6 years is quite impairing, nearly half these youth with ADHD experience school exclusion from mainstream preschool classes due to related emotional and behavioral outbursts. While a range of behavior rating scales and subjective measures are used to assess these youth, objective methods of assessment and prediction derived from technology have potential to improve therapeutic and academic interventions outcomes for these youths. We hypothesized that biometric sensors would provide objective, highly sensitive and specific information regarding the physiological status of children prior to an impulsive outburst and could be feasibly implemented using a wearable device in the special education classroom. METHODS/UNASSIGNED: = 5 youth from the first grade) of a specialized therapeutic day-school for youth with ADHD and other psychiatric and developmental disorders to examine feasibility of obtaining continuous physiological data associated with behavioral and emotional outbursts through smartwatch use. Children wore a sensor watch during their daily classroom activities for two weeks and trained observers collected data using behavioral logs. Using Ecological Momentary Assessment methodology, to examine correlations between objective sensor data and observer observation. Data collected from parents regarding prior night's sleep was also examined. RESULTS/UNASSIGNED:All participants completed the study. With a few tolerability or palatability issues. Associations were found between physiological and behavioral/questionnaire data. The methodology holds promise for reliably measuring behavioral and emotional outbursts in young children. CONCLUSIONS/UNASSIGNED:among severely dysregulated pre-school aged youth throughout a full school day. This study established the feasibility of utilizing sensor derived physiological data as an objective biomarker of ADHD within the special education therapeutic classroom. Further research with larger samples is required to build a more robust and personalized AI predictive model.

INTRODUCTION/BACKGROUND:Foundational preacademic skills are crucial for academic success and serve as predictors of socioeconomic status, income and access to healthcare. However, there is a gap in our understanding of neurodevelopmental patterns underlying preacademic skills in children across low-income and middle-income countries (LMICs). It is essential to identify primary global and regional factors that drive children's neurodevelopment in LMICs. This study aims to characterise the typical development of healthy children and factors that influence child development in Bahir Dar, Ethiopia. METHODS AND ANALYSIS/METHODS:The Bahir Dar Child Development Study is a cross-sectional study implemented in two health centres, Shimbit and Abaymado and in Felege Hiwot Comprehensive Specialized Hospital (FHCSH) in Bahir Dar, Amhara, Ethiopia. Healthy children between 6 and 60 months of age will be recruited from the health centres during vaccination visits or via community outreach. Young children aged 6-36 months will complete the Global Scale for Early Development. A battery of paper and tablet-based assessments of neurocognitive outcomes including visual and verbal reasoning, executive functions and school readiness will be completed for children aged 48-60 months. Caregivers will respond to surveys covering sociodemographic information, the child's medical history and nutrition, and psychosocial experiences including parental stress and mental health. During a second visit, participants will undergo a low-field MRI scan using the ultra-low-field point-of-care Hyperfine MRI machine at FHCSH. Analyses will examine relationships between risk and protective factors, brain volumes and neurocognitive/developmental outcomes. ETHICS AND DISSEMINATION/BACKGROUND:The study is approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/lRERC/004/2023/Al/05-2024), Mass General Brigham Hospital (2022P002539) and Brown University (STUDY00000474). Findings will be disseminated via local dissemination events, international conferences and publications. TRIAL REGISTERATION NUMBER/BACKGROUND:NCT06648863.

Children presenting comorbid attention-deficit/hyperactivity disorder (ADHD) and depression symptoms have higher risks of later suicidal ideation and attempt. However, it is unclear to what extent this risk stems from individual differences in the genetic predisposition for ADHD and/or depression. We investigated the unique and combined contribution of genetic predisposition to ADHD and depression to suicidal ideation and attempt by early adulthood. Data were from two longitudinal population-based birth cohorts, the Quebec Longitudinal Study of Child Development and the Quebec Newborn Twin Study (total N = 1207). Genetic predisposition for ADHD and depression were measured using polygenic scores. Suicidal ideation and attempt by age 20 years were self-reported via questionnaires. Across the two cohorts, suicidal ideation and attempt were reported by 99 (8.2%) and 75 (6.1%) individuals, respectively. A higher polygenic score for depression was associated with significantly higher risk of suicidal ideation and attempt, while no significant associations were found for ADHD polygenic score. However, we found an interaction between polygenic scores for depression and ADHD in the association with suicide attempt (P = 0.012), but not suicidal ideation (P = 0.897). The association between polygenic score for depression and suicide attempt was significantly stronger for individuals with a higher polygenic score for ADHD. Individuals scoring ≥ 1-SD above the mean for both polygenic scores were at increased risk for suicide attempt compared to individuals with lower scores (OR 4.03, CI 1.64-9.90), as well as compared to individuals scoring ≥ 1-SD above the mean in only depression (OR 2.92, CI 1.01-8.50) or only ADHD (OR 4.88, CI 1.56-15.26) polygenic scores. Our findings suggest that genetic predisposition for ADHD and depression contributes to increase the risk of suicide attempt in a multiplicative, rather that additive, way. Our results contribute to our understanding of the etiology of suicide risk and may inform screening and risk stratification.

IMPORTANCE/UNASSIGNED:Down syndrome, resulting from trisomy 21, is the most prevalent chromosomal disorder and a leading cause of intellectual disability. Despite its significant impact on brain development, research on the white matter microstructure in infants with Down syndrome remains limited. OBJECTIVE/UNASSIGNED:To investigate early white matter microstructure in infants with Down syndrome using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI). DESIGN/UNASSIGNED:Infants were recruited and scanned between March 2019 and May 2024 as participants in prospective studies conducted by the Infant Brain Imaging Study (IBIS) Network. Data were analyzed in October 2024. SETTING/UNASSIGNED:Data collection occurred at five research centers in Minnesota, Missouri, North Carolina, Pennsylvania, and Washington. PARTICIPANTS/UNASSIGNED:Down syndrome and control infants were scanned at 6 months of age. Control infants had no Down syndrome diagnosis and either had a typically developing older sibling or, if they had an older sibling with autism, were confirmed not to meet clinical best estimate criteria for an autism diagnosis. EXPOSURE/UNASSIGNED:Diagnosis of Down syndrome. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The outcome of interest was white matter microstructure quantified using DTI and NODDI measures. RESULTS/UNASSIGNED:A total of 49 Down syndrome (28 [57.14%] female) and 37 control (18 [48.65%] female) infants were included. Infants with Down syndrome showed significant reductions in fractional anisotropy and neurite density index across multiple association tracts, particularly in the inferior fronto-occipital fasciculus and superior longitudinal fasciculus II, consistent with reduced structural integrity and neurite density. These tracts also demonstrated increased radial diffusivity, suggesting delayed myelination. The inferior fronto-occipital fasciculus and uncinate fasciculus exhibited increased neurite dispersion and fanning in Down syndrome infants, reflected by elevated orientation dispersion index. Notably, the optic tracts in Down syndrome infants exhibited a distinct pattern of elevated fractional anisotropy and axial diffusivity, and lower radial diffusivity and orientation dispersion index, suggesting an early maturation of these pathways. CONCLUSIONS AND RELEVANCE/UNASSIGNED:This first characterization of white matter microstructure in Down syndrome infants reveals widespread white matter developmental delays. These findings provide new insights into the early neurodevelopment of Down syndrome and may inform early therapeutic interventions.

The use of Attention-Deficit/Hyperactivity Disorder (ADHD) medications during pregnancy is increasing, raising concerns about potential long-term effects on offspring. This study investigates in utero exposure to methylphenidate, amphetamines and atomoxetine and risk of offspring neurodevelopmental disorders (NDDs). The population-based cohort study identified from Swedish registers included 861,650 children born by 572,731 mothers from 2008-2017. We categorized exposure based on redeemed medication during pregnancy and compared exposed children to those whose mothers discontinued medication before conception. Main outcomes were any NDD, including ADHD and autism spectrum disorder (ASD). Cox proportional hazards regression estimated hazard ratios (HRs), adjusting for maternal psychiatric and sociodemographic factors. Sensitivity analyses included stratifications by medication type, timing, and duration of exposure, and sibling comparisons. We also performed a meta-analysis combining data from the present study with those from a previous Danish study. Results showed no increased risk for any NDD (HR_adjusted 0.95, 95% CI 0.82-1.11), ADHD (HR_adjusted 0.92, 95% CI 0.78-1.08), or ASD (HR_adjusted 0.86, 95% CI 0.63-1.18). Sensitivity analyses showed consistent patterns of no increased risks across different exposure durations, medication types and between siblings. Meta-analyses further supported the findings (pooled HR for any NDD 1.00, 95% CI 0.83;1.20). Our study provides evidence that in utero exposure to ADHD medications does not increase the risk of long-term NDDs in offspring. This study replicates safety data for methylphenidate and extends it with new safety data on amphetamines and atomoxetine. These findings are crucial for informing clinical guidelines and helping healthcare providers and expectant mothers make informed decisions.