JAMA Pediatrics

Background and ObjectivesPatient portals allow adolescents and caregivers of pediatric patients to better engage with health care, improving their medication adherence, health knowledge, self-efficacy, and receipt of preventive care. However, disparities in access to and comfort with using these portals persist. Hospitalization represents a promising opportunity to address these disparities among a high-risk population. Design/MethodsWe conducted a cross-sectional analysis to identify disparities in portal enrollment and use (logins, messaging, or telehealth use) among patients admitted to two pediatric hospitals within a single health system from 2022-2024. We calculated unadjusted rates of portal enrollment and use before, during, and after hospitalization, stratified by patient-level factors (age, race/ethnicity, insurance coverage, medical complexity), household-level factors (preferred language), and population-level factors (neighborhood opportunity). We then used multivariable logistic regression to identify associations between these factors and portal enrollment and use. ResultsAmong 40,371 hospitalized patients, 93% had enrolled in our patient portal. Patients who identified as Non-Hispanic Black, were publicly insured, had a household language other than English, and lived in lower opportunity neighborhoods had significantly decreased odds of portal enrollment and use before, during, and after hospitalization. ConclusionsDespite high overall rates of portal enrollment among our patient population, we observed persistent disparities in portal enrollment and use. Efforts to promote equitable portal usage among hospitalized children may be most effective when focused on families who are publicly insured, prefer languages other than English, or live in lower opportunity neighborhoods.

BackgroundEarly relational health (ERH) is thought to buffer the association between early life stress (ELS) and child psychopathology, but limited work has directly tested this hypothesis. ObjectiveWe evaluate mother-infant emotional connection, a facet of ERH, as a buffer of combined and individual impacts of specific ELS exposures (maternal mental health and interpartner conflict) on child psychopathology. MethodsParticipants included mother-infant dyads (n=100) followed longitudinally in the COMBO cohort, a convenience sample recruited during the COVID-19 pandemic. ERH was assessed via a remote mother-infant face-to-face interaction at ~4mo postpartum coded for emotional connection. An ELS Index was estimated using measures of maternal self-reported postpartum anxiety, depression, stress, and inter-partner conflict. Mothers rated emerging signs of child psychopathology symptoms at 2-3yrs on the Child Behavior Checklist for Ages 1[1/2]-5 (CBCL/1[1/2]-5). Main and interactive effects of ELS and ERH on emerging signs of child psychopathology were tested in generalized linear models. ResultsGreater ELS Index scores were associated with a higher rate of emerging psychopathology symptoms (aRR=1.32, p<.001), but this association was moderated by a significant interaction between the ELS Index and emotional connection (aRR=0.99, p=.03), such that at higher levels of emotional connection, the association of ELS with child psychopathology symptoms was weaker (aRR=1.16, p<.001). ConclusionParent-infant emotional connection may buffer the impact of ELS exposure in infancy on child emerging symptoms of psychopathology in toddlerhood, supporting efforts to invest in pediatric interventions that target ERH.

ImportanceWhole genome sequencing (WGS) is increasingly used to diagnose severely ill children, yet the long-term impact of a genetic diagnosis on healthcare utilization and resource allocation remains poorly understood. ObjectiveTo determine the influence of a genetic diagnosis via WGS on long-term healthcare utilization metrics in severely ill children. DesignA retrospective cohort study using data from the Next Generation Children study (2016-2020) with record linkage and analysis of primary care records conducted between 2022 and 2024. SettingA multicenter study involving primary care and hospital records linked via the UK National Health Research Institute (NIHR) Rare Disease Bioresource, Cambridge, UK. ParticipantsA referred sample of 270 severely ill children who underwent WGS. Exposure(s)Receipt of a genetic diagnosis (87/270; 32%) compared to those who remained undiagnosed (183/270; 68%) following WGS. Main Outcome(s) and Measure(s)Comparison of 36 healthcare utilization parameters, including hospitalizations, primary care prescriptions, and diagnostic tests. ResultsAmong the 270 children analyzed, those receiving a genetic diagnosis (n=87) exhibited significantly higher overall healthcare utilization compared to undiagnosed peers (n=183). This included increased hospital admissions and outpatient visits, particularly for neurodevelopmental and seizure-related conditions. Diagnosed children received a higher volume of neurological, gastrointestinal, and nutritional prescriptions. The most pronounced differences in utilization were observed in children initially diagnosed in neonatal (NICU) or pediatric (PICU) intensive care settings. While genetic diagnosis was not associated with reduced healthcare costs during the study period, it was linked to more targeted, condition-specific medical care. Conclusions and RelevanceWGS diagnosis facilitates the integration of specialist care and the alignment of healthcare resources with the specific needs of children with complex disorders. These findings suggest that while costs may not decrease immediately, a diagnosis enables more precise and targeted clinical management. Key PointsO_ST_ABSQuestionC_ST_ABSDoes a genetic diagnosis through whole genome sequencing influence long-term healthcare utilization in severely ill children? FindingsIn this cohort study of 270 children, those who received a genetic diagnosis demonstrated significantly greater overall healthcare utilization, including more hospitalizations and targeted prescriptions, compared with undiagnosed children. MeaningA genetic diagnosis facilitates the integration of specialized, condition-specific care, helping to align healthcare resources with the individual needs of children with complex disorders.

ObjectiveTo examine whether screen time predicts interindividual variability regarding pubertal development across adolescence. Study designThis longitudinal cohort study included 10786 participants (47.9% female) from the Adolescent Brain Cognitive Development (ABCD) study. First, associations were examined between average daily screen time (hours/day, parent-reported Screen Time Survey) at baseline (mean age = 9.91 {+/-} 0.63 years) and pubertal timing, derived from Pubertal Development Scale (PDS) scores through 4-year follow-up (mean age = 14.08 {+/-} 0.68 years) and standardized by age and sex. Second, associations were examined between screen time groups (very low: 0-1.29 h/day; low: 1.29-2.07 h/day; moderate: 2.07-2.86 h/day; high: 2.86-4.0 h/day; very high: 4.00-12.43 h/day) and age at mid-puberty, defined as the age at first parent report of Pubertal Development Scale (PDS) category at least 3. ResultsIn linear mixed models adjusting for age, sex, race/ethnicity, socioeconomic status, BMI, and physical activity, higher log-transformed screen time at baseline was associated with more advanced pubertal timing at 1-, 2- and 3- year follow-ups, with the strongest effect observed at year 2 (standardized {beta}=0.07 [95%-CI, 0.05 to 0.10]). The associations were more pronounced in girls. The group of participants with very high screen time reached mid-puberty 2.47 months earlier [adjusted effect size, 95%-CI, -3.38 to -1.56) than participants with very low screen time. ConclusionThese findings suggest that screen time in late childhood is linked with earlier pubertal development and highlight its relevance for parental guidance on preadolescents screen media use.

BackgroundGastrointestinal (GI) symptoms are prevalent, persistent, and frequently disabling among autistic individuals. Existing research has focused predominantly on children, with comparatively little attention to GI experiences in adulthood. Qualitative studies in pediatric populations document substantial unmet GI-related healthcare needs, including negative healthcare encounters and limited access to autism-informed services. MethodsUsing a community-based participatory research (CBPR) framework, we conducted qualitative interviews with 26 participants (21 autistic adults, 5 parents reporting on behalf of an adult autistic child), of varying race, sexual orientation, genders, socioeconomic and educational statuses, and ages. Interviews were conducted on Zoom, ranging from 22-110 minutes long, exploring the physical, emotional, and functional impacts of GI symptoms; how these experiences relate to autism; barriers to treatment; and participants needs and priorities for improving GI health care (priorities reported elsewhere). We conducted a reflexive thematic analysis following Braun and Clarke, using an interpretivist-constructivist epistemological stance. Coding and theme development were inductive and data-driven. Themes were refined collaboratively through repeated engagement with the data, analytic memoing, and discussion of areas of interpretive uncertainty until shared meaning and coherent thematic structure were achieved. Once the codebook and thematic structure were finalized, all transcripts were systematically coded for analysis. ResultsParticipants described gastrointestinal symptoms as chronic, unpredictable, and highly consequential, shaping physical functioning, emotional wellbeing, daily routines, autonomy, and social participation. Symptoms were understood as arising from interacting biological, sensory, emotional, and contextual factors, with triggers often difficult to identify or anticipate. Experiences with healthcare were frequently characterized by dismissal, communication barriers, system complexity, and prior trauma, contributing to delayed or avoided care and heightened distress. In response, autistic adults and caregivers relied on individualized, trial-and-error management strategies - including avoidance of triggers, routine and environmental planning, dietary and pharmacologic approaches, and sensory or emotional regulation - alongside social support and peer communities to cope with persistent uncertainty and limited clinical guidance. ConclusionGI symptoms in autistic adults frequently have dramatic negative impacts on everyday life, reducing both quality of life and restricting the ability to fully engage in society and desired activities. Despite the clear magnitude of impact, knowledge and support are lacking and management remains difficult, confusing, and often unsuccessful. Improving care will require multi-layered, neurodiversity-informed approaches that recognize autistic adults as central knowledge-holders and active partners in research and clinical decision-making.

BackgroundPediatric long COVID is associated with substantial symptom burden, yet evidence-based pharmacologic treatments remain limited. Low-dose naltrexone (LDN) has been proposed as a potential symptomatic therapy, but data in pediatric populations is lacking. MethodsWe conducted a retrospective analysis of pediatric and young adult patients ([&le;]25 years) with a clinical diagnosis of long COVID who were prescribed LDN between July 2020 and July 2025 at three multidisciplinary pediatric long COVID programs in the United States. Deidentified clinical data were extracted from medical records. Outcomes included symptom prevalence, dosing practices, treatment continuation or discontinuation, adverse effects, and available patient-reported quality-of-life measures (PedsQL and PROMIS(R)). FindingsThe study included 62 patients (mean age, 15.6 years [range, 8-23]; 53.2% male and 46.8% female). Fatigue was nearly universal (98.4%), followed by headaches (87.1%), brain fog (74.2%), dizziness/lightheadedness (67.7%), anxiety (66.1%), and post-exertional malaise (56.5%). LDN-treated patients demonstrated a higher prevalence of neurocognitive and autonomic symptoms, compared to general clinic cohorts. Most patients (71.0%) reported no adverse effects; the most common were vivid dreams (9.7%) and insomnia (9.7%). At follow-up, 66.1% of patients remained on LDN. Medication discontinuation was attributed to perceived lack of benefit (43.8%) or side effects (25.0%). Baseline quality-of-life measures at initiation showed marked impairment: PedsQL Physical Health (M=38.0, SD=20.9) and Multidimensional Fatigue (M=35.7, SD=15.8) scores were low. PROMIS scores indicated reduced physical functioning (M=36.8, SD=8.7) and cognitive functioning (M=40.8, SD=7.6), with elevated fatigue (M=68.0, SD=10.4) and pain interference (M=58.6, SD=8.2) relative to population norms. The study was not designed to assess efficacy. InterpretationLDN was primarily prescribed to patients with prominent fatigue, neurocognitive symptoms, and autonomic dysfunction, and was generally well tolerated. These findings provide descriptive evidence of real-world prescribing practices and support the need for clinical trials to systematically evaluate LDNs efficacy in pediatric long COVID.

Patient portals are designed to enhance patient and caregiver engagement by providing access to health information, communication with care teams, and telehealth services, yet their impact on health care utilization among hospitalized children is not well understood. In this cross-sectional study, we examined associations between patient portal enrollment and use and hospitalization outcomes among 40,377 children admitted to an urban quaternary or suburban tertiary pediatric hospital between 2022 and 2024. Portal activity was defined by enrollment and any use (login, messaging, or telehealth) within specified periods before or during hospitalization. Using multivariable regression models adjusted for sociodemographic factors, neighborhood opportunity, insurance type, language, medical complexity, hospital site, and year, we evaluated associations with critical care admission, hospital length of stay (LOS), and 30-day readmissions. Portal enrollment and use in the year prior to hospitalization were associated with significantly lower odds of critical care admission and shorter LOS, with average reductions of 1.56 days for enrollment and 1.21 days for use. Neither portal enrollment nor use was significantly associated with 30-day readmissions. Future research should explore any potential mechanisms facilitating lower acuity at admission and shorter hospitalizations for those engaged with digital health.

BackgroundChildren in contact with childrens social care (CSC) services have high levels of hospital utilisation, but patterns before and after referral remain insufficiently understood. ObjectiveTo evaluate healthcare utilisation two years before and after CSC referral. Participants and settingRetrospective cohort using ECHILD linked health and social care data, including children with a first CSC referral between 2009 and 2018 in England. MethodsWe compared monthly planned and unplanned hospital contact rates for Children in Need, Children under Protection Plans, and Children Looked After with age-sex-matched cohorts. We used interrupted time series analysis to examine how healthcare utilisation changed following referral. We also explored reasons for hospital contacts. ResultsWe analysed >12 million hospital contacts for 1,014,330 Children in Need, 204,240 Children under Protection Plan and 177,640 Children Looked After. Children Looked After had the highest average number of total contacts (11.8 per child over a 4 year period), followed by Children in Need (8.8) and Children under Protection Plans (8.4). All CSC groups had about twice the contacts of matched peers. Healthcare utilisation increased sharply prior to referral, with a peak around referral. After referral, planned care increased and unplanned care decreased, with pre-referral upward trends slowing or reversing. The most common reason for healthcare utilisation was mental health-related ConclusionsAt a population level, CSC referral marks a pivotal point in healthcare utilisation, with a shift from unplanned to planned care. This may reflect more structured engagement with health services and coordinated support for children and families.

BackgroundLinked administrative data covering whole populations are fundamental resources for longitudinal studies of children with rare conditions (cases) and unaffected peers (comparators). Data minimisation regulations sometimes limit the number of comparators per case (sampled comparators, SC), with unknown impact on study findings. MethodsUsing Monte Carlo draws, we simulated 100 000 children with and without an exemplar condition, congenital hypothyroidism (CHT), with covariates (sex and comorbidity). Three outcomes (Y: Maths tests z-score, age 11 years; L: achieving expected Maths attainment (binary); T: months to neurodevelopmental disorder diagnosis) were modelled as linear combinations of CHT, sex and comorbidity. Varying parameters (comorbidity prevalence; comorbidity-CHT association; CHT effect on Y/L/T) factorially produced 36 data-generating mechanisms (DGMs). We used regression coefficients (CHT effect), standard errors (SEs) and p-values from 1000 simulations to evaluate power, precision and bias, comparing SCn (n=5/10/15/25/50/100) versus full cohort (FC). ResultsMean p-values and SEs for SC25 generally deviated [&le;]5% versus FC with medium effects (z-score difference=0.3; odds/hazard ratios[&ge;]2), and [&le;]2% for large effects (z-score difference[&ge;]0.6; odds/hazard ratios[&ge;]5). For all outcomes, no SC nor FC had sufficient power (>80% of p-values[&le;]0.05) with small or medium effects, whilst all SC had sufficient power with large effects. Compared with FC, precision loss for SC25 was 2.0-4.3%, 5.0-8.9%, 6.7-15.5% for Y, L, T respectively. SC was not associated with bias. ConclusionSC25 provided comparable performance as FC for rare disease studies under several scenarios, but small effects posed challenges, notwithstanding sampling. This approach generates cost-effective recommendations for study design and data minimisation. Key messagesWhat is the minimum ratio of children without disease (comparators) to children with disease (cases) needed to reliably quantify differences in health and educational outcomes, if whole population data were not accessible? Sampling 25 comparators per case would generally provide comparable inferences as whole population data for typical scenarios likely to be encountered in longitudinal studies involving children with rare diseases. Decreasing sample sizes helps studies to fulfil data minimisation principles, guides negotiations with data providers and facilitates approvals by research governance bodies, without compromising the quality of research findings.

Sleep is essential for childrens health and development, yet sleep problems are common worldwide. Comfort items such as soft toys or blankets are widely used to promote independent sleep, but their effects have not been evaluated in a randomised controlled trial (RCT). The REST trial emerged from a child-led citizen-science study (The Kids Trial) where children co-created and designed the trial. Therefore, this paper had two aims, to assess whether sleeping with a comfort item affected childrens sleep; and to assess the feasibility of conducting an online, child-led citizen-science RCT. The REST (Randomised Evaluation of Sleeping with a Toy or comfort item) trial was an online two-arm, parallel-group, superiority RCT. Children, aged 7 to 12 years, were randomised (1:1) to either sleep with a self-chosen comfort item ( Try-it-Out group) or refrain from using one ("Wait-and-See" group) for one week. The primary outcome was sleep-related impairment (SRI; PROMIS Pediatric Short Form v1.0 SRI 4a). The secondary outcome was overall sleep quality (Single Item Sleep Quality Scale, SQS). Analyses followed an intention-to-treat principle using mixed-effects models adjusted for baseline measures. A total of 139 children from 11 countries were randomised (mean age: 9.8 years; 45% female); 101 children (73%) completed post-test measures at one week. The adjusted mean difference (Intervention minus Control) in SRI T-scores was -0.53 (95% CI: -3.40 to 2.34; p = 0.714), equivalent to approximately -0.05 SD on a scale where 10 points = 1 SD. This indicated a trivial effect, well below the minimal important difference (MID) of 3 points. The adjusted mean difference in SQS was 0.28 (95% CI: 0.01 to 0.55; p = 0.040), suggesting a small and uncertain difference in favour of the intervention group. However, this result was not supported in subsequent sensitivity or exploratory subgroup analyses. No adverse events were reported. Sleeping with a comfort item for one week did not influence sleep-related impairment. A small statistically significant difference in perceived sleep quality was observed in the primary analysis, but was not sustained in the per-protocol analysis. Together, these findings suggest that any benefit of comfort items for sleep is small and uncertain. The trial demonstrated that children can meaningfully engage in online, citizen-science research, supporting the feasibility of child-led RCTs. Trial registrationISRCTN13756306 (registered 10 January 2025)

Typically-developing children progress through three distinct language-comprehension phenotypes. 1) The Command Phenotype, emerging by age 2, is characterized by understanding single words and simple commands. 2) The Modifier Phenotype, observed around age 3, is characterized by understanding adjective-noun combinations. 3) The Syntactic Phenotype, reached by age 4, is characterized by understanding stories and complex syntactic structures. This study examined language-comprehension trajectories in autistic children using parent-submitted longitudinal assessments from 6,736 participants, with a mean observation period of 2.2 {+/-} 1.3 years, spanning ages 1.5-22 years. Autistic children advanced through the same three phenotypes as neurotypical children but showed systematic differences. Increasing autism severity both reduced the likelihood of attaining higher-level phenotypes and lengthened the time required to reach them. The Command Phenotype was retained by 11%, 19%, and 39% of individuals with mild, moderate, and severe autism. Among individuals who advanced, median ages for acquiring the Modifier Phenotype were 3.7, 4.6, and 5.7 years for those with mild, moderate, and severe autism. For the Syntactic Phenotype, median ages were 4.8, 5.9, and 6.5 years across the same groups. These findings provide the first large-scale quantification of language-comprehension trajectories in autism and underscore the importance of early intervention.

PurposeGenetic diseases often present and are first diagnosed in the neonatal intensive care unit (NICU). Accurate identification of neonates with genetic diagnoses (GDs) in electronic health records (EHR) would enable a more complete understanding of their phenotypic spectrum, advancing care and personalized medicine. Prior research has used International Classification of Diseases (ICD) billing codes as proxies for GDs, though their accuracy for detecting confirmed GDs is uncertain. We evaluate the ICD codes for neonates with confirmed GDs and compare ICD billing code patterns between neonates with and without GD in two independent NICU cohorts. MethodsRetrospective analysis of patients admitted to the Boston Childrens Hospital (BCH) level IV NICU (1,344 neonates) and Nationwide Childrens Hospital (NCH)s neonatal network (33,315 neonates, mixed Level III/IV). For both cohorts, GDs captured by phecodes, aggregates of ICD codes, were compared with confirmed GDs. Two separate phenome-wide association studies (PheWAS) compared phecode patterns between neonates with GDs and those without, adjusting for sex, age at admission, gestational age, and NICU length of stay. ResultsGenetic phecodes were able to correctly identify 43.5% of neonates that received a GD in the BCH or NCH NICUs. Among 719 individuals with two or more genetic phecodes at BCH or NCH, 566 (78.72%) had a true GD. The BCH PheWAS analysis revealed a statistically significant positive association with atrioventricular septal defects and a negative association with bronchopulmonary dysplasia. The NCH pheWAS revealed 179 significantly associated phecodes, including many congenital anomalies. ConclusionThe use of ICD codes to identify NICU infants with GDs is neither sensitive nor accurate, though phecode analysis demonstrated stronger accuracy than sensitivity. Our data highlight clinical features of NICU infants more commonly seen in those that receive a GD (congenital heart defects) and those that are not (BPD). Our results can help to better predict and identify NICU neonates that receive a GD.

BackgroundOrganization, time management, and planning (OTMP) difficulties are associated with academic underachievement. OTMP skills training programs are effective in reducing OTMP deficits and improving academic performance. A randomized controlled trial of Homework, Organization, and Planning Skills (HOPS) for students ages 11-14 (1) found it to be effective with medium to large effects. In that study, HOPS was provided by counselors employed by the research team. This study is a replication examining HOPS under more authentic conditions when providers are employed by schools serving enrolled students. The primary aim is to evaluate HOPS offered by school providers in relation to treatment-as-usual/waitlist (TAU/WL). To respond to limited school resources post-COVID-19, HOPS is also provided by research team members, creating the opportunity to replicate the findings from the prior trial (1) and explore differential effectiveness when HOPS is implemented by school vs. research providers. MethodsStudents in about 30 schools serving students ages 11-14 will be enrolled. Schools are randomly assigned to HOPS vs. TAU/WL on a 2:1 ratio. Students assigned to HOPS schools are randomly assigned to a school vs. research provider on a 1:1 basis. Providers receive two hours of training and additional assistance on request. Child outcomes related to OTMP skills, homework, and academic performance are assessed at post-treatment, 6-month (from baseline) follow-up, and 12-month follow-up. HOPS sessions are video recorded for fidelity coding. Potential effect modifiers include student ADHD, oppositional defiant, and internalizing symptoms, and family socioeconomic level. Analyses will use mixed effects modeling. The goal of the study is to enroll 135 participants, yielding a minimal detectable effect size of 0.50, within the expected range based on prior research. DiscussionThe study is unique in examining intervention implementation and effectiveness when intervention is provided under authentic practice conditions. Trial RegistrationThis study was registered with clinicaltrials.gov (NCT04465708).

BackgroundCaregiver skills training programmes are well-researched in the fields of autism and intellectual disability, but children with motor disorders such as cerebral palsy remain underrepresented despite their high prevalence. These caregivers face unique challenges, and group programmes may provide family-centred care through information provision, problem-solving and peer support. MethodsSystematic searches of five databases (CINAHL, Medline, Embase, PsychINFO and ERIC) were conducted for interventional studies of group programmes aiming to improve the skills, confidence and wellbeing of caregivers of children with neurodisability focusing on motor disorders. Data were extracted on study and intervention characteristics and outcomes. Risk of bias was assessed, effect sizes calculated, and results summarised descriptively using forest plots. ResultsOf 6093 studies identified, 21 studies met inclusion criteria (nine randomised-controlled trials, two quasi-experimental and ten pre-post designs). Most reported on programmes developed in resource-constrained settings and addressed caregiver skills, coping strategies, or health-promoting behaviours. Outcomes were grouped according to caregiver wellbeing, caregiver skills and confidence, and social support and family functioning. Child outcomes were reported separately. Most caregiver outcomes showed positive effects, though most studies had high risk of bias due to self-reported outcomes and lack of blinding of intervention allocation and outcome measurement. DiscussionGroup-based training programmes show promise for improving caregiver skills and wellbeing. Clinicians and stakeholders in high-income countries may learn from these innovations in low-resource settings. Future research should strengthen protocol reporting, address attrition, control for confounding factors, and establish a core set of caregiver-reported outcomes to better capture programme impact. Systematic review registrationPROSPERO registration CRD42024595002

PurposeWhile genomic testing is integral to pediatric inborn errors of immunity (IEI) care, few studies have examined strategies to support its optimal delivery. This study aimed to characterize a pediatric IEI cohort and assess the impact of implementing a mainstream model-of-care (MoC). Materials/MethodsComprehensive chart audit was conducted for patients ([&le;]18y) who received IEI genomic testing in Queensland, Australia, from 2017-2025. Descriptive analyses captured demographic and clinical characteristics, genomic testing and results, and management outcomes. Inferential analyses assessed changes in genomic practices pre-MoC (<2021) and post-MoC ([&ge;]2021). Results322 patients met eligibility criteria (n=481 genomic test). Diagnostic yield (27.6%) varied by testing indication, with the highest rate among phagocytic defects (n=4/4;100%) and severe combined immunodeficiency (n=8/10;80%). Very-early-onset inflammatory bowel disease had the lowest diagnostic yield (n=3/68;4.4%), prompting changes to testing criteria. Molecular diagnosis resulted in management changes for 90.5% patients. Genomic testing was widely used pre-MoC (n=251 genomic tests). All outcomes significantly improved pre-and post-MoC (p<0.05): duplicate testing decreased (13.9% to 0%); variants of uncertain significance reduced (37.7% to 7.1%); informed consent documentation increased (70.5% to 88.4%); and diagnostic yield increased (16.2% to 27.4%). ConclusionTargeted interventions are needed to support delivery of genomic testing and strengthen service effectiveness.

ObjectiveYouth mental health is shaped by interacting individual, relational, and structural factors that vary across communities, yet few tools integrate these drivers into youth-specific, geographically granular measures for decision-making. This study describes the development and preliminary validation of ThriveAtlasTM, a geographically granular index designed to identify factors that prevent youth from thriving. MethodsThriveAtlas was developed through a multi-step process to identify, operationalize, and validate contextual determinants of youth mental health and well-being. This process included a literature review; selection and construction of indicators from public and proprietary data; aggregation into thematic domains and a composite index; and preliminary validation using county-level mental health outcomes in two U.S. states. Principal components analyses using California and Washington data were used to derive dimensions of youth mental health, which were correlated with ThriveAtlas index and subthemes. ResultsThe review identified key gaps in existing tools: youth-focused indices often emphasize general well-being rather than mental health, while structurally-focused indices lack youth specificity or sub-state granularity. ThriveAtlas revealed geographic variability in vulnerability, including regional clusters and isolated high-risk counties. Validation analyses showed expected patterns in California, where higher vulnerability aligned with greater distress and lower well-being. In Washington, correlations varied by outcome, with stronger correlations observed for crisis-related mental health indicators than overall distress. ConclusionThriveAtlas addresses a critical measurement gap by providing a youth-centered, multidimensional, and geographically granular index of vulnerability. Early validation supports its utility as a decision-relevant signal to identify communities with elevated youth mental health challenges and inform targeted intervention strategies.

BackgroundAnti-seizure medications (ASMs) are widely used in neonatal intensive care, but there is limited evidence for their safety and long-term outcomes. Phenobarbital is the only ASM generally recommended for use in neonates, but it has been linked with adverse effects in infants. Other anti-seizure medications, such as fosphenytoin, levetiracetam, and midazolam are used off-label in this population. MethodsWe performed a retrospective observational study of 18,548 infants in intensive care at an academic medical center, examining links between neonatal ASM exposure and neurological outcomes over the follow-up period of median 4{middle dot}5 years (IQR 1{middle dot}6 - 9{middle dot}2 years). The real-world clinical data included comprehensive maternal, perinatal, and medication data. The outcomes of interest were cerebral palsy, epilepsy, intellectual disability, and visual impairment. Multivariable cause-specific Cox models were used to estimate hazard ratios (HRs) for phenobarbital, levetiracetam, midazolam, and fosphenytoin exposure. Models were adjusted for major perinatal confounders, including gestational age, birth weight, mode of delivery, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and stroke. FindingsExposure to the median cumulative dose of phenobarbital was associated with increased HR for epilepsy (HR 1{middle dot}35; 95% CI, 1{middle dot}11-1{middle dot}62, p = 0{middle dot}002) visual impairment (HR 1{middle dot}20; 95% CI, 0{middle dot}99-1{middle dot}45, p = 0{middle dot}06), and intellectual disability (HR 1{middle dot}18; 95% CI, 0{middle dot}99-1{middle dot}41, p = 0{middle dot}06). In contrast, levetiracetam was associated with smaller risk increases for cerebral palsy (HR 1{middle dot}13; 95% CI, 1{middle dot}03-1{middle dot}23, p = 0{middle dot}006, epilepsy (HR 1{middle dot}14; 965% CI 1{middle dot}05-1{middle dot}24, p = 0{middle dot}002 and visual impairment (HR 1{middle dot}18; 95% CI 1{middle dot}11-1{middle dot}26, p <0{middle dot}0001). Midazolam exposure was associated with slightly increased risk of intellectual disability (HR 1{middle dot}09, 95% CI, 1{middle dot}02- 1{middle dot}16). Results for fosphenytoin were statistically not significant. We did not find evidence of a dose-dependent effect of phenobarbital, but increased maximum phenobarbital blood concentration were associated with elevated hazard ratios for cerebral palsy (HR 1{middle dot}48; 95% CI, 1{middle dot}07-2{middle dot}06, p = 0{middle dot}02 for 50 {micro}mol/l increase) and epilepsy (HR 1{middle dot}64; 95% CI, 1{middle dot}14-2{middle dot}35, p = 0{middle dot}007 for 50 {micro}mol/l increase). InterpretationThe results align with previous findings linking phenobarbital to neurodevelopmental harm and emphasize the need for its cautious use in neonates. Levetiracetam had more favorable safety profile. These findings highlight the potential of real-world data to inform evidence-based neonatal pharmacotherapy when randomized trials are impractical. FundingThe Foundation for Pediatric Research (Finland), the Association of Friends of the University Childrens Hospitals (Lastenklinikoiden Kummit ry), and internal institutional funding.

BackgroundChildren with tracheostomies experience frequent and recurrent acute respiratory infections (ARIs). While cultured respiratory pathogens can inform ARI diagnosis, it is unknown if their presence in the airway affects future ARI risk. ObjectiveTo identify predictors of frequent (3+) ARIs within 36 months of tracheostomy. MethodsWe conducted a single-center, retrospective cohort study of children with tracheostomies placed between 2010-2016. Medical records were reviewed for each encounter in which a respiratory culture was obtained over the 3 years post-tracheostomy. ARIs were defined using encounter ICD-9/10 codes. Logistic and Poisson regression were used to model the association between clinical and microbiologic predictor variables with having frequent (3+) ARIs and the total number of ARIs per child. Mediation analysis using stepwise regression models further evaluated the role of P. aeruginosa. ResultsAmong 436 children, 631 diagnosed ARIs occurred within 36 months of tracheostomy; 20.2% of children had 3+ ARIs. Pseudomonas aeruginosa was isolated in 25% of children and was more common among those with 3+ ARIs compared with 0-2 ARIs (56.8% vs 20.7%, p<0.001). Those with early P. aeruginosa isolation were more likely to have 3+ ARIs (aOR 3.38, 95% CI 1.97-5.81), and this relationship persisted when analyzing ARIs and P. aeruginosa counts. Identification of P. aeruginosa partially mediated the relationship of ventilator dependence with ARI frequency. ConclusionIsolation of P. aeruginosa, particularly early and repeated isolation, is associated with frequent ARIs in the 3 years after tracheostomy and is an important partial mediator. Findings may inform risk stratification and targeted treatment strategies.

Background and ObjectivesAnnual tuberculosis (TB) screening is recommended for all children and adolescents in the United States, but gaps remain in the diagnosis and treatment of latent TB infection (LTBI). We utilized the electronic health record (EHR) to examine the pediatric LTBI care cascade and assessed if an EHR note template could increase risk factor screening. MethodsWe extracted EHR data from well-child and -adolescent visits at a federally qualified health center in Northern California from 2014-2020. We constructed the LTBI care cascade from screening through treatment and performed multivariable logistic regression to assess factors associated with completion of cascade steps. A TB risk factor question was added to the progress note template in 2014, and we measured the change in TB risk factor screening and testing over time. ResultsWe included 10,409 children from 18,681 visits, with median age of 6.9 years (IQR 2.8-12.1). Most visits (90%) had completed risk factor screening, and the note template significantly increased screening over time. However, 20% with a TB risk factor had testing ordered, though the proportion increased from 7% to 33% throughout the period. Of those tested, 4% had a positive test, and the majority completed subsequent steps. Children under 5 years old were more likely to have risk factor screening than older children but were less likely to be tested. ConclusionsLTBI risk factor screening is high, but ongoing gaps in testing could have led to underdiagnosis. Simple EHR-based solutions have the potential to improve pediatric TB care. Article SummaryWe examined the care cascade for latent tuberculosis infection (LTBI) in children and evaluated the role of the electronic health record to support LTBI care. Whats Known on This SubjectThe American Academy of Pediatrics recommends annual tuberculosis screening at well-child visits, but gaps remain in completion of the care cascade. Electronic health record (EHR) systems can be utilized to monitor and guide completion of health maintenance activities. What This Study AddsPrior efforts to characterize the latent tuberculosis infection (LTBI) care cascade for children were incomplete, with limited EHR-based interventions. This study provides a full assessment of the LTBI care cascade and examines the role of the EHR to improve screening.

PurposeCaregivers of children with complex neurodisability frequently experience high caregiving demands, social isolation, unmet support needs, and reduced wellbeing. This paper explores caregivers perceptions of the impact of "Encompass", a ten-modular, community-based group support programme for caregivers of children under five with complex neurodisability, co-facilitated by an expert parent. Materials and methodsThis study formed part of a pilot and feasibility study conducted in two socially disadvantaged, ethnically diverse urban areas in the United Kingdom. Outcome measures were collected pre-intervention, post-intervention and at three-month follow-up to explore caregiver wellbeing, empowerment, activation, and quality of life. Semi-structured qualitative interviews were conducted within three months of programme completion. Interview data were analysed using deductive coding informed by the "Encompass" programme theory alongside inductive analysis to explore mechanisms and unanticipated benefits. Results and conclusionsSeven participating caregivers described improved wellbeing, increased confidence in caring for their child, navigating services, advocating for their family and engaging in the community. Peer support, shared learning and expert parent facilitation were key identified mechanisms of impact. Data from outcome measures showed patterns of improvement post-intervention, with less consistent eYects at follow-up. Findings confirmed the key change mechanisms, informing future iterations and other caregiver group programmes. Trial RegistrationClinicalTrials.gov Identifier: NCT06310681