Pediatrics

Gastrointestinal (GI) conditions are common among children with neurodevelopmental disabilities (NDDs), and are associated with functional impairment, behavioral symptoms, and increased health care utilization. A unique relationship between autism and GI dysfunction has been proposed, leading to a focus on autism in GI research, management guidelines, and clinical tool development. Leveraging >20 years of electronic health record data and a cohort of 42,204 cases with attention-deficit/hyperactivity disorder, autism, cerebral palsy, epilepsy, or intellectual disability and 297,402 controls without NDDs, we quantified associations between NDDs and GI conditions in children. GI conditions were more common in cases than controls across all individual NDDs; intellectual disability and cerebral palsy were most strongly associated with having a GI condition. In this work, clinically recognized GI morbidity was elevated across all NDDs and not unique to autism, suggesting that a broader, transdiagnostic approach to GI dysfunction in children with NDDs is warranted.

Background: Socioeconomic deprivation is associated with childhood morbidity, but nationwide evidence on critical illness and death in a health system with universal insurance coverage is scarce. We assessed the association between area-level deprivation and the population-level incidence of hospital admission, complex intensive care treatment (CICT), and CICT-related mortality in German children, and changes over time. Methods: Population-based analysis of complete German hospital discharge data, 2016 to 2023, covering all cases aged > 28 days to < 18 years. Cases were linked to the German Index of Socioeconomic Deprivation (GISD) via the municipality of residence and grouped into quintiles (Q1 least, Q5 most deprived). Incidence rates were calculated per 100,000 child years. Negative binomial regression adjusted for calendar year, with population as offset, yielded adjusted incidence rate ratios (aIRR) per one-quintile increase in deprivation; sensitivity analyses additionally adjusted for age group. Excess cases were estimated by applying Q1 incidence rates to Q2 to Q5. Results: Of 8,890,103 pediatric cases, 140,509 (1.6 %) received CICT and 3,386 (2.40 %) of these died. Incidence rose with deprivation from Q1 to Q5: admissions 6,191 to 9,255 per 100,000 child years, CICT 97 to 128, mortality 2.54 to 2.96. Each one-quintile increase was associated with higher risk of admission (aIRR 1.10, 95 % CI 1.10-1.11), CICT (1.07, 1.05-1.08), and mortality (1.04, 1.01-1.06); estimates were unchanged after age adjustment. Relative to Q1 rates, Q2 to Q5 accounted for 1,295,896 excess admissions (20.8 %), 11,254 excess CICT cases (12.6 %), and 194 excess deaths (8.7 %). Case fatality among CICT cases was lower in more deprived quintiles (2.35 % in Q5 versus 2.64 % in Q1), as were organ dysfunction and chronic conditions. Disparities in admission and CICT narrowed over time, whereas the mortality gradient persisted. Conclusions: Universal health insurance did not eliminate socioeconomic inequalities in pediatric critical illness. Deprivation increased the population burden of admission, intensive care, and death, but did not worsen outcomes once intensive care had begun, indicating that inequalities arise before pediatric intensive care and that prevention upstream in the care continuum is the primary target.

Importance: Respiratory syncytial virus (RSV) hospitalization rates are highest among children <2 years of age. RSV immunization with infant monoclonal antibody or maternal vaccine is recommended to protect all U.S. infants in their first RSV season. For certain high-risk children aged 8-19 months entering their second RSV season, the monoclonal antibody nirsevimab is recommended. Little is known regarding preexisting health conditions as risk factors for RSV-associated respiratory failure in children during their second season. Objectives: To describe children admitted to the pediatric intensive care unit (PICU) for RSV during their second RSV season by preexisting health conditions, and to compare demographic and clinical characteristics across groups. Design, Setting, and Participants: Surveillance registry of children 8- <24 months old admitted to the PICU in 30 pediatric hospitals in the 2023-2024/2024-2025 RSV seasons. All children had an RSV-positive respiratory sample and received respiratory support with high flow nasal cannula, noninvasive ventilation, or invasive mechanical ventilation (IMV). Exposure: Preexisting health conditions potentially increasing risk of severe RSV disease. Main Outcomes and Measures: Patients were classified into four mutually exclusive groups by preexisting health conditions: 1) U.S. nirsevimab eligible criteria, 2) other identified RSV risk conditions (with some evidence of increased risk for severe RSV), 3) other preexisting conditions, and 4) no preexisting conditions. Patient demographic characteristics and level of respiratory support received were compared. Results: Among 574 children: 47 (8.2%) had U.S. nirsevimab eligibility criteria, 76 (13.2%) had other RSV risk conditions, 96 (16.7%) had other preexisting conditions, and 355 (61.8%) had none. A higher proportion of children with nirsevimab eligibility factors (40.4%) than those with other identified RSV risk conditions (17.1%) required IMV, which was higher than other (10.4%) or no (5.9%) preexisting health conditions (ptrend<0.001). Conclusions and Relevance: Approximately 20% of children admitted to the PICU with severe RSV were in the defined groups that met U.S. nirsevimab-eligibility criteria or that had an identified RSV risk condition associated with known risk for severe RSV. A considerable proportion of both groups of children required IMV for respiratory support. These findings may help inform future deliberations regarding U.S. second season nirsevimab-eligibility recommendations.

Importance: Understanding population differences in epidemiology, clinical presentation, and genetic architecture remains a major challenge for all rare genetic disorders. Hirschsprung disease (HSCR), despite being the commonest cause of neonatal intestinal obstruction, has been poorly studied with respect to its significant heterogeneity across U.S. populations. Objective: To characterize self-identified race and ethnicity differences in HSCR incidence, clinical presentation, and genetic architecture in the United States from diverse data sources. Design, Setting, and Participants: We used retrospective, population-based surveillance data from 3 independent US wide sources - (1) The National Birth Defects Prevention Network (NBDPN; 1996-2010), (2) aggregated electronic health record data from Epic COSMOS (1997-2025), and (3) individual level clinical and genomic data from the Hirschsprung Disease Research Collaborative (HDRC; 2011-2025). Statistical analyses of incident HSCR cases identified at birth, across time and geography, in conjunction with clinical phenotypes and genome sequences from unrelated HDRC probands were performed to characterize epidemiologic, phenotypic and genetic heterogeneity in HSCR. Exposures: HSCR cases were identified based on standardized clinical diagnostic criteria, primarily rectal biopsy with histopathologic confirmation of aganglionosis. The disease was defined using ICD-9-CM code 751.3, CDC/BPA code 751.30-751.34. and ICD-10-CM code Q43.1. Patients were classified by self-identified race and ethnicity (SIRE), with primary comparisons conducted between non-Hispanic Blacks/African Americans (Blacks) and non-Hispanic Whites (Whites). Main Outcomes and Measures: HSCR incidence and the frequency of clinical features were estimated overall and by SIRE. We also estimated the individual and total genetic burden of rare pathogenic coding variants and common noncoding regulatory variants at established HSCR genes by population. Results: Overall HSCR incidence in the U.S. was 2.04 per 10,000 live births (95% CI, 1.99-2.09) as previously estimated. We show, Blacks have the highest HSCR incidence (2.83-3.13 per 10 000 live births), in comparison to Whites (1.89-2.02) and Asians (1.54-1.98), a difference not previously ascertained from previous smaller cohorts from limited geographical regions. This difference persists across surveillance times and geography. This incidence difference from NBDPN is consistent with Epic COSMOS, a nation-wide, independent hospital-based data source. Clinically, Blacks are more likely to present with isolated HSCR and with milder manifestations at birth, including chronic severe constipation (CSC). Genetically, the burden of pathogenic coding variants did not differ between Blacks and Whites. However, Blacks had a significantly higher enrichment of two non-coding regulatory variants (rs199582499 and rs28735659) at the SOX10 gene locus, as compared with Whites. Conclusions and Relevance: This study demonstrates, for the first time, that Black HSCR patients in the U.S. have a higher incidence accompanied by milder clinical presentation and distinct noncoding regulatory SOX10 variants as compared to White patients. Nevertheless, Blacks are severely under-represented in U.S. studies of HSCR leading to significant health disparities in their care and management.

Introduction: Early childhood vision screening is critical for detecting amblyopia and other vision-threatening conditions. Despite screening recommendations during well-child visits, rates remain low. Red reflex assessment is recommended to identify serious ocular pathology, yet its use in primary care is not well described. We examined rates and drivers of vision screening in pediatric primary care. Methods: We conducted a retrospective review of electronic health records for children 3 to 5 years attending well-child visits in 2022 in one of three representative primary care clinics within a university health system. Outcomes were documented red reflex and functional vision tests. We evaluated associations with patient demographics and clinic site using multivariable logistic regression Results: Among 1,003 visits, 21.1% (n=212) had a documented red reflex assessment, and 60.8% (n=610) a functional vision test. Younger children (ages 3 and 4 vs. 5 years) had higher odds of red reflex assessment [adjusted odds ratio (aOR) 9.00 and 8.64], and lower odds of a functional vision (aOR 0.47 and 0.59) test. Females had higher odds of red reflex assessment (aOR 1.53). Other/Multiracial children had lower odds of red reflex assessment than Non-Hispanic White children (aOR 0.48). Screening rates varied significantly by clinic site Conclusions: Visual function and red reflex assessment are inconsistently performed in pediatric primary care, with particularly low rates of red reflex documentation. Screening rates varied between clinics and were affected by age. These findings highlight missed opportunities for early detection of vision-threatening conditions and identify targets for improving adherence to pediatric vision screening recommendations

Abstract Importance Acute otitis media is the most common infection in children and a major reason for antibiotic prescriptions, up to one third of which may be unnecessary. Sector of care may influence AOM management through differences in access to care, specialist involvement, parental expectations and financial foundation. Objective The objective is to examine differences in antibiotic prescribing practices between healthcare sectors. Design This is a nationwide register-based study comparing data from different healthcare sectors. Setting Finnish primary and secondary healthcare, covering both public- and private-sector visits. Prescriptions and sociodemographic information were linked from nationwide registers. Participants We included children under 18 years old who received a diagnosis of acute otitis media, defined by ICD-10 codes H65-H67, between January 1, 2017 and December 31, 2022. Exposures The exposure is the sector of care (public sector vs. private sector). Main Outcomes and Measures Primary outcomes were antibiotic prescribing, guideline adherence of the prescribed antibiotics, and rates of management failure. Secondary outcomes included antibiotic selection and guideline-adherent eligibility for tympanostomy tube placement. Associations were estimated using adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results The study included 295 064 children with 596 634 acute otitis media index visits, of which 77.6% resulted in an antibiotic prescription. Private-sector visits were associated with higher odds of antibiotic being prescribed (adjusted odds ratio [aOR]: 1.45; 95% CI: 1.41-1.49). Overall, 87.3% of antibiotic prescriptions were guideline adherent, but private-sector care was associated with lower odds of guideline-adherent prescribing (aOR: 0.64; 95% CI: 0.60-0.69). Compared with amoxicillin, the private sector showed higher odds of prescribing amoxicillin-clavulanic acid (32.8% vs. 8.3%; aOR: 3.00; 95% CI: 2.91-3.10). Management failure occurred in 7.0% of episodes and was more common in the private sector (aOR:1.52; 95% CI: 1.48-1.56). Only 48.7% of all tympanostomy tube insertions met the eligibility criteria. Conclusions and Relevance In this study overall adherence to guideline-recommended antibiotic treatment for AOM was high in Finland. Nevertheless, observed clinically meaningful sectoral differences in antibiotic selection, treatment failure, and tympanostomy eligibility adherence indicate a need for targeted antimicrobial stewardship and quality-improvement efforts, especially in the private sector.

Background: Wolfram syndrome is a rare neurodegenerative disorder, most commonly caused by pathogenic variants in WFS1, while cases due to CISD2 are exceedingly rare. The estimated prevalence is 1 in 160,000 to 770,000 individuals worldwide. In these clinical guidelines, disorders caused by WFS1 are referred to as WFS1-Wolfram syndrome, and those caused by CISD2 as CISD2-Wolfram syndrome. Historically, it has been characterized by early-onset, antibody-negative, insulin-dependent diabetes mellitus, progressive optic atrophy, sensorineural hearing loss, arginine vasopressin deficiency, and brainstem and cerebellar atrophy. More recently, partial and late onset forms have been identified. There are currently no licensed disease-modifying treatments, and international clinical guidelines have not previously been established. Methods: An international steering committee systematically reviewed 273 peer-reviewed publications and generated draft consensus statements across six clinical domains. These statements were evaluated by international specialists in endocrinology, clinical genetics, neurology, ophthalmology and neuro-ophthalmology, psychiatry, and urology, drawn from North America, Europe, Latin America, Oceania, and Asia, using a modified three-round Delphi process. Additional feedback was incorporated from nurses specializing in multidisciplinary Wolfram syndrome care, from leaders of international patient organizations, and from specialists in the genetic diagnosis of monogenic diabetes. Structured feedback from patients and families was gathered through multiple international patient advocacy organizations. Consensus was defined as [&ge;]80% agreement. Results: All 35 final consensus statements reached the pre-specified consensus threshold of [&ge;]80% agreement, spanning diagnosis and genetic testing, multidisciplinary care organization, neuro-ophthalmology, neurology, endocrinology, urology, gastroenterology, and psychiatry. Conclusions: These guidelines are the first international clinical consensus for Wolfram syndrome and provide actionable recommendations for clinicians worldwide. Implementation should be accompanied by a prospective audit to expand the evidence base and support future iterations.

IMPORTANCE: Most United States children with neurodevelopmental disorders have not received genetic testing aligned with current guidelines. Integration of genetic counselors into non-genetics departments is a potential strategy to improve uptake, but prevalence and details of integrated care models are unknown. OBJECTIVE: To characterize availability, utilization, and perceived need for genetic counselors across non-genetics departments caring for patients with neurodevelopmental disorders DESIGN: Cross-sectional observational department-level survey SETTING: Child neurology, adult neurology, developmental pediatrics, child psychiatry, and adult psychiatry departments at Intellectual and Developmental Disabilities Research Centers PARTICIPANTS: The survey was distributed to 67 departments across 15 institutions. The departmental response rate was 52% (35/67), with at least one response from 87% (13/15) of institutions. EXPOSURE: Presence/absence of dedicated genetic counselor(s), where "dedicated" was defined as hired by the department MAIN OUTCOME(S) AND MEASURE(S): This was a descriptive study only, with no comparative statistical analyses due to the exploratory nature. RESULTS: One third of departments (34%; 12/35) reported having dedicated clinical genetic counselors. Prevalence was highest in child neurology (67%; 8/12), followed by adult neurology (40%; 2/5) and developmental pediatrics (22%; 2/9), with none in child psychiatry (0/7) or adult psychiatry (0/2). In almost all departments with genetic counselors (92%; 11/12), they directly billed for their services, which universally included pre-test counseling/consent and post-test counseling. In departments without genetic counselors, only 39% (9/23) reported providers ordered their own genetic testing. Among all departments, over half (57%) were interested in adding/increasing genetic counseling support, while 26% were unsure and 17% uninterested. Insufficient funding was the most cited barrier; only one department reported insufficient need. CONCLUSIONS AND RELEVANCE: Though currently implemented in only one third of departments, our findings suggest those with dedicated genetic counselors directly pursue genetic testing (without referring to genetics) more than those without genetic counselors. Interest in increasing or adding genetic counseling support was high, and though funding was a reported barrier, feasible funding models were described. In the context of limited medical geneticists and expanding precision therapies, alternate delivery models for neurodevelopmental genetic testing including genetic counselor integration in non-genetics departments may help to scale and sustain uptake.

Objective Beckwith-Wiedemann spectrum (BWSp) is an overgrowth and cancer predisposition disorder caused by genetic and epigenetic alterations of chromosome 11p15. The 2018 international consensus produced a clinical scoring system to capture the phenotypic variability of BWSp and guide genetic testing and clinical management, including tumor screening, in patients without molecular confirmation. In this study, we evaluated BWSp predictors to identify the most informative features. Methods Supervised machine learning analyzed 25 phenotypic features in 555 patients with BWSp and 150 controls. Logistic regression, combined with a purposeful stepwise selection algorithm, identified a subset of features that can accurately classify subjects. Model performance was evaluated in a testing set and validated externally. Results The final model included six predictors: macroglossia, lateralized overgrowth, midface flattening, hepatomegaly, omphalocele, and developmental delay. Developmental delay was the only negative predictor; macroglossia (OR 46.10) and lateralized overgrowth (OR 27.87) were the strongest predictors. The proposed model and 2018 system did not differ in classification performance for testing (P = .39) or external (P = .15) sets. Conclusion A simplified diagnostic model, driven by macroglossia and lateralized overgrowth, differentiates between patients with BWSp and controls with performance comparable to the 2018 system. And may help physicians prioritize BWSp evaluation.

Question Are adverse childhood experiences (ACEs) associated with altered growth trajectories in childhood? Findings In this cohort study of 412,549 children and adolescents, ACEs were associated with lower height throughout childhood, earlier pubertal timing, and shorter final stature. Height differences emerged approximately 2 years before ACE documentation and were greatest among those with earlier documentation. Meaning These findings suggest that early adversity affects physical growth in children and may serve as a measurable indicator of the biological consequences of early-life stress, especially in those with documentation of ACEs prior to the onset of typical pubertal growth. Importance Adverse childhood experiences (ACEs) are among the strongest risk factors for long-term mental and physical health complications, yet their impact on physical growth in childhood remains incompletely understood. Objective To determine the association of ACEs on childhood growth trajectories and growth dynamics. Design, Setting and Participants Retrospective cohort study using longitudinal electronic health record data. Data was collected from participants between February 1999 and August 2025. A large academic medical center biobank linked to deidentified electronic health records in the southeastern United States. A total of 412,549 individuals with at least 2 recorded height measurements between the ages of 2 and 20 were included in the primary analysis. Growth curve analyses were performed in a subset of 199,844 individuals with at least 3 height measurements spanning at least 2 years. Genetic analyses were performed in a subset of 10,114 individuals of primarily European ancestry. Exposure(s) Documented exposure to adverse childhood experiences before age 18 years identified through a natural language processing algorithm. Main Outcome(s) and Measure(s) Height-for-age z-scores across childhood, final attained height, and growth curve parameters estimated using SuperImposition by Translation and Rotation (SITAR) modeling. Results Among 412,549 participants, 18,502 (4.5%) had clinically documented ACEs during childhood. ACE documentation was associated with lower height-for-age z-scores throughout childhood and adolescence. Final attained height was significantly lower among ACE-documented individuals, with mean differences of -3.0 cm among males (174.0 cm vs 177.0 cm, p < 0.001) and -1.3 cm among females (161.8 cm vs 163.1 cm, p < 0.001). Height differences emerged approximately 2 years before clinical ACE documentation. Earlier age at first ACE documentation was associated with progressively shorter final attained height, with each year decrease in age at ACE documentation associated with a decrease in final height of -0.20 cm in females and -0.35 cm in males. Those with first ACE documented prior to pubertal age also showed the most pronounced growth dynamic differences, with males demonstrating a mean reduction in size of 5.25 cm (95% CI, -6.79 cm to -3.70 cm) and 1.26-year earlier pubertal timing (95% CI, -1.50 to -1.03 years), and females demonstrating a reduction in growth curve size of 3.62 cm (95% CI, -4.83 to -2.41 cm) and 1.14-year earlier pubertal timing (95% CI, -1.29 to -0.99 years). Conclusions and Relevance In this large clinical cohort, clinically documented ACEs were associated with time-dependent reductions in stature, earlier pubertal timing, and short final attained height. These findings suggest that early childhood adversity may have lasting effects on physical development and highlight growth trajectories as a potential marker of the biological consequences of early-life stress.

The evolving epidemiology of COVID-19, driven by successive SARS-CoV-2 variants of concern (VOCs), has prompted ongoing evaluation of their impact on disease severity in children. In low- and middle-income countries (LMICs), children experience a higher burden of severe respiratory illness and pneumonia-related mortality due to factors such as malnutrition, incomplete immunisation, HIV exposure or infection, tuberculosis, and disparities in access to healthcare services. Hospital-based paediatric studies from LMICs are therefore needed to understand how the epidemiology and severity of COVID-19 have changed across pandemic waves. This study examined 354 hospitalised children with SARS-CoV-2 infection during the ancestral, pre-Omicron (Beta and Delta), and Omicron waves at Tygerberg Hospital in Cape Town, South Africa. We analysed data collected over an extended period, from March 2020 to June 2022. Statistical analyses were used to describe clinical characteristics across variant periods, and multivariable logistic regression models were applied to evaluate associations between potential risk factors and disease severity. Paediatric COVID-19 severity varied across VOC periods, with the highest burden observed during the pre-Omicron (Beta and Delta) waves. In multivariable analyses, younger age and circulating variants were associated with disease severity; CRP levels emerged as a marker associated with more severe illness, and corticosteroid treatment, while also associated with disease severity, reflects clinical response to more severe cases. These findings contribute to a better understanding of the epidemiology and clinical impact of COVID-19 in children and highlight the importance of context-specific surveillance and treatment strategies in resource-limited settings.

Primary ciliary dyskinesia (PCD) is a rare, genetic, multiorgan disease requiring lifelong management. Although PCD affects everyday life, little is known about how people with PCD experience social functioning (SF). We conducted a study within the international participatory Living with PCD study to comprehensively explore SF. First, we conducted a focus group and two semi-structured interviews with adults and parents of people with PCD. We analysed qualitative data thematically and used the findings to develop a multilingual online questionnaire on SF. The questionnaire was completed by 277 participants: 225 adults and adolescents with PCD (81%) and 52 parents of children with PCD (19%). Participants reported active social lives and strong close relationships. PCD had a positive impact on family relationships for 39% of adult/adolescent participants and 41% of parents reporting for children. Among adult/adolescent participants, 49% reported positive or no impact on romantic/intimate relationships, while 17% had avoided or ended a relationship because of PCD. PCD affected the ability to meet responsibilities for 54% of participants, free time for 58%, and planning effort for 53%. Participants were more comfortable discussing PCD with family, friends, and partners than in work or educational settings, where only 29% reported receiving support. Financial support, flexible work, or educational policies and better-trained healthcare professionals were the most frequently identified unmet needs. This study suggests that maintaining SF with PCD requires substantial individual and relational work. Improving SF for people with PCD requires systemic responses in healthcare, education, and employment, alongside support from close networks.

AIM: To evaluate whether selective motor control quantified from spontaneous infant movement recordings provides diagnostic and prognostic information for cerebral palsy (CP) beyond established movement-based assessments. METHOD: This multicenter diagnostic and prognostic accuracy study included 302 infants (151 with CP) with spontaneous movement recordings obtained between 10 and 20 weeks corrected age from cohorts in Australia and the United States. All eligible infants with CP were included, and a comparison sample without CP was randomly selected. Recordings were scored using the Baby Observational Selective Control Appraisal (BabyOSCAR), Motor Optimality Score Revised (MOS-R), and General Movements Assessment (GMA). Outcomes at 2 years or older included CP diagnosis, Gross Motor Function Classification System (GMFCS) level, and motor distribution. RESULTS: BabyOSCAR discriminated CP diagnosis (area under the curve [AUC] 0.98), including children later classified in GMFCS level I. Among infants with CP, BabyOSCAR discriminated GMFCS levels I - II from III - V (AUC 0.89). BabyOSCAR absolute asymmetry also discriminated unilateral CP from all other infants (AUC 0.90). Diagnostic discrimination was also observed for MOS-R (AUC 0.94) and GMA (AUC 0.86). INTERPRETATION: Quantifying selective motor control from brief infant movement recordings may provide complementary early information about CP diagnosis, functional level, and motor distribution.

Purpose: Outcome consequences of critically ill children treated outside of pediatric intensive care units (PICU) are unknown. We assessed case fatality of children receiving complex intensive care treatment (CICT) by treating department in Germany and explored reasons for admission to adult intensive care units (AICU). Methods: Retrospective study using the German nationwide hospital discharge dataset 2016 to 2023. Cases aged [&ge;] 28 days and < 18 years receiving CICT were classified as PICU, AICU, or interdisciplinary by department codes. Odds ratios (OR) for in-hospital case fatality were estimated in generalized linear mixed models with the hospital as random effect, adjusted for age, acute organ dysfunction, and chronic conditions. Excess deaths were estimated and a survey among pediatric and adult intensivists was analyzed qualitatively. Results: Of 143,034 cases, 67.8 % were treated in PICUs, 14.0 % in AICUs, and 18.2 % were interdisciplinary. The crude OR for death in PICUs versus AICUs was 1.14 (95 % CI 1.03 to 1.26), reversing to 0.73 (0.63 to 0.84) after adjustment. For PICU and interdisciplinary cases combined versus AICU, the fully adjusted OR was 0.61 (0.54 to 0.70). Estimated excess deaths across the study period were 100, rising to 191 when interdisciplinary cases counted as pediatric. Capacity constraints, organizational factors, and clinical expertise were the main domains underlying AICU admissions. Conclusions: Children treated outside of PICUs had higher risk-adjusted case fatality, while crude figures pointed in the opposite direction. The findings support treating critically ill children in settings with routine pediatric intensive care experience.

Background: Chronic pain affects approximately 20% of children and youth worldwide and is associated with mental and physical health impacts. Canada-specific data on the prevalence of chronic pain in children and youth are limited, highlighting the need for current high-quality population-based estimates Aims: The aim of this study is to provide national estimates of self-reported chronic pain among Canadian children and youth by pain type (headache stomach ache, backache), sex (female, male), age group (5-11, 12-17 years) and province or territory. Methods: Publicly available data were used from the 2019 Canadian Health Survey on Children and Youth (CHSCY), a population-based survey conducted by Statistics Canada using a nationally representative sample of Canadian children and youth Results: Overall, headaches were the most commonly reported pain type (15.4%), followed by stomach aches (12.5%), and backaches (11.1%). Prevalence was consistently higher among females than males and among youth than children, with youth girls reporting the highest prevalence across all pain types. Prevalence also varied geographically, with some of the highest estimates observed in the Atlantic Provinces. Conclusions: Chronic pain affects substantial proportions of Canadian children and youth with disparities observed by pain type, sex, age, and geography. These findings under score pediatric chronic pain as an important public health issue and highlight the need for equity-oriented approaches that address the needs of populations experiencing the greatest burden.

Background In a retrospective online survey, we assessed the extent to which people with symptomatic hypermobility are at risk of Long COVID with a high degree of post-exertional symptom exacerbation, a form of Long COVID similar to myalgic encephalomyelitis. Methods Participants were 1,816 adults with prior COVID-19 infection; 19.4% reported Long COVID, defined as symptoms persisting [&ge;]3 months. Survey measures identified Long COVID with high post-exertional symptom exacerbation, generalized joint hypermobility (GJH), extreme hypermobility, and a pre-COVID orthostatic/neurocognitive symptom burden (ONS profile). Logistic regression assessed whether ONS profile and hypermobility, together defined as symptomatic hypermobility, were associated with increased risk of Long COVID with post-exertional symptom exacerbation. Results In the full sample, both extreme hypermobility (OR 3.15, 95 % CI 2.00-4.95) and an ONS profile pre-COVID (OR 3.29, 95% CI 2.34-4.61) were strongly predictive of Long COVID with high post-exertional symptom exacerbation. These effects were cumulative, leading to an OR of 9.46 (95% CI 4.93-18.17) for people with both conditions. People who both had an ONS profile pre-COVID and had generalized joint hypermobility also had a higher risk of Long COVID with high post-exertional symptom exacerbation (OR 5.54, 95% CI 3.51-8.75). Conclusions In this dataset, people with symptomatic hypermobility were at high risk of Long COVID with high levels of post-exertional symptom exacerbation. Further research is needed to understand the biological mechanisms of viral-onset illness to promote more effective and targeted treatments tailored to the disease pathways shared by groups of individuals with common vulnerabilities.

Background: Vitamin K prophylaxis is universally recommended for newborns to prevent life threatening vitamin K deficiency bleeding. Although not on the immunization schedule, vitamin K prophylaxis is often coadministered with hepatitis B birth dose and erythromycin ophthalmic ointment, and rising hesitancy around vaccines/preventive care may spill over into vitamin K administration. Methods: We conducted a retrospective cohort study using Truveta electronic health record data with linked mother-child dyads. Live births to mothers aged 15-49 from January 1, 2019 through June 30, 2026 were included. Vitamin K administration was defined as documentation on the birth date or following day. Logistic regression assessed sociodemographic predictors of non-receipt, and interrupted time series analysis evaluated changes after January 2026. Results: Among 1,026,375 infants, 995,628 (96.97%) had documented vitamin K administration. Non-receipt increased from an average of 2.1% during 2019-2022 to 4.3% in 2025 and 6.1% in 2026, reaching 8.10% in June 2026. Older maternal age, non-Hispanic or Latino ethnicity, Medicaid or unknown insurance, and year of delivery were associated with greater odds of non-receipt. After January 2026, there was no immediate step change, but the odds of vitamin K receipt declined an additional 10% per month (OR: 0.90; 95% CI, 0.88-0.91). Conclusions: Vitamin K non-receipt increased over the study period and accelerated after January 2026. Because vitamin K recommendations were not changed by the January vaccine schedule, this association may reflect broader impacts to confidence in newborn preventive care. Future studies should examine causal mechanisms, parental decision-making, and associated clinical outcomes.

Background Early-life respiratory syncytial virus (RSV) infection is associated with childhood recurrent wheeze or asthma (RW/A), but causality and shared genetic liability remain unclear. Methods We combined Finnish nationwide registries and Nordic genetic cohorts. First, in 965 312 Finnish children born between 1998 and 2014, we defined severe RSV as RSV hospitalisation before age 1 year, and recurrent wheezing or asthma (RW/A) as inhaled medication reimbursement between ages 1 and 7 years, and compared medication and eosinophil trajectories by RSV history. Second, we assessed familial confounding in 527 776 full siblings and 15 667 RW/A-discordant pairs. Third, we performed a genome-wide association study (GWAS) of RSV susceptibility with meta-analysis across six Nordic cohorts (3 107 cases, 92 031 controls) and two-sample Mendelian randomisation (2SMR) using 155 asthma-associated variants. Findings RSV-associated RW/A showed higher inhaled medication use at ages 1-2 years but lower use after age 4, and lower mean blood eosinophils (0.34 vs 0.39*10e9/L; p=0.003) than RW/A without RSV hospitalisation. In RW/A-discordant sibling pairs, RSV hospitalisation was associated with RW/A (OR 2.8; 95% CI 2.4-3.2), while unaffected siblings also had elevated RW/A prevalence. GWAS identified an RSV association at APBB1IP (rs787036; beta=0.209; p=8.80*10e-9). 2SMR provided no evidence that asthma genetic liability influenced RSV susceptibility. Interpretation The RSV-asthma association is unlikely to be explained by shared genetic or environmental factors, and RSV-associated RW/A shows a distinct trajectory. These findings help prioritise long-term outcomes for RSV prevention trials and monitoring. Funding: Paivikki and Sakari Sohlberg Foundation, Foundation for Pediatric Research, Sigrid Juselius Foundation, Orion Research Foundation, the Research Council of Norway.

Importance Pharmacogenomic (PGx) guidelines can improve medication efficacy and reduce toxicity, but their application in pediatric intensive care units (PICUs) remains largely unexplored. Objective To determine the frequency of medications with established PGx guidelines administered in the PICU and assess the capacity of exome sequencing to capture PGx phenotypes for these medications. Design Retrospective cohort study integrating electronic medical record and exome sequencing data. Setting Morgan Stanley Children's Hospital of NewYork-Presbyterian, a single center tertiary care children's hospital. Participants A total of 4,939 children admitted to the PICU (2020 - 2024), and 192 children admitted to the PICU who underwent exome sequencing for research purposes (2015 - 2023). Exposure Critical illness requiring PICU admission. Main Outcomes and Measures Frequencies of administration of medications with established PGx guidelines in the PICU and the proportion of individuals with exome sequencing with identifiable PGx phenotypes. Results Among 4,939 PICU patients, 37.2% (n=1,837) received at least one medication with established PGx guidelines and 14.4% (n=712) received two or more such medications. Twenty PGx genes were implicated; CYP2C9 was most common (17.3%, n=853). An estimated 8.2% of patients received medications for which PGx-guided recommendations would have altered clinical management. Among 192 patients who underwent exome sequencing, at least one metabolizer phenotype was identified in 62% (n=119). Conclusions and Relevance Many critically ill children receive medications with established PGx guidelines. This study highlights an opportunity for more personalized medicine for critically ill children admitted to a tertiary care hospital and assesses the strengths and weaknesses of exome sequencing to uncover pertinent PGx phenotypes.

ScreenPlus is a consented pilot program that aims to screen 100,000 babies for a panel of rare disorders. Given its size, ScreenPlus provides a unique opportunity to learn about optimal recruitment practices. ScreenPlus recruitment strategy includes recruiter-initiated Active and Hybrid modes and parent-initiated Independent mode. Active recruitment occurs in-person at the postpartum bedside, whereas Hybrid recruitment includes other attempt types. In Independent recruitment, parents access online educational and e-consent forms. Analysis of 47,642 completed recruitment profiles from May 2021 through April 2025 showed that Active recruitment was used in 72.2% and had the highest percentage of parents consenting (65.5%) in an average of 1.2 days. Hybrid recruitment was used in 27.1% of profiles and resulted in a 44.5% consent rate in an average of 8.6 days, with electronic medical record messaging being the attempt type most likely to lead to a consent. Independent recruitment was used in less than 1% of profiles. In Active and Hybrid Recruitment, non-English speakers were more likely to consent compared with English speakers. Collectively, these findings emphasize that although optimal pilot NBS recruitment is multi-modal, direct communication between parents and study team has the highest consent yield.