Pediatrics

Importance Age based screening and prevention guidelines in healthcare are developed largely in populations without Down syndrome (DS). If disease risk among individuals with DS differs significantly relative to typically developing (TD) individuals of similar ages, standard guidelines may overlook critical windows of care. Objective To determine the age specific risk of ten common conditions in individuals with DS compared to a matched TD cohort to evaluate the presence of risk modification by age. Design Retrospective longitudinal cohort study. Setting Midwest healthcare system. Participants 4,912 individuals with DS and 37,924 TD controls, with clinical encounters between January 2005 and May 2025. Total person years (PYs) were 25,896 and 149,078 respectively. Exposure DS status Main Outcomes and Measures Incidence of acute sinusitis, anxiety, asthma, depression, gastroesophageal reflux disorder, nervous system disorders, respiratory failure, thyroid gland disorders, vasomotor/allergic rhinitis, and vitamin D deficiency. Incidence rate ratios (IRR) trajectories were analyzed using generalized additive mixed models. Wald tests assessed the presence of age modification. Results In our DS cohort (median age 24, 48% female), we found evidence of age-related risk modification in 6 of 10 conditions examined. The relative incidence of anxiety was significantly lower among individuals with DS in early childhood (at age 5, IRR 0.23, 95%CI 0.19, 0.29), compared to TD controls of the same age. However, risk in the DS cohort increased with age approaching equal levels with controls around ages 65. Similar trends were observed for depression. The association between DS and gastroesophageal disease was largely null except between ages 1 to 8, where the incidence among DS cohort was elevated (5 to 7 cases per 1000 PYs) compared to controls (2 to 3 cases per 1000 PYs). The association between DS and respiratory failure was statistically insignificant until age 53 to 70, where incidence among individuals with DS rose sharply (13 to 30 cases per 1000 PYs), while for TD counterparts it remained constant at 8-9 cases per 1000 PYs. Lastly, risk of vitamin D deficiency fluctuated with a peak at age 20 (IRR 2.34, 95%CI 2.02, 2.72). Conclusions and Relevance These findings demonstrate age effect modification among individuals with DS across a variety of disease conditions and highlight the importance of population-specific care guidelines.

Background Pontocerebellar hypoplasia Type 2A (PCH2A) is a rare, autosomal recessive disorder with reduced life expectancy. Clinical features include profound developmental delay, microcephaly, and a dyskinetic movement disorder. Additional symptoms frequently observed are feeding difficulties, vomiting, dystonic attacks, and seizures. Compared to parents of typically developing children, parents of children with PCH2A experience decreased health-related quality of life. The aim of this study was to provide a follow-up on survival, symptoms, and perceived disease burden. Methods Patients were primarily recruited via the German patients' organization (PCH-Familie e.V.). Inclusion required genetic confirmation of PCH2A. Data were collected from 2020-2022 using parent questionnaires and medical reports; uncertainties were clarified during semi-standardized telephone interviews. Statistical analysis was quantitative, appropriate statistical tests were used, depending on the data distribution. Results Sixty-five patients participated, with a median age of 6.4 years and balanced gender distribution. Sixteen patients (25%) died at a median age of 5.5 years. Ten-year survival rate was 71.5%. Feeding difficulties, dyskinesia, and sleep disturbances were common and persistent symptoms. Seizures increased with age, whereas vomiting and dystonic attacks decreased over time. Perceived disease burden differed among families, but most reported overall impaired quality of life. The most burdensome symptoms were restlessness, sleep disorder, and gastrointestinal issues, while seizures/epilepsy were ranked as least impactful. With increasing age, perceived burden from feeding and swallowing disorders, gastrointestinal problems, episodic abdominal pain, and overall quality of life decreased significantly. Conclusions Life expectancy in PCH2A remains limited, but survival appears to have improved in more recent birth cohorts. Most symptoms persist with age, though a few, like reflux and dystonic attacks, improve in tendency. Conversely, respiratory symptoms and seizures tend to worsen. Notably, perceived disease burden generally decreases as patients age. Restlessness proved to be the most burdensome symptom, although it has not been clearly described before.

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.

Abstract Background: Having a usual source of care (USC) supports continuity and access to health services. Recent national trends among U.S. children have not been comprehensively characterized. We examined changes in USC prevalence, subgroup heterogeneity, and reported reasons for not having a USC using the 2015-2024 Medical Expenditure Panel Survey. Methods: We analyzed the 2015-2024 Medical Expenditure Panel Survey Household Full-Year Consolidated Data. Annual prevalence rates were estimated for children aged 0 to 17 years overall and by sex, age group, race and ethnicity, and insurance status. The reported reasons for not having a USC were grouped to low perceived need, preference or self-management, access or continuity barrier, and other reasons. The distribution of grouped reasons was analyzed for each study year. Temporal differences in yearly estimates were evaluated using two-sample z-tests between 2015 and 2019 and between 2015 and 2024, and average annual changes were estimated using generalized linear regression. Results: Overall USC prevalence declined from 92.9% (95% confidence interval [CI], 91.9%, 93.8%) in 2015 to 87.2% (95% CI, 85.1%, 89.2%) in 2024. The estimated average annual change was -0.8 percentage points (95% CI, -1.0 to -0.6). Declines were observed across most subgroups and were largest among uninsured children, whose prevalence decreased from 78.4% to 53.6%. Low perceived need remained the most common reported reason for not having a USC, while the proportion reporting access or continuity barriers decreased and the proportion classified as other reasons increased. Conclusions: Estimates based on the Medical Expenditure Panel Survey indicated a substantial decline in the prevalence of having a USC among U.S. children, with notable heterogeneity by insurance status and race and ethnicity. Further research is needed to determine whether the decline reflects changing access, organization and use of pediatric care, survey measurement, or a combination of these factors.

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.

Importance: Nirsevimab, a monoclonal antibody against RSV, was implemented in France in September 2023. Recently, rare resistance-associated substitutions were described in RSV but the effectiveness according to lineages remains unclear. Objective: We aimed to estimate the effectiveness of nirsevimab against hospitalization for RSV bronchiolitis according to RSV lineages. Design: We conducted a multicenter test-negative case-control study from October 15, 2023 to March 15, 2025. Setting: This study was based on data from three national multicentric prospective studies. The 12 participating centers were secondary or tertiary hospital with a pediatric department located in France. Participants: We included all children younger than 12 months who were hospitalized for RSV bronchiolitis in one of the participating centers in France during the two first RSV epidemic seasons following the implementation of nirsevimab (from October 15, 2023 to February 29, 2024, and from October 10, 2024 to March 15, 2025). Main outcomes and measures: The main outcome of the study was the RSV test result of bronchiolitis cases. RSV whole-genome sequencing was performed using a tiled amplicon approach covering the complete viral genome, as previously described in the POLYRES studies. We estimated the effectiveness of nirsevimab by a multivariable logistic regression model adjusted for potential confounders. We estimated the adjusted risk of immunization failure for each lineage by calculating relative odds ratio to a reference lineage. A range of sensitivity analyses were conducted. Results: We included 3019 infants with bronchiolitis among which 2273 had a positive RSV test (case patients) and 746 had a negative RSV test (control patients). Overall, 373/2273 (16.4%) case patients were immunized by nirsevimab versus 423/746 (56.7%) control patients. The adjusted effectiveness of nirsevimab against hospitalization for bronchiolitis was 88.4% (95% CI, 84.5-91.4) with RSV-B and 79.4% (95% CI, 73.7-83.8) with RSV-A. The risk of immunization failure was 3.2-fold (95% CI 1.8-5.7) higher for lineages derived from A.D.3 than for lineages derived from B.D.4.1. Conclusion and relevance: In this multicentric case-control study, we observed that nirsevimab effectiveness was variable across RSV lineages, with a lower effectiveness against A.D.3 lineages compare to others. Further surveillance is needed to confirm these findings and assess their implication on RSV lineages epidemiology as nirsevimab use expands.

Objective: To compare healthcare access among U.S. children with attention-deficit/hyperactivity disorder (ADHD) only, autism only, and co-occurring ADHD-autism, and to identify social inequities associated with unmet care using recent nationally representative data. Methods: We analyzed combined 2023-2024 National Survey of Childrens Health data for 13,576 children aged 3-17 years with current ADHD and/or autism. Six healthcare-access outcomes were examined: forgone healthcare, unmet mental health care, no medical home, coverage gap or inadequate insurance, unmet specialist care, and unmet care coordination. Survey-weighted modified Poisson regression estimated adjusted prevalence ratios (aPRs) and 95 percent confidence intervals (CIs). Six multiply imputed poverty measures were combined using Rubins rules. Sensitivity models additionally adjusted for functional difficulty. Results: Compared with ADHD only, co-occurring ADHD-autism was associated with higher prevalence of forgone healthcare (aPR, 1.73; 95 percent CI, 1.38-2.16), no medical home (1.11; 1.02-1.20), inadequate or discontinuous insurance (1.14; 1.03-1.28), unmet specialist care (1.49; 1.14-1.94), and unmet care coordination (1.15; 1.04-1.28). Autism only was associated with unmet mental health care (1.49; 1.13-1.97) and care coordination (1.13; 1.02-1.25). Food insufficiency, housing instability, and non-supportive neighborhood conditions were consistently associated with poorer access. After adjustment for functional difficulty, associations remained for co-occurring ADHD-autism with forgone and specialist care and for autism only with unmet mental health care. Conclusions: Healthcare access inequities differed by neurodevelopmental diagnostic group and social context. Pediatric systems should strengthen care coordination, specialty and mental health access, insurance continuity, family navigation, and responses to food and housing hardship. Keywords: attention-deficit/hyperactivity disorder; autism spectrum disorder; healthcare access; health disparities; social determinants of health

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: Pertussis has resurged in the post-COVID-19 era, yet diagnostic delay remains a barrier to timely treatment and transmission interruption, particularly among adults. Methods: Retrospective observational cohort study of 787 patients with confirmed pertussis from January 2016 through March 2026 across two South Carolina health systems. Electronic health record data from the 60 days preceding confirmation were used to characterize diagnostic timing (same-day vs. delayed), delay duration, and respiratory pathogen testing patterns including pertussis test modality. Results: Adults accounted for 48.4% of cases (median age 16 years [IQR 4-52]; 61.6% female). Same-day diagnosis was highest among children aged 1-4 years (75.4%) and lowest among adults aged 50 and older (approximately 50%). Among the 305 patients (38.8%) with delayed diagnosis, median delay ranged from 7-12 days in children to 22.5-26.5 days in adults aged 50 and older. Delay did not vary significantly by COVID-19 period, race, ethnicity, or insurance type. Testing breadth was greater in inpatient and emergency settings than outpatient. Pertussis testing was predominantly PCR-based in children but serologic in adults, potentially reflecting later clinical presentation relative to illness onset; however, the near-absence of PCR testing in older adults may contribute to missed diagnoses during the early illness window when PCR sensitivity is highest. Conclusions: Older adults experienced markedly delayed pertussis diagnoses compared with children. Earlier consideration of pertussis in adults with prolonged cough, including PCR testing early in illness before serologic conversion, may reduce diagnostic delay and facilitate timelier treatment and contact tracing.

PurposeTo examine the association between BMI-for-age z-score (BAZ) and BMI status with refractive error prevalence, incidence, subtypes, and quantitative refraction in Vietnamese schoolchildren. MethodsWe retrospectively analyzed body mass index and refractive error data from annual school health checks in three Vietnamese cities, 2022 to 2024. The main analysis set was restricted to children age 6 and older (49,415 examinations, 31,522 children). Refractive error subtypes and quantitative refraction came from a Hanoi autorefractor sub-cohort (13,059 examinations). We used sex-stratified Poisson models with generalized estimating equations, adjusted for age, city, and year, plus linear mixed models for quantitative outcomes. ResultsAny refractive error followed a U shaped curve across BAZ in both sexes, significant in girls (prevalence ratio 1.01 per 1-SD BAZ, p = 0.027) but not boys (p = 0.099). Obesity was associated with higher any refractive error prevalence in girls (adjusted prevalence ratio 1.05, p = 0.017). Astigmatism was associated with BAZ in both sexes (p < 0.001), anisometropia in boys only (p < 0.001), with no association for myopia or hyperopia. Spherical equivalent shifted slightly toward hyperopia, not myopia, with higher BAZ. A supplementary check over 1 to 2 years found no evidence that prior BAZ predicted new refractive error onset (prevalence ratio 1.02, p > 0.6 in both sexes), and the nonlinear pattern did not reappear. ConclusionsAdiposity relates cross-sectionally to refractive error in a nonlinear, sex specific way concentrated in astigmatism and anisometropia rather than myopia, though this did not hold up short term.

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.

Purpose Children with suspected rare genetic disorders often remain undiagnosed after exome, gene panel, or chromosomal microarray testing. We sought to define recurrent missed-diagnosis mechanisms and evaluate an integrated clinical-genomic reanalysis framework. Methods We studied 75 participants with rare or striking pediatric-onset phenotypes who remained undiagnosed after prior genetic testing. Trio genome sequencing evaluated SNVs, indels and copy-number variants. RNA sequencing was performed in 63 participants to assess aberrant expression and splicing, with targeted follow-up assays used selectively for prioritized variants. Clinician-genome scientist review integrated longitudinal phenotyping, physician input, and inheritance. Unresolved cases underwent research-level candidate prioritization. Results Clinically reportable findings were returned in 9, including two with multilocus findings: 5 explained the primary phenotype and 4, while not fully explanatory, were clinically relevant and informing surveillance, management, or family follow-up. Previously missed findings reflected technical limitations, including deep intronic splice-altering variants supported by transcriptome analysis and a genomic deletion, and interpretive limitations related to incomplete phenotype integration or narrowly scoped prior testing. Research-level analysis prioritized six candidate genes, including biallelic ACHE variants with reduced enzymatic activity. Conclusion Integrated clinical-genomic reanalysis framework identified diagnostic gaps, recovered care-informing findings, and prioritized candidate genes for rare disease discovery.

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.

BackgroundCOVID-19 pandemic modified trends of infant bronchiolitis, leading cause of emergency room (ER) attendance in infants in high income countries, primarily due to Respiratory Syncytial Virus. Understanding recent pandemic-related epidemiological shifts could inform affordable prevention efforts to improve sustainability and coverage of prophylactic treatments beyond maternal vaccines and infant monoclonal antibodies. MethodsWe estimated incidence rates (IR) of bronchiolitis ER presentations in 0-6month olds in 2012-2023 in a region-wide cohort of almost 1 million births using administrative health data from Lombardy, Italy. To assess potential contributors, we investigated direct and indirect COVID-19-related factors, including disease severity, shape of the epidemic peak, parental health seeking behaviour and vaccine coverage. We estimated COVID-19 maternal vaccination associations using mothers-infants data linkages and multivariable-adjusted logistic regression. FindingsCompared to pre-pandemic levels, IRs doubled in 2021-2023 (from 2 to [&ge;] 4/100 person-time). The surge could not be explained by changes in infant age at ER visit, clinical severity or in the shape of the epidemic peak. Adjusted models showed little support for a role of infant routine or maternal COVID-19 vaccination on bronchiolitis episodes (respectively hazard ratio 1.09, 95%CI: 0.98-1.22 and odds ratio 0.91, 95%CI: 0.76-1.09). InterpretationThe post-pandemic increase in infant bronchiolitis is likely driven by multiple epidemiological changes rather than a single factor. As maternal RSV vaccination and infant RSV monoclonal antibodies are introduced and scale up, identifying these mechanisms will be critical to maximise their public health impact, inform complementary prevention strategies, and improve preparedness for future RSV epidemics.

INTRODUCTION: Asthma has been associated with obesity in both adults and children. We investigated the association between longitudinal BMI trajectories and asthma at ages 8-9, 12-13, and 16-17 years in a UK cohort of White and South Asian children and adolescents. METHODS: We analysed data from the Leicester Respiratory Cohorts, population-based cohort studies that recruited 0-4-year-old children in 1990 (N = 1650) and 1998 (N = 8700) and followed them up until 2010. Outcome data on asthma came from postal questionnaires throughout infancy, childhood, and adolescence. BMI data came from birth records, well-child visits, questionnaires, and a clinical study visit. We used Group-based trajectory modelling to identify distinct BMI trajectories and used multivariable logistic regression to investigate the association with asthma. RESULTS: Out of 10,350 participants in the Leicester Respiratory Cohorts, we were able to model BMI trajectories for 5571 (54%); 1801 (17%) had information on asthma at 8-9 years of age, 1269 (12%) at 12-13 years, and 575 (6%) at 16-17 years. We identified five BMI trajectories: stable normal BMI (47%), persistent low BMI (30%), early overweight resolving (8%), childhood onset obesity (4%) adolescent onset overweight (11%). The persistent low BMI trajectory was associated with lower odds for asthma at age 8-9 years (0.56 [0.37-0.83]) and 12-13 years (0.38 [0.22-0.63]). Early overweight resolving was very similar to the reference stable normal BMI. The childhood onset obesity trajectory was associated with higher odds for asthma at 16-17 years (5.58 [1.35-24.40]). The adolescent onset overweight trajectory was not associated with asthma. When analysed separately, boys and girls and children of European and South Asian ancestry showed similar associations. CONCLUSION: This study strengthens the current understanding of obesity as a contributing factor in asthma development and highlights that early intervention and management of overweight and obesity in childhood, to achieve a normal BMI, may prevent secondary health impairments such as asthma.

Objective: to estimate reconsultation risk and trajectories after a new episode of musculoskeletal pain in children and young people (CYP), and to determine routinely recorded prognostic factors associated with reconsultation. Design: Population based retrospective cohort study. Setting: Clinical Practice Research Datalink (CPRD) Aurum, 2005-2021. Participants: CYP aged 8-18 years consulting primary care for a new musculoskeletal pain episode (no musculoskeletal consultation in prior 12-months). Main Outcome Measures: Musculoskeletal pain reconsultation within 12-months, and 3-year musculoskeletal reconsultation trajectories derived using latent class growth analysis. Prognostic factors selected from a literature search and two-year symptom histories (sample prevalence >1%) were examined using regression models (conditional logistic; multinomial). Results: Among 313,830 CYP with >12 months' follow-up, 32% reconsulted for musculoskeletal pain within 12 months. Among 240,384 CYP with >3 years' follow-up, three trajectories were observed: single episode (62%), early reconsultation (18%), and persistent reconsultation (20%). Older age; female gender; hip, knee, multisite and back pain on index; previous headache; previous abdominal pain; and analgesic prescribing were associated with higher reconsultation risk. Asian or Black ethnicity, and residing in more deprived areas, were associated with lower recorded reconsultation. Conclusion: Most CYP had no further recorded consultation, but 38% followed early or persistent reconsultation trajectories. Routinely recorded prognostic factors, particularly index pain side and prior pain/symptom history, may differentiate groups who could benefit from proactive follow-up. Lower recorded reconsultation among Asian and Black individuals, and living in more deprived areas, should not imply lower need and warrants equity-sensitive monitoring of access, health-seeking, and coding.

Background. Refractive error is a leading cause of childhood visual impairment worldwide, yet longitudinal, multi-city data from Vietnam remain scarce, especially for children younger than school age. We aimed to describe the prevalence and secular trends of refractive error in a large urban Vietnamese school health program. Methods. We conducted a retrospective analysis of repeated cross-sectional school health screening data collected from 2021 to 2024 across three major Vietnamese cities (Hanoi, Ho Chi Minh City, and Hai Phong), among children aged 3 to 18 years. The dataset included 141,339 examinations, with a Hanoi sub-cohort of 19,788 examinations that had quantitative autorefractor measurements. We estimated crude prevalence and adjusted prevalence ratios using Poisson regression. Results. The prevalence of any refractive error stayed high throughout the study period, ranging from 53.9% to 57.1% (P for trend < 0.001), and was higher in Hai Phong (68.4%) and Hanoi (61.6%) than Ho Chi Minh City (35.9%), higher in girls than boys (58.5% vs 53.1%), and higher with older age (P < 0.001). In the Hanoi sub-cohort, confirmed myopia prevalence nearly tripled, from 3.7% in 2022 to 11.0% in 2024 (P < 0.001), while hyperopia declined. Conclusions. Refractive error is highly prevalent among urban Vietnamese schoolchildren, and confirmed myopia appears to be rising rapidly at younger ages. These findings support closer surveillance and earlier school-based intervention in Vietnam and similar settings.