The Journal of Pediatrics

Objectives: Acute gastroenteritis is a leading cause of pediatric emergency department (ED) visits. While ondansetron reduces vomiting, intravenous rehydration, and hospital admissions, its efficacy when initiated at triage remains unclear. We aimed to evaluate whether triage nurse-initiated administration of ondansetron in children with suspected gastroenteritis reduces the proportion of patients requiring observation following initial physician assessment. Methods: We conducted a randomized, double-blind, placebo-controlled trial in a tertiary pediatric ED in Canada. Children aged 6 months to 17 years presenting with morae than 3 episodes of vomiting in the preceding 24 hours (including 1 within 2 hours of arrival), were eligible. At triage, we randomized participants to receive liquid ondansetron or a color- and taste-matched placebo. The primary outcome was the proportion of patients requiring observation after the first physician evaluation. Secondary outcomes included post-intervention vomiting, ED length of stay, patient comfort, and 48-hour return visits. The trial was registered at ClinicalTrials.gov (NCT03052361). Results: Recruitment was stopped prematurely due to the COVID-19 pandemic. Ninety-one participants were randomized to ondansetron (n= 44) or placebo (n= 47). Overall, 40 patients (45%) were discharged immediately after the initial physician assessment, with no difference between the ondansetron and placebo groups (44% vs. 45%; absolute difference -1%, 95% CI: -20% to 19%). No significant differences were observed in all secondary outcomes. Conclusion: In this trial, triage nurse-initiated ondansetron administration did not reduce the need for ED observation in children with presumed gastroenteritis. While being underpowered, this study could inform researchers planning larger clinical trials.

BackgroundPatent ductus arteriosus (PDA) is a common and potentially serious cardiovascular condition in preterm infants, particularly those with low gestational age and birth weight. Its management remains controversial due to variability in screening, diagnostic criteria, and treatment strategies. This study aimed to evaluate risk factors, outcomes, and management strategies for PDA in preterm infants, and to identify predictors of clinical and echocardiographic response to therapy. MethodsWe conducted a retrospective cohort study over a 4-year period (2016-2019) in the neonatal intensive care unit (NICU) of a tertiary care center. All consecutive preterm infants admitted during the study period were eligible. Infants with echocardiographically confirmed PDA who received pharmacological treatment with intravenous paracetamol or ibuprofen were included in the analysis. Missing data were minimal and handled using available-case analysis. Statistical analyses included descriptive statistics, Pearsons chi-square test, and multivariable logistic regression. ResultsAmong 2154 preterm infants admitted to the NICU, 60 were diagnosed with PDA (incidence : 2.8%). The mean gestational age was 29 {+/-} 2.6 weeks, and the median birth weight was 1200 g. Respiratory distress occurred in 95% of cases, mainly due to hyaline membrane disease (86.7%). PDA was symptomatic in 80% of infants. First-line treatment resulted in clinical improvement in 77% and ductal closure in 83.3% of cases, most within 3 days. Predictors of successful closure included gestational age [&ge;] 28 weeks (OR = 5.9; 95% CI : 1.7-20.2) and antenatal corticosteroid exposure (OR = 1.2; 95% CI : 1.0-1.6). Overall mortality was 35% and was significantly higher in infants < 28 weeks (OR = 5.0; 95% CI : 2.4-10.3). Clinical improvement (OR = 3.7) and echocardiographic closure (OR = 4.5) after first-line treatment were associated with reduced mortality. ConclusionsPDA in preterm infants is associated with substantial morbidity and mortality, particularly in those born before 28 weeks of gestation. Early diagnosis, antenatal corticosteroid exposure, and timely pharmacological treatment may improve outcomes. Systematic echocardiographic screening in high-risk neonates should be considered.

Objective Cerebral palsy (CP) affects approximately 1 million Americans and 18 million individuals worldwide, yet contemporary US epidemiologic data remains limited. We aimed to use Cerebral Palsy Research Network (CPRN) clinical registry to describe demographics and clinical characteristics of individuals with CP across the US and determine associations with gross motor function and genetic etiology. Methods Registry subjects were included if they had clinician-confirmed CP and prospectively entered data for Gross Motor Function Classification System (GMFCS) Level, gestational age, genetic etiology, CP distribution, and tone/movement types. Logistic regression was used to determine which of these variables plus race, sex, ethnicity, and age were associated with GMFCS level and genetic etiology. Results A total of 9,756 children and adults with CP from 22 CPRN sites met inclusion criteria. Participants were predominantly White (73.0%), male (57.3%), non-Hispanic (87.8%), and younger than 18 years (73.7%). Most were classified as GMFCS levels I-III (55.6%), born preterm (52.8%), had spasticity (83.8%), and had quadriplegia (41.9%); 12.2% were identified as having a genetic etiology. Tone/movement types, CP distribution, and gestational age were significantly associated with both GMFCS level and genetic etiology (p<0.001). Compared to White individuals, Black individuals were more likely to have greater gross motor impairment (p<0.001). Conclusion In this large US cohort, clinical and demographic factors, including race, were associated with gross motor function and genetic etiology in CP. These findings highlight persistent disparities and demonstrate the value of a national clinical registry for informing prognostication, quality improvement efforts, and targeted genetic testing strategies.

Objectives. To compare the efficacy and safety of invasive sacral neuromodulation (SNM) and noninvasive enteral neuromodulation (ENM) in children with refractory gastrointestinal motility disorders (GMD). Materials and Methods. This prospective interventional trial enrolled pediatric patients with GMD between 2019 and 2024 at a single tertiary referral center. Children with inflammatory bowel disease or mechanical causes of GMD were excluded. Participants received either SNM via an implanted device or ENM via surface electrodes. Stimulation was delivered at 14 Hz, 210 s pulse width, with individualized intensity (median 1.0 mA for SNM; 6.0 mA for ENM). Primary outcomes were abdominal pain, fecal incontinence, defecation frequency, and stool consistency. Treatment success was defined as clinically significant improvement in at least two of these four domains. Quality of life was assessed at baseline and 12 weeks. Safety outcomes were monitored over a 12-month follow-up. Results. Of 70 eligible patients, 48 completed the study (18 SNM; 30 ENM). Diagnoses included Hirschsprung disease, functional constipation, and congenital neuronal malformations. Severe comorbidities were more frequent in the SNM group (45%) than the ENM group (3%; P = .0018). Treatment success was observed in 80% of ENM and 83% of SNM patients (P = 1.00). No significant differences were found between groups for individual outcomes. No major complications occurred. Minor adverse events were comparable (ENM 27% vs SNM 17%; P = .50). Conclusions. Both SNM and ENM are effective and safe options for treating pediatric GMD and may be considered within a multimodal therapeutic approach.

Background: Extrauterine growth restriction (EUGR) is a common and clinically significant complication among preterm infants, contributing to adverse neurodevelopmental and metabolic outcomes. Early and individualized risk prediction remains challenging. This study aimed to develop and validate an interpretable machine learning model for early prediction of EUGR using routinely available clinical variables, and to implement a user-friendly web-based calculator for clinical use. Methods: We retrospectively analyzed 1,431 preterm infants admitted within 24 hours after birth to our hospital between May 2020 and March 2025. Infants from the Yangpu campus (n=863) formed the training set, and those from the Huangpu campus (n=568) formed the validation set. Early clinical variables available within 48-72 hours were screened using the Boruta algorithm. Logistic regression, XGBoost, random forest, decision tree, and support vector machine models were developed and compared. Model performance was evaluated using area under the curve (AUC), accuracy, sensitivity, specificity, F1 score, and Brier score. SHapley Additive exPlanations (SHAP) were applied to assess global and individual feature contributions, nonlinear effects, and interactions. A web-based calculator was constructed based on the optimal model. Results: Nine variables were identified as important predictors: birth weight, small for gestational age status, gestational age, breastfeeding, multiple gestation, neonatal respiratory distress syndrome, patent ductus arteriosus, maternal hypertension, and maternal group B Streptococcus infection. Among the five models, XGBoost achieved the best performance in the validation set (AUC 0.922, accuracy 0.849, Brier score 0.108). SHAP analysis showed that low birth weight, small for gestational age, maternal group B Streptococcus infection, and patent ductus arteriosus were major risk factors, while breastfeeding was protective. Notable nonlinear and interactive effects were observed, particularly between birth weight and gestational age and between breastfeeding and patent ductus arteriosus. The web-based calculator provides real-time individualized risk estimation and visualized interpretation. Conclusions: An interpretable XGBoost-based model and web calculator were successfully developed and validated for early prediction of EUGR in preterm infants. This tool may support clinicians in identifying high-risk infants and guiding individualized nutritional and clinical management.

Premature very low birth weight (VLBW) infants have high rates of mortality and morbidity from sepsis, necrotizing enterocolitis, and respiratory failure requiring intubation and mechanical ventilation. Earlier detection of cardiorespiratory deterioration using vital signs from continuous physiological monitoring may lead to more timely interventions and improved outcomes. To further this research area, we present PreMo, a publicly available dataset of continuous heart rate and oxygen saturation, demographics, clinical events, and outcomes for 3,829 VLBW patients from four Neonatal Intensive Care Units (NICUs) in the United States. The PreMo dataset consists of a collection of parquet files, RO-Crate metadata, and sample usage code scripts hosted on the University of Virginia LibraData Dataverse website.

Background: Children with congenital heart disease (CHD) require specialized care and may face worse outcomes if they experience food insecurity (FI). FI is associated with poor nutrition, hospitalizations, and developmental delays, compounding cardiac risks. Limited research evaluated impact of FI on health status among children with CHD. This study examines socioeconomic factors and the relationship between FI and health status in children with CHD. Methods: 2023 National Survey of Children?s Health (NSCH) data were used to compare rates of FI between children ages < 17 years with and without CHD and to assess overall health status of those with CHD. Descriptive, univariate, and multivariable logistic regression were utilized. Results: Among 53,477 children, 1,233(2%) had CHD. FI was reported in 35% of children with CHD vs. 27% without CHD(p=0.005). After adjustment, children with CHD had higher odds of FI (OR 1.49; 95% CI: 1.05?2.12). Hispanic ethnicity, residence in Midwest or South, lower household education, and lower poverty index were significantly associated with FI. Households receiving food assistance had higher FI. Living in grandparent household was associated with lower odds of FI. Within the CHD subgroup, 5% reported fair or poor health. Children with CHD experiencing FI had greater odds of fair or poor health than those without FI (OR 3.91, 95% CI 1.70?9.02; p=0.001). Conclusions: Children with CHD face higher odds of FI, which is strongly associated with worse reported health. Addressing socioeconomic vulnerability and FI may improve outcomes and reduce disparities in this high-risk population through targeted screening and intervention strategies nationwide. Keywords: Congenital Heart Disease, Food Insecurity Screening, National Survey of Children?s Health (NSCH), Health Disparities

Background: Preterm births contribute to approximately 35% of neonatal deaths globally, with an estimated 13.4 million infants born prematurely each year. Despite this substantial burden, limited evidence exists on time to discharge and its determinants among preterm neonates admitted to Neonatal Intensive Care Units (NICUs), particularly in rural Ugandan settings. This study aimed to investigate time to discharge and associated factors among preterm neonates admitted to Kiwoko Hospital in Nakaseke District, Uganda. Methods: A retrospective cohort study was conducted using secondary data from Kiwoko Hospital on preterm neonates admitted to the Neonatal Intensive Care Unit (NICU) between 2020 and 2021 (n = 847). The cumulative incidence function was used to estimate the probability of discharge within 28 days of admission, accounting for competing events. A Fine and Gray sub-distribution hazard regression model was fitted to identify factors associated with time to discharge. Results: Of the 847 preterm admissions, 70.1% were discharged alive within 28 days. The median time to discharge was 14 days. The cumulative incidence of discharge by 28 days was 68%, accounting for competing events. During follow-up, 165 neonates did not complete the 28-day period, including 88 deaths. Factors significantly associated with time to discharge included place of delivery (SHR: 0.62; 95% CI: 0.53-0.73; p<0.001), maternal residence in other districts (SHR: 0.69; 95% CI: 0.48-0.99; p=0.044), extreme preterm (SHR: 0.05; 95% CI: 0.03-0.09; p<0.001), very preterm (SHR: 0.18; 95% CI: 0.14-0.25; p<0.001), moderate preterm (SHR: 0.59; 95% CI: 0.46-0.76; p<0.001), triplet births (SHR: 0.40; 95% CI: 0.23-0.68; p=0.001), 2-4 ANC visits (SHR: 0.70; 95% CI: 0.56-0.87; p=0.002), <=1 ANC visit (SHR: 0.64; 95% CI: 0.49-0.85; p=0.002), respiratory distress syndrome (SHR: 0.64; 95% CI: 0.48-0.74; p<0.001), and birth trauma (SHR: 2.62; 95% CI: 1.60-4.29; p<0.001). Conclusions: Respiratory distress syndrome, fewer antenatal care visits, out-of-district residence, and higher degrees of prematurity were associated with prolonged time to discharge among preterm neonates. Strengthening antenatal care utilization and improving access to quality neonatal care in underserved areas may enhance discharge outcomes.

ImportanceGuideline-concordant care for young children with attention-deficit/hyperactivity disorder (ADHD) includes recommending parent training in behavior management (PTBM) as first-line treatment. However, assessing guideline adherence through manual chart review is time-consuming and costly, limiting scalable and timely quality-of-care measurement. ObjectiveTo evaluate the accuracy and explainability of large language models (LLMs) in identifying PTBM recommendations in pediatric electronic health record (EHR) notes as a scalable alternative to manual chart review. Design, Setting, and ParticipantsThis retrospective cohort study was conducted in a community-based pediatric healthcare network in California consisting of 27 primary care clinics. The study cohort included children aged 4-6 years with [&ge;] 2 primary care visits between 2020-2024 and ICD-10 diagnoses of ADHD or ADHD symptoms (n=542 patients). Clinical notes from the first ADHD-related visit were included. A stratified subset of 122 notes, including all cases with model disagreement, was manually annotated to assess model performance in identifying PTBM recommendations and rank model explanations. ExposuresAssessment and plan sections of clinical notes were analyzed using three generative large language models (Claude-3.5, GPT-4o, and LLaMA-3.3-70B) to identify the presence of PTBM recommendations and generate explanatory rationales and documentation evidence. Main Outcomes and MeasuresModel performance in identifying PTBM recommendations (measured by sensitivity, positive predictive value (PPV), and F1-score) and qualitative explainability ratings of model-generated rationales (based on the QUEST framework). ResultsAll three models demonstrated high performance compared to expert chart review. Claude-3.5 showed balanced performance (sensitivity=0.89, PPV=0.95, and F1-score=0.92) and ranked highest in explainability. LLaMA3.3-70B achieved sensitivity=0.91, PPV=0.89, and F1-score=0.90, ranking second for explainability. GPT-4o had the highest PPV [0.97] but lowest sensitivity [0.82], with an F1-score of 0.89 and the lowest explainability ranking. Based on classifications from the best-performing model, Claude-3.5, 26.4% (143/542) of patients had documented PTBM recommendations at their first ADHD-related visit. Conclusions and RelevanceLLMs can accurately extract guideline-concordant clinician recommendations for non-pharmacological ADHD treatment from unstructured clinical notes while providing clear explanations and supporting evidence. Evaluating model explainability as part of LLM implementation for medical chart review tasks can promote transparent and scalable solutions for quality-of-care measurement.

Background: Lifestyle interventions incorporating medically-tailored meal delivery may support rapid behavior change among pregnant individuals with gestational diabetes (GDM). Purpose: To examine the feasibility and acceptability of a multicomponent lifestyle intervention for pregnant individuals with GDM. Primary outcomes included recruitment, retention, intervention receipt, and acceptability. Methods: We conducted a pilot randomized feasibility trial among pregnant individuals with GDM recruited from maternal fetal medicine clinics in the Hartford, Connecticut area. Participants were randomized to usual GDM care or the Meals4Moms intervention plus usual care. The intervention included medically-tailored meal delivery, personalized physical activity support, and multimodal education with digital tools. Participants completed a survey and three 24-hour dietary recalls at baseline and post-intervention. Meals4Moms participants also completed a semi-structured interview at follow-up. Intervention receipt was tracked by study staff. Results: Of 30 individuals approached, we screened 80% (n=24), of whom 75% (n=18/24) were eligible; we randomized 8 participants. Seventy-five percent (n=6/8) completed at least one component of the follow-up assessment (100%, n=4/4 Meals4Moms, 50%, n=2/4 Usual Care). One participant spent [&ge;]80% of her total food budget (n=1/4, 25%), and no participants completed [&ge;]80% of prescribed exercise sessions (range: 0-50%). All (n=4) Meals4Moms participants reported they would be very likely to participate in the program if they had GDM again, and 100% (n=4) would be very likely to recommend the program to a friend with GDM. Conclusions: While the Meals4Moms intervention was highly acceptable to participants, procedural refinements are needed prior to conducting a full-scale efficacy trial.

Background. Brain development is altered in neonates with congenital heart disease (CHD). However, development in the perioperative period remains incompletely understood. Purpose. This study used Structural Covariance Component (SCC) analysis to identify brain regions showing spatial patterns of coordinated expansion and contraction that differ between neonates with CHD after cardiac intervention and healthy controls, as well as pre-to postoperative changes and effects of perioperative risk factors. Study type. Prospective. Population. The cohort included 41 neonates with CHD who underwent cardiac surgery or catheterization and 359 healthy neonates. Field strength and sequence. 3 Tesla T2-weighted turbo-spin-echo sequence. Assessment: Brain MRI were motion-corrected and reconstructed using an established neonatal algorithm. Jacobian determinants calculated from non-linear registration of MRI to a neonatal template were input into an Independent Component Analysis to identify SCCs (N=40). SCC weightings were extracted, reflecting the degree to which the pattern of covariance is expressed in each neonate. Statistical tests. Postoperative SCC weightings were compared to healthy neonates using a general linear model or robust regression. Pre- and postoperative SCC weightings were compared using a linear mixed effect model. Pre- to postoperative differences were calculated and associations with age at surgery, cardiopulmonary bypass duration, and postoperative paediatric intensive care unit stay were assessed using partial spearman's rank correlation. Analyses were adjusted for covariates and corrected for multiple comparisons using False Discovery Rate. Results. 16/40 SCCs showed significant differences between neonates with CHD after surgery and controls, including white matter, cortical- and deep grey matter, brainstem, and CSF regions, with seven also showing significant perioperative change. A further nine SCCs only showed significant perioperative change. Perioperative risk factors were not associated with perioperative change. Data conclusion. This data-driven approach highlights region-specific postoperative alterations and perioperative changes in brain morphology of neonates with CHD. Evidence level. 1. Technical Efficacy. Stage 3.

Objective: To describe the clinical characteristics of term neonates with neonatal bacterial meningitis (NBM) and explore the association between different pathogens and imaging complications, providing clinical evidence for early identification and individualized management. Methods: A retrospective study was conducted on 531 term neonates diagnosed with NBM admitted to the Capital Institute of Pediatrics from 2013 to 2025. Demographics, clinical manifestations, laboratory parameters, etiological results, imaging complications and treatment measures were collected. Patients were divided into favorable/adverse discharge outcome groups and pathogen-positive/negative groups. Statistical analyses were performed using appropriate tests, and Cramers V coefficient was used to analyze the association between pathogens and imaging complications. Results: (1) The most common clinical manifestations were abnormal body temperature (79.85%), altered consciousness (55.18%) and jaundice (46.52%). CSF/blood culture was positive in 133 cases (25.05%), with Escherichia coli (27.07%), group B streptococcus (17.29%) and Staphylococcus species (16.54%) as predominant pathogens. The overall incidence of imaging complications was 22.22%, mainly hydrocephalus (5.84%), subdural effusion (4.90%) and encephalomalacia (2.64%). (2) Adverse discharge outcomes occurred in 107 cases (20.15%). Compared with the favorable group, the adverse group had higher incidences of convulsions, altered consciousness, anterior fontanelle bulging, abnormal muscle tone and primitive reflexes (all P<0.001), more obvious laboratory abnormalities (higher CRP, CSF leukocytes and protein, lower CSF glucose, all P<0.05), higher culture positive rates and greater need for adjuvant therapy (all P<0.001). (3) Pathogen-positive patients had higher imaging complication rates. Gram-negative infections were associated with higher hydrocephalus and subdural effusion rates, while Gram-positive infections had higher brain abscess risk. Specifically, Escherichia coli correlated with hydrocephalus and subdural effusion; group B streptococcus with cerebral infarction and encephalomalacia; LM with intracranial hemorrhage and brain abscess; negative cultures correlated with no imaging complications (all P<0.05). Conclusion: Term NBM neonates have non-specific manifestations, mainly abnormal body temperature and altered consciousness. Predominant pathogens are Escherichia coli, group B streptococcus and Staphylococcus species, with hydrocephalus and subdural effusion as common imaging complications. Adverse outcomes are associated with severe symptoms, obvious laboratory abnormalities and higher pathogen positivity. Specific pathogens correlate with distinct imaging complications.

Introduction: The Pubertal Development Scale (PDS) is widely used for puberty assessment, yet its psychometric properties and norms are limited to research data. This study examined the psychometric properties of parent- and self-report PDS and established continuous norms in nationally representative samples. Methods: We analyzed two deidentified survey samples: a parent-report sample of children aged 6-18 (N=2000, Mage=11.37, 47.2% female, 74.9% White), and a youth self-report sample aged 12-18 (N=754, Mage=14.33, 49.6% female, 75.3% White). Both samples were representative of the U.S. population on key demographics, and the self-report sample consisted entirely of children whose parents also participated in the parent sample, thus creating parent-child dyads. Internal consistency was evaluated using Cronbach's alpha and McDonald's Omega. Cross-informant agreement was assessed with Intraclass Correlation Coefficient (ICC; two-way model, absolute agreement, single unit) and Bland-Altman plots. Age-dependent norms of each sex were established with Generalized Additive Models for Location, Scale, and Shape (GAMLSS), with 5th-95th percentile curves and reference tables provided. Results: Parent- and self-report PDS demonstrated acceptable-to-good internal consistency (Cronbach's alpha: 0.78-0.89; McDonald's omega: 0.79-0.90). Among the 754 parent-youth dyads, excellent cross-informant agreement was observed for both sexes (ICC(2,1)=0.88). Parents' and children's PDS total scores did not differ significantly for boys; for girls, parents rated pubertal development on average 0.13 points lower than children's self-report. Regardless of informants, PDS scores increased nonlinearly with age and exhibited sex-specific developmental patterns. Girls showed earlier pubertal onset, faster progression, and greater convergence toward pubertal completion by late adolescence. Discussion: The PDS demonstrated strong psychometrics in national samples, supporting its utility in the general pediatric population. The national norms provide empirical benchmarks for PDS score interpretation, strengthening its value as a broad estimation of pubertal status and a pre-screening tool for identifying early or delayed puberty.

Wolfram syndrome is a rare autosomal recessive disorder caused by pathogenic variants in the WFS1 gene, characterized by early-onset diabetes mellitus, optic atrophy, sensorineural hearing loss, arginine vasopressin deficiency, and progressive neurodegeneration. The condition selectively affects pancreatic {beta} cells and neurons via chronic endoplasmic reticulum (ER) stress, and no proven disease-modifying therapy currently exists. Diabetes mellitus is typically the first manifestation, presenting at a mean age of 6 years as an insulin-dependent phenotype with preserved C-peptide and negative diabetes-related autoantibodies. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are well-established agents in the management of type 2 diabetes, augmenting glucose-dependent insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting satiety. Preclinical evidence further suggests that GLP-1 RAs preserve {beta}-cell mass, attenuate ER stress, and confer neuroprotective effects, properties of particular therapeutic relevance to Wolfram syndrome. We conducted a retrospective cohort study of 84 participants with genetically confirmed Wolfram syndrome and insulin-dependent diabetes mellitus enrolled in the Washington University Wolfram Syndrome International Registry and Clinical Study. Clinical data were extracted from medical records; for participants concurrently enrolled in the Tracking Neurodegeneration in Early Wolfram Syndrome study, longitudinal data were obtained from that source as well. Thirty-five percent of eligible participants had received a GLP-1 RA at some point during follow-up. We characterize the prevalence of GLP-1 RA use, documented rationale for initiation, observed effects on glycemic control and visual outcomes, adverse effects, and reasons for discontinuation. No statistically significant changes in hemoglobin A1c (HbA1c) or body mass index (BMI) were observed. Visual acuity declined significantly at two years, consistent with expected disease progression. Gastrointestinal adverse effects were common and contributed to frequent discontinuation. These observational data provide important clinical context and a foundation for future prospective trials evaluating GLP-1 RAs as a potential disease-modifying strategy in Wolfram syndrome.

ObjectiveTo establish a fetal lamb model of complex gastroschisis and characterize the impact on the intestines over time. Summary Background DataGastroschisis is a congenital abdominal wall defect and in its complex form is associated with serious morbidity. Robust large-animal models may help understanding are lacking. MethodsAt gestational day 75, gastroschisis was induced by creating a 1-cm abdominal wall defect reinforced by a silicone ring. Fetuses were assessed either at term or at mid-gestation (13-21 days post-induction). The primary outcome was complex gastroschisis occurrence, defined by bowel stenosis, atresia, volvulus, perforation or necrosis; otherwise classified as simple. At mid-gestation, occurrence was compared between early (13-16 days) and late (17-21 days) intervals. Secondary outcomes included prenatal ultrasound findings, in vivo bowel motility and morphology, ex-vivo bowel contractility, amniotic fluid composition, and histology across complex, simple, and normal groups. ResultsGastroschisis was induced in 32 fetuses. At term (n=14), all survivors (7/14; 50%) had complex gastroschisis, with impaired bowel motility, altered enteric neural contractile responses and smooth muscle remodeling. At mid-gestation (n=18), complex gastroschisis occurred more frequently in the late than in the early group (71% vs. 11%; p=0.035). Mid-gestation gastroschisis fetuses showed greater intra-abdominal bowel dilatation on ultrasound and higher amniotic fluid digestive enzyme levels compared with non-operated littermates, with the greatest dilation observed in complex gastroschisis. ConclusionsThis model consistently reproduces complex gastroschisis in term survivors. After induction, complex gastroschisis occurrence increases with disease duration and is accompanied by structural and functional bowel changes.

Objective The decline of the perinatal demise rate is slowing and demises are often unexplained. Significant research has been done regarding diagnostic yield and genetic causes of demise, but little is known about how Geneticist involvement impacts outcomes. The goal of the study was to evaluate post-mortem genetic testing practices and effects of the geneticists involvement. Methods Retrospective data from 111 perinatal demise cases was examined, including rates of prenatal genetic counseling, post-delivery genetics consult, genetic testing, and autopsy investigation. Results In this cohort 54% received genetic testing and 25% received a genetics consult. When compared to those without, cases with genetic specialist involvement were associated with significant increases in testing uptake (p=0.007), diagnostic yield (p<0.001), and patient education (p<0.001). Second trimester stillbirths and those with fewer ultrasound (US) abnormalities were less likely to receive genetic testing (both p values <0.001) and consults (p<0.001, p=0.020). Conclusion Though it was not possible to avoid ascertainment bias, this data demonstrates that geneticist involvement correlates with a higher rate of testing, greater diagnostic yield, and more thorough counseling. These findings underscore the importance of integrating genetics providers into perinatal postmortem healthcare teams.

Neonates requiring intensive care are at increased risk for long-term neuropsychiatric disorders. However, clinical adoption of risk prediction models remains limited when their performance lacks adequate interpretability for informed clinical decision-making. Here, we investigated whether longitudinal neonatal electronic health record (EHR) data from the first 90 days of life can support clinically meaningful interpretation of long-term risk signals for major neuropsychiatric diagnoses by age seven. In a retrospective register-based cohort of 17,655 at-risk children from an academic medical center, of whom 8.0\% (1,420) received a major neuropsychiatric diagnosis during follow-up, we applied a time-aware transformer model (Self-supervised Transformer for Time-Series; STraTS) and thoroughly evaluated its predictions using three complementary interpretability approaches: perturbation-based variable importance, value-dependent effect analysis, and leave-one-out (LOO) feature attribution. STraTS achieved the highest area under the precision--recall curve (AUPRC 0.171 {+/-} 0.022), compared with Random Forest (0.166 {+/-} 0.008), logistic regression (0.151 {+/-} 0.007), and XGBoost (0.128 {+/-} 0.010). Across interpretability methods, five predictors were consistently identified: birth weight, gender, Apgar score at 1 minute, umbilical serum thyroid stimulating hormone (uS-TSH), and treatment time in hospital. Indicators of early clinical severity, including chromosomal abnormalities and neonatal cerebral-status disturbances, showed the largest risk-increasing effects. Furthermore, the model's learned vector representations of subject-specific EHR sequences formed clinically coherent latent embeddings that reflect population heterogeneity along established perinatal risk dimensions. These findings demonstrate that combining multiple complementary interpretability methods yields stable, clinically plausible risk signals while revealing limitations that would remain undetected by any single approach, highlighting the importance of careful interpretability analysis of deep learning-based risk predictions.

OBJECTIVE This study investigates the long-term impacts of childhood exposure to voiding cystourethrogram (VCUG), a diagnostic procedure for vesicoureteral reflux. Primary outcomes include long-term health outcomes, mental health disorders, healthcare avoidance, and participation in risky behaviors compared to a control group. METHODS A 9-month retrospective cohort study was conducted with adults who received most of their medical care in the U.S. Respondents self-reported health metrics, behaviors, and outcomes via a 20-minute survey. Respondents were divided into two groups: those who remembered undergoing at least one VCUG in childhood (VCUG group), and those who did not (control group). RESULTS Of 334 respondents, 204 (61%) were in the VCUG group (mean age: 29, 70% female) and 130 (39%) were controls (mean age: 34, 70% female). Notable findings include: 47% of VCUG respondents were diagnosed with depression compared to 27% of controls. 15% of female-born VCUG respondents reported they would never visit a gynecologist compared to 2% of controls. 34% of VCUG respondents smoked regularly compared to 5% of controls, and 11% of VCUG respondents regularly missed work compared to 1% of controls. These findings highlight the need for further research and clinical consideration of VCUG's long-term consequences. CONCLUSIONS This study suggests that the effects of childhood VCUG extend into adulthood. Our findings underscore the need to reassess informed consent protocols and consider full-scale studies to minimize bias.

Background: Hereditary transthyretin amyloidosis (hATTR) manifests as cardiomyopathy and/or polyneuropathy. The V142I variant predominantly causes cardiac disease in African Americans, though neurological involvement may be underrecognized. We characterized neuropathy documentation and treatment patterns in a predominantly V142I cohort. Methods: Retrospective review of 54 hATTR patients at a major academic medical center. Neuropathy was classified as: objective (abnormal EMG), possible polyneuropathy (documented symptoms suggestive of polyneuropathy), symptoms only (neuropathic symptoms without specialist evaluation), or unclear. Treatment with stabilizers (tafamidis, acoramidis, diflunisal) and gene silencers (patisiran, vutrisiran, eplontersen) was assessed. Results: Of 54 patients (88.9% African American, 85.2% V142I), 51 (94.4%) had confirmed cardiac involvement. Among cardiac patients, 40/42 eligible (95.2%) received stabilizers. Overall, 16 patients (29.6%) received gene silencers, with 13 (24.1%) receiving both a stabilizer and gene silencer concurrently. Possible neuropathy (objective, possible polyneuropathy, or symptoms) was documented in 30 patients (55.6%). Gene silencer use was highest among those with objective neuropathy (8/17, 47.1%) versus symptoms only (1/10, 10.0%). All three patients without confirmed cardiac disease received gene silencers. Conclusions: In this V142I-predominant cohort with 94.4% cardiac involvement, stabilizer use was high (95.2%) among eligible patients. Over half had possible neuropathy based on clinical documentation, though EMG completion was limited (57.4%). Gene silencer use was associated with objective neuropathy documentation and non-cardiac phenotype. These findings support systematic neurological assessment in hATTR, even when cardiac disease predominates.

Background Intracranial aneurysm rupture is the leading cause of spontaneous subarachnoid hemorrhage and is associated with substantial mortality and long term neurological disability. Emerging evidence suggests that the gut microbiome may influence vascular inflammation and endothelial integrity through immune and metabolic pathways, yet human evidence linking gut microbial alterations to intracranial aneurysm remains fragmented and inconsistent. Objective This systematic review and meta analysis aimed to synthesize available human evidence on the association between gut microbiome alterations and intracranial aneurysm formation or rupture, with a primary focus on microbial dysbiosis and differences in gut microbial alpha diversity. Methods This study was conducted according to PRISMA 2020 guidelines and the protocol was prospectively registered in PROSPERO (CRD420261360785). A comprehensive search of PubMed, Scopus, Web of Science, Embase, and Cochrane CENTRAL was performed from database inception until April 1, 2026, with additional screening of grey literature sources. Observational human studies evaluating gut microbiome characteristics in patients with intracranial aneurysm were included. Mendelian randomization (MR) studies investigating genetically predicted microbial taxa and aneurysm outcomes were also reviewed. Random effects meta analysis using standardized mean differences (SMD) was performed for alpha diversity outcomes. MR taxa reported in at least two independent studies were quantitatively synthesized using inverse variance weighting of log odds ratios. Results The systematic search identified 396 records. After removal of duplicates and eligibility screening, 20 studies met inclusion criteria, including 12 observational clinical studies and 8 Mendelian randomization analyses. Meta analysis of three microbiome sequencing studies demonstrated significantly reduced gut microbial alpha diversity in patients with ruptured intracranial aneurysms compared with controls. Sensitivity analyses confirmed the robustness of pooled estimates. In addition, MR evidence identified several microbial taxa, including Ruminococcus1, Bilophila, Fusicatenibacter, and Porphyromonadaceae, as potentially protective factors against aneurysm related outcomes. Across observational studies, gut dysbiosis was frequently associated with inflammatory pathways and alterations in microbial metabolites implicated in vascular dysfunction. Conclusion Current human evidence suggests a potential association between gut microbiome dysbiosis and intracranial aneurysm pathophysiology, particularly in relation to aneurysm rupture. Reduced microbial diversity and specific microbial taxa may influence vascular inflammation and aneurysm wall stability. However, existing evidence remains limited and heterogeneous. Large prospective cohorts and mechanistic studies are required to clarify causal relationships and evaluate whether microbiome targeted interventions could contribute to aneurysm risk stratification or prevention strategies.