OBJECTIVES: To investigate the effect of preterm birth on physical activity (PA) in 9- to 12-year-old children, and to describe group differences in relationships between PA and lung function, and PA and respiratory morb...OBJECTIVES: To investigate the effect of preterm birth on physical activity (PA) in 9- to 12-year-old children, and to describe group differences in relationships between PA and lung function, and PA and respiratory morbidity, between children born preterm and term. STUDY DESIGN: A total of 343 children completed follow-up including children born very preterm (VPT; <30 weeks of gestation, n = 91), moderate-to-late preterm (MLPT; 32-36 weeks of gestation, n = 139), and term (n = 113). PA was measured using 7-day accelerometry and the Physical Activity Questionnaire for Older Children (PAQ-C). Imputation models were used to handle missing data as the total sample recruited at birth included 551 participants. RESULTS: Children born VPT had more stationary (mean difference (MD): 32 minutes, 95% CI 4, 60; P= .024) and screen time (MD: 25 minutes, 95% CI 0.2, 50; P= .048), and had lower PAQ-C scores (MD: -0.3, 95% CI -0.4, -0.1; P= .001) than term-born children. Children born MLPT completed more screen time (MD: 22 minutes, 95% CI 1, 43; P= .038) than term-born children. All children failed to meet moderate-vigorous PA recommendations (≥60 minutes/day), with 16.6 minutes on average observed across all participants. CONCLUSIONS: Children born VPT were more sedentary with lower PAQ-C scores, and both preterm groups (VPT and MLPT) had higher screen time than children born at term. No children met moderate-vigorous PA guidelines, indicating early, targeted strategies to curb sedentary behavior and promote activity should be prioritized.
OBJECTIVE: To evaluate racial and ethnic differences in referral timing, diagnostic evaluation, and treatment of central precocious puberty (CPP) among girls referred to a pediatric endocrinology clinic. STUDY DESIGN: A...OBJECTIVE: To evaluate racial and ethnic differences in referral timing, diagnostic evaluation, and treatment of central precocious puberty (CPP) among girls referred to a pediatric endocrinology clinic. STUDY DESIGN: A retrospective chart review of female patients referred for early puberty between January 2010 and January 2023 and subsequently diagnosed with CPP. Extracted data included age at referral, race and ethnicity, insurance type, pubertal stage at first visit, laboratory evaluation, imaging, and treatment. Patients with alternative diagnoses, those referred for other endocrine concerns, or those transferring care with a prior CPP diagnosis were excluded. Statistical analyses were performed using SAS 9.4. RESULTS: Of 485 referred patients, 259 met inclusion criteria. Referral age did not differ significantly across racial and ethnic groups (P=.08), nor did age at endocrinology appointment (P=.17). Median time from referral to appointment differed across racial and ethnic groups (P=.04), although absolute differences were small. Tanner staging at presentation did not significantly differ (breast stage P=.10; pubic hair stage P=.09). Diagnostic evaluation, including laboratory testing and imaging, was similar by race and ethnicity. Gonadotropin-releasing hormone agonists were prescribed to 44-71% of patients across racial groups without significant difference (P=.40), and time from first endocrinology visit to treatment initiation did not differ (P=.13). However, cumulative time from referral to treatment initiation differed by race and ethnicity (P=.01). Analyses stratified by insurance type and neighborhood deprivation index showed no significant differences in referral timing, evaluation, or treatment. CONCLUSIONS: We found no significant racial or ethnic disparities in CPP referral timing, evaluation, or treatment. A small difference in referral-to-appointment time was identified but is likely not clinically meaningful. Further research is needed to determine whether disparities in CPP recognition or referral patterns exist upstream from specialty care.
OBJECTIVE: To assess pulse oximetry saturation (SpO to arterial oxygen saturation (SaO) bias relative to skin pigmentation in newborns and to address potentially occult hypoxemia, defined as SaO lower than SpO. STUDY DES...OBJECTIVE: To assess pulse oximetry saturation (SpO to arterial oxygen saturation (SaO) bias relative to skin pigmentation in newborns and to address potentially occult hypoxemia, defined as SaO lower than SpO. STUDY DESIGN: We conducted a prospective, diagnostic accuracy study at 2 tertiary neonatal intensive care units between 2022-2025 to assess SpO-SaO differences in relation to skin pigmentation in newborns. Newborns younger than 10 postnatal days with an arterial catheter undergoing an arterial blood gas collection were enrolled. A pulse oximeter was placed on the extremity corresponding to the arterial sampling site, and SpO values were recorded during blood gas collection. Skin pigmentation was measured noninvasively using individual typology angle (ITA), melanin index, and visual assessments. Mean SpO was calculated from the 30 seconds immediately preceding arterial sampling or from the most stable 30-second average when timestamps were unavailable and compared with SaO to calculate SpO-SaO bias. RESULTS: A total of 136 matched SpO-SaO pairs from 70 patients were analyzed, of whom 40% were Black. The overall mean bias was -0·98 ± 2·8% (95% CI -1·4 to -0·52), indicating an underestimation of SaO by SpO. Across categorical skin-pigmentation measures and race, no statistically significant differences in SpO-SaO bias were observed. When analyzed continuously, bias became less negative with lighter skin pigmentation for both ITA and melanin index, reaching significance only for ITA when analyses were restricted to the first measurement per patient (slope +0·016 per ITA unit, 95% CI 0·001-0·032, p=0·041). Occult hypoxemia was rare, occurring in one newborn with light skin pigmentation. CONCLUSION: In this prospective neonatal study with tightly paired measurements, SpO slightly underestimated SaO but did not demonstrate clinically significant disparities across skin pigmentation.
OBJECTIVE: To characterize barriers and facilitators influencing caregiver decision-making regarding living donor liver transplantation (LDLT) for children with end-stage liver disease. STUDY DESIGN: This qualitative stu...OBJECTIVE: To characterize barriers and facilitators influencing caregiver decision-making regarding living donor liver transplantation (LDLT) for children with end-stage liver disease. STUDY DESIGN: This qualitative study used semistructured, in-depth interviews conducted between May 2023 and March 2025 with caregivers of pediatric liver transplant recipients enrolled in the Social & Contextual Impact on Children Undergoing Liver Transplantation study cohort. Interviews were recorded and professionally transcribed, then independently coded by 3 reviewers using a codebook informed by the capability, opportunity, motivation - behavior model, an implementation science framework. Codes were compared and reconciled to generate themes. RESULTS: Eighteen caregivers participated; 50% reported household incomes <150% of the federal poverty level. Seven themes emerged: (1) insufficient time to comprehend transplant options, (2) perceived or actual lack of eligible donors in caregiver's social network, (3) concern about donor health consequences, (4) challenge of being both a caregiver and donor, (5) discordance between discomfort asking others to donate and response received, (6) limited knowledge about differences between whole and split liver, and (7) the appeal of flexible surgical scheduling offered by LDLT. These themes highlight the interplay between cognitive, social, and practical factors influencing pursuit of living donation. CONCLUSIONS: Strategies to support decision-making about LDLT should include counseling about the procedure's benefits early in the transplant evaluation process, helping identify nondirected donors and reducing the caregiving burden during the donor recovery period. Such efforts should prioritize under-resourced families to enhance equitable outcomes for children with end-stage liver disease. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT04551742.
OBJECTIVE: To characterize unintentional pediatric exposures to hemp-derived cannabinoids (eg, Δ8-tetrahydrocannabinol [THC], Δ10-THC, tetrahydrocannabinol-O-acetate) and evaluate how these exposures compare with those f...OBJECTIVE: To characterize unintentional pediatric exposures to hemp-derived cannabinoids (eg, Δ8-tetrahydrocannabinol [THC], Δ10-THC, tetrahydrocannabinol-O-acetate) and evaluate how these exposures compare with those following Δ9-THC, the primary psychoactive component of cannabis. METHODS: We conducted a retrospective analysis of the National Poison Data System for single-substance exposures to cannabis edibles reported to contain either Δ9-THC or to hemp-derived cannabinoids in children ≤5 years from January 1, 2023, to December 31, 2024. Clinical effects, interventions, and outcomes were compared using chi-square tests. RESULTS: During the study period, 9667 Δ9-THC and 2169 hemp-derived cannabinoid cases were identified. In univariate analyses, hemp-derived cannabinoid ingestions were associated with higher rates of respiratory depression (5.9% vs 4.6%; P= .01) and hypotension (3.87% vs 2.97%; P= .03) compared with Δ9-THC exposures. Vasopressor use was more frequent in the hemp-derived cannabinoid group (0.37% vs 0.13%; P= .02), yet rates of central nervous system depression, seizures, and intubation were similar. Children exposed to hemp-derived cannabinoids had higher critical care admission (11.3% vs 8.58%; P< .001) and overall admission rates (28.35% vs 26.13%; P= .03). No deaths were reported. CONCLUSIONS: Pediatric exposures to hemp-derived cannabinoids were associated with similar or greater clinical severity and health care utilization than Δ9-THC exposures. The lack of dose regulation for hemp-derived products may contribute to these findings. Prospective studies capturing dose data are needed to clarify risk and inform policy.
OBJECTIVE: To determine the diagnostic performance of vibration-controlled transient elastography (VCTE) measured the same day as liver biopsy in screening and risk stratification of steatosis and fibrosis in children an...OBJECTIVE: To determine the diagnostic performance of vibration-controlled transient elastography (VCTE) measured the same day as liver biopsy in screening and risk stratification of steatosis and fibrosis in children and adolescents. STUDY DESIGN: We compared VCTE measures of hepatic steatosis and fibrosis with liver biopsy histology as the reference standard. Sequential patients undergoing liver biopsy in a hospital-based pediatric gastroenterology practice were included. In primary analyses, we determined area under the receiver operating characteristic (AUC), sensitivity, and specificity for VCTE-derived measures of steatosis and fibrosis. In post hoc subgroup analyses, we examined VCTE measures of steatosis and fibrosis among patients according to metabolic dysfunction-associated steatotic liver disease (MASLD) diagnosis. RESULTS: Among 145 children, with mean age 13.6 years (SD: 5.1 years), VCTE measures of any steatosis (≥5%) showed AUC 0.89 (95% CI 0.83-0.94), sensitivity 0.90 (95% CI 0.79-0.97), and specificity 0.74 (95% CI 0.64-0.83). VCTE measures for fibrosis stage F2 or greater had AUC 0.71 (0.59-0.82), sensitivity 0.75 (0.53-0.90), and specificity 0.63 (0.54-0.72). In post hoc subgroup analyses among the subgroup of 37 patients with MASLD, VCTE had low ability to detect greater grades of steatosis (AUC 0.61 for S2 or greater) and low ability to detect clinically meaningful fibrosis (AUC 0.56 for F2 or greater). CONCLUSIONS: In the overall cohort, VCTE measurements on the same day as liver biopsy showed moderate ability to detect steatosis and limited ability to detect F2 fibrosis. Diagnostic discrimination for steatosis and fibrosis was low among the subgroup with MASLD. Disease-specific studies, rather than heterogeneous cohorts of mixed disease types, are needed to advance clinical implementation of noninvasive steatosis and fibrosis measures.
OBJECTIVE: To characterize baseline xanthoma prevalence and severity in Alagille syndrome, assess their impact on quality of life, evaluate longitudinal changes in xanthoma burden with maralixibat therapy, and identify c...OBJECTIVE: To characterize baseline xanthoma prevalence and severity in Alagille syndrome, assess their impact on quality of life, evaluate longitudinal changes in xanthoma burden with maralixibat therapy, and identify clinical and biochemical predictors of treatment response in children enrolled across 2 clinical trials. STUDY DESIGN: This integrated analysis from the ICONIC and ITCH trials assessed xanthoma severity using the Clinician Xanthoma Scale (CXS). Response was defined as a ≥1-point reduction from baseline in CXS. Outcomes included changes in serum lipids, serum bile acids (sBA), pruritus, and Pediatric Quality of Life Inventory scores through week 96. Baseline characteristics were compared across xanthoma severity groups using the Jonckheere-Terpstra test for continuous variables and the Cochran-Armitage trend test for categorical variables. The changes in xanthoma severity category (3 levels) from baseline to weeks 48 and 96 were tested using Bowker's test of symmetry. Change from baseline (CFB) of continuous outcomes was tested using the Wilcoxon signed-rank test. Differences in CFB of outcomes between xanthoma responders and nonresponders were evaluated using the Wilcoxon rank-sum test for continuous variables and Fisher exact test for categorical outcomes. RESULTS: Among 63 children (ICONIC, n = 29; ITCH, n = 34), 43% had xanthomas at baseline. Higher CXS was associated with younger age (P = .03); elevated sBA (P < .001), bilirubin (P < .001), alanine aminotransferase (P = .008), and gamma-glutamyl transferase (P = .02); and worse lipid profiles (total cholesterol, P < .001; high-density lipoprotein, P < .001). Quality of life declined with increasing CXS. After 96 weeks of follow-up (ICONIC, n = 18; ITCH, n = 17), mean CXS decreased (P = .004), and CXS 0 prevalence increased from 60% to 86% (P = .03). There was a significant decline in cholesterol (mean CFB, -55 mg/dL, P < .001) and sBA (mean CFB, -85 μmol/L, P < .001). Among participants with baseline CXS ≥1 (n = 14; ICONIC, n = 8; ITCH, n = 6), 71% and 64% were xanthoma responders at weeks 48 and 96. Responders had greater cholesterol reductions at week 48 (mean CFB, -189 vs -11 mg/dL, P = .005) and more frequent pruritus improvement (94% vs 68%, P = .047). CONCLUSIONS: Maralixibat may reduce xanthoma burden and improve metabolic parameters, supporting therapeutic potential of the drug for xanthomas in Alagille syndrome. CLINICAL TRIAL REGISTRATION: This is not a clinical trial, but an integrated analysis of 2 trials; these trials are registered with ClinicalTrials.gov. • ICONIC: NCT02160782, https://clinicaltrials.gov/study/NCT02160782 • ITCH: NCT02057692, https://clinicaltrials.gov/study/NCT02057692 • IMAGINE-II (long-term extension of ITCH): NCT02117713, https://clinicaltrials.gov/study/NCT02117713.
OBJECTIVE: To describe the association between parenting stress levels during early childhood and subsequent emotional health outcomes and resilience of their children with congenital heart disease (CHD) as young adults....OBJECTIVE: To describe the association between parenting stress levels during early childhood and subsequent emotional health outcomes and resilience of their children with congenital heart disease (CHD) as young adults. STUDY DESIGN: This prospective cohort study included 202 dyads of young adults with CHD and their caregivers. The young adults had undergone surgery with cardiopulmonary bypass at ≤ 6 months of life and were enrolled in a longitudinal study of neurodevelopmental outcomes in CHD. Resilience and general health status of the young adults were evaluated using self-report standardized questionnaires (14-Item Resilience Scale [RS-14] and 36-Item Short-Form Health Survey [SF-36]). Parenting stress in the preschool period was assessed using the Parenting Stress Index (PSI), completed by caregivers. RESULTS: An underlying mental health condition was self-reported by 120 (59%) of the young adults. Median PSI score (PSI total score = 58; interquartile ranges 46.25-71) indicated normal parenting stress levels. Mean SF-36 score (46, SD 11) was just below general population average (50), and mean RS-14 score (77, SD14) was similar to population average (76). Higher parenting stress was associated with lower young adults' resilience, with a unit increase in PSI total score associated with 0.14 (95% CI 0.02 - 0.26) decrease in RS-14 total score. CONCLUSIONS: Higher reported parenting stress during early childhood was associated with lower self-reported resilience in young adulthood for patients with CHD. This suggests that identification of an at-risk population early in life is possible and may provide an opportunity for targeted family-based interventions to improve psychosocial development with increased resilience.
OBJECTIVE: To assess the extent to which food allergies and food-specific IgE levels in childhood and adolescence differ among children who had infant colic, excessive crying without colic, or neither condition. STUDY DE...OBJECTIVE: To assess the extent to which food allergies and food-specific IgE levels in childhood and adolescence differ among children who had infant colic, excessive crying without colic, or neither condition. STUDY DESIGN: We prospectively followed children in the unselected Project Viva pre-birth cohort. We assessed parent-reported colic (unsoothable crying + apparent abdominal discomfort) and excessive crying without colic in infancy and examined associations with parent-reported food allergy from early childhood through mid-adolescence using multivariable logistic regression. In a subset (n = 242) with available biomarkers, we examined associations of colic with food-specific IgE sensitization in early childhood. RESULTS: The study sample of 1263 participants was 50% female and 70% non-Hispanic White. Participants who had colic (25%) had a greater risk of any food allergy in early childhood than those unaffected by crying or colic (13% vs 8%; OR 1.7, 95% CI 1.1-2.7). In early adolescence, the colic group had 2.1 times the risk of peanut allergy (8% vs 4%; 95% CI 1.1-4.1) and 2.6 times the risk of tree nut allergy (8% vs 3%; 95% CI: 1.3, 5.2) vs the unaffected group; risks persisted into mid-adolescence. In the subset with IgE, the colic group had 2.5 times the risk of early childhood IgE sensitization to peanuts compared with the unaffected (22% vs 11%; 95% CI 1.1-5.6). Excessive crying (10%) was not associated with food allergy outcomes. CONCLUSIONS: Colic may be an early marker of food allergy risk. Infants with colic may benefit from proven food allergy prevention strategies, including early, consistent introduction of potentially allergenic foods.
Children with cancer may not have a do not resuscitate (DNR) order, yet absence rarely guarantees cardiopulmonary resuscitation (CPR). In a review of 344 inpatient deaths over a decade, 85% had DNR orders; 20% received C...Children with cancer may not have a do not resuscitate (DNR) order, yet absence rarely guarantees cardiopulmonary resuscitation (CPR). In a review of 344 inpatient deaths over a decade, 85% had DNR orders; 20% received CPR, mostly for perceived reversibility. Intensive care unit location and active chemotherapy were associated with fewer DNR orders. Families often declined CPR, despite absence of a DNR order, when death was imminent.
OBJECTIVE: To determine patterns and causes of neonatal deaths in Canadian neonatal intensive care units (NICUs) over the last decade. STUDY DESIGN: All neonatal deaths reported by NICUs participating in the Canadian Neo...OBJECTIVE: To determine patterns and causes of neonatal deaths in Canadian neonatal intensive care units (NICUs) over the last decade. STUDY DESIGN: All neonatal deaths reported by NICUs participating in the Canadian Neonatal Network 2010-2022 were divided retrospectively into 2 groups by gestational age (GA), <33 weeks and ≥33 weeks. Cause of death was assigned using prespecified classification criteria adapted from published criteria. Demographic, perinatal, and neonatal characteristics of newborns who died were compared with those of the survivors. Trends in birth characteristics and causes of death over 3 epochs (2010-2013, 2014-2017, and 2018-2022) were evaluated. RESULTS: A total of 5646 (2.96%) newborns died after receiving intensive care; 3782 (67%) were born at <33 weeks and 1864 (33%) at ≥33 weeks GA. The most common cause of death at <33 GA weeks was extreme prematurity (<28 weeks), followed by respiratory causes. Among those with GA ≥33 weeks, the leading cause of death was central nervous system conditions, followed by congenital anomalies and malformations. Most deaths occurred between days 2-7, followed by days 8-28 after birth. Over the 3 epochs studied, deaths associated with extreme preterm birth decreased significantly, but other causes of death remained unchanged. CONCLUSIONS: In Canadian NICUs, among infants with GA <33 weeks, extreme preterm birth was the leading cause of mortality. Central nervous system-related conditions were the predominant cause of death in infants born ≥33 weeks. Deaths due to extreme preterm birth decreased over the last decade in Canada, likely reflecting increased provision of active resuscitative care.