Slagle CL, Vuong KT, Krallman KA
… +17 more, Casey L, Gist KM, Jetton JG, Joseph C, Luckritz K, Martin SD, Morgan J, Merrill KA, Plomaritas K, Ramirez D, Tran CL, Shin HS, Snyder AN, Van Wyk B, Yalon L, Goldstein SL, Menon S
We conducted a retrospective cohort study of 29 499 neonatal cases requiring extracorporeal life support (ECLS) at 237 centers from 2000 to 2023; there were 6747 infants with congenital diaphragmatic hernia (CDH) and 22...We conducted a retrospective cohort study of 29 499 neonatal cases requiring extracorporeal life support (ECLS) at 237 centers from 2000 to 2023; there were 6747 infants with congenital diaphragmatic hernia (CDH) and 22 752 without CDH. Infants with CDH treated at ECLS centers with low total neonatal volumes (<28.5 total cases) had increased odds of inpatient mortality compared with those at high-volume centers (> 140 total cases, adjusted odds ratio [aOR]: 1.9; 95% confidence interval [CI]: 1.2-2.9). Similarly, centers with low non-CDH ECLS volumes were associated with higher odds of mortality among infants with CDH (aOR: 1.7; 95% CI: 1.1-2.5). Combined analysis of neonates with and without CDH also showed that low-volume centers were associated with higher odds of mortality compared with high-volume centers (aOR: 1.6; 95% CI: 1.3-2.0). These findings underscore the importance of procedural experience and support further investigation into the potential best practices adopted by high-volume centers.
Nelson JE, Petit CJ, Goldstein BH
… +16 more, Glatz AC, Zhang Y, McCracken CE, Mascio CE, Weber R, Nicholson GT, Zampi JD, Romano JC, O'Byrne ML, Law MA, Shahanavaz S, Meadows JJ, Qureshi AM, Ligon RA, Lee TM, Additional Authors from the Congenital Cardiac Research Collaborative (see Appendix)
OBJECTIVE: To assess associations between the presence of genetic diagnoses and survival and morbidity of patients with symptomatic tetralogy of Fallot (sTOF) requiring neonatal intervention. STUDY DESIGN: We performed a...OBJECTIVE: To assess associations between the presence of genetic diagnoses and survival and morbidity of patients with symptomatic tetralogy of Fallot (sTOF) requiring neonatal intervention. STUDY DESIGN: We performed an analysis of a multicenter, retrospective study of sTOF patients from 2005 to 2017 from the Congenital Cardiac Research Collaborative. The primary outcome was transplant-free survival, evaluated by Cox proportional hazards regression modeling, adjusted for center, repair strategy, anatomical diagnosis, prematurity, and invasive ventilation before intervention. Genetic diagnoses were retrospectively collected from hospital records. RESULTS: The study group included 572 neonates with sTOF, of whom 151 (26.4%) had an identifiable genetic diagnosis, including 22q11 deletion (n = 63, 41.7%), trisomy 21 (n = 28, 18.5%), and other genetic diagnoses (n = 60, 39.7%). At a median follow-up of 4.12 (1.53, 7.47) years, there was no significantly increased hazard ratio of death in patients with a genetic diagnosis (adjusted hazard ratio 1.71 [95% CI 0.96-3.07], P = .07). However, patients with a genetic diagnosis had longer median intensive care unit and total hospital stays ([13 vs 9 days, P < .001] and [32.5 vs 24 days, P < .001], respectively) and were more likely to be discharged with feeding tubes (OR 2.1 [95% CI 1.31-3.37], P = .002). CONCLUSIONS: Neonates with sTOF with a genetic diagnosis had no significant survival difference to those without but did have a higher risk for other hospital morbidities, including longer admissions and the need for feeding tubes. Genetic testing in this population can inform clinicians and families regarding these important considerations within this congenital heart disease population.
Ali SA, Shen Y, Bone JN
… +19 more, Richter LL, Lisonkova S, Gette F, Kieran E, Chan ES, Mammen C, Lam C, Roberts A, Kang KT, Rumsey DG, McGrath T, Harris KC, Yang CL, Wong J, Chan NH, Lee J, Rassekh SR, Chan AKC, Ting JY
OBJECTIVE: To assess the risk of middle-childhood (ages 5-10 years) morbidities among children born preterm. STUDY DESIGN: We conducted a population-based cohort study of children born in British Columbia, Canada (2004-2...OBJECTIVE: To assess the risk of middle-childhood (ages 5-10 years) morbidities among children born preterm. STUDY DESIGN: We conducted a population-based cohort study of children born in British Columbia, Canada (2004-2017), followed from ages 5 to 10 years. Gestational age was categorized as 22-28, 29-33, 34-36, 37-41 (reference), and 42-44 weeks. Morbidity outcomes were allergic, cardiac, dermatologic, endocrine, hematologic, renal, neurologic, oncologic, respiratory, rheumatologic, and sleep. Cox proportional hazard models were used to compute adjusted hazard ratios (aHRs) and 95% CIs. RESULTS: In the cohort of 510 424 children, 9.50% were born preterm. Morbidity rates ranged from <1.0% (eg, cardiac, gastrointestinal, epilepsy, and oncologic disorders) to 16.37% (allergic), with greater rates among children born preterm than at term. A dose-response relationship was observed for several outcomes, with risks increasing as gestational age decreased. For puberty and disorders of sexual development, aHRs (95% CIs) were 2.17 (1.51-3.11), 1.99 (1.67-2.37), and 1.28 (1.14-1.43) among children born at 22-28, 29-33, and 34-36 weeks, respectively. Corresponding aHRs (95% CIs) for cardiac conditions were 4.20 (2.87-6.14), 1.90 (1.47-2.45), and 1.51 (1.30-1.75); for neurologic conditions were 3.20 (2.96-3.46), 1.54 (1.47-1.61), and 1.27 (1.23-1.30); and for respiratory conditions were 2.55 (2.33-2.78), 1.52 (1.45-1.60), and 1.23 (1.19-1.26), respectively. CONCLUSIONS: Children born preterm show elevated morbidity risks at ages 5-10 years. Risks increased with decreasing gestational age, reinforcing the need for ongoing monitoring and interventions to reduce long-term health complications.
OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of macitentan vs standard of care (SoC) in pediatric pulmonary arterial hypertension (PAH). STUDY DESIGN: TOMORROW was a multicenter, open-label, phase 3...OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of macitentan vs standard of care (SoC) in pediatric pulmonary arterial hypertension (PAH). STUDY DESIGN: TOMORROW was a multicenter, open-label, phase 3 clinical trial in patients aged ≥2-<18 years World Health Organization Functional Class I-III. Patients were randomized (1:1) to macitentan (bodyweight-based dosing) or SoC (≤2 PAH-specific therapies). The primary endpoint was steady-state C plasma concentration of macitentan and aprocitentan (active metabolite) at week 12. Secondary endpoints included time-to-first clinical event committee-confirmed disease progression, safety/tolerability, change in NT-proBNP, and quality of life. RESULTS: We randomized 148 patients (macitentan: n = 73; SoC: n = 75). The PK profile was consistent with adults; mean (SD) steady-state C concentrations were 185 (114.3) and 983 (324.1) ng/mL. Mean treatment duration was 183.36 weeks (macitentan) and 130.59 weeks (SoC). Hazard ratios (95% CI) for time-to-event analyses (macitentan vs SoC) were 0.828 (0.460-1.492) for disease progression, 0.912 (0.393-2.118) for PAH hospitalization, and 1.530 (0.429-5.457) for PAH mortality (P > .05 for all). Percentage of baseline NT-proBNP was 72% (macitentan) vs 101% (SoC) at week 12 (P = .086) and 76% vs 78% at week 24 (P = .884). Macitentan showed clinically meaningful improvements in quality of life assessments vs SoC for children (P = .043) and parents (P = .020) at week 24. The safety profile of macitentan was consistent with that seen in adults. CONCLUSIONS: TOMORROW was a novel study assessing PK and the long-term efficacy and safety of macitentan vs SoC in pediatric PAH. The results confirm the adequacy of the macitentan dosing in this population and provided signals of potential benefit of macitentan over SoC for children with PAH. TRIAL REGISTRATION: ClinicalTrials.gov (ID number, NCT02932410; https://clinicaltrials.gov/study/NCT02932410).
OBJECTIVE: To examine associations of prenatal perceived stress with child autism-related traits and to evaluate effect modification by both child sex and co-occurring prenatal depressive symptoms. STUDY DESIGN: The samp...OBJECTIVE: To examine associations of prenatal perceived stress with child autism-related traits and to evaluate effect modification by both child sex and co-occurring prenatal depressive symptoms. STUDY DESIGN: The sample was drawn from Environmental Influences on Child Health Outcomes cohort sites with data on prenatal perceived stress (Perceived Stress Scale [PSS]) and autism-related traits (Social Responsiveness Scale, second Edition [SRS-2]). We used linear and logistic regression models to determine associations between PSS and either SRS-2 T-scores or odds of moderate-to-severe autism-related traits (SRS-2 T-score ≥65) and evaluated effect modification by sex and prenatal depressive symptoms. RESULTS: Among 4115 mother-child pairs, higher PSS was associated with increased severity of autism-related traits (β = 0.15 [95% CI = 0.13-0.18]) and odds of moderate-to-severe traits (OR = 1.04 [1.04-1.05]). There was evidence for sex-by-exposure interaction for continuous (β = 0.18 [0.14-0.22]; β = 0.13 [0.10-0.16], P = 0.03) but not dichotomous trait severity (OR = 1.05 [1.03-1.06]; OR = 1.04 [1.03-1.05], P = 0.52). Associations did not differ by prenatal depressive symptoms (low: n = 2,538, b = 0.14 [0.11-0.18]; high: n = 889, b = 0.10 [0.04-0.15]; P = 0.66). CONCLUSIONS: We found small yet significant associations between prenatal stress and autism-related traits. Limited evidence for effect modification by sex or prenatal depressive symptoms suggests prenatal perceived stress influences autism-related traits after accounting for these factors.
Neurofibromatosis 1-associated optic pathway gliomas (OPGs) may co-occur with central precocious puberty (CPP). Using large language model-based data analysis from 2 NF centers, we compared OPGs in children with NF1, wit...Neurofibromatosis 1-associated optic pathway gliomas (OPGs) may co-occur with central precocious puberty (CPP). Using large language model-based data analysis from 2 NF centers, we compared OPGs in children with NF1, with and without CPP. CPP was associated with hypothalamic involvement, poorer vision, and a higher likelihood of OPG treatment.
OBJECTIVE: To quantify the misclassification of Child Opportunity Index (COI) quintiles when using ZIP codes instead of census tracts and to compare the strength of associations with ambulatory care sensitive condition (...OBJECTIVE: To quantify the misclassification of Child Opportunity Index (COI) quintiles when using ZIP codes instead of census tracts and to compare the strength of associations with ambulatory care sensitive condition (ACSC) hospitalization rates when using COI linked to these 2 geographies. STUDY DESIGN: This retrospective, cross-sectional study analyzed pediatric ACSC hospitalizations from 2 Midwest children's hospitals between 2013 and 2018. Patient home addresses were geocoded and linked to the COI 3.0 at ZIP code and census tract levels. COI scores were assessed as nationally-normed quintiles, percentiles, and z-scores. Misclassification was defined as ZIP code COI differing by ≥ 2 quintile levels from census tract quintile assignment. Geospatial and regression analyses assessed the impact of misclassification on associations with ACSC hospitalization rates. RESULTS: There were 26 512 ACSC hospitalizations for youth from 2 metropolitan areas comprised of 604 943 children. Misclassification occurred in 8.1% of ACSC hospitalizations. Regression analyses indicated lower hospitalization rates for areas with higher opportunity. Between the census tract and ZIP code geographies, there was no significant difference in the percent change of ACSC hospitalization rates for every COI quantile increase when using COI quintiles (-21.7% vs -22.0%; P = .51) and percentiles (-1.2% vs -1.2%; P = .6); however, there was a significant difference between the geographies when using COI z-scores (-35.1% vs -28.5%; P < .001). CONCLUSIONS: Using ZIP codes to assign COI scores with the most common approaches - quintiles and percentiles - is likely acceptable for correlational analyses in large datasets. However, ZIP code COI scores may underestimate true associations between neighborhood opportunity and health outcomes when using z-scores.
OBJECTIVES: To define clinically the initial (<24 hour) hemodynamic phenotypes (no/mild pulmonary hypertension [PH], precapillary PH, and postcapillary PH) in neonates with congenital diaphragmatic hernia (CDH) by echoca...OBJECTIVES: To define clinically the initial (<24 hour) hemodynamic phenotypes (no/mild pulmonary hypertension [PH], precapillary PH, and postcapillary PH) in neonates with congenital diaphragmatic hernia (CDH) by echocardiography, and to assess their relationship with clinical outcomes. STUDY DESIGN: This was a retrospective, single-center, observational study that included all neonates with CDH with an echocardiogram in the first 24 hours from 2018 to 2025. Phenotypes were categorized via an a priori-defined algorithm, characterized by clinical and echocardiography indices and were evaluated for association with mortality, need for extracorporeal life support, and key clinical outcomes. RESULTS: Despite bidirectional atrial and/or ductal shunts in every echocardiogram (n = 28), phenotype identification was feasible with 2 (7%) no/mild PH, 18 (64%) precapillary PH, and 8 (29%) postcapillary PH phenotype. There was no association between phenotype and mortality or extracorporeal life support; however, the postcapillary phenotype was associated with earlier mortality, decreased surgical repair, and mortality when exposed to inhaled nitric oxide. CONCLUSIONS: An algorithmic approach that includes early echocardiography can reliably identify hemodynamic phenotypes even in the presence of bidirectional shunts. Phenotypes may have distinct clinical trajectories in neonates with CDH.
OBJECTIVE: To assess the predictive accuracy of urine neutrophil gelatinase-associated lipocalin (NGAL) and the Shannon Diversity Index in diagnosing urinary tract infection (UTI) in children with spina bifida. STUDY DES...OBJECTIVE: To assess the predictive accuracy of urine neutrophil gelatinase-associated lipocalin (NGAL) and the Shannon Diversity Index in diagnosing urinary tract infection (UTI) in children with spina bifida. STUDY DESIGN: This was a cross-sectional study of children with spina bifida who were evaluated for UTI in the emergency department. We included patients younger than the age of 22 years with spina bifida who used clean intermittent catheterization and had a urinalysis and urine culture sent. We measured urine NGAL and completed 16SrRNA sequencing. We generated receiver operating characteristic curves to assess the predictive accuracy of urinary NGAL and Shannon Diversity Index. RESULTS: There were 51 children, 13 with UTI, in this study. The median Shannon Diversity Index was lower in children with UTI compared with those without, whereas median NGAL was significantly greater in the UTI vs the no-UTI group. The area under the curve for the combination of NGAL and Shannon Diversity was 0.88 (0.78-0.99), which is not significantly different from either the under the curve for NGAL or Shannon Diversity Index alone. NGAL was more specific, whereas the Shannon Diversity Index was more sensitive for the diagnosis of UTI. CONCLUSIONS: NGAL is specific, and Shannon Diversity Index is sensitive, for diagnosing UTI in children with spina bifida who use clean intermittent catheterization. However, the combination of the 2 markers does not create improved predictive accuracy over either alone.
Peebles PJ, Reiter JG, Wildenhain PJ
… +22 more, Shults J, Herrick HM, Brajkovic I, DeMartino C, DeMeo SD, Glass KM, Hodgson KA, Iben S, Jung P, Kim JH, May LA, McKanna J, Moussa A, Narvey M, Pouppirt N, Puia-Dumitrescu M, Rumpel JA, Shay RL, Tyler MD, Wagner M, Nishisaki A, Foglia EE
OBJECTIVES: To compare procedural safety and success outcomes between catheter placement for minimally invasive surfactant therapy (MIST) and tracheal intubation (TI) for surfactant, and to identify characteristics assoc...OBJECTIVES: To compare procedural safety and success outcomes between catheter placement for minimally invasive surfactant therapy (MIST) and tracheal intubation (TI) for surfactant, and to identify characteristics associated with improved procedural outcomes among patients treated with MIST. STUDY DESIGN: We conducted a retrospective, multicenter, observational, matched cohort study from an international airway registry from 2016 to 2024. Patients treated with MIST and patients who received TI for surfactant without paralytic premedication, were matched 1:1 on gestational age, procedure location, and laryngoscope type. The primary outcome was severe oxygen desaturation (≥20% SpO2 decrease). Secondary outcomes included SpO2 <80%, any adverse event, and first attempt success. Using conditional logistic regression, the association between procedure type and outcomes was assessed. Among patients who received MIST, a multiple logistic regression model assessed the association between procedural characteristics and outcomes. RESULTS: There were 383 patients treated with MIST matched to 383 patients who underwent TI for surfactant. Compared with TI, MIST procedures were associated with lower adjusted odds of severe oxygen desaturation (aOR 0.66, 95% CI 0.45-0.97) and SpO2 <80% (aOR 0.59 95% CI: 0.40-0.85) and higher odds of first attempt success (aOR 2.93 95% CI 1.94-4.43). Odds of adverse events did not differ (aOR 0.88 95% CI 0.50-1.56). Factors associated with improved MIST outcomes included video laryngoscopy, first airway provider, commercial catheter type, and patient weight. CONCLUSIONS: MIST is associated with improved procedural safety and success compared with TI for surfactant. Several factors are associated with improved MIST procedural outcomes.