Journal of Pediatrics最新文献

Objective: To evaluate in children the cytotoxic and mutagenic effects of exposure to drinking water contaminated with potentially toxic elements (PTEs).

Study design: Forty-nine children (6 and 14 years), residing in a region with environmental PTE contamination, and 19 children from an unexposed region, were assessed. Cytotoxicity and mutagenicity were analyzed by the micronucleus assay in exfoliated buccal mucosal cells. Water contamination was evaluated by inductively coupled plasma mass spectrometry. The Mann-Whitney U test was applied to compare the exposed and unexposed groups. Principal component analysis and Spearman's correlation test were used to evaluate the association between cellular effects and each PTE.

Results: Significantly higher mean values of binucleated cells and karyolysis were observed in the exposed group, while micronuclei, karyorrhexis, pyknosis, and normal cells were significantly reduced compared with the unexposed group (p ≤ 0.002). Analysis of drinking water samples from the exposed area revealed lead (Pb), antimony (Sb), arsenic (As), and cadmium (Cd) concentrations below the maximum permitted values. There was a moderate association between binucleated cells and Pb (r = 0.64) and between karyolysis and As (r = 0.61) and Sb (r = 0.61). Pyknosis and karyorrhexis were negatively correlated with As (r = -0.65 and -0.52) and Sb (r = -0.64 and -0.53).

Conclusions: Children residing in areas with PTE-contaminated water, even at minimal levels, exhibited elevated frequencies of karyolysis and binucleated cells. Although the levels of PTE do not exceed the permitted limits, chronic exposure was associated with DNA damage.

Objective: To test the hypothesis that a cohort-based training program for physician-scientists, which includes didactic and experiential curricula, could foster participants' scientific development.

Study design: We created the Chan Zuckerberg Biohub (CZB) Physician-Scientist Fellowship Program (PSFP) and conducted a study from July 2020 through August 2024. Twenty-four inaugural program participants at UCSF and Stanford University (median postgraduate year at program start, 5.5; 17 clinical specialties represented; 10 [42%] identified as female; 7 [29%] identified as underrepresented in medicine) were included. Participants (physicians without prior formal research training) attended a 2-week immersive training at the program outset, and subsequently, weekly curricular and scientific meetings throughout the program while conducting research.

Results: Primary outcome measures included pre-participation, 1-month, and 12-month assessments of confidence in research skills, career skills, and self-identification as scientists. After 12 months, 100% (N=16) reported satisfaction with the program and participants demonstrated increased confidence in research skills (median [IQR], 4.0 [2.5-5.0] pre-bootcamp to 5.5 [4.0-6.0] 12-mo], career skills significantly increased (median [IQR], 4.0 [4.0-5.0] pre-bootcamp to 5.5 [5.0-6.0]12-mo], perceptions of belonging significantly increased (median (IQR), 4.0 [2.5-5.4] pre-bootcamp to 5.5 [5.1-7.0] 12-mo), and scientific identity significantly increased (median [IQR], 5.0 [4.0-5.5] pre-bootcamp to 6.0 [5.5-7.0] 12-mo).

Conclusions: Participants demonstrated significant gains in confidence in core research and career skills and personal identification as scientists, demonstrating the efficacy of the approach. The strategy could be readily adopted and implemented at other institutions. The strategy may be particularly beneficial for physicians with an late-emerging scientific interest, especially women physicians with young children.

Objective: To assess any potential associations between epilepsy and up-to-date vaccination status or cumulative aluminum exposures from vaccines among children under 4 years of age.

Study design: We conducted a case-control study in the Vaccine Safety Datalink (VSD) cohort from 2008 through 2018. Epilepsy cases were identified up to 4 years of age by diagnosis codes with accompanying by antiseizure medication prescriptions. Controls had no diagnosis codes for epilepsy/seizures and no antiseizure medication before 4 years of age. Each case was matched to up to 10 controls. Cases and controls were matched on birthdate, sex, and VSD site. The exposures were age-specific up-to-date vaccination status categories, and continuous, cumulative aluminum content per adjuvant formulation from vaccination. Conditional logistic regression was used to estimate adjusted odds ratios and 95% confidence intervals for the associated risk of epilepsy. Secondary analyses were performed by age subgroups and limited to children with epilepsy of unknown etiology.

Results: The primary analysis included 2,089 cases and 20,139 matched controls. No adjusted odds ratio (aOR) for risk of epilepsy was greater than 1 either for up-to-date immunization status or for cumulative exposure to aluminum per mg increase per adjuvant formulation. In addition, there was no statistically significant relationship in analyses by age group or limitation to children with epilepsy of unknown etiology.

Conclusion: Incident epilepsy was not associated with up-to-date vaccination status or cumulative vaccine aluminum exposure among children less than 4 years of age.

Objective: To investigate the effect of fetal growth restriction (FGR) on cardiovascular structure and function in childhood in a growth-discordant identical twin model, thereby adjusting naturally for genetic, obstetric, and environmental confounding factors.

Study design: This study is part of the LEMON cohort study of growth-discordant identical twins born at the Leiden University Medical Center, The Netherlands. Echocardiography was prospectively performed in 42 twin pairs aged between 5 and 17 years. Growth discordance was defined as a birth weight discordance ≥20%. Outcome measures were compared between the smaller and larger twin and included structural measures (left ventricular [LV] dimensions and carotid intima-media thickness [cIMT]) as well as functional measures (LV systolic and diastolic function using Doppler and LV strain imaging, and aortic pulsed wave velocity [aPWV]).

Results: Median gestational age at birth was 34.1 weeks (IQR 31.6-36.0) with median birth weights of 1471 grams (IQR 1114-1876) and 2025 grams (IQR 1623-2705) for the smaller and larger twin, respectively. Median age at echocardiography was 11 years (IQR 9-14). Smaller twins presented with significantly lower LV global longitudinal strain (-19.6% vs -20.7%), and higher mitral peak E and A velocities, and mitral E/e' ratio compared with larger co-twins. No within-pair differences were found regarding structural cardiovascular parameters, cIMT and aPWV.

Conclusions: In a growth-discordant identical twin model, FGR is associated with subclinical changes in myocardial structure and systolic and diastolic LV function in the smaller growth-restricted twin compared with the larger appropriately-grown co-twin. This finding indicates that adverse cardiovascular remodeling after FGR persists into childhood, potentially influencing long-term risk of cardiovascular disease.

Objective: To assess associations between exposure to intrauterine SARS-CoV-2 and subsequent child neurodevelopment in a large, diverse cohort with confirmation of maternal SARS-CoV-2 status.

Study design: The Researching COVID to Enhance Recovery (RECOVER) Pregnancy Cohort enrolled adults with and without SARS-CoV-2 during pregnancy and their offspring born January 2020 through December 2023 at 23 sites across the US. Neurodevelopment was assessed at 12 months with the Ages and Stages Questionnaire, 3^rd edition (ASQ-3) and at 18 months with the ASQ Social-Emotional (ASQ-SE) and the Modified Checklist for Autism in Toddlers-Revised (M-CHAT-R). We compared exposed and unexposed infants' ASQ-3 total and subdomain scores, ASQ-SE and M-CHAT-R scores, and proportions meeting published referral thresholds, using multivariable linear and logistic regression.

Results: Among 1179 participants enrolled, 1008 (85.5%) had exposure, with 806 (80.0%) exposed during Omicron predominance. Of those with known timing, 349 (41.4%) and 295 (35.0%) were exposed in the second and third trimesters of pregnancy respectively. Exposure was not associated with differences in ASQ-3 (adjusted difference: -0.61, 95% CI: -10.03, 8.81) or ASQ-3 subdomains at 12 months, ASQ-SE at 18 months (adjusted difference: 0.19, 95% CI: -4.02, 4.41), or M-CHAT-R scores. Findings were similar for proportions meeting referral thresholds, and when stratified by variant or by trimester.

Conclusions: In this multicenter cohort largely exposed since Omicron and in second or third trimester, intrauterine SARS-CoV-2 exposure was not associated with neurodevelopmental screening outcomes through 18 months of age. Further assessments of the impact of intrauterine SARS-CoV-2 on neurodevelopment beyond 18 months of age are needed.

Objective: To quantify the impact of non-hemodynamically significant PDA (non-hsPDA) on pulmonary function in neonates.

Study design: We analyzed a retrospective cohort of very low birthweight (<1500 g) infants born <32 weeks' gestation admitted to a single tertiary neonatal intensive care unit between 2019-2023 who underwent both echocardiography and pulmonary function testing (PFT) at approximately 34 weeks postmenstrual age. Infants with ventricular or atrial septal defects were excluded. Passive respiratory compliance (Crs) was compared among infants with hsPDA, non-hsPDA, and age-matched controls without PDA using one-sided t-tests and ANOVA, with multivariable regression controlling for birth weight and length.

Results: Twenty-four infants were analyzed (8 hsPDA, 8 non-hsPDA, 8 controls). Mean Crs was significantly reduced in both hsPDA (0.83 ± 0.34 mL/cmH₂O/kg) and non-hsPDA (0.92 ± 0.21) groups compared with controls (1.23 ± 0.34; p<0.05). The presence of PDA demonstrated a stepwise inverse relationship with Crs that persisted after adjustment for covariates.

Conclusions: Even non-hemodynamically significant PDAs are associated with measurable reductions in pulmonary compliance among preterm infants. These findings suggest that current binary classifications of PDA significance may underestimate pulmonary impact and support reevaluation of management thresholds for "non-significant" shunts.

Objective: To evaluate the risks of incident dyslipidemia and abnormal body mass index (BMI) during the 28-179-day post-acute phase after documented SARS-CoV-2 infection in a large pediatric sample.

Study design: A retrospective cohort study using the RECOVER pediatric electronic health record (EHR) datasets from 25 US children's hospitals and health institutions, from March 2020 to September 2023. This study included 384,289 COVID-19-positive patients aged 0-21 years for dyslipidemia analyses and 285,559 aged 2-21 years for BMI analyses, each with at least 6 months of follow-up. COVID-19-negative controls included 1,080,413 and 817,315 patients, respectively. SARS-CoV-2 infection was defined by a positive polymerase-chain-reaction (PCR), antigen, or serologic test; a clinical diagnosis of COVID-19; or a documented diagnosis of post-acute sequelae of SARS-CoV-2 (PASC). Incident dyslipidemia and abnormal BMI were identified using age-specific laboratory or anthropometric thresholds. Adjusted relative risks (aRRs) were estimated using propensity-score-stratified modified Poisson regression with multiple sensitivity analyses.

Results: During the post-acute phase, the COVID-19-positive cohort had higher rates of new-onset composite dyslipidemia (aRR 1.24; 95% CI 1.18-1.29) and abnormal BMI (aRR 1.15; 95% CI, 1.12-1.18). Results were robust to sensitivity and stratified analyses.

Conclusion: Children and adolescents with documented COVID-19 infection were associated with an increased risk of new-onset dyslipidemia and abnormal BMI during the post-acute phase, highlighting the need for metabolic monitoring after infection.

Objective: To build a time-series machine learning (ML) model that improves BPD prediction compared with published online calculators.

Study design: We used a single-center, extremely low gestational age newborn cohort (ELGANs, inborn, birth year 2016-2021, N=438). The primary outcome was a 5-level class outcome for BPD as defined by the Neonatal Research Network (NRN) in 2019. Flowsheet data were extracted from the electronic medical record. Time-series data were generated from birth onward, with 14 static and 35 dynamic input attributes. Iterative static (regression) and dynamic (ML) modeling was performed, comparing model performance with the NRN BPD calculator at several time points (postnatal day [PND] 1, 3, 7, 14, and 28) and ranking feature leverage at each time point.

Results: Of the original cohort, 92 infants met all inclusion criteria (gestational age 25.6 ± 1.4 weeks). Static models performed comparably with the NRN BPD calculator (AUC=0.7460), improving to 0.7978 with forward/backward selection. In contrast, dynamic long short-term memory (LSTM) models outperformed static models at all time points, reaching a peak AUC of 0.8400 on PND 28. LSTM models performed best for no BPD and severe disease/death. Principal component analysis (PCA) revealed that respiratory support, ventilator settings, supplemental oxygen requirements, medications, and pre/postnatal growth were major factors driving BPD severity.

Conclusions: LSTM-based ML time-series analysis substantially outperformed static approaches for predicting BPD and death among ELGANs. Integrating ML methods into clinical applications holds promise for enhancing real-time BPD trajectory mapping.

Antimicrobial resistance is life-threatening to pediatric patients with medical complexity who receive multiple courses of broad-spectrum antibiotics. Bacteriophages offer a safe treatment alternative when our antibiotic armamentarium is no longer sufficient. We describe successful use of bacteriophage therapy on a patient with a recalcitrant Pseudomonasaeruginosa infection after receiving a multiorgan transplant.