Pediatric Research最新文献

Background: Apnea in newborns causes the glottis to adduct and prevents gas from entering the lungs. As hypoxia is an inhibitor of fetal breathing, we have investigated the effect of hypoxia on glottis patency and breathing in preterm newborn rabbits.

Methods: Rabbit kittens (29 d gestation, term ~32 d; n = 12) were delivered by c-section, fitted with a custom face mask and oesophageal catheter to measure breathing efforts. After birth, kittens underwent phase contrast X-ray imaging while receiving CPAP using the following sequence of gases: (i) room-air, (ii) 100% oxygen, (iii) 100% nitrogen and (iv) 100% oxygen again. Glottis patency was visually assessed to determine %time that the glottis was open in each gas.

Results: The glottis remained open for longer (44.7 ± 1.8% vs. 15.5 ± 1.8%, p < 0.0001) and breathing rates were higher (18.1 ± 0.5 breaths/min vs. 11.3 ± 1.1 breaths/min, p = 0.0001) when kittens were exposed to 100% oxygen compared to room-air. When exposed to 100% nitrogen, breathing became unstable and resulted in apnea and a fully closed glottis in all kittens. Glottis patency and breathing were restored by resuscitating with 100% oxygen.

Conclusion: These results highlight the importance of avoiding hypoxia and promoting stable breathing to ensure the glottis is open when giving CPAP.

Impact: While preterm newborns commonly receive non-invasive respiratory support (CPAP) in the delivery room, this can be ineffective, particularly if the infant is apneic. We have demonstrated that hypoxia induces unstable breathing patterns in preterm newborn kittens, eventually causing apnea. When breathing is unstable, the glottis opens but only during inspiration. Between breaths and during apnea, the glottis remains closed, which prevents effective delivery of CPAP via face mask. This study highlights that adequate oxygenation is critically important for maintaining breathing activity and the use of oxygen in the delivery room can enhance the effectiveness of non-invasive respiratory support.

Background: Acute kidney injury (AKI) is a common complication after pediatric cardiac surgery using cardiopulmonary bypass (CPB). This study evaluated renal regional oxygen saturation (R-rSO₂), measured via near-infrared spectroscopy (NIRS), as an AKI predictor.

Methods: 120 pediatric patients undergoing CPB-assisted congenital heart surgery were prospectively enrolled. Continuous intraoperative R-rSO₂ monitoring was performed. Four multivariable logistic regression models (adjusted for age, pre-SCr, pre-hemoglobin, RACHS-2, cyanosis, and CPB time) assessed distinct R-rSO₂ metrics during CPB for predicting AKI (pRIFLE criteria).

Results: AKI incidence was 35.8% (n = 43). The model using the area under the curve (AUC) for R-rSO₂ decrease ≥5% during CPB showed superior predictive performance (C-index = 0.854) and fit. Within this model, a greater AUC for R-rSO₂ decrease ≥5% during CPB was independently associated with increased AKI risk (OR 1.02, 95% CI 1.00-1.03, P = 0.014). Prolonged CPB duration (OR 1.02, 95% CI 1.00-1.04, P = 0.028) and lower preoperative serum creatinine (OR 0.87, 95% CI 0.76-0.99, P = 0.031) were also significant predictors. AKI correlated with prolonged ventilation (P < 0.001) and higher costs (P < 0.001).

Conclusion: Renal tissue desaturation during CPB, quantified as the AUC for R-rSO₂ decrease ≥5%, is significantly associated with postoperative AKI in children. Higher preoperative creatinine (mature function) was protective, while longer CPB time increased risk.

Impact: The cumulative burden of renal desaturation specifically during CPB is the outstanding intraoperative predictor of postoperative AKI in children undergoing congenital heart surgery. This study defines a quantitative metric-the cumulative area under the curve for renal regional oxygen saturation decrease ≥5% during CPB-which demonstrates high specificity and provides a potential, actionable intraoperative monitoring threshold for predicting AKI risk.

Purpose: To explore the efficacy of perioperative medications in preventing emergence agitation (EA) in children after sevoflurane anaesthesia.

Methods: This network meta-analysis used a frequency-analysis model. PubMed, Embase, Cochrane Library, Web of Science, Google Scholar and ClinicalTrials.gov databases were searched from inception to March 11, 2023.

Results: A total of 19 drugs were analysed in 70 studies involving 7617 participants. In the cumulative ranking area under the curve (SUCRA) analysis, sufentanil, esketamine, dexmedetomidine, nalbuphine, tropisetron, ketamine, magnesium sulphate, propofol, fentanyl, remifentanil, and midazolam showed significant EA-preventing effects. Further direct comparisons between the drugs and the control group revealed that fentanyl (Log OR = -1.28, 95% CI -1.76, -0.80, P < 0.001), ketamine (Log OR = -1.77, 95% CI -2.45, -1.10, P < 0.001), dexmedetomidine (Log OR = -1.60, 95% CI -1.88, -1.33, P < 0.001), midazolam (Log OR = -0.96, 95% CI -1.34, -0.57, P < 0.001), propofol (Log OR = -1.34, 95% CI -1.83, -0.85, P < 0.001), and nalbuphine (Log OR = -1.32, 95% CI -1.66, -0.98, P < 0.001) significantly reduced the incidence of EA in children.

Conclusion: Dexmedetomidine, propofol, midazolam, fentanyl, nalbuphine, and ketamine showed favourable EA-preventing effects in children.

Registration number: CRD42023470892.

Impact: This review provides a detailed network meta-analysis comparing 19 perioperative medications, offering a ranked efficacy profile (via SUCRA analysis) for preventing emergence agitation (EA) in children after sevoflurane anaesthesia, which consolidates and expands upon previous pairwise comparisons. It identifies dexmedetomidine, propofol, midazolam, fentanyl, nalbuphine, and ketamine as the most effective drugs for EA prevention, supporting evidence-based decision-making in paediatric anaesthesia practice.

Sleep plays a critical role in child and adolescent development, supporting physical growth, cognition, and emotional regulation. Children with cerebral palsy (CP) experience higher rates of sleep disturbances compared to children without CP, including difficulties initiating and maintaining sleep, sleep disordered breathing, and excessive daytime sleepiness. These disruptions can further hinder developmental progress. While sleep research has highlighted the importance of sufficient quality sleep for cognitive and behavioral growth in typically developing children, the complexities of CP make it challenging to establish a clear link between sleep disturbances, comorbidities, and developmental outcomes. The severity of clinical phenotype and comorbidities contribute to sleep difficulties in CP. Despite the critical need for objective sleep assessments like EEG-polysomnography, most research relies on caregiver reports, which are not always validated for this population. The current body of research also faces limitations, including small sample sizes and a lack of longitudinal studies on the long-term impact of sleep disturbances in children with CP. Future research should prioritize  large-scale longitudinal and  comparative studies and utilize objective tools to improve early diagnosis and guide the development of therapeutic interventions, ultimately enhancing developmental outcomes during the critical stages of neuroplasticity in early childhood.

In recent years, there has been a significant increase in reported cases of pulmonary thromboembolism associated with Mycoplasma pneumoniae pneumonia in pediatric patients, and its standardized treatment and effective prevention have increasingly attracted clinical attention. This article reviews the latest treatment approach for pulmonary thromboembolism complicated by Mycoplasma pneumoniae pneumonia in children, including anticoagulant therapy, systemic thrombolytic therapy, interventional therapy, and surgical therapy. Meanwhile, progress in research on the risk factors of this condition is also reviewed, aiming to provide new directions for future preventive studies. IMPACT: While several reviews have addressed the clinical characteristics of pulmonary thromboembolism (PTE) associated with Mycoplasma Pneumoniae pneumonia (MPP) in pediatric patients, there remains a lack of comprehensive syntheses focusing specifically on treatment and prevention. This review provides an integrated analysis of the latest evidence on treatment strategies over the past 5 years, facilitating informed clinical decision-making. Moreover, this review is the first to systematically map the studies on the risk factors of PTE induced by MPP, directly informing the directions of future preventive studies.

Background: Pulmonary hemorrhage (PH) in very low birth weight (VLBW) infants is a catastrophic event with significant mortality. Predicting PH clinically is challenging, with no tools for early detection. Our objective was to identify candidate physiologic biomarkers using heart rate (HR) and pulse oximetry (SpO₂) predictive of PH events in VLBW infants.

Methods: We conducted a retrospective case-control study of VLBW infants from two level IV NICUs (2016-2023). We matched infants with PH to controls using gestational age, birth weight, and postnatal age. Taking HR and SpO₂ data from 72 hours before and after PH diagnosis and age-matched times for controls, we calculated a pulse oximetry warning score (POWS) using hourly mean, skewness, kurtosis, and cross-correlation of HR and SpO₂.

Results: We analyzed 48 infants, 24 PH cases, and 24 controls, with similar characteristics. Infants who developed PH exhibited a three-fold rise in POWS starting 24 hours before PH diagnosis. Control infants showed no significant change in POWS.

Conclusion: POWS, a predictive model for cardiorespiratory deterioration, showed a rise in predicted risk before the clinical diagnosis of PH. This suggests that cardiorespiratory deterioration signatures precede the clinical diagnosis of PH and can be recognized with a computer algorithm.

Impact: There are subtle vital sign changes that may indicate impending pulmonary hemorrhage in very low birth weight infants. Cardiorespiratory predictive monitoring could be useful for early warning of deterioration due to pulmonary hemorrhage. This study lays the foundation for the utility of predictive analytics for pulmonary hemorrhage prediction and suggests that a dedicated predictive model for pulmonary hemorrhage may be helpful.

Background: Cerebral palsy (CP) arises from non-progressive brain damage occurring during the prenatal, perinatal, or postnatal period. We analyzed CP incidence and risk factors in South Korea over a 20-year period.

Methods: We included children newly diagnosed with CP between the first year of life and 5 years from 2005 to 2024 and examined their CP risk factors. Annual incidence rates were calculated by dividing the number of new cases each year by the population of children aged ≤5 years, with age- and sex-standardization. The CP cumulative incidence at the 5-year follow-up was analyzed by birth year. Temporal incidence trends were assessed using Joinpoint regression.

Results: The annual age- and sex-standardized CP incidence rate decreased from 6.6 to 3.6/10,000 between 2005 and 2024. The 5-year cumulative CP incidence also declined from 4.26/1000 live births in 2005 to 2.51/1000 live births in 2020. The most prevalent risk factors were birth-related complications, prematurity/low birth weight, and metabolic diseases, all showing increasing trends.

Conclusion: From 2005 to 2024, the CP incidence in South Korea declined, possibly reflecting perinatal-care improvements, particularly among children aged ≤2 years. Nationwide developmental-screening programs may have also enhanced milder-case detection, perhaps increasing the relative proportion diagnosed at ages 4-5 years.

Impact: Over the past 20 years, the annual incidence of cerebral palsy diagnosis in children between the first year of life and 5 years old has gradually decreased in South Korea. Cerebral palsy was the most frequently diagnosed at 1 year of age, and birth-related conditions, prematurity or low birth weight, and metabolic diseases were the most prevalent risk factors showing an increasing trend. This study suggests that advances in perinatal care might have contributed to the decline in CP incidence and the developmental screening test for infants and children implemented in South Korea may have contributed to reduction of missed diagnoses.

Background: Maternal breast milk is the optimal nutrition for preterm infants, supporting immune and gut maturation. When unavailable, alternatives include infant formulas or pasteurized donor milk, the latter conferring greater protection against feeding intolerance and necrotizing enterocolitis. This study examined the impact of cow's milk-derived extensively hydrolyzed proteins (eHP), widely used in formulas and human milk fortifiers, on intestinal barrier function and gene expression in fetal human intestinal organoid-derived monolayers, modeling premature epithelium.

Methods: Monolayers were exposed to free amino acids (AA), intact cow milk proteins (WP), or eHP at different concentrations, followed by inflammatory cytokines or commensal bacteria, to mimic physiologic gut conditions. Barrier integrity, permeability, and viability were measured using FITC-Dextran diffusion and LDH release. RNA-seq assessed transcriptional changes.

Results: eHP at low and high concentrations decreased epithelial permeability at baseline, AA showed no effect, and WP only at high concentrations. Under inflammatory conditions, eHP significantly reduced epithelial barrier permeability; both eHP and AA improved cell viability at low concentrations. Transcriptomic analysis revealed modulation of proliferation- and regulation-related pathways, including NOTCH and WNT signaling.

Conclusion: In this gut model, eHP enhanced barrier function under baseline and inflammatory conditions, supporting their role in nutrition, though further validation is needed.

Impact: Extensively hydrolyzed proteins (eHP) derived from cow's milk improve intestinal barrier function and cell viability in a fetal organoid-derived model of premature human intestine. This is the first study to assess the functional and transcriptomic impact of eHP on primary intestinal epithelial cells derived from fetal organoids, a highly relevant model for preterm gut physiology. It demonstrates that eHP-unlike intact proteins or free amino acids-can mitigate inflammation-induced permeability and modulate pathways involved in epithelial proliferation and repair (e.g., NOTCH, WNT, E2F, G2M checkpoint). These findings highlight the potential of eHP as a nutritional strategy to enhance gut integrity and limit inflammatory damage in preterm infants, who are at high risk of intestinal complications such as NEC. This study paves the way for further mechanistic and clinical research on how peptide-based formulas might support immature gut function and reduce extraintestinal risks.