Pediatric Research最新文献

Background: The severe, degenerative muscle condition known as Duchenne Muscular Dystrophy (DMD) typically manifests in early childhood.

Objective: This study aims to investigate how DMD cases express the genes for Ewing's Tumor-associated Antigen 1 (ETAA1), Topoisomerase IIβ-binding protein 1 (TOPBP1), and ATR (Ataxia Telangiectasia and Rad3-related).

Subjects and methods: A total of 50 ambulatory male patients with DMD attending pediatric neurology clinic at Menoufia University Hospital were included and compared to 25 healthy control males matched for age. General clinical information, neurological information, and laboratory tests were performed. This included measuring serum levels of creatine phosphokinase CPK, human creatine kinase, muscle (CK-mm), human lactate dehydrogenase (LDH), total antioxidant status (TAS), total oxidant status (TOS), and quantitative expression of the genes ETAA1, TOPBP1, and ATR.

Results: In contrast to those in good health, the expression levels of the ETAA1, TOPBP1, and ATR genes were significantly greater in DMD cases. Additionally blood levels of CPK, CK-mm, LDH, and TOS were significantly higher in DMD than those of healthy individuals.

Conclusion: The gene expression of ETAA1, TOPBP1, and ATR is substantially elevated in cases with severe DMD, making them potentially significant indicators of the severity of DMD cases.

Impact: This study evaluates the expression of DNA damage response genes-ETAA1, TOPBP1, and ATR-in patients with Duchenne Muscular Dystrophy (DMD). The results demonstrate that DMD patients have much greater gene expression levels and oxidative stress indicators than healthy controls. These genes show a favorable correlation with clinical severity indicators such as CKMM, CPK, and LDH. Combining the three markers improves diagnostic sensitivity and specificity, indicating their potential as a multi-gene biomarker panel. The findings shed fresh light on DMD etiology by correlating genomic instability to disease progression and identifying possible molecular targets for early detection and future treatment approaches.

Background: CFTR modulators such as lumacaftor/ivacaftor (LUM/IVA) may reshape microbiota-mycobiota composition in the lungs and gut. While the gut-lung axis is established in other settings, little is known about its role following modulator therapy, particularly in the 2-11 age group.

Methods: In a prospective national multicentre study, 116 children with cystic fibrosis (2-11 years) starting LUM/IVA were followed for 12 months. Stool and sputum were collected at baseline, 3, 6 and 12 months. Bacterial and fungal communities were profiled by 16S rRNA and ITS2 sequencing; diversity, dysbiosis indices, faecal and sputum calprotectin, and gut-lung microbial networks were analysed.

Results: LUM/IVA was associated with increased bacterial diversity and compositional shifts in gut and lung microbiota, alongside a significant reduction in faecal calprotectin. Airway mycobiota diversity remained stable. Two lung microbiome response profiles emerged: "responders" (greater bacterial diversity gain) and "non-responders" (minimal change). Baseline gut and lung composition predicted these profiles with 81% accuracy in a random-forest model. Inter-organ microbial interactions peaked at 3 months after initiation and then diverged between profiles, indicating distinct gut-lung axis remodelling.

Conclusion: LUM/IVA influences gut-lung microbiota-mycobiota dynamics, with heterogeneous responses between paediatric patients. Identifying factors predictive of response is a key future challenge.

Impact: In 116 children aged 2-11, lumacaftor/ivacaftor reshaped gut and lung microbiota and reduced fecal calprotectin over 12 months. First pediatric multicenter study integrating bacterial and fungal profiling of stool and sputum with gut-lung network analyses; identifies two distinct lung microbiome response profiles. Baseline gut and lung composition predicted the response profile with approximately 81% accuracy. Highlights a 3-month interaction peak and baseline profiling as practical markers to guide monitoring and microbiome-informed precision care.

Background: Cardiorespiratory coupling (cardiovascular-respiratory interactions) is a marker of autonomic nervous system function and maturation. We hypothesize that differences in autonomic maturation are associated with disparate outcomes of premature infants.

Methods: We collected continuous bedside cardiorespiratory data from birth to 40 weeks post-menstrual age (PMA) for 191 preterm infants born between 23-0/7 weeks to 28-6/7 weeks of gestation. Using the respiratory and ECG wave forms, we calculated cardiorespiratory phase synchronization (CRPS) as a measure of cardiorespiratory coupling. Using linear mixed effects modeling, we studied the trajectory of CRPS as a function of PMA and chronological age (CA) and any difference between groups separated by discharge status, respiratory outcome and neurological outcomes at the 40th week PMA, and different gestational ages.

Results: CRPS showed a decline reaching a nadir at approximately 3 weeks of age followed by a gradual increase toward term. The infants born at later GA showed higher values and steeper increases than infants of lower GA. Contrary to our hypothesis, the trajectory of the increase was similar regardless of outcome assessed.

Conclusion: Autonomic maturation following preterm birth shows a fixed predictable pattern that appears to be independent of respiratory or neurologic outcomes or clinicians' assessment of readiness for discharge.

Impact: Cardiorespiratory phase synchronization (CRPS) trajectories, a marker of autonomic nervous system functio is provided for 175 extremely preterm infants across post-menstrual age (PMA) and chronological age (CA). CRPS initially declines but subsequently increases with advancing PMA and CA, irrespective of discharge status and respiratory and neurological outcomes at 40 weeks PMA. At all CAs after the initial decrease, CRPS was higher for infants born at 27-28 weeks compared to those born earlier.

Background: A previous study reported that among patients with complete Kawasaki Disease (KD), those exhibiting all six principal clinical features were more likely to develop coronary artery (CA) sequelae than those exhibiting only five features. We aimed to determine which specific features are associated with CA sequelae.

Methods: This retrospective cohort study analyzed 14,732 patients diagnosed with complete KD across Japan from January 2019 to March 2020. Separate multivariable conditional logistic regression analyses were performed to evaluate relative risk for CA sequelae in patients with all six principal clinical features, compared individually to those lacking each specific feature.

Results: 7234 (49.1%) exhibited all six principal clinical features, while 7498 (50.9%) presented with five features. CA sequelae occurred in 2.1% of those with six features versus 1.7% with five. Multivariable conditional logistic regression analysis determined that patients with conjunctival injection were significantly more likely to develop CA sequelae compared with those lacking it (adjusted odds ratio [95% confidence interval], 3.6 [1.3-10.1]).

Conclusions: Among patients with complete KD, the absence of conjunctival injection-a relatively rare presentation-was associated with a lower cumulative incidence of CA sequelae. This finding may help identify distinct low-risk phenotypes of KD and support risk stratification.

Impact: This study emphasizes the importance of feature-specific risk for coronary artery (CA) sequelae among patients with complete Kawasaki Disease (KD). We found that among patients with complete KD, those with conjunctival injection were more likely to develop CA sequelae than were those lacking it. The absence of conjunctival injection-a relatively rare presentation in KD-is associated with a markedly lower cumulative incidence of CA sequelae. This finding may help identify a distinct low-risk phenotype of KD and aid risk stratification.

Background: Pediatric epilepsy may adversely affect cardiac function. This study examined cardiac outcomes in children with controlled and drug-resistant epilepsy (DRE).

Methods: Sixty children with epilepsy (30 DRE, 30 drug-responsive) and 30 healthy controls underwent 12-lead ECG, M-mode echocardiography, and speckle tracking echocardiography (STE) to assess cardiac electrical activity, left ventricular (LV) volumes, ejection fraction (EF), fractional shortening (FS), and global longitudinal strain (GLS).

Results: ECG findings were comparable among the three groups. LV end-diastolic (LVEDV) and end-systolic volumes (LVESV), FS, and EF were significantly lower in DRE vs. controls (p < 0.05). LVEDV and EF were significantly lower in DRE vs. drug-responsive epilepsy (p < 0.05), while drug-responsive cases had lower LVEDV vs. controls (p = 0.015). LV GLS was significantly lower in DRE (-19.34 ± 1.80) vs. drug-responsive epilepsy (-20.33 ± 1.45) (p = 0.023) and controls (-20.58 ± 0.91) (p = 0.003). LV GLS correlated positively with time since last seizure (p = 0.007) and negatively with the number of antiseizure medications (p = 0.007).

Conclusions: Children with DRE exhibit significant cardiac dysfunction. STE enables early detection of subclinical cardiac abnormalities in DRE, advocating for its integration into routine monitoring.

Impact: Compares cardiac function in pediatric drug-resistant epilepsy (DRE) and drug-responsive epilepsy, identifying impaired systolic function and global longitudinal strain (GLS) in DRE. Correlates GLS abnormalities with antiseizure medication burden and time since last seizure, linking cardiac dysfunction to treatment intensity and epilepsy disease course. Advocates STE for early cardiac monitoring in DRE and urges longitudinal studies to disentangle epilepsy-related cardiovascular risks from drug-driven effects.

The trajectory of sleep in the first year of age is highly dynamic and correlates with developmental progress from the neonatal to the infantile period. During this critical period of brain growth, sleep facilitates neural maturation and memory consolidation. This review article examines the current evidence regarding the relationship between sleep and neurodevelopment in the first year of age. Over the first year, total sleep time decreases, nocturnal sleep consolidates with less nocturnal awakenings, and daytime sleep decreases. The dominant sleep state shifts from active sleep in neonates to non-rapid eye movement sleep at 12 months. Specific electroencephalogram (EEG) features include tracé alternant in neonates and sleep spindles and K complexes in infants. Characteristics of sleep spindles serve as biomarkers for neurodevelopmental outcomes. Adequate sleep duration is associated with enhanced white matter development. Healthy sleep parameters are linked to improved memory, language, executive function, sensorimotor skills, and overall cognitive development, whereas abnormal sleep during infancy is associated with cognitive, behavioral, and emotional disturbances. Developmental brain disorders and certain medical conditions are also associated with sleep disruption, indicating a bidirectional relationship. Sleep evolves rapidly in the first year of age, and adequate quantity and quality of sleep are critical for neurodevelopment. IMPACT: Sleep evolves significantly and rapidly during the first year, serving critical and active processes for neuromaturation. These sleep changes occur concurrently with major neurodevelopmental progress. Certain medical conditions, environmental exposures, and socioeconomic factors can disrupt sleep, potentially resulting in neurodevelopmental delay. Additionally, neurodevelopmental disorders are frequently associated with disruption in normal sleep architecture, suggesting a bidirectional relationship between sleep disruption and abnormal neurodevelopment. Future research should explore the neurodevelopmental consequences of medical and socioeconomic conditions that disrupt sleep. It is also essential to identify interventions to mitigate cognitive and behavioral disturbance arising from sleep disruption and to protect sleep health.

Background: Prenatal alcohol exposure (PAE) is a major public health concern, yet no reliable clinical tools are available for assessing levels of drinking during pregnancy. Fatty acid ethyl esters (FAEEs), the non-oxidative metabolites of ethanol in meconium, are potential biomarkers for quantifying PAE.

Methods: In a prospective birth cohort of children exposed to alcohol and drugs in utero, meconium from 216 newborns was analyzed. FAEE concentrations were quantified with gas chromatography via a flame ionization detector. A factor score was derived via a principal component analysis of six FAEE analytes. Expressive and receptive language were assessed in 189 children (56% girls) at ages 10 and/or 12.

Results: Higher FAEE factor scores were related to lower receptive language, with its harmful effect mitigated by non-kinship care at lower levels of FAEEs (p = 0.03). This relationship remained significant after adjusting for child IQ (p = 0.008). Expressive language showed a non-significant trend (p = 0.09), which disappeared after IQ adjustment (p > 0.30). Other prenatal drug exposures were unrelated to the effects of FAEEs on language skills.

Conclusions: Elevated levels of FAEEs in meconium can be potential biomarkers for identifying newborns at risk for poor language development related to PAE.

Impact: Higher concentrations of Fatty acid ethyl esters (FAEEs), the non-oxidative metabolites of ethanol, analyzed in meconium, are associated with lower receptive language at 10 and 12 years of age, but their harmful effect was mitigated at lower levels of FAEEs by the more enriched caregiving environment of non-kinship care. Elevated levels of FAEEs in meconium can be potential biomarkers for identifying newborns at risk for poor language development related to prenatal alcohol exposure (PAE). FAEEs may provide diagnostic clarity for PAE, allowing the identification of moderate and episodic PAE, which is unlikely to be detected at birth.