Pediatric Research最新文献

Background: To assess the prognostic value of serum cystatin C for predicting 10-year major adverse kidney events (MAKE) in pediatric patients with urologic malformations (UTMs).

Methods: This retrospective cohort study used the TriNetX global federated research network of electronic health records. Children aged 0-18 years with UTMs (including congenital urinary tract anomalies, vesicoureteral reflux, obstructive uropathy, neurogenic bladder, and spina bifida) and available serum cystatin C measurements were included. The primary outcome was MAKE, defined as the first occurrence of dialysis initiation, kidney transplantation, chronic kidney disease, albuminuria, or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² within 10 years. Secondary outcomes were the individual components of MAKE.

Results: After 1:1 propensity score matching, 2062 patients were analyzed (mean follow-up 1025 days). Elevated cystatin C (≥1.3 mg/L) was associated with higher MAKE incidence (39.3% vs 29.2%; HR 2.5, 95% CI 2.00-3.12, p < 0.001). Significant risks were observed for CKD (HR 3.55), dialysis (HR 9.09), and albuminuria (HR 1.83). No significant differences were found for renal transplantation (HR 0.52) or eGFR decline <60 (HR 1.48).

Conclusions: High cystatin C independently predicts MAKE and CKD in children with UTMs. Routine testing may enable early risk stratification and guide long-term renal surveillance.

Impact: Pediatric patients with urologic malformations have increased chronic kidney disease risk, often requiring dialysis with a significant healthcare and quality-of-life burden. Traditional markers like serum creatinine and eGFR have limitations in detecting early renal impairment in growing children. Serum cystatin C, unaffected by muscle mass or growth, offers superior kidney function assessment but has not been evaluated for predicting long-term outcomes in pediatric urinary tract malformations. This study is the first to evaluate cystatin C's prognostic value for Major Adverse Kidney Events in this population. Incorporating cystatin C into routine monitoring may improve early risk stratification and guide surveillance strategies.

Background: Premature birth can pose challenges to parent-infant attachment and increase parental anxiety. Music therapy has been proposed as an intervention, but its effectiveness remains unclear.

Methods: Six databases (Cochrane Library, Web of Science, EBSCO, Embase, PubMed, and Scopus) were searched until January 15, 2025. Eligible studies were randomized controlled trials that evaluated the effects of music intervention versus routine care on parental anxiety and parent-infant attachment in caring for premature infants. Quality assessment was conducted using the Cochrane Risk of Bias 2 tool. Random-effects meta-analyses were performed with heterogeneity assessed via I² statistics and Q tests. The Grading of Recommendations, Assessment, Development and Evaluation approach evaluated overall evidence quality.

Results: After comprehensive screening, 13 randomized controlled trials published between 2014 and 2024 were included, encompassing 1034 participants with preterm infants. The meta-analysis revealed no statistically significant improvement in parent-infant attachment or parental anxiety with music therapy compared to conventional care. However, subgroup analysis indicated that frequent music therapy interventions (≥once daily) positively influenced parent-infant attachment (SMD = -1.08, 95% CI: [-1.92, -0.24], p = 0.01).

Conclusions: Overall, music therapy may not reduce parental anxiety or improve attachment, but frequent interventions demonstrated promising potential and warrant further investigation.

Registration number: PROSPERO CRD42025643424.

Impact statement: This review indicates that music therapy, compared to standard care, shows no significant effects on parent-infant attachment or parental anxiety in the care of premature infants. However, more frequent (≥once daily) music therapy shows more promising results in improving parent-infant attachment, suggesting the importance of intervention intensity. These insights inform the development of targeted daily therapy protocol to enhance preterm care outcomes.

Background: To assess the longitudinal effects of intraventricular hemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD) on cerebral oxygenation using near-infrared spectroscopy (NIRS).

Methods: This prospective cohort study included preterm neonates born <34 weeks' gestation between 2013 and 2024. Regional cerebral oxygen saturation (rScO₂) was measured from IVH diagnosis until term-equivalent age. Duration of abnormal rScO₂ values (<55%; >85%) and cerebral fractional tissue oxygen extraction (cFTOE) were analyzed.

Results: A total of 154 preterm infants with IVH (median gestational age: 25⁺⁴ weeks) were included, of whom 65 (42.2%) developed PHVD, with 56 (86.2%) requiring temporizing neurosurgical intervention. Analysis of over 30,000 hours of NIRS data revealed a significant decline in cerebral oxygenation with increasing IVH severity (p = 0.023). Infants with PHVD had lower rScO₂ (p < 0.001), spent more time with rScO₂ < 55% (p < 0.001), and exhibited higher cFTOE (p < 0.001) than those without PHVD. Within the PHVD group, more interventions were associated with lower rScO₂ levels (p = 0.010) and higher cFTOE values (p = 0.005).

Conclusion: IVH and PHVD profoundly impair cerebral oxygenation. High-grade IVH leads to rScO₂ deterioration, further exacerbated in infants with greater PHVD burden. These findings highlight the need for targeted strategies to stabilize cerebral oxygenation in this vulnerable population.

Impact: Cerebral oxygenation declines with increasing intraventricular hemorrhage (IVH) severity in preterm infants. Posthemorrhagic ventricular dilatation (PHVD) severity, reflected by the number of neurosurgical interventions, is linked to worsening cerebral oxygenation and increased oxygen extraction. This prospective cohort study provides a comprehensive longitudinal dataset using near-infrared spectroscopy (NIRS) to link IVH severity and PHVD to cerebral oxygenation dynamics. Findings underscore the urgent need for targeted neuroprotective interventions to stabilize brain oxygenation in preterm infants with severe IVH and PHVD.

Background: Shared storybook reading in early childhood is crucial for cognitive and social development, but its association with broader developmental domains is less established. This study aimed to investigate the association between the frequency of shared storybook reading and overall child development.

Methods: This study analyzed data from the Japan Environment and Children's Study, a nationwide prospective birth cohort study. The frequency of shared storybook reading was assessed at multiple time points up to age 3. Child development was assessed using the Ages and Stages Questionnaire-3 (ASQ-3). The association was analyzed using multivariate models adjusted for parental background, opportunities to play with the child, and media exposure.

Results: A total of 36,866 mother-child pairs were analyzed. The frequency of storybook reading positively correlated with the ASQ-3 scores across all developmental domains. After adjustments, frequent reading at age 3 was associated with a 5.5-point increase (95% CI: 5.0-6.0, p < 0.001) in communication scores compared to rare reading. Among children whose ASQ-3 scores fell below the cutoff at the age of 1 year, more frequent reading at subsequent ages was associated with greater score improvements.

Conclusion: Frequent shared storybook reading positively correlated with the overall developmental progress in early childhood.

Impact: Based on a large-scale nationwide birth cohort study, frequent shared storybook reading is positively associated with the overall developmental progress in early childhood. Even for children with developmental delays at age one, continuous reading was positively associated with their development.

With increased access to advanced prenatal neuroimaging and genetic testing, neurological disorders such as brain malformations, brain injuries, and genetic disorders, are increasingly being diagnosed during pregnancy. In this review, we address neonatal neurocritical care considerations for the population with prenatally identified neurological disorders. We identify antenatal considerations, including planning location of delivery, as well as postnatal considerations, including clinical phenotyping, neuromonitoring, neuroimaging, and genetic testing. The importance of interdisciplinary collaboration between obstetrics, maternal-fetal medicine, neonatology, pediatric neurology, neuroradiology, genetics, palliative care, early intervention and habilitative services is emphasized. We outline high-priority research gaps, and highlight the need for large, multicenter studies that capture diverse geographies, populations, care practices and settings longitudinally. IMPACT: Fetal neurology is a rapidly evolving field owing to the increased prenatal diagnosis of neurological disorders; however, the natural history of many fetal neurological disorders is not well known. We identify interdisciplinary neonatal neurocritical care considerations for newborns with prenatally diagnosed neurological disorders, such as neuroimaging, neuromonitoring, and family support. We outline high-priority research gaps in fetal neurology relevant to neurocritical care, including the need to prioritize large-scale longitudinal studies on the etiologies, short- and long-term outcomes of fetal neurologic disorders across diverse geographies and populations to improve counseling and care.

Background: To compare the outcomes of whole-body hypothermia (WBH) in infants with neonatal encephalopathy born at 34^0/7-35^6/7 versus 36^0/7-37^6/7 weeks' gestation.

Methods: Retrospective analysis of 122 outborn infants in a single unit: Group 1 (n = 63; 34^0/7-6/7 weeks n = 17, 35^0/7-6/7 weeks n = 46) and Group 2 (n = 59; 36^0/7-6/7 weeks n = 25, 37^0/7-6/7 weeks n = 34). Clinical, electrographic, neuroimaging, neurodevelopmental data at 18 months were assessed.

Results: Group 1 had more hemodynamic instability (67% vs. 32%, p < 0.001), hypoglycemia (54% vs 36%, p = 0.04), and higher white-matter and total brain-injury scores (medians 7 vs. 4 and 10 vs. 5, both p ≤ 0.05), compared with Group 2. Overall mortality was 22% (14/63) vs. 12% (7/59), respectively (adjusted odds ratio [aOR] 3.49, 95% CI 1.06-11.50). Composite outcome of death or moderate-severe neurodevelopmental impairment (NDI) was more common in Group 1 (42% vs. 21%; aOR 2.94, 95% CI 1.02-8.46). The 35^0/7-6/7 vs. 36^0/7-6/7-week subgroup comparison did not reach statistical significance for composite outcome (aOR 2.42, 95% CI 0.60-9.78, p = 0.2). However, among 35^0/7-6/7-week infants, composite outcome was more common occurring in 45% compared with 21% at 36^0/7-37^6/7 weeks (aOR 3.37, 95% CI 1.09-10.44, p = 0.03).

Conclusion: At 34^0/7-35^6/7 weeks, WBH was associated with greater physiological instability, more severe brain injury, and adverse outcomes.

Impact: Late preterm infants born at 34^0/7-35^6/7 weeks' gestation had higher rates of physiological instability, including hemodynamic instability and hypoglycemia during whole-body hypothermia compared to those born at 36^0/7-37^6/7 weeks. Post-rewarming brain MRI showed higher white matter injury subscores and total brain injury scores in infants born at 34^0/7-35^6/7 weeks' gestation compared to those born at 36^0/7-37^6/7 weeks. After adjustment for encephalopathy severity, 34^0/7-35^6/7 weeks' gestation late preterm infants had higher mortality and nearly twice the rate of composite adverse outcomes, highlighting their greater vulnerability to adverse outcomes following whole-body hypothermia compared with the more mature 36^0/7-37^6/7 weeks group.

Background: Inconsistent findings regarding the long-term effects of prenatal antidepressant exposure on child behavior may stem from a lack of attention to exposure propensity.

Methods: We used data from the Longitudinal Study of Australian Children (LSAC), a nationally representative birth cohort. Prenatal antidepressant exposure was based on self-reported use during pregnancy. Emotional problems and hyperactivity were assessed at ages 4, 6, and 8. We applied inverse probability weighting (IPW) to growth curve models (GCMs) and repeated measures mixed models (RMMMs) to evaluate behavioral trajectories.

Results: Prenatal antidepressant exposure was not significantly associated with baseline emotional problems or hyperactivity. However, exposed children showed a steeper increase in emotional problems over time (GCM interaction: β = 0.05, p = 0.003; RMMM age 6 vs. 4: β = 0.12, p < 0.001; age 8 vs. 4: β = 0.09, p = 0.006). Hyperactivity differences became significant only at age 8 (GCM interaction: β = 0.15, p < 0.001; RMMM age 8 vs. 4: β = 0.30, p < 0.001).

Conclusions: While not associated with immediate behavioral differences, prenatal antidepressant exposure may shape the developmental trajectory of emotional and behavioral outcomes, emphasizing the need for long-term monitoring.

Impact: Prenatal antidepressant exposure is not associated with immediate emotional or behavioral differences in early childhood, but may influence developmental trajectories, with emotional problems progressively increasing and hyperactivity emerging later. This study highlights the value of modeling symptom trajectories over time and incorporates inverse probability weighting to better account for exposure propensity and reduce confounding bias. The findings support the need for long-term monitoring of exposed children and inform clinical and policy efforts to integrate maternal mental health care with early developmental surveillance.

Background: Improved survival of very preterm (<32 weeks of gestation) infants has highlighted neurodevelopmental and socio-emotional challenges. As altered gaze behavior and autonomic functioning may contribute to these difficulties, we investigated this in thirty-nine very preterm and thirty-eight full-term 8-to-12-year-old children.

Methods: We assessed gaze behavior during a semi-structured conversation. Autonomic functioning was evaluated through heart rate variability and skin conductance responses at rest and during an eye contact paradigm.

Results: Preterms exhibited shorter but more frequent gazes toward their conversation partner than full-terms. Moreover, both at rest and during the eye contact paradigm, they demonstrated higher heart rate variability. No group differences in skin conductance responses were observed at rest, but during the eye contact paradigm, preterms displayed more pronounced skin conductance responses regardless of condition.

Conclusion: Very preterm children exhibited reduced sustained social attention and heightened autonomic activity. Nevertheless, reported subjective experiences were similar among both groups, suggesting that heightened arousal reflects general physiological reactivity rather than perceived stress. This underscores the importance of potential interventions targeting attentional control to improve socio-emotional outcomes in very preterm children.

Impact: Very preterm (VPT) survivors often face socio-emotional challenges, including altered gaze behavior and autonomic functioning. VPT children engaged in shorter but more frequent gazes toward conversation partners compared to FT peers, indicating difficulties with sustained attention. Assessments in middle childhood reveal increased parasympathetic activity, heightened sympathetic arousal, and faster skin conductance recovery during eye contact, highlighting the need for supportive interventions.

Background: Children with congenital heart disease (CHD) often exhibit elevated preoperative NT-proBNP, linked to prolonged postoperative mechanical ventilation. Age-adjusted ZlogNT-proBNP outperforms raw NT-proBNP in predicting outcomes, but its relationship with ventilation duration and underlying inflammatory pathways remain unclear.

Methods: This retrospective cohort study included 113 CHD children. Preoperative ZlogNT-proBNP were quantified and perioperative cytokines (IL-6, IL-8, IL-10) were measured, as well as postoperative ventilation duration were recorded. Multivariable regression and mediation analyses assessed direct and indirect cytokine-mediated effects on prolonged ventilation.

Results: Among the 113 children, 28 (25%) experienced prolonged mechanical ventilation and had significantly higher preoperative ZlogNT-proBNP compared to those with shorter mechanical ventilation durations. Postoperatively, IL-6, IL-8, and IL-10 levels were significantly elevated in the prolonged mechanical ventilation group. Mediation analysis revealed that IL-6, IL-8, and IL-10 partially mediated the association between ZlogNT-proBNP and prolonged mechanical ventilation, with mediation proportions of 28%, 38%, and 37%, respectively.

Conclusion: Elevated preoperative ZlogNT-proBNP was significantly associated with prolonged mechanical ventilation, partly via cytokine-mediated inflammatory pathways. These findings suggest that targeting inflammatory pathways may help optimize perioperative care and reduce ventilation duration.

Impact: 1. Preoperative ZlogNT-proBNP levels and postoperative inflammatory markers (IL-6, IL-8, and IL-10) are significantly associated with prolonged postoperative mechanical ventilation duration. 2. Postoperative inflammatory cytokines (IL-6, IL-8, and IL-10) partially mediate the association between preoperative ZlogNT-proBNP levels and prolonged MV duration.