Pediatric Research最新文献

Background: Essential metals may play roles in neurodevelopment. The aim was to evaluate the associations of magnesium (Mg), iron (Fe), copper (Cu), and zinc (Zn) levels with neurodevelopment among preschool children.

Methods: The medical records of eligible children enrolled between January 2019 and July 2022 were retrospectively reviewed for required information. The quantitative measurement of metals was conducted using atomic absorption spectroscopy, while screening of neurodevelopment was performed using the Ages and Stages Questionnaire. Modified Poisson regression and Bayesian kernel machine regression (BKMR) analyses were used to evaluate the prevalence ratio (PR) of their independent and joint associations.

Results: 662 (14.8%) children were found to have possible neurodevelopmental delays. Modified Poisson regression showed that Mg, Cu, and Zn levels were independently and negatively associated with the risk of neurodevelopmental delay. The PRs (95% CIs) for per log₂ increment of the above metals were 0.35 (0.19-0.62), 0.57 (0.42-0.77), and 0.63 (0.42-0.96). These negative associations were more pronounced in the gross motor and personal-social domains while considering the concrete five domains. BKMR showed a negative association of metal mixture with the risk of neurodevelopmental delay.

Conclusion: Mg, Cu, and Zn were inversely associated with neurodevelopmental delay. Sufficient essential metal levels are important for neurodevelopment.

Impact: Essential metals play a key role in neurodevelopment. The association of essential metal mixture with neurodevelopment is relatively scarce. Preschool children with possible neurodevelopmental delay are found to have lower Mg, Cu, and Zn levels than their counterparts. Single Mg, Cu, Zn levels, and elevated essential metal mixture are negatively associated with the risk of possible neurodevelopmental delay.

Background: Intestinal fatty acid binding protein (I-FABP) is an intestinal epithelial protein detectable in infants with necrotizing enterocolitis (NEC). The longitudinal behavior of I-FABP following NEC or its association with gastrointestinal or neurodevelopmental outcomes is unknown.

Methods: In this secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, we compared infants with and without NEC. Urine I-FABP concentrations in matched infants (n = 70) were measured serially using ELISA and compared using paired analysis. In infants with NEC, the associations of I-FABP levels with short-term outcomes and neurodevelopmental outcomes at 22-26 months corrected age were determined using non-parametric analysis.

Results: Infants with NEC were more likely to have cholestasis, death or severe neurodevelopmental impairment, cerebral palsy, and lower Bayley-III motor scores. Baseline urinary I-FABP levels were similar between groups. When compared to controls, infants with NEC had urinary I-FABP concentrations that were higher at diagnosis (median 11 vs 2.6 ng/ml, p = 0.006) and lower post-NEC (median 1 vs 5 ng/ml, p = 0.002). Diagnosis I-FABP levels were not associated with gastrointestinal or neurodevelopmental outcomes at 22-26 months corrected age.

Conclusions: In extremely preterm infants, urinary I-FABP was elevated at NEC diagnosis and lower post-NEC compared to matched controls. I-FABP levels were not associated with adverse gastrointestinal or neurodevelopmental outcomes.

Impact: Urinary intestinal fatty acid binding protein (I-FABP) levels are increased at diagnosis of NEC and fall to below baseline after NEC in extremely preterm infants. Urine I-FABP levels at NEC diagnosis are not associated with cholestasis, intestinal stricture or obstruction, need for additional intestinal surgery after NEC, or neurodevelopmental outcomes at 22-26 months corrected age. Urine I-FABP levels may be useful in the diagnosis of NEC. Diagnostic I-FABP levels do not predict short-term gastrointestinal or neurodevelopmental outcomes after NEC.

Impact: This study identifies an association between increased recreational screen time and vitamin D deficiency among children and adolescents. Children and adolescents engaging in five or more hours of daily screen time exhibited more than double the risk of vitamin D deficiency compared to those with lower screen exposure. These findings underscore the importance of clinicians assessing screen habits in pediatric patients, as excessive screen time may reduce outdoor activity and sunlight exposure, leading to health risks. Monitoring and managing screen time, alongside considering vitamin D supplementation and outdoor activity, may help mitigate deficiency and associated conditions.

Oxytocin research is rapidly evolving and increasingly reveals that epigenetic modifications to the oxytocin receptor gene (OXTR) are functional, plastic, and reliable components of oxytocinergic system function. This review outlines how OXTR epigenetics are shaped by the early life environment, impact social-developmental outcomes, and have strong potential to serve as therapeutic targets. We first establish the malleability of OXTR epigenetics in infancy in both animal models and humans through research demonstrating the impact of the early life environment on OXTR DNA methylation (OXTRm) and subsequent social behavior. Next, we detail how OXTRm serves as a predictive mechanism for neurodevelopmental outcomes in animal models of social behavior such as the prairie vole, and summarize the role of OXTRm in psychiatric disorders, emotional processing, and attachment behavior in humans. We discuss the potential of further OXTRm research to improve oxytocin therapeutics by highlighting how a deeper knowledge of OXTRm could improve the therapeutic potential of exogenous oxytocin, how OXTRm may impact additional cellular mechanisms with therapeutic potential including control of the perinatal GABA switch, and how early life therapies may target the tuning of endogenous OXTRm. Finally, we review limitations of previous oxytocin research and make recommendations for future research. IMPACT: Previous research into oxytocin therapeutics has been hampered by methodological difficulties that may be improved by assay of the oxytocin receptor gene (OXTR) and its methylation (OXTRm) Key sites of OXTRm modification link early life exposures to developmental and behavioral outcomes OXTRm appears to have a critical period of development in early life Epigenetic modification of the oxytocin receptor gene could serve as a powerful target for therapeutic interventions.

Background: Investigate the utility of cardiovascular responses such as heart rate (HR), blood pressure (BP), and heart rate variability (HRV) in the prognosis of children with acute acquired brain injury (ABI).

Methods: Children under 18 years with severe acute acquired brain injury (ABI) who survived at least 12 h after PICU admission were included in a prospective observational cohort in a tertiary academic PICU. Physiological variables, neurological data, laboratory tests (chemistry and hematology), and medications were recorded within 12 h of admission. Linear and nonlinear HRV indices, CT scans, PICU scores, and survival rates were evaluated.

Results: Seventy-two children, median age 10.7 years (IQR 4.1-13.6), were eligible for the study; 28 (38.9%) were diagnosed with brain death (BD). Tachycardia, SBP and MBP < 5th percentile, and MBP and DBP> 99th percentile were significantly associated with mortality. Poincaré SD1/SD2 was significantly associated with mortality after adjusting for age, sex and ongoing medication.

Conclusion: Tachycardia, systolic hypotension and median hypo and hypertension were associated to mortality in children with severe ABI. While further validation through larger, multicenter studies is necessary, the Poincaré SD1/SD2 ratio has shown promise as a prognostic tool for predicting mortality in children with severe ABI.

Impact statement: This study explores cardiovascular changes, including heart rate and blood pressure, and linear/nonlinear HRV measures using ECG at 1000 Hz, and compare them with other prognostic factors like brain tomography and PICU scores. Tachycardia, hypo/hypertension in the early hours after admission are linked to early mortality in children with severe traumatic and non-traumatic brain injury. Linear/non-linear measures of HRV were also related to survival. Higher HRV values indicating better survival chances. We identified Poincaré SD1/SD2 ratio as a promising tool for predicting mortality in children with severe ABI.

Background: Adequate enteral nutrition is associated with improved outcomes in hospitalized children. Common interruptions to enteral nutrition include fasting status for planned procedures. We sought to describe current fasting duration for patients in the pediatric intensive care unit (PICU) undergoing planned anesthesia events.

Methods: We completed a retrospective cohort study of patients ≤21 years old in a PICU from January 2015 to December 2020 who underwent a procedure or imaging study and were tolerating enteral nutrition prior to the procedure.

Results: A total of 189 patients met inclusion criteria. Anesthesia events requiring NPO status included radiologic studies (32.8%), neurosurgery (19.6%) and general surgery (13.8%). The median duration of fasting status was 13.3 h (IQR 8.0-23.0), exceeding recommendations of 2-6 h at our institution. Thirty-five patients (18.5%) were intubated prior to NPO status. Forty-five (23.8%) of NPO orders were placed to start at midnight.

Conclusion: This study shows that fasting duration in children previously tolerating enteral nutrition in the PICU can exceed the recommended minimum duration in non-emergent cases requiring anesthesia. An opportunity exists to evaluate barriers and facilitators to enhance active decision making surrounding fasting status for hospitalized patients undergoing planned anesthesia events to maximize nutrition and minimize harm.

Impact: Adequate enteral nutrition is crucial to healing in hospitalized children, especially those who are critically ill in the PICU. Interruptions to enteral nutrition are common in hospitalized patients. In this study, we demonstrate that children in the PICU who were previously tolerating enteral nutrition and underwent a planned general anesthesia event were made nil per os (NPO) for a median time of over 13 h, which exceeds institutional and societal guidelines of 2-6 h. This study has identified opportunities to improve compliance with fasting guidelines for this population to reduce enteral nutrition interruptions for hospitalized patients in the PICU.

Background: In type 1 diabetes, telomere length (TL) may predict complications and could be influenced by glycaemic control and physical activity, but its relationship with physical fitness in youths remains unexplored. The aim of the study was to assess the association between physical fitness and TL in youth with type 1 diabetes, both at baseline and one year later.

Methods: Eighty-three children and adolescents (aged 6-18 years; 44.6% girls) with type 1 diabetes from the Diactive-1 Cohort Study were involved in this study. Physical fitness was assessed using spirometry on a cycloergometer (i.e., peak oxygen consumption), dynamometry, and maximal isometric strength (one-repetition maximum [1RM]), and muscle power. Leucocyte TL was assessed using multiplex monochrome real-time quantitative polymerase chain reaction.

Results: Positive cross-sectional associations were identified between 1RM (unstandardized beta coefficient [B] = 0.042, 95% bias corrected and accelerated [BCa] confidence interval [CI] 0.012-0.069), muscle power (B = 0.056, 95% BCa CI 0.02-0.250), and overall physical fitness (B = 0.043, 95% BCa CI 0.015-0.071) with TL independent of maturation, glycated haemoglobin, and diabetes duration. However, no associations were observed one year later.

Conclusion: Higher levels of fitness, particularly muscle strength, may play a role in telomere dynamics in youth with type 1 diabetes, suggesting that strength training exercise could be beneficial.

Impact: This is the first study to examine cross-sectional and longitudinal perspectives on the correlation among muscle strength, peak oxygen consumption [VO_2peak] and telomere length in youths with type 1 diabetes. Higher physical fitness levels, as assessed by measures such as one-repetition maximum, muscle power, and overall physical fitness, are positively associated with telomere length in youths with type 1 diabetes. Understanding this link could improve management strategies, prioritizing muscle strength training for better long-term health in type 1 diabetes.

The developmental origins of health and disease hypothesis propose that lifelong health is programmed during foetal development, in utero. The world's population is ageing due to increased longevity but expanding morbidity and the associated burden on health systems around the planet, are associated with this. Consequently, resources are strained and spent largely on treating patients rather than preventing chronic diseases at their source. Research on early life exposures, starting in the womb, is needed to identify new potential biomarkers linked with the development of chronic diseases during adulthood. Evidence from maternal-offspring cohorts investigating associations between pregnancy exposures and childhood metabolic health is reviewed (The GUSTO study in Singapore, the Copenhagen Prospective Studies on Asthma in Childhood, a mother-child cohort in rural Gambia, the MINIMat study in Bangladesh, The Iodine Status in Pregnancy and Offspring Health Cohort in China, the OBESO cohort in Mexico, the Pune Nutrition study in India, The Reus-Tarragona Birth Cohort study in Spain). Collectively, evidence from prospective observational studies, randomised controlled trials and animal studies, supports the hypothesis that maternal diet, lifestyle and nutritional status during pregnancy are associated with childhood metabolic health in the offspring. However, the evidence is scant and further research is needed.