Pediatric Research最新文献

Background: The High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial for neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia demonstrated no neurodevelopmental benefit but was associated with a higher rate of serious adverse events (SAEs). Understanding if targeted Epo plasma exposures were achieved in the HEAL trial and if SAEs were associated with higher exposures would help future therapeutic programs of Epo as a candidate neuroprotective treatment.

Methods: Ancillary study of a subset of HEAL neonates who received Epo (1000 U/kg IV on days 1, 2, 3, 4, and 7) and had plasma drug concentrations measured. Within a Bayesian pharmacokinetic framework, the area under the curve during the first 48 h (AUC_48h) and 7 days (AUC_7d) of treatment was estimated. The % of neonates who achieved animal model neuroprotective targets of AUC_48h >140,000 mU*h/ml and AUC_7d >420,000 mU*h/ml was calculated. The relationship between AUC_7d and SAEs after study drug was evaluated using logistic regression.

Results: Among n = 89 neonates, variation in Epo exposure was low, and over 95% of neonates achieved the target AUC_48h and AUC_7d. No meaningful relationship was seen between AUC_7d and risk of SAE.

Conclusions: The Epo dosing strategy in the HEAL trial consistently achieved target plasma exposures. Higher exposures were not associated with SAEs.

Impact: In the HEAL randomized, placebo-controlled trial of high-dose erythropoietin (Epo) for neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia, the Epo dosing strategy achieved animal model neuroprotective plasma exposure targets in >95% of neonates. This understanding further strengthens the HEAL trial's primary conclusion that Epo provides no additional benefit in neonates with HIE also receiving therapeutic hypothermia. While Epo treatment was associated with a higher rate of serious adverse events (SAEs) compared to placebo in the primary HEAL trial, higher plasma exposures of Epo were not associated with the risk of SAEs.

Background: While the incidence of neonatal intensive care unit (NICU) admission steadily increases, neonatology lacks evidence of a safe, effective, and preventive analgesic for treating procedural pain. Given its role in nociception and promoting healthy neurodevelopment, the endogenous neuropeptide oxytocin (OT) emerges as a promising candidate.

Methods: This study investigates the use of daily repeated subcutaneous OT (1 mg/kg) treatment in an established model of neonatal repetitive procedural pain and assesses the effectivity of OT treatment on mechanical sensitivity and body weight.

Results: Contrary to our hypothesis repeated daily OT treatment did not prevent the development of mechanical hypersensitivity following needle pricks. Furthermore, treatment with OT diminished body weight gain in neonatal pups, a major side effect observed throughout the neonatal week. These results highlight the unique nature of the maturing nociceptive system that makes the identification and selection of analgesic options for the treatment of acute neonatal procedural pain a major challenge.

Conclusion: In conclusion, our preclinical results do not support the use of repeated OT for acute pain relief in the NICU, and the side effects on body weight gain raise concerns about the use of OT in the NICU.

Impact: Repeated daily OT treatment inhibits weight gain in neonatal rat pus. Repetitive daily OT administration does not prevent the development of mechanical hypersensitivity in a model of neonatal procedural pain. Future research must focus on the unique physiology of the developing nociceptive system to establish safe, effective and protective treatment of neonatal procedural pain.

Background: The choice of the ideal antiseptic is not only based on its efficacy but also on safety and skin-friendliness. There are no standard recommendations regarding ideal skin preparation in neonates.

Methods: This was a prospective cohort study to evaluate the efficacy of 3 antiseptics[10% Povidone Iodine(PI), 70% isopropyl alcohol(AL), 2% chlorhexidine in 70% alcohol(CHG-IPA)] in disinfecting the skin before venipuncture in term neonates as assessed by logarithmic reduction in skin bacterial colony counts post-application. Secondary objectives were to assess the changes in skin condition. Measurements were done pre-, post-antiseptic and 6-24 h (for residual effect) later. Fifty neonates were enrolled in each group.

Results: All three antiseptics caused a significant reduction in bacterial load post-application, but maximal efficacy [2.6(2.2-2.8)log reduction] and, maximal residual effect at 6-24 h was seen with CHG-IPA [2.4(2.2-2.6)log reduction]. The logarithmic reduction in colony counts from pre-intervention to 6-24 h later remained significant for all three groups [(PI, p-0.039; CHG-IPA, p-0.00; AL, p - 0.01)]. After an initial alteration in hydration, and skin condition score, there was a return to baseline after 6-24 h.

Conclusion(s): 2% CHG-IPA had better efficacy than AL or PI for skin antisepsis in term neonates. There was no significant change in skin integrity in all three groups.

Impact: All three antiseptics [2% chlorhexidine gluconate in 70% isopropyl alcohol(CHG + IPA), 10% Povidone Iodine(PI), and 70% isopropyl alcohol(AL)] cause significant reduction in bacterial colony counts. CHG + IPA has the maximum efficacy as assessed by log reduction of bacterial colony counts with optimal residual effect favouring its usage in term neonates. The least efficacy is seen with 70% isopropyl alcohol. All three antiseptics are skin-friendly and do not affect the skin integrity. Future studies addressing the clinical outcomes and safety in preterm populations with these commonly used antiseptics should be done.

Newborn screening (NBS) in the United States began in the 1960s to detect inborn errors of metabolism that benefited from presymptomatic treatment compared with treatment after the development of symptoms and diagnosis. Over time, it expanded to include endocrinological disorders, hematological disorders, immunodeficiencies, and other treatable diseases such as lysosomal storage diseases (LSD), cystic fibrosis, X-linked adrenoleukodystrophy, and spinal muscular dystrophy. This expansion has been driven by new technologies (e.g., tandem mass spectrometry) and novel treatments (e.g., enzyme replacement therapy and stem cell transplant for LSDs). Advances in next-generation gene sequencing (NGS) enable rapid identification of many additional conditions that might benefit from early presymptomatic intervention. We review the NGS technologies that evolved as diagnostic testing and suggest issues to be resolved before their potential application to screening the asymptomatic population. We illustrate the importance of selecting diseases to be screened and propose recommendations to follow when variants of uncertain significance are found. We address ethical issues around achieving equity in the sensitivity of genomic NBS, access to follow-up and management, especially for people from diverse backgrounds, and other considerations. Finally, we discuss the potential benefits and harms of genomic NBS to the overall health of children with monogenic diseases. IMPACT: Genomic newborn screening programs are ongoing worldwide. Public discussion is needed as to whether genomic newborn screening should be offered as a public health program and, if so, what conditions should be screened for. Providers should understand that the sensitivity of genomic newborn screening is especially low for newborns from non-European populations. Methylation, large structural variants and repeat expansion variants are not amenable to next-generation sequencing-based genomic newborn screening. The article serves as a comprehensive guide to understanding issues that need to be solved before genomic newborn screening is implemented as a public health program.

Burning of fossil fuels along with deforestation and ecological disruption have led to the warming of the Earth and climate change. Children are especially vulnerable to adverse health effects of climate change associated changes in the air, soil, and water as their organs are still developing, have a faster breathing rate, higher per pound ingested and inhaled exposures, and greater relative body surface area. To protect this vulnerable population, health care professionals need to play a leading role. In 2015, the American Academy of Pediatrics (AAP) updated their original 2007 Global Climate Change and Children's Health policy statement (again updated in 2024) stating that, "failure to take prompt, substantive action would be an act of injustice to all children." Health care professionals need to educate themselves and their patients of the health risks posed by climate change and incorporate climate change counseling into their practice. They also need to go beyond the framework of the healthcare system and work collaboratively with communities, corporations, and governments to advocate for policies and solutions to mitigate and adapt to climate change. The health and wellbeing of future generations rests upon the actions we take today. IMPACT: Summarizes the adverse effects of increased anthropogenic activity and burning of fossil fuels on planetary and human health Details the increased vulnerability of children to environmental assaults and their long-term effects Provides guidance and resources to health care professionals to empower them to act as advocates for systemic and structural changes that protect children's health.

Objective: To investigate the associations of television (TV) watching time with bone parameters and to examine whether high lean mass attenuates the negative impact of watching TV more than one hour per day on bone parameters.

Methods: This cross-sectional study comprised 116 young paediatric cancer survivors. Dual-energy X-ray Absorptiometry was used to obtain total body and regional areal bone mineral density (g/cm²), and lean mass (kg) outcomes. Hip Structural Analysis was performed at the narrowest point of the femoral neck. Trabecular Bone Score was obtained in the lumbar spine. TV watching time was obtained using the "Youth Activity Profile" questionnaire.

Results: Multiple linear regression models showed negative associations of watching TV more than one hour with bone parameters in peri/post pubertal survivors (β = -0.359 to -0.614, P < 0.001 to 0.047). Those survivors watching TV more than one hour per day and with high lean mass presented higher bone parameter Z-score than those with low lean mass.

Conclusion: These findings underline the necessity of identifying strategies that promote musculoskeletal development while reducing TV watching time in young paediatric cancer survivors to maximise bone regeneration.

Impact: The results indicate that watching television (TV) more than one hour (compared to not watching TV) is negatively associated with bone parameters in peri/post pubertal survivors. Survivors with high lean mass counteract these negative associations of watching TV with bone parameters. It is important to promote musculoskeletal development in this vulnerable population to maximise bone regeneration.