Frontiers in Pediatrics最新文献

Acid sphingomyelinase deficiency (ASMD) is a rare, progressive lysosomal storage disorder resulting from a deficiency in acid sphingomyelinase, leading to sphingomyelin accumulation and multi-organ damage. ASMD presents a broad phenotypic spectrum with a continuum of severity, making it challenging to predict the phenotype in very young children and differentiate between acute and chronic neurovisceral disease. No disease-specific treatments existed for ASMD. Recently, Olipudase-alfa, an intravenous enzyme replacement therapy, has been approved for non-neurological manifestations based on clinical trial results showing significant improvements. This report details the compassionate use of Olipudase-alfa in a 8-month-old boy. At baseline, he exhibited hepatosplenomegaly, elevated transaminases, and normal developmental milestones, consistent with a chronic neurovisceral phenotype. The treatment commenced at 8 months of age, escalating from 0.03 mg/kg to 3 mg/kg bi-weekly. Throughout the two-year period, the child tolerated the therapy well, with no severe adverse events reported. Notable clinical outcomes included a significant reduction in spleen and liver size, normalization of liver function tests, and stabilization of the lipid profile. The biomarker Lyso-sphingomyelin significantly reduced but never normalized, while oxysterols completely normalized. In the following months, the patient exhibited neurocognitive regression, allowing to define an acute neurovisceral phenotype. Although not impacting on the neurological manifestations, treatment with Olipudase-alfa strikingly improved the child's visceral symptoms, contrasting with the typical progressive decline seen in untreated patients. This report highlights the importance of early intervention, even in patients with neurovisceral phenotypes, as it can enhance quality of life for both patients and their families. Our findings advocate for reconsidering treatment eligibility criteria based solely on clinical phenotype definitions, highlighting the need for a tailored approach in ASMD management.

Background: Magnetic resonance imaging (MRI) is a crucial non-invasive diagnostic tool for pediatric diseases, requiring patients to remain still, often with the use of sedatives. Midazolam and dexmedetomidine are commonly used for sedation in children, but their combined effect needs further study. This study aims to evaluate the safety and effectiveness of combining intranasal dexmedetomidine (ID) with oral midazolam (OM) in children undergoing MRI, and assess its clinical feasibility.

Methods: A prospective, randomized controlled trial was conducted with 196 pediatric patients undergoing MRI from January 2022 to December 2023. Patients were randomly assigned to a control group (OM alone) or an observation group (OM + ID), with 98 cases each. Total sedation time, wake-up time, onset time, and adverse reactions were evaluated. Sedation effectiveness was assessed using the Ramsay Sedation Score.

Results: The observation group had significantly longer total sedation time (P = 0.039) and higher one-time sedation success rate (P = 0.038) compared to the control group. The Ramsay score indicated better sedation effects in the observation group (P < 0.05). Adverse events were similar between groups and resolved with rest.

Conclusion: Combining ID with OM provides effective sedation for pediatric MRI, with an acceptable safety profile, supporting its use in clinical practice.

Purpose: To investigate the clinical features of necrotizing enterocolitis-associated intestinal perforation (NEC-IP) in neonates with different gestational ages (GAs). Furthermore, we also want to identify the risk factors of poor prognosis for these patients.

Methods: The retrospective study of patients with NEC-IP was conducted with basic information, comorbidity, intraoperative findings, related treatment, and prognosis. According to the GA, patients were divided into three groups: early (GA: 28-<32 weeks, Group 1), mid-term (GA: 32-<34 weeks, Group 2), and late (GA: 34-<37 weeks, Group 3). The clinical features of the three groups were analyzed, and risk factors for poor prognosis were identified.

Results: Of the 113 cases, the number of cases in Groups 1 to 3 was 36 (31.9%), 44 (38.9%), and 33 (29.2%), respectively; and the overall proportion of poor prognosis was 19.4% (22/113). For basic information, the birth weight of Group 1 was lower than that of Group 2 and Group 3, while the postnatal day at the time of surgery of NEC and the onset age were higher than that of Group 2 (onset age: G1 12.0[7.00;20.5], G2 9.00[4.00;13.0]; postnatal day at the time of surgery: G1 22.0[13.8;27.2], G2 13.0[8.00;21.0]) (P < 0.016). For comorbidity, the incidence of sepsis, coagulopathy, type of (congenital heart disease) CHD, and hypoproteinemia in Group 1 was higher than that in Group 2 (all P < 0.016), and the incidence of respiratory failure, hypoproteinemia in Group 1 was higher than that in Group 3 (all P < 0.016). For related treatment, the usage rate of vasoactive substances and mechanical ventilation in Group 1 was higher than that of Group 2 and Group 3 (all P < 0.016). By Lasso and Logistic regression analysis, we found that GA (OR: 0.274, 95%CI: 0.078-0.796), sepsis (OR: 7.955, 95%CI: 1.424-65.21), coagulopathy (OR: 19.51, 95%CI: 3.393-179.1), CHD (OR: 6.99, 95%CI: 1.418-54.83) and diseased bowel segment (OR: 2.804, 95%CI: 1.301-7.316) were the independent factors for poor prognosis (all P < 0.05).

Conclusions: The clinical features of NEC-IP patients differ based on GA, particularly in terms of CHD type, postnatal day at the time of surgery, utilization of vasoactive substances, and prognosis. Furthermore, GA, sepsis, coagulopathy, CHD, and diseased bowel segment are independent factors for poor prognosis of patients with NEC-IP.

Background: Breast milk is the primary source of nutrition during early life, and existing research indicates that the development of jaundice in breastfed newborns may be linked to specific nutrients or bioactive substances present in breast milk. However, the association between the microbiota and small-molecule metabolites in breast milk and the development of neonatal jaundice remains unproven. This study aimed to investigate the development of jaundice in breastfed neonates in relation to breast milk microbiota and metabolites.

Methods: Based on the conditions of exclusive breastfeeding, we selected healthy newborns without significant jaundice and their mothers on day 4 (96-120 h after birth) as the healthy control group, and jaundiced newborns and their mothers as the jaundice group. Breast milk samples were collected from mothers in both groups on postnatal day 4 and analyzed for microbiota and small-molecule metabolites using 16S rRNA gene sequencing and an liquid chromatography-tandem mass spectrometry techniques.

Results: A total of 104 mother-child pairs were included in the study, of which 51 pairs were in the healthy control group and the other 53 pairs were in the jaundice group. Our results demonstrated that there was no significant difference between the species composition and diversity of the breast milk flora in the healthy control and jaundice groups. At the genus level, the abundance of Lactobacillus, Ackermannia, and Bifidobacterium was significantly higher in the breast milk of the healthy control group than in the jaundice group. Metabolomics analysis revealed a total of 27 significantly different metabolites between the two groups. Notably, breast milk from the healthy control group had elevated levels of 24 metabolites, predominantly lipids family, including sphingolipids, phospholipids, and fatty acid derivatives.

Conclusion: This study suggests that there is a link between the development of neonatal jaundice and breast milk microbiota and metabolites. Breast milk from mothers of healthy newborns contains higher levels of beneficial bacteria and lipid family compared to mothers of newborns with jaundice. This study offers new insights into the relationship between breastfeeding and neonatal jaundice.

Background: To investigate the effect of basic intermittent exotropia (IXT) on myopic shift in children during 12-month follow-up.

Methods: 165 children aged 4-15 years were recruited prospectively in this study and divided into 3 groups: Group A, consisted of 64 patients with basic IXT without surgery; Group B, consisted of 51 patients 1-month after IXT-corrected surgery; and Group C, consisted of 50 patients without any form of strabismus. All patients underwent assessments of spherical equivalent (SE), axial length (AL), exodeviation, and binocular function relating to accommodation and convergence. Examinations were conducted at baseline and 12-month. SE and AL changes were compared among groups. Univariate and multivariate linear analyses were employed to investigate the association between myopic shift and IXT, as well as other clinical parameters.

Results: Three groups showed comparable ages, genders and SEs at baseline (all P > .05). During 12-month follow-up, the rate of myopic shift varied among groups. Significant differences in SE progression (P = .006) and AL elongation (P = .014) between Group A and Group C were observed. Although SE progression and AL elongation in Group B were less than Group A, no significant differences were found (P = .125; P = .038). In the multivariate analysis, increases in exodeviation angle were significantly associated with both SE progression (β = 0.010, P = .041) and AL elongation (β = -0.005, P = .026). Each one prism diopter increase in the exodeviation angle was correlated with a 0.01D SE progression and a 0.005 mm AL elongation.

Conclusions: Children with basic IXT exhibited faster myopia shift compared to those without strabismus. Although surgical correction of strabismus appeared to slow this process, the effect was not statistically significant. Furthermore, greater increase in exodeviation angle was associated with higher rate of SE progression and AL elongation.

Trial registration: The study was approved by the Ethics Committee of Beijing TongRen Hospital (approved number: TRECKY2020-142, approved date: 2020.10.30).

Background: Children with acute lymphoblastic leukemia (ALL) have excellent outcomes, with >85% survival without relapse following contemporary therapies. Clinical and complete blood count (CBC) assessments are commonly used surveillance methods to detect relapses. We aimed to evaluate the efficacy of routine blood testing for detecting relapse using a systematic method of assessing normal and abnormal results.

Methods: This a retrospective, single center study included children aged 1-14 years diagnosed with ALL who completed therapy and were in complete remission. Demographic data, leukemia subtypes, risk stratification, treatment responses, and outcomes were also reviewed. CBC tests were evaluated, and abnormal results were categorized. The relapse groups were classified as asymptomatic and symptomatic relapses. The clinical outcomes of relapse and complications were analyzed. The sensitivity, specificity, positive predictive value, and negative predictive value of surveillance laboratory tests for predicting relapse after the end of treatment were evaluated.

Results: In total, 187 patients underwent 2074 CBC tests. Ten patients underwent full surveillance, whereas the remaining patients underwent partial surveillance. The median number of surveillance blood draws per patient was 12. Relapse was observed in nine patients. Only three patients had asymptomatic relapses. Neutropenia, leukopenia, pancytopenia, thrombocytopenia, and anemia were observed in 98, 89, 10, 6, and 3 patients respectively. The sensitivity and specificity of neutropenia, leukopenia, thrombocytopenia, anemia, and pancytopenia were 11.11% and 47.9%, 0% and 50%, 33.3% and 98.31%, 0% and 99.4%, and 33.3% and 96.07%, respectively. No differences were observed between patients who had asymptomatic relapses and those whose clinical outcomes or consequences had symptomatic relapses.

Conclusion: Relapse after completion of therapy in ALL is rare. Regular blood count surveillance does not predict clinical outcomes or relapse. Prospective studies are required to assess appropriate risk-based surveillance and its effects on patient outcomes and quality of life.

Introduction: This study focused on understanding the experiences of forced migrant families and the health care professionals who care for them within palliative care. Palliative care for children requires an active, holistic approach to care, with a focus upon improving quality of life. Forced migrant families encounter a range of additional challenges including the loss of family, belongings, and all sources of familiarity and support. The difficulties of navigating complex bureaucratic systems can confound access and communication difficulties.

Methods: Interpretative Phenomenological Analysis methodology was used in this study to privilege participant perspectives and apply an active in-depth cyclical process of reflection and reflexivity. Advisory group members provided expertise in childhood illness, palliative care and forced migration, throughout the study. The Silences Framework offered novel theoretical and philosophical concepts, which helped to situate and prioritise the "silences" within the marginalised discourses of forced migration and palliative care. Seven family members and seven health care professional participants were interviewed from hospital, hospice and community palliative care settings in the UK.

Results: Four overarching themes were identified related to experiences of loss and grief, communication, faith and coping strategies and alienation and discrimination. Compassionate, empathetic, family-centred care which valued family belief systems and coping strategies, optimised care. Learning with and from families was described by all participants, which enhanced understanding and fostered mutual respect. However, barriers included poor access to services and resources, protocol-led care, limited time with families, communication barriers and staff burnout.

Discussion: The findings suggest the need for a specific educational pathway for palliative care professionals to include spiritual care provision, cultural humility, and moral reasoning. Interdisciplinary education including the use of lived-experience expert insights is also advocated. Sufficient time to build relationships, the importance of interpreter support and the need for better access to hospice care for forced migrant families is also recommended.

Introduction: Hypervirulent carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) poses an increasing public health risk due to its high treatment difficulty and associated mortality, especially in bone marrow transplant (BMT) patients. The emergence of strains with multiple resistance mechanisms further complicates the management of these infections.

Methods: We isolated and characterized a novel ST11-KL64 hv-CRKP strain from a pediatric bone marrow transplantation patient. Antimicrobial susceptibility testing was performed to determine resistance patterns. Comprehensive genomic analysis was conducted to identify plasmid types, virulence factors, and antimicrobial resistance genes, as well as potential resistance mechanisms associated with mutations and plasmid-mediated variants.

Results: The isolated hv-CRKP strain exhibited multidrug resistance to carbapenem, tigecycline, and polymyxin. Genomic analysis revealed that the IncHI1B/repB plasmid carried virulence factors (rmpA, ΔrmpA2, iucABCD, iutA), while IncFII/IncR and IncFII plasmids harbored resistance genes [bla _{C T X - M - 6 5} , bla _{T E M - 1 B} , rmtB, bla _{S H V - 1 2} , bla _{K P C - 2} , qnrS1, bla _{L A P - 2} , sul2, dfrA14, tet(A), tet(R)]. The coexistence of bla _{C T X - M - 6 5} , bla _{T E M - 1 B} , bla _{S H V - 1 2} , bla _{L A P - 2} ,and bla _{K P C - 2} in one hv-CRKP strain is exceptionally rare. Additionally, the Tet(A)-S251A variant in the conjugative plasmid pTET-4 may confer tigecycline resistance. Mutations in MgrB, PhoPQ, and PmrABCDK were identified as potential contributors to increased polymyxin resistance. Interestingly, plasmid-encoded restriction-modification systems and Retron regions were identified, which could potentially confer phage resistance.

Discussion: The combination of virulence and antimicrobial resistance factors in the ST11-KL64 hv-CRKP strain represents a significant challenge for treating immunocompromised pediatric patients. Particularly concerning is the resistance to polymyxin and tigecycline, which are often last-resort treatments for multidrug-resistant infections. The findings highlight the urgent need for effective surveillance, infection control measures, and novel therapeutic strategies to manage such hypervirulent and multidrug-resistant pathogens.

Bronchopulmonary dysplasia is a prevalent respiratory disorder posing a significant threat to the quality of life in premature infants. Its pathogenesis is intricate, and therapeutic options are limited. Besides genetic coding, protein post-translational modification plays a pivotal role in regulating cellular function, contributing complexity and diversity to substrate proteins and influencing various cellular processes. Substantial evidence indicates that post-translational modifications of several substrate proteins are intricately related to the molecular mechanisms underlying bronchopulmonary dysplasia. These modifications facilitate the progression of bronchopulmonary dysplasia through a cascade of signal transduction events. This review outlines the relationships between substrate protein phosphorylation, acetylation, ubiquitination, SUMOylation, methylation, glycosylation, glycation, S-glutathionylation, S-nitrosylation and bronchopulmonary dysplasia. The aim is to provide novel insights into bronchopulmonary dysplasia's pathogenesis and potential therapeutic targets for clinical management.

Purpose: The Japan Association of Neonatal Nursing evaluated the pain care provided by parents to their infants admitted to the neonatal intensive care unit (NICU). However, further collaborations with families based on family-centered care are necessary to clarify the parental intentions and requests regarding pain care for their infants. This study aimed to describe the experiences and content of nonpharmacological pain care provided by parents to their infants, the intentions and requests of parents regarding each type of recommended pain care (irrespective of whether they had provided pain care at the NICU), and the reasons for their hesitation to implement specific pain management methods.

Methods: A total of 108 parents with NICU-hospitalized infants, including 66 (65.6%) infants with a birth weight of <1,000 g, voluntarily responded to an anonymous self-administered online electronic survey. Sociodemographic and clinical data were quantitatively analyzed.

Results: In our study population, 30.6% (N = 33) had provided pain care to their infants, 56.5% (N = 61) hoped to provide pain care in the future, and 40.7% (N = 44) expected advice for pain care options from healthcare professionals (HCPs). Swaddling, facilitated tucking, and skin-to-skin contact were the most popular options (≥60%). By contrast, the use of sucrose and breastfeeding (both 13.0%), skin-to-skin contact (7%), and use of expressed breast milk and non-nutritive sucking (both 3.7%) were less frequently used due to indifference or doubts, lack of knowledge about pain care, differences between recommended pain care methods and parental values, and pain care methods being inappropriate for the child's condition.

Conclusions: This survey demonstrated that when parents provide pain care for their children in the NICU, they are required to make choices based on the advice and knowledge offered by HCPs, taking into account the diverse values of parents as well as the overall condition of their infant and their breastfeeding status. Therefore, we suggest that HCPs support parents in choosing not only the recommended care but also the most appropriate pain care for the condition of their infant.