Abstract:Late-onset sepsis (LOS) is commonly seen in neonates who are hospitalized for extended periods, particularly in very low birth weight infants (VLBWI) and extremely low birth weight infants (ELBWI). Currently, the management of LOS in preterm infants faces dual challenges of delayed diagnosis and treatment, as well as antibiotic overtreatment. To address these issues, the Hunan Neonatal Medical Quality Control Center and the Neonatology Group of Perinatal Medical Committee of Hunan Medical Association organized a group of neonatal experts from Hunan Province to formulate recommendations based on published literature and statistical data from the Hunan Neonatal Medical Quality Control Center, as well as real-world practices in most neonatal intensive care units in Hunan Province. The group of neonatal experts proposed 15 recommendations for the diagnosis and antibiotic treatment of LOS in hospitalized preterm infants in the neonatal intensive care unit.

Abstract:Objective To explore the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with risk of congenital heart disease (CHD) in offspring.Methods The parents of children with simple CHD aged 0 to 1 year (n=683) were recruited as the case group, while the parents of healthy children aged 0 to 1 year (n=740) served as the control group. A case-control study was conducted, and a questionnaire was used to collect information on perinatal exposures. After controlling for relevant confounding factors using multivariate logistic regression analysis and propensity score matching, the associations of parental smoking and alcohol consumption during the periconceptional period and their interactions with CHD were examined, as well as the cumulative effects of smoking and drinking on CHD risk.Results Maternal active smoking (OR=2.91, 95%CI: 1.60-5.30), passive smoking (OR=1.94, 95%CI: 1.56-2.42), and alcohol consumption (OR=2.59, 95%CI: 1.89-3.54), as well as paternal smoking (OR=1.52; 95%CI: 1.22-1.90) and drinking (OR=1.48, 95%CI: 1.19-1.84), were associated with an increased risk of CHD in offspring. There was no interaction between parental smoking and drinking behaviors during the periconceptional period concerning the risk of CHD in offspring (P>0.05). The more parents' smoking and drinking behaviors during the perinatal pregnancy, the higher the risk of CHD in their offspring (OR=1.50, 95%CI: 1.36-1.65).Conclusions Parental smoking and alcohol consumption during the periconceptional period are associated with the occurrence of CHD in offspring, and there is a cumulative effect on CHD risk, suggesting that reducing tobacco and alcohol exposure during the periconceptional period may lower the incidence of CHD.

Abstract:Objective To investigate the clinical features and risk factors of cholestasis in small for gestational age (SGA) preterm infants.Methods This study selected SGA preterm infants born at less than 37 weeks of gestation and admitted to the Department of Neonatology, Children's Hospital of Soochow University within 24 hours after birth. The infants were divided into two groups: a cholestasis group and a non-cholestasis group. Clinical data from July 2017 to June 2022 were collected and retrospectively analyzed.Results Among the 553 SGA preterm infants included, 100 infants (18.1%) developed cholestasis. The incidence rates in different gestational age and birth weight groups were as follows: extremely preterm infants 50.0%, very preterm infants 46.6%, moderate preterm infants 32.7%, and late preterm infants 9.8%; birth weight (BW) <1 000 g 60.9%, 1 000 g≤BW<1 500 g 33.9%, and 1 500 g≤BW<2 500 g 10.7%. Multivariate regression analysis showed that low birth weight, intracranial hemorrhage, duration of invasive ventilation, total amino acid accumulation in the second week, total lipid emulsion accumulation in the first week, and total lipid emulsion accumulation in the second week were independent risk factors for cholestasis in SGA preterm infants (P<0.05).Conclusions The incidence of cholestasis in SGA preterm infants increases with decreasing gestational age and birth weight. The occurrence of cholestasis in SGA preterm infants is influenced by multiple risk factors, including low birth weight, intracranial hemorrhage, invasive ventilation, and the accumulation of amino acids and lipid emulsions, highlighting the need for comprehensive treatment measures to reduce its occurrence.

Abstract:Objective To investigate the levels of intrinsic positive end-expiratory pressure (PEEPi) in infants with severe bronchopulmonary dysplasia (sBPD) and the relationship between different levels of PEEPi and clinical outcomes.Methods A retrospective analysis was conducted on the clinical data of 12 sBPD infants who underwent PEEPi measurement and were hospitalized at Guangzhou Women and Children's Medical Center from January 2022 to June 2023. The clinical manifestations and outcomes at discharge were compared between infants with very high PEEPi (≥10 cmH₂O) and those with lower PEEPi (<10 cmH₂O).Results PEEPi measurements were taken in 12 sBPD infants between gestational age 31⁺³ and 67⁺² weeks postmenstrual age, with the lowest PEEPi measured at 0.9 cmH₂O and the highest at 19.6 cmH₂O; 50% (6/12) of the infants had PEEPi ≥10 cmH₂O. All infants with very high PEEPi exhibited ineffective triggering and patient-ventilator asynchrony. Among them, 5 infants could not be weaned off invasive ventilation, resulting in 4 deaths and 1 infant being discharged with a tracheostomy and ventilator support. In contrast, among the infants with PEEPi <10 cmH₂O, only 1 infant died, while the others were successfully extubated and discharged.Conclusions Infants with sBPD may have elevated PEEPi levels, and very high PEEPi may be associated with adverse outcomes in these patients.

Abstract:Objective To explore the effects of antenatal corticosteroids (ACS) on the outcomes of very premature infants (VPIs) and neurodevelopment during infancy.Methods A retrospective study was conducted on 190 VPIs admitted to the Department of Pediatrics of the First Affiliated Hospital of Anhui Medical University from January 2020 to December 2022. The infants were categorized into four groups based on ACS usage and dosage: no ACS group (n=18), single-course group (n=88), multi-course group (n=40), and partial-course group (n=44). The clinical outcomes, Neonatal Behavioral and Neurological Assessment (NBNA) scores at 40 weeks of corrected age, and Gesell Developmental Schedule (Gesell) scores at 1 year of corrected age were compared among the four groups. The impact of timing of ACS use on the Gesell scores of infants at 1 year of corrected age in VPIs with specific gestational ages was analyzed.Results The incidence rates of neonatal respiratory distress syndrome, bronchopulmonary dysplasia, transient tachypnea of the newborn, and neonatal pneumonia were significantly lower in the partial-course, single-course, and multiple-course groups compared with the no ACS group (P<0.008). However, there was no significant difference among the partial-course, single-course, and multiple-course groups (P>0.008). The NBNA scores (behavioral ability, active muscle tone, primitive reflexes, and general assessment) at 40 weeks of corrected age were significantly higher in the no ACS, partial-course, and single-course groups than in the multiple-course group (P<0.008). The proportion of VPIs with normal neurodevelopment at 1 year of corrected age was significantly higher in the no ACS, partial-course, and single-course groups than in the multiple-course group (P<0.008). The timing of ACS use had no significant effect on neurodevelopment at a corrected age of 1 year in infants with various gestational ages (P>0.05).Conclusions ACS is crucial for the development of the respiratory system in VPIs, but multiple courses of ACS may cause neurodevelopmental abnormalities. The impact of ACS use on neurodevelopment is independent of gestational age and the timing of ACS use.

Abstract:Objective To investigate the correlation between optimal placement depth (OPD) and physical measurement parameters in preterm infants receiving placement of peripherally inserted central catheter (PICC) through the great saphenous vein (GSV), and to establish a predictive formula for OPD during the placement of PICC through the GSV.Methods A retrospective analysis was performed for the preterm infants who received the placement of PICC through the GSV in the Neonatal Intensive Care Unit of the Third Xiangya Hospital of Central South University from December 2022 to February 2024. According to the site of puncture [GSV of the knee joint (KJ) or the ankle joint (AJ)], they were divided into a GSV-KJ placement group (n=38) and a GSV-AJ placement group (n=33). The infants were measured in terms of body weight (BW), body length, the length of the upper and lower parts of the body, head circumference, and abdominal circumference at the time of placement. The Pearson correlation analysis was used to investigate the correlation between the above variables and OPD. A predictive formula was established for OPD in the placement of PICC via the GSV in preterm infants, and the predicted residual between the predicted depth and the ideal OPD was compared between the conventional predictive formula and the new predictive formula.Results The Pearson correlation analysis showed that PICC OPD was significantly positively correlated with BW, body length, the length of the upper and lower parts of the body, head circumference, and abdominal circumference in both the GSV-KJ placement group and GSV-AJ placement group (P<0.05), with the highest degree of correlation between OPD and BW. The univariate linear regression analysis showed a linear relationship between PICC OPD and BW in both groups. The predictive formulas for OPD were as follows: GSV-KJ PICC OPD (cm) = 13.1 + 2.7 × BW (kg) and GSV-AJ PICC OPD (cm) = 13.4 + 6.0 × BW (kg), and the new predictive formulas had a significantly lower predicted residual than the conventional predictive formula (P<0.05).Conclusions OPD for PICC through the GSV is positively correlated with BW, and the prediction results of the new predictive formula based on BW are closer to the ideal OPD.

Abstract:Objective To investigate the early cognitive development characteristics of children with Williams syndrome (WS) at different age stages.Methods From September 2018 to June 2023, 106 children diagnosed with WS at the Department of Pediatric Health Care, Children's Hospital, Zhejiang University School of Medicine, aged 1 to <5 years, were prospectively enrolled. All children underwent Gesell developmental diagnostic assessments to analyze the cognitive development characteristics of WS children across different age groups.Results The average age of the 106 WS children was (3.1±1.2) years; 58 were male, and 48 were female. There were no significant differences in developmental levels between males and females in the five domains of gross motor skills, fine motor skills, language, personal-social skills, and adaptive behavior (P>0.05). The incidence rates of mild, moderate, severe, and profound developmental disabilities among children of different age groups showed no significant differences (P>0.05). Comparisons of developmental levels in gross motor skills, language, personal-social skills, and adaptive behavior among different age groups were also not statistically significant (P>0.05). With the increase of age, the developmental level of fine motor skills showed a decreasing trend (P<0.05). There were no significant differences in verbal IQ and non-verbal IQ within each age group of WS children (P>0.05).Conclusions The overall developmental level of WS children stabilizes with age, and their early language abilities do not significantly exceed their non-verbal abilities.

Abstract:Objective To investigate the prevalence of tension-type headache (TTH) in children and adolescents aged 0-19 years globally in 1990-2021, and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data, the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years, with different sexes, age groups, sociodemographic index (SDI) regions and countries/territories.Results The age-standardized prevalence rate (ASPR) of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000, which was increased by 1.73% since 1990. The ASPR in females was slightly higher than that in males (1990: 17 707.65/100 000 vs 16 403.78/100 000; 2021: 17 946.29/100 000 vs 16 763.09/100 000). The ASPR in adolescence was significantly higher than that in school-aged and preschool periods (1990: 27 672.04/100 000 vs 10 134.16/100 000; 2021: 28 239.04/100 000 vs 10 059.39/100 000). Regions with high SDI exhibited a higher ASPR than the other regions, with significant differences in prevalence rates across different countries. From 1990 to 2021, there was a slight increase in global ASPR, with an average annual percentage change (AAPC) of 0.06%. Females experienced a smaller increase than males based on AAPC (0.04% vs 0.07%). There was reduction in ASPR in preschool and school-aged groups, with an AAPC of -0.02%, while there was a significant increase in ASPR in adolescence, with an AAPC of 0.07%. ASPR decreased in regions with low-middle and low levels of SDI, with an AAPC of -0.02% and -0.04%, respectively, while it increased in regions with middle SDI, with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally, with significant differences across sexes, age groups, SDI regions and countries/territories.

Abstract:Objective To explore the application of neurofeedback (NFB) combined with learning style profile (LSP) intervention training in children with high-functioning autism (HFA).Methods A prospective study was conducted to select 86 children with HFA admitted to the hospital from February 2022 to February 2024. They were divided into two groups according to the random number table method, with 43 cases in each group. In this double-blind study, the control group was given LSP intervention training, and the observation group was given NFB intervention on the basis of the treatment used in the control group. Both groups were treated for 6 months. The scores of Autism Behavior Checklist (ABC), Autism Treatment Evaluation Checklist (ATEC), Social Responsiveness Scale (SRS), and Pediatric Quality of Life (PedsQL) were compared between the two groups before intervention and at 6 months after intervention. The relationship of PedsQL score with ABC, ATEC, and SRS scores was analyzed in children with HFA.Results After 6 months of intervention, the scores of ABC, ATEC, and SRS in the observation group were significantly lower than those in the control group, while the PedsQL score in the observation group was significantly higher than that in the control group (P<0.05). The PedsQL score was negatively correlated with the ABC, ATEC, and SRS scores in children with HFA (r=-0.238, -0.381, -0.219 respectively; P<0.001).Conclusions NFB combined with LSP can effectively improve the clinical symptoms and social ability, control the development of the disease, and improve the quality of life in children with HFA.

Abstract:Objective To investigate the relationship of cerebrospinal fluid and serum levels of soluble interleukin-2 receptor (SIL-2R), endothelial nitric oxide synthase (eNOS), and cluster of differentiation 93 (CD93) with the progression and prognosis of viral encephalitis (VE) in children.Methods Prospectively, 102 children with VE admitted from January 2021 to January 2024 were selected as the VE group. The patients were divided into a mild subgroup (64 patients) and a severe subgroup (38 patients) according to disease progression. The patients were also divided into a good prognosis subgroup (29 patients) and a poor prognosis subgroup (73 patients) according to prognosis. A control group of 102 children with central nervous system diseases who were examined and found not to have VE during the same period was selected. The factors contributing to the poor prognosis of children with VE and the predictive value of SIL-2R, eNOS, and CD93 in cerebrospinal fluid and serum for the poor prognosis of children with VE were evaluated.Results Cerebrospinal fluid and serum SIL-2R, eNOS, and CD93 levels were significantly increased in the VE group, severe subgroup, and poor prognosis subgroup (P<0.05). Multivariate logistic regression analysis showed that high SIL-2R, eNOS, and CD93 levels in cerebrospinal fluid and serum were risk factors for poor prognosis in children with VE (P<0.05). Receiver operating characteristic curve analysis showed that the combination of cerebrospinal fluid SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE (P<0.05). Similarly, the combination of serum SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE (P<0.05).Conclusions The cerebrospinal fluid and serum levels of SIL-2R, eNOS, and CD93 are significantly elevated in children with VE, and they are associated with VE progression and prognosis.

Abstract:Objective To investigate the clinical features and prognosis of children with fungal bloodstream infection (BSI) following chemotherapy for acute leukemia (AL).Methods A retrospective analysis was performed on 23 children with fungal BSI following chemotherapy for AL in three hospitals in Fujian Province, China, from January 2015 to December 2023. Their clinical features and prognosis were analyzed.Results Among all children following chemotherapy for AL, the incidence rate of fungal BSI was 1.38% (23/1 668). At the time of fungal BSI, 87% (20/23) of the children had neutrophil deficiency for more than one week, and all the children presented with fever, while 22% (5/23) of them experienced septic shock. All 23 children exhibited significant increases in C-reactive protein and procalcitonin levels. A total of 23 fungal isolates were detected in peripheral blood cultures, with Candida tropicalis being the most common isolate (52%, 12/23). Caspofungin or micafungin combined with liposomal amphotericin B had a relatively high response rate (75%, 12/16), and the median duration of antifungal therapy was 3.0 months. The overall mortality rate in the patients with fungal BSI was 35% (8/23), and the attributable death rate was 22% (5/23).Conclusions Fungal BSI following chemotherapy in children with AL often occurs in children with persistent neutrophil deficiency and lacks specific clinical manifestations. The children with fungal BSI following chemotherapy for AL experience a prolonged course of antifungal therapy and have a high mortality rate, with Candida tropicalis being the most common pathogen.

Abstract:Objective To explore the current application of high-throughput drug sensitivity (HDS) testing in children with relapsed and refractory acute leukemia (RR-AL) and analyze the feasibility of salvage treatment plans.Methods A retrospective collection of clinical data from children with RR-AL who underwent HDS testing at the Department of Children's Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University from November 2021 to October 2023 was conducted, followed by an analysis of drug sensitivity results and treatment outcomes.Results A total of 17 children with RR-AL underwent HDS testing, including 7 cases of relapsed refractory acute myeloid leukemia and 10 cases of relapsed refractory acute lymphoblastic leukemia. The detection rate of highly sensitive chemotherapy drugs/regimens was 53% (9/17), while the detection rate of moderately sensitive chemotherapy drugs/regimens was 100% (17/17). Among the 17 RR-AL patients with highly and moderately sensitive chemotherapy drugs and regimens, the MOACD regimen (mitoxantrone + vincristine + cytarabine + cyclophosphamide + dexamethasone) accounted for 100%, with the highest inhibition rate for single-agent mitoxantrone (94%, 16/17), and the highest inhibition rate for targeted therapy being bortezomib (94%, 16/17). Nine patients adjusted their chemotherapy based on HDS testing results, with 4 undergoing hematopoietic stem cell transplantation. Four patients achieved disease-free survival, while 5 died. Eight patients received empirical chemotherapy, with 2 undergoing hematopoietic stem cell transplantation; 4 achieved disease-free survival, while 4 died.Conclusions HDS testing can identify highly sensitive drugs/regimens for children with RR-AL, improving the rate of re-remission and creating conditions for subsequent hematopoietic stem cell transplantation.

Abstract:Objective To study the composition, abundance, and functional profiles of the intestinal microbiota in infants and young children with Kawasaki disease (KD) during the acute phase, and to explore the potential role of intestinal microbiota in the pathogenesis of KD.Methods Six children aged 0-3 years with acute KD admitted to the Department of Cardiology, Children's Hospital Affiliated to Capital Institute of Pediatrics from July to October 2021 were prospectively included as the KD group. Six age- and sex-matched healthy children who underwent physical examinations at the hospital during the same period were selected as the healthy control group. Metagenomics sequencing was used to detect and compare the differences in the microflora structure and functional profiles of fecal samples between the two groups.Results There were significant differences in the structural composition and diversity of intestinal microbiota between the two groups (P<0.05). Compared with the healthy control group, the abundance of Listeria_monocytogenes (family Listeriaceae and genus Listeria), Bifidobacterium_rousetti, Enterococcus_avium, and Enterococcus_hirae was significantly higher in the intestinal microbiota in the KD group (|LDA|>2.0, P<0.05). The steroid degradation and apoptosis pathways were significantly upregulated in the KD group compared with the healthy control group, while the Bacterial_secretion_system, Sulfur_metabolism, Butanoate_metabolism, Benzoate_degradation, β-alanine metabolism, and α-linolenic acid pathways were significantly downregulated (|LDA|>2, P<0.05).Conclusions There are significant differences in the structure and diversity of intestinal microbiota between children aged 0-3 years with acute KD and healthy children, suggesting that disturbances in intestinal microbiota occur during the acute phase of KD. In particular, Listeria_monocytogenes, Enterococcus_avium, and Enterococcus_hirae may be involved in the pathogenesis of KD through steroid degradation and apoptosis pathways.

Abstract:Objective To evaluate the preventive effects of Saccharomyces boulardii powder and tetragenous viable Bifidobacterium tablets on antibiotic-associated diarrhea (AAD) in infants and young children.Methods Children under three years old admitted to the Department of Pediatrics, Affiliated Hospital of Xuzhou Medical University due to non-gastrointestinal infections and requiring antibiotic treatment from July to December 2023 were enrolled. The children were randomly divided into a control group (n=47), a Saccharomyces boulardii group (n=70), and a Bifidobacterium group (n=65) using a random number table method. The control group received antibiotics and symptomatic supportive treatment according to relevant clinical guidelines. In addition to the treatment given to the control group, the Saccharomyces boulardii group and the Bifidobacterium group were respectively administered with Saccharomyces boulardii powder and tetragenous viable Bifidobacterium tablets. Based on the duration of probiotic use (7 days, 14 days, and 21 days), the Saccharomyces boulardii group was further divided into 7 d, 14 d, and 21 d subgroups, and similarly for the Bifidobacterium group. The incidence of AAD and ratio of cocci to bacilli in feces were compared among the groups after treatment.Results The incidence rate of AAD in both the Saccharomyces boulardii group and the Bifidobacterium group was lower than that in the control group (P<0.017). The duration of AAD and the length of hospital stay were shorter in the Saccharomyces boulardii and Bifidobacterium groups compared to the control group (P<0.05). In the control group, the ratio of cocci to bacilli in feces on days 7, 14, and 21 was higher than on day 1 (P<0.05). Within-group comparisons showed that the ratio of cocci to bacilli in feces on day 14 in the Bifidobacterium 14 d and 21 d groups were lower than on day 1 (P<0.05); and the ratios on day 14 in the control group, Saccharomyces boulardii 14 d group, Saccharomyces boulardii 21 d group, Bifidobacterium 14 d group, and Bifidobacterium 21 d group were lower than on day 7 (P<0.05). The ratios on day 21 in the control group and the Saccharomyces boulardii 21 d group were lower than on days 7 and 14 (P<0.05). Between-group comparisons indicated that on day 7, the ratios of cocci to bacilli in feces in the Saccharomyces boulardii 7 d, 14 d, 21 d groups, and Bifidobacterium 7 d, 14 d, 21 d groups were all lower than in the control group (P<0.05); on day 14, the ratios of cocci to bacilli in feces 14 d and 21 d groups were lower than in the control group and the Bifidobacterium 7 d group (P<0.05).Conclusions Both Saccharomyces boulardii and tetragenous viable Bifidobacterium can effectively improve gut microbiota and prevent the occurrence of AAD in infants and young children. Compared to short-term treatment, appropriately extending the duration of probiotic therapy can further improve the structure of gut microbiota.

Abstract:Objective To investigate the effects of propranolol on the proliferation, apoptosis, migration, and tube formation ability of human umbilical vein endothelial cells (HUVEC), as well as its impact on the expression of sex-determining region Y-box 18 (SOX18), matrix metalloproteinase-7 (MMP-7), and vascular endothelial growth factor A (VEGFA).Methods HUVEC were treated with different concentrations of propranolol, and cell viability was assessed using the CCK-8 method to determine the optimal concentration and treatment duration. The experiment consisted of a control group and groups treated with different concentrations of propranolol (50, 100, 150 μmol/L). Apoptosis, migration, and tube formation of HUVEC were observed using flow cytometry, wound healing assays, and tube formation assays. Western blot and real-time quantitative PCR were used to detect the expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA.Results Compared to the control group, the apoptosis rate in the propranolol treatment groups increased significantly (P<0.05), and it rose significantly with increasing drug concentration (P<0.05). The wound healing rate decreased in the propranolol treatment groups, and both the number of tube formation nodes and total tube length were reduced (P<0.05). The expression levels of SOX18, MMP-7, and VEGFA proteins and mRNA were downregulated in the propranolol treatment groups (P<0.05).Conclusions Propranolol can inhibit the proliferation, migration, and tube formation ability of HUVEC and promote cell apoptosis, resulting in decreased expression levels of SOX18, MMP-7, and VEGFA.

Abstract:Peutz-Jeghers syndrome (PJS) is an autosomal dominant genetic disorder characterized by mucocutaneous pigmentation and multiple hamartomatous polyps, which leads to an increased susceptibility to tumors. The clinical incidence is rare, and the only currently identified pathogenic gene is the serine/threonine kinase 11/liver kinase B1 (STK11/LKB1) located on the short arm of chromosome 19 (19p13.3). This condition can lead to various complications, such as gastrointestinal bleeding, intussusception, intestinal obstruction, and malignancy. In childhood, the greatest risk is associated with intussusception, which increases the risk of surgical intervention and significantly impacts the growth, development, and quality of life of the children. This article provides an overview of the current research status regarding the clinical characteristics, etiology, pathogenesis, diagnosis, and treatment of PJS in children.