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Vol 19, No 6
Vol 19, No 6 June 2023 ISSN 1708-8569
Review article
Original articles
Research letters
Review article:
Biomarkers of hypoxic每ischemic encephalopathy: a systematic review
  In那s Caramelo, Margarida Coelho, Miguel Rosado, Carla M. P. Cardoso, Alexandra Dinis, Carlos B. Duarte, M芍rio Grãos, Bruno Manadas
Background: Current diagnostic criteria for hypoxic每ischemic encephalopathy in the early hours lack objective measurement tools. Therefore, this systematic review aims to identify putative molecules that can be used in diagnosis in daily clinical practice (PROSPERO ID: CRD42021272610).
Data sources: Searches were performed in PubMed, Web of Science, and Science Direct databases until November 2020. English original papers analyzing samples from newborns > 36 weeks that met at least two American College of Obstetricians and Gynecologists diagnostic criteria and/or imaging evidence of cerebral damage were included. Bias was assessed by the Newcastle每Ottawa Scale. The search and data extraction were verified by two authors separately.
Results: From 373 papers, 30 met the inclusion criteria. Data from samples collected in the first 72 hours were extracted, and increased serum levels of neuron-specific enolase and S100-calcium-binding protein-B were associated with a worse prognosis in newborns that suffered an episode of perinatal asphyxia. In addition, the levels of glial fibrillary acidic protein, ubiquitin carboxyl terminal hydrolase isozyme-L1, glutamic pyruvic transaminase-2, lactate, and glucose were elevated in newborns diagnosed with hypoxic每ischemic encephalopathy. Moreover, pathway analysis revealed insulin-like growth factor signaling and alanine, aspartate and glutamate metabolism to be involved in the early molecular response to insult.
Conclusions: Neuron-specific enolase and S100-calcium-binding protein-B are potential biomarkers, since they are correlated with an unfavorable outcome of hypoxic每ischemic encephalopathy newborns. However, more studies are required to determine the sensitivity and specificity of this approach to be validated for clinical practice.
  [Abstract] [Full Text] [PDF]  
Risk of asthma in preterm infants with bronchopulmonary dysplasia: a systematic review and meta-analysis
  Tong Sun, Hai-Yang Yu, Miao Yang, Yi-Fan Song, Jian-Hua Fu
Background: This study aimed to systematically review and meta-analyze the available literature on the association between preterm infant bronchopulmonary dysplasia (BPD) and pre-adulthood asthma.
Methods: Studies examining the association between BPD and asthma in children and adolescents were systematically reviewed, and a meta-analysis was conducted. We searched Scopus, Embase, Web of Science, PubMed, and Cochrane Library from the database inception to March 26, 2022. The pooled odds ratio (OR) estimate was used in our meta-analysis to calculate the correlation between BPD and the probability of developing asthma before adulthood. Stata 12.0 was used to conduct the statistical analysis.
Results: The correlation between asthma and BPD in preterm newborns was examined in nine studies. We used a random effect model to pool the OR estimate. Our results indicated a marked increase in the risk of subsequent asthma in preterm infants with BPD [OR = 1.73, 95% confidence interval (CI) = 1.43每2.09]. Moreover, there was no obvious heterogeneity across the studies (P = 0.617, I2 = 0%). The pooled OR remained stable and ranged from 1.65 (95% CI = 1.35每2.01) to 1.78 (95% CI = 1.43每2.21). Regarding publication bias, the funnel plot for asthma risk did not reveal any noticeable asymmetry. We further performed Begg*s and Egger*s tests to quantitatively evaluate publication bias. There was no evidence of a publication bias for asthma risk (P > | Z | = 0.602 for Begg*s test, and P > | t | = 0.991 for Egger*s test).
Conclusions: Our findings indicate that preterm infants with BPD have a much higher risk of developing asthma in the future (OR = 1.73, 95% CI = 1.43每2.09). Preterm infants with BPD may benefit from long-term follow-up.
  [Abstract] [Full Text] [PDF]  
Original articles:
Characteristics of home oxygen therapy for preterm infants with bronchopulmonary dysplasia in China: results of a multicenter cohort study
  Wen-Xing Jiang, Yan-Chen Wang, Hong-Xia Song, Mi Xiao, Fan He, Si-Yuan Jiang, Xin-Yue Gu, Jian-Hua Sun, Yun Cao, Wen-Hao Zhou, Shoo Kim Lee, Li-Ping Chen, Li-Yuan Hu, on behalf of Chinese Neonatal Network
Background: Home oxygen therapy (HOT) is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia (BPD). There is a lack of evidence-based consensus on the indication for HOT among these infants. Because wide variation in the institutional use of HOT exists, little is known about the role of regional social-economic level in the wide variation of HOT.
Methods: This was a secondary analysis of Chinese Neonatal Network (CHNN) data from January 1, 2019 to December 31, 2019. Infants at gestational ages < 32 weeks, with a birth weight < 1500 g, and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study. Infants with major congenital anomalies and those who were discharged against medical advice were excluded.
Results: Of 1768 preterm infants with BPD, 474 infants (26.8%) were discharged to home with oxygen. The proportion of HOT use in participating member hospitals varied from 0 to 89%, with five of 52 hospitals* observing proportions of HOT use that were significantly greater than expected, with 14 hospitals with observing proportions significantly less than expected, and with 33 hospitals with appropriate proportions. We noted a negative correlation between different performance groups of HOT and median GDP per capita (P = 0.04).
Conclusions: The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels. A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China.
  [Abstract] [Full Text] [PDF]  
Risk factors and machine learning prediction models for bronchopulmonary dysplasia severity in the Chinese population
  Wen He, Lan Zhang, Rui Feng, Wei-Han Fang, Yun Cao, Si-Qi Sun, Peng Shi, Jian-Guo Zhou, Liang-Feng Tang, Xiao-Bo Zhang, Yuan-Yuan Qi
Background: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in extremely preterm neonates. The outcome and clinical burden vary dramatically according to severity. Although some prediction tools for BPD exist, they seldom pay attention to disease severity and are based on populations in developed countries. This study aimed to develop machine learning prediction models for BPD severity based on selected clinical factors in a Chinese population.
Methods: In this retrospective, single-center study, we included patients with a gestational age < 32 weeks who were diagnosed with BPD in our neonatal intensive care unit from 2016 to 2020. We collected their clinical information during the maternal, birth and early postnatal periods. Risk factors were selected through univariable and ordinal logistic regression analyses. Prediction models based on logistic regression (LR), gradient boosting decision tree, XGBoost (XGB) and random forest (RF) models were implemented and assessed by the area under the receiver operating characteristic curve (AUC).
Results: We ultimately included 471 patients (279 mild, 147 moderate, and 45 severe cases). On ordinal logistic regression, gestational diabetes mellitus, initial fraction of inspiration O 2 value, invasive ventilation, acidosis, hypochloremia, C-reactive protein level, patent ductus arteriosus and Gram-negative respiratory culture were independent risk factors for BPD severity. All the XGB, LR and RF models (AUC = 0.85, 0.86 and 0.84, respectively) all had good performance.
Conclusions: We found risk factors for BPD severity in our population and developed machine learning models based on them. The models have good performance and can be used to aid in predicting BPD severity in the Chinese population.
  [Abstract] [Full Text] [PDF]  
Longer duration of initial invasive mechanical ventilation is still a crucial risk factor for moderate-to-severe bronchopulmonary dysplasia in very preterm infants: a multicentrer prospective study
  Cong Dou, Yong-Hui Yu, Qing-Cui Zhuo, Jian-Hong Qi, Lei Huang, Yan-Jie Ding, De-Juan Yang, Li Li, Dan Li, Xiao-Kang Wang, Yan Wang, Xin Qiao, Xiang Zhang, Bing-Jin Zhang, Hai-Yan Jiang, Zhong-Liang Li, Simmy Reddy
Background: We aimed to evaluate the risk factors for moderate-to-severe bronchopulmonary dysplasia (BPD) and focus on discussing its relationship with the duration of initial invasive mechanical ventilation (IMV) in very preterm neonates less than 32 weeks of gestational age (GA).
Methods: We performed a prospective cohort study involving infants born at 23每31 weeks of GA who were admitted to 47 different neonatal intensive care unit (NICU) hospitals in China from January 2018 to December 2021. Patient data were obtained from the Sina-northern Neonatal Network (SNN) Database.
Results: We identified 6538 very preterm infants, of whom 49.5% (3236/6538) received initial IMV support, and 12.6% (823/6538) were diagnosed with moderate-to-severe BPD symptoms. The median duration of initial IMV in the moderateto-severe BPD group was 26 (17每41) days, while in the no or mild BPD group, it was 6 (3每10) days. The incidence rate of moderate-to-severe BPD and the median duration of initial IMV were quite different across different GAs. Multivariable logistic regression analysis showed that the onset of moderate-to-severe BPD was significantly associated with the duration of initial IMV [adjusted odds ratio (AOR): 1.97; 95% confidence interval (CI): 1.10每2.67], late-onset neonatal sepsis (LONS), and patent ductus arteriosus (PDA).
Conclusion: In this multicenter cohort study, the duration of initial IMV was still relatively long in very premature infants, and the longer duration of initial IMV accounts for the increased risk of moderate-to-severe BPD.
  [Abstract] [Full Text] [PDF]  
Systemic postnatal corticosteroid use for the prevention of bronchopulmonary dysplasia and its relationship to early neurodevelopment in extremely preterm infants
  Emilia Esterman, Traci-Anne Goyen, Pranav Jani, Gemma Lowe, Jane Baird, Rajesh Maheshwari, Daphne D*Cruz, Melissa Luig, Dharmesh Shah
Background: Systemic postnatal corticosteroid use in extremely preterm infants poses a risk of adverse neurodevelopmental outcomes. This study explores their use beyond seven days of age with early neurodevelopmental assessments during the fidgety period (9每20 weeks postterm age).
Methods: This retrospective single-center cohort study included inborn extremely preterm infants from 1 January 2014 to 31 December 2018. Outborn infants, those with congenital or genetic abnormalities, and those who received postnatal corticosteroids for nonrespiratory reasons were excluded. The cohort was dichotomized based on the status of corticosteroid receipt. Early neurodevelopmental outcomes were reported using Prechtl*s General Movements Assessment.
Results: Of the 282 infants, 67 (23.75%) received corticosteroids. Of these, 34 (50.75%) received them for dependency on invasive ventilation (intermittent positive-pressure ventilation), and the remainder received them for dependency on noninvasive ventilation continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP). Abnormal or absent fidgety movements were observed in 13% of infants (7/54) who received corticosteroids compared to 2% of infants (3/146) who did not. An increased odds for an abnormal general movements assessment from corticosteroid use after adjusting for gestational age [adjusted odds ratio (aOR) = 5.5, 95% confidence interval (CI) = 1.14每26.56] was observed. The motor optimality scores differed between the two groups [corticosteroid group: 25.5 (23每26) versus no-corticosteroid group: 26 (24每28); z = −2.02]. A motor optimality score < 20 was observed in 14.8% of infants (8/54) in the corticosteroid group compared to 2% of infants (3/146) in the noncorticosteroid group. This difference was significant after adjustment for gestational age (aOR 5.96, 95% CI 1.28每27.74).
Conclusions: Abnormal early neurodevelopment was observed in infants who received systemic postnatal corticosteroids. The relationship between these findings and other factors influencing early neurodevelopment needs further exploration.
  [Abstract] [Full Text] [PDF]  
Impact of time to diagnosis on the occurrence of cardiogenic shock in MIS-C post-COVID-19 infection
  Saïd Bichali, Mathilde Bonnet, Marie-Emilie Lampin, Jean-Benoit Baudelet, H谷loïse Reumaux, Olivia Domanski, Thameur Rakza, Alexandre Delarue, Morgan Recher, J谷rôme Soquet, Francois Dubos, St谷phane Leteurtre, Ali Houeijeh, Francois Godart
Background: In multisystem inflammatory syndrome in children (MIS-C), diagnostic delay could be associated with severity. This study aims to measure the time to diagnosis in MIS-C, assess its impact on the occurrence of cardiogenic shock, and specify its determinants.
Methods: A single-center prospective cohort observational study was conducted between May 2020 and July 2022 at a tertiary care hospital. Children meeting the World Health Organization MIS-C criteria were included. A long time to diagnosis was defined as six days or more. Data on time to diagnosis were collected by two independent physicians. The primary outcome was the occurrence of cardiogenic shock. Logistic regression and receiver operating characteristic curve analysis were used for outcomes, and a Cox proportional hazards model was used for determinants.
Results: Totally 60 children were assessed for inclusion, and 31 were finally analyzed [52% males, median age 8.8 (5.7每10.7) years]. The median time to diagnosis was 5.3 (4.2每6.2) days. In univariable analysis, age above the median, time to diagnosis, high C-reactive protein, and high N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with cardiogenic shock [odds ratio (OR) 6.13 (1.02每36.9), 2.79 (1.15每6.74), 2.08 (1.05每4.12), and 1.70 (1.04每2.78), respectively]. In multivariable analysis, time to diagnosis ≡ 6 days was associated with cardiogenic shock [adjusted OR (aOR) 21.2 (1.98每227)]. Time to diagnosis ≡ 6 days had a sensitivity of 89% and a specificity of 77% in predicting cardiogenic shock; the addition of age > 8 years and NT-proBNP at diagnosis ≡ 11,254 ng/L increased the specificity to 91%. Independent determinants of short time to diagnosis were age < 8.8 years [aHR 0.34 (0.13每0.88)], short distance to tertiary care hospital [aHR 0.27 (0.08每0.92)], and the late period of the COVID-19 pandemic [aHR 2.48 (1.05每5.85)].
Conclusions: Time to diagnosis ≡ 6 days was independently associated with cardiogenic shock in MIS-C. Early diagnosis and treatment are crucial to avoid the use of inotropes and limit morbidity, especially in older children.
  [Abstract] [Full Text] [PDF]  
Clinical experiences in the management of critically ill patients with COVID-19 in a designated children*s hospital in China
  Gong-Bao Liu, Ying Gu, Ying-Wen Wang, Chuan-Qing Wang, Jian Ma, Mei Zeng, Guo-Ping Lu, Zhong-Lin Wang, Ai-Mei Xia, Jin-Hao Tao, Xiao-Wen Zhai, Wen-Hao Zhou, Hong Xu, Yong-Hao Gui, Guo-Ying Huang, Xiao-Bo Zhang
  [Abstract] [Full Text] [PDF]  
Research letters:
Epidemiology and clinical characteristics of pediatric osteomyelitis in northern California
  Xiao Ben Wang, Navendu Samant, Justin Searns, Carol Glaser
  [Abstract] [Full Text] [PDF]  
Core needle biopsy and embolization of fat-poor renal tumors in children with tuberous sclerosis complex
  Derek J. Roebuck, Samantha Chippington, Bligh D. Berry, Craig Gibson
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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