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Vol 15, No 2
Vol 15, No 2 April 2019 ISSN 1708-8569
Review articles
Original articles
Letter to the editor
Application of artificial intelligence in pediatrics: past, present and future
  Li-Qi Shu, Yi-Kan Sun, Lin-Hua Tan, Qiang Shu, Anthony C. Chang
  [Abstract] [Full Text] [PDF]  
Review articles:
Current perspectives on the correlation of nocturnal enuresis with obstructive sleep apnea in children
  Miao-Shang Su, Li Xu, Wen-Feng Pan, Chang-Chong Li
Background: Obstructive sleep apnea (OSA) and nocturnal enuresis (NE) are common clinical problems in children. OSA and NE are thought to be interrelated, but the exact pathophysiological mechanisms are not yet clear. This review aims to explain the possible pathogenesis of NE in children with OSA.
Data sources: We have retrieved all relevant original articles from Database that have been published so far, including the prevalence studies of NE and OSA in children, sleep characteristic studies that use polysomnography (PSG) to focus on children with NE, and studies on the relationship between OSA and NE.
Results: Clinical studies have revealed that the risk of NE in children with OSA was increased compared with that of their healthy peers. This increased risk may be associated with sleep disorders, bladder instability, detrusor overactivity, nocturnal polyuria, endocrine and metabolic disorders, and inflammation.
Conclusions: Cardiopulmonary and renal reflex-induced neuroendocrine disorder may play an important role in the mechanism of NE in children with OSA, but this remains to be confirmed by animal studies. Other causes such as oxidative stress and inflammatory responses need to be further researched.
  [Abstract] [Full Text] [PDF]  
Liver fibrosis in biliary atresia
  Wen-Jun Shen, Gong Chen, Min Wang, Shan Zheng
Background: Biliary atresia (BA) is the most common cause of obstructive jaundice in infants. Although the Kasai procedure has greatly improved the prognosis, most patients still need liver transplantation (LT) for long-term survival. The pathogenesis of BA has not been fully clarified, and liver fibrosis in BA is far beyond biliary obstructive cirrhosis.
Data sources: Literature reviews were underwent through PubMed. Persistent inflammation, immune response, biliary epithelial每mesenchymal transition, matrix deposition, decompensated angiogenesis, and unique biliary structure development all contribute to the fibrosis process. Observed evidences in such fields have been collected and form the backbone of this review.
Results: Interactions of the multiple pathways accelerate this process.
Conclusions: Understanding the mechanisms of the liver fibrosis in BA may pave the way to improved survival after the Kasai procedure.
  [Abstract] [Full Text] [PDF]  
Evaluation and management of the child with hypothyroidism
  Alexander K. C. Leung, Alexander A. C. Leung
Background: Thyroid hormones are critical for early neurocognitive development as well as growth and development throughout childhood. Prompt recognition and treatment of hypothyroidism is, therefore, of utmost importance to optimize physical and neurodevelopmental outcomes.
Data sources: A PubMed search was completed in Clinical Queries using the key terms ※hypothyroidism§.
Results: Hypothyroidism may be present at birth (congenital hypothyroidism) or develop later in life (acquired hypothyroidism). Thyroid dysgenesis and dyshormonogenesis account for approximately 85% and 15% of permanent cases of congenital primary hypothyroidism, respectively. More than 95% of infants with congenital hypothyroidism have few, if any, clinical manifestations of hypothyroidism. Newborn screening programs allow early detection of congenital hypothyroidism. In developed countries, Hashimoto thyroiditis is the most common cause of goiter and acquired hypothyroidism in children and adolescents. Globally, iodine deficiency associated with goiter is the most common cause of hypothyroidism. Central hypothyroidism is uncommon and may be associated with other congenital syndromes and deficiencies of other pituitary hormones. Familiarity of the clinical features would allow prompt diagnosis and institution of treatment.
Conclusions: To optimize neurocognitive outcome in infants with congenital hypothyroidism, treatment with levothyroxine should be started as soon as possible, preferably within the first 2 weeks of life. Children with acquired hypothyroidism should also be treated early to ensure normal growth and development as well as cognitive outcome. The target is to keep serum TSH < 5 mIU/L and to maintain serum free T4 or total T4 within the upper half of the age-specific reference range, with elimination of all symptoms and signs of hypothyroidism.
  [Abstract] [Full Text] [PDF]  
Original articles:
Effect of metoclopramide administration to mothers on neonatal bilirubin and maternal prolactin: a randomized, controlled, clinical trial
  Shirin Osouli Tabrizi, Mojgan Mirghafourvand, Abdollah Jannat Dost, Sakineh Mohammad-Alizadeh-Charandabi, Yousef Javadzadeh, Robabe Seyedi
Background: Jaundice is a common neonatal problem. This study was conducted to determine the effect of metoclopramide on neonatal bilirubin and maternal prolactin (primary outcomes) and milk volume (secondary outcome).
Methods: This triple-blind, randomized, controlled, clinical trial was conducted on 112 mothers. The participants were assigned to the intervention (metoclopramide) and control groups (placebo) using block randomization. Ten-mg metoclopramide and placebo tablets were taken by the participants three times a day. The intervention began in the first 2每10 hours after childbirth and continued until the fifth day. The mothers* prolactin level was measured on the first morning after the intervention and on the sixth day (1 day after the intervention was over). Neonatal total bilirubin was also measured before the intervention and on the sixth day.
Results: After the intervention, the two groups did not differ significantly in terms of the mean neonatal indirect bilirubin (P = 0.565) and milk volume (P = 0.261), but the mean serum prolactin was significantly higher in the metoclopramide group compared to the placebo group (adjusted mean difference 37; 95% confidence interval 58.1每16.5; P = 0.001).
Conclusions: Metoclopramide increased maternal serum prolactin but had no effects on neonatal jaundice. The insufficient numbers of studies on this subject mandate further research.
  [Abstract] [Full Text] [PDF]  
Clinical significance of low transaminase levels in children with inflammatory bowel disease
  Murat Cakir, Elif Sag, Guzide Dogan, Fatih Unal, Erhun Kasirga
Background: Low alanine aminotransaminase (LALT) levels may be seen in patients with inflammatory bowel disease (IBD), but there has been no study about the frequency and its clinical significance. We aimed to analyze the frequency of LALT, and its clinical significance in children with IBD.
Methods: The study included the 89 patients with IBD without hepatobiliary involvement. LALT was defined as ALT levels < 5 U/L. Demographic and clinical findings and outcome of the patients with and without LALT were compared.
Results: LALT was found 47.1% of the patients. At initial examination, it was more common in female patients (92.3 vs. 41.3%, P < 0.001) and patients with CD (57.7 vs. 30.2%, P = 0.01). 75% of the patients with penetrating Crohn*s disease (CD) had LALT (P = 0.002). Hemoglobin (10.4 ㊣ 2.1 vs. 11.7 ㊣ 1.9 g/dL, P = 0.01), folic acid (5.2 ㊣ 3.3 vs. 8.6 ㊣ 5.9 ng/mL, P = 0.02) and serum albumin levels (3.6 ㊣ 0.8 vs. 4.7 ㊣ 5 g/dL, P = 0.002) were significantly low in patients with LALT. LALT was associted with the disease relapse within 2 weeks in 12 of the 16 patients with LALT whereas it was seen in 16 of the 73 patients without LALT during the follow-up (75 vs. 21.9%, P < 0.001). Additionally, steroid dependency was more common in patients with LALT during the follow-up (62.5 vs. 12.3%, P < 0.001).
Conclusions: LALT is common in children with IBD especially in CD and associated with low hemoglobin, albumin and folic acid levels. It may be a marker of relapse and steroid dependency.
  [Abstract] [Full Text] [PDF]  
Long-term prognosis of low-risk neuroblastoma treated by surgery alone: an experience from a single institution of China
  Wei Yao, Kai Li, Kui-Ran Dong, Shan Zheng, Xian-Min Xiao
Background: Low-risk neuroblastomas have favorable biologic characteristics. Children Oncology Group (COG) proposed that surgical resection of the primary tumor was sufficient. We evaluated the long-term prognosis of surgery alone for patients with low-risk neuroblastoma in China.
Methods: A total of 34 patients with low-risk neuroblastoma were treated in our center between Jan 2009 and Dec 2013. The medical records of these patients were reviewed.
Results: The primary lesion was located in the adrenal gland in 19 patients, the retroperitoneum in 5, the posterior mediastinum in 9 and the neck in 1. The tumor diameters and volumes were 1.80每10.0 cm (average 5.5 ㊣ 2.3 cm) and 1.28每424.10 cm 3 (average 58.81 ㊣ 92.00 cm 3 ), respectively. The stages of the patients were as follows: stage I in 25, stage II in 7, and stage IVs in 2. All patients were in the low-risk group according to COG risk stratification criteria. No patients showed MYCN amplification. The primary tumors of all patients were completely resected. Nine adrenal tumors were completely resected by laparoscopy. All patients were successfully followed for 66每115 (average 89.71 ㊣ 16.17) months. Recurrence was observed in 4 patients. In addition to one local recurrence, another three recurrences were metastases. The lesions were effectively controlled in all patients with recurrences. All patients survived, including 28 cases of tumor-free survival; the 4-year overall and event-free survival rates were both 100%.
Conclusions: Surgery alone is a safe and effective treatment strategy for low-risk neuroblastoma. Recurrent lesions may be controlled and treated by rescue chemotherapy and surgery.
  [Abstract] [Full Text] [PDF]  
Association between fetal macrosomia and risk of obesity in children under 3 years in Western China: a cohort study
  Xiong-Fei Pan, Li Tang, Andy H. Lee, Colin Binns, Chun-Xia Yang, Zhu-Ping Xu, Jian-Li Zhang, Yong Yang, Hong Wang, Xin Sun
Background: Fetal macrosomia, defined as birth weight equal or over 4000 g, is a major concern for both neonatal and maternal health. A rapid increasing trend in fetal macrosomia is observed in different regions of China. We aimed to examine the association between fetal macrosomia and risk of childhood obesity in Western China.
Methods: All macrosomic live singletons (≡ 4000 g), and a random sample of singletons with normal birth weight (2500每3999 g) born in four districts of Chengdu, Western China, in 2011 were included in the cohort study. Maternal demographics, obstetric factors, labor and delivery summary at baseline were extracted from the Chengdu Maternal and Child Health Management System. Anthropometric measurements before 3 years and infant feeding information at around 6 months were also collected. Childhood obesity under 3 years was primarily defined as a weight-for-length/height z score ≡ 1.645 using the WHO growth reference. Secondary definitions were based on weight-for-age and body mass index (BMI)-for-age over the same cut-offs.
Results: A total of 1767 infants were included in the analyses, of whom 714 were macrosomic. After controlling for maternal age, parity, gestational age and anemia at the fi rst antenatal visit, pre-pregnancy BMI, gestational weight gain, gestational age at birth, baby age and sex, and breastfeeding practices at 6 months, the risk of childhood obesity defined according to weight-for-length/height among macrosomic babies was 1.90 (95% confidence interval 1.04每3.49) times that of babies with normal birth weight. The risk of childhood obesity for macrosomic babies was 3.74 (1.96每7.14) and 1.64 (0.89每3.00) times higher based on weight-for-age and BMI-for-age, respectively.
Conclusion: Fetal macrosomia is associated with increased risk of obesity in children under 3 years in Western China.
  [Abstract] [Full Text] [PDF]  
Pediatric bloodstream infections in metropolitan Australia
  Shakif Mohammad Shakur, John Whitehall, Poonam Mudgil
Background: Bloodstream infections (BSIs) cause significant morbidity and mortality of children worldwide. The aim of this study was to investigate BSI in children and determine the identity of causative organism and their susceptibility patterns in a metropolitan public hospital in Australia.
Methods: We retrospectively reviewed children aged 0每16 years admitted to a public hospital from January 1, 2010 to August 31, 2014 inclusive, and whose blood cultures revealed bacteraemia. Data were collected regarding patient demographics, species of bacteria isolated, antimicrobial susceptibility of these isolates, and clinical outcomes.
Results: Out of 96 patients with BSI, 55 (57.3%) were males. The median age was 3.35 years (IQR 0.44每7.46), and there were 2 mortalities. Common sites of infection were the respiratory tract (16.6%, n = 16), bone and joints (15.6%, n = 15) and the urinary tract (11.5%, n = 11). The most frequent isolates were Staphylococcus aureus (27.0%), Escherichia coli (14.0%) and Streptococcus pneumoniae (12.0%). Whilst most bacterial isolates displayed susceptibility (> 90%) to common antimicrobial agents, only 57.1% (8/14) of Escherichia coli isolates were susceptible to ampicillin and 58.3% (7/12) were susceptible to co-trimoxazole.
Conclusions: Gram-positive bacteria accounted for the majority of pediatric BSIs, of which invasive pneumococcal disease remains a noteworthy cause. The majority of isolates, except Escherichia coli, were susceptible to commonly used antimicrobials. This study confirms the knowledge of high rates of resistance of Escherichia coli to ampicillin. Therefore, empirical treatment should still include gentamicin. Monitoring of resistance patterns is warranted to ensure that antibiotic therapy remains appropriate.
  [Abstract] [Full Text] [PDF]  
Biomarkers of intravenous immunoglobulin resistance and coronary artery lesions in Kawasaki disease
  Wei-Xing Kong, Fei-Yue Ma, Song-Ling Fu, Wei Wang, Chun-Hong Xie, Yi-Ying Zhang, Fang-Qi Gong
Background: Currently, there are no reliable indicators for predicting intravenous immunoglobulin resistance and coronary artery lesions in the early stage of Kawasaki disease.
Methods: A total of 300 patients with Kawasaki disease were studied retrospectively. Laboratory data were compared between the intravenous immunoglobulin resistant (29 patients) and responsive groups, and between the groups with coronary artery lesions (48 patients) and without coronary artery lesions.
Results: The intravenous immunoglobulin resistant group had significantly higher D-dimer, globulin, interleukin-6 and serum ferritin levels in comparison to the intravenous immunoglobulin responder group. D-dimer level had a sensitivity of 87.0% and a specificity of 56.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 1.09 mg/L. Globulin had a sensitivity of 62.1% and a specificity of 82.3% for predicting intravenous immunoglobulin resistance at a cutoff point of 34.7 g/L. Serum ferritin level had a sensitivity of 42.9% and a specificity of 88.8% for predicting intravenous immunoglobulin resistance at a cutoff point of 269.7 ng/mL. The patients with coronary artery lesions had higher D-dimer and tumor necrosis factor-汐 level. D-dimer level had a sensitivity of 50% and a specificity of 78.6% for predicting coronary artery lesions at a cutoff point of 1.84 mg/L. Based on analysis by multivariate logistic regression, serum ferritin and globulin were independent risks for intravenous immunoglobulin resistance, D-dimer was independent risk for coronary artery lesions.
Conclusions: Elevated serum ferritin, globulin and D-dimer levels are significantly associated with intravenous immunoglobulin resistance in Kawasaki disease. Moreover, serum D-dimer is significantly increased in Kawasaki disease with coronary artery lesions.
  [Abstract] [Full Text] [PDF]  
Changes of feeding patterns in Chinese city children under 2 years from 1985 to 2015: results from a series of national cross-sectional surveys
  Hua-Hong Wu, Ya-Qin Zhang, Xin-Nan Zong, Hui Li
Background: In China, as the social transformation and economic development from 1985 to 2015, children*s feeding pattern has undergone some changes. So we aimed to analyze the secular trend on feeding patterns of city children in China.
Methods: All data were from a series of national survey which implemented once every 10 years in China from 1985 to 2015. We use same indexes to evaluate the feeding pattern of children in these four surveys.
Results: From 1985 to 2005, the exclusive breastfeeding rates in infants under 6 months of age decreased, especially in suburban areas decreased by 17.7%; the continuous breastfeeding rate of 1-year-old children in suburban area decreased from 60.1 to 27.6%. However, from 2005 to 2015, the exclusive breastfeeding rates under 6 months of age increased by 16.0% in urban areas and 5.9% in suburban areas; the continuous breastfeeding rate of 1-year-old children in urban increased from 17.0 to 36.0%. The overall feeding rate of complementary food in infants under 6 months of age declined from 1985 to 2015; the average age at introduction of all complementary foods was around 6 months of age in 2015.
Conclusions: There is an obvious trend on feeding pattern of Chinese children. From 1985 to 2005, the breastfeeding rate decreased, the duration time of breastfeeding was shortened and the age at introduction of complementary food was advanced. From 2005 to 2015, the breastfeeding rate increased, the duration time of breastfeeding was prolonged, and the age at introduction of complementary food was postponed.
  [Abstract] [Full Text] [PDF]  
US children with special health care needs and ethnic discrimination: results from multivariate modeling
  Guillermo Montes
Background: To determine the prevalence of parent-reported ethnic/racial discrimination, and to determine if children with special health care needs are more likely to experience ethnic discrimination than other children who have similar family income, age, sex, race, parental education and Hispanic ethnicity.
Methods: Using the National Survey of Children*s Health 2011每2012 (n = 95,677), ethnic discrimination was measured by two questions that asked ※was child ever treated or judged unfairly because of his/her race or ethnic group?§ and if so, how often it occurred in the last 12 months prior to the survey.
Results: An estimated 3 million US children aged 0每17 years have experienced parent-reported ethnic discrimination (1.4% White, 9.1% Black, 9.9% other race, 4.7% Hispanic). The likelihood to experience ethnic discrimination is much higher for Black and other race children, compared to White children. Children with special health care needs were two times more likely to experience ethnic discrimination frequently in the 12 months prior to the survey than comparable children in terms of age, sex, race, family income, parental education, and social capital. Higher family income did not prevent the exposure to ethnic discrimination but was associated with fewer instances.
Conclusions: Theoretical frameworks, such as social determinants of health, must account for the bidirectional nature of the relationship between health and ethnic discrimination. Pediatric care must assess if ethnic discrimination has occurred and whether trauma-informed approaches are needed.
  [Abstract] [Full Text] [PDF]  
The data and characteristics of the human milk banks in mainland China
  Xi-Hong Liu, Shu-Ping Han, Qiu-Fen Wei, Feng-Ying Zheng, Ting Zhang, Hui-Min Chen, Meng Mao, National Human Milk Bank Group, Children Health of the Chinese Medical Doctors Association, Group of Child Health Care, Society of Pediatrics, Chinese Medical Association
Background: Human milk banks (HMB) have been established for over 100 years in North America and Europe. This study aimed to describe and summarize the operation and characteristics of the HMBs in mainland China since the first nonprofit HMB operated in 2013.
Methods: Operation of HMB in mainland China is based on the standards and guidelines of the Human Milk Banking Association of North America and some countries in Europe and was modified to meet the needs and circumstances in China such as donation only in the local HMB by medical staff. We reviewed the descriptive data of these 14 HMBs and the clinical characteristics of recipients, the eligible milk donors and the donor milk retrospectively.
Results: In mainland China, from March 2013 to December 2016, 14 nonprofit HMBs were developed and operational in public hospitals except one and located in the south, east, north and northwest of mainland China. In total, 2680 eligible donors donated 4608.2 L of breast milk. The mean age of these donors was 29.4 years with 60.6% receiving college education and 90.6% term delivery. A total of 4678 recipients including preterm infants (n = 2990, 63.9%), feeding intolerance (n = 711, 15.2%), maternal illness (n = 345, 7.4%), serious infection (n = 314, 6.7%), necrotising enterocolitis (n = 244, 5.2%), post-surgery (n = 38, 0.8%) and others (n = 36, 0.8%). The rate of discarded raw milk was only 4.4% because of hepatitis B and C or cytomegalovirus positivity.
Conclusions: HMB has been developing rapidly in mainland China. Donor human milk was used not only for preterm infants but also for other ill children. But the sustainability of milk banking needs proper management and more financial support by relative health authorities and the government.
  [Abstract] [Full Text] [PDF]  
Genetics of congenital and infantile nephrotic syndrome
  Sara Nawfal Sharief, Nada Abdullatif Hefni, Walaa Ali Alzahrani, Iman Ibrahim Nazer, Marwa Abdullah Bayazeed, Khalid A. Alhasan, Osama Y. Safdar, Sherif M. El-Desoky, Jameela Abdulaziz Kari
Background: Congenital and infantile nephrotic syndrome (CNS and INS) are rare inherited defects in glomerular filtration involving a variety of gene mutations. This study aimed to analyze all genetic mutations associated with congenital and infantile nephrotic syndrome treated at our institution. We also discussed our different approach secondary to culture and resources.
Methods: A retrospective single-center study of all children diagnosed as NS before the age of 1 year over a duration of over one decade.
Results: Twenty-nine children (12 boys) were included in the study. Their median age (range) was 2.4 (0.1每12) months (20 CNS and 9 INS). Consanguinity was present in 90% of children. The genetic analysis* results were only available for 20 children. An underlying causative homozygous mutation was detected in 18 children (90%): NPHS1 (9), NPHS2 (2), LAMB2 (3), PLCE1 (1), WT1 (1), and ITSN1 novel mutation (2). One child had heterozygous mutation of NPHS2 and another child had heterozygous mutation of NPHS1 which could not explain the disease. All CNS cases were all managed with intermittent intravenous albumin infusion, ACEi, diuretics, and indomethacin. None of the children were managed by nephrectomy followed by peritoneal dialysis (PD) because of limited resources. Only one child achieved partial remission, while 15 children died at a median (range) age of 5.8 (1.25每29) months. The remaining 14 children were followed up for an average of 36 (3.9每120) months. Three children progressed to end-stage kidney disease and PD was performed in only two children.
Conclusions: NPHS1 is the main underlying cause of CNS and INS in our study population. CNS and INS were associated with high morbidity and mortality.
  [Abstract] [Full Text] [PDF]  
Letter to the editor:
Children with abnormal DMSA nuclear scan present a higher risk of recurrent febrile urinary tract infections
  Luke Harper, Yan Lefevre, Xavier Delforge, David Bourquard, Cyril Ferdynus
  [Abstract] [Full Text] [PDF]  
Tribute to Reviewers (January 1, 2018每December 31, 2018)
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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