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Vol 17, No 3
Vol 17, No 3 June 2021 ISSN 1708-8569
Review articles
Original articles
Letters to the editor
Review articles:
Correlation of computed tomography findings and lung function in children and adolescents with cystic fibrosis
  Andrew Fretzayas, Ioanna Loukou, Maria Moustaki, Konstantinos Douros
Background: The timely and appropriate monitoring of pulmonary status is of utmost importance for patients with cystic fibrosis (CF). Computed tomography (CT) has been used in clinical and research settings for tracking lung involvement in CF patients. However, as CT delivers a considerable amount of radiation, its sequential use in CF patients remains a concern. The application of CT, therefore, should take into account its potential risks. This review aims to understand whether and to what extent the CT findings correlate with the findings from other monitoring tools in CF lung disease.
Data sources: PubMed was searched for articles about the correlation of chest CT findings with spirometric indices and with lung clearance index in children and adolescents with CF. The most relevant articles were reviewed and are presented herein.
Results: Most studies have shown that forced expiratory volume in the first second (FEV1) and other spirometric indices correlate moderately with CT structural lung damage. However, at the individual level, there were patients with FEV1 within the normal range and abnormal CT and vice versa. Furthermore, longitudinal studies have indicated that the deterioration of structural lung damage does not occur in parallel with the progression of lung function. Lung clearance index is a better predictor of CT findings.
Conclusions: In general, the existing studies do not support the use of lung function tests as surrogates of chest CT.
  [Abstract] [Full Text] [PDF]  
Glomerular podocyte dysfunction in inherited renal tubular disease
  Li-Min Huang, Jian-Hua Mao
Background: Hereditary renal tubular disease can cause hypercalciuria, acid-base imbalance, hypokalemia, hypomagnesemia, rickets, kidney stones, etc. If these diseases are not diagnosed or treated in time, they can cause kidney damage and electrolyte disturbances, which can be detrimental to the maturation and development of the child. Glomerular involvement in renal tubular disease patients has only been considered recently.
Methods: We screened 71 papers (including experimental research, clinical research, etc.) about Dent*s disease, Gitelman syndrome, and cystinosis from PubMed, and made reference.
Results: Glomerular disease was initially underestimated among the clinical signs of renal tubular disease or was treated merely as a consequence of the tubular damage. Renal tubular diseases affect glomerular podocytes through certain mechanisms resulting in functional damage, morphological changes, and glomerular lesions.
Conclusions: This article focuses on the progress of changes in glomerular podocyte function in Dent disease, Gitelman syndrome, and cystinosis for the purposes of facilitating clinically accurate diagnosis and scientific treatment and improving prognosis.
  [Abstract] [Full Text] [PDF]  
Chest computed tomography findings of COVID-19 in children younger than 1 year: a systematic review
  Alireza Ghodsi, Moniba Bijari, Seyed Ali Alamdaran, Amin Saberi, Elnaz Mahmoudabadi, Mohammad Reza Balali, Sara Ghahremani
Background: The aim of this systematic review is to evaluate the chest computed tomography (CT) findings in infants with confirmed COVID-19 infection by providing a comprehensive review of the existing literature.
Data sources: A systematic search was conducted on PubMed and Embase from the onset of the COVID-19 outbreak to October 20, 2020, for studies that discussed the chest CT findings in infants younger than 1 year with COVID-19 infection.
Results: A total of 35 studies comprising 70 COVID-19 (58.5% boys) confirmed infants were included. The mean age of the included patients was 4.1 months with a range of 1 day to 12 months. Chest CT scans showed bilateral abnormalities in 34 patients, and unilateral lung involvement in 25 patients. Ground-glass opacities (GGO) (71.43%) were found to be the most prevalent chest CT manifestation, followed by peribronchial thickening (60%), linear or band-shaped opacities (32.8%), consolidation (28.57%), nodule (18.57%), effusion (7.14%) and focal lucency (7.14%).
Conclusions: GGO and peribronchial thickening were the most prevalent findings in the infants* chest CT scans. Linear or band-shaped opacities, consolidation, and pulmonary nodules are more common in infants than in adults. These findings suggest that the disease is more likely to be presented as an atypical pneumonia (peribronchial thickening and linear or bandshaped opacities) in this age group. Other chest CT scan manifestations can be classified as typical COVID-19 infection (peripheral GGO), lobar pneumonia (consolidation) and opportunistic infections (pulmonary nodules).
  [Abstract] [Full Text] [PDF]  
Efficacy and safety of Huaiqihuang granule as adjuvant treatment for primary nephrotic syndrome in children: a meta-analysis and systematic review
  Jiao Lin, Li-Min Huang, Jing-Jing Wang, Jian-Hua Mao
Background: Huaiqihuang (HQH) granule is a traditional Chinese herbal complex that has been used as an adjuvant treatment in clinics for the primary nephrotic syndrome (PNS) for many years. However, the effectiveness and safety of HQH have not been systematically discussed. This review aimed to evaluate the effectiveness and safety of HQH in paediatric patients with PNS.
Methods: The following databases were searched from inception to Mar 2019: MEDLINE, Cochrane Library, EMBASE, CNKI, Wanfang Database, the Chinese Scientific Journal Database and the Chinese biomedical literature service system. All the randomized controlled trials (RCTs) eligible for inclusion were included. The primary outcomes were relapse, infection, remission and adverse events. The secondary outcomes included serum immunoglobulin levels (IgA, IgG or IgM), T-lymphocyte subtype (CD3+ , CD4+ , CD8+ , CD4+ /CD8+), IL-10, TNF-, TNF-, total cholesterol and time of proteinuria turning negative.
Results: Fourteen RCTs (885 patients) were identified. Treatment with HQH reduced the chance of relapse [relative risk (RR): 0.47; 95% CI: 0.34, 0.66; P < 0.001] and infections (RR: 0.47; 95% CI: 0.35, 0.62; P < 0.001). No significant difference was found in adverse events. HQH also increased the serum levels of IgA [weighted mean difference (WMD): 0.40; 95% CI: 0.20, 0.60; P < 0.001] and IgG (WMD: 1.58; 95% CI: 1.38每1.78; P < 0.001), as well as CD4 + [standard mean difference (SMD): 0.90; 95% CI: 0.12每1.68; P = 0.02], CD3 + (WMD: 4.04; 95% CI: 3.27每4.82; P < 0.001), and the CD4 + /CD8 + ratio (WMD: 0.31; 95% CI: 0.21每0.41; P < 0.001), but decreased the level of CD8 + cells (WMD: 每3.39; 95% CI: −5.73每1.05; P = 0.004). No statistically significant difference was found in IgM (WMD: 0.05; 95% CI: −0.13, 0.24; P = 0.57).
Conclusions: HQH could reduce the rate of relapse and the frequency of infection in children with PNS. No apparent adverse effects were found. Moreover, the beneficial influence of HQH may act through immunomodulation. Additional multi-center, large-sample, high-quality studies are needed to confirm the effectiveness and safety of HQH.
  [Abstract] [Full Text] [PDF]  
Original articles:
Short-term developmental outcomes in neonates born to mothers with COVID-19 from Wuhan, China
  Ling-Kong Zeng, Hua-Ping Zhu, Tian-Tian Xiao, Si-Cong Peng, Wen-Hao Yuan, Jian-Bo Shao, Lai-Shuan Wang, Fei-Fan Xiao, Shi-Wen Xia, Shoo K. Lee, Kai Yan, Wen-Hao Zhou
Background: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is an emerging disease. The consequences of SARS-CoV-2 exposure in infants remain unknown. Therefore, this study aims to investigate whether neonates born to mothers with COVID-19 have adverse brain development.
Methods: This multicenter observational study was conducted at two designated maternal and children*s hospitals in Hubei Province, mainland China from February 1, 2020 to May 15, 2020. Neonates born to mothers with COVID-19 were enrolled. Brain magnetic resonance imaging (MRI) findings, and volumes of grey and white matters, and physical growth parameters were observed at 44 weeks corrected gestational age.
Results: Of 72 neonates born to mothers with COVID-19, 8 (11%) were diagnosed with COVID-19, 8 (11%) were critically ill, and no deaths were reported. Among the eight neonates that underwent brain MRI at corrected gestational age of 44 weeks, five neonates were diagnosed with COVID-19. Among these five neonates, three presented abnormal MRI findings including abnormal signal in white matter and delayed myelination in newborn 2, delayed myelination and brain dysplasia in newborn 3, and abnormal signal in the bilateral periventricular in newborn 5. The other three neonates without COVID-19 presented no significantly changes of brain MRI findings and the volumes of grey matter and white matter compared to those of healthy newborns at the equivalent age (P > 0.05). Physical growth parameters for weight, length, and head circumference at gestational age of 44 weeks were all above the 3rd percentile for all neonates.
Conclusions: Some of the neonates born to mothers with COVID-19 had abnormal brain MRI findings but these neonates did not appear to have poor physical growth. These findings may provide the information on the follow-up schedule on the neonates exposed to SARS-CoV-2, but further study is required to evaluate the association between the abnormal MRI findings and the exposure to SARS-CoV-2.
  [Abstract] [Full Text] [PDF]  
Clinical characteristics of Kawasaki disease and concurrent pathogens during isolation in COVID-19 pandemic
  Yue-Yue Ding, Yan Ren, Jie Qin, Guang-Hui Qian, Yun-Jia Tang, Ye Chen, Xuan Li, Lei Xu, Chun-Hong Qiao, Ling Sun, Hai-Tao Lv
Background: The aim of this study is to explore the characteristics of Kawasaki disease (KD) and concurrent pathogens due to a stay-at-home isolation policy during coronavirus disease 2019 (COVID-19) epidemic.
Methods: All patients with KD admitted between February and April in 2015-2020, were classified into before (group 1, in 2015每2019) and after (group 2, in 2020) isolation groups. A total of 4742 patients [with KD (n = 98) and non-KD (n = 4644)] referred to Mycoplasma pneumoniae (MP) and virus detection were analyzed in 2020. Clinical characteristics, laboratory data, and 13 pathogens were analyzed retrospectively.
Results: Group 2 had a significantly increased incidence of KD (0.11%) with 107 patients compared to that of group 1 (0.03%) with 493 patients. The comparisons of oral mucosal change, strawberry tongue, desquamation of the fingertips, cervical lymphadenopathy and neutrophil percentage decreased in group 2 compared to group 1. The infection rate of MP increased significantly in group 2 (34.7%) compared to group 1 (19.3%), while the positive rate of viruses decreased significantly in group 2 (5.3%) compared to group 1 (14.3%). In 2020, the positive rate of MP infection increased significantly in patients with KD compared to the increase in patients with non-KD. The infection rate of MP for younger children aged less than 3 years old was higher in group 2 than in group 1.
Conclusion: Compared with the characteristics of KD from 2015 to 2019 years, the incidence of KD was increased in 2020 and was accompanied by a high incidence of MP infection, especially in younger children (less than 3 years old) during the isolation due to COVID-19 pandemic.
  [Abstract] [Full Text] [PDF]  
Distinctive clinical and laboratory features of COVID-19 and H1N1 influenza infections among hospitalized pediatric patients
  Ali Alsuheel Asseri, Ayed A. Shati, Saleh M. Al-Qahtani, Ibrahim A. Alzaydani, Ahmed A. Al-Jarie, Mohammed J. Alaliani, Abdelwahid Saeed Ali
Background: It had been documented in many studies that pediatric coronavirus disease 2019 (COVID-19) is characterized by low infectivity rates, low mortalities, and benign disease course. On the other hand, influenza type A viruses are recognized to cause severe and fatal infections in children populations worldwide. This study is aimed to compare the clinical and laboratory characteristics of COVID-19 and H1N1 influenza infections.
Methods: A retrospective study comprising 107 children hospitalized at Abha Maternity and Children Hospital, Southern region of Saudi Arabia, with laboratory-confirmed COVID-19 and H1N1 influenza infections was carried out. A complete follow-up for all patients from the hospital admission until discharge or death was made. The clinical data and laboratory parameters for these patients were collected from the medical records of the hospital.
Results: Out of the total enrolled patients, 73 (68.2%) were diagnosed with COVID-19, and 34 (31.8%) were diagnosed with H1N1 influenza. The median age is 12 months for COVID-19 patients and 36 months for influenza patients. A relatively higher number of patients with influenza had a fever and respiratory symptoms than COVID-19 patients. In contrast, gastrointestinal symptoms were observed in a higher number of COVID-19 patients than in influenza patients. A statistically significant increase in white cell counts is noted in COVID-19 but not in influenza patients (P < 0.05). There are no obvious variations in the mean period of duration of hospitalization between COVID-19 and influenza patients. However, the total intensive care unit length of stay was longer for influenza compared to COVID-19 patients.
Conclusions: A considerable number of children infected with COVID-19 and H1N1 influenza were noted and reported in this study. There were no significant variations in the severity of the symptomatology and laboratory findings between the two groups of patients. Significant differences between these patients in some hospitalization factors and diagnosis upon admission also were not observed. However, more severe clinical manifestations and serious consequences were observed among pediatric patients hospitalized with influenza infections than among those with COVID-19.
  [Abstract] [Full Text] [PDF]  
Maternal mental health and well-being during the COVID-19 pandemic in Beijing, China
  Zhuang Wei, Ming-Yue Gao, Mary Fewtrell, Jonathan Wells, Jin-Yue Yu
Background: The aim of this study is to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on breastfeeding women and to identify predictors of maternal mental health and coping.
Methods: Mothers aged ≡ 18 years with a breast-fed infant ≒ 18 months of age during the COVID-19 pandemic in Beijing, China, completed a questionnaire. Descriptive analysis of lockdown consequences was performed and predictors of these outcomes were examined using stepwise linear regression.
Results: Of 2233 participants, 29.9%, 20.0% and 34.7% felt down, lonely, and worried, respectively, during the lockdown; however, 85.3% felt able to cope. Poorer maternal mental health was predicted by maternal (younger age, higher education) and infant (older age, lower gestation) characteristics, and social circumstances (husband unemployed or working from home, receiving advice from family, having enough space for the baby, living close to a park or green space). Conversely, better maternal mental health was predicted by higher income, employment requiring higher qualifications, more personal space at home, shopping or walking > once/week and lack of impact of COVID-19 on job or income. Mothers with higher education, more bedrooms, fair division of household chores and attending an online mother and baby group > once/week reported better coping.
Conclusion: The findings highlight maternal characteristics and circumstances that predict poorer mental health and reduced coping which could be used to target interventions in any future public health emergencies requiring social restrictions.
  [Abstract] [Full Text] [PDF]  
Causes of severe neonatal hyperbilirubinemia: a multicenter study of three regions in China
  Xiao-Yue Dong, Qiu-Fen Wei, Zhan-Kui Li, Jie Gu, Dan-Hua Meng, Jin-Zhen Guo, Xiao-Li He, Xiao-Fan Sun, Zhang-Bin Yu, Shu-Ping Han
Background: Available evidence suggests that our country bear great burden of severe hyperbilirubinemia. However, the causes have not been explored recently in different regions of China to guide necessary clinical and public health interventions.
Methods: This was a prospective, observational study conducted from March 1, 2018, to February 28, 2019. Four hospitals in three regions of China participated in the survey. Data from infants with a gestational age ≡ 35 weeks, birth weight ≡ 2000 g, and total serum bilirubin (TSB) level ≡ 17 mg/dL (342 米mol/L) were prospectively collected.
Results: A total of 783 cases were reported. Causes were identified in 259 cases. The major causes were ABO incompatibility (n = 101), glucose-6-phosphate dehydrogenase deficiency (n = 76), and intracranial hemorrhage (n = 70). All infants with glucose-6-phosphate dehydrogenase deficiency were from the central south region. Those from the central south region had much higher peak total bilirubin levels [mean, 404 米mol/L; standard deviation (SD), 75 米mol/L] than those from the other regions (mean, 373 米mol/L; SD, 35 米mol/L) (P < 0.001).
Conclusions: ABO incompatibility was the leading cause in the east and northwest regions, but cases in the central south region were mainly caused by both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency, and infants in this region had a much higher peak total bilirubin level. Intracranial hemorrhage may be another common cause. More thorough assessments and rigorous bilirubin follow-up strategies are needed in the central south region.
  [Abstract] [Full Text] [PDF]  
Hedgehog signaling pathway gene variant influences bronchopulmonary dysplasia in extremely low birth weight infants
  Shaili Amatya, Sharina Rajbhandari, Sandeep Pradhan, Van Trinh, Umesh Paudel, Lance A. Parton
Background: Genome wide association study identified hedgehog interacting protein gene (HHIP) variants with chronic obstructive pulmonary disease and asthma. Loss of HHIP, a key regulator of the hedgehog signaling pathway, leads to impaired lung morphogenesis and lethality in animal models, through unimpeded sonic hedgehog expression blocking mesenchymal-expressed fibroblast growth factor 10 (FGF10). Since bronchopulmonary dysplasia (BPD) is also associated with altered lung development and worsens with stimuli including mechanical ventilation, reactive oxygen species, and inflammation, HHIP and FGF10 may be candidate genes.
Methods: This was an observational, cohort study including extremely low birth weight infants that who developed BPD and those who did not. DNA was isolated from buccal swabs and subjected to allelic discrimination, using specific HHIP and FGF10 probes. Protein levels were measured in tracheal aspirates. Student*s t test, Chi-square, Z test and logistic regression were used.
Results: Demographic characteristics did not differ except that birth weight (715 ㊣ 153 vs. 835 ㊣ 132 g) and gestational age (25 vs. 26 weeks) were less in babies with BPD. HHIP variant rs13147758 (GG genotype) was found to be independently protective for BPD (odds ratio 0.35, 95% confidence interval 0.15-0.82, P = − 0.02). Early airway HHIP protein levels were increased in infants with BPD compared to those without [median (interquartile range) 130.6 (55.6-297.0) and 41.2 (22.1-145.6) pg/mL, respectively; P = 0.05]. The FGF10 single nucleotide polymorphisms were not associated with BPD.
Conclusion: HHIP, as a regulator of lung bud formation, affects BPD susceptibility, and may be valuable in understanding the specific mechanisms for this disease as well as for identifying therapeutic targets in the era of personalized medicine.
  [Abstract] [Full Text] [PDF]  
Genetic etiologies associated with infantile hydrocephalus in a Chinese infantile cohort
  Hong-Fang Mei, Xin-Ran Dong, Hui-Yao Chen, Yu-Lan Lu, Bing-Bing Wu, Hui-Jun Wang, Guo-Qiang Cheng, Lai-Shuan Wang, Yun Cao, Lin Yang, Wen-Hao Zhou
Background: Infantile hydrocephalus (IHC) is commonly related to other central nervous system diseases, which may have adverse effects on prognosis. The causes of IHC are heterogeneous, and the genetic etiologies are not fully understood. This study aimed to analyze the genetic etiologies of an IHC cohort.
Methods: The data for 110 IHC patients who had received exome sequencing at the Clinical Genetic Center of the Children*s Hospital of Fudan University between 2016 and 2019 were reviewed and analyzed retrospectively. An exome-wide association analysis (EWAS) was performed within this cohort using IHC as the study phenotype.
Results: Of the 110 IHC patients, a pathogenic or likely pathogenic variant was identified in 16 (15%) patients, spanning 13 genes. The genes were mainly associated with metabolic disorders, brain abnormalities, and genetic syndromes. IHC patients who had unclear clinical etiology were more likely to possess a genetic etiology. Based on previous studies and on our EWAS results, ZEB1, SBF2, and GNAI2 were over-represented among IHC patients and might affect the signaling pathways involved in IHC formation
Conclusions: Our study showed heterogeneous genetic etiologies in an IHC cohort. It is essential to perform genetic testing on IHC patients who have unclear clinical etiology, and genes associated with metabolic disorders, brain abnormalities, and genetic syndromes should be noted. In addition, when aiming to discover IHC susceptibility genes, genes that might influence the signaling pathways involved in IHC formation should be prioritized.
  [Abstract] [Full Text] [PDF]  
Associations between measures of pediatric human resources and the under-five mortality rate: a nationwide study in China in 2014
  Xi Zhang, Jian Wang, Li-Su Huang, Xin Zhou, Julian Little, Therese Hesketh, Yong-Jun Zhang, Kun Sun
Background: To quantify the associations between the under-fi ve mortality rate (U5MR) and measures of pediatric human resources, including pediatricians per thousand children (PPTC) and the geographical distribution of pediatricians.
Methods: We analyzed data from a national survey in 2015-2016 in 2636 counties, accounting for 31 mainland provinces of China. We evaluated the associations between measures of pediatric human resources and the risk of a high U5MR (≡ 18 deaths per 1000 live births) using logistic regression and restricted cubic spline regression models with adjustments for potential confounders. PPTC and pediatricians per 10,000 km2 were categorized into quartiles. The highest quartiles were used as reference.
Results: The median values of PPTC and pediatricians per 10,000 km2 were 0.35 (0.20-0.70) and 150 (50-500), respectively. Compared to the counties with the highest PPTC (≡ 0.7), those with the lowest PPTC (< 0.2) had a 52% higher risk of a high U5MR, with an L-shaped relationship. An inverted J-shaped relationship was found that the risk of a high U5MR was 3.74 [95% confidence interval (CI) 2.55每5.48], 3.07 (95% CI 2.11每4.47), and 2.25 times (95% CI 1.52每3.31) higher in counties with < 50, 50每149, and 150每499 pediatricians per 10,000 km2, respectively, than in counties with ≡ 500 physicians per 10,000 km2. The joint association analyses show a stronger association with the risk of a high U5MR in geographical pediatrician density than PPTC.
Conclusion: Both population and geographical pediatrician density should be considered when planning child health care services, even in areas with high numbers of PPTC.
  [Abstract] [Full Text] [PDF]  
Letters to the editor:
Characteristics of abnormal serum creatine kinase-MB levels in children with COVID-19
  Juan-Juan Wang, Zhao Hu, Jian-Ying Chen
  [Abstract] [Full Text] [PDF]  
COVID-19 ocular findings in children: a case series
  Celia Fern芍ndez Alcalde, Maria Granados Fern芍ndez, Maria Nieves Moreno, Cristina Calvo Rey, Iker Falces Romero, Susana Noval Mart赤n
  [Abstract] [Full Text] [PDF]  
World Journal of Pediatric Surgery
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