Objective: To evaluate the accuracy and false positive rate of congenital heart disease (CHD) screening protocols for early detection of critical CHD (CCHD) in neonates. Methods: Literature search and selection were carried out during the development of the neonatal CCHD screening (NCCHDS) guideline. The reference standard for the diagnosis of CCHD was echocardiography, or through signs and symptoms of neonates during follow-up with confirmation of CCHD by echocardiography, surgery, or cardiac catheterization. The risk of bias and clinical applicability of the included literature were evaluated with the QUADAS-2 scale. Data were extracted and diagnostic parameters including sensitivity and specificity were summarized with the random effect model. Results: Twenty-one articles were included in this meta-analysis, and three different protocols were reported for screening neonatal CCHD: pulse oximetry alone (POX; n=21)，POX+clinical evaluation (CE) (n=3), POX+murmur (MUR) (n=2). The sample size of the included studies ranged from 435 to 167,190. There were 7 studies from the United States, 9 from Europe, 4 from Asia, and 1 from Africa. The sensitivity and specificity of POX alone, POX+CE and POX+MUR screening were 72.2%（95%CI: 60.4%-81.6%）, 91.0%（95%CI: 86.3%-94.2%）and 93.7%（95%CI: 89.2%-96.4%）, respectively and 99.8%（95%CI: 99.7%-99.9%）, 98.5%（95%CI: 96.7%-99.3%）and 98.3%（95%CI: 97.2%-99.0%）, respectively. The AUC was 0.973, 0.964 and 0.982, respectively. Subgroup analysis of POX screening alone showed there were no statistically significant differences in sensitivity across all subgroups (P＜0.01 after correction) and repeated measurement had higher false positive rates compared with single measurement. Heterogeneity of sensitivity and specificity of POX screening for neonatal CCHD was possibly related to whether the screener has been trained, level of hospital, different core technical aspects of screening instruments, and use of reusable or disposable probes or different probe types. Conclusion: The differences among AUC of POX alone, POX+CE, POX+MUR are small. POX alone is available for the moderate sensitivity of screening. POX+CE and POX+MUR are recommended for the higher sensitivity of screening and POX+MUR is recommended for optimizing screening indicators.
ObjectiveTo explore the effect of different antibacterial drugs on reducing the risk of catheter-related bloodstream infections for different populations of pediatrics with a central venous access device (CVAD). MethodsPediatric patients applicable to CVADs were included from inpatient, outpatient and home settings. With antimicrobial lock and/or systemic intravenous antibiotic therapy in the intervention group, the control group was treated with non-antimicrobial lock and/or systemic intravenous antibiotic therapy. Suspected, possible and confirmed catheter-related bloodstream infections were the primary outcome. Literature was searched in both of English and Chinese databases including PubMed, Ovid-EMBASE and SinoMed from the establishment to September 24, 2020. Search terms were antimicrobial lock, central venous catheter, catheter-related bloodstream infection and children. Cochrane risk-of-bias tool for randomized trials and ROBINS-I were used to evaluate the risk of bias for RCTs and non-RCTs respectively. ResultsA total of 30 studies were included into the analysis with 17 RCTs and 13 non-RCTs. According to whether there was a clear catheter-related bloodstream infection at the beginning of the intervention, they were divided into the category of prevention (n=30) and treatment (n=1). In terms of study populations, there were 9 studies for children with intestinal failure, 13 for children with tumors, 4 for PICU and/or NICU, and 4 for others. Based on 29 studies focusing on different locking fluids (ethanol, taurolidine, urokinase, and antibiotics) to prevent catheter-related bloodstream infections, the overall risk density was RR=0.32(95%CI: 0.24-0.43) with statistically significant differences (P<0.01). Random effect model was used with I2=75%. Among them, there were 8 RCTs taking antibiotics as the locking fluid (RR=0.38, 95%CI: 0.18-0.82, P<0.05, I2=70%). Clinical heterogeneity was likely to come from patients with tumors, immunosuppression and vancomycin. Three RCTs were about urokinase (RR=0.71, 95%CI: 0.53-0.95, I2=0). Ten studies were about ethanol (RR=0.31, 95%CI: 0.22-0.43, P< 0.01, I2=57%) and clinical heterogeneity was likely to come from patients with intestinal failure. Eight studies were about (RR=0.23, 95%CI: 0.12-0.42, P<0.01,I2=72%) and clinical heterogeneity was likely to come from patients with intestinal failure, surgery and customized high-risk patients. One study was about catheter-related bloodstream infections treated with hydrochloric acid as the locking fluid (RR=0.84, 95%CI: 0.52-1.37, P=0.49). Among the secondary outcomes, there were statistically significant differences between the intervention group of catheter bacterial colonization and the control group only when taurolidine was used as the locking fluid. Adverse reactions after antimicrobial lock therapy included abnormal taste, vomiting, nausea, dizziness, and flushing. ConclusionThe use of locking fluids can reduce the risk density of CVAD-related bloodstream infections by 68%. Taurolidine has the best preventive effect, followed by ethanol, antibiotics and urokinase in a descending order. However, the effect of antimicrobial lock therapy may be overstated, and further research is likely to affect the credibility of the results of this efficacy evaluation.
Objective: To evaluate the relationship between maternal pre-pregnancy overweight/obese status and offspring attention deficit hyperactivity disorder(ADHD). Methods: The Chinese and English databases, including CNKI, Wanfang Data, Sinomed, PubMed, Embase, and Cochrane library, were searched for cohort studies on the association between maternal overweight/obese status before pregnancy and offspring ADHD from the time of establishment to 11th February, 2020. The retrieving methods combined Mesh subject terms and free terms related to maternal pre-pregnancy BMI, offspring ADHD and cohort. Two researchers did the primary and full-text selection and extracted data individually. Pre-pregnancy BMI was the only indicator for the classification of being underweight, normal, overweight and obese. ADHD evaluation scale was filled by teachers or parents, and inattention, hyperactivity/impulsivity or combined type of ADHD were counted. Exposure factors of different cohorts were extracted. Newcastle-Ottawa scale (NOS) was used for quality assessment. Data analysis was performed by Stata 15.0. Results: A total of 13 studies were included in this study with 16 cohorts and 12 of them were prospective cohort studies. A total of 801,834（511-649,043，median 3,803）subjects were recruited. The results of the meta-analysis showed that both of being maternal overweight (OR=1.21, 95%CI:1.16-1.27, I2=18.3%) and obese (OR=1.35, 95%CI: 1.19-1.55, I2=84.0%) were significantly associated with offspring ADHD, while being maternal underweight was not significantly associated with ADHD (OR=1.05, 95%CI: 0.97-1.13，I2=0%）. Heterogeneity analysis results showed that: a. Regional subgroup analysis revealed the results of being pre-pregnancy overweight and obese in European and North America cohort was OR=1.22（95%CI, 1.19-1.26），OR=1.45（95%CI, 1.31-1.61）and OR=1.14（95%CI, 0.85-1.52），OR=1.94（95%CI, 1.05-3.58）, respectively. b. Subgroup analysis based on offspring age (preschool, school age and not given) indicated pre-pregnancy obesity was not related to increased risk of preschool ADHD. c. Subgroup analysis based on ADHD clinical types revealed that being pre-pregnancy overweight and obese increased the risk of combined ADHD (OR=1.22, 95%CI: 1.19-1.25，OR=1.41, 95%CI: 1.22-1.63) and pre-pregnancy overweight status increased the risk of inattention ADHD (OR=1.40, 95%CI: 1.06-1.87). There was no publication bias by the Begg rank correlation test and the Egger linear regression test. Conclusion: This meta-analysis suggests that maternal pre-pregnancy overweight/obese status may increase the risk of ADHD in offspring while maternal pre-pregnancy underweight status may not.
Objective: To summarize the clinical and imaging characteristics of children with pneumocystis jirovecii pneumonia (PJP) infected by non-human immunodeficiency virus (HIV). Methods: The consecutive cases of PJP with HIV negative confirmed and treated in PICU of Anhui Children's Hospital between August 1st, 2014 and July 31st, 2019 were included. Clinical data of survival and died children after 90 days of admission to PICU were compared. Results: Thirteen cases were analyzed in this study, including 7 males and 6 females， with the onset age of (80.8±23.8) months. Twelve cases had underlying diseases, most of which were primary nephrotic syndrome, congenital immunodeficiency disease and hematologic tumor. Ten cases were treated with immunosuppressive agents before the onset of the disease, and all of 13 cases failed to respond to antibiotics. Clinical symptoms included fever, shortness of breath, cough (mostly dry cough), anorexia /weight loss, and progressive dyspnea. Moans were common in small infants, and moist rales could be heard and fixed in 2 cases. LDH was increased in 13 cases ［(646±122) U·L-1］, and BDG was increased in 8 cases ［(184±119) pg·mL-1］. Chest imaging examination showed that 13 cases had ground-glass opacity in both lungs, and 3 cases had pneumothorax, subcutaneous emphysema and mediastinal emphysema.Compared with the survival group, the lymphocyte count (P=0.012) and oxygenation index (PaO2/FIO2) were lower in the death group (P=0.027), and the time from onset to SMZ treatment was longer(P<0.038). Conclusion: When immunocompromised children have symptoms such as fever, shortness of breath, dry cough, progressive dyspnea, and ground-glass opacity in both lungs by CT, PJP should be considered.
ObjectiveTo analyze the clinical manifestations, endoscopic and histopathological characteristics of eosinophilic gastroenteritis（EGE）and to evaluate the efficacy and prognosis of diet and glucocorticoid therapy. MethodsA retrospective analysis was made for clinical data of patients with EGE who were hospitalized in the Department of Gastroenterology of Anhui Provincial Children's Hospital from February 2016 to February 2020, including gender, age at first diagnosis, course of disease, time of diagnosis, clinical manifestations, history of allergy, family history, EGE classification, laboratory examination, imaging examination, endoscopy, pathology, treatment and follow-up. ResultsA total of 22 patients were included into the analysis with 15 males and 7 females， with the median age of 7 years (3 months to 13 years). The most common gastrointestinal symptoms were abdominal pain (16 cases, 72.7%), diarrhea (13 cases, 59.1%) and abdominal distention (9 cases, 40.9%). In addition, the most common extraintestinal symptoms were anemia (10 cases, 45.5%) and weight loss (5 cases, 22.7%). The serum total IgE level, the ratio of eosinophil in peripheral blood and D-dimer were elevated for 18 cases (81.8%),15 cases (68.2%) and 7 cases (31.8%) ，respectively. In gastroscopy, 12 out of 22 cases (54.6%) were ulcers and 3 cases (13.6%) showed atrophy of duodenal villi. In colonoscopy, 4 out of 14 cases (28.6%) showed normal mucosa and 6 cases (42.9%) were affected on the terminal ileum. The positive rate was high(≥20 eos·HPF-1) in duodenum (52.6%) and terminal ileum (46.2%). Diet therapy and glucocorticoid therapy could alleviate symptoms. In particular, glucocorticoid therapy combined with diet could heavily reduce the infiltration of eosinophils in histology, which presented statistically significant differences compared with that of the single diet therapy（P＝0.002）. The recurrence rate reached 15.8%. ConclusionEGE gives no specific clinical symptoms. Possibility of EGE should be taken into consideration for patients with high level of serum total IgE and high ratio of eosinophil in peripheral blood. Multi-point endoscopic biopsy and histological examination are helpful for the diagnosis.
ObjectiveTo describe the incidence trend and clinical characteristics of children with adenovirus infection in medical institutions in Shanghai. MethodsA cross-sectional study was designed to collect the demographic characteristics, clinical diagnosis and virological detection of children with adenovirus infection in outpatient and emergency settings and hospitalization in 38 medical institutions in Shanghai from January 1st, 2018 to May 31st, 2019，and compare the clinical characteristics of children with adenovirus infection in the same period of 2019 and 2018 (from January to May). ResultsA total of 618 children with adenovirus infection were included in this analysis. Sixteen patients (2.6%) were admitted to PICU and there were no deaths. There were 298 children with adenovirus positive detected in outpatient and emergency settings, including 176 male cases (59.1%) and 104 adenovirus pneumonia cases (34.9%). There were 320 hospitalized children, including 204 male cases (63.7%) and 278 adenovirus pneumonia cases (86.9%). In January of 2018 and 2019, the number of children with adenovirus infection in outpatient and emergency settings reached its peak. After January 2018, the peak of infection dropped rapidly, and from January to May in 2019 the peak decreased but still remained at a relatively high level. In 2019, compared with the same period in 2018 (from January to May), the incidence of pediatric adenovirus infection in outpatient and emergency settings and hospitalization increased by 1.8 times (148/84) and 2.3 times (157/69), respectively; the proportion of emergency visits increased (37.2% vs 9.5%); the mean age was younger (3.0 vs 4.0); the proportion of children under 2 years old was higher; the proportion of adenovirus pneumonia increased (50.0% vs 13.0%). There were statistically significant differences (P<0.05). Adenovirus detection methods in children's specialized hospital mainly include deep sputum antigen detection, the rapid detection of nasal swab antigen and serum IgM antibody detection. The detection methods of adenovirus in general hospital mainly include the rapid detection of nasal swab antigen and serum IgM antibody detection. ConclusionCompared with the same period of 2018 (from January to May), the incidence of adenovirus infection in Shanghai showed a higher trend in 2019 and lasted until May at least, with a higher proportion of adenovirus pneumonia and adenovirus infection in children under 2 years old.
ObjectiveTo analyze the prenatal echocardiographic features of anatomically corrected malposition of the great arteries (ACMGA) {S,D,L} in order to improve the prenatal diagnosis accuracy. MethodsFetal echocardiographic features were retrospectively analyzed with prenatal diagnosis of ACMGA {S,D,L} at Beijing Anzhen Hospital between November 2016 and August 2020, and the fetal echocardiography characteristics of ACMGA {S,D,L} and the key points of its identification were summarized. ResultsThere were 5 fetuses with ACMGA. The age of pregnant women was 26 to 35 (29.4±3.6) years old, and the pregnancy period was 23 to 28 （24.2±2.2） weeks. Four cases had induced labor including 1 case of diagnosis confirmation by postmortem examination. One case was confirmed by echocardiography, cardiac CT and surgery (pulmonary artery banding) after birth. Echocardiographic features included: a. The viscera and atria were in situs solitus, the type of ventricular loop was d-loop and atrioventricular connections was normal. b. The aorta originated above the left ventricle, the pulmonary artery originated above the anatomically right ventricle and their proximal segments were parallel to each other. c. The spatial relationship between the arota and pulmonary artery was abnormal and the aorta was to the left of the pulmonary artery. d. The muscular conus (subaortic and/or subpulmonary) was showed between the two arteries. e. A muscular subaortic conus separated the aortic and mitral valves. f. There was always no muscular subpulmonary conus between pulmonary valve and tricuspid valve. g. The left ventricular outflow tract was longer and the shape was like "swan neck". h. This malformation was usually associated with ventricular septal defect (VSD), bilateral atrial appendage juxtaposition, persistent left superior venacava (PLSVC)， and other intracardiac malformations. ConclusionThe Van Praagh segmental analysis principle should be strictly followed during the scan to determine the anatomical status of each cardiac segment. The differential diagnosis of ACMGA {S,D,L} is mainly with the double outlet right ventricular (DORV）.
ObjectiveTo investigate clinical manifestations and preventive measures of tumor lysis syndrome (TLS) and to provide the basis for the integrated management of TLS. MethodsA retrospective analysis was performed on the clinical data including the clinical characteristics, auxiliary examination results before and after chemotherapy, treatment and prognosis from children with TLS treated in Beijing Children's Hospital from April 2016 to April 2019. ResultsA total of 40 patients at the age of 1 to16.3 years were included into the analysis with 28 males (70%) and 12 females. Among them, there were 8 cases of acute leukemia and 32 cases of non-Hodgkin's lymphoma. Thirty-four cases (85%) occurred TLS within 72 hours. Of 40 cases, 2 cases (5%) had nausea and vomiting, 2 cases (5%) had fever and fatigue, 7 cases (17.5%) had chest congestion and dyspnea, 3 cases (7.5%) had abdominal pain, 6 cases (15%) had low urine output and edema, and 5 cases (12.5%) had tetany. Laboratory tests showed there were 4 cases of hyperkalemia (10%), 26 cases of hyperphosphatemia (65%), 12 cases of hypocalcemia (30%) and 37 cases of hyperuricemia (92.5%). The differences between the effect of uric acid oxidase and allopurinol on reducing the level of uric acid (78.6% vs 49.9%) and the incidence of acute kidney injury (AKI) (4.3% vs 25%) were statistically significant. ConclusionPatients with hematological malignancies are prone to developing TLS in the early stage of chemotherapy. Biochemical indicators should be closely monitored in order to perform hydration and correct electrolyte disorders timely. Uric acid oxidase can effectively reduce the incidence of AKI and the mortality in the early stage of chemotherapy for patients with hematological malignancies.
Abstract Objective: To investigate the clinical features of eosinophilic gastroenteritis（EGE）in children with moderate or severe anemia as initial presentation. Methods: Medical records of EGE patients with moderate and severe anemia as initial presentation admitted to Affiliated Children's Hospital of Capital Institute of Pediatrics from January 2015 to December 2019 were retrospectively analyzed. The diagnosis and classification of EGE were performed according to Talley's and Klein's criteria. Results: A total of 6 children were included with two females and four males. The age of onset was from 1 year and 3 months old to 11 years old. All of 6 cases had symptoms of anemia as initial presentation including pale face, poor spirit and fatigue. There were 3 cases of black stool, 3 cases of abdominal pain, 1 case of vomiting, and 1 case of edema and hypoproteinemia. Blood smear showed hemoglobin 53 to 78 g·L-1 as microcytic hypochromic anemia. Blood eosinophils increased in 5 cases ［(0.75 to 4.20)×109·L-1］. The occult blood of stool was positive in 6 cases. Serum IgE increased in 5 cases. Imaging and endoscopic examination showed that 6 cases involved gastric and duodenal lesions, 3 cases involved terminal ileum lesions and 2 cases involved colon and rectum lesions. Endoscopy showed congestion, swelling, erythema, erosion and ulcers. The pathological manifestations were chronic inflammation of gastric, duodenal, colon and rectum mucosa and inherent layer of a large number of eosinophilic infiltration. Gastroscopy showed that the ulcer had not been healed in 3 cases after treatment with proton pump inhibitor. Six patients were all treated with glucocorticoid. The digestive tract symptoms disappeared within 1 week of treatment and the blood eosinophil count decreased to the normal level. Three cases with gastrointestinal ulcers required long-term maintenance of methylprednisolone. Conclusion: Children with symptoms of anemia as initial presentation should be considered not only blood system diseases, but also EGE of less obvious gastrointestinal symptoms complicated with chronic gastrointestinal bleeding. Differential diagnosis of refractory upper gastrointestinal ulcers should take EGE into consideration. Recurrence and glucocorticoid dependence are more common for children with gastric or duodenal ulcers.
Abstract Objective: To explore the clinical application value of Nanopore metagenomics sequencing in the rapid detection of pediatric respiratory tract pathogens. Methods: We collected a bronchoalveolar lavage fluid sample from a severe pneumonia patient, which was positive for adenovirus antigen by conventional tests and Mycoplasma pneumoniae and Epstein-Barr virus by PCR. The patient was discharged after recovery. After DNA extraction, Nanopore and Illumina sequencing were performed respectively. We constructed microbe reference genome database and developed real-time analysis pipeline for Nanopore sequencing data. Nanopore and Illumina sequencing data were mapped to the reference database to detect the pathogens. Results: From receipt of sample to the detection of adenovirus, Nanopore, Illumina and conventional methods took 3.2 hours, 55.5 hours and 48 hours respectively, and cost 4,200, 3,600 and 1,790 RMB respectively. We detected 1,093 adenovirus reads at 12 minutes after the start of Nanopore sequencing. A total of 4,920,000 reads were sequenced. Among them, we detected 99,284 adenovirus reads, accounting for 2.02% of all the sequencing reads. In addition to adenovirus, Mycoplasma pneumoniae and Epstein-Barr virus reads were also detected. The same sample was validated by Illumina sequencing and the detected microbial composition was similar to Nanopore. Conclusion: Nanopore metagenomics sequencing could rapidly and real-timely detect all potential pediatric respiratory track pathogens.
Abstract Objective：To explore the possible mechanism of high homocysteine (Hcy) in the pathogenesis of autism spectrum disorder (ASD). Methods：cDNA samples from children with ASD and the control group were from the preliminary study of the research team. The cell lines in the experiment included human embryonic kidney epithelial cell line HEK-293T, mouse neural stem cell line NE-4C and mouse hippocampal neuron cell line HT22. The experimental animals were wild type C57BL/6J mice. Real-time fluorescence quantitative PCR was used to compare the expression levels of methionyl-tRNA synthetase (MARS) in peripheral blood cDNA of ASD children and the control group. Tandem affinity purification method was used to detect transcription factors that interacted with MARS. Immunoprecipitation and liquid chromatography-mass spectrometry was used to detect the modification of Hcy to the transcription factor and possible lysine residue modification sites. Chromatin immunoprecipitation assay was used to verify that the binding of the transcription factor to its downstream target gene promoters was affected by MARS or Hcy in cell line and mice. The transcription levels of target genes were compared in cDNA samples from children with ASD and the control group. Results： a. The MARS transcription levels of children with ASD were higher than those of the control group (P＜0.01). MARS interacted with MeCP2. b. Hcy modified 7 lysine residues of MeCP2. The modifications of Hcy inhibited the binding of MeCP2 with DNA methylated CpG. The transcription levels of neurodevelopmental genes GRIN2A and BDNF regulated by MeCP2 increased significantly (P＜0.01). c. The transcription levels of GRIN2A, BDNF and EAAT1-4 genes in 42.9% of children with ASD were higher than the average level of the control group. The average transcription levels of EAAT2 and EAAT4 genes in children with ASD were higher than control group (P＜0.05). Conclusion： High MARS expression and high Hcy made MeCP2 become N-homocysteinylation (Hcy modification), which reduced the binding activity of MeCP2 protein and DNA-methylated-CpG, affecting the transcription levels of MeCP2 downstream neurodevelopmental genes.
