Objective To observe the global and Chinese children clinical trial registration. Methods By Using advanced search of ClinicalTrials.gov database, some search rules were limited and the number of children aged from 0 to 17 clinical trial registration was collected. We ascertained the countries to obtain the number of children clinical trial registration. According to the different groups as sub-population, recruitment and study type, registration number was further stratified for analysis.Results There were 43 349 studies had been registered in the ClinicalTrials.gov until December 31, 2015, America, Europe, Asia, Australia, Africa accounts for 53.8%, 21.27%, 14.5%, 2.30%, 4.2% from total, respectively. The top 5 countries in registration numbers were United States, Canada, China, France and United Kingdom, Mainland China ranked 9th in countries list. It was found that registration number was highly correlated with the GDP (dollars) of country (correlation = 0.92), this indicator in children series was equal to 0.62. The ratio of the number of Preparing, Recruiting, Activated and Completion projects in United States was 1∶12∶5.5∶26.5, however, this ratio was 1∶8.6∶1.6∶8.0 in China. The number of observational study was one third of interventional's. Top 5 provinces in Mainland China were Beijing, Shanghai, Guangdong, Jiangsu and Zhejiang, they accounted for 95.4%（1 151/1 207） of children clinical trial registration in Mainland China.Conclusion From the point of registration number, there is still a huge gap among China and Euro-American developed countries. Moreover, regional difference in China is very serious. Although change of concept for clinical trial registration from establishment to automatic registration is a slow and gradual process, but it can improve the quality of children clinical trial for China.
Objective To investigate the association between early sucking patterns and neurodevelopmental outcomes in preterm infants without obvious brain injury.Methods Sucking behaviors of 128 preterm infants born at 28 to 37 weeks of gestation were videotaped. The Neonatal Oral-Motor Assessment Scale (NOMAS) was used to assess initial 2-min sucking behaviors of the subjects. The subjects were divided into normal and abnormal sucking pattern groups based on the NOMAS scores at 36~37 weeks postmenstrual age. At 6 months corrected age, infants were administered the Bayley Scales of Infant Development (BISD) test and anthropometry measurements.Results The infants in abnormal sucking pattern group had significantly lower Mental Development Index and Psychomotor Development Index of the BISD than normal sucking pattern group (P=0.002, P=0.032). Infants in abnormal sucking group showed a higher rate of below average scores than normal group (P=0.026). The incoordination of sucking, swallowing, and breathing significantly increased the odds of adverse neurodevelopmental outcomes at 6 month corrected age (RR=3.53, 95%CI: 1.48-8.42).Conclusion Sucking patterns in preterm infants without obvious brain injury are associated with adverse neurodevelopmental outcomes. But the clinical predictive value of abnormal sucking patterns for developmental delay needs to be determined in a longer term follow-up. Incoordination of sucking, swallowing, and breathing may be an early signal of adverse neurodevelopmental outcomes.
Objective To evaluate the risk factors of chronic peritoneal dialysis (CPD) related peritonitis in children.Methods All end-stage renal disease (ESRD) patients who received the CPD in Children's Hospital of Fudan University were collected retrospectively. The patients were grouped as peritonitis group and non-peritonitis group. According to the consecutive follow-up data, demographic factors, dialysis characteristics and main indicators of dialysis adequacy were analyzed.Results A total of 109 children who received the CPD from 2001 to 2014 in our hospital were enrolled in this study. 60 cases (55%) were boys and the other 49 were girls. The median age started CPD was 9.9 years and median duration of dialysis was 13.4 months. 15 cases (13.8%) received continuous ambulatory peritoneal dialysis (CAPD) and the other 94 received automated peritoneal dialysis (APD). At the latest follow-up, 43 cases (39.4%) still received CPD, 50 cases (45.9%) received renal transplantation, 7 cases (6.4%) were transferred to hemodialysis, 6 cases (5.5%) died and the other 3 cases (2.8%) were lost to follow-up. 1-year, 2-year, 3 year and 5-year patient survival rate was 97.1%, 93.3%, 90.1% and 90.1%, respectively. Totally, 33 patients suffered from 57 times of peritonitis. The incidence of peritoneal dialysis related peritonitis was 1 episode per 35.1 patient-month. There were significant differences in height at the start of dialysis (P=0.01), duration of dialysis (P<0.001) and serum albumin level (P=0.01) between peritonitis group and non-peritonitis group. The results of Logistic regression analysis indicated that height SDS<-2.0 at the start of dialysis (OR=12.746, 95%CI: 2.436-66.675, P=0.003) and more than one year duration of dialysis (OR=8.162, 95%CI: 2.514-26.500, P<0.001) were the independent risk factors of peritoneal dialysis related peritonitis.Conclusion Height SDS<-2.0 at the start of dialysis and more than one year duration dialysis were the independent risk factors of peritoneal dialysis related peritonitis in children.
Objective To investigate the risk factors and prediction of unresponsiveness to intravenous immunoglobulin (IVIG) retreatment in patients with Kawasaki disease(KD).Methods From Jan 2010 to Jan 2015, the clinical and laboratory features of 81KD patients in Children's Hospital of Chongqing Medical University retreated with IVIG were retrospectively analyzed.Results Eighty one KD patients were enrolled. The incidence of IVIG retreatment - responsive group was 75.31% (61/81), while IVIG retreatment - unresponsive group was 24.69% (20/81). There were no statistical differences in the gender, age, the clinical features before or after initial IVIG treatment, the interval of IVIG for two times between two groups. Before initial IVIG, there were no statistical differences in the incidences of coronary artery lesions, laboratory features including WBC, PLT, Hb, N, CRP, ALT, AST and electrolyte between two groups. After initial IVIG treatment, there were no statistical differences in the amplitude of variation in WBC, PLT,N%, Hb and CRP between two groups.Conclusion The clinical manifestations and laboratory features before initial IVIG treatment could not predict the unresponsiveness to IVIG retreatment. Similarly, the clinical manifestations and the peripheral blood cell counts examination after initial IVIG treatment had no prediction for the unresponsiveness to IVIG retreatment.
Objective Quartile method and discriminant analysis method were used to establish cut-off value of congenital adrenal hyperplasia(CAH) screening, expecting to increase screening accuracy.Methods Newborn CAH screening data were retrospective investigated from Jun. 2012 to Jun. 2015 in Guangxi Province. 17-OHP≥30 nmol·L-1 was considered as suspected positive case. Quartile method was used according to different gestation age(＜28， -32，-36 and ≥37 weeks) to establish 17-OHP cut-off (P99) respectively. Unstandardized Fisher analysis was used to establish cut-off according to gestation age, birth weight and 17-OHP level. Recalling the suspected positive cases, after thorough clinical test, highly suspected case was performed for gene test(gold standard). Two methods were compared with gold standard respectively to calculate sensitivity and specificity of CAH diagnosis.Results In all 215 900 newborns, 1 110 were suspected positive(positive rate 0.51%), 994 were recalled(recall rate 89.6%). ①17-OHP cut-off (P99) of ＜28， -32，-36 and ≥37 weeks was 236.0、113.7、50.0 and 29.0 nmol·L-1 respectively, which was decreased as gestation age growng. These new cut-offs were used to recalculate the screening result, 547 cases were positive (including 50 cases with 17-OHP<30 nmol·L-1), while 613 former positive cases turned to negative(55.2%).②The discriminant equation was Z= (-0.207·gestation age)+ (-0.000242·birth weight)+ 0.54·17-OHP level+ 8.25, cut-off was 24.24. Using this cut-off, 439 were positive, while 671 turned to negative. ③Using these two methods together could figure out 291 positive(0.13%) cases and 819 turned to negative. ④965 recalled positive cases could be excluded by clinical test, the rest 29 cases were performed for gene test, while 12 of them were diagnosed as CAH. Quartile method, discriminant analysis method and combination of the two methods compared with gold standard, sensitivity was 100%, specificity was 5.9%, 11.8% and 17.7% respectively.Conclusion Both quartile method and discriminant analysis method can increase screening accuracy. Using these two methods together is even better in screening.
Objective To analyze the effect of empirical antibiotic therapy on the intestinal microbiota of preterm infants and its dynamic change by 16S rDNA PCR-denaturing gradient gel electrophoresis(DGGE).Methods In the period from January 2014 to January 2015, twenty-four hospitalized preterm infants in Children′s Hospital of Chongqing Medical University were enrolled and divided into piperacillin-tazobactam treatment (PT) group and antibiotic free (AF) group. The meconium and fecal samples on d3, d5 and d7 were collected during the first week of life. After DNA extraction and PCR amplification, the microbial community diversity was analyzed through DGGE fingerprints. The distributions of common dominant bacteria were investigated by TA cloning and sequencing.Results A total of 96 fecal samples were analyzed. The amplification of bacterial DNA from 24 meconium (＜12 h) was failed and DGGE analysis was not performed. ①The median (P25-P75) of Shannon index of PT group on d3, 5 and 7 was 1.64 (1.16-1.92)、1.97 (1.69-2.20) and 1.22 (0.69-2.1) respectively, and that of AF group at the same time point was 1.39 (0.94-1.94)、2.24 (2.07-2.49) and 2.38 (2.07-2.61). On d3 and d5 of postnatal life, PT and AF infants did not differ in the diversity index of the fecal bacterial community, but on d7, the Shannon index of PT group was significantly lower than that of the AF group(P<0.05). ②The result of DGGE at all the 3 time points showed that the Shannon index of AF group gradually increased during the first week of life, while the Shannon index of PT group had a tendency of decrease. ③The bacterial composition on day 7 from DGGE fingerprint showed that Klebsiella sp. was dominant (35.5% and 42.4%) and the proportion of lactobacillus sp. was low (1.6% and 0.8%)in both groups. The proportions of Enterococcus sp. and Streptococcus sp. in PT group were higher (21.0% vs 7.2%,25.8% vs 4.0%), while the proportion of Enterobacter sp. was lower than that of AF group (3.2% vs 12.8%). Veillonella sp. and Clostridium sp. could only be detected in the AF group.Conclusion The gut microbiota of preterms has a simple structure. The antibiotic therapy can reduce the diversity.
Objective To reveal the characteristics and regularity of unintentional injuries among children of the tropical island on the basis of the investigation and analysis of the epidemiological characteristics of unintentional injuries among children in HaiKou, to improve local unintentional injuries prevention level.Methods A dedicated survey record was established, the epidemiological information of unintentional injuries among children from 2012.1.1-2014.12.31 was collected in four third-grade class-A and second-grade class-A hospitals in HaiKou City.Results There were 2006 cases of unintentional injuries, with the male: female ratio 1.25:1. The number of male injury was more than female in 5-14 years group（P<0.05）,there was no difference in 1-4 years group （P＞0.05）, the children of 1-4 years group were the most of trauma，the number of children was decreased with aging（P<0.05）. From July to August and January to February more trauma occurred. Unintentional injuries occurred more at home in the rural children than urban children（P<0.01）, less at school and on road（P<0.05）. Falling and the incidence of traffic accidents occurred more in the urban children than rural children, drowning and burns were less（P<0.05）. The top three causes of death were drowning, falling and road traffic injuries .The prognosis of unintentional injuries had statistical significance in different groups（P<0.05）.Conclusion The epidemiological characteristics of unintentional injuries as drowning and traffic accidents among children were different from other areas. Government, schools, hospitals and parents should develop new effective options for prevention on the basis of the epidemiological characteristics of unintentional injuries among children to ensure the health of children.
Objective The study of pharmacogenomics focused on how mutations of essential enzyme genes would lead to different drug response. It would be of great importance to identify warfarin-response-related variants of the patients before clinical treatment, especially for pediatrics.Methods In this study, the allele frequencies of reported clinically significant warfarin-response-related variants were evaluated based on 620 WES data collected from Children Hospital of Fudan University. Then the local allele frequencies were compared with public population-based databases, including 1000 Genomes project.Results 27 warfarin-response-related variants that have clinical significance were detected in the 620 WES data that we used. These variants were distributed in 12 genes. There were 27 warfarin-related variants, and the frequency of 3 variants in our data showed no difference with European and East Asian population of 1000 Genome project（P≥0.01）, 10 of them showed no difference with East Asian （P≥0.01） but were significantly different from European population （P<0.01）, 1 variant showed no difference with European and different fromh East Asian（P≥0.01）, and 13 variants were different from both population frequency data（P<0.01）.Conclusion Warfarin-response-related variants detected in our database also show population-specificity, which indicates that sufficient genome-wide data preparation are necessary for the personized drug usage and the practice of precise medicine.
Objective To improve the recognition and treatment level of central precocious puberty in Turner syndrome (TS).Methods A case of central precocious puberty in 45,X TS was reported, and the related literatures were reviewed.Results ①A 7.5-year-old girl was referred with complaints of breast budding. Her height was 117.9 cm and weight was 32.5 kg, a physical examination revealed a Tanner stage Ⅱ for breast development and Tanner stage Ⅰ for pubic hair development, She showed no signs of Turner syndrome, such as webbed neck, cubitus valgus, high arched palate, and shield chest deformity. Lab examination: gonadotropin-releasing hormone stimulation test peak: luteinizing hormone was 11.9 U·L-1, follicule stimulating hormone was 34.2 U·L-1, estradiol was 39.3 ng·L-1, pelvis ultrasound showed enlarged ovaries, her bone age was 9.7 years. The patient was treated with gonadotropin releasing hormone analog for 2.7 years, her height was 131.4 cm and bone age was 12 years. Further, she has been given gonadotropin releasing hormone analog and recombinant human growth hormone for 2.3 years, her height was 148.4 cm and bone age was 13 years. After discontinuing drugs for 1.5 years, her height was 154.2 cm closed to genetic height. Lab examination showed luteinizing hormone was 11.9 U·L-1, follicule stimulating hormone was 50.5 U·L-1, estradiol was 38.9 ng·L-1, Chromosome analysis showed a karyotype of 45,X. ②A total of six patients associated with central precocious puberty in TS has been reported so far. Five of them were mosaic TS and other one was 46,X,del(X)(p11.2).Conclusion Central precocious puberty can occur in X-monosomy TS, the treatment of gonadotropin releasing hormone analog combined with recombinant human growth hormone can improve patient′s final height.
bjective To summarize the clinical features and gene mutation characteristics of a de novo COL1A2 gene mutation in a fetus with severe osteogenesis imperfect (OI), and to provide evidence for prenatal counseling.Methods DNA was extracted from the fetal abortion tissues, and primers of the whole exons and splicing sites of COL1A1 and COL1A2 genes were designed. Using Sanger sequencing, the fetal sequences of the whole exons and splicing sites of COL1A1 and COL1A2 genes were analyzed and confirmed with the parents' samples. According to HGMD, literatures on clinical symptoms of the diseases caused by COL1A2 mutation were reviewed.Results The variants on both COL1A1 and COL1A2 gene were detected. On COL1A2 gene a de novo heterozygous mutation (c.3142G>T, p. Glu1048Cys) was detected, which had never been reported in dbSNP, HGMD and osteogenesis imperfecta & Ehlers-Danlos syndrome variant databases. Compared with the common database and online prediction software the mutation was predicted to be a the disease-causing mutation. HGMD professional version was searched with "COL1A2"and 387 disease-causing mutations were found to be related to 21 diseases or their subtypes. Ninety-two percent of the mutations caused OI or its subtypes; others caused Ehlers-Danlos syndrome or its subtype. Combined with the clinical symptoms of the disease caused by COL1A2 gene, the fetus was more consistent with the OI type Ⅱ. Conclusion A fetus OI type Ⅱ caused by a de novo mutation in COL1A2（c.3142G>T, p. Glu1048Cys）was diagnosed with prenatal ultrasound imaging and genotyping. Glycine in 400 to 480 amino acid and MLBR 3 region of the protein encoded by COL1A2 gene replaced by aspartate acid or glutamic will cause sever OI. This article provides the basis for accurate prediction of fetal outcome and clinical decision-making.
Objective To get a better understanding and to explore a proper criteria for early diagnosis and treatment of nephrotic syndrome(NS)with cerebral venous thrombosis (CVT) in children from clinical analysis. Methods From Jan. 2012 to Sep. 2015, data of children of NS with CVT who had been diagnosed by brain CT scan and head MRI in Shanghai Children's Hospital were enrolled. Clinical symptom features, laboratory data and radiographs findings, treatment effect and prognosis of all cases were collected and analyzed.Results Four cases of NS patients with CVT were included in the analysis. Four cases were all male. The age range was from 5 years 4 months to 11 years 4 months. When they had CVT, the onset of NS was 1 months to 7 years later. Clinical manifestations of all patients were different, and they were mainly manifested as neurological symptoms. And they all had no positive signs of nervous system. D-dimer and FDP of 3 cases abnormally elevated significantly, and AT-Ⅲ dropped. After these children had been diagnosed, D-dimer and FDP increased further. Serum albumin levels of 4 cases obviously decreased, and total cholesterol obviously increased. The patients with clinical symptoms were requested to do head enhanced MRI+ MRV+MRA on the same day or the second day, and 3 cases were confirmed with the left sigmoid sinus thrombosis, 1 case was cerebral embolism. 3cases were treated immediately with urokinase thrombolysis, low molecular weight heparin calcium and dipyridamole anticoagulant after confirmed diagnosis. One child with cerebral embolism had symptomatic treatment and anticoagulation therapy. Patient's symptoms were rapidly relieved. Follow-up with head enhanced MRI+ MRV of 3 cases showed that intracranial abnormal signals had been absorbed with different degree.Conclusion NS with CVT in children was easy to occur in the left sigmoid sinus thrombosis. When suspected abnormal nervous-mental system symptom appeared during NS course, timely head MRI related examination may be helpful to make early diagnosis of CVT. Prompt thrombolysis therapy had a favourable prognosis.
Objective To report two cases with neonatal respiratory distress syndrome(NRDS) carrying surfactant protein C gene(SFTPC) mutations.Methods The clinical, radiological and genetic testing data of the two cases were analyzed and related literatures were reviewed.Results The two cases were a full-term(38+3 weeks) newborn and a premature(35+2 weeks) neonate respectively. Both newborns developed respiratory distress shortly after birth requiring surfactant replacement and positive-pressure assisted ventilation. Imaging findings were consistent with NRDS for each case. Various etiology examinations were negative. Family history of pulmonary diseases was negative for each case. A heterozygous missense SP-C mutation SFTPC: c.68G >G/A,p.R23Q was identified in the full-term newborn which had not been reported yet. A heterozygous missense SP-C mutation SFTPC: c.115G>G/T,p.V39L was detected in another case which had been reported to be a cause of childhood interstitial lung disease. Seven RDS cases with SFTPC mutations and detailed clinical information were reported in six articles. Altogether with the two cases in this study, all nine cases presented respiratory distress at birth and required surfactant administration and mechanical ventilation with a main radiological feature of bilateral diffuse haziness and/or interstitial changes. As for the outcomes, two cases died, one survived with interstitial lung disease, one had bronchopulmonary dysplasia, four stayed healthy and one was lost in the follow-up.Conclusion Chinese patients with NRDS carrying SP-C gene mutations may be disease-causing. Identification of these gene mutations will be beneficial to early intervention, prognosis evaluation and genetic counseling.
Objective To study the clinical profile of the posterior reversible encephalopathy syndrome (PRES) in children with systemic lupus erythematosus (SLE).Methods The analysis was based on 4 PRES patients with SLE admitted to our department (PUMCH) and 11 cases retrieved from PubMed to analyze the clinical manifestation, PRES features, laboratory abnormalities, treatment and outcomes.Results Firstly, 4 cases were diagnosed in our hospital, disease duration of SLE ranged from 1month to 63months. Nephritis was found in all these patients, and methylprednisolone and cyclophosphamide pulse therapy was administered in one patient. Four children with PRES presented seizures, headache and hypertension. Magnetic resonance showed predominantly posterior distribution involved. Secondly, 11 cases were retrieved from PubMed, together with our 4 cases, 15 cases (14 girls) were analyzed. The minimum age was 8 years. The average duration between SLE diagnosis and primary onset of PRES was 6 months (ranged from 1 month to 6 years). Clinical manifestations of PRES in children with SLE were seizures (all of 15 cases, 100.0%), headache (10/15, 66.7%), vomiting (7, 46.7%), loss of consciousness (9, 60.0%) and vision loss (7/15, 46.7%). Hypertension was seen in all 15 patients; 12 had nephritis; 4 were treated with methylprednisolone pulse therapy; 3 were treated with cyclophosphamide pulse therapy; 2 were treated with hydroxychloroquine; 1 was treated with cyclosporine A; 1 was treated with Rituximab. PRES occurred 2 days to 4years after immunosuppressive drugs therapy. All patients underwent MRI and the white matter of posterior region was mainly involved, and involvement in areas such as parietal lobes, brain stem and cerebellum was also found. 12 cases were treated with antihypertensive drugs. 10 cases were treated with anticonvulsant drugs in short duration. Glucocorticoid and immunosuppressive drug were used in 9 patients with active lupus, but they were withheld or reduced if the child was not accompanied by active lupus. All patients improved without neurological deficit. Follow up MRI showed marked improvement.Conclusion PRES in children with SLE presented seizures, headache, vomiting, loss of consciousness and vision loss. SLE patients with lupus nephritis, hypertension and use of immunosuppressive drug could precede the occurrence of PRES. Brain MRI is important for diagnosis of PRES. Early diagnosis, prompt control of blood pressure and seizure and appropriate use of glucocorticoid and immunosuppressive drug are keys to successful management of PRES.
Objective To investigate the levels of serum amyloid P component in the lung and brain tissues in different stages in fourteen-day old BALB/c suckling mice infected with EV71.Methods Mice were randomly divided into two groups, the experimental group with 35 suckling mice and the control group with 29 suckling mice. Animals in the experimental group were injected intraperitoneally with 0.1 mL 1 × 107 TCID50/mL EV71 stocks, and those in the mock control group were mock-infected with an equal amount of phosphate-buffered saline (PBS). Mice were monitored daily to observe activity, rash, reactivity, hair color, physical activity and paralysis, and experimental group was divided into 5 stages according to the signs and symptoms of infection. Mental reaction period (day 2), partial paralysis period (day 3), paralysis stage (day 3), death (3-4 days) and the convalescent phase (on day 10 mice were still alive). 6-8 mice that showed lethargy, weakness, limb shake, or paralysis were chosen, and killed upon symptom onset. Other survivors were monitored for up to 10 days and then killed. Tissue samples, including brain and lung, were collected from the mice. Levels of SAP were determined by enzyme-linked immunosorbent assay (ELISA) and the changing trend of SAP levels in different stages was analyzed.Results ①Mice showed less activity on day 2 post-infection and some were limb shake, some even paralysis to death on day 3 post-infection. It suggested that EV71 infected mice model was established successfully. There was no significant difference in body weight between the experimental group and the control group during the period of mental reaction, but the difference was statistically significant between two groups in the period of partial paralysis, paralysis, death and recovery period. ③ There was significant difference of SAP levels in both lung and brain tissues between the experimental groups and controls in five stages (P<0.05). In the experimental group, level of brain SAP was 2-9 times than that in the control group, and level of SAP in lung tissues was 1.5-8 times than in the control group. Brain SAP levels in experimental group in partial paralysis, paralysis period and period of death were significantly higher than those in mental reaction period (P<0.05). But it showed no statistical significance in lung between partial paralysis, paralysis, death and the convalescent. Levels SAP of recovery period decreased significantly in brain and lung tissue than those in period of mental reaction, but still higher than the level of the control group.Conclusion SAP is highly expressed in the brain and lung tissues of suckling mice infected with EV71, and it may be used as an index for judging the severity and prognosis of EV71 infection.
2014年WHO国家结核病规划指南——儿童结核病管理（第2版）系列解读之——儿童结核病的诊断方法及新进展
