Objective:To establish the growth standard curves of weight/head circumference ratio and length/head circumference ratio for Chinese newborns, in order to provide reference for the comprehensive assessment of physical growth at birth. Methods:Singleton live births with gestational age of 24-42 weeks were investigated in thirteen cities including Beijing, Harbin, Xi'an, Shanghai, Nanjing, Wuhan, Guangzhou, Fuzhou, Kunming, Tianjin, Shenyang, Changsha and Shenzhen from June 2015 to November 2018, and those newborn babies who were not healthy or whose mothers had high health risk were excluded. Percentile reference values and growth curves of weight/head circumference ratio and length/head circumference ratio of newborn infants with gestational age of 24-42 weeks were established by the Generalized Additive Model for Location, Scale and Shape (GAMLSS). Results:A total of 24,375 neonates with gestational age of 24-42 weeks were included in this study, with 13,197 males and 11,178 females. Weight/head circumference ratio presented a rapid increase by gestational age, and length/head circumference ratio showed an increase below 37 weeks of gestation but no obvious increase above 37 weeks. The 3rd, 10th, 25th, 50th, 75th, 90th and 97th percentile reference values and growth curves of weight/head circumference ratio and length/head circumference ratio were obtained for male and female neonates with gestational age of 24-42 weeks. Weight/head circumference ratios of males in all gestational ages were slightly higher than those of females, with the differences of 0.21 to 0.37 kg/m at the 10th, 50th and 90th percentile curves. There was no substantial differences for length/head circumference ratio between males and females, with the difference of -0.01 to 0.01 in all gestational ages at the 10th, 50th and 90th percentile curves. The fitted values of weight/head circumference ratio were very close to the observed values at main empirical percentile curves, and the fitted values of length/head circumference ratio were consistent with the observed values above 32 weeks of gestation but slightly different from the observed values below 32 weeks of gestation. Conclusion:Based on contemporary, nationally representative, large sample data, this study established standardized reference values and growth curves of weight/head circumference ratio and length/head circumference ratio for Chinese newborn infants with 24-42 weeks of gestation, which might be useful for clinical practice and scientific research.
Objective：To explore the association between parent-child interaction and early childhood development, and to inform further positive parenting intervention. Methods：This is a cross-sectional survey. In November 2016, stratified cluster random sample method was used to select newly enrolled preschoolers from Shanghai kindergartens for an online survey of Chinese Parent-Child Interaction Scale (CPCIS) and the Early Human Capability Index (eHCI). Children's demographic information included gender, age, maternal education level, household annual income, primary caregiver, siblings, and parental marital status. CPCIS includes 12 items, and the total scores added from all items were used in the analysis. The CPCIS total score is divided into <P25, ~P50, ~P75 and >P75 according to the quartiles. In the eHCI, this research focused on children's overall development, literacy and numeracy. Results：A total of 19,051 preschoolers were included in the analysis. The mean age was 3.73 (95% CI: 3.73-3.74) years, and 52.45% (95% CI: 51.45-53.44) was male. The reliability of CPCIS was at a high level (α=0.88), and the reliability of overall development (α=0.87) , literacy and numeracy (α=0.84) were both at a high level. The lower parent-child interaction frequency was associated with male, grandparents or others as the primary caregiver, parents divorce, mothers with the education level of or below high school, household annual income <100,000 RMB, and children with siblings or older age (continuous variables). The average score of CPCIS in Shanghai was 2.68 (95% CI: 2.66-2.70). Adjusting for gender, age, maternal education level, household annual income, primary caregiver, siblings, and parental marital status, the parent-child interaction level was positively correlated with the overall development, literacy and numeracy. Conclusion：Parent-child interaction is associated with early childhood development, indicating benefits of parent-child interaction intervention for promoting early childhood development.
Objective:To determine the value of stool color card and bilirubin measurements in biliary atresia(BA) screening. Methods:According to the retrieval method, literature was searched in PubMed, Embase, Medline from the establishment of the database and in the Chinese CBM database from January 1, 2000 to April 26, 2020. Literature was screened and selected based on the inclusion and exclusion criteria set by the ongoing clinical practice guideline on BA. The QUADAS-2 scale was used to evaluate the risk of bias and applicability concerns. Data were extracted and diagnostic parameters were calculated for the combined data. ResultsF:ive studies on stool color card screening were included in this meta-analysis. The combined sensitivity and specificity were 84% (95% CI: 76%-90%) and 100% (95% CI: 100%-100%) respectively with I2 of 0% and 86.37%. The AUC was 0.99 (95% CI: 0.98-1.00). One study was included for bilirubin detection of heel-prick blood by mass spectrum. The sensitivity was 100% (95% CI: 56.1%-100%) and specificity was 99.9% (95% CI: 99.9%-99.9%). Ten studies were included in the liver biopsy meta-study. The combined sensitivity was 96% (95% CI: 91%-98%), specificity was 96% (95% CI: 92%-97%), and the AUC was 0.98 (95% CI: 0.97-0.99). MMP-7 included 4 studies, with sensitivity of 96% (95% CI: 93%-98%) and specificity of 91% (95% CI: 85%-95%). AUC of SROC curve was 0.97 (95% CI: 0.95-0.98). Seven studies were included in meta-analysis of the duodenum drainage fluid study. The combined sensitivity was 96% (95% CI: 92%-96%), specificity was 86% (95% CI: 79%-91%), and the AUC was 0.97 (95% CI: 0.96-0.98). The GGT test included 15 studies. The sensitivity was 81% (95% CI: 73%-88%) and specificity was 79% (95% CI: 72%-84%). The SROC curve showed the area under curve (AUC) was 0.87 (95% CI: 0.83-0.86). Conclusion:Stool color card is a noninvasive, convenient and effective way to screen biliary atresia. Bilirubin measurements from neonatal heel stick, however, need more clinical trials to determine its value in BA screening. Duodenal drainage and liver biopsy are both valuable way to diagnosis BA, but MMP-7 exceeds those tests in its convenience and precision. Although as a clinical routine, GGT tests showed a limited value in diagnosing BA.
Objective：To systematically evaluate the protection and risk factors of central venous catheter (CVAD)-related thrombosis. Methods：A systematic search was performed in both of English and Chinese databases of Ovid-medline, Embase, Cochrane Library, CNKI and SinoMed for cohort and case-control studies from the time of their establishment to November 16th, 2020. Both of hospitalized neonates and young adults with CVADs were included and the pediatric population who used CVAD for renal replacement therapy was excluded. The quality of evidence body was evaluated by GRADE methodology. Results：Thirteen cohort studies and 1 nested case-control study were included. There were 13 articles published after the year of 2000, including 10 from North America and Europe. CVAD-related thrombosis (CRT) was diagnosed by venography or intravenous ultrasonography (incidence rate 3.3%-30.3 %). A total of 3,848 CVAD catheters were included in the analysis, including 538 PICCs, 509 non-tunnel catheters, 241 tunnel catheters and 583 totally implantable venous access ports. Among them, there were 360 in the internal jugular vein, 354 in the subclavian vein and 162 in the femoral vein. Two hundred and nineteen catheters had catheter dysfunction. CVAD-related factors included non-tunnel catheter (OR=0.37, 95%CI: 0.21-0.63), femoral venous catheterization (OR=1.99, 95% CI: 1.15-3.44), catheter dysfunction (OR=2.44, 95%CI: 1.59-3.76), and every additional day of catheter indwelling time (OR=1.01, 95%CI: 1.00-1.02) with statistically significant difference. Disease state factors included acute leukemia (OR=2.96, 95%CI: 2.02-4.32) and there was statistically significant difference. Factors of treatment process included the usage of asparaginase (OR=3.86, 95%CI: 1.82-8.20) and parenteral nutrition (OR=1.85, 95%CI: 1.25-2.75). The overall quality of evidence was very low. Conclusion：For the occurrence of CRT, non-tunnel catheter is a protection factor and risk factors are acute leukemia, sepsis, femoral venous catheterization, catheter dysfunction, parenteral nutrition in treatment, and long catheter indwelling time.
Objective：To study the relationship between respiratory tract Ureaplasma urealyticum (UU) colonization and bronchopulmonary dysplasia (BPD) in preterm infants. Methods：This is a retrospective cohort study. We enrolled hospitalized premature infants who received respiratory secretions test for UU. UU positives (colonization) and negatives were assigned to the exposure and non-exposure group, respectively. Discharge from NICU was taken as the end of the cohort. We observed the relationship between UU colonization in preterm infants and BPD. Preterm infants with UU colonization were divided into different subgroups according to the cut-off value of ROC curve between UU-DNA copies and the start time of antibiotic therapy. Results：A total of 399 preterm infants were included in the analyses with 105 cases (26.3%) of UU colonization and 294 cases of non-UU colonization. The gestational age and birth weight of infants with UU colonization were lower than those of infants in the control group. But the proportion of premature rupture of membranes and moderate or severe BPD were higher. After adjusting for several covariates, no significant relation was found in BPD between infants with UU colonization and infants without colonization. But UU-colonization might be related to higher oxygen demand (OR=4.22, 95%CI: 1.34-13.26). UU colonization with higher copies(≥4.47×105·mL-1), and treatment starting later than 8 days after birth were related to a higher incidence of BPD. Conclusion：Respiratory tract UU colonization is not significantly related to the risk of BPD in preterm infants. Late drug treatment and higher DNA copies may be risk factors for BPD.
Objective：To investigate the related indicators associated with poor short-term prognosis of ischemic stroke (IS) in PICU, and to establish a multivariate prognostic prediction model for IS in PICU. Methods：The consecutive hospitalized patients with acute IS who were admitted to PICU in Children's Hospital of Fudan University from January 2013 to December 2018 were included. Short-term prognosis was evaluated according to Pediatric Cerebral Performance Category score (PCPC) at hospital discharge. The poor prognosis was defined as PCPC≥4 at hospital discharge, and the good prognosis was PCPC＜4. Univariate analysis and binary logistic stepwise regression analysis were performed to screen the related indicators associated with poor prognosis including patients' basic information, clinical situation, imaging and VEEG characteristic. A multivariate prognostic prediction model was established based on the above predictive indicators, and its internal effectiveness was evaluated. Results：A total of 114 patients with IS who met the inclusion and exclusion criteria of this study were included in the analysis with 64 males (56.1%) and 50 females. The median age was 30.0 (9.0-102.8) months. There were 78 cases (68.4%) with focal manifestations, 101 cases (88.6%) with systemic manifestations and 65 cases (57.0%) with both focal and systemic manifestations. Sixty-one cases (53.5%) had symptomatic ictus epilepticus after IS. The modified GCS was evaluated when IS patients were admitted to PICU, ranging from 3 to 15(10.5±3.2). Arterial IS (112 cases) accounted for 98.2% of all IS. The infarctus laterally involved 42 cases (36.8%) of bilateral brain simultaneously, 37 cases (32.5%) of left brain and 35 cases (30.7%) of right brain respectively. There were 70 patients(61.4%) with Synek classification score of VEEG≥3. Recurrent IS occurred in 8 cases (7%), 7 of which were males. The median interval between recurrence and the first onset was 4.5 (1.3-14.0) months. There were 81 (71.1%) cases with good prognosis and 33 cases with poor prognosis. Seven patients died (mortality rate 6.1% at discharge). Among the rest 107 survivors, 95 cases (88.8%) had different degree and varied forms of dysfunction including dyskinesia, cognitive impairment, speech disorder and symptomatic epilepsy in a descending order of frequency. None of the dead patients were recurrent cases and all of the dead patients had systemic manifestations, 4 of which had acute symptomatic ictus epilepticus after IS. The modified GCS (OR=0.601, 95%CI: 0.460-0.784) and Synek classification score of VEEG (OR=4.518, 95%CI: 1.682-12.137) were independent predictors of poor prognosis of pediatric IS in PICU. The internal validation of the multivariate prognostic prediction model which was established based on the above predictors showed that the prediction accuracy was 89.5% and the area under ROC curve of the prediction probability was 0.946(95%CI: 0.906-0.986). Conclusion：The incidence of pediatric IS in PICU was low (1.38%), the overall short-term prognosis was good, the mortality rate at discharge was low, but the disability rate was high. The combination of modified GCS and Synek classification score of VEEG got high prediction efficiency which had potential clinical application value.
Objective: To investigate the consistency between the Greulich-Pyle method and the China 05 method for assessing bone age in normal children, and to compare the assessment results with the chronological age. Methods: All subjects, collected from 5 primary and secondary schools in Xuhui and Jing'an districts of Shanghai, were taken with orthotopic left-handed DR digital radiography, and two experts performed the GP method and the China 05 method, respectively. Pearson's analysis was used to analyze the correlation of the two methods and Kappa analysis was used to test the consistency of differences between the assessment results and the chronological age. Results: A total of 4,151 students, including 2,184 males and 1,967 females, completed the bone age sampling from December 2015 to October 2016. Pearson's analysis showed two assessment results were highly correlated in general and by developmental stages(r=0.888-0.988, P<0.000 1). The correlation coefficient r between the two methods and the chronological age ranged from 0.487 to 0.851 (P<0.001 for both). Kappa analysis showed the Kappa values were below 0.5 for both boys and girls in general and by age. The GP method values were less than that of the China 05 method (P<0.000 1) for males before the age of 10 and females before the age of 9. Assessment results of the two methods were basically the same for females at the age of 9 (P> 0.05) and the GP method values were greater than that of the China 05 method (P< 0.000 1) for males and females after the age of 9. The China 05 results were closer to the chronological age for both sexes. Conclusion: The consistency between the two methods of bone age assessment is low for normal children and adolescents, and the assessment of maturity status should be combined with other growth indicators. In this sample, the China 05 method was slightly better than the GP method.
Objective: To analyze the clinical and imaging features of children with posterior reversible encephalopathy syndrome(PRES). Methods: Clinical data and imaging results of the patients with PRES diagnosed in Children's Hospital of Chongqing Medical University from January 1st, 2012 to April 30th, 2019 were retrospectively reviewed. The correlations between recorded scores of clinical manifestations, imaging findings and gender, age, hypertension and cytotoxic drugs were analyzed. Results: A total of 55 children were included into the analysis with 33 males(60%) , and the median age of onset was 10(1~15) years old. The common clinical manifestations were convulsive seizures (92.7%) and dizziness and headache (52.7%). There were 32 children with convulsion as the first manifestation. After removing risk factors and performing symptomatic treatment, the symptoms of 49 cases (89.1%) were relieved. Seizures recurred in 2 children and only 1 child developed cerebral hernia. In univariate analysis, scores of neurological symptoms were higher in girls than that of boys (6 vs 4, P<0.05). Age, severity of hypertension, glucocorticoids and cytotoxic drugs were not correlated with severity of clinical symptoms and imaging results. Conclusion: The most common clinical manifestation of children with PRES is convulsion. The clinical neurological symptoms of female children may be more serious than those of male ones. For children with hypertension or using glucocorticoids or immunosuppressants, convulsions should be kept vigilant by pediatricians.
Objective: To analyze the clinical characteristics and gene mutations of juvenile myelomonocytic leukemia (JMML). Methods: The clinical data of children diagnosed with JMML from January 2013 to December 2019 in the Department of Pediatric Hematology and Oncology of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: Among the 19 children with JMML, there were 14 males and 5 females. The age at the time of visit was (16.8±16.4) months old, and 5 patients were older than 2 years old. The most common symptoms at the time of the visit were fever and pale skin. All 19 cases had hepatosplenomegaly, with the maximum of 12 cm and 13 cm under the costal margin of the liver and spleen, respectively. Lymphadenopathy was found in 11 cases, and the common sites were neck and axilla. The WBC, monocyte and PLT in peripheral blood were 37.3×109·L-1, 7.2×109·L-1 and 32×109·L-1 , respectively. Four children had higher hemoglobin F (HbF) level than normal. Viral IgM was positive in 12 cases, with CMV being the most common (8 cases). The median percentage of primordial granulocytes in the bone marrow of 15 children was 1.2% (0-6.4%). Chromosome karyotype analysis was performed in 7 cases, and chromosome 7 monosomy was found in 2 cases. The BCR/ABL1 fusion gene test was negative in 15 children. The number of patients with KRAS, NF1 and NRAS gene mutations was 4, 2 and 1, respectively. Fourteen cases gave up treatment. Five patients were followed up, and as of June 1, 2020, three died and two survived, with a median survival time of 2 (1-34) months. Of the two surviving children, one was treated with chemotherapy and awaited hematopoietic stem cell transplantation, and the other one was transformed into acute myeloid leukemia M5, which was treated with chemotherapy according to the treatment regimen of acute myeloid leukemia. None of the 3 deaths was treated with chemotherapy, and the survival time was 1 to 2 months. Conclusion: In this study, KRAS gene mutations were common in JMML children. Children with untreated JMML had shorter survival time.
Objective: To summarize the clinical and genetic characteristics of SATB2-associated syndrome (SAS), and to provide evidence for early intervention and prenatal counseling. Methods: Children diagnosed as SAS by genetic testing were recruited from January 2016 to June 2020 in Children's Hospital of Fudan University. We analyzed the clinical and genetic features of these patients retrospectively. According to Human Gene Mutation Database(HGMD) and PubMed, literature on clinical phenotype and genetic characteristics of SAS were reviewed. Results: Thirteen children with SAS were included in this study, consisting of 7 males and 6 females. The age of genetic test ranged from 3 days to 9 years and 7 months (median age of 14 months). After psychomotor development was evaluated in 13 patients during the follow-up, all of them presented with developmental delay and all children over 1 year old had language retardation. Of the 8 cases undergoing brain MR examinations, 7 cases showed abnormal brain imaging. Four cases presented epilepsy. Two patients presented bone dysplasia and 4 individuals were hypotonia. Congenital heart defects were identified in 2 children. Physical examination showed that all of 13 children had malformation of small jaw and teeth, 4 cases were diagnosed with cleft palate, 3 patients' weight was 2 standard deviations lower than those of their peers, 2 children presented salivation, and 1 case occurred corneal leukoplakia. There were 4 cases of recurrent pulmonary infection and 1 patient accompanied with congenital laryngomalacia and vocal cord paralysis. Thirteen mutations of SATB2 were detected in 13 patients, including 6 missenses mutations (p.E436A, p.L261P, p.L626P, p.R399C, p.A590T, p.E566K ), 2 nonsense mutation (Q666Ter, R239 Ter), and 5 copy number variations resulting from deletion/duplication in region 3 of the long arm of chromosome 2. The mutations of R239 Ter and E566K were recorded in HGMD, and other variations were novel. Conclusion: SATB2-associated syndrome involves multiple system abnormalities, which needs to be confirmed by genetic testing. SATB2 gene can be regarded as an important candidate gene for the screening and diagnosis of neurodevelopmental disorders with unknown causes.
Objective: To summarize initial clinical characteristics and gene mutations of infants with methylmalonic acidemia (MMA) and to analyze genotype-phenotype correlation. Methods: Infants diagnosed as MMA by genetic testing were recruited from June 2016 to June 2019 in Center for Molecular Medicine of Children's Hospital of Fudan University. Clinical characteristics and genetic test results were included for analysis. We compared patients' phenotypes based on genotype. Results: Forty-one infants were included in this study. Of them, twenty-six patients were males and the median age of onset was 21 days. Totally, 25 patients referred to hospital at neonatal time, 12 patients referred to hospital in 28 days to 6 months of age, and 4 patients referred to hospital in 6 months to 12 months of age. The most common chief complaints were poor postnatal response (24 patients) and suspected MMA by newborn screen (8 patients). Two genes (MUT and MMACHC) were detected in these patients and forty-seven kinds of pathogenic or likely pathogenic variants were detected. The hot mutations included c.729_730insTT, c.323G>A, and c.1677-1G>A for MUT gene. For MMACHC gene, c.609G>A, c.567dupT, and c.80A>G were hot mutations. A total of thirty-three patients presented clinical features, 22 patients detected with MUT gene variations and 11 patients detected with MMACHC gene variations. For two gene variations, the common clinical characteristics were dystonia, abnormal breathing, and feeding intolerance. No statistical differences were found in these two groups. Compared with patients with MMACHC mutations, patients with MUT mutations were more easily presented acidosis (50.0% vs 9.1%, P=0.027); however, patients with MMACHC mutations were easily presented cardiomyopathy than patients with MUT mutations (36.4% vs 4.5%, P=0.037). A total of five patients gave up treatments and died. Conclusion: Infants, who presented with poor response, dystonia, abnormal breathing, and feeding intolerance, should be consider the possibility of MMA.MMA patients with MMACHC variations were easily presented cardiomyopathy and patients with MUT variations were easily presented acidosis.
