Expert Consensus on the Prevention and Treatment of Chronic Hepatitis B in Children

The aim of this consensus is to standardize the prevention, diagnosis, and treatment of chronic hepatitis B in children and to achieve the goal of “eliminating viral hepatitis as a major public health threat by 2030” issued by the World Health Organization. Formulated by organized experts of the Chinese Society of Infectious Diseases and Chinese Society of Hepatology, Chinese Medical Association;Group of Infectious Diseases, Chinese Pediatric Society, Chinese Medical Association;and the National Clinical Research Center for Infectious Diseases (Beijing), the consensus provides the latest evidence and recommendations for the prevention, diagnosis, and treatment of chronic hepatitis B in children.

Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study

Background:Antenatal corticosteroids(ACS)can significantly improve the outcomes of preterm infants.This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units(NICU)and to explore perinatal factors associated with ACS use,using the largest contemporary cohort of very preterm infants in China.Methods:This cross-sectional study enrolled all infants born at 24^(+0)to 31^(+6)weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st,2019 to December 30th,2019.The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery.Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage.Results:A total of 7828 infants were enrolled,among which 6103(78.0%)infants received ACS.ACS use rates increased with increasing gestational age(GA),from 177/259(68.3%)at 24 to 25 weeks’gestation to 3120/3960(78.8%)at 30 to 31 weeks’gestation.Among infants exposed to ACS,2999 of 6103(49.1%)infants received a single complete course,and 33.4%(2039/6103)infants received a partial course.ACS use rates varied from 30.2%to 100%among different hospitals.Multivariate regression showed that increasing GA,born in hospital(inborn),increasing maternal age,maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS.Conclusions:The use rate of ACS remained low for infants at 24 to 31 weeks’gestation admitted to Chinese NICUs,with fewer infants receiving a complete course.The use rates varied significantly among different hospitals.Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.

Characteristics of home oxygen therapy for preterm infants with bronchopulmonary dysplasia in China:results of a multicenter cohort

Background Home oxygen therapy(HOT)is indicated upon discharge in some preterm infants with severe bronchopulmonary dysplasia(BPD).There is a lack of evidence-based consensus on the indication for HOT among these infants.Because wide variation in the institutional use of HOT exists,little is known about the role of regional social-economic level in the wide variation of HOT.Methods This was a secondary analysis of Chinese Neonatal Network(CHNN)data from January 1,2019 to December 31,2019.Infants at gestational ages<32 weeks,with a birth weight<1500 g,and with moderate or severe BPD who survived to discharge from tertiary hospitals located in 25 provinces were included in this study.Infants with major congenital anomalies and those who were discharged against medical advice were excluded.Results Of 1768 preterm infants with BPD,474 infants(26.8%)were discharged to home with oxygen.The proportion of HOT use in participating member hospitals varied from 0 to 89%,with five of 52 hospitals’observing proportions of HOT use that were significantly greater than expected,with 14 hospitals with observing proportions significantly less than expected,and with 33 hospitals with appropriate proportions.We noted a negative correlation between different performance groups of HOT and median GDP per capita(P=0.04).Conclusions The use of HOT varied across China and was negatively correlated with the levels of provincial economic levels.A local HOT guideline is needed to address the wide variation in HOT use with respect to different regional economic levels in countries like China.

Genetic background of idiopathic neurodevelopmental delay patients with significant brain deviation volume

Background:Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay(NDD),but its genetic basis has not been fully characterized.This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume(WBDV).Methods:We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years.We recruited only NDD patients without acquired etiologies or positive genetic results.Cranial magnetic resonance imaging(MRI)and clinical exome sequencing(2742 genes)data were acquired.A genetic burden test was performed,and the results were compared between patients with and without significant WBDV.Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.Results:We recruited a total of 253 NDD patients.Among them,26 had significantly decreased WBDV(<-2 standard deviations[SDs]),and 14 had significantly increased WBDV(>+2 SDs).NDD patients with significant WBDV had higher rates of motor development delay(49.8%[106/213]vs.75.0%[30/40],P=0.003)than patients without significant WBDV.Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV.Analyses of the literature further demonstrated that these genes were not randomly identified:burden genes were more related to the brain development than background genes(P=1.656e^(-9)).In seven human brain regions related to motor development,we observed burden genes had higher expression before 37-week gestational age than postnatal stages.Functional analyses found that burden genes were enriched in embryonic brain development,with positive regulation of synaptic growth at the neuromuscular junction,positive regulation of deoxyribonucleic acid templated transcription,and response to hormone,and these genes were shown to be expressed in neural progenitors.Based on single cell sequencing analyses,we found TUBB2B gene had elevated expression levels in neural progenitor cells,interneuron,and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.Conclusion:Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay,which could be explained by the genetic differences characterized herein.

Identification of eight novel mutations in 11 Chinese patients with maple syrup urine disease

Background Maple syrup urine disease(MSUD)is an autosomal recessive inherited disorder that affects the degradation of branched-chain amino acids and is associated with acute and chronic brain dysfunction.This study presents 11 new patients with MSUD and describes the clinical characteristics and gene mutations reported in Chinese individuals.Methods During 2011–2018,11 pedaitric patients with MSUD from 11 Chinese families were analyzed based on clinical characteristics and mass spectrometry,with confirmation via gene sequencing.Novel mutations affecting protein function were predicted with Mutation-Taster,PolyPhen-2,CADD and SIFT software.3D models of the mutated proteins were generated by using the SWISS-MODEL online server,and the models were visualized in PyMOL.The characteristics and gene mutations in patients with MSUD were analyzed retrospectively.Results Seventeen mutations in the BCKDHA,BCKDHB and DBT genes were found,8 of which are novel:c.55C>/T,c.349C>T,c.565C>T,c.808G>A,c.859C>G,and c.1270dupC in BCKDHA;c.275-2A>G in BCKDHB;and c.1291C>T in DBT.Eight patients died.Two patients had severe mental retardation and were physically handicapped.One patient with the intermediate type had relatively good prognosis,with mild psychomotor retardation and adiposity.Four mothers underwent amniocentesis for prenatal diagnosis during their second pregnancy;two fetuses were wild type,and two were carriers of one heterozygous mutation.Conclusions Eight novel mutations were associated with MSUD in Chinese patients.Prenatal diagnosis was successfully performed by genetic analysis.Mutations in the BCKDHB gene were found in the majority of Chinese patients with MSUD.

CYP2C9^(*)3 Increases the Ibuprofen Response of Hemodynamically Significant Patent Ductus Arteriosus in the Infants with Gestational Age of More Than 30 Weeks

Hemodynamically significant patent ductus arteriosus(hsPDA)is a severe condition in newborns.Ibuprofen is an effective treatment to reduce the severe complications and the need for surgical treatment.Several single-nucleotide polymorphisms(SNPs)were related to the ibuprofen metabolism,treatment effects,and the onset of side effects.The effects of SNPs on hsPDA response after ibuprofen treatment are unknown.Therefore,in this study,we recruited hsPDA patients with standard ibuprofen treatment.Those patients had participated in China Neonatal Genomes Project(CNGP,ClinicalTrials.gov Identifier:NCT03931707)with next-generation sequencing data.We reanalyzed the sequencing data and compared the allele frequencies of known ibuprofen-related SNPs between ibuprofen Responder and Non-responder groups.In total,185 hsPDA patients were recruited with gestational age(GA)ranging from 24 to 40 weeks.No significant differences were detected in the basic information,period of ibuprofen treatment,rate of conservative treatment,complications,and side effects between ibuprofen Responder group and Non-responder group.Totally,17 hsPDA carried CYP2C9^(*)3 and one with CYP2C9^(*)2 were detected.In the GA group of more than 30 GA weeks(GA>30 wks group),we found higher allele frequency of CYP2C9^(*)3 in Responder group than in Non-responder group(16%vs.0,p=0.0391).In the GA group of less than 30 GA weeks(GA≤30 wks group),the sum allele frequency of CYP2C9^(*)3 and CYP2C9^(*)2 had no stastical difference between two groups(Responder group vs.Non-responder group,13%vs.11%,p=0.768).Therefore,we came to conclude that genetic tests of CYP2C9^(*)3 site may benefit the prediction of ibuprofen treatment outcome for hsPDA patients with gestational age of more than 30 weeks.