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Objective:To investigate the clinical characteristics of children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, and the impact factors of duration of cycle threshold (Ct) values turning to ≥35 detected by nucleotide test.Methods:Children aged 0 to 14 years with clinical symptoms of Omicron variants infection who admitted to designated hospital in Shanghai City (Renji Hospital, South Branch, Shanghai Jiao Tong University School of Medicine) from April 7 to June 2, 2022 were enrolled. The daily nasopharyngeal swab specimens were used for SARS-CoV-2 nucleic acid detecting by polymerase chain reaction and the results were expressed as Ct values. The T Ct≥ x was defined as from the symptom onset or first positive nucleic acid test results (the earlier data) to Ct≥ x of the open reading frame 1ab ( ORF1 ab) gene, which was the time duration from the initial to a specific Ct value.Clinical data were collected, including age, sex, vaccination and comorbidities.Cox model was performed to analyzed the impact factors of T Ct≥35. Results:A total of 871 pediatric cases with a median age of two years (ranging from one month to 14 years old) were included. Among them, 474 cases (54.4%) were male, and 89 cases (10.2%) had underlying diseases including congenital heart disease, solid tumors and epilepsy. There were 572(65.7%) mild cases, 298(34.2%) common cases, one (0.1%) severe case and no critical cases or deaths. The T Ct≥35 was 12(10, 14) days. Cox model indicated that compared to children aged one to 12 months, children aged 37 to 84 months and 85 to 168 months had shorter T Ct≥35 (hazard ratio ( HR)=1.55 and 1.84, respectively, both P<0.001). After adjusted with age, comparing to unvaccinated patients, patients with one or two shots vaccine had shorter T Ct≥35 (adjected hazard ratio (a HR)=1.49, P=0.011), and common patients had longer T Ct≥35 than mild patients (a HR=0.78, P=0.002), and patients with comorbidities had longer T Ct≥35than patients without comorbidities (a HR=0.38, P<0.001).The duration of T Ct≥28, T Ct≥30, T Ct≥33 and T Ct≥35 in children without underlying diseases were 7(6, 9) d, 9(7, 10) d, 10(8, 11) d and 12(10, 14) d, respectively. Conclusions:Age, vaccination, disease severity and underlying diseases could affect the duration of SARS-CoV-2 nucleotide turning to negative (Ct value≥35) in children infected with Omicron variants.
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Objective:To study the past 10 years' experiences of neonatal hydrocephalus in a single-center.Methods:From January 2010 to December 2019, clinical data of infants with hydrocephalus admitted to Neonatology Department of our hospital were retrospectively analyzed. The infants were assigned into different groups according to gestational age, different etiologies and treatments. Their clinical characteristics and outcomes were compared.Results:A total of 223 infants with hydrocephalus were included. 136 (61.0%) infants were in the preterm group and 87 (39.0%) in the full-term group. The incidence of post-intracranial hemorrhage (ICH) hydrocephalus in preterm infants was significantly higher than full-term infants ( P<0.001). According to the etiologies, 58 infants (26.0%) had congenital hydrocephalus (congenital group), 82 cases (36.8%) developed post-ICH hydrocephalus (ICH group), 48 cases (21.5%) had post-CNS-infection hydrocephalus (infection group) and 35 cases (15.7%) had post-ICH+CNS-infection hydrocephalus (ICH+infection group). The incidences of perinatal asphyxia, neonatal resuscitation and endotracheal intubation within 3 d after birth in the ICH group were significantly higher than the other groups ( P<0.05). Among the four groups, the infection group had the highest incidence of neonatal sepsis, the congenital group had the highest incidence of patent ductus arteriosus and the ICH group had the highest incidence of respiratory diseases (all P<0.05).137 cases (61.4%) received non-surgical therapy, 48 cases (21.5%) had temporary drainage, 37 cases (16.6%) with permanent shunt and 1 case (0.4%) intracranial hematoma removal. The congenital group and ICH group with permanent shunt showed significantly higher rate of improvement than temporary drainage group and non-surgical group ( P<0.001). Conclusions:The main etiologies of neonatal hydrocephalus are ICH and CNS infection. The incidence of post-ICH hydrocephalus in premature infants was quite high. Hydrocephalus of different etiologies have different comorbidities. Maternal and infant care during pregnancy and delivery, prevention of neonatal sepsis and ICH are crucial in the prevention of hydrocephalus. More studies are needed for better treatment.
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Neonatal critical illness score(NCIS) has been published for over 20 years in China and has played an active role in critical neonatal transport, illness severity assessment, and prognosis evaluation.However, there are still some limitations in the scoring system with the development of medical technology, such as failure to include crucial perinatal information, unable to quantify single indicators, difficulty in obtaining PaO 2 without oxygen inhalation, complex evaluation indicators, long evaluation time and data was difficult for scientific research, etc.Therefore, it is necessary to update and simplify it for the clinical treatment and scientific study of critically ill newborns.This review summarized NCIS application in China and compared it with foreign neonatal critical scores such as score for neonatal acute physiology, clinical risk index for babies, etc.Combined with the rising technology of artificial intelligence and deep learning in recent years, it was more straightforward and optimized to enhance its accuracy and applicability, which was aimed to play a more active role in the treatment of critical newborns and scientific research.
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Primary ciliary dyskinesia (PCD) is an inherited disease characterized by impaired ciliary ultrastructure and function.Respiratory symptoms are the most important clinical manifestations of PCD.More than 50 pathogenic genes responsible for PCD have been identified, which have been contributed to clarify the etiology of PCD.At present, special therapy and gold standard for the diagnosis of PCD are scant.Gene therapy can restore ciliary function.Gene testing can identify the genetic etiology of PCD, and promote the development of individualized gene therapy.This review aims to summarize the research progress on genetic etiology of PCD and its genetic testing and gene therapy.
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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.
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Child , Humans , Neurodevelopmental Disorders/epidemiology , Genetic Testing , Phenotype , Brain/pathology , Genetic Background , SOX Transcription Factors/geneticsABSTRACT
Objective:To study the role of neonatal panel detection based on next generation sequencing (NGS) combined with multiplex ligation-dependent probe amplification (MLPA) in the etiological differentiation of neonatal hypotonia.Methods:The clinical characteristics and gene test results of newborns with hypotonia as the main clinical manifestation treated at the Department of Neonatology of Jiangxi Provincial Children's Hospital from March 2017 to March 2021 were retrospectively analyzed.Results:A total of 23 children with hypotonia and feeding difficulties diagnosed by gene tests were included. 17 cases (73.9%) had obvious abnormal appearance, and 11 cases (47.8%) had congenital heart disease (atrial septal defect and/or patent ductus arteriosus). Among the 23 infants, 21 were detected by panel gene, 10 by methylation specific MLPA (MS-MLPA) and 4 by MLPA (SMN1 / SMN2). 14 cases of Prader-Willi syndrome, 4 cases of spinal muscular atrophy, 3 cases of congenital myopathy and 2 cases of Schaaf-Yang syndrome were diagnosed. 11 cases died (47.8%), 9 cases had growth retardation (39.1%), 2 cases had normal growth and development (8.7%), and 1 case survived without detailed information (4.3%). Newborns with unknown etiology and low muscle tone are often complicated with abnormal appearance and congenital heart disease. Neonatal panel combined with MLPA is helpful for accurate diagnosis.Conclusions:The detection of neonatal panel combined with MLPA is cheap, and can provide accurate diagnosis for most newborns with unexplained hypotonia in a short diagnosis cycle, which is conducive to the early formulation of clinical decision-making, and guide the treatment, follow-up and genetic consultation of children.
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Real-world evidence has become the basis for approval and regulation of drugs and medical devices. Real-world study has played a more and more important role with the continuous updating and iteration of medical technologies. The diseases and their underlying mechanisms in the neonatal period, the early stage of life, are significantly different from other stages of life and early high-quality clinical management has a profound impact on the long-term outcomes. Therefore, it is necessary to provide robust evidence for clinical diagnosis and treatment through real-world study. This paper explores the access to high-quality medical care in the neonatal period based on the application, challenges, and thinking of the China Neonatal Network (CHNN) in the real world and the integration of the China Neonatal Genome Project and other multi-omics data.
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Blended teaching method has become an important part of the educational reform. Massive open online courses (MOOC) combined with flipped classroom in pediatrics education consists of online courses, flipped classroom and online communication. Students are promoted to engage in education actively through the online homework, tests, discussions and examinations, thus reaching the best teaching effect. This paper aims to introduce the establishment and accomplishments of this blended teaching method in Pediatrics education in Fudan University.
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Objective:To explore the predictive value of amplitude integrated electroencephalography(aEEG)in the neurological prognosis of children with neonatal bacterial meningitis(NBM).Methods:The clinical data and aEEG results from 148 children diagnosed with NBM who completed aEEG examinations in the Department of Neonatology at Kunming Children′s Hospital from January 2018 to December 2019 were retrospectively analyzed.According to whether aEEG is abnormal, the children were divided into aEEG abnormal group and aEEG non-abnormal group.According to the degree of aEEG abnormality, children with aEEG abnormality were divided into aEEG mild abnormal group and aEEG severe abnormal group.The abnormal rate and abnormal characteristics of aEEG were analyzed; The clinical data of two groups were compared.Results:(1)Among the 148 children with NBM, 49 children had abnormal aEEG, 99 children had no abnormality, and the aEEG abnormal rate was 33.1%.The abnormal aEEG was manifested as delayed sleep-wake cycle maturation in 39 (26.3%) cases, abnormal discharge in eight (5.4%) cases, and abnormal background activity in one (0.6%) case.(2)The proportion of children with convulsive seizures and refractory NBM in aEEG abnormal group were significantly higher than those in aEEG non-abnormal group ( P<0.05). In the routine and biochemical abnormal indexes of cerebrospinal fluid, the proportion of protein >3 g/L, cerebrospinal fluid leukocyte>500×10 6/L, cerebrospinal fluid glucose<1.5 mmol/L, positive cerebrospinal fluid culture, positive blood and cerebrospinal fluid culture, abnormal head MRI in aEEG abnormal group significantly increased ( P<0.05); While there was no significant difference regarding blood routine leukocyte abnormality, CRP increase, and positive blood culture ratio between two groups ( P>0.05). (3) 148 cases of NBM children were followed up to 15 months old, 119 (80.4%) cases completed the follow-up, the loss rate was 19.6%, three cases died, and 11 cases had psychomotor retardation.Compared with the children with abnormal aEEG, the prognosis of children with NBM was significantly different, the Spearman rank correlation coefficient r was 0.315 ( P<0.05). COX regression was used to analyze the predictive value of each index for adverse outcomes. Abnormal aEEG was an independent risk factor for adverse outcomes in children with NBM ( OR=7.452, 95% CI 1.605-34.591, P<0.05). Conclusion:The aEEG monitoring of children with NBM, if abnormal, may indicate severe NBM, which is likely to be transformed into refractory NBM or has a poor prognosis.
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Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has mutated multiple times since the first report in December 2019 and is still spreading globally. A variant of SARS-CoV-2, Omicron, was prevalent in Shanghai from March to May 2022. Based on published data and the experience in the management of neonatal COVID-19 cases and infants of mothers with COVID-19 during the pandemic in Shanghai, it is suggested that neonates are infected with SARS-CoV-2 mainly through postnatal horizontal transmission, but rarely through vertical transmission. The risk of SARS-CoV-2 infection in infants born to mothers with COVID-19 is low if quarantine measures are appropriately implemented. Even if they are infected, the risk of severe neonatal COVID-19 is low, but long-term neurological prognosis needs to be followed closely. Human milk feeding without contact is advocated for infants of infected mothers. During the COVID-19 pandemic, attention should also be paid to indirect effect on neonatal health due to possible inadequate medical resources.
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Objective:To investigate the clinical and genetic features of 3-methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome(MEGDHEL syndrome) caused by SERAC1 gene variation. Methods:This study retrospectively described the clinical and molecular features and prognosis of a baby boy who was transferred to Children's Hospital of Fudan University and later diagnosed with MEGDHEL syndrome in August 2016. A summary of the clinical and genetic manifestations of MEGDHEL syndrome cases reported in China and foreign areas was conducted through a literature review.Results:(1) Case report: The 2-day-old patient was transferred to Children's Hospital of Fudan University due to hyperlactic acidemia after birth. Physical examination revealed scattered petechiae and ecchymoses of the skin. Laboratory examination showed coagulation disorders and cranial MRI revealed abnormal signals in both basal ganglia. A homozygous variation of c.442C>T(p.Arg148*) in the SERAC1 gene was detected in the patient, which is a pathogenic variant included in the Human Gene Mutation Database. Both of his parents were heterozygous carriers, thereby the diagnosis of MEGDHEL syndrome was confirmed. Followed up to the age of three years and 11 months, he was found to have psychomotor retardation, spasticity, dystonia, deafness, and loss of language ability. (2)Literature review: Together with the case reported in this study, a total of 88 cases were retrieved, involving 57 different variants. The clinical features were homogenous, with onset mostly in the neonatal period (72%, 62/86), and severe reversible liver dysfunction (49%, 38/77) and neonatal hypoglycemia (44%, 35/80) were the main features. Nervous system was affected since infancy and common symptoms, included hypotonia (86%, 68/79), progressive spasticity (82%, 67/82), dystonia (80%, 66/82), intellectual disability (88%, 58/66) and sensorineural hearing impairment (74%, 59/80). Furthermore, bilateral basal ganglia involvement on cranial MRI (93%,70/75) and 3-methylglutaconic aciduria (98%,80/82) were also seen. Supportive care is currently the main management, however, the prognosis is extremely poor. Conclusions:MEGDHEL syndrome should be highly suspected when reversible neonatal liver dysfunction or hypoglycemia of unknown reasons in neonatal period, followed by progressive deafness-dystonia syndrome in infancy. As the prognosis of these patients is usually poor, genetic testing may provide an early diagnosis in neonatal period.
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Objective:To study the characteristics of video electroencephalogram (VEEG) and cranial magnetic resonance imaging (MRI) in neonates with inborn errors of metabolism (IEM) and to determine the predictive value for prognostic.Method:From June 2016 to December 2018, a retrospective study was performed on newborns diagnosed with IEM receiving VEEG examinations at the Neonatology Department of our hospital. VEEG and cranial MRI were used as prognostic indicators and the follow-up results were used as criteria predicting the accuracy of prognosis. The accuracy of the prediction was calculated using a 4 × 4 table.Result:A total of 21 eligible cases with 14 types of IEM were included. The most common type of IEM was organic acidemia (47.6%, 10/21). 16 cases (76.2%) had abnormal VEEG background patterns, including 8 cases of organic acidemia, 3 cases of urea cycle disorders, 1 case of energy metabolism disorder and 4 cases of other IEMs. No significant differences existed in the abnormality rate of VEEG background patterns among these groups ( P=0.882). VEEG showed 3 cases of seizures including 2 cases of electrographic-only seizures. Interburst interval durations were shortened on VEEG background with the decrease of blood ammonia level. The positive predictive values of the moderate-to-severe abnormal VEEG background and the presence of major cerebral lesions on MRI in predicting poor prognosis were 90.0% (95% CI 55.5%~99.7%) and 100% (95% CI 66.4%~100%), respectively, and the negative predictive values were 50.0% (95% CI 18.7%~81.3%) and 85.7% (95% CI 42.1%~99.6%), respectively. Conclusion:Neonates with IEM have higher incidences of abnormal VEEG. Continuous VEEG may accurately diagnose neonatal seizures and effectively monitor brain function. VEEG is a useful tool monitoring infants with IEM and predicting adverse outcomes, especially when used in combination with brain MRI.
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Breaking the limitation of time and space, telemedicine has been applied to the clinical diagnosis and treatment of rare diseases.It establishes connections between doctors and patients, doctors and doctors, as well as patients and patients, building a new patient-centered medical service system.Finally, integrating telegenetics into the current system of rare diseases will provide all-round health protection for patients around the world.
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Seizure is the most common neurological critical disease in the neonatal period, most of which is symptomatic.Seizure is usually caused by acute brain injury, and only electrical seizure is more commonly seen.Neonatal seizures are not easy to be included in the epilepsy classification established by the International League Against Epilepsy (ILAE). As a result, a Neonatal Seizures Task Force was established by the ILAE to develop a modification of the 2017 ILAE classification of seizures and epilepsies.The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of neonatal seizure, which includes a classification of seizure types especially in newborns.The type of seizure in adults and older children mainly depends on clinical characteristics, while many newborns only have electric seizures.Therefore, electric seizures are included in the classification scheme.Clinical events without corresponding EEG changes are not included.Neonatal seizures are all focal seizures, and focal and generalized seizures are unnecessarily to be categorized.Seizures can be classified by abnormal motor episodes (automata, clonic, myoclonic, tonic) and non-motor episodes (autonomic, behavioral changes) or sequential presentation.The new classification can be used to more specifically classify neonatal seizures.
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Objective:To evaluate the effectiveness of integrated pediatric training course of extracorporeal membrane oxygenation(ECMO)based on simulation teaching.Methods:The instructors of ECMO team of Children′s Hospital of Fudan University developed the teaching curriculum.Team members as a unit were recruited to study simulation-based courses, whose theoretical knowledge, skills and teamwork were assessed, and feedback from the trainees were gathered.Results:Since May 2018, 22 teams of pediatric specialized hospitals or general hospitals have taken part in our ECMO simulation, with totally 132 participants, including 45 ICU doctors(34.1%), 60 ICU nurses(45.5%), 23 thoracic surgeons(17.4%) and four anesthesiologists(3.0%). Twelve of them(9.1%)had a little ECMO experience.After training, the trainees had a high evaluation on each part of the course, with average score more than four, of which the theoretical score was lowest.Their self-evaluation on the theory, skills, teamwork and confidence in the implementation of ECMO had been significantly improved.Most(80.3%)of the trainees were confident to carry out ECMO in their local hospitals.The trainees′ baseline score of theoretical knowledge was 55.2±7.6, and increased to 67.1±7.3 after training( P<0.001). The average teamwork score of the 22 teams was 70.2±8.2, and the qualified rate was up to 86.4%.The most prominent skill problems in operation assessment were no albumin and blood priming(90.9%), non-skill problems were extremely anxious during the overall assessment(84.8%)of the participants, poor team work(74.2%), poor leadership(68.2%). For the feedback of the whole course, 97.0% and 94.7% of the trainees thought that integrated training and simulation teaching were the highlights of the course.At present, 13(59.1%)units have successfully developed ECMO technology after the course, and the number of children treated has been up to 83, with a survival rate of discharge of 54.2%.However, it was found that the skill level of some participants decreased about 2 weeks after the course. Conclusion:As a new attempt of ECMO teaching, this curriculum has achieved certain efficiency in both teaching and clinical practice.At the same time, our study also plays a role in promoting the development of ECMO in pediatrics.
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In 2013, Shanghai Medical College of Fudan University restarted the enrollment of the undergraduate students in directional pediatrics. To cultivate medical talents in pediatrics, a serious of educational innovations and practices have been carried out guided by competency training, including training a team of teachers with simulated teaching skills and establishing a teaching platform for simulation teaching. Medical students can practice medicine and gain experience through the risk-free simulated scenarios, that is helpful to enhance their confidence in clinical skills and communications and decrease medical errors in their future careers.
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OBJECTIVE@#To carry out genetic and metabolite analysis for an infant with cerebral creatine deficiency syndrome type 2 (CCDS2).@*METHODS@#Clinical data of the child was collected. Whole-exome sequencing was carried out to identify potential variants by next generation sequencing. Candidate variants were confirmed by Sanger sequencing. Metabolites were determined by tandem mass spectrometry and magnetic resonance spectroscopy. Treatment was carried out following the diagnosis and genetic counseling for the affected family.@*RESULTS@#Two novel heterozygous variants (c.289delC and c.392-1G>C) of the GAMT gene were identified in the proband, which were respectively inherited from her father and mother. In silico analysis suggested both variants to be pathogenic. Creatine (Cr) level of the child was very low, and cerebral guanidinoacetate (GAA) level was slightly increased. But both had recovered to normal in two weeks, and cerebral Cr level was significantly improved after two months. Intellectual and motor development of the child were significantly improved.@*CONCLUSION@#The child was diagnosed with CCDS type 2, for which pathogenic variants of the GAMT gene may be accountable. Treatment has attained a satisfactory effect for the patient.
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Management of the neonatal hypoxic-ischemic encephalopathy (HIE) has been evolving from a pre-cooling era with supportive therapy to standardized cooling era and currently to a post-cooling era over the last two decades. To further decrease the mortality and morbidity of HIE in post-cooling era, we need to focus on the selection of HIE patients who may benefit from cooling and optimization of the available cooling approaches, and to identify research gaps with regard to therapeutic strategies such as combining cooling with promising neuroprotective agents.
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With the recent development in diagnostic tools and bio-information, significant progress has been made in clinical understanding of the etiology of neonatal encephalopathy, however, which continues to be a challenge in clinical management. Therefore, we summarize the concept and causes of neonatal encephalopathy and explore how to provide individualized, precise treatment and prognostic assessment for children with neonatal encephalopathy from the following aspects: the standardization and systematization of perinatal history, diagnosis and treatment strategy informed by the bio-information tools, neuro-neonatal intensive care with multi-modal monitoring, and long-term follow-up with family-centered care.
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Objective@#To study the relationship between nutrition status and physical fitness in 8-10 year-old children in 3 cities, and to provide a scientific reference for improving physical condition of chidren of pre-school age.@*Methods@#To investigate the weight, height and physical fitness (standing long jump, endurance running, rope skipping in one minute and sit-ups in one minute) of 1 384 children in grade four from 24 primary schools in Beijing, Changzhi, Urumchi in 2018. Evaluated overweight and obesity by using the standard of “Screening for Overweight and Obesity among School-age Children”. Then used mixed linear model to compare the physical fitness of students with different nutritional status and to analyze the relationship between BMI and physical fitness.@*Results@#The prevalence of overweight and obesity were 17.41% and 23.48%, respectively. And the prevalence in boys was both more than that in girls(χ2=9.84，47.68，P<0.01). The increase in BMI of children from the same age and the same gender was related with the decrease in physical fitness by correlation analysis(P<0.05). In comparison method, the performance of the students of normal weight was better than obese students, but the male and female students had got the same results in their physical fitness test(P<0.05).@*Conclusion@#There is a negative correlation between nutrition status and physical fitness and the physical fitness in normal weight and obese children are better than the overweight children or obese children.