Objective:To study the genetic profiles and clinical characteristics of neonatal-onset genetic epilepsy.Methods:From July 2016 to May 2021, patients with neonatal-onset genetic epilepsy admitted to our hospital and received second-generation genetic sequencing were enrolled in this study. According to the types of genetic variations, the patients were assigned into ion channel group and non-ion channel group. Clinical characteristics, treatments and prognosis of the two groups were compared.Results:A total of 36 patients with identified genetic variations were enrolled, involving 15 epilepsy-related genes. KCNQ2, SCN2A and STXBP1 were the most common pathogenic genes. 20 cases (55.6%) were in the ion channel group and 16 cases (44.4%) in the non-ion channel group. No significant differences existed in their general status, seizure types, EEG characteristics, treatments and outcomes between the two groups ( P>0.05). Among all 36 cases, the age of onset ranged from 10 min to 24 d after birth and 28 cases (78.8%) developed epilepsy within 1 week after birth. Developmental and epileptic encephalopathies were diagnosed in 20 patients. 7 patients were diagnosed with self-limited neonatal epilepsy, 2 were pyridoxine dependence, 2 were Zellweger syndrome and 1 case of self-limited familial neonatal-infantile epilepsy, Turner type mental retardation with epilepsy, PURA syndrome, Rett syndrome and 22q11.2 deletion syndrome, each. The patients received antiepileptic drugs including phenobarbital, levetiracetam, oxcarbazepine, topiramate, valproic acid, benzodiazepines (nizepam/clonazepam /clobazam/midazolam), lacosamide and lamotrigine. 5 patients died after giving up treatment. 31 patients were followed up for 6 to 50 months. 22 cases (71.0%) were controlled at 1- to 35-month-old including 21 cases (56.7%) with developmental delay. 6 cases (19.4%) had ineffective seizure control and 3 cases (9.7%) showed reduced seizures, all with varying degrees of developmental delay. Conclusions:Neonatal-onset epilepsy is correlated with multiple genes. KCNQ2, SCN2A, STXBP1 are the common pathogenic genes with multiple variants of KCNQ2 gene. Most patients have seizures within 1 week after birth. More than half of patients have ion channel related gene variations. Sodium channel blockers have certain effects as treatment.

Objective:To explore the clinical manifestations, genetic disorder, prognosis of 14 neonates with primary immunodeficiency disease(PID).Methods:A total of 14 newborns with PID admitted to Department of Neonatology at Beijing Children′s Hospital from January 2017 to December 2019 were enrolled for retrospective analysis, focusing on their clinical manifestation, peripheral blood cell examnations, gene mutation, and outcomes after hemotopoietic stem cell transplantation(HSCT).Results:The average gestational age of the newborn was (38.6±1.2) weeks, the birth weight was (3 265±325)g, and the median diagnosis time was 57.5 days.Fourteen newborns with PID were diagnosed by whole exome sequencing as chronic granuloma (6/14), DiGeogre syndrome (3/14), Wiskott-Aldrich syndrome (2/14), severe combined immunodeficiency (2/14) and selective IgA deficiency (1/14). Regarding the clinical manifestations, fever, pneumounia and colitis accounted for 7/14, the decrease of T lymphocytes in peripheral blood accounted for 6/14, and the decrease of B lymphocytes accounted for 5/14.The absolute value of eosinophils increased (>500 cells/mm 3) accounted for 12/14, of which moderately increased (1 500 to 5 000 cells/mm 3) accounted for 5/12, and the absolute value of monocytes increased (median>1.5×10 9/L) accounted for 7/14.Follow-up children received HSCT accounted for 7/14, and the median time of receiving transplantation was 330 days after birth.By the time of follow-up, the primary disease resolved after HSCT accounted for 5/7, and the survival rate was 85.7%.Among them, two children with chronic granulomatosis were diagnosed with inflammatory bowel disease before transplantation, and the primary disease improved after HSCT.Three-quarters of the deaths had inflammatory bowel disease-like manifestations and died of infectious shock. Conclusion:The clinical manifestations of children with PID during the neonatal period are not specific.The manifestations of colitis need more attention.Some of the newborns with PID will evolve into inflammatory bowel disease or have inflammatory bowel disease-like manifestations or even die of it.HSCT is a fundamental treatment for the primary disease.

Objective:To explore the clinical characteristics and prognosis of children with inborn error of immunity (IEI) onset in the neonatal period.Methods:The clinical data of 21 cases of IEI neonates admitted to the Neonatal Center of Beijing Children′s Hospital were collected, and their clinical manifestations, peripheral blood test characteristics, genetic diagnosis, and primary disease during hospitalization were collected.The prognosis follow-up results were summarized and analyzed.Results:Twenty-one children with IEI were finally diagnosed by whole exome sequencing, including 15 cases of primary immunodeficiency(including 6 cases of chronic granulomatous disease, 3 cases of DiGeogre syndrome, 2 cases of Wiskott-Aldrich syndrome, 2 cases of severe combined immunodeficiency disease, 1 case of selective IgA deficiency, and 1 case of ectodermal dysplasia with immunodeficiency), 5 cases of infantile inflammatory bowel disease, and 1 case of familial haemophagocytic lymphohistiocytosis.Clinical manifestations of sepsis and colitis were the most common(accounting for 12/21), and 16/21 of the children had an increase in the absolute value of eosinophils(>0.5×10 9/L). Children received hematopoietic stem cell transplantation accounted for 7/21, and the median time of receiving transplantation was 11 months after birth.By the time of follow-up, the primary disease remission after hematopoietic stem cell transplantation accounted for 5/7.Among them, 2 cases were diagnosed with CGD associated inflammatory bowel disease before transplantation, and the primary disease resolved after hematopoietic stem cell transplantation.Of the 14 children who did not receive hematopoietic stem cell transplantation, 10 children died.Five of the 11 deaths were treated with systematic steroid before diagnosised. Conclusion:The clinical manifestations of IEI in the neonatal period are not specific.Sepsis and colitis are the most common manifestations.Most of the cases have elevated eosinophils in the peripheral blood.Systematic streoid therapy needs to be cautious, and timely evaluation for hematopoietic stem cells transplantation is an effective option to resolution.

Objective:To summarize the clinical characteristics and treatment outcome of neonates with laryngopharyngeal congenital structural abnormalities in intensive care unit.Methods:The clinical data of neonates with congenital laryngopharyngeal structural abnormalities in the Neonatal Intensive Care Unit of the National Center of Beijing Children′s Hospital, Capital Medical University from January 2017 to December 2018 were retrospectively analyzed.The general data, birth status, disease types and clinical characteristics of abnormal laryngeal structure, complications, treatment and follow-up of some children with special diseases were summarized.These neonates were divided into the operation group and the conservative treatment group according to treatment methods, and then the outcomes of the two groups were compared.Results:A total of 133 cases of neonates with laryngopharyngeal congenital structural abnormalities were enrolled, including 73 cases(54.88%) with laryngomalacia, and 60 cases(45.12%) with special structural abnormalities.Of 60 cases with special structural abnormalities, 26 cases (19.54%) had pharynx and larynx cysts, 18 cases (13.53%) had vocal cord paralysis, 4 cases (3.00%) had laryngeal cleft, 2 cases (1.50%) had subglottic hemangioma, 3 cases (2.25%) had Pireer Robin, 1 case (0.75%) had laryngeal poof, 5 cases (3.75%) had pharynx softening, 1 case (0.75%) had subglottic stenosis.Nine patients had special structural abnormalities and laryngomalacia simultaneously.Fiber nasopharyngoscope and enhanced CT were main auxiliary examinations.Twenty-two(16.5%) cases received surgical treatment.Conclusions:Early diagnosis is needed for the neonates and abnormal laryngeal structure.The best treatment scheme should be evaluated according to the condition of the newborn.For some acute cases, early operation and multidisciplinary comprehensive treatment are warranted.

Objective:To analyze the diagnosis and treatment of neonatal neuroblastoma (NB) by summarizing its clinical characteristics.Methods:This study retrospectively recruited 14 neonates with NB in Beijing Children's Hospital (National Center for Children's Health) from February 1, 2015, to February 1, 2020. Medical records and follow-up data as of February 29, 2020, were collected, and clinical staging based on International Neuroblastoma Staging System, risk grouping based on American Childhood Oncology Group risk grouping system, diagnosis, treatment, and prognosis were analyzed. According to whether surgical treatment was performed in the neonatal period or not, these subjects were divided into surgical and non-surgical groups. A descriptive statistical analysis was used for data analysis.Results:(1) Neonates with NB accounted for 0.063% (14/22 006) of the total number of newborns admitted to the hospital during the same period. The 14 cases were all full-term aged 15 d (8 h-23 d) at admission. Tumors were found in seven cases in prenatal examinations, while others presented with shortness of breath (three cases), abdominal distension (two cases), fever (one case), and dysuria and difficult defecation after birth (one case). (2) The primary tumor sites included the adrenal gland (eight cases), posterior mediastinum (three cases), retroperitoneum (two cases), and sacrococcygeal (one case). Three cases had extensive diffuse liver metastasis at admission. (3) Except for two cases who refused to examine, the serum neuron-specific enolase of 12 cases was 57.2 ng/ml (35.9-158.3 ng/ml) during hospitalization, and the urine vanillyl-mandelic acid creatinine of four cases was 2 304.940 (685.748-9 595.314). (4) Primary tumor sites were found in 14 cases by imaging examination. Bone scanning was performed in three cases, including one with a concentrated shadow of the right sacroiliac joint and two with no abnormalities. Ten cases underwent bone marrow aspiration and all with normal results. (5) Of the ten neonates received surgery (the surgical group), nine had the primary tumor wholly removed, without chemotherapy after the operation, and the tumor-free survival period was 19 months (1-45 months). One case (case 5) had a substantial primary tumor that could not be completely resected. The patient underwent a second surgery five months after the first operation due to disease progression and received postoperative chemotherapy. The child had stopped chemotherapy for 24 months and survived without a tumor. (6) In the non-surgical group (cases 11 to 14), the tumor in case 11 who refused chemotherapy shrank spontaneously after discharge, and the patient survived for 20 months with the tumor. The parents of the case 12 withdrew treatment during hospitalization, while the primary tumor and metastases disappeared after discharge, and the specific tumor markers gradually decreased to normal levels. The patient has been tumor-free survived for 25 months. Case 13 received mediastinal tumor resection and chemotherapy during infancy. At the end of the follow-up, chemotherapy had been stopped for 12 months, and the patient survived without a tumor. Case 14 withdrew treatment and died. (7) Among the ten cases in the surgical group, one patient's pathological result indicated a composite tumor, while the others were low differentiated neuroblastoma. There was no MYCN gene amplification, 1p36 deletion, or 11q23 deletion in the ten cases. (8) Among the ten children in the surgical group, nine were in stage 1, and one was in stage 4S (case 5). Nine cases were classified into extremely low-risk groups, while the other was in the low-risk group. The four cases in the non-surgical group could not be grouped by risk. Conclusions:Clinical manifestations of neonatal NB are often atypical. NB in stage 4S might resolve spontaneously, and expectant observation may be considered. The overall prognosis of neonatal NB is generally good, but further researches are needed.

Objective:To analyze the molecular and virulence characteristics of Staphylococcus aureus ( S. aureus) isolated from neonates. Methods:A total of 189 S. aureus isolates were collected from Beijing Children′s Hospital from January 2013 to October 2019 and analyzed by multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCC mec) typing and Spa typing. Panton-valentine leucocidin (PVL)-encoding gene ( pvl) and 21 superantigen virulence genes were also detected. Results:The 189 S. aureus strains were isolated from respiratory secretions ( n=125), pus ( n=55), blood ( n=8) and pleural effusion ( n=1). There were 98 methicillin-susceptible S. aureus (MSSA) belonging to 42 MSSA clones and 91 methicillin-resistant S. aureus (MRSA) belonging to 26 MRSA clones. ST188-t189 and ST59-SCC mecⅣa-t437 were the predominant MSSA and MRSA clones accounting for 11% and 53%, respectively. The prevalence of pvl gene in MRSA isolates was significantly higher than that in MSSA isolates (32% vs 10%, P<0.01). There were 166 isolates (88%) carrying at least one superantigen virulence gene and among the 21 genes, seq and seb were the most common genes accounting for 47% and 43%, respectively. The most common superantigen genotype was seb- sek- seq. The positive rates of superantigen genes in MRSA and MSSA isolates were 85% (77/91) and 90% (88/98), respectively ( P>0.05). Conclusions:The main clones of MRSA and MSSA were different in neonates. ST59-SCC mecⅣa-t437 was the most predominant MRSA clone, while ST188-t189 was the most predominant MSSA clone. MSSA clones were more dispersed. The prevalence of pvl gene in MRSA was higher than that in MSSA. No significant difference in the prevalence of superantigen genes was observed between MRSA and MSSA.

Objective To analyze the clinical and molecular features of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infection in neonates and to investigate their antibiotic resistance profiles.Methods A total of 35 invasive CA-MRSA strains were collected from six hospitals in 2014.Multilocus sequence typing (MLST), staphylococcal cassette chromosome mec (SCCmec) typing and spa typing were used to analyze these isolated CA-MRSA strains.In vitro antibiotic susceptibilities of those strains to 15 antibiotics were analyzed by using agar dilution method.Results Up to 88.6% patients were late-onset infection and septicemia (24, 68.5%) was the most common infection among the 35 cases.A total of 16 patients (45.7%) suffered from complications.Caesarean section and premature birth were risk factors for invasive CA-MRSA infection.ST59-MRSA-SCCmecⅣa-t437 (14, 40%) was the most predominant CA-MRSA clone, followed by ST59-MRSA-SCCmecⅤ-t437 (13, 37.1%).The incidence of severe complications caused by ST59-MRSA-SCCmecⅤ-t437 was higher than that caused by ST59-MRSA-SCCmecⅣa-t437 (P<0.05).Up to 85.7% of the isolated CA-MRSA strains were multidrug-resistant strains.Conclusion This study shows that neonatal invasive CA-MRSA infections mainly result in septicemia and are often accompanied by complications and involve multiple organs.Multidrug-resistant CA-MRSA strains are prevalent in neonates.ST59-MRSA-SCCmecⅣa-t437 is the predominant clone causing neonatal invasive CA-MRSA infection.

Objective To discuss the relationship between the clinical pathogenesis and progression in neonatal pulmonary hypertension in different stages.Methods Total 169 cases of pulmonary hypertension were admitted in our NICU from June 2006 to May 2012,all the cases were involved in this retrospective study.They were divided into two groups in chronological order:early group 79 cases (from June 2006 to May 2009) and late group 90 cases (from June 2009 to May 2012).The data records include gender,gestational age,protopathy,echocardiography examination results.Furthermore,the cause and development of neonatal pulmonary hypertension were analyzed in different stages.Results The admission time in the early group was later than the late group [(2.15 ± 1.2) d vs (1.41 ±0.70) d].Meconium aspiration syndrome in the early group were 25 cases (31.6％) and the late group were 14 cases (15.6％).Other complications,such as congenital diaphragmatic hernia,neonatal respiratory distress syndrome,aspiration pneumonia,wet lung/sepsis,neonatal asphyxia,neonatal infectious pneumonia had no difference between the two groups(P ＞0.05).Neonatal pulmonary hypertension in two groups had no statistical difference between term and post term patients,but premature in the early group (11 cases,13.9％) were less than the late group (23 cases,25.6％).Echocardiography was recorded after admission,mild and moderate pulmonary hypertension had no statistical differences in the two groups (P ＞ 0.05).The severe pulmonary hypertension cases in the early group were more than those in the late group (26 cases vs 17 cases).Conclusion Along with the improvement of perinatal monitoring and resuscitation technology in different stages,the cases of meconium aspiration syndrome with pulmonary hypertension are fallen down and the patients transferred to the superior hospital decreased.The amount of pulmonary hypertension in preterm infants increases,and the admission time of patients with neonatal pulmonary hypertension are shortened.The amount of severe pulmonary hypertension are less than those in the early time.It plays a positive role in best approach to improving treatment and outcomes.

Objective To analyze of the risk factors for persistent pulmonary hypertension of newborn(PPHN) after resuscitation in neonatal asphyxia.Methods Total 92 cases of PPHN in neonatal asphyxia were admitted in NICU,Beijing Children's Hospital Affiliated to Capital Medical University from Jan.2009 to Dec.2013 as PPHN group.According to patients condition,to case-control study method were randomly selected 92 cases without PPHN in neonatal asphyxia in the same period as control group.Except for other serious complications with PPHN,such as respiratory distress syndrome,meconium inhalation,pulmonary hemorrhage,neonatal severe pulmonary infection and diaphragmatic hernia.Apgar score and rescue measures after asphyxia based on the newborn perinatal questionnaire and body temperature,blood sugar,arterial blood gas and echocardiography on admission were recorded.Results Respiratory treatment of PPHN group and control group were 71 cases (77.2％) vs 28 cases (30.4％),respectively.There was significant difference (x2 =6.380,P =0.012).On admission,mean arterial pressure [(32.36 ± 11.52) mmHg],temperature [(34.3 ±0.28) ℃],blood sugar [(2.56 ±0.77) mmol/L] and arterial blood pH value (7.16 ±0.21) in PPHN group were lower than those of the control group [(38.55 ± 9.18) mmHg,(36.5 ± 0.71) ℃,(3.46 ± 0.53) mmol/L,7.21 ±0.14].For mild and severe asphyxia cases in the PPHN group,blood gas and pulmonary hypertension had no statistical difference after rescucitation in the delivery hospital.Conclusions Acidosis,hypothermia,low blood pressure and hypoglycaemia after resuscitation in neonatal asphyxia are major risk factors for genesis of PPHN.This research shows that rescue after asphyxia timely,early and respiratory support effectively,monitoring closely,treatment of hypoglycemia and hypothermia,correct acidosis and maintain blood pressure can play a positive role in decreasing the morbidity of PPHN in neonatal asphyxia.

Objective To investigate the cardiac structure and hypertrophic cardiomyopathy of infant of diabetic mother(IDM),to analyze of the outcome of hypertrophic cardiomyopathy in IDM.Methods Totally 23 cases of IDM admitted in NICU from Feb.2012 to Jan.2013 were selected as observation group,randomly selected from the same period with gestational age of diabetic mother baby 23 cases as control group.The interventricular septum thickness,left ventricular posterior wall thickness,aortic valve internal diameter,right ventricular diameter,ejection fraction were detected and compared between the 2 groups.And echocardiography was followed up in 3 months and 6 months old.Results In IDM group,interventricular septum thickness [(3.20 ± 0.28) mm],left ventricular posterior wall thickness [(3.40 ± 0.31) mm] were significantly higher than those in control group (all P ＜ 0.05).Ejection fraction [(54.00 ± 3.76) × 10-2] was significantly lower than that in control group(P ＜ 0.05).Follow-up after 3 months,6 months old,interventricular septum thickness,left ventricular posterior wall thickness and ejection fraction returned to normal.Four of the 23 cases(17.4％) had cardiac malformations.Conclusions IDM has high morbidity of congenital heart disease,echocardiography should be done to identify hypertrophic cardiomyopathy and congenital heart disease after birth.IDM combined with hypertrophic cardiomyopathy is a transient,benign process,prognosis is good.