Objective To compare the efficacy of less invasive surfactant administration (LISA) and intubation-surfactant-extubation to CPAP (INSURE) techniques in premature infants with respiratory distress syndrome (RDS).Method From January 2016 to January 2017,premature infants with RDS admitted to our hospital were prospectively and randomly assigned into the LISA group and the INSURE group.A 6F suction tube was used to drip pulmonary surfactant (PS) into the trachea with non-invasive respiratory support in the LISA group.INSURE technique and endotracheal intubation with surfactant administration were used in the INSURE group.The following indicators were examined:the time needed for intubation,the change of percutaneous oxygen partial pressure and the incidence of bradycardia during administration,regurgitation after administration,oxygen therapy duration,mechanical ventilation duration,re-administration of PS and apnea.Secondary indicators included the incidences of pneumothorax,pulmonary hemorrhage,neonatal necrotizing enterocolitis (NEC),intraventricular hemorrhage (IVH),bronchopulmonary dysplasia (BPD),preterm retinopathy (ROP),and periventricular leukomalacia (PVL).Result A total of 145 cases were included including 76 in LISA group and 69 in INSURE group.The gestational age was 27～34 weeks.The birth weight was (1 650±480) g.No statistically significant differences existed between the two groups on the time needed for intubation,the change of percutaneous oxygen partial pressure,mechanical ventilation duration,oxygen therapy duration,the incidence of bradycardia,re-administration of PS,apnea and other complications (P＞0.05).Statistically significant differences existed in the incidence of regurgitation (46.1％ in LISA group vs.29.0％ in INSURE group),mechanical ventilation within 72 hours (13.2％ in LISA group vs.27.5％ in INSURE group) and the incidence of BPD (6.6％ in LISA group vs.17.4％ in INSURE group) (P＜0.05).Conclusion Compared with INSURE,LISA technique is effective for the treatment of RDS and reduce invasive ventilation duration and the occurrence of BPD.

Objective To study the relationship of serum 25-hydroxy vitamin D [25-(OH) D] and vitamin D binding protein (DBP) in premature infants with bronchopulmonary dysplasia (BPD) and their clinical significance.Method From March 2017 to September 2018,the premature infants with gestational age (GA)＜32 weeks admitted to the neonatal department of our hospital were prospectively studied.All the premature infants were given 800 IU/d vitamin D supplement from one week after birth.Venous blood sample were collected at birth and 28 d after birth to measure 25-(OH) D aud DBP levels.The infants were evaluated for BPD at 28 d after birth and then assigned into the BPD group and the non-BPD group.The differences of 25-(OH) D and DBP levels were compared.Result A total of 170 premature infants (GA＜32 weeks) were included,including 56 cases in the BPD group and 114 cases in the non-BPD group.The BPD group had 34 males,the GA was (29.8±1.2) weeks,the birth weight (BW) was (1 198± 157) g.The non-BPD group had 95 males,the GA was (30.2± 1.5) weeks,the BW was (1 243± 146) g.No significant differences existed in GA,BW and male gender proportion between BPD group and non-BPD group (P＞0.05).The BPD group had a lower levels of serum 25-(OH) D at birth [(27.8±5.9) nmol/L vs.(30.4±1.1) nmol/L,P＜0.05].The levels of serum 25-(OH) D in moderate/severe BPD group were significantly lower than mild BPD group [(25.3±4.9) nmol/L vs.(29.7±5.9) nmol/L,P＜0.05];25-(OH) D in BPD group was still lower than the non-BPD group at 28 days after birth (after vitamin D supplement) [(77.5±11.7) nmol/L vs.(83.8±11.6) nmol/L,P＜0.05].Comparison of serum DBP levels between the two groups showed that,DBP at 28 d after birth in BPD group were significantly lower than the non-BPD group,and DBP in moderate/severe BPD group were significantly lower than the mild BPD group [(373.9± 19.1) μg/ml vs.(391.4±23.6) μg/ml],the differences were both statistically significant (P＜0.05).Multivariate analysis showed that the high serum 25-(OH)D level at birth (OR=0.827,95％CI0.693～0.987) was protective factors for BPD,while neonatal pneumonia (OR=4.331,95％CI 1.269～14.784) and neonatal sepsis (OR=4.020,95％CI 1.153～14.015) were risk factors for BPD.Conclusion The high serum 25-(OH) D level at birth in preterm infants was protective factors for BPD,while neonatal pneumonia and sepsis were the risk factors for BPD.Moreover,low serum 25-(OH) D level at birth and low serum DBP level at 28 d after birth maybe useful indicators for the severity of BPD.

Objective To study the relationship between single nucleotide polymorphisms (SNPs) of vascular endothelial growth factor A (VEGFA) gene and neonatal necrotizing enterocolitis (NEC).Method From August 2014 to December 2016,preterm infants with a ≥ Ⅱ stage (Modified Bell staging criteria) of NEC admitted to our hospitals were assigned as NEC group.Preterm infants without NEC with similar gestational age and body weight during the same period were assigned as the control group.SNPs of VEGFA including rs1005230,rs833067,rs3025010,rs3025035,rs3025036,rs10434,and rs6905288 were analyzed using SEQUENOM MassARRAY platform and multiplex allele-specific PCR.The concentration of VEGFA in the plasma of the two groups was examined using enzyme-linked immunosorbent assay (ELISA).Result A total of 110 infants were reviewed,including 30 infants in NEC group and 80 infants in the control group.The results showed a significant association of the minor allele frequency (MAF) for T in rs1005230 and C in rs833067 with NEC.The frequencies of C/T (OR=4.810,95％CI 1.742～13.278) and C/T-T/T (OR=4.892,95％CI 1.801～13.246) genotypes in rs1005230,and frequencies of T/C (OR=4.373,95％CI 1.578～12.129) and T/C-C/C (OR=4.000,95％CI 1.484～10.828) genotypes in rs833067 were significantly higher in NEC group than the control group (P＜0.05).Infants with MAF in rs1005230 and rs833067 had significantly lower plasma level of VEGFA than infants without MAF (P＜0.01).Conclusion The SNPs of rs1005230 and rs833067 may be associated with lower level of VEGFA in plasma and higher risk for NEC.

Objective To study the survival rate,complications and risk factors affecting clinical outcomes in extremely low birth weight (ELBW) premature infants.Method From January 2008 to December 2017,clinical data of ELBW infants admitted to the department of neonatology of our hospital were collected.The survival rates and the incidences of complications were compared between different subgroups of different birth weight (BW) and discharging date.The risk factors affecting the survival rate of ELBW infants were analysed using multivariate unconditional Logistic regression analysis.Result (1) A total of 438 ELBW infants were enrolled,representing 4.9％ (438/8 910) of all discharged preterm infants,and 2.6％ (438/16 948) of all discharged neonates during the study period.Among them,3 were excluded because of incomplete data and lost of follow-up.The BW was 900 (750,950) g and the gestational age was (28.0±2.1) weeks.The overall survival rate was 81.6％ (209/256) with 179 cases excluded for giving up treatment.(2) From 2008 to 2017,the percentages of ELBW infants among all discharged newborns and all discharged premature infants increased annually (x2 trend=6.818,27.850,P=0.009,＜0.001).(3) No significant differences existed in the survival rates of ELBW infants between 2013-2017 and 2008-2012(P＞0.05).The survival rates of different BW groups (＜700 g,700～799 g,800～899 g,and 900～999 g)increased from 40.0％ (6/15) to 88.5％ (139/157) (x2 trend=32.648,P＜0.001).(4) The main complications in ELBW infants were respiratory distress syndrome 87.5％ (224/256),retinopathy of prematurity 63.1％ (123/195),and bronchopulmonary dysplasia 63.0％ (126/200).(5) Multivariate unconditional logistic regression analysis showed that BW＜900 g (＜700 g∶ OR=10.147,95％CI 2.684～38.360;700～799 g∶ OR=6.978,95％CI 1.647～29.555;800～899 g∶ 0R=4.727,95％CI 1.060～21.082,P＜0.05),and gestational age＜28 weeks (OR=3.529,95％CI 1.601～7.778,P=0.002) were the risk factors for survival rate and antenatal steroids was the protective factor(OR=0.155,95％CI 0.069～0.353,P＜0.001).Conclusion The number of ELBW infants discharged from neonatology department increased annually.The survival rate of ELBW infants was positively correlated with BW.Antenatal steroids may improve the survival rate of ELBW infants.

Objective To study the etiology and clinical features of arrhythmia in neonates with cardiac cardiomegaly.Method A retrospective study was conducted on newborns with arrhythmia hospitalized in the neonatal intensive care unit of our Hospiatal from January 2016 to May 2018.The eases were assigned into arrhythmia with cardiac enlargement group and non-benign arrhythmia without cardiac enlargement group cardiomegaly.The etiology,clinical features and prognosis of newborns with arrhythmia and cardiac enlargement were analyzed.Result There were 15 newborns with arrhythmia accompanied with cardiac enlargement,all of them were non-benign arrhythmias,which accounted for 26.8％ (15/56) of all non-benign arrhythmias in the same period.The causes included infections viral myocarditis,pneumonia and digestive tract infection,electrolytes and acid-base imbalance hypocalcemia,hyperkalemia and metabolic acidosis,structural cardiac abnormalities,metabolic cardiomyopathy,nodular sclerosis and indwelling central venous catheter.The median age of onset was 9 (0,19) days,and the median medical history was 2 (1,7) days,the significance of which were not different from those of non-benign arrhythmias without cardiac enlargement group (41 cases).The rate of cesarean section and ventricular rate＞160 bpm at admission were higher than those in the non-benign arrhythmias without cardiac enlargement group.12 of 15 cases began with weak responses,poor appetite and dyspnea.The common arrhythmia types were paroxysmal supraventricular tachycardia (6 cases),atrial tachycardia (4 cases) and atrial flutter (4 cases).The proportion of atrial flutter was higher than that of the non-benign arrhythmias without cardiac enlargement group.8 cases received respiratory support.The average length of stay was (18.4±8.6) days.The mortality rate during hospitalization was 6.7％.The echocardiographic results showed that left atrioventricular enlargement and ejection fraction of left ventricle less than 60％ during arrhythmic episode.The cardiac size and systolic functions of left ventricle reverting to normal after improvement.During the follow-up period,1 case died and 2 cases lost to follow-up,all of them were discharged against medical advice.The median follow-up time of other cases was 1.6 (1.3,2.2) years.All of them recovered well without abnormalities in cardiac size or cardiac function by echocardiography.Conclusion Most newborns with arrhythmia accompanied by cardiac enlargement had insidious onset.Tachyarrhythmia was common and infection was the main cause.Attention should be paid to screening of rare causes in clinical practice.Non-benign arrhythmias with or without cardiac enlargement have no significant difference in the overall prognosis by active treatment.

Objective To study the influences of meconium-stained amniotic fluid (MSAF) and chorioamnionitis (CA) on maternal and infant infection.Method From July to December 2014,full-term single birth newborns with MSAF born in our hospital were assigned into the MSAF group.According to the pathological characteristics of the placenta,they were further assigned into CA group and non-CA group.The healthy single birth full-term infants without MSAF were assigned into the control group.The influences of MSAF and CA on maternal and infant infection were analyzed.Result A total of 178 MASF cases were enrolled,including 57 cases with CA and 121 cases without CA.42 infants were in the control group.The incidence of CA with MSAF (32.0％,57/178) was significantly higher than the control group (4.8％,2/42) (P＜0.05).The white blood cell counts on the first day of the CA group and non-CA group were (29.4±8.9)x 109/Land (22.8±4.8)x 109/L,respectively.36.8％ of the CA group had increased CRP within 3 days after birth,while 15.7％ in the non-CA group.The incidence of neonatal infection were 49.1％(28/57) in the CA group,and 20.7％(25/121) in the non-CA group.The incidence of meconium aspiration syndrome was 28.1％(16/57)in the CA group,and 8.3％(10/121) in the nou-CA group.The differences between the two groups were statistically significant (P＜0.05).The proportion of neutrophils of the mother was (80.3±7.3)％ in the CA group,and (76.4±7.6)％ in the non-CA group.22.8％(13/57) of the mothers in the CA group had fever before and after delivery,and 9.9％(12/121) in the non-CA group.The incidence of uterine infection was 8.8％(5/57) in the CA group and 0％(0/121) in the non-CA group.The postpartum hemorrhage rate was 24.6％(14/57) in the CA group,and 3.3％(4/121) in the non-CA group.The differences were statistically significant (P＜0.05).Conclusion The incidence of CA in MSAF neonates is higher,resulting increased incidences of neonatal infection,maternal fever,and uterine infection.

Objective To summarize the gene mutation,treatment and prognosis of neonatal congenital hyperinsulinism (CHI) cases.Method The gene mutation and treatment of newborn infants who were admitted to the neonatal center of Beijing Children's Hospital between February 2015 and February 2018 with confirmed CHI diagnosis and whole exome sequencing (WES) results were retrospectively summarized.Result Totally 8 infants (5 boys and 3girls) were included.The onset age was (13.2±6.1) h (2 h ～ 2 d).The main clinical presentations were inactivity,seizures and poor feeding.Among the 8 patients,3 were positively responded to diazoxide,5 were negative and then been treated by octreotide.Among these 5 cases,3 were positively responded to octreotide (with stable blood glucose level after discharged home and till 6 months of age) and 2 were negative to both diazoxide and octreotide (1 had partial pancreatectomy afterwards but still had 1～2 episodes pf hypoglycemia till 6 months post-operational periods,another 1 died with unknown detail information soon after the parents quit further medical intervention).All 8 cases had heterozygous gene mutations.7 out of the 8 cases were ABCC8 gene (encoding islet beta-cell potassium channel protein sulfonylurea receptor protein SUR1) mutation on different sites including c.4414G＞A,c.221G＞A,c.1773C＞G,c.4352T＞C,c.2924-9C＞T,c.4198+ 1G＞T,c.2509C＞T,c.2331G＞A,c.4316A＞G and c.47G＞C.Among these 7 cases,3 were complicated heterozygous mutations with completely no response to diazoxide (2 out of the 3 were positively responded to octreotide,1 out of the 3 was negative to octreotide)and the other 4 were simple heterozygous mutations (2 out of the 4 were positively responded to diazoxide,1 out of the 4 was negative to diazoxide but positive to octreotide,and 1 out of the 4 was negative to both diazoxide and octreotide).1 out of the 8 cases was heterozygous GLUD1 gene mutation at c.1388A＞T site and had positive therapeutic responses to diazoxide.All 5 out of the 8 cases with negative therapeutic response to diazoxide had ABCC8 gene mutation.Conclusion ABCC8 gene encoding islet beta-cellpotassium channel protein sulfonylurea receptor protein SUR1 is the most common gene to have mutation io CHI.Mutations at multiple sites of this gene may cause CHI.Various therapeutic responses to medications might be related to different types of gene mutation.

Objective To study the effect of small interfering ribonucleic acid (siRNA) silencing apoptosis signal-regulating kinase 1 (ASK1) on inflammatory response of lipopolysaccharide-induced alveolar epithelial A549 cells and its mechanism.Method Cell inflammation model of A549 cells was induced by lipopolysaccharide.The expression of ASK 1 in A549 cells was silenced by liposome transfection of siRNA.The mRNA and expression levels of ASK1,interleukin 6 (IL-6),interleukin 8 (IL-8) and tumor necrosis factor alpha (TNF-α) in A549 cells were detected by immunoblotting,real-time fluorescence quantitative polymerase chain reaction and enzyme-linked immunosorbent assay.Result The expression of IL-6,IL-8 and TNF-α in the experimental group was significantly higher than that in the control group (P＜0.001),which indicated that the inflammatory model of A549 cells was successfully constructed.The mRNA level and expression of ASK1 in the interference group was significantly lower than that in the negative control group and the blank control group (P＜0.01),indicating that silencing ASK1 was also successful.The expressions of IL-6,IL-8 and TNF-α in the interference group (0.37±0.04,0.32±0.04,0.48 ±0.13) were significantly lower than those in the negative control group (1.04±0.11,1.22±0.19,0.93±0.14) and the blank control group (1.01±0.14,1.01 ±0.23,1.02±0.25).The expression of IL-6,IL-8 and TNF-α protein in the interference group (pg/ml) (122.6± 11.0,537.2±42.4,159.2± 19.6) were also significantly lower than those in the negative control group (267.4±20.4,1 289.8±55.3,327.0±26.3) and blank control group (246.6±18.7,1 300.3±35.6,325.2± 18.3),with significant difference (P＜0.05).There was no significant difference in each value between negative control group and blank control group (P＞0.05).Conclusion Silencing ASK1 by siRNA can down-regulate the expression of IL-6,IL-8 and TNF-α in A549 cells,suggesting that ASK 1 may be involved in the regulation of lipopolysaccharide-induced inflammation in A549 cells.

Objective To study the clinical manifestations, risk factors, treatment and prognosis of carbapenem-resistant klebsiella pneumoniae (CRKP) sepsis in premature infants. Method A retrospective analysis was done for the premature infants diagnosed with klebsiella pneumoniae sepsis and admitted to the neonatal wards of the Hospital from April 2015 to March 2018. According to the results of drug sensitive test, the infants was assigned to CRKP group and non-CRKP group. The perinatal factors, clinical manifestations, treatment, and prognosis of the two groups were analyzed. Furthermore, high risk factors for CRKP group were analyzed. Result A total of 39 premature infants with KP sepsis were included in our study. There were 23 cases in the CRKP group and 16 cases in the non-CPAP group. In CPKP group, the gestational age was (29.5 ± 0.6) weeks, the birth weight was (1177 ± 272) g. In non-CRKP group, the gestational age was (30.0 ± 0.5) weeks, the birth weight was (1387 ± 220) g. Univariate Logistic regression analysis showed that low birth weight was a risk factor for CRKP sepsis in premature infants (OR=1.203, 95％CI 1.068～1.355, P=0.002). The proportion of that required combination treatment with antibiotics and the incidence of intracranial hemorrhage after infection in the CPKP group were both higher than that in the non-CRKP group (P<0.05). The proportion and duration of antibiotics used in the first week before the onset of infection in infants with CRKP sepsis and combined antibiotic treatment were significantly higher than those in infants with CPKP sepsis and single antibiotic treatment. The use of antibiotics in the first week before the onset of infection was an independent risk factor for the combined drug treatment of premature infants with CRKP sepsis (OR=10.500, 95％CI 1.015～108.577, P=0.049). In the CRKP group, the improvement rate was 87.0％(20/23), 2 cases were withdrew, and 1 case deceased. In the non-CPKP group, the improvement rate was 87.5％(14/16), and 2 deceased. Conclusion The lower the birth weight, the greater the risk of infection with CRKP sepsis. The proportion of need combination treatment with antibiotics is high in infants with CRKP sepsis. The use of antibiotics in the first week before the onset of infection is a risk factor for combined antibiotic treatment in premature infants with CRKP sepsis .

Objective To study the clinical effects of continuous blood purification (CBP) in the treatment of newborns with severe sepsis and multiple organ dysfunction syndrome (MODS). Method From May 2013 to November 2018, the clinical data of infants with severe sepsis and MODS receiving CBP in the neonatal department of our hospital were retrospectively analysed. Changes of blood pressure, arterial partial pressure of oxygen/inhaled oxygen concentration (PaO2/FiO2), pH, serum potassium, sodium, urea nitrogen, creatinine, urine volume and maintenance dose of adrenaline at different time points before and after CBP were analysed. Result According to the inclusion and exclusion criteria, a total of 8 newborns with sepsis and MODS were enrolled in the study. One patient had the complication of perforated colon, and the other one had acute renal failure. The number of affected organs in these infants was 3～5. Six cases began CBP treatment within 1～5 days after admission, and the other two cases began CBP treatment on the 38th and 47th days after admission. The average treatment duration was (58.6±25.9) h. The effective rate of CBP in the treatment of severe sepsis with MODS was 75.0％(6/8). Blood pressure was increased at 6 h, 12 h, 24 h and 48 h after treatment and at the end of treatment. PaO2/FiO2 and blood pH were increased. The urine volume was increased at 24 h and 48 h after treatment and at the end of treatment (P<0.05). Serum potassium, urea nitrogen and creatinine were significantly decreased (P<0.05). The maintenance dose of adrenaline was also decreased significantly at 12 h after CBP (P<0.05), and withdrawn at 48 h after treatment. Only one case experienced membrane blockage during CBP. Dialysis was continued after the replacement of filtration membrane. No other complications existed. Conclusion CBP is effective in the treatment of neonatal severe sepsis with MODS. It can improve the circulation and renal function.