| Objective:As a population-based clinical epidemiological survey of all hospitalized neonates with sepsis in Handan in 2020,this study was aimed to profile the demographic characteristics of neonatal sepsis,including ratios and proportions of incidence,case mortality,and mortality risk factors,to investigate the baseline characteristics,etiology and outcome of severe neonatal sepsis,so as to enrich the epidemiological data of local neonatal infectious diseases.This study also can provide a reference for empirical treatment of neonatal sepsis,which is of great significance for reducing neonatal mortality in this region.Methods:The clinical data of 244 neonatal sepsis cases,hospitalized in 38 secondary and tertiary hospitals in Handan city between January 1st 2020 and December31th 2020,were retrospectively collected by means of a network database for clinical information and completed individual case questionnaires,（including information of birth status,clinical presentation,laboratory examination,diagnosis and treatment,prognosis,and maternal epidemiology,etc.）.Group comparisons were made by early-onset sepsis（EOS）and late-onset sepsis（LOS）and statistical analysis was performed,such as neonatal morbidity,mortality,and case-mortality risk factors,by according to clinico-epidemiological criteria.All the data were analyzed by using SPSS26.0software.Results:1.The total population of Handan births in 2020 was 79 290 with exclusion of 278 stillbirths and 79 012 livebirths.The total hospitalized population was10840,of whom 244 had neonatal sepsis,representing a total live birth population prevalence of 3.1 percent and total hospitalization prevalence of2.3%.Thirty-four patients with sepsis died during hospitalization or in the neonatal period,with an in-hospital mortality rate of 13.9%,a case fatality rate of 0.3%based on the total hospitalized population,and a mortality rate of 0.4‰based on the total live birth population.The overall morbidity rate was 1.2%for EOS and 14.8%for LOS;the overall morbidity rate was 1.0%for EOS and12.8%for LOS..2.Perinatal epidemiological features of neonates with sepsis:The male-to-female sex ratio was 1.74:1.The median gestational age[interquartile range]was 38.0[7.29]weeks.The median birth weight[interquartile range]was 2845[1645]grams.Resuscitation in delivery room were needed in 47.1 percent of neonates with sepsis.The proportion of resuscitation in the delivery room of neonates with various gestational ages(<28 weeks,28-31+6weeks,32-36+6weeks,37-41+6weeks,42 weeks)were 100%,93.9%,88.9%,14.5%,and0%respectively.The smaller the gestational age,the higher the odds of artificial resuscitation,and the more needs for advanced resuscitation.3.General data were compared between EOS and LOS groups:There were135 cases in the EOS group and 109 cases in the LOS group.The male to female ratios in the EOS and LOS groups were 1.76:1 and 1.73:1 respectively.There was no statistical difference in the sex ratio between the two groups（P>0.05）.EOS group was dominated by full-term infants,and the LOS group was dominated by preterm infants.There was statistically significant difference in the composition ratio between the two groups（P<0.05）.The percentage of low birth weight infants was significantly higher in the LOS group than in the EOS group,and there were statistical differences（P<0.001）.4.Comparison of maternal epidemiological data between EOS and LOS groups:The ratio of natural childbirth to cesarean delivery in the EOS group was 0.85:1 and 1.81:1 in the LOS group.The proportion of multiple births was higher in the EOS group than in the LOS group,with a statistical difference（P=0.005）.The prevalence of antenatal infections and premature rupture of membranes>18 h was significantly higher in the EOS group than in the LOS group（P=0.003 and P=0.04）.There were no significant differences between the two groups in other factors such as maternal pregnancy,number of deliveries,mode of delivery,method of delivery,amniotic fluid,placenta,umbilical cord status,gestational diabetes,gestational hypertension,and anemia（P>0.05）.5.Comparison of epidemiological data of neonates in EOS and LOS groups:Although the rates of intrauterine distress did not differ significantly between the two groups（P=0.342）,The proportion of birth asphyxia,Apgar1min≤7 and need for intrapartum resuscitation were significantly higher in the LOS group than in the EOS group,with significant differences between the two groups（P=0.003,0.009,and 0.016 respectively）.The proportions of mechanical ventilation,treatment with pulmonary surfactant and parenteral intravenous nutrition were significantly higher in the LOS group than in the EOS group（P<0.001,P<0.001,P=0.005）.The rates of invasive procedures such as endotracheal intubation,peripherally inserted central catheter,and umbilical vascular catheterization were also significantly higher in the LOS group than in the EOS group（P<0.001,P=0.026,P=0.007,P<0.001）.6.Comparison of clinical performance in EOS and LOS groups:Compared with the LOS group,the EOS group had a higher rate of edema（25.2%versus 9.2%）than the LOS group with statistically significant difference between the groups（P<0.001）.There was no statistically significant difference in the rate of other systemic abnormalities between the two groups.（P>0.05）.Signs of respiratory,urinary,and hypotonic symptoms were more frequent in the EOS group than in the LOS group,with statistical differences between the two groups（P<0.001,P=0.005,P<0.05）.Digestive,circulatory and hematologic parameters were not significantly different between the two groups（P>0.05）.7.Comparison of laboratory data from the EOS and LOS groups:The incidence of procalcitonin and cardiomyocyte CK-MB abnormalities was significantly higher in the EOS group than in the LOS group,and the difference between the two groups had statistical significance（P<0.05 for all）.The incidence leukocyte counts,platelet counts and C-reactive protein abnormalities was not significantly different between the two groups（P>0.05 for all）.8.Comparison of etiological data between the EOS and LOS groups:The frequency of blood cultures from septic neonates was 80.7%,with a positive rate of 25.9%;the frequency of cerebrospinal fluid cultures from septic patient was 27.5%,with a positive rate of 4.5%.All 54 blood/CSF culture-positive pathogens were single strains.Both EOS and LOS pathogens were predominantly Gram-positive（66.67%）,and the most common bacteria were Staphylococcus epidermidis（24.08%）,Escherichia coli（18.52%）,and Staphylococcus hemolyticusus（9.26%）.Gram-positive bacteria were resistant to Oxacillin in 53.8%and sensitive to gentamicin,vancomycin,and linezolid,whereas gram-negative bacteria were resistant to ampicillin in 70.0%and sensitive to ceftriaxone,levofloxacin,and ciprofloxacin.There were no significant differences in the detection rate between the EOS and the LOS groups with 16 and 38 isolates in both groups respectively（P>0.05）.9.Comparison of the application of antibiotics in the EOS and LOS groups:All patients with sepsis were treated with varying doses of antibiotics for a median of 7 days.Seventy-four（30.3%）patients with sepsis were treated with long-term antibiotic therapy（≥14 days）.The proportion of patients in the EOS group receiving two or more antimicrobial agents and the proportion of patients in the LOS group receiving long-term antimicrobial therapy were significantly higher（P<0.05 and P=0.042）.10.Comparison of complications in the EOS and LOS group:Septic neonates had the following common complications:infectious pneumonia（48.4%）,purulent meningitis（11.9%）,necrotic enterocolitis（8.2%）.The rate of purulent meningitis complication was higher in the EOS compared with LOS group（P=0.045）,and the incidence of other complications was not statistically different between the two groups（P>0.05）.11.Comparison of outcomes in the EOS and LOS group:the median hospital expenses for neonatal sepsis was 2.53[IQR 3.93]million,with a median hospital stay of 10.5[13.0]days and a recovery rate of 86.1%.Hospital costs were significantly higher in the LOS group than in the EOS group（P<<0.05）,but there was no significant difference between the two groups in hospital stay,recovery rate,or hospital mortality（P>0.05）.12.Analysis of risk factors for death:Malnutrition,septic shock,and necrotizing enterocolitis were independent risk factors for neonatal sepsis mortality（OR>1,P<0.05）,and malnutrition in particular was a strong risk factor for neonatal sepsis mortality（OR>7）.Conclusion:1.The incidence of neonatal sepsis in the regional live births,total hospitalization rate,and cure rate were similar to those reported in domestic and abroad regions,indicating that significant progress has been made in Handan in neonatal sepsis rescue;nevertheless,the hospital mortality rate in Handan is higher than in the regions in more economically developed country,indicating that the level of neonatal rescue for critically ill neonates in Handan city is still very far behind from that in other developed regions.2.Patients with EOS had a higher rate of premature rupture of membrane and prenatal infection.Patients with LOS had a higher rate of resuscitation and invasive procedures.This study suggests that standardized management of perinatal premature rupture of membrane should be strengthened to reduce severe postnatal infections in the early postnatal period,and intensive management of preterm infants should be performed to avoid birth asphyxia and nosocomial infections so as to reducing the prevalence and mortality of neonatal sepsis.3.The clinical feature of neonatal sepsis is atypical.EOS is more likely to present with edema,symptoms of respiratory and urinary systems,and hypotonic signs,with a high rate of complicated pyogenic meningitis.Poor feeding is a strong risk factor for neonatal mortality in neonates with sepsis,suggesting clinicians to improve the identification ability of high-risk newborns,and to treat severe complications aggressively such as septic shock and necrotizing enterocolitis,in order to reduce mortality of critically ill sepsis.4.Cultured specimens in this region have low yield,high rate of pathogen resistance,high rate of long-term use of antimicrobial agents,and high multi-species yield.We should strengthen the awareness of etiological diagnosis,familiarize ourselves with the local bacterial spectrum and drug resistance,start empiric rescue medications as soon as possible,use antibiotics appropriately according to the results of drug sensitivity of the causative microorganism,reduce invasive procedures,so as to reduce the risk of recurrent infant deaths ultimately.5.Analysis of high-risk factors for septic mortality suggests that clinicians should pay attention to poor feeding,beware of early symptoms,and actively treat complications such as septic shock and necrotizing enterocolitis so as to reduce mortality in neonates with severe sepsis.6.In clinical practice,clinicians should provide health care relying on sensitive,continuous observation of clinical manifestation and assessment of perinatal risk factors,early identification of potentially infected neonates,accurately and promptly diagnosis,comprehensive assessment of severity of illness,prediction of the risk of deterioration and even death,and active treatment of serious complications,which is the key to the successful therapy of critical ill patients with sepsis. |
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