| Objective:In this study,a retrospective multicenter epidemiological investigation of parenteral nutrition-related cholestasis（parenteral nutrition-associated cholestasis,PNAC）in preterm infants in Hebei Province was conducted to explore the incidence of PNAC in preterm infants and its related risk factors,so as to provide a theoretical basis for the development of early intervention strategies and prevention and treatment measures for PNAC.Methods:1.This study was initiated by the Third Hospital of Hebei Medical University and the leader unit of Hebei Neonatal Cooperative Network.According to the principle of random sampling,12 neonatology units from hospitals in Hebei province were selected as the research sites.A multi-center epidemiological questionnaire for PNAC in preterm infants in Hebei Province was made.A retrospective investigation was conducted to select preterm infants from the neonatal department of the 12 hospitals from January 1,2014to August 30,2019.2.Inclusion criteria:gestational age<37 weeks,parenteral nutrition≥14days.Exclusion criteria:jaundice and liver function injury caused by other causes were excluded,such as viral hepatitis,congenital biliary dysplasia,genetic metabolic diseases,etc.3.According to the diagnostic criteria of PNAC in premature infants（Duration of PN≥14 days;Clinically presenting dark yellow skin with progressive aggravation,and/or hepatosplenomegaly,white stool color,etc.,which cannot be explained by primary disease;Direct bilirubin（DBIL）>34umol/L（2mg/d L）;Other clear causes of cholestasis,such as digestive tract malformations,genetic metabolic diseases,and congenital viral infections,were excluded）,the preterm infants meeting the inclusion and exclusion criteria were divided into PNAC group and non-PNAC group.The birth data and hospitalization data of the included premature infants were collected.Microsoft 365 was used to establish a database,and SAS 9.4 software was used for statistical analysis.4.Quantitative data will be described by means of mean,standard deviation,median,quartile,minimum and maximum,and t test or rank sum test will be used for comparison between groups according to the data situation.Enumeration data were described by frequency and percentage.Chi-square test or Fisher’s exact probability method was used for comparison between groups according to data conditions.If there is no special explanation,multivariate logistic regression analysis was used to analyze the influencing factors of PNAC.P?0.05 indicates that the difference is statistically significant.Results:1.A total of 1547 premature infants were included in this study and divided into two groups,including 98 in the PNAC group and 1449 in the non-PNAC group,with an incidence rate of 6.33%.There was no statistical difference in gender between groups（P?0.05）.There was significant statistical difference in delivery methods between groups（P=0.0008）.2.Gestational age ranged from 24+4 to 36+6 weeks,with an average gestational age of 31.493±2.07 weeks.The birth weight is between 650 and3600 grams,and the average birth weight is 1490±375.57 grams.There is significant statistical difference in gestational age and birth weight between groups（P?0.0001）.There was no statistical difference in Apgar score and maternal infection diseases during pregnancy between groups（P?0.05）.The incidence of neonatal infection,bronchopulmonary dysplasia,patent ductus arteriosus,neonatal respiratory distress syndrome,neonatal pneumonia and intracranial hemorrhage were statistically different between groups（P?0.0001）,while there was no statistical difference in the incidence of retinopathy of prematurity,neonatal anemia and necrotizing enterocolitis（P?0.05）.3.The duration of PN was 25.0±10.24d.The use time of amino acids was24.5±10.03d.The total amount of amino acids was 48.16±29.02（g/kg）.The use time of fat milk was 22.5±12.24d.The total amount of fat milk was45.86±30.62（g/kg）.The use time of glucose was 25.1±11.24d.The total amount of glucose was 177.61±97.46（g/kg）,and the average daily weight gain in PN period was 13.76±10.16（g/kg）.There were statistical differences in PN duration,amino acid use time,total amino acid,fat milk use time,total fat milk use time,glucose use time,total glucose use time,average daily weight gain in PN period between groups（P<0.05）.4.The fasting time was 1.4±2.34 days.Among the feeding methods,15cases were breast fed,567 cases were formula fed,and 965 cases were mixed fed.There were 209 children with umbilical artery intubation,387 children with umbilical vein intubation,869 children with PICC,and 1124 children with ventilator.There were 1521 cases using fluconazole,78 cases using ceftriaxone,177 cases using UDCA,43 cases using erythromycin and 506cases using probiotics.There were statistical differences in fasting time,feeding pattern,umbilical artery intubation,umbilical vein intubation,PICC,ventilator application,UDCA,probiotics and ceftriaxone between groups（P<0.05）,while there was no statistical difference between fluconazole and erythromycin（P?0.05）.5.Multivariate regression analysis showed that birth weight,neonatal respiratory distress syndrome,neonatal pneumonia,neonatal infection,intracranial hemorrhage,feeding pattern,fasting,duration of amino acid use,ventilator application,ceftriaxone,UDCA and probiotics were related risk factors for PNAC.Conclusions:1.The incidence of PNAC in 1547 premature infants included in this study was 6.33%.The lower the gestational age and birth weight,the higher the incidence.Low birth weight was an independent risk factor for PNAC.2.Among neonatal complications,neonatal infection,neonatal respiratory distress syndrome,pneumonia and intracranial hemorrhage are closely related to PNAC,and they are independent risk factors for PNAC.3.Formula feeding,fasting and long duration of amino acid is an independent risk factor for PNAC.In clinical treatment,mixed feeding,reducing the duration of fasting and PN,and carrying out enteral nutrition as soon as possible are the key factors to reduce the incidence of PNAC.4.Ventilator use is a protective factor for PNAC.Further study is needed to determine the influence of different type of ventilator and duration of ventilator use on the incidence of PNAC.Ceftriaxone can cause definite liver injury.This study showed that ceftriaxone is an independent risk factor for PNAC,which should be used with caution in clinical treatment.The application of probiotics is a protective factor of PNAC,which can effectively reduce the risk of PNAC in premature infants with PN duration≥14 days.The protective effect and security of probiotics in preterm infants with different gestational age and birth weight still needs to be confirmed by more studies.5.The incidence of PNAC is related to a variety of factors.In clinical prevention and treatment,the key factors to reduce the incidence of PNAC are to reduce fasting,carry out intestinal feeding as early as possible,shorten the duration of PN effectively,control complications,and pay attention to the choice of treatment measures and drugs. |
