Clinical Features Of Parenteral Nutrition Associated Cholestasis In Very Low Birth Weight Infants

Parenteral nutrition(PN)is an important nutrition technology in neonatal intensive care unit(NICU).It improves the survival rate of preterm infant,especially very low birth weight(VLBW)infant and extremely low birth weight(ELBW)infant.With the improvement of PN technology,the complications were gradually recognized,which include metabolic imbalance,thrombus embolism,sepsis,cholestasis,and so on.Parenteral nutrition-associated cholestasis(PNAC)is the most common and serious complication,with a small proportion developing cholestatic liver failure or cirrhosis.ObjectiveThe aim of this study is to investigate the clinical features and risk factors of PNAC in VLBW infant,and improve the early diagnosis,therapy and prevention as well.MethodsThe medical records of 82 VLBW infants admitted to the NICU in Children's Hospital of Zhejiang University School of Medicine from January 2014 to June 2016 were reviewed.Inclusion criteria included patients for gestational age less than 37 weeks and gestational weight less than 1500g.All patients received PN over 14 days and admitted to our hospital within the first three days of life.Exclusion criteria included the cholestasis attributable to congenital infection,anatomic obstruction of the hepatobiliary tract,inherited metabolic disorders.In addition,PNAC was defined as the direct bilirubin greater than 34?mol/L(2.0mg/dl)during the entire course of PN.A total of 21 patients who had PNAC were aligned into the PNAC group,the remaining 61 patients without PNAC were defined as non-PANC group.All infants with cholestasis underwent liver ultrasound and testing for infections hepatitis.Hepatic function damage was defined as elevated glutamic-pyruvic transaminase(ALT)>50U/L,and/or glutamic oxalacetic transaminase(AST)>50U/L,without hemolysis.PN was started with 6%amino acid solution in the first 24 hours of life and 20%lipid solution in the first 2-3 days of life.The starting dose of amino acid and lipid solution were 1-3g/(kg·d),and increased by 0.5-1g/(kg·d)until 4.5g/(kg·d)and 3.0g/(kg·d),respectively.The starting volume of total infusion was 80-100ml/(kg·d),and increased by 10-20ml/(kg·d)until 140-180ml/(kg·d).Dextrose was initiated on the first day,with the glucose infusion dose of 6-8g/(kg·d)and advanced to maximum of 16-18g/(kg·d)when needed.Calories of glucose were more than 50%total calories.Non-nitrogenous calories all nutrient solutions provided were 86-210J/(kg·d).Liver function tests,total bilirubin and direct bilirubin were checked at weekly intervals to monitor for PN complications.The clinic data,including the incidence,time of onset and hepatic injury of PNAC,were investigated.The independent t-test was used for measurement data,and chi-square test or Fisher exact test was used for enumeration data.Multivariate logistic regression analysis was performed to evaluate the independent factors of PNAC.Significance lever was set at p<0.05.ResultThe incidence of PNAC in VLBW infant was 25.6%and the time of onset was(44±13.3)days after beginning PN.Among PNAC patients,52.4%suffered from hepatic injury,hepatic injury occurred(57±10.1)days after beginning PN.Compare the clinic data between the groups,feeding intolerance,neonatal necrotizing necroticolitis(NEC),patent ductusarteriosus(PDA),and neonatal sepsis were obvious different between the two groups.The duration of PN exposure,fasting time,average amounts of lipids,cumulative dose of acid,lipids and glucose,the calories ratio of protein to nonprotein,mechanical ventilation,surgical operation of PDA,and intracranial hemorrhage were significantly different between the two groups.Multivariate logistic regression analysis showed that longer duration of fasting,PDA and feeding intolerance were independent risk factors of PNAC.Firstly,fasting time have positive correlation with PNAC.The longer fasting time,the incidence of PNAC is higher.Secondly,infants with PDA have higher incidence of PNAC comparing with infants without PDA.Thirdly,the more feeding intolerance,the incidence of PNAC is higher.Conclusion1.PNAC is one common complication of PN.2.Longer duration of fasting,PDA and feeding intolerance were risk factors of PNAC.