Parenteral Nutrition-associated Cholestasis In Neonates Research Articles

Sepsis and bronchopulmonary dysplasia as potential risk factors for parenteral nutrition-associated cholestasis in neonates: a meta-analysis of retrospective studies.

The aim of this study was to evaluate whether sepsis and bronchopulmonary dysplasia (BPD) are risk factors for parenteral nutrition-associated cholestasis (PNAC) and to provide suggestions for the prevention of PNAC in infants. Electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) were searched for studies published up to October 22, 2017. Associations between sepsis, BPD and PNAC were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic, and subgroup analyses were performed. Nine studies incorporating a total of 2248 cases were included in the meta-analysis. Sepsis was significantly associated with PNAC (pooled OR=2.04; 95% CI: 1.23-2.85), but BPD was not (pooled OR=1.22; 95% CI: 0.65-1.78). In a subgroup analysis, BPD was not associated with PNAC in either the non-Asian group (pooled OR=1.38; 95% CI: 0.58-2.18) or the Asian group (pooled OR=1.05; 95% CI: 0.26-1.84). Sepsis, but not BPD, was a risk factor for PNAC in this meta-analysis. Further studies are needed to confirm the findings.

Comparison of Two Lipid Emulsions on the Incidence of Parenteral Nutrition Associated Cholestasis in Neonates.

Lipid emulsion contributes to parenteral nutrition associated cholestasis (PNAC). For decades, soybean oil-based intravenous lipid emulsion (SO-ILE) was the predominant product. Recently, a multicomponent lipid emulsion containing soybean oil, medium-chain triglycerides, olive oil and fish oil (SMOF-ILE) has been used off-label in neonatal care. This study evaluates the incidence of PNAC in neonates who received SMOF-ILE or SO-ILE. This was a retrospective review of neonates who received SMOF-ILE or SO-ILE for at least 14 days. Patients receiving SMOF-ILE were matched based on gestational age (GA) and birth weight to a historical cohort receiving SO-ILE. The primary outcomes were the incidences of PNAC among all patients and patients without intestinal failure. The secondary outcomes were clinical outcomes and incidence of PNAC stratified by GA. Clinical outcomes included liver function tests, growth parameters, and development of retinopathy of prematurity and intraventricular hemorrhage. Forty-three neonates who received SMOF-ILE were matched to 43 neonates who received SOILE. There were no significant differences in baseline characteristics. The incidence of PNAC in the total population was 12% in the SMOF-ILE cohort and 23% in the SO-ILE cohort (p = 0.26). The lipid dosage of SMOF-ILE was significantly higher at time of peak direct serum bilirubin concentration compared with SO-ILE cohort (p = 0.05). Clinically significant differences were noted in laboratory endpoints in several subgroups. There was no significant difference in the incidence of PNAC among neonates in a SMOFILE cohort compared with a historical SO-ILE cohort.

Sepsis and bronchopulmonary dysplasia as potential risk factors for parenteral nutrition-associated cholestasis in neonates: a meta-analysis of retrospective studies

The aim of this study was to evaluate whether sepsis and bronchopulmonary dysplasia (BPD) are risk factors for parenteral nutrition-associated cholestasis (PNAC) and to provide suggestions for the prevention of PNAC in infants. Electronic databases (PubMed, EBSCO, Elsevier, Springer, Wiley, and Cochrane) were searched for studies published up to October 22, 2017. Associations between sepsis, BPD and PNAC were assessed using odds ratios (ORs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic, and subgroup analyses were performed. Nine studies incorporating a total of 2248 cases were included in the meta-analysis. Sepsis was significantly associated with PNAC (pooled OR 2.04; 95%CI 1.23-2.85), but BPD was not (pooled OR 1.22; 95%CI 0.65-1.78). In a subgroup analysis, BPD was not associated with PNAC in either the non-Asian group (pooled OR 1.38; 95%CI 0.58-2.18) or the Asian group (pooled OR 1.05; 95%CI 0.26- 1.84). Sepsis, but not BPD, was a risk factor for PNAC in this meta- analysis. Further studies are needed to confirm the findings.

Parenteral nutrition associated cholestasis

Parenteral nutrition (PN) is life saving for many preterm infants and other neonates with severe illness, but prolonged use of PN can lead to intrahepatic cholestasis, referred to as parenteral nutrition–associated cholestasis (PNAC). It is defined as direct bilirubin greater than 2.0 mg/dL persistent for at least 2 consecutive tests duringthe administration of PN, not associated with other known causes of cholestasis [1-3]. With the increasing survival of preterm infants and neonates requiring intensive care, PNAC has become a more common clinical challenge. The incidence of PNAC varywidely depending on the population studied, with high incidencein populations carrying several risk factors for PNAC. It increases with duration of PN and ranges from 10% to 85% in infants [4-8]. A multifactorial aetiology has been proposed for the development of PNAC. Recognized risk factors for PNAC include low birth weight, low gestational age, necrotizing enterocolitis, intestinal malformations, and intestinal surgery. A further risk factor is the occurrence ofsevere infections, due to the requirement for central line for infusion of PN, and bacterial overgrowth caused by enteralstarvation and immature immune function[9-13]. However, exposure to PN is demonstratedas the main factor in the development of PNAC. Intravenous hyper-alimentationhas been implicated, such as thetotal caloric overload, the quality of aminoacid solutions, the cumulative amount and the quality of lipid infusion, the presence of excessivealuminium in the PN solution, and the high manganese intake with PN [1,14-17]. Ursodeoxycholic acid, cyclic PN, light protection for PN, tapering the soybean-based lipid emulsion, and antibiotics to decontaminate bacterial overgrowth are used to treat PNAC [18-21]. In recent years, increasing attention has been paid to the lipid content in PN. It has been found that fish oil–containing lipid emulsions could be useful in infants to reverse PNAC for whom enteral feeding is intolerable. However, no evidence supports the use of fish oil–containing lipid emulsions to prevent PNAC in neonates, including preterm infants [22]. Enteral feeding remains the best strategy to reverse and prevent PNAC, with as little as 10% of caloric intake showing beneficial effects [5,22].

Parenteral Fish Oil–Containing Lipid Emulsions May Reverse Parenteral Nutrition–Associated Cholestasis in Neonates: A Systematic Review and Meta-Analysis ,

Growing evidence indicates that fish oil-containing lipid emulsions have a beneficial effect on parenteral nutrition-associated cholestasis (PNAC) in adults; however, data are limited in neonates regarding the effect of fish oil on PNAC. We conducted a meta-analysis of studies that addressed the effect of fish oil-containing lipid emulsions on reversing and preventing PNAC. We searched PubMed, the EMBASE database, and the Cochrane Library for this systematic review and meta-analysis. The methodologic assessment of studies was performed with the Jadad scale and the Newcastle-Ottawa Scale. Comprehensive Met-Analysis version 2.0 was used for the statistical analysis. We performed a meta-analysis with the primary outcomes of reversal of PNAC and the occurrence of PNAC in newborn infants, including preterm infants, after parenteral administration of fish oil-containing lipid emulsions. Of the 36 studies identified, 7 fulfilled the inclusion criteria and were used in this meta-analysis, including 3 studies with 93 participants in which reversal of PNAC was an outcome and 4 studies with 1012 participants on preventing PNAC. The use of fish oil-containing lipid emulsions was more likely to reverse PNAC (OR: 6.14; 95% CI: 2.27, 16.6; P < 0.01), but the use of fish oil-containing lipid emulsions did not have a significant effect on the development of PNAC (OR: 0.56; 95% CI: 0.28, 1.10; P = 0.09) compared with soybean-based or olive oil-based lipid emulsions. The pooled data suggest that the use of fish oil-containing lipid emulsions is effective for reversing PNAC but cannot prevent PNAC in neonates who require prolonged parenteral nutritional support.

Cumulative Amount of Intravenous Lipid Intake and Parenteral Nutrition-Associated Cholestasis in Neonates with Gastrointestinal Surgical Disorders

To evaluate if cumulative amount of intravenous lipid (IL) intake is associated with severity of parenteral nutrition (PN)-associated cholestasis (PNAC) in neonates with gastrointestinal surgical disorders (GISD). The authors performed a retrospective study including 36 neonates > 34 weeks gestational age with GISD. Neonates with metabolic liver disorders, chromosomal disorders, TORCH infections, which includes toxoplasmosis, other (syphilis, varicella-zoster, parvovirus B19), rubella, cytomegalovirus (CMV), and herpes, biliary tract anomalies, or direct hyperbilirubinemia (DHB) within first postnatal week were excluded. There was no significant difference in clinical factors between three groups of neonates: (1) without PNAC (n = 13), (2) with mild-to-moderate PNAC (DHB 1-5 mg/dL, n = 12), and (3) with severe PNAC (DHB > 5 mg/dL or PNAC with elevated amino-transaminases, n = 11) except for duration of enteral starvation and PN. Using ordered logistic regression, cumulative amount of IL, glucose, and protein intake were independently associated with severity of PNAC (p < 0.05). Comparing macronutrients as predictors of severe PNAC using receiver operating characteristic curves, the area under the curve for IL (0.583) intake was significantly larger (p = 0.008) compared with intravenous protein (0.257) and glucose (0.431) intake. IL intake is associated with and is a better predictor of severity of PNAC in neonates with GISD.

Male gender is related to the development of parenteral nutrition-associated cholestasis in neonates

Objective: The development of cholestatic jaundice is a well-recognized complication of parenteral nutrition (PN). The etiology of PN-associated cholestasis (PNAC) has not been fully established. The aim of this study was to identify the risk factors for PNAC in newborn infants. Methods: Patients who received PN containing amino acids for more than a week were enrolled. The roles of gestational age, small for gestational age, sex, surgery, sepsis, days of starting enteral feeding (EF), days until EF more than 100 mL/kg per day was attained, and composition of PN in the development of PNAC were evaluated by multiple logistic regression analysis. Results: Fifty-eight infants were exposed to PN for more than a week during the study period. Cholestasis developed in 12 of 58 subjects after the start of PN. Male gender was associated significantly with a higher incidence of cholestasis compared with female gender (83.3% vs 45.7%, respectively). Other confounding factors did not correlate significantly with the development of cholestasis. Multiple logistic regression analysis revealed that male gender was the only independent factor (odds ratio, 8.2; 95% CI, 1.4-47.0) associated with cholestasis. Conclusions: Male infants had a significantly higher risk of development of PN-associated cholestasis compared with female infants.

Parenteral nutrition-associated cholestasis in neonates: the role of aluminum.

Parenteral nutrition (PN) is an essential component in the care of premature and ill infants. The incidence of parenteral nutrition-associated cholestasis (PNAC) ranges from 7.4 to 84%. One substance in PN solutions that has been implicated in PNAC is aluminum. Aluminum loading in animals and humans causes hepatic accumulation and damage. The degree of aluminum contamination of PN solutions has decreased over time, but contamination still significantly exceeds levels that are safe for human neonates. Further study into the relationship between aluminum contamination in neonatal PN solutions and the development of PNAC is necessary.

Effect of intravenous lipid emulsions on hepatic cholesterol metabolism.

Total parenteral nutrition offers the chance of survival to children who have had extensive gut resections or gut failure. However, in infants it is often associated with serious complications including cholestatic liver disease. The causes of these complications remain unclear, although it has been suggested that the lipid emulsions used in total parenteral nutrition may be responsible. An in vitro system was developed to study the effect of lipid emulsions on hepatic cholesterol metabolism using cultured hepatocytes. Incubations of Hep G2 cells with medium containing Intralipid (Pharmacia and Upjohn, Milton Keynes, UK) demonstrated that the fat emulsion mediated a powerful dose-dependent but reversible inhibition of cholesterol uptake. In addition Intralipid was shown to stimulate the efflux of cholesterol from Hep G2 cells. The component or components of the Intralipid responsible for these effects and the mechanism by which they act remain to be established. Intravenous lipid emulsions may interfere with hepatic cholesterol metabolism in vivo. This may have implications for the development of total parenteral nutrition-associated cholestasis in neonates.