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Background: Intestinal failure–associated liver disease (IFALD), initially manifesting as cholestasis, is a complication in neonates receiving parenteral nutrition (PN). Soybean oil lipid emulsion (SOLE), though implicated in IFALD, was the only US Food and Drug Administration (FDA)–approved initial intravenous lipid emulsion (ILE) for infants and children in the United States. A mixed‐oil lipid emulsion (MOLE) gained popularity in patients at risk for IFALD and was recently FDA approved as an initial ILE in children. Given the presence of soybean oil in MOLE, we hypothesized that MOLE would not be effective at preventing cholestasis in surgical neonates. Methods: Neonates with gastrointestinal surgical conditions necessitating PN for ≥14 days and receiving MOLE (SMOFlipid) from July 2016 to July 2019 were analyzed retrospectively. Unpaired and pair‐matched historical surgical neonates treated with SOLE (Intralipid) served as controls. The primary outcome measure was development of cholestasis (direct bilirubin ≥2 mg/dl). Results: Overall, 63% (10 of 16) of MOLE patients and 22% (30 of 136) of SOLE patients developed cholestasis after ≥14 days of therapy (P = 0.005). The latency to developing cholestasis was significantly shorter in MOLE patients compared with SOLE patients. Conclusion: In surgical neonates, MOLE may not prevent cholestasis and should not be considered hepatoprotective. Regardless of ILE source, all surgical neonates should be closely monitored for development of IFALD. To date, there is still no ILE able to prevent IFALD. [ABSTRACT FROM AUTHOR]

Background: Parenteral nutrition-associated cholestasis (PNAC) is a major cause of morbidity and mortality in premature infants. Early predictors of PNAC would have clinical value. We sought to evaluate risk factors and liver function testing as predictors of PNAC in premature infants with intestinal perforation.Methods: Medical records of infants with a gestational age <34 weeks, birth weight <2000 g, and intestinal perforation due to either necrotizing enterocolitis or spontaneous intestinal perforation were reviewed. We analyzed clinical data and the maximum values of the aspartate aminotransferase (AST) to platelet ratio index (APRI), alanine aminotransferase (ALT), AST to ALT ratio, and total bilirubin (TB).Results: Sixty infants were identified, 17 infants with PNAC and 43 infants without PNAC. Sepsis, time to initiation of enteral feeds after perforation, and duration of PN were associated with PNAC. Within 2 weeks following intestinal perforation, APRI, ALT, and TB each differed significantly between infants who later developed PNAC and those that did not. The best APRI cut-point was 0.4775 within 2 weeks after perforation (area under the receiver operating characteristic curve, 0.90; positive predictive value, 85%; and negative predictive value, 87%); the cut-point for ALT was 13.5 (0.90, 85%, 84%), and the cut-point for TB was 3.55 (0.82, 69%, 83%), respectively, at 2 weeks after perforation. AST to ALT ratio did not differ between groups.Conclusions: APRI and ALT had reasonable predictive value for PNAC in premature infants with intestinal perforation, with the APRI the best predictor within 2 weeks after perforation. [ABSTRACT FROM AUTHOR]

Aim: Parenteral nutrition (PN) provides an alternative nutrition source for preterm infants who are intolerant of enteral nutrition. However, prolonged PN increases the risk of PN-associated cholestasis (PNAC). We conducted this study to determine the incidence and risk factors of PNAC in extremely low birth weight (ELBW) infants.Methods: We retrospectively reviewed the medical records of ELBW infants from March 2010 to April 2015. PNAC was diagnosed in infants with a history of PN for at least two weeks and direct bilirubin concentrations >2 mg/dL after other causes of neonatal cholestasis were excluded.Results: Of the 114 eligible ELBW infants, 41 (36%) were diagnosed with PNAC. The multivariate analysis showed that birth weight, sepsis, necrotising enterocolitis, fluconazole prophylaxis and the duration of PN and hospitalisation were independent risk factors for the development of PNAC (p < 0.05). However, parenteral fish oil-based lipid preparation (FOLP) did not reduce the risk of PNAC. Although PNAC was not a direct cause of death, it was associated with an increased risk of mortality.Conclusion: PNAC was common in ELBW infants, was associated with various clinical factors and increased the risk of mortality. However, we did not observe the protective effect of FOLP against PNAC. [ABSTRACT FROM AUTHOR]

Purpose: Parenteral nutrition (PN)-associated cholestasis (PNAC) is one of the most common complications in very low birth weight infants (VLBWIs). The aim of this study is to evaluate the risk factors of PNAC in VBLWIs. Methods: We retrospectively reviewed the medical records of 322 VLBWIs admitted to the neonatal intensive care unit of our hospital from July 1, 2009 to December 31, 2013. We excluded 72 dead infants; 6 infants were transferred to another hospital, and 57 infants were transferred to our hospital at 2 weeks after birth. The infants were divided into the cholestasis and the non-cholestasis groups. PNAC was defined as a direct bilirubin level of ≥2.0 mg/dL in infants administered with PN for ≥2 weeks. Results: A total of 187 VLBWI were enrolled in this study; of these, 46 infants developed PNAC. Multivariate logistic regression analysis showed that the risk factors of PNAC in VLBWI were longer duration of antimicrobial use (odds ratio [OR] 4.49, 95% confidence interval [95% CI] 4.42-4.58), longer duration of PN (OR 2.68, 95% CI 2.41-3.00), long-term lack of enteral nutrition (OR 2.89, 95% CI 2.43-3.37), occurrence of necrotizing enterocolitis (OR 2.40, 95% CI 2.16-2.83), and gastrointestinal operation (OR 2.19, 95% CI 2.03-2.58). Conclusion: The results of this study suggest that shorter PN, aggressive enteral nutrition, and appropriate antimicrobial use are important strategies in preventing PNAC. [ABSTRACT FROM AUTHOR]

Background: Infants receiving prolonged parenteral nutrition (PN) are at risk of PN-associated cholestasis (PNAC). This can progress to hepatic failure and death if PN cannot be discontinued. Fish oil-based parenteral lipid preparation (FOLP) has been shown to be beneficial in case studies. Objectives: (1) To evaluate whether FOLP could halt or reverse the progression of PNAC compared with soy-based parenteral lipid preparation (SLP) and (2) to assess the effects of FOLP on liver function and physical growth. Methods: Design: double-blind randomised controlled trial. Setting: level III neonatal intensive care unit. Participants: infants with PNAC (plasma-conjugated bilirubin concentration ≥34 µmol/l or 2 mg/dl) expected to be PN-dependent for >2 weeks. Intervention: to receive either FOLP or SLP at 1.5 g/kg/day. Primary outcome measure: reversal of PNAC within 4 months after commencement of lipid treatment; secondary outcomes: rate of change of weekly liver function tests, infant growth parameters, blood lipid profile and episodes of late-onset sepsis. Results: A total of 9 infants were randomised to the FOLP group and 7 to the SLP group. There was no significant difference in reversal of PNAC at 4 months between groups. Rates of increase of plasma-conjugated bilirubin and alanine aminotransferase in the SLP group were significantly greater than the FOLP group (13.5 vs. 0.6 µmol/l per week and 9.1 vs. 1.1 IU/l per week, respectively, p = 0.03). Increased enteral nutrition was associated with significant improvement of PNAC in infants receiving FOLP compared with SLP (-8.5 vs. -1.6 µmol/l per 10% increase in enteral nutrition, respectively). The study was terminated prematurely. Conclusions: progression of PNAC in PN-dependent infants can be halted by replacing SLP with FOLP and reversed by increasing the proportion of enteral nutrition in infants receiving FOLP. Replacement of SLP with FOLP in PN-dependent infants who develop PNAC may be considered. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Exposure to parenteral nutrition (PN) is one major factor in the development of cholestasis. The aim of this retrospective study was to compare the effect of these two different PN regimens on PN-associated cholestasis (PNAC). The files of the patients who have received different PN regimens for >14 d in 2005 and 2009 were retrospectively reviewed. 133 patients have received PN more than 14 d. 22 (16.5%) patients had PNAC. 90 neonates were in Group low-dose parenteral (LDpn) and 43 neonates in Group high-dose parenteral. Mean gestational age and birth weight were statistically significantly lower in LDpn Group ( p = 0.016, p = 0.434). Cholestasis rate was significantly higher in high dose group. ( p = 0.023). Although several risk factors for PNAC are unavoidable, research is still needed to define the optimal parenteral amino acid solution for neonatal patients. Individualized PN may be more affective in allowing growth and minimizing side effects. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: Surgical infants requiring long-term parenteral nutrition (PN) are at risk for parenteral nutrition-associated liver disease (PNALD). The purpose of this study was to determine the effect of a lipid restricted PN regimen in preventing the development of PNALD in surgical infants. Methods: In 2009, we implemented a lipid restricted strategy in surgical infants expected to be on long-term PN using a soy-based lipid emulsion at a goal provision of 1g/kg/day throughout a patient''s entire PN course. An experimental cohort of surgical infants treated with lipid restriction from 2009 to 2011 (n=82) was retrospectively compared to a control cohort of infants from 2005 to 2008 receiving standard intravenous lipid dosing (n=132). A multivariable relative risk regression model was constructed analyzing the association between lipid restriction and PNALD. Results: Patients admitted during the lipid restriction era had reduced daily lipid provisions compared to the control group (p<0.001). There were no significant differences in demographic or measured clinical characteristics between the two groups. A significant reduction in the incidence of PNALD was demonstrated in the lipid restricted group compared to the control group (22% vs. 43%, p=0.002). On multivariable relative risk regression, patients treated with standard lipid provisions were 1.77 times more likely to develop PNALD than patients who were lipid restricted (95% CI: 1.2–2.7; p=0.007). Conclusion: Restriction of intravenous soy-based lipid in PN-fed surgical infants is associated with a reduction in the incidence of liver disease. Early lipid restriction should be considered in all surgical infants who require PN as a preventative measure against PNALD. [Copyright &y& Elsevier]

Background. Parenteral nutrition (PN) is an effective method of nourishing the neonate who is unable to receive full enteral feeds. Cholestasis canbe a complicationof PNandcan lead to severe liverdamage. Aim. We describe our patient population and determine risk factors for developing PN cholestasis. Methods. Retrospective chart review of newborns admitted from January 2006 to May 2011 to the Neonatal Intensive Care Unit at our institution and received PN >14 days. Cholestasis was defined as serum conjugated bilirubin >50 μmol/L. Results. Eighty-seven newborns were included; 18 (20.7%) developed PN cholestasis. The most frequent surgical condition for both groups was gastroschisis (8/87; 9.2%). No significant differences were found between the cholestasis and control groups for the following parameters: birth weight, gestational age, intrauterine growth restriction, Apgar scores, and day of life at initiation of enteral feeds. Duration of PN in days and dosage of carbohydrates in g/kg/day were significantly higher in the cholestasis group than the control group. Conclusion. PN-related cholestasis presented in one-fifth of neonates receiving PN for more than two weeks. Longer duration of PN and higher dosage of carbohydrates were independent risk factors for the development of PN cholestasis in this population. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: The aim of this study was to determine the incidence of cholestasis and the correlation between cholestasis and weight-for-age z scores in parenteral nutrition–dependent neonates with gastroschisis. Methods: A single-center retrospective review of 59 infants born with gastroschisis from January 2000 to June 2007 was conducted. Demographic and clinical data were collected and analyzed. Subjects were divided into cholestatic and noncholestatic groups. Statistical analyses included the Student t test, Wilcoxon rank sum test, Fisher exact test, and a general linear model. Results: Fifty-nine neonates with gastroschisis were identified, and 16 (28%) of 58 patients developed cholestasis. Younger gestational age and cholestasis were found to be independently associated with weight-for-age z score in 30 of 58 patients with available long-term follow-up data. Conclusions: Parenteral nutrition–dependent neonates with gastroschisis remain at considerable risk for the development of cholestasis. Both gestational age and cholestasis were found to be independent risk factors, predisposing these neonates to poor postnatal growth. [Copyright &y& Elsevier]

Abstract: Background/purpose: Despite advances in pediatric nutritional support and a renewed focus on management of intestinal failure, there are limited recent data regarding the risk of parenteral nutrition (PN)–associated liver disease in surgical infants. This study investigated the incidence of cholestasis from PN and risk factors for its development in this population. Methods: A retrospective review was performed of all neonates in our institution who underwent abdominal surgery and required postoperative PN from 2001 to 2006. Cholestasis was defined as 2 conjugated bilirubin levels greater than 2 mg/dL over 14 days. Nonparametric univariate analyses and multivariate logistic regression were used to model the likelihood of developing cholestasis. Median values with range are presented. Results: One hundred seventy-six infants met inclusion criteria, and patients received PN for 28 days (range, 2-256 days). The incidence of cholestasis was 24%. Cholestatic infants were born at an earlier gestational age (34 vs 36 weeks; P < .01), required a 3-fold longer PN duration (76 vs 21 days; P < .001), had longer inpatient stays (86 vs 29 days; P < .001), and were more likely to be discharged on PN. The median time to cholestasis was 23 days. Cholestasis was an early development; 77% of cholestatic infants developed cholestasis by 5 weeks of PN exposure. On multivariate regression, only prematurity was significantly associated with development of cholestasis (P < .05). Conclusion: In this analysis, the development of PN-associated liver disease occurred early in the course of exposure to PN. These data help to define the time course and prognosis for PN-associated cholestasis in surgical infants. [Copyright &y& Elsevier]

The infusion of Intralipid® is a main risk factor for parenteral nutrition-associated cholestasis in infants with short bowel syndrome. Early provision of enteral fat to reduce the use of Intralipid while providing adequate fat for the growth of infants with short bowel has not been reported. We present 2 cases of premature infants with short bowel who received early supplementation of enteral Microlipid® and fish oil. This approach allowed us to discontinue Intralipid shortly after initiating feedings. The infants tolerated Microlipid/fish oil well without adverse reactions, had appropriate weight gain and ostomy output. They underwent bowel reanastomosis 3 weeks after enteral feeding began, and were discharged on full oral feedings. In case 1, the infant did not develop parenteral nutrition-associated cholestasis; in case 2, cholestasis had developed before initiating feeds, but was not aggravated by enteral fat and was improving prior to discharge. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Parenteral nutrition associated liver disease (PNALD) is an important problem in patients who require long-term parenteral nutrition as well as in preterm infants. Prevalence varies according to different series. Clinical presentation is different in adults and infants. Although since its first descriptions several hypothesis have been elucidated, the aetiology is not quite clear. It is possible that different factors could be involved. PNALD risk factors can be classified in three groups: 1) those derived from the lack of enteral nutrition stimulus; 2) parenteral nutrition components acting as toxic or the lack of specific nutrients and 3) those due to the underlying disease. If PNALD appears in short-term PN and it presents only as a mild elevation of liver enzymes, there is no need to treat. On the contrary, when direct bilirubin is > 2 mg/dL and lasts longer, there is a need to consider different causes and to minimize risk factors. We review the different approaches to manage PNALD, including optimizing enteral nutrition, modify parenteral solutions, use of specific nutrients -taurine, choline, etc.- or the use of drugs (mainly ursodeoxicolic acid) If liver disease progresses to a cirrhosis a liver transplant must be considered. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Parenteral nutrition–associated cholestasis (PNAC) occurs in up to 60% of surgical neonates with intestinal failure, and 10% will develop end-stage liver failure. Our aim was to evaluate the effectiveness of percutaneous transhepatic transcholecystic cholangiography (PTTC) in the treatment of PNAC in surgical neonates. Methods: A retrospective double cohort study of surgical neonates with PNAC was conducted. Patients with PNAC who received PTTC were compared to controls matched by gestational age, birth weight, sex, and parenteral nutrition duration. Percutaneous transhepatic transcholecystic cholangiography was performed under general anesthesia with ultrasound guidance. Analysis was performed using paired Student''s t test and McNemar χ 2 test. Results: Nine PTTC patients and 9 controls were similar in mean age (35.5 ± 3.1 vs 35.6 ± 4.2 weeks, P = .85), birth weight (2531 ± 879 vs 2692 ± 1052 g, P = .28), sex (all males), and parenteral nutrition duration (51.2 ± 29.8 vs 53.3 ± 33.3 days, P = .74). Percutaneous transhepatic transcholecystic cholangiography was performed in 9 patients at mean corrected age of 5.5 ± 3.4 weeks and weight of 3621 ± 546 g. All control patients and 8 (88.9%) of 9 PTTC patients had eventual resolution of hyperbilirubinemia. Percutaneous transhepatic transcholecystic cholangiography patients experienced a more rapid rate of resolution of their cholestasis, and the mean time to resolution of conjugated bilirubin was less in the PTTC group (8.5 ± 3.2 vs 18.5 ± 7.6 weeks, P = .02). Conclusion: Therapeutic PTTC results in a 50% reduction in the time to PNAC resolution. Percutaneous transhepatic transcholecystic cholangiography may have a role as active therapy to slow progression of PNAC in surgical neonates with intestinal failure. [Copyright &y& Elsevier]

Abstract: Objective: Infants with chronic cholestasis may require parenteral nutrition with lipid emulsions to provide energy and essential fatty acids but the optimal strategy is controversial. Methods: We studied the effects of parenteral lipid emulsions with long-chain triacylglycerols (LCTs) or a mixture of LCTs and medium-chain triacylglycerols (MCTs/LCTs) on serum bilirubin and lipid metabolism in cholestatic infants who received these 20% emulsions in alternating order for 3 d each, together with a glucose and amino acid infusion. Results: Of 11 recruited infants, two dropped out because enteral feeding could be established. In nine infants (2–8 mo of age, mean age 4.2 mo) who completed the study, serum bilirubin decreased from baseline to 6 h after the end of LCT infusion (from 8.5 ± 2.0 to 7.8 ± 1.8 mg/dL, mean ± SEM, P < 0.05) and MCT/LCT infusion (7.9 ± 6.5 to 7.1 ± 6.5 mg/dL, P < 0.05). Cholesterol, triacylglycerol, and phospholipid concentrations in plasma and in chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein were not changed by either emulsion. Total polyunsaturated fatty acid contents in high-density lipoprotein phospholipids increased during LCT infusion (from 29.8 ± 0.9 to 35.9 ± 1.4% wt/wt, P < 0.05) and MCT/LCT infusion (from 30.4 ± 1.0 to 33.0 ± 0.7%, P < 0.05). The long-chain polyunsaturated fatty acid docosahexaenoic acid increased only with the LCT infusion. Because docosahexaenoic acid availability during infancy is important for early visual and cognitive development, the use of soybean oil–based lipid emulsions may be preferable for infants with severe progressive cholestasis. Conclusion: The MCT/LCT and LCT emulsions showed a good metabolic tolerance in infants with chronic cholestasis but had a differential effect on high-density lipoprotein phospholipid contents of arachidonic and docosahexaenoic acids. [Copyright &y& Elsevier]

Abstract: Background: The role of isolated liver transplantation in infants with parenteral nutrition–associated cholestasis (PNAC) associated with short bowel syndrome (SBS) is unclear. Methods: We performed a retrospective descriptive study of infants with PNAC and SBS who received an isolated liver transplant at our institution. Review of the literature was also performed. Results: Three infants (aged 7, 8, and 13 months) with SBS and PNAC received an isolated liver transplant. Etiology of SBS was necrotizing enterocolitis, gastroschisis, and volvulus. Two patients with pretransplant small bowel length of 40 and 80 cm, who were receiving 65% and 79% of intake enterally, demonstrated good graft function (bilirubin, 0 and 7 μmol/L) at 41 and 58 months posttransplant. Despite full tolerance of enteral feeds, both remain on parenteral nutrition (PN) (4 and 7 nights per week) for poor weight gain. One child with 25 cm of small bowel, who received 65% of energy enterally pretransplant, died 7 months posttransplant from PNAC. A literature review revealed 22 cases of isolated liver transplant for PNAC associated with SBS. Overall survival was 77%, with 76% of survivors demonstrating independence from PN. Conclusions: Isolated liver transplantation is an acceptable option for select infants with PNAC associated with SBS when further intestinal adaptation and freedom from PN are anticipated. [Copyright &y& Elsevier]

OBJECTIVE:: To compare the incidence of parenteral nutrition-associated cholestasis (PNAC) between two pediatric parenteral amino-acid formulations, Aminosyn PF (APF) and Trophamine (TA). STUDY DESIGN:: Setting: Tertiary newborn intensive-care nursery. Subjects: A total of 661 neonates who received either TA or APF. Design: Retrospective. The incidence of PNAC was determined in three groups: Group I (TA, 8/19/97 to 8/19/98, n=335), Group II (APF, 8/20/98 to 1/28/99, n=157), and Group III (TA, 1/29/99 to 8/1/99, n=169). RESULTS:: No PNAC developed in any infant receiving parenteral nutrition (PN) for <3 weeks. Of 141 patients given PN for =21 days, 24 were diagnosed with PNAC: Group I (TA, 10/78, 12.8%), Group II (APF, 9/27, 33.3%), and Group III (TA, 5/36, 13.9%). The incidence of PNAC was significantly higher in infants who received APF (p=0.043). Using logistic regression, only birth weight, duration of PN, and use of APF were significant risk factors for the development of PNAC. Despite an earlier initiation of enteral feedings, APF recipients developed PNAC sooner, had higher peak direct bilirubin levels, and remained jaundiced longer. CONCLUSIONS:: The use of APF was temporally associated with a greater than two-fold increase in the incidence of PNAC compared to periods of exclusive TA use. In the absence of significant differences in parenteral nutrient or energy intake in neonates who developed PNAC, we speculate that possible differences between the amino-acid compositions of TA and APF may be responsible for the observed differences in the incidence of PNAC.Journal of Perinatology (2003) 23, 444-450. doi:10.1038/sj.jp.7210965 [ABSTRACT FROM AUTHOR]

Pathological icterus with elevation of direct bilirubin (cholestasis) may be caused by many reasons, but immature liver of a premature child is particularly prone to cholestasis due to various etiological factors. We present a case of a premature infant with cholestasis in the course of parenteral nutrition and generalized infection. We emphasize that in the developmental period diagnostic examinations should be thorough and multidirectional. [ABSTRACT FROM AUTHOR]