Hyperuricemia and intravenous fat emulsion are risk factors for gout flares during active gastrointestinal bleeding: a case control study.

OBJECTIVE: It is well-established that patients with a history of gout are more susceptible to experiencing gastrointestinal bleeding. Gout flare during active gastrointestinal bleeding poses a significant challenge due to the gastrointestinal side effects of anti-inflammatory therapy. This study sought to investigate the risk factors associated with gout flares during episodes of gastrointestinal bleeding. METHODS: We conducted a retrospective observational study involving 94 patients who experienced active gastrointestinal bleeding and had a history of gout. This study was conducted at Jinhua Municipal Central Hospital from January 2019 to October 2022. We collected and recorded demographic information and clinical characteristics. RESULTS: Among the gout flare patients, hyperuricemia and intravenous fat emulsion therapy were more prevalent compared to those who remained stable (81.6% vs. 57.8% and 46.9% vs. 24.4%, p < 0.05). Multivariate logistic regression analysis revealed that both hyperuricemia (odds ratio 2.741, 95% CI 1.014-7.413, p = 0.047) and intravenous fat emulsion therapy (odds ratio 2.645, 95% CI 1.046-6.686, p = 0.040) were independent predictors of gout flares. Furthermore, gout attacks occurred sooner in patients receiving intravenous fat emulsion therapy compared to those not receiving it (median: 4 days (interquartile range: 2) vs. median: 5 days (interquartile range: 2.25), p = 0.049). CONCLUSION: Our study revealed a high incidence of gout flares during episodes of active gastrointestinal bleeding, with patients undergoing intravenous fat emulsion therapy and those with hyperuricemia being at increased risk.

Clinical effects and adverse effects of intravenous lipid emulsion treatment in dogs and cats with suspected poisoning.

This retrospective study aimed to evaluate the effects on the clinical signs of poisoning and adverse effects of intravenous lipid emulsion treatment in 82 animals (dogs and cats) with suspected poisonings over 18 months. Physical examination parameters and state of consciousness were documented every hour after the intravenous administration of a bolus of 2 ml/kg and 0.25 ml/kg/min over 60 minutes of a 20% intravenous lipid emulsion. The modified Glasgow coma scale and laboratory findings (blood gas analysis, triglyceride, lactate) were evaluated initially and three hours after discontinuing intravenous lipid emulsion administration. A statistical evaluation of the occurrence of adverse effects and the development of laboratory values was performed. A decrease in respiratory rate in the second control (8-12 hours) after ILE was observed. Three hours after completing of the intravenous lipid emulsion, triglyceride concentration increased about 10 times (p <0.001). Venous carbon dioxide partial pressure, bicarbonate, base excess, as well as the electrolytes sodium, potassium and ionized calcium decreased significantly (p <0.001). Patients who experienced a worsening of the modified Glasgow coma scale had a higher increase in triglyceride concentrations (p = 0.041) and plasma lactate (p = 0.034) and a larger decrease in bicarbonate concentrations (p = 0.053) compared to others. About 54% (n = 44) of the patients showed adverse effects which could be attributed to the administration of intravenous lipid emulsion and may be associated with a higher triglyceride increase. All of them were completely reversible within 33 hours. Adverse effects associated with intravenous lipid emulsion therapy were observed in half of the patients and were associated with a higher increase in triglycerides.

Association between two different lipid injectable emulsions and parenteral nutrition-associated cholestasis in very low birth weight infants: A retrospective cohort study.

BACKGROUND: Using soybean oil-based lipid emulsions (Intralipid), which contain higher amounts of ω-6 fatty acids and phytosterols in parenteral nutrition, is a risk factor for cholestasis (parenteral nutrition-associated cholestasis [PNAC]). An alternative form of a mixed lipid emulsion (SMOFlipid) has been developed to reduce the risk of PNAC, but significant benefits over Intralipid in very low birth weight (VLBW) infants have yet to be demonstrated. The aim of this study was to compare the differences in PNAC incidence in VLBW infants receiving SMOFlipid vs Intralipid. METHODS: The study was conducted in Sir Run Run Shaw Hospital of the Zhejiang University School of Medicine, Hangzhou, China, from January 2016 to March 2022. In total, 235 VLBW infants were administered SMOFlipid or Intralipid for ≥21 days and were included in the study. The primary outcome was the incidence of PNAC. Secondary outcomes included bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, length of stay, weight 28 days after birth, severity of PNAC, and the time to reversal of PNAC. RESULTS: Forty-four VLBW infants (35.5%) in the SMOFlipid group vs 41 (36.9%) in the Intralipid group achieved PNAC (P = 0.817). The subgroup analysis showed that the peak direct bilirubin level was lower (median [interquartile range] 55.6 [36.4] vs 118.4 [77.2] µmol/L; P < 0.001), and the time to reversal of PNAC was shorter (44 [49] vs 96 [61]; P < 0.001) in the SMOFlipid group than in the Intralipid group. CONCLUSION: SMOFlipid may represent a better alternative for VLBW infants who require prolonged parenteral nutrition.

Effect of SMOF lipid emulsion on physical growth and extrauterine growth retardation in very preterm infants: Insights from a multicenter retrospective cohort study.

OBJECTIVE: The aim of this study was to investigate the effects of soybean, medium-chain triacylglycerols (MCTs), olive oil, and fish oil (SMOF) on short-term clinical outcomes, physical growth, and extrauterine growth retardation (EUGR) in very preterm infants. METHODS: This was a multicenter retrospective cohort study of very preterm infants hospitalized in neonatal intensive care units at five tertiary hospitals in China between January 2021 and December 2021. According to the type of fat emulsion used in parenteral nutrition (PN), eligible very preterm infants were divided into the MCTs/long-chain triacylglycerol (MCT/LCT) group and SMOF group. Change in weight z-score (weight Δz) between measurements at birth and at 36 wk of postmenstrual age or at discharge, the incidence of EUGR, and short-term clinical outcomes between the two groups were compared and analyzed. RESULTS: We enrolled 409 very preterm infants, including 205 in the MCT/LCT group and 204 in the SMOF group. Univariate analysis showed that infants in the SMOF group had significantly longer duration of invasive mechanical ventilation and PN, longer days to reach total enteral nutrition, and a higher proportion of maximum weight loss than those in MCT/LCT group (all P < 0.05). After adjusting for the confounding variables, multifactorial logistic regression analysis of short-term clinical outcomes showed that SMOF had protective effects on PN-associated cholestasis (odds ratio [OR], 0.470; 95% confidence interval [CI], 0.266-0.831) and metabolic bone disease of prematurity (OR, 0.263; 95% CI, 0.078-0.880). Additionally, SMOF was an independent risk factor for lower weight growth velocity (ß = -0.733; 95% CI, -1.452 to -0.015) but had no effect on the incidence of EUGR (OR, 1.567; 95% CI, 0.912 to -2.693). CONCLUSION: Compared with MCT/LCT, SMOF can reduce the risk for PN-associated cholestasis and metabolic bone disease of prematurity in very preterm infants and has a negative effect on growth velocity but has no effect on the incidence of EUGR.

Effects of mixed oil emulsion on short-term clinical outcomes in premature infants: A prospective, multicenter, randomized controlled trial.

OBJECTIVE: This study compared the clinical effects of two different lipid emulsions in premature infants with gestational age < 32 weeks (VPI) or birth weight < 1500 g (VLBWI) to provide an evidence-based medicine basis for optimizing intravenous lipid emulsion. METHODS: This was a prospective multicenter randomized controlled study. A total of 465 VPIs or VLBWIs, admitted to the neonatal intensive care unit of five tertiary hospitals in China from March 1, 2021 to December 31, 2021, were recruited. All subjects were randomly allocated into two groups, namely, medium-chain triglycerides/long-chain triglycerides (MCT/LCT) group (n = 231) and soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) group (n = 234). Clinical features, biochemical indexes, nutrition support therapy, and complications were analyzed and compared between the two groups. RESULTS: No significant differences were found in perinatal data, hospitalization, parenteral and enteral nutrition support between the two groups (P > 0.05). Compared with the MCT/LCT group, the incidence of neonates with a peak value of total bilirubin (TB) > 5 mg/dL (84/231 [36.4% vs. 60/234 [25.6%]), a peak value of direct bilirubin (DB) ≥ 2 mg/dL (26/231 [11.3% vs. 14/234 [6.0%]), a peak value of alkaline phosphatase (ALP) > 900 IU/L (17/231 [7.4% vs. 7/234 [3.0%]), and a peak value of triglycerides (TG) > 3.4 mmol/L (13/231 [5.6% vs. 4/234[1.7%]]) were lower in the SMOF group (P < 0.05). Univariate analysis showed that in the subgroup analysis of < 28 weeks, the incidence of parenteral nutrition-associated cholestasis (PNAC) and metabolic bone disease of prematurity (MBDP) were lower in the SMOF group (P = 0.043 and 0.029, respectively), whereas no significant differences were present in the incidence of PNAC and MBDP between the two groups at > 28 weeks group (P = 0.177 and 0.991, respectively). Multivariate logistic regression analysis revealed that the incidence of PNAC (aRR: 0.38, 95% confidence interval [CI]: 0.20-0.70, P = 0.002) and MBDP (aRR: 0.12, 95% CI: 0.19-0.81, P = 0.029) in the SMOF group were lower than that in the MCT/LCT group. In addition, no significant differences were recorded in the incidence of patent ductus arteriosus, feeding intolerance, necrotizing enterocolitis (Bell's stage ≥ 2), late-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity and extrauterine growth retardation between the two groups (P > 0.05). CONCLUSIONS: The application of mixed oil emulsion in VPI or VLBWI can reduce the risk of plasma TB > 5 mg/dL, DB ≥ 2 mg/dL, ALP > 900 IU/L, and TG > 3.4 mmol/L during hospitalization. SMOF has better lipid tolerance, reduces the incidence of PNAC and MBDP, and exerts more benefits in preterm infants with gestational age < 28 weeks.

Intestinal Failure-Associated Liver Disease and Growth Pre- and Post-Transition to a Composite Lipid Emulsion.

OBJECTIVES: Infants with intestinal failure have an increased risk of intestinal failure-associated liver disease (IFALD). Composite intravenous lipid emulsion (ILE) may reduce the risk of cholestasis. The primary outcome was to compare IFALD rates in infants with intestinal failure, between those receiving a composite ILE versus soybean oil ILE. The secondary outcome compared growth between these 2 groups. METHODS: At our 2 tertiary neonatal/pediatric hospitals, we identified all patients (≤1 year old) who received ≥6 weeks parenteral nutrition (PN) from 2010 to 2018. Data included liver and growth parameters. IFALD was defined as serum conjugated bilirubin (CB) >33 µmol/L (≥2 mg/dL). Nonparametric tests were used for all comparisons. RESULTS: Fifty infants (35 composite ILE, 15 soybean oil ILE) were included. Those on composite ILE received PN for longer (10.1 vs 7.6 weeks; P = 0.001) and had higher baseline CB (29 vs 6.5 µmol/L; P = 0.001). No differences were found by 6 weeks (14.5 vs 5 µmol/L; P = 0.54) and by PN cessation (4 vs 4 µmol/L; P = 0.33). The proportion of patients with IFALD decreased from 54% to 20% for composite ILE, while stable given soybean oil ILE (7%). There were no differences in weight, length, or head circumference z scores ( P > 0.05). CONCLUSIONS: In our institutions, over 8 years, chronic intestinal failure was rare. Composite ILE was the predominant lipid choice for infants who needed longer courses of PN or had developed cholestasis. Despite longer PN duration, and higher baseline CB, overall rates of IFALD decreased with composite ILE. Regardless of parenteral lipid used, there were no differences in growth.

Hepatic dysfunction in patients receiving intravenous lipid emulsions.

PURPOSE OF REVIEW: Until recently, intravenous lipid emulsions (ILEs) have consisted of soybean oil (SO) only. This review addresses recent developments in the field, including the problem of intestinal failure associated liver disease (IFALD) that can occur with the use of ILEs in children and adults, and newer ILEs that may minimize and reverse IFALD. RECENT FINDINGS: Cholestasis is the primary manifestation of IFALD in premature infants receiving ILEs, whereas in older children and adults, steatosis is predominant. Two alternative ILEs have been extensively investigated for both safety and efficacy. SMOF, an ILE containing medium chain triglyceride, soybean oil, olive oil and fish oil (FO), is now widely used in both children and adults. A newer FO ILE is approved for use in children only. However, in case reports FO ILE has been shown to improve IFALD in adults. A number of new studies suggest that cholestasis from ILEs is dose-related. IFALD does not improve in many patients after transition from SO to SMOF, but partial or complete replacement with FO can halt and reverse IFALD. SUMMARY: Adverse hepatic effects from ILEs are to some extent dose-related. Overfeeding with fat or with carbohydrate, or simply providing excessive calories in general, may be responsible. More research is needed investigating dose-related effects of macronutrients on liver injury.

Clinical Effects of Inadvertent Increased Lipid Infusion in Neonates: Two Case Reports.

BACKGROUND: Utility of total parenteral nutrition (TPN) with an intravenous lipid emulsion (IVLE) component is common in the neonatal intensive care unit; however, there are inherent risks to TPN use. With IVLE administered separate from other TPN components, opportunities exist for additional error and subsequent potential harm. CLINICAL FINDINGS: We present 2 cases in term infants where IVLE infusions were noted to be inadvertently administered at higher than prescribed rates, prompting concern for lipemia and end-organ damage due to hyperviscosity. PRIMARY DIAGNOSIS: Both infants developed iatrogenic hypertriglyceridemia and hyponatremia. INTERVENTION: Upon recognition of the error, IVLE was immediately discontinued in each case. Triglyceride levels were serially monitored until they reached a normal level. Electrolyte panels and hepatic function panels were also drawn to assess for electrolyte derangements and function. Radiologic studies were performed for evaluation of end-organ effects of hyperviscosity. OUTCOMES: Triglyceride levels for both infants normalized within 7 hours. Both infants survived to discharge without any known effects related to the inadvertent excessive lipid infusion. CONCLUSION: It is helpful to perform a root-cause analysis for these types of events; have the exact amount of lipids in the bag needed and no overfill; consider having lipids in 4-hour dosage aliquots; require 2 nurses to verify infusion rates hourly; and educational sessions and unit protocols for any infusion may reduce the risk of administration error.

Comparison of catheter-related bloodstream infection rates in pediatric patients receiving parenteral nutrition with soybean oil-based intravenous fat emulsion versus a mixed oil fat emulsion.

STUDY OBJECTIVE: To compare rates of catheter-related bloodstream infections (CR-BSI) in pediatric patients who received parenteral nutrition (PN) with either soybean oil-based intravenous fat emulsion (SO-IFE) or mixed oil-IFE (MO-IFE). We hypothesized that the use of MO-IFE would be independently associated with reduced infection rates compared with SO-IFE. DESIGN: Retrospective cohort study. SETTING: Tertiary referral children's hospital and its associated gastrointestinal rehabilitation clinic (01 January, 2015-31 July, 2019). PATIENTS: Days of IFE exposure were counted for patients aged <18 years on IFE initiated during the review period, who had a central venous catheter (CVC) placed for PN administration, received IFE at least three times weekly, and for at least 7 days. MEASUREMENTS: The primary outcome included total and categorical CR-BSI rates expressed as the average with standard error (SE) number of infections per 1000 fat emulsion days. The following categories were specified: Candida albicans, non-albicans Candida spp., coagulase-negative Staphylococcus (CoNS), Enterobacterales, methicillin-resistant S. aureus, methicillin-susceptible S. aureus, and Pseudomonadales. Average infection rate comparisons were quantified as incidence rate ratios (IRR) using generalized linear mixed modeling with a Poisson distribution. MAIN RESULTS: Seven hundred and forty-three SO-IFE and 450 MO-IFE exposures were reviewed from 1131 patients, totaling 37,599 and 19,796 days of therapy, respectively. From those found significantly different, the average rate of infections with CoNS was 3.58 (SE 0.5)/1000 days of SO-IFE and 1.39 (SE 0.45)/1000 days of MO-IFE (IRR [95% confidence interval, CI]: 0.27 [0.16-0.46]; p < 0.01). Total average rates of infection were 7.33 (SE 0.76)/1000 days of SO-IFE and 4.52 (SE 0.75)/1000 days of MO-IFE (IRR [95% CI]: 0.60 [0.44-0.81]; p < 0.01). Other factors associated with higher infection rates include female gender, neonatal age, and inpatient-only IFE exposure. CONCLUSIONS: Receipt of MO-IFE was associated with lower rates of CoNS and total CR-BSIs compared with SO-IFE in pediatric patients. These findings could have major implications on IFE selection for pediatric patients receiving PN.

Clinical impact of lipid injectable emulsion in internal medicine inpatients exclusively receiving parenteral nutrition: a propensity score matching analysis from a Japanese medical claims database.

BACKGROUND: Although guidelines recommend lipid injectable emulsions (ILEs) be used as a part of parenteral nutrition, many patients in Japan receive lipid-free parenteral nutrition. Furthermore, little is known about the effect of ILEs on clinical outcomes in medical inpatients managed with parenteral nutrition. The aim of this study was to investigate the clinical impact of ILEs on internal medicine inpatients receiving parenteral nutrition. METHODS: A propensity score matching (PSM) analysis was performed using a medical claims database covering 451 hospitals in Japan. Participants included the following internal medicine inpatients, ages ≥ 18 years, fasting > 10 days, and receiving exclusively parenteral nutrition, between 2011 and 2020. Participants were divided into 2 groups: those who did and did not receive ILEs. The primary endpoint was in-hospital mortality. The secondary endpoints included intravenous catheter infection, activities of daily living (ADL), hospital length of stay (LOS), and total medical costs. To adjust for energy doses, logistic or multiple regression analyses were performed using energy dose as an additional explanatory variable. RESULTS: After PSM, 19,602 matched pairs were formed out of 61,437 patients. The ILE group had significantly lower incidences than the non-ILE group of in-hospital mortality (20.3% vs. 26.9%; odds ratio [OR], 0.69; 95% confidence interval [CI], 0.66-0.72; p < 0.001), deteriorated ADL (10.8% vs. 12.5%; OR, 0.85; 95% CI, 0.79-0.92; p < 0.001), and shorter LOS (regression coefficient, - 0.8; 95% CI, - 1.6-0.0; p = 0.045). After adjusting for energy dose, these ORs or regression coefficients demonstrated the same tendencies and statistical significance. The mean total medical costs were $21,009 in the ILE group and $21,402 in the non-ILE group (p = 0.08), and the adjusted regression coefficient for the ILE vs. the non-ILE group was - $860 (95% CI, - $1252 to - $47). CONCLUSIONS: ILE use was associated with improved clinical outcomes, including lower in-hospital mortality, in internal medicine inpatients receiving parenteral nutrition.

Hypertriglyceridemia in Preterm Infants.

Preterm and critically ill infants are at risk for hypertriglyceridemia (HTG). Common risk factors for HTG include prematurity, intravenous lipid emulsion dose and oil composition, reduced lipoprotein lipase activity, fetal growth restriction, sepsis, and renal failure. Despite these risk factors, clinicians lack a universally agreed upon definition for HTG and evidence-based approach to HTG management. This review provides a detailed overview of triglyceride and intravenous lipid emulsion metabolism and how this relates to specific HTG risk factors, along with some practical considerations for managing HTG in the neonatal population.

Randomized controlled phase I trial for a novel peripheral parenteral nutrition formula containing dextrose, amino acids, fat emulsion, electrolytes, and FDA2000 recommendation-based vitamins.

BACKGROUND & AIMS: We developed the world's first all-in-one type peripheral parenteral nutrition product containing dextrose, amino acids, fat emulsion, electrolytes and vitamins, according to the FDA 2000 recommendation. This phase I trial examined the safety and changes in nutritional parameters in healthy participants. METHODS: A single-center, randomized, open-label, active-controlled trial was performed in single ascending dose (SAD: Step 1-3) and multiple dose (Step 4) studies. Participants were administered a single dose of OPF-105 (test solution: 150 g of dextrose, 60 g of amino acids, 40 g of fat, 1240 kcal of total energy per 2200 mL, and 106 NPC/N ratio, with multivitamins, n = 17) or BFI (control solution: 150 g of dextrose, 60 g of amino acids, 840 kcal of total energy per 2000 mL, and 64 NPC/N ratio, with vitamin B1, n = 18) with three ascending doses (Step 1: 550 mL, Step 2: 1100 mL, and Step 3: 2200 mL) in the SAD study, or received multiple doses with Step 3 amount of OPF-105 (n = 5) or BFI (n = 6) for 3 days (Step 4) via peripherally inserted venous catheters. The safety and nutritional parameters were assessed. RESULTS: There were no serious adverse events or events requiring discontinuation of the solution administration in either group. Blood urea nitrogen (BUN) levels remained within the normal range in both groups (Step 1-4). However, they gradually increased during the time course of the study in the BFI group but not in the OPF group (Step 4), suggesting the prevention of body protein breakdown. Blood triglyceride (TG) levels increased after administration in the OPF group but promptly returned to the pre-administration level (Step 1-4). Blood total ketone body levels increased the day after administration in both groups, which may imply a lower degree of starvation (Step 1-3), but the increase in the OPF group was milder than that in the BFI group (Step 4). Blood vitamin B6 and folic acid levels were maintained within the normal ranges in the OPF group but were near the lower limit in the BFI group (Step 1-4). Blood vitamin C levels showed almost lower limit in the two groups (Step 1-3), but increased only in the OPF group (Step 4). Blood vitamin K levels in the BFI group remained near the lower limit of the normal range, but those in the OPF group were higher than the upper limit at the end of administration and quickly returned to the pre-administration level (Step 1-4). CONCLUSIONS: This trial suggests that the newly developed formula (OPF-105) improves fat metabolism, maintains vitamin profiles, and may prevent body protein and fat breakdown and can be safely administered to healthy participants. Registration number of Clinical Trial: UMIN000046915; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000053479.

Lipid emulsion-induced hypertension post resection of pediatric neuroblastoma: a case report and literature review.

BACKGROUND: Parenteral Nutrition (PN) is preferred when patient is unable to eat. Most clinically widely used lipid emulsion is now attracting more attention in its stability and adverse reactions. We report here the first case of lipid emulsions caused hypertension. CASE PRESENTATION: A 1.5 years old girl was diagnosed with neuroblastoma and underwent chemotherapy subsequently followed by resection surgery. She received PN for nutritional support after surgery. with the initiation of PN, this patient developed hypertension. Possible causes of hypertension were evaluated. After the discontinuation of lipid emulsions in PN, her hypertensive symptoms ceased. The lipid emulsion was therefore considered as the cause of her hypertension. CONCLUSIONS: The pathogenesis of hypertension caused by fatty milk is possibly associated with increased production of reactive oxygen species, increased oxidative stress and vasoconstriction.

Rapid infusion of fish oil-based lipid emulsions: Is there a risk of fat overload syndrome? A case report of rapid administration.

WHAT IS KNOWN AND OBJECTIVES: Errors involving the delivery of IVFE containing soybean oil have known significant complications, including fat overload syndrome. However, little is known regarding the risks of fat overload syndrome with other types of lipid emulsions. CASE SUMMARY: We describe a medication administration error that resulted in rapid fish oil-base lipid emulsion (Omegaven) infusion in a five-month-old infant with parenteral nutrition associated liver disease (PNALD). The medication administration error resulted in bolus infusion of Omegaven over 12 min (5 g/kg/h) instead of 12 h (0.083 g/kg/h). WHAT IS NEW AND CONCLUSION: No adverse reactions were notes because of the rapid infusion, supporting conclusion that rapid infusion of fish oil will not result in fat overload syndrome.

Exploring the long-term risk factors associated with intestinal failure-associated liver disease in pediatric and adult patients: The role of lipid injectable emulsions in the development of liver disease.

BACKGROUND: Despite parenteral nutrition (PN) being life sustaining, one of the risk factors associated with its long-term use is intestinal failure-associated liver disease (IFALD), which increases the risk for morbidity and mortality. This review examines some of the risk factors associated with IFALD. METHODS: A literature review using the databases PubMed, EMBASE, and CINAHL between 2010 and 2020 was performed using search terms, including long-term total PN and liver failure, serum plant sterols and liver failure, and complications and PN. Articles in English using both human and animal participants were included. RESULTS: The pathophysiology associated with PN and liver disease is multifactorial and influenced by the remaining small-bowel length, presence of the ileal cecal valve, lack of enteral stimulation, type of lipid injectable emulsion (ILE), plant sterol content, and excessive calories. The type of ILE plays a major role because of the phytosterol (PS) content, affecting the microbiome composition and inhibiting key gut signals. The PS content is highest in soy oil (SO)-based ILE, which increases inflammation and impairs biliary flow. CONCLUSION: Serum PS correlates with liver biomarker abnormalities and is highest in SO-based ILE use compared with mixed-oil emulsions. Selection of a low-PS content ILE is recommended to reduce the risk of biliary cholestasis. Stimulation of the gut, if possible, is recommended to maintain gut integrity and reduce bacterial overgrowth. Fish oil (FO) shows promise in IFALD reversal however, large randomized controlled trials are needed to further establish support for the use of FO in adults.

Intestinal failure-associated liver disease in the neonatal ICU: what we know and where we're going.

PURPOSE OF REVIEW: Parenteral nutrition is an integral part of the care of infants in the neonatal ICU. However, prolonged use of parenteral nutrition can be associated with adverse outcomes, most notably parenteral nutrition-associated liver disease, now known as intestinal failure-associated liver disease (IFALD). This review highlights pertinent developments in the epidemiology of IFALD as it pertains to neonates and showcases recent advances in the pathophysiology, treatment, and outcomes of neonates with IFALD. RECENT FINDINGS: The role of intravenous lipid emulsions in the pathogenesis, prevention, and treatment of IFALD remains a target for investigative studies. Recent data continues to support the use of fish-oil based intravenous lipids, but its use is limited due to concerns for essential fatty acid deficiency. Use of soy-based lipids and mixed lipids is not wrought with such concerns as these are often used at greater doses but their use is limited due to higher proinflammatory fatty acid content, increased phytosterols and decreased antioxidants, risk factors for the development of IFALD. SUMMARY: Hepatic complications may limit the use of parenteral nutrition in the neonatal ICU. However, the pathophysiology of IFALD is continuing to be further elucidated and novel targets are being developed for the treatment of IFALD. As noninvasive disease monitoring strategies continue to be developed, early enteral nutrition ameliorates the risk of IFALD and should be considered when possible.

Use of Intravenous Soybean and Fish Oil Emulsions in Pediatric Intestinal Failure-Associated Liver Disease: A Multicenter Integrated Analysis Report on Extrahepatic Adverse Events.

OBJECTIVE: To compare extrahepatic adverse events during fish oil lipid emulsion (FOLE) or soybean oil lipid emulsion (SOLE) treatment in children with intestinal failure-associated liver disease (IFALD). STUDY DESIGN: In this multicenter integrated analysis, bleeding, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), infections, and signs of lipid emulsion intolerance were compared between FOLE recipients (1 g/kg/d) (n = 189) and historical controls who received SOLE (≤3 g/kg/d) (n = 73). RESULTS: When compared with SOLE recipients, FOLE recipients had a lower gestational age (30.5 vs 33.0 weeks; P = .0350) and higher baseline direct bilirubin (DB) (5.8 vs 3.0 mg/dL; P < .0001). FOLE recipients had a decreased incidence of bleeding (P < .0001), BPD (P < .001), ROP (P < .0156), bacterial and fungal infections (P < .0001), and lipid intolerance signs (P < .02 for all). Patients with bleeding vs patients without bleeding had higher baseline DB; the ORs for baseline DB (by mg/dL) and treatment (FOLE vs SOLE) were 1.20 (95% CI: 1.10, 1.31; P ≤ .0001) and 0.22 (95% CI: 0.11, 0.46; P ≤ .0001), respectively. In preterm infants, a higher BPD (P < .0001) and ROP incidence (P = .0071) was observed in SOLE recipients vs FOLE recipients. CONCLUSIONS: Children with IFALD who received FOLE had fewer extrahepatic adverse events, including a decreased incidence of bleeding, preterm comorbidities, and lipid intolerance signs compared with children with IFALD who received SOLE. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT00910104 and NCT00738101.

Depletion and enrichment of phytosterols in soybean oil lipid emulsions directly associate with serum markers of cholestasis in preterm parenteral nutrition-fed pigs.

BACKGROUND: Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets. METHODS: Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or parenteral nutrition (PN) prepared from a soybean oil-based emulsion containing either 24.0% (depleted [DEP]), 100% (Intralipid; normal phytosterol [NP] concentration), or 144% (enriched [ENR]) total phytosterol concentration. RESULTS: At the end of the study, plasma and liver phytosterol concentrations were highest in the ENR group, followed by NP and then DEP and ENT. Serum direct bilirubin, serum bile acids, and γ-glutamyltransferase were higher in the ENR and NP groups compared with either DEP or ENT groups. All PN lipid groups showed evidence of mild hepatic steatosis but no change in hepatic expression of proinflammatory cytokines or Farnesoid X receptor target genes. CONCLUSION: The increase in serum direct bilirubin was lower in the DEP group vs the lipid emulsions with normal or ENR phytosterols. Our results provide additional evidence that phytosterols are linked to an increase in serum markers of cholestasis in preterm PN-fed pigs.