Multicomponent Lipid Emulsion Research Articles

Effects of a Multicomponent Lipid Emulsion on Brain Volumes in Extremely Low Birth Weight Infants.

During the early weeks of life optimization of nutrition in extremely preterm infants presents a critical opportunity to attenuate the adverse neurological consequences of prematurity and potentially improve neurodevelopmental outcome. We hypothesized that the use of multicomponent lipid emulsion (MLE) in parenteral nutrition (PN) would be related to larger volume of the cerebellum on brain magnetic resonance at term of equivalent age (TEA) in extremely low birth weight (ELBW) infants. We analyzed the brain magnetic resonance imaging (MRI) at TEA of a cohort of preterm infants with gestational age ≤28 weeks and/or birth weight <1,000 g randomly assigned in our previous trial to receive an MLE or soybean-based lipid emulsion (SLE). The primary outcome of the study was the cerebellar volume (CeV), valued on MRI acquired at TEA. Secondary outcomes included total brain volume (TBV), supratentorial volume, brainstem volume, and CeV corrected for TBV evaluated on MRI acquired at TEA. MRIs at TEA of 34 infants were then analyzed: 17 in the MLE group and 17 in the SLE group. The postmenstrual age (PMA) at which MRIs were performed were comparable between the two study groups. The CeV as well as the PMA-corrected CeV were significantly higher in the MLE group than in the SLE group. No difference was found among the other brain volumes considered. Our results suggest that the use of MLE in PN could promote CeV growth in ELBW infants, valued with MRI at TEA. · Optimization of nutrition in extremely low birthweight infants.. · Use of multicomponent lipid emulsions in parenteral nutrition.. · Larger cerebellar volume with use of multicomponent lipid emulsion..

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.

Beyond lipids: Novel mechanisms for parenteral nutrition-associated liver disease.

Parenteral nutrition (PN) is a therapy that delivers essential nutrients intravenously to patients who are unable to meet their nutrition requirements via standard enteral feeding. This methodology is often referred to as PN when accompanied by minimal or no enteral nutrition (EN). Although PN is lifesaving, significant complications can arise, such as intestinal failure-associated liver disease and gut-mucosal atrophy. The exact mechanism of injury remains ill defined. This review was designed to explore the available literature related to the drivers of injury mechanisms. The Farnesoid X receptor and fibroblast growth factor 19 signaling pathway seems to play an important role in gut-systemic signaling, and its alteration during PN provides insights into mechanistic links. Central line infections also play a key role in mediating PN-associated injury. Although lipid reduction strategies, as well as the use of multicomponent lipid emulsions and vitamin E, have shown promise, the cornerstone of preventing injury is the early establishment of EN.

Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses in Preterm Pigs.

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1 ± 0.0 to 9.7 ± 1.9, p < 0.001), docosahexaenoic acid, DHA (day 0 = 2.5 ± 0.7 to 13.6 ± 2.9, p < 0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1β increased at the first hour of LPS infusion (296.6 ± 308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p < 0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit the initial LPS-induced inflammatory responses in preterm pigs.

Growth of Head Circumference and Body Length in Preterm Infants Receiving a Multicomponent vs a Soybean-Based Lipid Emulsion: A Randomized Controlled Trial.

The growth of very low-birth-weight (VLBW) infants relies, to a large extent, on parenteral nutrition (PN) during the early weeks of life. Despite the parenteral nutrients supply, extrauterine growth restriction remains the main concern for these infants. A parenteral multicomponent lipid emulsion (MLE) might improve growth and neurological outcomes, delivering fats for brain growth that the traditional soybean-based lipid emulsion (SLE) fails to provide. We hypothesize that the use of an MLE in PN may reduce the loss of head circumference (HC) z-score from birth to 36 weeks' postmenstrual age (PMA) or at discharge compared with the use of an SLE in VLBW infants. Infants with BW ≤1250 g, without malformations or chromosomal abnormalities, were randomly assigned to receive an MLE or an SLE. The primary outcome was the change in HC z-score (HC Δ z-score) from birth to 36 weeks' PMA or at discharge. Secondary outcomes included the change in weight and length z-score (W Δ z-score and L Δ z-score) as well as incidence of late-onset sepsis and PN-associated cholestasis (PNAC). Of the 128 infants randomized, 51 infants in the MLE group and 50 infants in the SLE group were analyzed. The MLE was significantly associated with a decreased loss in HC and length z-scores from birth to 36 weeks' PMA or at discharge. This is the first randomized controlled trial providing the evidence that an MLE is associated with improved HC growth in comparison with a pure SLE.

Parenteral lipids shape gut bile acid pools and microbiota profiles in the prevention of cholestasis in preterm pigs

Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition [experimental emulsion (EXP)], or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e., bilirubin, bile acids, and γ-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. The colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid-sensitive gram-positive bacteria.

Fish oil-containing multicomponent lipid emulsion vs soy-based lipid emulsion and neurodevelopmental outcomes of children born < 29 weeks' gestation.

To compare neurodevelopmental outcomes of extremely preterm children who received soy-medium chain triglycerides-olive-fish oil-containing lipid emulsion (SMOF-LE) vs soy-based LE. We conducted a pre-post comparative cohort study of children born < 29 weeks' gestation who received > 7 days of LE. Outcomes were mortality/significant neurodevelopmental impairment (NDI), mortality/any NDI, significant NDI, any NDI, and individual components of NDI. Among children with follow-up data (Intralipid: n = 340/442, 77%; SMOF-LE: n = 214/286, 75%), baseline characteristics were comparable except for postnatal steroids. There was no significant difference in death/significant NDI between groups. Adjusted odds of death/any NDI [0.68 (95% CI 0.48, 0.97)], any NDI [0.64 (95% CI 0.44, 0.93)] and Bayley-III language score < 85 and <70 were significantly lower in the SMOF-LE group. In extremely preterm children, a change from soy-based LE to SMOF-LE was not associated with deleterious effect on neurodevelopmental outcomes and may have been associated with some improvement.

Growth and Clinical Outcome in Very Low-Birth-Weight Infants After the Introduction of a Multicomponent Intravenous Lipid Emulsion.

Very low-birth-weight (VLBW; birth weight < 1500 g) infants are often dependent on intravenous nutrition after birth. Conventional soy-based intravenous lipid emulsions (Soy LE) are associated with inflammatory and metabolic complications that may be harmful to preterm infants. Evidence to support any clinical benefit associated with newer multicomponent emulsions (Mixed LE), remains inconsistent and unsubstantiated in appropriate studies. This retrospective study aimed to determine whether growth and clinical outcomes differed between VLBW infants given Mixed LE vs Soy LE at Auckland City Hospital. Data were collected on nutrition, growth, and neonatal morbidities for the first 4 weeks after birth. Outcomes were compared between 2 lipid cohorts, Soy LE (February 2013 - August 2014) and Mixed LE (August 2014 - December 2015), using univariate and multivariate analysis. 207 infants (Soy LE, 105 vs Mixed LE, 102) were included in the study. Significantly fewer infants in the Mixed LE cohort developed any stage retinopathy of prematurity (Soy LE 59% vs Mixed LE 39%, P=.005) or intraventricular hemorrhage (Soy LE 27% vs Mixed LE 15%, P=.03) during their admission. Mixed LE was also associated with significantly lower mean (P=.01), minimum (P=.03), and maximum (P=.04) total bilirubin concentrations across the first 4 weeks after birth. There was no difference in growth velocity or weight, length, and head circumference z-score change. SMOFlipid may represent a favorable alternative to conventional lipid emulsions in neonatal parenteral nutrition regimens; however, long-term effects should be further evaluated.

Long-term parenteral nutrition

Intestinal failure (IF) is a term applied when intestinal function becomes insufficient to allow adequate absorption of fluid, electrolytes, or nutrients required for normal growth and survival. The development of parenteral nutrition (PN) as a treatment modality has greatly improved the outcome for children with IF and has contributed to improved outcomes in neonates and children from intensive care settings. Home parenteral nutrition (HPN) is central to the care of patients when IF is expected to last for more than 3–6 months. Normal growth and long-term survival is now expected for most children and young people on HPN when only 10 years ago, the prognosis for survival was poor. Adolescents with IF now successfully transfer to adult services, many of which will have been dependent on PN since early infancy. This article reviews the current indications for PN and the recent advances in PN that have contributed to better outcomes. A guideline on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN) supported by the European Society of Paediatric Research (ESPR) was published in 2010. This has been recently updated (ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition, 2018) with up-to-date evidence for health professionals working with infants, children and adolescents receiving PN. This update includes details the use of Taurolock™ to prevent central venous catheter (CVC) related sepsis, and the role of new multicomponent lipid emulsions. Recommendations have been given with regard to the use of in-line filtration and photoprotection of PN fluids and advice on energy, fluid, electrolyte, macro-and micronutrient intake has been updated.

New generation lipid emulsions increase brain DHA and improve body composition, but not short-term neurodevelopment in parenterally-fed preterm piglets

New generation, multicomponent parenteral lipid emulsions provide key fatty acids for brain growth and development, such as docosahexaenoic acid (DHA) and arachidonic acid (AA), yet the content may be suboptimal for preterm infants. Our aim was to test whether DHA and AA-enriched lipid emulsions would increase activity, growth, and neurodevelopment in preterm piglets and limit brain inflammation. Cesarean-delivered preterm pigs were given three weeks of either enteral preterm infant formula (ENT) or TPN with one of three parenteral lipid emulsions: Intralipid (IL), SMOFlipid (SMOF) or an experimental emulsion (EXP). Activity was continuously monitored and weekly blood sampling and behavioral field testing performed. At termination of the study, whole body and tissue metrics were collected. Neuronal density was assessed in sections of hippocampus (HC), thalamus, and cortex. Frontal cortex (FC) and HC tissue were assayed for fatty acid profiles and expression of genes of neuronal growth and inflammation. After 3 weeks of treatment, brain DHA content in SMOF, EXP and ENT pigs was higher (P < 0.01) in FC but not HC vs. IL pigs. There were no differences in brain weight or neuron density among treatment groups. Inflammatory cytokine TNFα and IL-1β expression in brain regions were increased in IL pigs (P < 0.05) compared to other groups. Overall growth velocity was similar among groups, but IL pigs had higher percent body fat and increased insulin resistance compared to other treatments (P < 0.05). ENT pigs spent more time in higher physical activity levels compared to all TPN groups, but there were no differences in exploratory behavior among groups. We conclude that a soybean oil emulsion increased select brain inflammatory cytokines and multicomponent lipid emulsions enriched with DHA and AA in parenteral lipids results in increased cortical DHA and improved body composition without affecting short term neurodevelopmental outcomes.

Wide variation in organisation and clinical practice of paediatric intestinal failure teams: an international survey

We aimed to assess the current organisation and clinical practice of teams treating children with intestinal failure (IF) across Europe and compare the results with the current guideline. A two-part online survey was sent to all the major European specialist IF services. The first part concerned general information about the team and patients monitored. The second part concerned important care topics such as vascular access and monitoring of complications. No patient identifiers were collected. Seventy-three respondents completed the first part, representing 61 teams in 20 countries. The median number of children on parenteral nutrition (PN) at home per team was 15 (range 1-125). Teams consisted of the following members: paediatric gastroenterologist (present in 100% of the teams), dietitian (95%), specialist nurse (92%), paediatric surgeon (89%), pharmacist (82%), psychologist (66%), social worker (62%), speech therapist (48%), physiotherapist (38%), general paediatrician (33%). The second part was completed by 67/73 respondents (59/61 teams). Vascular access care was comparable with the guideline. Somatostatin analogues were prescribed by 14% of the IF teams and probiotics by 44% of the teams. Prophylactic anticoagulation was used by 46% of the teams. In 81% of the teams a multicomponent lipid emulsion containing fish oil was routinely used. Bone densitometry was regularly performed in 75% of teams, but never performed in 19%. In conclusion, there is a wide diversity of composition of IF teams and their number of patients treated. Overall, there is good compliance to the current guideline. Clinical practice that varied most was the standard use of medication such as probiotics and somatostatin analogues, and standard monitoring of long-term complications. Experience regarding specific treatment options should be shared. Moreover, international agreement on standards of care with focus on implementation of the guideline is needed to optimise care and improve outcomes of children with IF.

A Clinical Audit of Growth and Clinical Outcome in Very Low Birthweight Babies at the Auckland City Hospital Neonatal Intensive Care Unit Before and After the Introduction of SMOFlipid

Introduction: Intestinal failure associated liver disease in very low birthweight (VLBW; birthweight <1,500 g) babies is associated with lipid emulsion use. Multicomponent lipid emulsions may reduce this risk. The aim of this audit was to determine whether a change from a purely soybean oil-based emulsion (Intralipid) to one containing soy, medium-chain triglycerides, olive oil and fish oil (SMOFlipid) would improve growth and clinical outcomes in VLBW babies born at Auckland City Hospital. Method: Consecutively-born VLBW babies were identified from a prospectively-maintained database. Data were collected from electronic clinical records and are presented as mean (SD). Data were available for 105 babies who received Intralipid and 102 babies who received SMOFlipid. Results: Change in Z-scores for weight, length and head circumference between birth and 28 days or discharge did not differ between cohorts. Significantly fewer babies in the SMOFlipid group developed any retinopathy of prematurity (59% vs. 39%, p=0.005) or intraventricular hemorrhage (15% vs. 27%, p=0.03) prior to discharge. Mean total bilirubin levels were similar between cohorts in weeks 1, 2 and 4 after birth, with a significant difference only observed in week 3 (46 (3–203) vs. 42 (1–158) μmol/L, p=0.04). However, repeated measures analyses indicated that both mean (p=0.01), minimum (p=0.03) and maximum (p=0.04) total bilirubin were significantly lower over the first four weeks of life collectively among babies who received SMOFlipid. Conclusion: These data indicate that SMOFlipid may be a favorable alternative to traditional lipid emulsions in neonatal parenteral nutrition regimens. This evidence will be used to inform the guidelines produced by the New Zealand National Intestinal Failure Service.

Growth and Fatty Acid Profiles of VLBW Infants Receiving a Multicomponent Lipid Emulsion From Birth

Very-low-birth-weight (VLBW) infants are dependent on parenteral nutrition after birth. A parenteral lipid emulsion with a multicomponent composition may improve growth and neurodevelopment and may prevent liver injury, which is often observed in association with long-term parenteral nutrition with pure soybean oil. Our aim was to evaluate the safety and efficacy of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triacylglycerol, 25% olive oil, and 15% fish oil compared with a conventional pure soybean oil emulsion in VLBW infants. We conducted a double-blind randomized controlled trial in VLBW infants randomized to parenteral nutrition with the multicomponent (study group) or pure soybean oil emulsion (control group) from birth at a dose of 2 to 3 g · kg(-1) · day(-1) until the infants were receiving full enteral nutrition. We assessed efficacy by growth rates and measuring plasma fatty acid profiles (representative subset). Safety was evaluated by assessing hematologic and biochemical parameters, potentially harmful phytosterol concentrations (same subset), and clinical neonatal outcome parameters. Ninety-six infants were included (subsets n = 21). The multicomponent emulsion was associated with higher weight and head circumference z scores during admission. Plasma eicosapentaenoic acid and docosahexaenoic acid concentrations were higher in the study group. The hematological, biochemical, and neonatal outcomes were not different between groups, whereas the plasma concentrations of phytosterols were higher in the control group. The multicomponent lipid emulsion was well tolerated and associated with improved growth and higher plasma fatty acid profiles in VLBW infants in comparison with the pure soybean oil emulsion.