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Capstone Prospectus: SMOFlipid vs Intralipid in Neonatal Cholestasis

PICO Question: In neonates diagnosed with cholestasis, does SMOFlipid in the TPN compared with the use of intralipid improve bilirubin secretion in the liver for improved liver function?

Hypothesis:

  • H0: SMOFlipid vs intralipid intervention in neonates diagnosed with cholestasis does not affect bilirubin secretion in the liver for improved liver function.
  • H1: SMOFlipid vs intralipid intervention in neonates diagnosed with cholestasis improves bilirubin secretion in the liver for improved liver function.

Methodology:

This research proposal prospectus is aimed at diving into cholestasis within the neonatal population and determining if SMOFlipid is more effective than intralipid in cholestatic improvement and bile excretion. Subject recruitment will be from neonatal populations within regional NICU’s across the United States. These NICU’s are typically the level IV trauma and are where surgical operations in neonates occur. Lower level NICU’s typically transport all their neonates who need surgical intervention to these regional NICU’s thus narrowing where cholestatic neonates will be admitted due to the complex nature of the condition. This population will not discriminate upon race or gender. All neonates’ families within the included Regional NICU’s that are diagnosed with cholestasis will then be contacted and presented with study information to then agree or decline to allow the neonate to participate in this research. Even if enteral feedings are being used as the intervention, they will still remain in the research should, at any point during their admission, they be administered total parenteral nutrition including lipids.

An a priori calculation was completed to determine an appropriate number of subjects to be included. A two-tailed G* Power test determined that 119 per group, or 238 total subjects, would be an appropriate sample size. The research will continue until adequate participation is reached with sufficient data from a population no less than 119 per intravenous lipid type.

Cholestatic neonates that are receiving or are transitioning to receive either SMOFlipid or Intralipid will then be enrolled in the research and begin the process to begin gather data. Once consents have been signed, lipid interventions, SMOFlipid or Intralipid, will be made via the interprofessional team and data analysis will be kept, recorded, and discerned for each patient. All interventions will be done during the patient’s admission.

All practices performed for the neonates and their condition will be agreed upon by the interprofessional team and will not solely be for the purpose of the study to avoid any potential risks. Neonates will have routine labs drawn and analyzed. Along with the complete metabolic panel, other additional labs that will be looked at include, but are not limited to, serum bile acid, cholic acid, total bilirubin, and conjugated bilirubin.4 While the neonate is receiving intravenous lipids, these labs will be monitored to determine status and improvement of cholestatic condition. This data will be separated between the patients receiving Intralipid and SMOFlipid and corresponding data accompanying each neonate. All data will be gathered during the duration of the intravenous lipid use. All information is to remain confidential and no identifiable information will be gathered by researchers thus keeping all data used and reported in the study anonymous.   All data collected and analyzed will be used to directly impact the population via intervention when on TPN.

Data Analysis:

Based on the nature of the research being gathered, quantitative data will primarily be the source of information that will be analyzed, and results will be drawn from. Data will come from neonatologist reporting regarding cholestatic condition that will be accompanied with the radiology scans that subsequently visually reveal additional progression or regression of the neonate’s cholestasis. Vital lab values will be routine drawn as part of the healthcare process, additionally conjugated bilirubin labs will be monitored upon diagnosis and compared throughout intervention to determine progress of cholestatic condition by the medical team.4Beginning and end conjugated bilirubin levels will be compared and analyzed for correlation.

Risks for this research study remain minimal, though there are some physical risks to be considered. The means by which blood draws will occur can often be uncomfortable and lead to significant discomfort, but only for a brief time during the draw. Trained and qualified personnel will oversee, perform, and supervise during any of the interventions that are being participated in.

Summary:

Jaundice is a frequent occurring condition in new neonates as 60% of term newborns and 80% of preterm newborns are reported to develop jaundice within the neonates first week after birth.1 Most of these cases will self-resolve with mild to no medical intervention. However, if a neonate is jaundiced for more than two weeks, it is recommended that serum bilirubin levels are checked and analyzed to test for a complex condition called cholestasis.2 Cholestasis in neonates is referred to as the condition where  impairment has occurred in areas of the liver responsible for forming and excreting bile from the body whereas the formation and flow of bile is not functioning correctly or obstructed.3,7 Neonatal cholestasis can be caused by a number of additional conditions that occur in infancy. Some of those conditions are biliary atresia, genetic disorders, metabolic diseases, and a-antitrypsin deficiency.5 Often times there is not specific treatment available during initial diagnosis, though during this time, it has been shown that neonates benefit greatly from optimization of nutrition which can impact overall cholestatic outcome.6

Of the many types of interventions available, the type of nutrition that the infant receives is important for overall outcome. In the setting of cholestasis, when nutrition is present in the GI tract, the flow of bile is halted between the liver and duodenum impairing the digestion and absorptions of fats.8 MCT (medium chain triglycerides) are often recommended as opposed to LCT (long chain triglycerides) as fat sources due to the different nature of absorption. MCT have shorter carbon lengths, water soluble, and are absorbed by passive diffusion via the portal systems and thus do not require formation of bile salts for absorption.8

During this condition, infants often do not tolerate enteral nutrition and require additional means of nutrition. A common neonatal intervention for these cases is to put the infant on bowel rest and begin administration of TPN (total parenteral nutrition) as well as intravenous lipids. There are two common lipids that are used which are called SMOFlipid and Intralipid. SMOFlipid has a more diverse lipid profile composed of soybean oil, MCT oil, olive oil, and fish oil whereas intralipid is primarily composed of soybean oil.9 Due to this composition, SMOFlipid is typically given to neonates with cholestasis. Research shows that neonates who receive SMOFlipid have lower levels of conjugated bilirubin (CB) not reaching a level of 34 umol/L, whereas those receiving Intralipid often reached a higher level of 50 umol/L.10 There is unclear research whether SMOFlipid will reduce the incidence of cholestasis compared with Intralipid, though SMOFlipid has been shown to significantly resolve hyperbilirubinemia at a quicker rate.11  Infants often remain on TPN and intravenous lipids during cholestasis until the interprofessional team determines enteral feedings are safe for the infant.

This research study aims to look at the impact of Intralipid and SMOFlipid during neonatal cholestasis and determine effectiveness of both uses in fat absorption and the impact on hyperbilirubinemia.

 

 

 

 

References

 

  1. Ansong-Assoku B, Shah SD, Adnan M, Ankola PA. Neonatal Jaundice. In: StatPearls. Treasure Island (FL): StatPearls Publishing; August 7, 2022.
  2. Feldman AG, Sokol RJ. Neonatal Cholestasis. Neoreviews. 2013;14(2):10.1542/neo.14-2-e63. doi:10.1542/neo.14-2-e63
  3. Ananth R. Neonatal Cholestasis: A Primer of Selected Etiologies. Pediatr Ann. 2018;47(11):e433-e439. doi:10.3928/19382359-20181018-01
  4. Feldman AG, Sokol RJ. Neonatal Cholestasis: Updates on Diagnostics, Therapeutics, and Prevention. Neoreviews. 2021;22(12):e819-e836. doi:10.1542/neo.22-12-e819
  5. ischler B, Lamireau T. Cholestasis in the newborn and infant. Clin Res Hepatol Gastroenterol. 2014;38(3):263-267. doi:10.1016/j.clinre.2014.03.010
  6. Yuksekkaya, H.A., Cakir, M., Tumgor, G. et al.Nutritional status of infants with neonatal cholestasis. Dig Dis Sci 53, 803–808 (2008). https://doi.org/10.1007/s10620-007-9917-y
  7. Choi HJ, Kim I, Lee HJ, et al. Clinical characteristics of neonatal cholestasis in a tertiary hospital and the development of a novel prediction model for mortality. EBioMedicine. 2022;77:103890. doi:10.1016/j.ebiom.2022.103890
  8. Send SR. Nutritional Management of Cholestasis. Clin Liver Dis (Hoboken). 2020;15(1):9-12. Published 2020 Feb 25. doi:10.1002/cld.865
  9. Wu MY, Kuo SC, Chuang SF, et al. Comparative study of the safety and efficacy of SMOFlipid vs non SMOFlipid as TPN for liver transplantation. Ann Med Surg (Lond). 2021;63:102094. Published 2021 Feb 18. doi:10.1016/j.amsu.2021.01.042
  10. Belza C, Wales JC, Courtney-Martin G, de Silva N, Avitzur Y, Wales PW. An Observational Study of Smoflipid vs Intralipid on the Evolution of Intestinal Failure-Associated Liver Disease in Infants With Intestinal Failure. JPEN J Parenter Enteral Nutr. 2020;44(4):688-696. doi:10.1002/jpen.1692
  11. Casson C, Nguyen V, Nayak P, et al. A Comparison of Smoflipid® and Intralipid® in the Early Management of Infants with Intestinal Failure. J Pediatr Surg. 2020;55(1):153-157. doi:10.1016/j.jpedsurg.2019.09.073

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