Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates

2014-08-27 03:16:34 | BioPortfolio


The goal of the study is to determine if parenteral nutrition-associated cholestasis (PNAC) is related to the amount of parenteral (intravenous) fat administered to premature babies until full enteral nutrition is achieved.


In the neonatal intensive care unit, parenteral nutrition is widely used to provide protein, energy, vitamins and minerals to infants who cannot accept enteral feeds.

Intravenous fat emulsion is an important component of parenteral nutrition because of the important caloric supply that it brings, but also for the essential fatty acids (linoleic and linolenic acid) that it provides. Because intravenous fat emulsion is the only supply of essential fatty acids, at least until the enteral feeds are established, there is a minimum of fat that has to be administered with at least 0.25g/kg /day for preterm babies and 0.1g/kg/day for term infants (Lee EJ, 1993). The maximal dose of intravenous fat safe to administer is difficult to determine. Although in larger preterm infants intravenous fat is tolerated well based on measurement of serum triglycerides, there are still question regarding tolerance in extremely low birth weight infants.

Parenteral nutrition has been associated with the development of liver disease-parenteral nutrition associated liver disease (PNALD). PNALD can range from cholestasis and a transient elevation of liver enzymes to more severe forms including fibrosis, liver cirrhosis and hepatic failure. Cholestasis, defined as hyperbilirubinemia with a direct bilirubin above 2 mg/dL or more than 15% of total bilirubin, is a hepatocellular injury of the liver that manifests after the administration of parenteral nutrition for at least two weeks. The mechanism by which the liver injury occurs is unknown and probably multifactorial. Risk factors associated with the development of PNAC include: prematurity, low birth weight, absence of enteral feeds, bacterial sepsis, necrotizing enterocolitis, prolonged use of parenteral nutrition, and multiple surgical procedures on the gastro-intestinal tract. In addition, many of the nutrients contained in parenteral nutrition, have been linked with the development of cholestasis.

Specific factors associated with intravenous fat emulsions that have been related to PNAC include : phytosterols, the rate of administration of the intravenous emulsion, the total amount of fat administered and toxic metabolites of intravenous fat emulsions.

The total amount of lipids was found to be a risk factor for cholestasis in children on long-term parenteral nutrition and decreased amount of fat was recommended for the prevention of this hepatic complication (Colomb V, 2000). In the adult population parenteral lipid intake of less than 1gr/kg of body weight decreased the risk of cholestasis in parenteral nutrition treated patients (Cavicchi, 2000).

Current Nutritional Management for VLBW infants in the NBSCU:

The administration of parenteral nutrition to all the preterm babies with a gestational age less than or equal to 29 weeks' is standard practice in the NBSCU for infants not receiving full enteral nutrition. Fat, as an integral part of the intravenous alimentation, is started in the first day of life at a dose of 0.5 grams/kg/day of an 20% fat emulsion(eg, Lyposyn II, Abbott Laboratories Chicago, IL). The amount of fat is then gradually increased by 0.5-1 grams/kg/day to total amount of 3 grams/kg/day as tolerated. The tolerance is checked by measuring serum triglyceride level the morning after 3 grams/kg/day has been reached for the first time serum triglyceride level ≤200 mg/dl are accepted for infants ≤52 weeks postmenstrual age. If the serum triglyceride level is >200 mg/dL, the intravenous fat emulsion is reduced for 24 hours, then the triglyceride level is checked again to ensure that it has dropped below 200 mg/dL. The fat emulsion is then restarted at 1-1.5 grams/kg/day and the serum triglyceride level is monitored as it is slowly increased.

Enteral nutrition is started initially as minimal enteral feedings, also called non-nutritive feedings, usually by 48±12 hours of age with about 12 ml/kg/day. The feedings are then advanced as tolerated with the goal to reach full enteral nutrition (>120 ml/kg/day) between 14-21days of life. As the enteral volumes reach 1/3, 1/2, and 2/3 of the total daily fluid volume, the rate of administration of the lipid emulsion is decreased in steps (ie, from 2 grams/kg/day to 1.5 to 1.0) , until the intravenous fat emulsion is stopped.

As part of standard NBSCU management guidelines screening of liver function consists of measuring serum direct bilirubin level after the baby has been on TPN for 10 days to two weeks and then biweekly, if PN continues. In addition, if the direct bilirubin level is greater than 2.5mg/dL, then liver enzymes will be checked .

Study Procedure:

All preterm babies with a gestational age less than or equal to 29 weeks' born at YNHH who will receive intravenous fat emulsion as part of their nutrition management are eligible to participate in the study. The parents of these babies will be approached during the first 24 hours of life, regarding the possible participation in the study. After informed consent will be obtained, the subjects will be randomized by YNHH Investigator pharmacy to one of the two groups: intervention (restricted intravenous fat intake) and control (standard intravenous fat intake).

Therefore, the purpose of this study will be to determine if PNAC is related to the amount of parenteral fat administered to premature babies until full enteral nutrition is reached.

Study Design

Allocation: Randomized, Control: Dose Comparison, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention


Parenteral Nutrition-Associated Cholestasis


Intravenous fat emulsion, Restriction of intravenous fat emulsion to 1 gm/kg/d


Yale University School of Medicine
New Haven
United States




Yale University

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:16:34-0400

Clinical Trials [3404 Associated Clinical Trials listed on BioPortfolio]

Immune Modulation by Parenteral Lipids

Immune modulating properties of parenteral lipid emulsions seem to contribute to the increased risk for infections which remains associated with the use of total parenteral nutrition. Emul...

Evaluation of Lipid Emulsion on GCX in Critically Ill Patients

Characterisation of the lipidome and parenteral nutrition modulate the endothelial glycocalyx. The aim of the study A is to detect any influence of the lipid emulsion on the endothelial ...

Effects of Lipid Emulsion on the Pharmacokinetic and Pharmacodynamic Properties of Metoprolol.

The aim of this study is to investigate whether intravenous lipid emulsion is effective in attenuating the clinical effects of a cardioactive drug, exemplified by the beta-blocking agent m...

Efficacy of an Omega-3 Enriched Intravenous Fat Emulsion in the Treatment of Parenteral Nutrition Associated Liver Disease in Infants

The purpose of this study is to determine whether Omegaven is effective in the treatment of parenteral nutrition associated liver disease (PNALD).

Effectiveness of Multicomponent Lipid Emulsion in Preterm Infants Requiring Parenteral Nutrition

The purpose of this study is to compare the effects of a multicomponent lipid emulsion containing 30% soybean oil, 30% medium-chain triglycerides, 25% olive oil, and 15% fish oil with a co...

PubMed Articles [4138 Associated PubMed Articles listed on BioPortfolio]

Compatibility of Intravenous Fat Emulsion with Antibiotics for Secondary Piggyback Infusion.

The Guidelines for Parenteral and Enteral Nutrition in Japan state that parenteral fat emulsion can be infused through a secondary administration set. We tested the compatibility of fat emulsion with ...

Intravenous lipid emulsions and liver function in adult patients with chronic intestinal failure: Results from a randomized clinical trial.

Intravenous lipid emulsion (ILE) can become a risk factor for intestinal failure associated liver disease (IFALD). Many ILEs are commercially available, however, a direct comparison of their impact on...

Effect of Delaying Replacement of Parenteral Nutrition Intravenous Administration Sets: Preclinical Experiments and a Dynamic Laboratory Model of Microbial Colonization.

Recommendations prescribe daily intravenous administration set (IVAS) replacement for parenteral nutrition (PN) comprising intravenous fat emulsions (IVFE) due to risk of micro-organism growth and res...

Propensity-Score Matched Comparative Study on Effects of Intravenous Human Serum Albumin Administration in Critically Ill Adult Patients Receiving Parenteral Nutrition.

The objective of this study was to assess the effect of intravenous human serum albumin administration (IV HSA) on nutrition markers, including non-serum-albumin plasma protein levels, in adult critic...

Hemodynamic effects of intravenous, high-dose lipid emulsion with and without metoprolol infusion in healthy volunteers: a randomized clinical trial.

In a double-blinded, randomized, cross-over trial, we investigated hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed four...

Medical and Biotech [MESH] Definitions


A monosaccharide in sweet fruits and honey that is soluble in water, alcohol, or ether. It is used as a preservative and an intravenous infusion in parenteral feeding.

Emulsions of fats or lipids used primarily in parenteral feeding.

Immunoglobulin preparations used in intravenous infusion, containing primarily IMMUNOGLOBULIN G. They are used to treat a variety of diseases associated with decreased or abnormal immunoglobulin levels including pediatric AIDS; primary HYPERGAMMAGLOBULINEMIA; SCID; CYTOMEGALOVIRUS infections in transplant recipients, LYMPHOCYTIC LEUKEMIA, CHRONIC; Kawasaki syndrome, infection in neonates, and IDIOPATHIC THROMBOCYTOPENIC PURPURA.

An emulsion of solid color which when spread over a surface leaves a thin decorative and or protective coating.

More From BioPortfolio on "Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates"

Quick Search


Relevant Topics

Public Health
Alternative Medicine Cleft Palate Complementary & Alternative Medicine Congenital Diseases Dentistry Ear Nose & Throat Food Safety Geriatrics Healthcare Hearing Medical Devices MRSA Muscular Dyst...

Women's Health
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...

Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...

Searches Linking to this Trial