Parenteral Nutrition-Associated Liver Disease Clinical Trial
Official title:
Low Dose Parenteral Fat for Prevention of Parenteral Nutrition Associated Cholestasis in Preterm Neonates
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.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention
| Status | Clinical Trial | Phase | |
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| No longer available |
NCT02925520 -
Expanded Access Use of Omegaven® in the Treatment of Parenteral Nutrition Induced Liver Injury in Children
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