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| Name | Class |
|---|---|
| University of California, Los Angeles | OTHER |
| Northwestern University | OTHER |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 3 gm/kg/day intravenous lipid emulsion | Active Comparator |
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| Intravenous Fat Emulsion-restricted | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intravenous fat emulsion | Other | An infusion of intravenous fat will start at 0.5 grams/kg on the first day of life, with increments of 0.5 -1.0 grams/kg every day, until a total dose of 3 grams/kg is reached. |
| Measure | Description | Time Frame |
|---|---|---|
| The Presence of Cholestasis at Age of 28 Days or When Full Enteral Nutrition is Achieved, Whichever is Longer. | 28 days of age or when full enteral nutrition is acheived, whichever is longer |
| Measure | Description | Time Frame |
|---|---|---|
| Mortality Rate- Death Rate Before Discharge From the Hospital | Discharge from the Newborn ICU | |
| Incidence of Bronchopulmonary Dysplasia (BPD) | 36 weeks PMA or discharge home,whichever comes first |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Richard A Ehrenkranz, MD | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale University School of Medicine | New Haven | Connecticut | 06520-8064 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 8461181 | Background | Lee EJ, Simmer K, Gibson RA. Essential fatty acid deficiency in parenterally fed preterm infants. J Paediatr Child Health. 1993 Feb;29(1):51-5. doi: 10.1111/j.1440-1754.1993.tb00440.x. | |
| 11071594 | Background | Colomb V, Jobert-Giraud A, Lacaille F, Goulet O, Fournet JC, Ricour C. Role of lipid emulsions in cholestasis associated with long-term parenteral nutrition in children. JPEN J Parenter Enteral Nutr. 2000 Nov-Dec;24(6):345-50. doi: 10.1177/0148607100024006345. |
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Bewtween May 2009 -November 2012- infants born and admitted to NICU were enrolled.
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| ID | Title | Description |
|---|---|---|
| FG000 | 3 gm/kg/Day Intravenous Lipid Emulsion | Intravenous fat emulsion : An infusion of intravenous fat will start at 0.5 grams/kg on the first day of life, with increments of 0.5 -1.0 grams/kg every day, until a total dose of 3 grams/kg is reached. |
| FG001 | Intravenous Fat Emulsion-restricted |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Restriction of intravenous fat emulsion to 1 gm/kg/d | Other | Intravenous fat will be started at 0.5 grams/kg on the first day of life and then increase to a dose of 1gram/kg/day the next day. There will be no further increase in the amount of intravenous fat. |
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| Incidence of Necrotizing Enterocolitis (NEC) | At discharge from Newborn ICU |
| Incidence of Retinopathy of Prematurity (ROP) | At discharge from Newborn ICU |
| Late Onset Sepsis | Bloodstream infection, defined as a positive blood culture obtained after 72 hours of life. | At the discharge from Newborn ICU |
| Length of Stay | Defines time to discharge or death. | At discharge from Newborn ICU/death |
| Anthropometric Measurements(Body Weight) | Change in body weight measurement reported in g/week | At age of 28 days and at discharge |
| Anthropometric Measurements(Length) | Change in body length measurement reported in cm/week | At age of 28 days and at discharge |
| Anthropometric Measurements(Head Circumference) | Change in head circumference measurement reported in cm/week | At age of 28 days and at discharge |
| 1071594 | Background | Boyd GW. An investigation of the prolonged pressor response to renin in the nephrectomized rat. Clin Sci Mol Med Suppl. 1976 Dec;3:151s-153s. doi: 10.1042/cs051151s. |
Restriction of intravenous fat emulsion to 1 gm/kg/d : Intravenous fat will be started at 0.5 grams/kg on the first day of life and then increase to a dose of 1gram/kg/day the next day. There will be no further increase in the amount of intravenous fat. |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | 3 gm/kg/Day Intravenous Lipid Emulsion | Intravenous fat emulsion : An infusion of intravenous fat will start at 0.5 grams/kg on the first day of life, with increments of 0.5 -1.0 grams/kg every day, until a total dose of 3 grams/kg is reached. |
| BG001 | Intravenous Fat Emulsion-restricted | Restriction of intravenous fat emulsion to 1 gm/kg/d : Intravenous fat will be started at 0.5 grams/kg on the first day of life and then increase to a dose of 1gram/kg/day the next day. There will be no further increase in the amount of intravenous fat. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
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| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Gestational age at enrollement | Gestational age, in full completed weeks at enrollement. | Mean | Standard Deviation | weeks |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | The Presence of Cholestasis at Age of 28 Days or When Full Enteral Nutrition is Achieved, Whichever is Longer. | Incidence of PNALD at Yale and UCLA NICU prior to the start of the study was around 40%. Our goal was to decrease incidence by 50%/ Alpha of 5%/ Power of 80% We calculated a sample size of 65 infants in each group | Posted | Number | participants who developed Cholestasis | 28 days of age or when full enteral nutrition is acheived, whichever is longer |
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| Secondary | Mortality Rate- Death Rate Before Discharge From the Hospital | Posted | Number | participants | Discharge from the Newborn ICU |
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| Secondary | Incidence of Bronchopulmonary Dysplasia (BPD) | Posted | Number | participants who developed BPD | 36 weeks PMA or discharge home,whichever comes first |
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| Secondary | Incidence of Necrotizing Enterocolitis (NEC) | Posted | Number | participants who developed NEC | At discharge from Newborn ICU |
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| Secondary | Incidence of Retinopathy of Prematurity (ROP) | Posted | Number | participants who developed ROP | At discharge from Newborn ICU |
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| Secondary | Late Onset Sepsis | Bloodstream infection, defined as a positive blood culture obtained after 72 hours of life. | Posted | Number | participants who developed LOS | At the discharge from Newborn ICU |
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| Secondary | Length of Stay | Defines time to discharge or death. | Posted | Mean | Inter-Quartile Range | Days | At discharge from Newborn ICU/death |
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| Secondary | Anthropometric Measurements(Body Weight) | Change in body weight measurement reported in g/week | Posted | Mean | Standard Deviation | g/week | At age of 28 days and at discharge |
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| Secondary | Anthropometric Measurements(Length) | Change in body length measurement reported in cm/week | Posted | Mean | Standard Deviation | cm/week | At age of 28 days and at discharge |
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| Secondary | Anthropometric Measurements(Head Circumference) | Change in head circumference measurement reported in cm/week | Posted | Mean | Standard Deviation | cm/week | At age of 28 days and at discharge |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 3 gm/kg/Day Intravenous Lipid Emulsion | Intravenous fat emulsion: An infusion of intravenous fat will start at 0.5 grams/kg on the first day of life, with increments of 0.5 -1.0 grams/kg every day, until a total dose of 3 grams/kg is reached. | 5 | 67 | 0 | 67 | ||
| EG001 | Intravenous Fat Emulsion-restricted | Restriction of intravenous fat emulsion to 1 gm/kg/d: Intravenous fat will be started at 0.5 grams/kg on the first day of life and then increase to a dose of 1gram/kg/day the next day. There will be no further increase in the amount of intravenous fat. | 6 | 69 | 0 | 69 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Mortality prior to discharge | General disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Orly Levit | Yale University | 203-688-2320 | orly.levit@yale.edu |
| ID | Term |
|---|---|
| D005217 | Fat Emulsions, Intravenous |
| ID | Term |
|---|---|
| D004655 | Emulsions |
| D003102 | Colloids |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| D057947 | Parenteral Nutrition Solutions |
| D019999 | Pharmaceutical Solutions |
| D012996 | Solutions |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
| D020164 | Chemical Actions and Uses |
| D020313 | Specialty Uses of Chemicals |
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| >=65 years |
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| Male |
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