Parenteral nutrition-associated cholestasis (PNAC) and liver disease (PNALD) are
associated with significant morbidity and mortality in neonates and is felt to be
exacerbated by soybean-based lipid emulsions. Much research is currently being directed
at identifying ways to reduce this risk. Reduction of the dose of soybean-based lipid
given as a component of parenteral nutrition is one possible strategy. In this study we
will compare standard dosing of soybean-based lipid (up to 3/kg/day) with a minimized
dose (1 g/kg/day) and evaluate for the development of cholestasis and adequate growth
between the two groups. Longterm followup will include an assessment of
neurodevelopmental outcomes at 12 and 24 months of age.

Funding source - FDA OOPD

Standard Lipid Therapy vs IVFE Minimization for Prevention of PNALD

Cholestasis

Intralipid 20% I.V. Fat Emulsion

Phase 3 Study of Standard Lipid Therapy Versus Intravenous Fat Emulsion Minimization for the Prevention of Parenteral Nutrition-Associated Liver Disease

The rate of rise (change over time) of direct bilirubin was compared between the two
groups at different time points.

Assistant Professor

The number of participants who had a direct bilirubin ≥2 mg/dL were compared between the
standard and reduced lipid groups. Bilirubin data was collected from baseline until 7
days after PN has been discontinued, but not to exceed a total of 12 weeks.

The number of participants with severe PNAC defined as a direct bilirubin ≥4 mg/dL were
compared between the standard and reduced lipid groups. Bilirubin data was collected from
baseline until 7 days after PN has been discontinued, but not to exceed a total of 12
weeks.

The time to development was compared between the standard and reduced lipid groups.

The time to development from randomization was compared between the standard and reduced
lipid groups.

The peak (highest) total bilirubin collected from each subject from after week 1 to end
of treatment. This was compared between the standard and reduced lipid groups.

The peak (highest) direct bilirubin collected from each subject from after week 1 to end
of treatment. This was compared between the standard and reduced lipid groups.

The number of participants who experienced EFAD was compared between the standard and
reduced lipid groups.

Z-scores were compared between subjects in the two treatment groups by week. Z-scores are
the number of standard deviations above (positive value) or below (negative value) the
median on the FENTON and WHO growth charts. Fenton scores were used for infants born <37
weeks gestation. WHO scores were used for infants born at ≥37 weeks gestation.

Z-scores were compared between subjects in the two treatment groups. Z-scores are the
number of standard deviations above (positive value) or below (negative value) the median
on the FENTON and WHO growth charts. Fenton scores were used for infants born <37 weeks
gestation. WHO scores were used for infants born at ≥37 weeks gestation.

The number of episodes were compared between the standard and reduced lipid groups of
suspected sepsis episodes, NEC, or catheter-related blood stream infections.

The Bayley Scales of Infant and Toddler Development (BSID-III) is designed to assess
developmental functioning of infants and toddlers, ages 1 month to 42 months. The
instrument includes five distinct scales, of which three scales and associated subscales
are utilized for the purposes of this study: cognitive, language (receptive and
expressive communication) and motor (fine motor and gross motor). Raw scores are
converted to scaled scores using age-standardized norm. The cognitive scaled scores range
from 1-19. 1 is a low score and 19 is a high score. The Language scaled scores are
calculated by adding the Receptive Communication scores ranging from 1-19 and the
Expressive communication scores ranging from 1-19 to give the Language Scaled score of
2-38. The Motor scaled scores are calculated by adding the Fine Motor scores ranging from
1-19 and the Gross Motor scores ranging from 1-19 to give the Motor scaled ranging from
2-38. Higher scores are better than lower scores.

The MacArthur-Bates Communicative Development Inventories (CDI) are parent report
instruments which capture information about children's developing abilities in early
language. Scores are reported as percentiles compared to age-standardized norms. Higher
scores are better than lower scores.

Dichotomous scores are generated based on cut-off scores, which identify subjects to be
at risk. The problem scale measures behaviors of the child that if present, represent a
problem. The competence scale measures behaviors of the child that if absent, represent a
problem. BITSEA percentile rankings are determined from a table that has a limited range
and are adjusted for age and sex. A high problem score leads to a low problem percentile.
A high competence score leads to a high competence percentile. Percentile rankings for
both problem and competence scores range from "4% or less" to "26% or higher". 4 is the
lowest percentile score and 26 is the highest percentile score. The 25th percentile is
the lower limit of the average range. Higher percentile scores are better than lower
percentile scores in both problem and competence categories.

This classification is based on observation with a scale of 1-5. A lower number
classification is better than a higher classification, with 1 being the best.

The Behavioral Assessment System for Children-Third Edition is a comprehensive set of
forms that helps to understand the behaviors and emotions of children. Scores are
reported as T-Scores. T-Scores range from 0-120. In a normative population, the mean of
standard scores is 50, and standard deviation is 10. For Externalizing Problems T-Score,
Internalizing Problems T-Score, Behavioral Symptoms Index T-Score, Clinical Probability
Index T-Score, and Functional Impairment Index T-Score lower scores are better than
higher scores. For these categories, higher scores are more problematic with scores
between 60-70 regarded as "at risk" and scores 70 and above regarded as clinically
significant and requiring further assessment and possible treatment. For Adaptive Skills
T-Score, a higher score is better than a lower score. For Adaptive Skills T-Score, lower
scores are more problematic with scores between 30-40 regarded as "at risk" and scores at
or below 30 regarded as clinically significant.

The Behavioral Assessment System for Children-Third Edition is a comprehensive set of
forms that helps to understand the behaviors and emotions of children. For Overall
Executive Functioning Index, Attentional Control Index, Behavioral Control Index, and
Emotional Control Index, scores are "Not Elevated" or "Elevated". Not Elevated is better
than Elevated.

Dichotomous scores are generated based on cut-off scores, which identify subjects to be
at risk. The problem scale measures behaviors of the child that if present, represent a
problem. The competence scale measures behaviors of the child that if absent, represent a
problem.

Subjects will receive a minimized dose (1 g/kg/day) of the soybean-based lipid component
of parenteral nutrition.

Subjects will receive the standard dose (up to 3 g/kg/day) of the soybean-based lipid
component of parenteral nutrition.

Standard Lipid Therapy vs IVFE Minimization for Prevention of PNALD

About this trial

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Placebo

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