Cholestasis
Conditions
Brief summary
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
Interventions
DRUGIntralipid 20% I.V. Fat Emulsion
Sponsors
Seattle Children's Hospital
University of Florida
Primary Children's Hospital
University of Colorado, Denver
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 1 Years
Healthy volunteers
No
Inclusion criteria
* neonates and infants who are at least 28 weeks corrected gestational age at the time of enrollment who are parenteral nutrition (PN) naive * current direct bilirubin \<2 mg/dL * any of the following conditions: * meconium ileus and peritonitis * gastroschisis * omphalocele \>4cm or with liver herniated outside of the abdominal cavity * necrotizing enterocolitis requiring surgical intervention * volvulus * intestinal atresia with \>50% bowel loss
Exclusion criteria
* weight \<1 kg * metabolic pathway defect which is associated with liver dysfunction in the neonatal period, including: hereditary fructose intolerance, galactosemia due to transferase deficiency and neonatal tyrosinemia, and/or disorder of lipid metabolism * hepatic insufficiency as documented by either a biopsy with cirrhosis and/or marked aberration in synthetic function * renal failure * primary or secondary liver disease, regardless of liver function (includes hepatitis) * use of extracorporeal membrane oxygenation (ECMO) * suspected congenital obstruction of the hepatobiliary tree * documented active infection which may be communicable, including infections hepatitis or HIV * previous receipt of choleretic agents * currently receiving phenobarbital or other barbiturates * history of PNAC * direct bilirubin \>=2 mg/dL at time of enrollment * congenital or acquired anomaly which will require major cardiovascular surgery * major congenital or chromosomal anomaly * hypoxic ischemic encephalopathy * congenital defect of the brain * major seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Rise of Direct Bilirubin as a Function of Time | 12 weeks | The rate of rise (change over time) of direct bilirubin was compared between the two groups at different time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 Weeks) | 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 of PNAC | 12 weeks | The time to development was compared between the standard and reduced lipid groups. |
| The Time to Development of Severe PNAC | 12 weeks | The time to development from randomization was compared between the standard and reduced lipid groups. |
| Peak Total Bilirubin Level | 12 weeks | 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. |
| Peak Direct Bilirubin Level | 12 weeks | 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 Prevalence of Essential Fatty Acid Deficiency (EFAD) | 12 weeks | The number of participants who experienced EFAD was compared between the standard and reduced lipid groups. |
| Adequacy of Growth as Evaluated by Z-scores for Weight | 12 weeks | 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. |
| Adequacy of Growth as Evaluated by Z-scores for Height | 12 weeks | 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. |
| Adequacy of Growth as Evaluated by Z-scores for Head Circumference | 12 weeks | 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. |
| Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL) | 12 weeks | 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. |
| Bayley Scales for Infant and Toddler Development (BSID-III) at One Year | 1 year | 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. |
| Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years | 2 years | 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. |
| MacArthur-Bates Communicative Development Inventories (CDI) | 2 years | 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. |
| Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2 | 2 years | 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. |
| Gross Motor Function Classification System (GMFCS) | 2 years | 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. |
| Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | 2 years | 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. |
| Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | 2 years | 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. |
| Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | 2 years | 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. |
| Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections | 12 weeks | The number of episodes were compared between the standard and reduced lipid groups of suspected sepsis episodes, NEC, or catheter-related blood stream infections. |
Countries
United States
Participant flow
Pre-assignment details
Patients who were enrolled were randomized shortly after enrollment. 1 patient was removed immediately after enrollment, before intervention, due to a screen fail.
Participants by arm
| Arm | Count |
|---|---|
| Reduced Lipid Subjects will receive a minimized dose (1 g/kg/day) of the soybean-based lipid component of parenteral nutrition.
Intralipid 20% I.V. Fat Emulsion | 12 |
| Standard Lipid Subjects will receive the standard dose (up to 3 g/kg/day) of the soybean-based lipid component of parenteral nutrition.
Intralipid 20% I.V. Fat Emulsion | 9 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Neurodevelopmental Outcome Follow Up | Became ineligible during follow-up | 1 | 0 |
| Neurodevelopmental Outcome Follow Up | Lost to Follow-up | 1 | 4 |
| Neurodevelopmental Outcome Follow Up | Scheduling error | 1 | 1 |
| Neurodevelopmental Outcome Follow Up | Withdrawal by Subject | 2 | 0 |
| Treatment Period | Physician Decision | 0 | 1 |
| Treatment Period | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Standard Lipid | Reduced Lipid | Total |
|---|---|---|---|
| Age, Continuous | 2 days | 2 days | 2 days |
| Diagnosis Gastroschisis | 8 Participants | 12 Participants | 20 Participants |
| Diagnosis Intestinal atresia | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 10 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized Black or African American | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 participants | 1 participants | 2 participants |
| Race/Ethnicity, Customized Other | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Unknown | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized White | 5 participants | 8 participants | 13 participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 12 | 0 / 9 |
| other Total, other adverse events | 8 / 12 | 4 / 9 |
| serious Total, serious adverse events | 5 / 12 | 4 / 9 |
Outcome results
Primary
Rate of Rise of Direct Bilirubin as a Function of Time
The rate of rise (change over time) of direct bilirubin was compared between the two groups at different time points.
Time frame: 12 weeks
Population: Analyzable data was not available for one participant in the Reduced Lipid Arm
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reduced Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 7 Days from Baseline | 1.025504411 mg/dL/day |
| Reduced Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 56 Days from Baseline | 0.96628119 mg/dL/day |
| Reduced Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 28 Days from Baseline | 0.999691048 mg/dL/day |
| Reduced Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 84 Days from Baseline | 0.933987896 mg/dL/day |
| Reduced Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 1 Day from Baseline | 1.033001353 mg/dL/day |
| Standard Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 84 Days from Baseline | 0.984138047 mg/dL/day |
| Standard Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 1 Day from Baseline | 1.05457485 mg/dL/day |
| Standard Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 7 Days from Baseline | 1.049318179 mg/dL/day |
| Standard Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 28 Days from Baseline | 1.031125269 mg/dL/day |
| Standard Lipid | Rate of Rise of Direct Bilirubin as a Function of Time | 56 Days from Baseline | 1.007357736 mg/dL/day |
Secondary
Adequacy of Growth as Evaluated by Z-scores for Head Circumference
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.
Time frame: 12 weeks
Population: All subjects aside from the screen fail. Z-scores were recorded while subjects were on treatment which meant that they were recorded until 7 days after parenteral nutrition (PN) had been discontinued, but not to exceed 12 weeks for subjects still on PN. This is why the participants analyzed each week is a different number and decreasing with time
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 12 | -0.63 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 4 | -1.745 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 1 | -1.18 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 6 | -1.34 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 9 | -1.44 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 7 | -0.79 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 2 | -1.36 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 8 | -0.845 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Birth | -0.99 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 10 | -0.84 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 3 | -1.67 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 11 | -0.935 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 5 | -1.225 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 11 | -1.19 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 5 | -1.38 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 8 | -1.455 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 12 | -1.31 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Birth | -0.94 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 1 | -1.3 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 2 | -0.82 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 3 | -1 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 4 | -1.1 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 6 | -1.56 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 7 | -1.095 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 9 | -1.39 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Head Circumference | Study Week 10 | -1.255 z-score |
Secondary
Adequacy of Growth as Evaluated by Z-scores for Height
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.
Time frame: 12 weeks
Population: All subjects aside from the screen fail. Z-scores were recorded while subjects were on treatment which meant that they were recorded until 7 days after parenteral nutrition (PN) had been discontinued, but not to exceed 12 weeks for subjects still on PN. This is why the participants analyzed each week is a different number and decreasing with time
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 6 | -1.81 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 7 | -1.56 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Birth | -1.06 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 1 | -1.365 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 2 | -1.53 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 3 | -2.19 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 4 | -2.15 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 5 | -3.21 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 8 | -0.98 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 9 | -1.42 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 10 | -1.58 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 11 | -1.94 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 12 | -0.935 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 11 | -2.81 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 6 | -2.37 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 5 | -2.11 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 7 | -2.39 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Birth | -0.87 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 10 | -2.62 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 1 | -1.22 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 8 | -2.51 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 2 | -1.55 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 12 | -2.775 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 3 | -1.775 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 9 | -2.865 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Height | Study Week 4 | -1.91 z-score |
Secondary
Adequacy of Growth as Evaluated by Z-scores for Weight
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.
Time frame: 12 weeks
Population: All subjects aside from the screen fail. Z-scores were recorded while subjects were on treatment which meant that they were recorded until 7 days after parenteral nutrition (PN) had been discontinued, but not to exceed 12 weeks for subjects still on PN. This is why the participants analyzed each week is a different number and decreasing with time
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 6 | -2.54 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 2 | -2.32 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 7 | -2.37 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 10 | -1.415 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 8 | -1.86 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 3 | -2.33 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 9 | -2.25 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 4 | -2.575 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 1 | -2.28 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 11 | -1.355 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 5 | -2.42 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 12 | -1.33 z-score |
| Reduced Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Birth | -1.36 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 12 | -1.885 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Birth | -0.93 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 1 | -1.85 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 2 | -1.3 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 4 | -1.59 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 5 | -1.78 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 6 | -1.88 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 7 | -1.62 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 8 | -1.745 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 9 | -1.745 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 10 | -1.785 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 11 | -1.885 z-score |
| Standard Lipid | Adequacy of Growth as Evaluated by Z-scores for Weight | Study Week 3 | -1.485 z-score |
Secondary
Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections
The number of episodes were compared between the standard and reduced lipid groups of suspected sepsis episodes, NEC, or catheter-related blood stream infections.
Time frame: 12 weeks
Population: Subjects who experienced an episode of suspected sepsis, catheter-related blood stream infection, or NEC
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reduced Lipid | Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections | Participant 3 | 1 episodes |
| Standard Lipid | Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections | Participant 1 | 2 episodes |
| Standard Lipid | Adverse Events, as Defined by Any Episode of Sepsis and Catheter-related Blood Stream Infections | Participant 2 | 3 episodes |
Secondary
Bayley Scales for Infant and Toddler Development (BSID-III) at One Year
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.
Time frame: 1 year
Population: Participants who returned for their one year follow up
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at One Year | Cognitive Scaled | 9 scores on a scale |
| Reduced Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at One Year | Language Scaled | 18 scores on a scale |
| Reduced Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at One Year | Motor Scaled | 15 scores on a scale |
| Standard Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at One Year | Motor Scaled | 20 scores on a scale |
| Standard Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at One Year | Cognitive Scaled | 10 scores on a scale |
| Standard Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at One Year | Language Scaled | 16 scores on a scale |
Secondary
Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years
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.
Time frame: 2 years
Population: Participants who returned for their 2 year follow-up (Note: subjects who did not do their one year follow up were included)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years | Cognitive Scaled | 7.5 score on a scale |
| Reduced Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years | Language Scaled | 17 score on a scale |
| Reduced Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years | Motor Scaled | 17.5 score on a scale |
| Standard Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years | Language Scaled | 23 score on a scale |
| Standard Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years | Cognitive Scaled | 10.5 score on a scale |
| Standard Lipid | Bayley Scales for Infant and Toddler Development (BSID-III) at Two Years | Motor Scaled | 22 score on a scale |
Secondary
Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2
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.
Time frame: 2 years
Population: Participants who returned for their 2 year follow-up (Note: subjects who did not do their one year follow up were included)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Clinical Probability Index T-Score | 51.5 T-Score |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Internalizing Problems T-Score | 47 T-Score |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Functional Impairment Index T-Score | 52 T-Score |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Externalizing Problems T-Score | 43 T-Score |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Adaptive Skills T-Score | 41 T-Score |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Behavioral Symptoms Index T-Score | 48.5 T-Score |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Adaptive Skills T-Score | 49.5 T-Score |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Externalizing Problems T-Score | 55.5 T-Score |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Internalizing Problems T-Score | 48 T-Score |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Clinical Probability Index T-Score | 50.5 T-Score |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Functional Impairment Index T-Score | 52 T-Score |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 1 of 2 | Behavioral Symptoms Index T-Score | 53 T-Score |
Secondary
Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2
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.
Time frame: 2 years
Population: Participants who returned for their 2 year follow-up (Note: subjects who did not do their one year follow up were included)
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Attentional Control Index | Elevated | 0 Participants |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Overall Executive Functioning Index | Not Elevated | 5 Participants |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Overall Executive Functioning Index | Elevated | 1 Participants |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Attentional Control Index | Not Elevated | 6 Participants |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Behavioral Control Index | Not Elevated | 5 Participants |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Behavioral Control Index | Elevated | 1 Participants |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Emotional Control Index | Not Elevated | 5 Participants |
| Reduced Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Emotional Control Index | Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Emotional Control Index | Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Behavioral Control Index | Not Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Overall Executive Functioning Index | Not Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Emotional Control Index | Not Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Overall Executive Functioning Index | Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Behavioral Control Index | Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Attentional Control Index | Not Elevated | 1 Participants |
| Standard Lipid | Behavioral Assessment System for Children-Third Edition (BASC3) Part 2 of 2 | Attentional Control Index | Elevated | 1 Participants |
Secondary
Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2
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.
Time frame: 2 years
Population: Participants who returned for their 2 year follow-up (Note: subjects who did not do their one year follow up were included)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2 | Problem Percentile | 26 percentile |
| Reduced Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2 | Competence Percentile | 25.5 percentile |
| Standard Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2 | Problem Percentile | 26 percentile |
| Standard Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 1 of 2 | Competence Percentile | 26 percentile |
Secondary
Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2
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.
Time frame: 2 years
Population: Participants who returned for their 2 year follow-up (Note: subjects who did not do their one year follow up were included)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | Possible Problem | 1 Participants |
| Reduced Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | No Problem | 5 Participants |
| Reduced Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | No Deficit/Delay | 5 Participants |
| Reduced Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | Possible Deficit/Delay | 1 Participants |
| Standard Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | Possible Deficit/Delay | 0 Participants |
| Standard Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | No Problem | 2 Participants |
| Standard Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | Possible Problem | 0 Participants |
| Standard Lipid | Brief Infant Toddler Social Emotional Assessment (BITSEA) Part 2 of 2 | No Deficit/Delay | 2 Participants |
Secondary
Gross Motor Function Classification System (GMFCS)
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.
Time frame: 2 years
Population: Subjects who were evaluated using the GMFCS.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 5 | 0 Participants |
| Reduced Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 1 | 5 Participants |
| Reduced Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 2 | 0 Participants |
| Reduced Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 3 | 0 Participants |
| Reduced Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 4 | 0 Participants |
| Standard Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 4 | 0 Participants |
| Standard Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 3 | 0 Participants |
| Standard Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 1 | 2 Participants |
| Standard Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 5 | 0 Participants |
| Standard Lipid | Gross Motor Function Classification System (GMFCS) | Subjects with a classification of 2 | 0 Participants |
Secondary
MacArthur-Bates Communicative Development Inventories (CDI)
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.
Time frame: 2 years
Population: Participants who returned for their 2 year follow-up (Note: subjects who did not do their one year follow up were included)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced Lipid | MacArthur-Bates Communicative Development Inventories (CDI) | Vocabulary Percentile | 25 percentile |
| Reduced Lipid | MacArthur-Bates Communicative Development Inventories (CDI) | Word Forms Percentile | 20 percentile |
| Reduced Lipid | MacArthur-Bates Communicative Development Inventories (CDI) | Complexity Percentile | 16.25 percentile |
| Standard Lipid | MacArthur-Bates Communicative Development Inventories (CDI) | Word Forms Percentile | 50 percentile |
| Standard Lipid | MacArthur-Bates Communicative Development Inventories (CDI) | Vocabulary Percentile | 57.5 percentile |
| Standard Lipid | MacArthur-Bates Communicative Development Inventories (CDI) | Complexity Percentile | 88.75 percentile |
Secondary
Peak Direct Bilirubin Level
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.
Time frame: 12 weeks
Population: Subjects with direct bilirubin values collected after 1 week
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lipid | Peak Direct Bilirubin Level | 0.8 mg/dL |
| Standard Lipid | Peak Direct Bilirubin Level | 1.7 mg/dL |
Secondary
Peak Total Bilirubin Level
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.
Time frame: 12 weeks
Population: Subjects with total bilirubin values collected after 1 week
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lipid | Peak Total Bilirubin Level | 1.7 mg/dL |
| Standard Lipid | Peak Total Bilirubin Level | 2.9 mg/dL |
Secondary
Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL)
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.
Time frame: 12 weeks
Population: Analyzable data was not available for one participant in the Reduced Lipid Arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Lipid | Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL) | 2 Participants |
| Standard Lipid | Prevalence of Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥2 mg/dL) | 3 Participants |
p-value: 0.617Fisher Exact
Secondary
Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 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.
Time frame: 12 weeks
Population: Analyzable data was not available for one participant in the Reduced Lipid Arm
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Lipid | Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 Weeks) | 0 Participants |
| Standard Lipid | Prevalence of Severe Parenteral Nutrition-associated Cholestasis (PNAC) (Direct Bilirubin ≥4 mg/dL in Subjects on Parenteral Nutrition for at Least 2 Weeks) | 1 Participants |
p-value: 0.45Fisher Exact
Secondary
The Prevalence of Essential Fatty Acid Deficiency (EFAD)
The number of participants who experienced EFAD was compared between the standard and reduced lipid groups.
Time frame: 12 weeks
Population: All patients in the reduced lipid group were analyzed. The standard lipid group had essential fatty acid profile drawn for one patient as not all patients in the standard group required the essential fatty acid profile to be drawn.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Lipid | The Prevalence of Essential Fatty Acid Deficiency (EFAD) | 2 Participants |
| Standard Lipid | The Prevalence of Essential Fatty Acid Deficiency (EFAD) | 0 Participants |
Secondary
The Time to Development of PNAC
The time to development was compared between the standard and reduced lipid groups.
Time frame: 12 weeks
Population: Only the subjects that developed PNAC were analyzed
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lipid | The Time to Development of PNAC | 19.50 days |
| Standard Lipid | The Time to Development of PNAC | 39.00 days |
p-value: 0.2716Log Rank
Secondary
The Time to Development of Severe PNAC
The time to development from randomization was compared between the standard and reduced lipid groups.
Time frame: 12 weeks
Population: Subjects who developed severe PNAC as defined by a direct bilirubin value of 4 mg/dL or greater
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Standard Lipid | The Time to Development of Severe PNAC | 42 Days |