Prematurity, Intestine Perforation, Necrotizing Enterocolitis (NEC), Short Bowel Syndrome (SBS)
Conditions
Keywords
NEC, SBS, enterostomy, fish oil, Microlipid, Intralipid,, enteral fat
Brief summary
Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are common devastating gastrointestinal diseases in premature infants. These infants often need surgical intervention to remove the dead bowel and create temporary enterostomies, resulting in short bowel syndrome (SBS), a malabsorption state due to insufficient bowel length or dysfunction to digest and absorb nutrients adequately. These infants are often nourished primarily with parental nutrition (PN) which can lead to many complications including PN-associated liver disease. However, with enteral feeding, the remaining bowel can adapt somewhat to the shortened state, reducing the need for PN. Enteral fats appear to be the most trophic macronutrients with the long chain polyunsaturated fatty acids (LCPUFA) being the most beneficial in promoting bowel adaptation. Fish oil (FO), a main source of n-3 LCPUFA, has been shown to promote bowel adaptation. Microlipid (ML) primarily contains n-6 PUFA and has been found to decrease ostomy output and increase weight gain in some SBS infants. WThe investigators will soon have completed a randomized clinical trial (EMLFO trial) (WFUHS IRB00011501, NCT01306838) entitled Early Supplementation of Enteral Lipid with Combination of Microlipid and Fish Oil in Infants with Enterostomies. The preliminary data suggest that (a) by supplementing enteral ML/FO, we were able to decrease the use of IL; (b) premature infants in the treatment group who received ML/FO achieved higher enteral calorie (% of total calorie) intake before reanastomosis and better weight gain (g/day) after reanastomosis than those who received routine care in control group; and (c) the direct bilirubin level before reanastomosis tended to be lower in the treatment group than the control group although the difference was not statistically significant. Because the intervention consisted of both an increase in enteral fat intake as well as a specific type of fat intake (i.e. FO), it is unclear whether improved outcomes in the ML/FO group are attributable to FO's anti-inflammatory effects or the increased fat intake. Therefore, the investigators have designed a next randomized clinical trial to compare ML alone versus ML plus FO. We hypothesize that as compared to ML alone, ML plus FO will result in decreased systemic inflammation, as indicated by blood levels of inflammation-related proteins and indicators of oxidative stress.
Detailed description
In comparison to EMLFO trial, the EMLFO-2 study will modify the eligibility criteria to only enroll the infants who have birthweight equal to or less than 1250 g with a jejunostomy or ileostomy as the result of surgical treatment for small intestine perforation or NEC in order to increase the homogeneity of patient population.
Interventions
DIETARY_SUPPLEMENTMicrolipid with fish oil
Fish oil will start with initial feeding after ostomy placement and Microlipid will start once infant tolerating enteral feeds at 20 ml /kg/d while weaning the Intralipid, which both will be continued until reanastomosis.
DIETARY_SUPPLEMENTMicrolipid
A small amount (ml) of Microlipid to match the amount of fish oil in ML/FO group will start with initial feeding after ostomy placement and Microlipid will start once infant tolerating enteral feeds at 20 ml /kg/d while weaning the Intralipid, which will be continued until reanastomosis.
Sponsors
Wake Forest University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Days to 2 Months
Healthy volunteers
No
Inclusion criteria
1. infants (age range: newborn to ≤ 2-month-old) whose birth weight are ≤ 1250g; 2. who are admitted to BCH NICU for surgical intervention for NEC or small intestine perforation and then to have a jejunostomy or ileostomy; 3. who are expected to need full or partial PN for at least 21days from the day of ostomy placement; and 4. who have received enteral feedings ≤ 4 days since ostomy placement.
Exclusion criteria
1. infant with birth weight \> 1250g; 2. infant with colostomy; 3. infants with enterostomy but * unable to obtain written informed consent from parent; * presence of congenital liver, renal, or metabolic diseases or syndromes or perinatal asphyxia; * ostomy caused by surgical treatment for a condition other than NEC or small intestine perforation; and * unable to initiate enteral feeding for more than 28 days since ostomy placement.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Serum Biomarkers of Inflammatory Cytokines | 2 years and 5 months | Compare the serum biomarkers of inflammatory cytokines of the infants receiving ML/FO to the infants only receiving ML between the initial feeding after placement of an ostomy and reanastomosis |
| The Serum Biomarkers of Oxidative Stress | 2 years and 5 months | Compare the serum biomarkers of oxidative stress of the infants receiving ML/FO to the infants only receiving ML between the initial feeding after placement of an ostomy and reanastomosis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Average Enteral Calorie (Total Calorie) Intake Before Reanast | 2 years and 5 months | To compare the average enteral calorie (total calorie) intake of infants receiving ML/FO to the group only receiving ML between the initial feeding after placement of an ostomy and reanastomosis |
| The Average Weight Gain (g/Day) After Reanastomosis | 2 years and 5 months | To compare the the average weight gain (g/day) of infants receiving ML/FO to the infants only receiving ML after reanastomosis |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Microlipid and Fish Oil Group This group will be given early enteral lipid supplementation with Microlipid and fish oil.
Microlipid and fish oil: Fish oil will start with initial feeding after ostomy placement and Microlipid will start once infant tolerating enteral feeds at 20 ml /kg/d while weaning the Intralipid, which both will be continued until reanastomosis. | 9 |
| Microlipid Group This group will be given early enteral lipid supplementation only with Microlipid.
Microlipid: A small amount (ml) of Microlipid to match the amount of fish oil in ML/FO group will start with initial feeding after ostomy placement and Microlipid will start once infant tolerating enteral feeds at 20 ml /kg/d while weaning the Intralipid, which will be continued until reanastomosis. | 9 |
| Total | 18 |
Baseline characteristics
| Characteristic | Microlipid and Fish Oil Group | Microlipid Group | Total |
|---|---|---|---|
| Age, Continuous | 26.3 weeks STANDARD_DEVIATION 2 | 25.9 weeks STANDARD_DEVIATION 2 | 26.1 weeks STANDARD_DEVIATION 2 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 9 |
| other Total, other adverse events | 0 / 9 | 0 / 9 |
| serious Total, serious adverse events | 0 / 9 | 0 / 9 |
Outcome results
Primary
The Serum Biomarkers of Inflammatory Cytokines
Compare the serum biomarkers of inflammatory cytokines of the infants receiving ML/FO to the infants only receiving ML between the initial feeding after placement of an ostomy and reanastomosis
Time frame: 2 years and 5 months
Population: No data collected
Primary
The Serum Biomarkers of Oxidative Stress
Compare the serum biomarkers of oxidative stress of the infants receiving ML/FO to the infants only receiving ML between the initial feeding after placement of an ostomy and reanastomosis
Time frame: 2 years and 5 months
Population: No data collected
Secondary
The Average Enteral Calorie (Total Calorie) Intake Before Reanast
To compare the average enteral calorie (total calorie) intake of infants receiving ML/FO to the group only receiving ML between the initial feeding after placement of an ostomy and reanastomosis
Time frame: 2 years and 5 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Microlipid and Fish Oil Group | The Average Enteral Calorie (Total Calorie) Intake Before Reanast | 52.1 kcal/kg/day | Standard Deviation 23.6 |
| Microlipid Group | The Average Enteral Calorie (Total Calorie) Intake Before Reanast | 56.7 kcal/kg/day | Standard Deviation 15.6 |
Secondary
The Average Weight Gain (g/Day) After Reanastomosis
To compare the the average weight gain (g/day) of infants receiving ML/FO to the infants only receiving ML after reanastomosis
Time frame: 2 years and 5 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Microlipid and Fish Oil Group | The Average Weight Gain (g/Day) After Reanastomosis | 26.6 g/d | Standard Deviation 8.5 |
| Microlipid Group | The Average Weight Gain (g/Day) After Reanastomosis | 20.9 g/d | Standard Deviation 12.2 |