Bilirubin Neurotoxicity (BN) and Neurodevelopmental Impairment (NDI) in Extremely Preterm (EP) Infants: Avoidable by Reducing the Usual Intravenous Lipid (UL) Administration

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effect of usual versus reduced lipid intake on unbound bilirubin levels, brainstem auditory evoked responses, and neurodevelopmental outcome at 2 years in extremely preterm infants.

Official Title
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Bilirubin Neurotoxicity (BN) and Neurodevelopmental Impairment (NDI) in Extremely Preterm (EP) Infants: Avoidable by Reducing the Usual Intravenous Lipid (UL) Administration

Conditions
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Bilirubin Encephalopathy

Intervention / Treatment
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* Drug: usual prescribed intralipid (UL) regimen
* Drug: restricted prescribed intralipid (RL) regimen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: no major congenital anomaly or overt nonbacterial infection mother has consented to inclusion of the infant for the Neonatal Research Network (NRN) Cycled Phototherapy Trial Exclusion Criteria: has received Intralipid

Ages Eligible for Study
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Maximum Age: 27 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: usual prescribed intralipid (UL) regimen<br> | Drug: usual prescribed intralipid (UL) regimen<br>* Intralipid will be started at 1 g/kg/day and routinely advanced by 1 g/kg/day each day to a max of 3 g/kg/day as per usual clinical practice<br>|
| Experimental: restricted prescribed intralipid (RL) regimen<br> | Drug: restricted prescribed intralipid (RL) regimen<br>* Intralipid will be started at 0.5 g/kg/day and routinely advanced by 0.5 g/kg/day each day to a max of 1.5 g/kg/day (half rate of usual clinical practice).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with unbound bilirubin (UB) concentration greater than 40 nM/L |  | within first 14 days of life | 
| Average unbound bilirubin (UB) concentration | 6 UB measurements will be taken per participant .Average of the 6 readings will be reported | within first 14 days of life | 
| Number of patients with a prolonged brain stem auditory-evoked response (BAER) V latency |  | 34-36 weeks post menstrual age(PMA) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean UB concentration |  | within first 14 days of life | 
| Number of patients with UB measurements greater than 40 nM/L |  | within first 14 days of life | 
| Peak UB concentration |  | within first 14 days of life | 
| Total unbound free fatty acids (FFA) | 6 FFA measurements will be taken for each participant.Average of the 6 readings will be reported | within first 14 days of life | 
| Peak total unbound free fatty acids (FFA) |  | within first 14 days of life | 
| Peak total serum bilirubin |  | within first 14 days of life | 
| Number of patients with Direct bilirubin greater than 1.5 mg/dL |  | Before discharge (discharge is on average 3 months after birth) | 
| Amount of protein given to participant in grams per kilograms per day |  | within first 14 days of life | 
| Amount of carbohydrates given to participant in grams per kilograms per day |  | within first 14 days of life | 
| Amount of fats given to participant in grams per kilograms per day |  | within first 14 days of life | 
| Change in weight(grams/kilogram/day) |  | birth,day 28 | 
| Change in weight(grams/kilogram/day) |  | birth,post menstrual age 36 weeks | 
| Number of patients with Bronchopulmonary dysplasia |  | 36 weeks post menstrual age | 
| number of patients with Perinatal and hospital acquired sepsis episodes |  | birth until discharge ( discharge will be about 3 months post birth) | 
| Number of patients who died |  | 24 months PMA | 
| Number of patients with neurodevelopmental impairment |  | 24 months PMA | 
| Number of patients with hearing loss |  | 24 months PMA | 
| Number of patients with cerebral palsy |  | 24 months PMA | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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preterm, bilirubin, lipid emulsions, unbound bilirubin, unbound free fatty acids