Metabolic Mechanisms Induced by Enteral DHA and ARA Supplementation in Preterm Infants

Study Overview
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Brief Summary
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A comprehensive analysis of the impact of exogenous enteral DHA and ARA supplementation on lipid metabolism including the production of downstream derived mediators and how this impacts important biological pathways such as metabolism, inflammation, and organogenic factors.

Detailed Description
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Infants will be randomized to receive the combined enteral DHA/ARA supplement within the first 48 hours after birth to 36 weeks postmenstrual age. The randomization procedure will follow a stratified permuted block scheme to fulfill two goals: (1) randomize infants into one of four arms and (2) ensure an adequate sample size within each week of gestational age. Preterm infants will be randomized using random permuted blocks within each of the 5 birth gestational age strata. When treatment assignment is open and sample size is not overtly large, a block randomization procedure with randomly chosen block sizes can maintain treatment assignment balance and reduce the potential for selection bias. This approach will also ensure that preterm infants of all eligible gestational ages at birth are approximately equally represented in each of 4 arms of the trial, thus ensuring that important comorbidities and standard of care applicable to infants of different gestational ages at birth are also approximately equally distributed across the study arms. There is no placebo for this study. There is no blinding in this study. Consent will also be obtained from the mother of the infant, as they will be asked to provide milk samples if they're breastfeeding their infant, and maternal medical history and demographical data will be recorded.

Official Title
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Metabolic Mechanisms Induced by Enteral Docosahexaenoic Acid (DHA) and Arachidonic Acid (ARA) Supplementation in Preterm Infants

Conditions
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Premature

Intervention / Treatment
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* Dietary Supplement: Enfamil® DHA & ARA Supplement for Special Dietary Use


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: born between 25 0/7 and 29 6/7 weeks of gestation less than 48 hours of age at first lipid dose (The cohort is defined by gestational age rather than birth weight to avoid an over-represented sample of growth-restricted infants in birth weight defined cohorts.) Exclusion Criteria: serious congenital anomalies conditions at birth that will require surgery prior to discharge imminent death such that withdrawal of intensive care support is anticipated within the first 72 hours after birth

Ages Eligible for Study
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Maximum Age: 36 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There will be four arms of the trial encompassing the period from enrollment to 36 weeks' postmenstrual age: (a) DHA/ARA supplement throughout the duration of the protocol, d-on; (b) no DHA/ARA supplement throughout the duration of the protocol, d-off; (c) a cross-over arm of DHA/ARA supplement from enrollment to 31 6/7 weeks post-menstrual age (PMA) then no supplement from 32 to 36 weeks' PMA, x- on/off; and (d) a cross-over arm of no DHA/ARA supplement till 31 6/7 weeks' then long-chain polyunsaturated fatty acids (LCPUFA) supplement from 32 to 36 weeks PMA, x-off/on.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: DHA/ARA supplement<br>DHA/ARA supplement throughout the duration of the protocol, d-on | Dietary Supplement: Enfamil® DHA & ARA Supplement for Special Dietary Use<br>* Dosage: 60 mg/kg/day of DHA and 120 mg/kg/day of ARA. Route of administration: enteral tube or by oral syringe<br>* Other names: DHA/ARA Supplement;|
| No Intervention: No DHA/ARA supplement<br>no DHA/ARA supplement throughout the duration of the protocol, d-off | |
| Other: DHA/ARA initially then no supplement<br>DHA/ARA supplement from enrollment to 31 6/7 weeks post-menstrual age (PMA) then no supplement from 32 to 36 weeks' PMA, x- on/off | Dietary Supplement: Enfamil® DHA & ARA Supplement for Special Dietary Use<br>* Dosage: 60 mg/kg/day of DHA and 120 mg/kg/day of ARA. Route of administration: enteral tube or by oral syringe<br>* Other names: DHA/ARA Supplement;|
| Other: No supplement initially then DHA/ARA supplement<br>No DHA/ARA supplement till 31 6/7 weeks' then long-chain polyunsaturated fatty acids (LCPUFA) supplement from 32 to 36 weeks PMA, x-off/on | Dietary Supplement: Enfamil® DHA & ARA Supplement for Special Dietary Use<br>* Dosage: 60 mg/kg/day of DHA and 120 mg/kg/day of ARA. Route of administration: enteral tube or by oral syringe<br>* Other names: DHA/ARA Supplement;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatty acid levels in plasma | Change in lipid metabolites reflected by levels in plasma | Baseline to 36 weeks | 
| Fatty acid levels in red blood cell (RBC) membranes | Change in fatty acid levels in RBC membranes | Baseline to 36 weeks | 
| Change in circulating biomarker Lipoxin A4 | Biomarker reflective of system development and function will be measured. There are no specific levels since there is no normative data in neonates. | Baseline to 36 weeks | 
| Change in biomarker Resolvin D1 | Biomarker reflective of system development and function will be measured. There are no specific levels since there is no normative data in neonates. | Baseline to 36 weeks | 
| Change in biomarker Resolvin E1 | Biomarker reflective of system development and function will be measured. There are no specific levels since there is no normative data in neonates. | Baseline to 36 weeks | 
| Change in Protectin/Neuroprotectin | Levels of protectin/neuroprotectin and fatty acids in the n3 and n6 pathways will be measured. | Baseline to 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in infant weigh | Recorded in grams (ounces) | Baseline to 36 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infant, premature, fatty acids, nutrition