Metabolic Effects of Choline and Docosahexaenoic Acid Supplementation in Preterm Infants

Study Overview
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Brief Summary
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To explore the effects of enteral choline and DHA supplementation on plasma choline and DHA-PC concentrations and metabolism, this randomized controlled study will assign 40 preterm infants to 1 of 4 groups: standard care, choline supplementation, DHA supplementation, and choline and DHA supplementation. After 7 days of supplementation, a single dose of stable isotope labelled choline will be administered and the kinetics of newly synthesized DHA-PC determined to assess plasma levels, uptake and distribution of choline and DHA. This study is designed to inform larger studies evaluating this approach of enteral co-application of choline and DHA on clinical important outcomes.

Detailed Description
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In utero, there is a constant high supply of choline to the fetus. Preterm delivery disrupts this maternal-fetal choline-transfer. We have shown that choline plasma levels rapidly half after preterm delivery. We also demonstrated that plasma DHA-PC rapidly falls after preterm delivery. DHA supplementation has been evaluated and found safe, however the clinical benefits have been smaller than expected. We speculate that choline deficiency may have contributed to the smaller than expected benefit of DHA supplementation in the past. This study verifies the hypothesis that concomitant supply of choline and DHA will improve DHA-PC availability and turn-over. This is important because DHA-PC is the transport molecule for the DHA transport to the brain and the retina. To explore the effects of enteral choline and DHA supplementation on plasma choline and DHA-PC concentrations, this randomized controlled study will assign 40 preterm infants to 1 of 4 groups: standard care, choline supplementation, DHA supplementation, and choline and DHA supplementation. After 7 days of supplementation, a single dose of stable isotope labelled choline will be administered and the kinetics of newly synthesized DHA-PC determined to assess plasma levels, uptake and distribution of choline and DHA. This study is designed to inform future larger studies evaluating this approach of enteral co-application of choline and DHA on important clinical outcomes.

Official Title
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Nahrungsergänzung Mit Cholin- Und Docosahexaensäure Bei Sehr Unreifen Frühgeborenen

Conditions
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Infant, Premature

Intervention / Treatment
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* Dietary Supplement: choline supplementation
* Dietary Supplement: DHA supplementation
* Dietary Supplement: standard nutrition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: preterm infants with a gestational age at birth between 24 and 32 weeks on almost complete enteral feeding (>75% of total fluid intake) Exclusion Criteria: insufficient enteral intake, gastrointestinal disease, missing parental consent

Ages Eligible for Study
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Minimum Age: 1 Week
Maximum Age: 2 Months

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: standard nutrition<br>standard nutrition | Dietary Supplement: standard nutrition<br>* standard nutrition<br>|
| Experimental: choline supplementation<br>in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days | Dietary Supplement: choline supplementation<br>* in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days<br>Dietary Supplement: standard nutrition<br>* standard nutrition<br>|
| Experimental: DHA supplementation<br>in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days | Dietary Supplement: DHA supplementation<br>* in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days<br>Dietary Supplement: standard nutrition<br>* standard nutrition<br>|
| Experimental: choline and DHA supplementation<br>in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride and 60mg/kg of DHA for 10 days | Dietary Supplement: choline supplementation<br>* in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days<br>Dietary Supplement: DHA supplementation<br>* in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days<br>Dietary Supplement: standard nutrition<br>* standard nutrition<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| plasma concentrations of choline |  | following 7 days of supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| de-novo DHA-phosphatidylcholine synthesis |  | following 7 days of supplementation at 12hours after D9-choline administration | 
| DHA-phosphatidylcholine turnover |  | following 7.5 days of supplementation, from 12hours to 60 hours after D9-choline administration | 
| fractions and concentrations of molecular species of phosphatidylcholine |  | baseline and following 7.5 and 10 days of supplementation | 
| plasma concentrations of choline |  | baseline and following 7.5 and 10 days of supplementation | 
| Plasma concentrations of betaine (a metabolite of choline) |  | baseline and following 7.5 and 10 days of supplementation | 
| Plasma concentrations of dimethylglycine (a metabolite of choline) |  | baseline and following 7.5 and 10 days of supplementation | 
| Plasma concentrations of trimethylamineoxide (TMAO, a metabolite of choline) |  | baseline and following 7.5 and 10 days of supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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choline, docosahexaenoic acid