Infant, Premature
Conditions
Keywords
choline, docosahexaenoic acid
Brief summary
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
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.
Interventions
DIETARY_SUPPLEMENTcholine supplementation
in addition to standard nutrition: enteral supplementation with 30mg/kg choline chloride for 10 days
DIETARY_SUPPLEMENTDHA supplementation
in addition to standard nutrition: enteral supplementation with 60mg/kg DHA for 10 days
DIETARY_SUPPLEMENTstandard nutrition
standard nutrition
Sponsors
University Hospital Tuebingen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Weeks to 2 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| plasma concentrations of choline | following 7 days of supplementation |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| de-novo DHA-phosphatidylcholine synthesis | following 7 days of supplementation at 12hours after D9-choline administration |
| 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 |
| Plasma concentrations of betaine (a metabolite of choline) | baseline and following 7.5 and 10 days of supplementation |
Countries
Germany
Outcome results
None listed