Related Experiment Video
Updated: Jul 9, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT
Sissel J Moltu1, Tone Nordvik1, Madelaine E Rossholt2
1Department of Neonatal Intensive Care, Oslo University Hospital, 0424 Oslo, Norway.
Insights
Early supplementation with arachidonic acid (ARA) and docosahexaenoic acid (DHA) improved white matter (WM) maturation in preterm infants. This suggests ARA and DHA support brain development in vulnerable newborns.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Nutritional Science
Background:
- Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are crucial for neural membrane structure and possess anti-inflammatory effects.
- Very preterm infants miss out on essential placental transfer of ARA and DHA.
- The impact of postnatal ARA and DHA supplementation on preterm infant brain development remains unclear.
Purpose of the Study:
- To investigate if early enteral supplementation with ARA and DHA enhances white matter (WM) microstructure in preterm infants.
- To assess brain maturation using diffusion-weighted magnetic resonance imaging (MRI) at term equivalent age.
Main Methods:
- A double-blind, randomized controlled trial involving infants born before 29 weeks gestational age.
- Infants received either ARA and DHA (100 mg/kg and 50 mg/kg, respectively) or medium-chain triglycerides (control).
- Supplementation occurred from the second day of life until 36 weeks postmenstrual age, with primary outcome assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS).
Main Results:
- The study included 120 infants; 92 underwent MRI, with 74 yielding acceptable DTI data.
- No significant differences in mean or axial diffusivity were observed between groups.
- Significantly higher fractional anisotropy and lower radial diffusivity were found in major WM tracts (e.g., corpus callosum, internal capsule) in the ARA:DHA group.
Conclusions:
- Early enteral supplementation with ARA and DHA, at doses mirroring estimated fetal accretion rates, appears to promote WM maturation in preterm infants.
- While WM microstructure shows improvement, further research is necessary to confirm any associated functional benefits.
Background:
Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age.
Methods:
In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis.
Results:
We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26+3 (22+6 - 28+6) weeks and postmenstrual age at scan was 41+3 (39+1 - 47+0) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group.
Conclusion:
This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit.
Clinical Trial Registration:
www.
Clinicaltrials:
gov; ID:NCT03555019.
