Related Experiment Video
Updated: May 17, 2026
Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
Effects of glutamine on brain development in very preterm children at school age
Jorrit F de Kieviet1, Jaap Oosterlaan, R Jeroen Vermeulen
1Department of Clinical Neuropsychology, VU University Amsterdam, Amsterdam, Netherlands. jf.de.kieviet@vu.nl
Insights
Early glutamine supplementation in very preterm infants improved brain development, increasing white matter, hippocampus, and brain stem volumes at school age. This benefit was linked to reduced serious neonatal infections.
Area of Science:
- Neonatal Medicine
- Neuroscience
- Nutritional Science
Background:
- Very preterm infants face risks of serious neonatal infections, potentially impacting long-term brain development.
- Glutamine, an amino acid, has shown promise in reducing these infections.
Purpose of the Study:
- To assess the long-term effects of early glutamine-enriched feeding on brain development in very preterm children.
- To investigate if reduced neonatal infections mediate the impact of glutamine on brain development.
Main Methods:
- Follow-up of 52 very preterm children from a randomized controlled trial on enteral glutamine supplementation.
- Brain development assessed at school age using volumetric MRI and fractional anisotropy (FA) of white matter tracts.
Main Results:
- Glutamine group showed increased white matter, hippocampus, and brain stem volumes at school age.
- Higher FA values in the cingulum hippocampal tract were observed in the glutamine group.
- Observed brain volume and FA differences were mediated by reduced serious neonatal infections.
Conclusions:
- Short-term glutamine supplementation in early infancy positively influences brain structure in very preterm children.
- The neurodevelopmental benefits are significantly mediated by a reduction in serious neonatal infections.
Objectives:
The amino acid glutamine has been shown to reduce the number of serious neonatal infections in very preterm children, which may benefit long-term brain development. The aims of the current follow-up study were to (1) determine the long-term effects of glutamine-enriched feeding in the first month after birth in very preterm children on measures of brain development at school age, and (2) elucidate a potential mediating role of serious neonatal infections.
Methods:
Fifty-two very preterm children who originally took part in a randomized controlled trial on enteral glutamine supplementation between day 3 and 30 after birth participated at a mean (SD) age of 8.6 (0.3) years. Measures of brain development included volumetric outcomes of major brain structures, as well as fractional anisotropy (FA) values of major white matter tracts.
Results:
Glutamine supplementation in the first month was associated with medium-sized increases in white matter (d = 0.54, P = .03), hippocampus (d = 0.47, P = .02), and brain stem (d = 0.54, P = .04) volumes at school age. Exploratory analyses using an uncorrected P value indicated higher FA values of the bilateral cingulum hippocampal tract in the glutamine group. All differences were either strongly associated (hippocampus volume, brain stem volume, and FA values of cingulum hippocampal tract) or completely mediated (white matter volume) by the lower number of serious neonatal infections in the glutamine group.
Conclusions:
Short-term glutamine supplementation after birth increases white matter, hippocampus, and brain stem volumes in very preterm children at school age, mediated by a decrease in serious neonatal infections.
Related Concept Videos
01:22Gut-Brain Axis
01:29Environmental Influences on Intelligence