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Published on: November 20, 2015
Brain metabolite alterations in infants born preterm with intrauterine growth restriction: association with
Rui V Simões1, Emma Muñoz-Moreno2, Mónica Cruz-Lemini3
1BCNatal-Barcelona Center for Maternal-Fetal and Neonatal Medicine (Hospital Clínic and Hospital Sant Joan de Déu), Fetal i+D Fetal Medicine Research Center, IDIBAPS, University of Barcelona, Barcelona, Spain; Centre for Biomedical Research on Rare Diseases (CIBER-ER), Barcelona, Spain; Fundació Hospital Sant Joan de Déu, Barcelona, Spain.
Insights
Preterm infants with intrauterine growth restriction show altered brain metabolism and structure, impacting neurodevelopmental outcomes. These findings highlight potential risks and the need for further research into altered neurodevelopmental trajectories.
Area of Science:
- Neuroscience
- Developmental Biology
- Medical Imaging
Background:
- Intrauterine growth restriction (IUGR) and premature birth are independent risk factors for impaired neurodevelopment.
- These conditions can occur together, potentially exacerbating neurodevelopmental deficits.
- Understanding the brain's metabolic and structural changes in these infants is crucial for early intervention.
Purpose of the Study:
- To assess frontal lobe metabolic profiles in 1-year-old infants with IUGR born prematurely.
- To compare these profiles with premature and term-born adequate-for-gestational-age controls.
- To associate metabolic profiles with brain structure, biophysics, and 2-year neurodevelopmental outcomes.
Main Methods:
- Brain MRI and magnetic resonance spectroscopy (MRS) were performed on 1-year-old infants (IUGR preterm, preterm AGA, term AGA).
- T1-weighted, diffusion-weighted images, and proton spectra from the frontal lobe were acquired.
- Neurodevelopment was assessed at 2 years using the Bayley Scales of Infant and Toddler Development, 3rd Edition.
Main Results:
- IUGR preterm infants exhibited smaller brain volumes and increased white matter diffusivity.
- Lower N-acetylaspartate (NAA) levels were observed in IUGR preterm infants compared to preterm AGA controls.
- Metabolite alterations correlated with reduced gray matter, increased diffusivity, and altered white matter integrity, alongside a trend for poorer neurodevelopmental outcomes.
Conclusions:
- Preterm IUGR infants display altered brain metabolite profiles during a critical maturation period.
- These metabolic changes are linked to structural and biophysical brain parameters.
- Altered neurodevelopmental trajectories are suggested in preterm IUGR and preterm AGA infants compared to term AGA infants.
Background:
Intrauterine growth restriction and premature birth represent 2 independent problems that may occur simultaneously and contribute to impaired neurodevelopment.
Objective:
The objective of the study was to assess changes in the frontal lobe metabolic profiles of 1 year old intrauterine growth restriction infants born prematurely and adequate-for-gestational-age controls, both premature and term adequate for gestational age and their association with brain structural and biophysical parameters and neurodevelopmental outcome at 2 years.
Study Design:
A total of 26 prematurely born intrauterine growth restriction infants (birthweight <10th centile for gestational age), 22 prematurely born but adequate for gestational age controls, and 26 term adequate-for-gestational-age infants underwent brain magnetic resonance imaging and magnetic resonance spectroscopy at 1 year of age during natural sleep, on a 3 Tesla scanner. All brain T1-weighted and diffusion-weighted images were acquired along with short echo time single-voxel proton spectra from the frontal lobe. Magnetic resonance imaging/magnetic resonance spectroscopy data were processed to derive structural, biophysical, and metabolic information, respectively. Neurodevelopment was evaluated at 2 years of age using the Bayley Scales 3rd edition, assessing cognitive, language, motor, socioemotional, and adaptive behavior.
Results:
Prematurely born intrauterine growth restriction infants had slightly smaller brain volumes and increased frontal lobe white matter mean diffusivity compared with both prematurely born but adequate for gestational age and term adequate for gestational age controls. Frontal lobe N-acetylaspartate levels were significantly lower in prematurely born intrauterine growth restriction than in prematurely born but adequate for gestational age infants but increased in prematurely born but adequate for gestational age compared with term adequate-for-gestational-age infants. The prematurely born intrauterine growth restriction group also showed slightly lower choline compounds, borderline decrements of estimated glutathione levels, and increased myoinositol to choline ratios, compared with prematurely born but adequate for gestational age controls. These specific metabolite changes were locally correlated to lower gray matter content and increased mean diffusivity and reduced white matter fraction and fractional anisotropy. Prematurely born intrauterine growth restriction infants also showed a tendency for poorer neurodevelopmental outcome at 2 years, associated with lower levels of frontal lobe N-acetylaspartate at 1 year within the preterm subset.
Conclusions:
Preterm intrauterine growth restriction infants showed altered brain metabolite profiles during a critical stage of brain maturation, which correlate with brain structural and biophysical parameters and neurodevelopmental outcome. Our results suggest altered neurodevelopmental trajectories in preterm intrauterine growth restriction and adequate-for-gestational-age infants, compared with term adequate-for-gestational-age infants, which require further characterization.
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