| 1. |
- Dean, Justin M, et al.
(författare)
-
Delayed cortical impairment following lipopolysaccharide exposure in preterm fetal sheep.
- 2011
-
Ingår i: Annals of neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 70:5, s. 846-856
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Preterm infants exhibit chronic deficits in white matter (WM) and cortical maturation. Although fetal infection/inflammation may contribute to WM pathology, the factors contributing to cortical changes are largely unknown. We examined the effect of fetal lipopolysaccharide (LPS) exposure on WM and cortical development as assessed by magnetic resonance imaging (MRI), electroencephalography (EEG), and histopathology in fetal sheep at preterm human equivalent age. METHODS: LPS was administered to fetal sheep at 102.5 ± 0.5 days of gestation. Continuous biophysical recordings were analyzed for 10 days after LPS. At postmortem, measurement of cerebral WM and cortical tissue volumes was achieved by stereological techniques. Specific effects of LPS on MRI-assessed T(1) -weighted and T(2) -weighted images, and immunohistochemical expression of oligodendrocytes, proliferating cells, cortical NeuN-positive and Nurr1-positive neurons (subplate marker), and cell death mechanisms were examined. RESULTS: We observed reductions in WM (∼21%; LPS, 1.19 ± 0.04 vs control, 1.51 ± 0.07cm(3) ; p < 0.001) and cortical (∼18%; LPS, 2.34 ± 0.10 vs control, 2.85 ± 0.07cm(3) ; p < 0.001) volumes, associated with overt and diffuse WM injury, T(1) -/T(2) -weighted signal alterations, and reduced numbers of WM oligodendrocytes (LPS, 485 ± 31 vs control, 699 ± 69 cells/mm(2) ; p = 0.0189) and NeuN-positive (LPS, 421 ± 71 vs control 718 ± 92 cells/mm(2) ; p = 0.04) and Nurr1-positive (control, 2.5 ± 0.6 vs LPS, 0.6 ± 0.1 cells/mm(2) ; p = 0.007) cortical neurons after LPS. Moreover, there was loss of the normal maturational increase in cortical EEG amplitude, which correlated with reduced cortical volumes. INTERPRETATION: Fetal exposure to LPS prior to myelination onset can impair both white matter and cortical development in a preclinical large animal model, supporting a role for maternal/fetal infection in the pathogenesis of preterm brain injury. ANN NEUROL 2011.
|
|
| 2. |
- Hansen-Pupp, Ingrid, et al.
(författare)
-
Postnatal Decrease in Circulating Insulin-Like Growth Factor-I and Low Brain Volumes in Very Preterm Infants.
- 2011
-
Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 96:4, s. 1129-1135
-
Tidskriftsartikel (refereegranskat)abstract
- Context: IGF-I and IGF binding protein-3 (IGFBP-3) are essential for growth and maturation of the developing brain. Objective: The aim of this study was to evaluate the association between postnatal serum concentrations of IGF-I and IGFBP-3 and brain volumes at term in very preterm infants. Design: Fifty-one infants with a mean (sd) gestational age (GA) of 26.4 (1.9) wk and birth weight (BW) of 888 (288) g were studied, with weekly blood sampling of IGF-I and IGFBP-3 from birth until 35 gestational weeks (GW) and daily calculation of protein and caloric intake. Magnetic resonance images obtained at 40 GW were segmented into total brain, cerebellar, cerebrospinal fluid, gray matter, and unmyelinated white matter volumes. Main Outcome Measures: We evaluated brain growth by measuring brain volumes using magnetic resonance imaging. Results: Mean IGF-I concentrations from birth to 35 GW correlated with total brain volume, unmyelinated white matter volume, gray matter volume, and cerebellar volume [r = 0.55 (P < 0.001); r = 0.55 (P < 0.001); r = 0.44 (P = 0.002); and r = 0.58 (P < 0.001), respectively]. Similar correlations were observed for IGFBP-3 concentrations. Correlations remained after adjustment for GA, mean protein and caloric intakes, gender, severe brain damage, and steroid treatment. Protein and caloric intakes were not related to brain volumes. Infants with BW small for GA had lower mean concentrations of IGF-I (P = 0.006) and smaller brain volumes (P = 0.001-0.013) than infants with BW appropriate for GA. Conclusion: Postnatal IGF-I and IGFBP-3 concentrations are positively associated with brain volumes at 40 GW in very preterm infants. Normalization of the IGF-I axis, directly or indirectly, may support normal brain development in very preterm infants.
|
|
| 3. |
- Moltu, Sissel J., et al.
(författare)
-
Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants : a double blind RCT
- 2024
-
Ingår i: Clinical Nutrition. - : Elsevier. - 0261-5614 .- 1532-1983. ; 43:1, s. 176-186
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 4. |
- Pupp, Ingrid, et al.
(författare)
-
Circulatory insulin-like growth factor-I and brain volumes in relation to neurodevelopmental outcome in very preterm infants
- 2013
-
Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447 .- 0047-2506 .- 1478-6990. ; 74:5, s. 564-569
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To evaluate the relationships between postnatal change in circulatory insulin-like growth factor-I (IGF-I) concentrations, brain volumes, and developmental outcome at 2 y of age in very preterm infants. METHODS: IGF-I was measured weekly, and nutritional intake was calculated daily from birth until a postmenstrual age (PMA) of 35 wk. Individual beta coefficients for IGF-I, IGF-I(B), representing the rate of increase in IGF-I from birth until a PMA of 35 wk were calculated. Brain magnetic resonance imaging was performed at term age, with segmentation into total brain, cerebellar, gray matter, and unmyelinated white matter volume (UWMV). Developmental outcome was evaluated using Bayley Scales of Infant Development-II. RESULTS: Forty-nine infants, with mean gestational age (GA) of 26.0 wk, were evaluated at mean 24.6 mo corrected age. Higher IGF-I(B), UWMV, and cerebellar volume were associated with a decreased risk for a Mental Developmental Index (MDI) <85 (odds ratio (95% confidence interval): 0.6 (0.4-0.9), 0.96 (0.94-0.99), and 0.78 (0.6-0.96), respectively). In multivariate analysis, higher IGF-I(B) and higher UWMV combined with female gender constituted the two models with the highest predictive value for MDI > 85. CONCLUSION: A higher rate of increase in circulating IGF-I is associated with a decreased risk for subnormal MDI at 2 y of corrected age. This relationship is in part dependent on brain volume at term age.
|
|
| 5. |
- van de Looij, Yohan, et al.
(författare)
-
High-field diffusion tensor imaging characterization of cerebral white matter injury in LPS-exposed fetal sheep.
- 2012
-
Ingår i: Pediatric research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 72, s. 285-92
-
Tidskriftsartikel (refereegranskat)abstract
- Background:In gyrencephalic species such as sheep, precise anatomical and microstructural characterization of the consequences of fetal inflammation remains scarce. The goal of this study was to characterize changes in white matter structure using advanced MRI following lipopolysaccharide (LPS) exposure in the preterm equivalent fetal sheep.Methods:Preterm (0.7 gestation) fetal sheep received vehicle (Sham group) or LPS (LPS group), and fetal brains were collected 10 days later for subsequent ex-vivo MRI. T(1)-Weighted (T(1)W), T(2)-Weighted (T(2)W), and diffusion tensor imaging (DTI) data were collected.Results:Fetuses exposed to LPS exhibited reductions in white matter volume and corpus callosum thickness at 10 days recovery. Characteristic patterns of diffuse and focal white matter lesions (necrosis or cysts) could be identified by various T(1), T(2) and DTI signal changes.Conclusion:Fetal LPS exposure induces a pattern of injury characterized by diffuse and focal white matter injury, which closely reproduces that observed clinically in preterm infants. This work provides anatomical and microstructural MRI assessment, as well as histopathological correlates, of the consequences of LPS exposure in an animal model with a white matter structure similar to the human brain. This work will help to further our understanding of MRI changes in preterm infants.
|
|
| 6. |
- Wikström, Sverre, 1978-, et al.
(författare)
-
Early Electroencephalography Suppression and Postnatal Morbidities Correlate with Cerebral Volume at Term-Equivalent Age in Very Preterm Infants
- 2018
-
Ingår i: Neonatology. - : S. Karger. - 1661-7800 .- 1661-7819. ; 113:1, s. 15-20
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early brain activity is associated with long-term outcome. Establishing a relation also with postnatal brain growth may increase our understanding of early life influences on preterm brain development.OBJECTIVES: The aim of this study was to investigate whether early electroencephalography (EEG) activity in infants born very preterm is associated with brain volumes at term, and whether postnatal morbidity affects this association.METHODS: Very preterm infants (n = 38) with a median gestational age (GA) of 25.6 weeks had early recordings of single-channel EEG. The percentage of suppressed EEG, i.e., interburst intervals (IBI%) between 24 and 72 h of age, was analyzed in relation to brain volumes on magnetic resonance imaging performed at term-equivalent age, taking into account neonatal morbidities.RESULTS: Early electrocortical depression and a higher IBI% were associated with increased cerebrospinal fluid volume (CSFV) and lower total brain volume relative to intracranial volume, also after adjustment for GA, postnatal morbidities, morphine administration, and postnatal head growth. Overall, an increase in IBI% to 1 SD from the mean corresponded with an increase in CSFV to +0.7 SD and a decrease in brain volume to -0.7 SD. The presence of 2 or more postnatal morbidities were associated with around 10% lower brain volumes.CONCLUSIONS: More suppressed early EEG activity of very preterm infants is associated with lower brain volume and increased CSFV at term age, also when adjusting for postnatal morbidities. The findings indicate the importance of pre- and early postpartal determinants of postnatal brain growth, possibly also including activity-dependent mechanisms for brain growth.
|
|
