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http://hdl.handle.net/20.500.14454/1634

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Being born extremely preterm with low-grade intraventricular haemorrhage had no impact on brain volumes or neurodevelopment in later childhood
(John Wiley and Sons Inc, 2025-05) Broström, Lina; Fernández de Gamarra Oca, Lexuri; Kvanta, Hedvig; Örtqvist, Maria; Padilla, Nelly; Ådén, Ulrika
Aim: Our aim was to investigate the impact that low-grade intraventricular haemorrhage (IVH) had on neonatal morbidities, brain volumes and neurodevelopmental outcomes in children born extremely preterm (EPT) and compare them with children born EPT without low-grade IVH. Methods: This prospective cohort study was carried out in Stockholm, Sweden. It focused on 103 children born EPT from 2004 to 2007, at less than 27 weeks of gestation, without major brain injuries. The group with low-grade IVH, defined as grades I–II, were compared with children born EPT without IVH. Around half (45%) underwent MRI scans at 10 years of age and 55% had neurodevelopmental assessments at 12 years. Results: The low-grade IVH group was sicker during the neonatal period than the children born EPT without IVH. They had lower gestational ages at birth, more days on mechanical ventilation, a higher incidence of necrotising enterocolitis and were more likely to need surgical ligation of patent ductus arteriosus. However, they did not have significantly smaller brain volumes at 10 years of age or worse neurodevelopmental outcomes at 12 years of age. Conclusion: Brain volumes or neurodevelopment were not affected in children born EPT with low-grade IVH, compared to children born EPT without IVH.
Brain volumes and cortical thickness and associations with cognition in children born extremely preterm
(Springer Nature, 2025-02) Kvanta, Hedvig; Padilla, Nelly; Nosko, Daniela; Mårtensson, Gustaf; Broström, Lina; Fernández de Gamarra Oca, Lexuri; Bolk, Jenny; Ådén, Ulrika
Background: Children born extremely preterm (EPT) have altered brain volumes and cortical thickness and lower cognition than children born at term. Associations between these have remained largely unexplored, due to the lack of studies focusing on children born EPT. Methods: Children underwent brain magnetic resonance imaging (MRI) at term and/or 10 years and cognitive assessments at 12 years. The study comprised of 42 children born EPT and 29 term-born controls with cognitive data and MRI data at 10 years, 25 children born EPT had MRI data at term age and 20 had longitudinal MRI data. Results: Cognition was positively associated with brain volumes at 10 years, but negatively associated with cortical thickness at 10 years. Most associations between term age brain volumes and cognitive outcomes were non-significant for children born EPT. Growth from term to 10 years in children born EPT was not associated with cognition. Insular volume was positively associated with cognition in children born EPT. Conclusion: Imaging assessments at 10 years had similar associations to cognition in children born EPT and term-born controls. Insular volume could be a biomarker for cognitive outcome. Associations between brain volumetric growth and cognition require further investigation. Impact: This study investigated brain volumes, volumetric growth, and cortical thickness in children born extremely preterm, who have rarely been studied exclusively, and compared the data with term-born controls. In both groups, brain volumes at 10 years were positively associated with cognitive outcome at 12 years, but cortical thickness at 10 years was negatively associated with cognitive outcome at 12 years. Volumetric growth from term age to 10 years was not associated with cognitive outcome in the subset of children born extremely preterm with longitudinal data. Insular volume may be a potential biomarker for cognitive outcome in children born extremely preterm.
Extreme prematurity and perinatal risk factors related to extremely preterm birth are associated with complex patterns of regional brain volume alterations at 10 years of age: a voxel-based morphometry study
(Frontiers Media S.A., 2023-05-19) Kvanta, Hedvig; Bolk, Jenny; Broström, Lina ; Fernández de Gamarra Oca, Lexuri; Padilla, Nelly ; Ådén, Ulrika
Objective: Structural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group. Methods: At 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age-specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term. Results: We found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05). Conclusions: Children born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age.
Hippocampal volumes and cognitive performance in children born extremely preterm with and without low-grade intraventricular haemorrhage
(Springer Science and Business Media Deutschland GmbH, 2023-06) Fernández de Gamarra Oca, Lexuri; Kvanta, Hedvig; Broström, Lina; Nosko, Daniela; Eklöf, E.; Ojeda del Pozo, Natalia; Zubiaurre Elorza, Leire; Padilla, Nelly; Ådén, Ulrika
Children born extremely preterm, especially those with intraventricular haemorrhage (IVH), are at increased risk of adverse cognitive outcomes during childhood. The present study aimed to explore the effects of IVH (grades I–II) on hippocampal volumes, and their correlates with cognitive performance. The sample consisted of 94 participants, including 54 children born extremely preterm (19 with IVH, grades I–II), and 40 children born at term. All participants underwent a magnetic resonance imaging study at the age of 10 (Mage = 10.20 years; SDage = 0.78), and 74 of them (45 extremely preterm and 29 full-term) carried out a cognitive assessment at 12 years old. Children born extremely preterm had lower scores in cognitive performance compared to their full-term peers. Significant positive partial correlations were observed between global bilateral hippocampus, left CA-field, and left subiculum volumes with processing speed in the full-term group, while no significant correlations were found in the extremely preterm group. Moderation analyses in the extremely preterm sample revealed that low-grade IVH moderated the relationship between right hippocampal volume and full-IQ (F(4,40) =5.42, p = 0.001, R2 = 0.35). Having greater right hippocampal volume had a protective effect on full-IQ in those children born extremely preterm with low-grade IVH.
Language performance and brain volumes, asymmetry, and cortical thickness in children born extremely preterm
(Springer Nature, 2024-03) Kvanta, Hedvig; Bolk, Jenny; Broström, Lina; Nosko, Daniela; Fernández de Gamarra Oca, Lexuri; Padilla, Nelly; Ådén, Ulrika
Background: Children born preterm are more prone to have language difficulties. Few studies focus on children born extremely preterm (EPT) and the structural differences in language-related regions between these children and children born at term. Methods: Our study used T1-weighted magnetic resonance imaging (MRI) scans to calculate the brain volumetry, brain asymmetry, and cortical thickness of language-related regions in 50 children born EPT and 37 term-born controls at 10 years of age. The language abilities of 41 of the children born EPT and 29 term-born controls were then assessed at 12 years of age, using the Wechsler Intelligence Scale for Children, Fifth Edition and the Clinical Evaluations of Language Fundamentals, Fourth Edition. The differences between MRI parameters and their associations with language outcomes were compared in the two groups. Results: Brain volume and cortical thickness of language-related regions were reduced in children born EPT, but volumetric asymmetry was not different between children born EPT and at term. In children born EPT the brain volume was related to language outcomes, prior to adjustments for full-scale IQ. Conclusions: These findings expand our understanding of the structural correlates underlying impaired language performance in children born with EPT. Impact: The article expands understanding of the structure-function relationship between magnetic resonance imaging measurements of language-related regions and language outcomes for children born extremely preterm beyond infancy. Most literature to date has focused on very preterm children, but the focus in this paper is on extreme prematurity and language outcomes. While the brain volume and cortical thickness of language-related regions were reduced in children born EPT only the volume, prior to adjustment for full-scale IQ, was associated with language outcomes. We found no differences in volumetric asymmetry between children born EPT and at term.

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