Extremely preterm birth : brain imaging and outcome at early school-age

There has been a dramatic increase in the survival of extremely preterm children over the last decades, and the awareness of the consequences of extremely preterm birth on the developing brain is increasing. This thesis aimed at investigating the neurodevelopmental outcome of extremely preterm children at early school-age, focusing on visual-motor integration and motor impairments, and their relation to findings on early magnetic resonance imaging of the brain. We used a population-based cohort study design, including all 6.5 year old children that had been born before 27 gestational weeks during three years in Stockholm for paper I and II, and in the whole of Sweden for Paper III and Paper IV- the EXPRESS (Extremely Preterm infants in Sweden Study) cohort.

In paper I we found that the preterm children with and without isolated subtle white matter changes, present on magnetic resonance imaging of the brain at term age in about half of extremely preterm children, was not related to visual-motor integration performance, motor function or other neurodevelopment at 6.5 years. In paper II we found correlations between the extremely preterm children’s neonatal brain volumes in the precentral gyrus, the cerebellum and the brainstem - areas known to be involved in visual-motor integration and fine motor skills – and visual-motor integration performance and/or fine motor skills at 6.5 years of age. In paper III we found that 55% of the preterm children had poor visual-motor integration at 6.5 years compared to term-born controls, 78% among children born at 22-23 weeks, and that visual-motor integration scores were associated with cognitive function and fine motor skills. In paper IV we found that motor impairments, defined as developmental coordination disorder, was common and present in 37.1% of apparently healthy extremely preterm children and in 5.5% of term-born controls (adjusted odds ratio 7.92, 99% confidence interval, 3.69-17.20) at 6.5 years. Developmental coordination disorder was associated with various behavioral problems and lower cognition. In half of the children the parents had not noticed the child's motor problems.

In summary, this thesis demonstrated that the extremely preterm children had affected visual-motor integration and motor function, associated with several other problems, at 6.5 years. Also, extremely preterm children with and without isolated subtle white matter changes had similar neurodevelopment at 6.5 years of age, and neonatal brain volumes correlated with visual-motor integration and fine motor skills scores at 6.5 years, indicating that the brain growth is affected already at the time of expected birth. The thesis provides information that can be used when counselling parents about subtle findings on magnetic resonance imaging, and supports the importance of structured long-term follow-up of extremely preterm children.

List of scientific papers

I. Lina Broström, Jenny Bolk, Nelly Padilla, Beatrice Skiöld, Eva Eklöf, Gustaf Mårtensson, Brigitte Vollmer, Ulrika Ådén. Clinical Implications of Diffuse Excessive High Signal Intensity (DEHSI) on Neonatal MRI in School Age Children Born Extremely Preterm. Plos One. 2016 Feb 17, volume: 11, issue: 2, Pages: e0149578.
https://doi.org/10.1371/journal.pone.0149578

II. Jenny Bolk, Nelly Padilla, Lea Forsman, Lina Broström, Kerstin Hellgren, Ulrika Åden. Visual-motor integration and fine motor skills at 6.5 years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: population-based cohort study. BMJ Open. 2018 Feb 17;8(2):e020478.
https://doi.org/10.1136/bmjopen-2017-020478

III. Jenny Bolk, Ylva Fredriksson Kaul, Lena Hellström-Westas, Karin Stjernqvist, Nelly Padilla, Fredrik Serenius, Kerstin Hellgren, Ulrika Åden. National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at 6.5 years. Acta Paediatrica. 2018 May;107(5):831-837.
https://doi.org/10.1111/apa.14231

IV. Jenny Bolk, Aijaz Farooqi, Maria Hafström, Ulrika Åden, Fredrik Serenius. Developmental Coordination Disorder at 6.5 years in apparently healthy children born extremely preterm. [Manuscript]