Imaging of the brain and of the lungs in young adults born prematurely and / or with a low birth weight. Radiological findings and associations with clinical features.
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Background and Purpose: Premature birth is defined as a birth occurring earlier than 37 gestational weeks, and typically occurs in 6% of all pregnancies in Europe (1). All premature babies are at risk for health problems but the earlier a baby is born, the greater the risk for serious complications (2). Two of the main organs greatly affected by premature birth are the lungs and the brain and the overall aim of this study was to address imaging techniques commonly used in the follow-up of these organs in prematurely born or babies with low birth weight, by - establishing a scoring system for pulmonary findings as assessed by High Resolution Computer Tomography (HRCT) - reporting the prevalence of pulmonary HRCT findings and investigate the associations of these HRCT findings with neonatal factors and lung function tests in children and young adults born with a birth weight below 1000g or a gestational age below 28 weeks - establishing Magnetic Resonance Imaging (MRI) based reference intervals for different brain structures and by - reporting the prevalence of cerebral MRI findings, with a special focus on the Corpus Callosum (CC), in young adults born with a birth weight below 2000g. Materials and Methods: All study subjects were born within a defined area of Western Norway (Hordaland and Sogn og Fjordane counties) during the period 1982 to 1992, and had their medical care at Haukeland University Hospital, which is the only provider of neonatal intensive care within this area. The present work is based on three cohorts. The lung study involved two different cohorts; one including a total of 46 adolescents born between 1982 and 1985, and a second cohort including 35 children born during 1991-1992. During these two periods, all those born with a gestational age (GA) 28 weeks or a birth weight 1000 g were included in prospective, longitudinal studies, of which a total of 74 were examined with HRCT during 2001-2002. The mean age at HRCT examination was 18 and 10 years, respectively. The lung function tests were performed within two weeks of the HRCT, and included assessment of airway dimensions, airway reactivity and lung volumes. For the purpose of the present study, we collected neonatal characteristics and whether or not there was a diagnosis of Bronchopulmonal Dysplasia (BPD) from previous reports. The brain study involved 174 subjects born with a BW < 2000g, between 1986 and 1988, of which 113 agreed to have a MRI examination (65.3% of the eligible cases) during 2006-2007. 91% of the cases were also born prematurely and 61% had a birth weight below 1500g. A control group born during the same period, and recruited at age 5 years, was also included in the present long-term follow-up during 2006-2007. All study (n=113) and control (n=100) subjects had a 3 Tesla MRI examination performed. The images were assessed both subjectively and objectively, with the observers masked for grouping and additional information. Data on socioeconomic status (SES) were obtained from questionnaires at a follow-up at 11 years of age, and cognitive abilities were assessed at five and 11 years using age appropriate Wechsler scales. At 19 years cognitive abilities were assessed using the Wechsler Abbreviated Scale of Ability (WASI) 25. Prorated IQ was estimated from the two subtests; word comprehension test and matrixes. Results: Lung: 87% of the premature survivors had abnormal findings at HRCT, with linear and triangular opacities being the more common. Only one case with emphysema was detected. The inter- and intra observer agreement was moderate to good for “total score”, as well as for “linear opacities”, “triangular opacities”, “mosaic perfusion” and “air trapping”, with weighted Kappa values ranging between 0.4 and 0.7. When using the old classification of for BPD, i.e. oxygen dependency and radiological findings at day 28 of life, no significant association between BPD and long-term HRCT findings was found. However, when using the new classification, i.e. oxygen dependency at postmenstrual age 36 weeks, a significant association was demonstrated between the total HRCT score and moderate/severe BPD. A history of prolonged requirements for oxygen treatment predicted subsequent HRCT abnormalities, and days of supplemental oxygen appeared to be the single most important factor predicting structural lung abnormalities. All of the assessed lung function variables (FEV1 , FEF 50 and FEF 25-75 and the ratio RV/TLC) were significantly associated with linear / triangular opacities and with the total HRCT score. Brain: Based on a subjective assessment of the 100 controls, two subjects were judged to have moderately and 36 to have mildly dilated lateral ventricles by observer one, while figures for observer two were one and 14, respectively. Overall, the two observers agreed on 15 having either mild or moderate dilatation (Kappa 0.43). Dilatation of the lateral ventricles and loss of bulk of white matter were seen in 40% of the Low birth weights vs.15% of the controls, while thinning of CC was seen in 20% of the Low birth weights and in 7% of the controls. The MRI findings were not significantly related to any of the pre-, peri- or early postnatal factors available for statistical analysis. Sex specific reference intervals for adolescents born term were presented. The Low birth weight survivors had a smaller total Corpus Callosum area than the controls, but this group difference disappeared when correcting for forebrain volume. When analysing the sub-divisions of the CC, we found a significant group difference regarding the posterior 3rd (splenium). Conclusions: The prevalence of pulmonary changes in premature survivors, as assessed by HRCT, is high, but the findings are subtle. Number of days with supplementary oxygen in the neonatal period is the most important factor for predicting these abnormal findings. The structural lung abnormalities are associated with airflow- and lung volume measurements. The accuracy of the proposed scoring system was acceptable. The refined and simplified scoring system allowed for assessment of a maximum score. Subjective assessment overestimates ventricular size compared with measurements and the use of reference intervals. Thus, a high total of 15% of healthy adolescents was judged to have dilated lateral ventricles as assessed by an experienced neuroradiologist, underscoring the need for our new, MRI based reference intervals. Separate reference intervals for healthy 19 years olds have been presented. Based on subjective assessment, dilatation of the lateral ventricles, loss of bulk of white matter and thinning of Corpus Callosum were more commonly seen among Low birth weights than among controls, however, the findings must be interpreted in the light of the aforementioned. Adolescents born with a BW < 2000g have a smaller posterior Corpus Callosum than their peers born term. Pulmonary HRCT and brain MRI demonstrated several findings consistent with prematurity / and or a low birth weight, and some of the findings were associated with neonatal factors and clinical findings. Our results do not justify the use of routine HRCT or brain MRI’s during follow-up of these individuals.
Paper I: American Journal of Roentgenology 187(4), Aukland, S. M.; Halvorsen, T.; Fosse, K. R.; Daltveit, A. K.; Rosendahl, K., High-Resolution CT of the Chest in Children and Young Adults Who Were Born Prematurely: Findings in a Population-Based Study, pp. 1012-1018. Copyright 2006 American Roentgen Ray Society. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.2214/AJR.05.0383Paper II: Thorax 64(5), Aukland, S. M.; Rosendahl, K.; Owens, C. M.; Fosse, K. R.; Eide, G. E.; Halvorsen, T., Neonatal bronchopulmonary dysplasia predicts abnormal pulmonary HRCT scans in long-term survivors of extreme preterm birth, pp. 405-410. Published by BMJ. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1136/thx.2008.103739Paper III: Neuroradiology 50(12), Aukland, S. M.; Odberg, M. D.; Gunny, R.; Chong, W. K.; Eide, G. E.; Rosendahl, K., Assessing ventricular size: is subjective evaluation accurate enough? New MRI-based normative standards for 19-year-olds, pp. 1005-1011. Copyright 2008 Springer-Verlag. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1007/s00234-008-0432-4Paper IV: Pediatric Neurology 43(4), Odberg, M. D.; Aukland, S. M.; Rosendahl, K.; Elgen, I. B., Cerebral MRI and cognition in nonhandicapped, low birth weight adults, pp. 258-262. Copyright 2010 Elsevier. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.1016/j.pediatrneurol.2010.05.014Paper V: American Journal of Neuroradiology 32(5), Aukland, S. M.; Westerhauen, R.; Plessen, K. J.; Odberg, M. D.; Elgen, I.; Peterson, B. S.; Ersland, L.; Eide, G. E.; Rosendahl, K., Selectively Reduced Posterior Corpus Callosum Size in a Population-Based Sample of Young Adults Born with Low Birth Weight, pp. 970-975. Copyright 2011 American Society of Neuroradiology. Full text not available in BORA due to publisher restrictions. The published version is available at: http://dx.doi.org/10.3174/ajnr.A2594