Physical activity and exercise capacity in survivors of preterm birth : A population-based cohort study of long-term consequences of prematurity
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Background: Physical activity (PA) is an important mediator of health. Extremely preterm (EP) (<28 weeks’ gestation) and extremely low birth weight (ELBW) (<1000 g) subjects are at increased risk of long-term sequelae that may influence their participation in physical activity (PA) and their exercise capacity. Aims: To compare PA and exercise capacity, by measuring peak oxygen consumption (VO2), as well as body composition between EP/ELBW-born subjects and term-born (TB) controls. Another aim was to identify factors associated with poorer outcomes related to participation and performance in PA and exercise capacity in the EP/ELBW-born group. Cardiopulmonary exercise testing (CPET) both with and without continuous laryngoscopy were used for assessing peak VO2. A method comparison study was therefore conducted to investigate the reliability of peak VO2 obtained by CPET performed with continuous laryngoscopy (CLE test), compared to standard CPET. Methods: A Norwegian national cohort of EP/ELBW children born during 1999-2000 and a regional sub-sample of that cohort and their TB controls were studied. At age 5 years, EP/ELBW-born children were assessed to identify motor- and behavioural problems, as well as deficits in intellectual functioning. At age 11 years, body composition was determined by dual-energy X-ray absorptiometry, and information on PA participation and performance was obtained from a parental questionnaire. A sub-group of particular interest comprising EP/ELBW-born adults who underwent neonatal patent ductus arteriosus (PDA) surgery were examined for left vocal cord paralysis (LVCP). In this PDA surgery group, peak VO2 measurements were obtained and laryngeal obstruction during exercise was assessed for by using the CLE test. The results on peak VO2 were compared to EP/ELBW-born controls with no history of PDA surgery, as well as to TB controls who underwent ordinary CPET. The reliability of gas exchange parameters obtained by the CLE test was determined by comparing gas exchange variables in healthy subjects performing CPET both with and without added CLE setup. Results: EP/ELBW-born children and young adults were less often physically active than TB controls. Parental reported data showed that EP/ELBW-born children had reduced endurance and poorer proficiency in sports and play and were less vigorous during PA than TB controls. EP/ELBW-born children with neurodevelopmental disability (NDD) had even poorer PA outcomes. Young EP/ELBW-born adults had reduced peak VO2 compared to TB controls with a mean difference (95% confidence interval (CI)) of 4.9 (1.8–8.0) ml/kg/min. In otherwise healthy EP/ELBW-born children, preschool motor coordination problems, behavioural problems, and borderline intellectual functioning predicted lower endurance and less vigorous PA at school age. Additionally, motor coordination problems and behavioural problems predicted poor proficiency in sports activities, and borderline intellectual functioning predicted fine motor clumsiness (odds ratios 2–5). Compared to TB controls, EP/ELBW-born children had lower values (mean difference, 95% CI) for total bone mineral density z-score (0.30, 0.13–0.52), muscle mass (0.9, 0.3–1.5 kg), and fat mass ratio (0.14, 0.06–0.21). The differences were reduced when adjusting for PA frequency. The positive association between PA frequency and bone mineral density and muscle mass was weaker in EP/ELBW-born children compared to TB controls. The prevalence of LVCP in 30 EP/ELBW-born adults who underwent PDA surgery was 53%. LVCP and observed laryngeal obstruction during exercise in the PDA surgery group were not associated with reduced peak VO2. Agreement (±95% limits of agreement) for peak VO2 when obtained by the CLE test and standard CPET was 0.2 (±3.7) ml/kg/min. Conclusions and future perspectives: This thesis found that EP/ELBW-born children and young adults were less physically active and that they had lower peak VO2 as adults, compared to TB controls. Children born EP/ELBW with NDD, motor coordination problems, behavioural problems, or borderline intellectual functioning had poorer outcomes related to later PA performance. These findings highlight the need for focused intervention in these groups to improve PA outcomes. The body composition profile in EP/ELBW-born children implies an increased risk of cardiometabolic disease and osteoporosis later in life. High prevalence of LVCP after neonatal PDA surgery has implications in terms of follow-up, although LVCP was not associated with reduced peak VO2. Peak VO2 obtained by the CLE test can be used interchangeably with peak VO2 obtained from standard CPET. Future studies should aim to determine factors that enhance PA participation in EP/ELBW-born individuals and to investigate short- and long-term health benefits of PA in the EP/ELBW-born population.
Består avPaper I: Engan M, Vollsæter M, Øymar K, Markestad T, Eide GE, Halvorsen T, Juliusson P, Clemm H. Comparison of physical activity and body composition in a cohort of children born extremely preterm or with extremely low birth weight to matched termborn controls: a follow-up study. BMJ Paediatr Open. 2019 Jun 29;3(1):e000481. The article is available at: https://hdl.handle.net/1956/23829
Paper II: Engan M, Engeseth MS, Fevang S, Vollsæter M, Eide GE, Røksund OD, Halvorsen T, Clemm H. Predicting physical activity in a national cohort of children born extremely preterm. Early Hum Dev. 2020 Jun;145:105037. The article is available at: https://hdl.handle.net/11250/2763329
Paper III: Engan M, Engeset MS, Sandvik L, Gamlemshaug OCO, Engesæter IØ, Øymar K, Vollsæter M, Røksund OD, Hufthammer KO, Halvorsen T, Clemm HH. Left vocal cord paralysis, lung function and exercise capacity in young adults born extremely preterm with a history of neonatal patent ductus arteriosus surgery – a national cohort study. Front Pediatr. 2022 Jan 3;9:780045. The article is available at: https://hdl.handle.net/11250/2994911
Paper IV: Engan M, Hammer IJ, Bekken M, Halvorsen T, Fretheim-Kelly ZL, Vollsæter M, Bovim LPV, Røksund OD, Clemm H. Reliability of maximum oxygen uptake in cardiopulmonary exercise testing with continuous laryngoscopy. ERJ Open Res. 2021 Feb 15;7(1):00825-2020. The article is available at: https://hdl.handle.net/11250/2763336