Physical activity and exercise capacity in survivors of preterm birth : A population-based cohort study of long-term consequences of prematurity

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.Doktorgradsavhandlin

Vascular endothelial function assessed by flow-mediated vasodilatation in young adults born very preterm or with extremely low birthweight: A regional cohort study

Background: Preterm birth and low birthweight have been associated with increased risk of cardiovascular disease in young adults. Endothelial dysfunction is established as an early marker for development of atherosclerotic cardiovascular disease. Previous studies of endothelial function in young adults born very preterm or with extremely low birthweight have, however, shown diverging results. Objective: We aimed to evaluate the risk of cardiovascular disease as measured by vascular endothelial function in young adults born very preterm (<29 weeks of gestation) or with extremely low birthweight (<1,000 g), compared with term-born controls. Methods: This study included 50 young adults born very preterm or with extremely low birthweight and 49 term-born controls born in Norway in the periods 1982–1985, 1991–1992, and 1999–2000 at mean age 28 (±6) years. The endothelial function was assessed by ultrasound measured flow-mediated dilatation (FMD) of the right brachial artery. The arterial diameter was measured at baseline, after release of 5 min of occlusion, and after sublingual administration of nitroglycerine. FMD was reported as absolute and percentage diameter change from baseline and relative to nitroglycerine-induced dilatation. Results: The participants were mainly normal weight non-smokers, without hypertension, diabetes, or established cardiovascular disease. The cases and controls had mean blood pressure 112/71 (SD 12/9) and 112/69 (SD 11/8) mmHg, body mass index 24.0 (SD 4.2) and 24.4 (SD 4.5) kg/m2, and HbA1c 32.7 (SD 2.5) and 33.0 (SD 2.6) mmol/mol, respectively. For both groups, 4 (8%) were smokers. Mean FMD for the adults born very preterm or with extremely low birthweight was 0.17 mm (95% CI 0.14, 0.21) vs. 0.24 mm (95% CI 0.20, 0.28) for the controls (p = 0.01), corresponding to a percentage increase of 5.4% (95% CI 4.2, 6.6) and 7.6% (95% CI 6.2, 8.9), respectively (p = 0.02). The FMD relative to maximal nitroglycerine-induced dilatation was 20% and 31%, respectively (p = 0.001). Conclusions: Young adults born very preterm or with extremely low birthweight have significantly lower FMD compared with the term-born controls suggesting an increased risk of cardiovascular disease.publishedVersio

Validation of a modified South African triage scale in a high-resource setting: a retrospective cohort study

Background: Triage systems are widely used in emergency departments, but are not always validated. The South African Triage Scale (SATS) has mainly been studied in resource-limited settings. The aim of this study was to determine the validity of a modified version of the SATS for the general population of patients admitted to an ED at a tertiary hospital in a high-income country. The secondary objective was to study the triage performance according to age and patient categories. Methods: We conducted a retrospective cohort study of patients presenting to the Emergency Department of Haukeland University Hospital in Norway during a four-year period. We used short-term mortality, ICU admission, and the need for immediate surgery and other interventions as the primary endpoints. Results: A total of 162,034 emergency department visits were included in the analysis. The negative predictive value of a low triage level to exclude severe illness was 99.1% (95% confidence interval: 99.0–99.2%). The level of overtriage, defined as the proportion of patients assigned to a high triage level who were not admitted to the hospital, was 4.1% (3.9–4.2%). Receiver operating characteristic (ROC) curves showed an area under the ROC for the detection of severe illness of 0.874 (95% confidence interval: 0.870–0.879) for all patients and 0.856 (0.837–0.875), 0.884 (0.878–0.890) and 0.869 (0.862–0.876) for children, adults and elderly individuals respectively. Conclusion: We found that the modified SATS had a good sensitivity to identify short-term mortality, ICU admission, and the need for rapid surgery and other interventions. The sensitivity was higher in adults than in children and higher in medical patients than in surgical patients. The over- and undertriage rates were acceptable.publishedVersio

Changes in pulmonary function and feasibility of portable continuous laryngoscopy during maximal uphill running

Objective To evaluate changes in pulmonary function and feasibility of portable continuous laryngoscopy during maximal uphill running. Methods Healthy volunteers participated in an uphill race. Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained before and 5 and 10 min after finishing the race. Capillary blood lactate concentration ([BLa-]) and Borg score for perceived exertion were registered immediately after the race. One participant wore a portable video-laryngoscope during the race, and the video was assessed for technical performance. Results Twenty adult subjects participated with a mean (SD) age of 40.2 (9.7) years. Mean (SD) race duration and post-exercise [BLa-] was 13.9 (2.3) min and 10.7 (2.1) mmol/L, respectively, and the median (range) Borg score for perceived exertion was 9 (5–10). Mean percentage change (95% CI) 5 and 10 min post-exercise in FEV1 were 6.9 (3.7 to 10.2) % and 5.9 (2.7 to 9.0) %, respectively, and in FVC 5.2 (2.3 to 8.1) % and 4.7 (1.6 to 7.9) %, respectively. The recorded video of the larynx was of good quality. Conclusions Maximal aerobic field exercise induced bronchodilatation in the majority of the healthy non-asthmatic participants. It is feasible to perform continuous video-laryngoscopy during heavy uphill exercise.publishedVersio

Predicting physical activity in a national cohort of children born extremely preterm

Predicting physical activity in a national cohort of children born extremely preterm. Objectives: To compare physical activity among school-aged children born extremely preterm or with extremely low birthweight (EP/ELBW) to term-born children, and to identify early predictors for physical inactivity in the EP/ELBW-children. Methods: A national cohort born during 1999–2000 at gestational age < 28 weeks or birthweight <1000 g and term-born controls were assessed. EP/ELBW-children without neurodevelopmental disabilities were labeled “healthy”. At five years, we examined the EP/ELBW-children's motor, mental and intellectual functioning using the Movement Assessment Battery for Children (MABC), The Strength and Difficulties Questionnaire (SDQ) and The Wechsler Preschool and Primary Scale of Intelligence-revised. At 11 years, the parents reported their children's physical activity (PA) in questionnaires. Results: Information was obtained from 231/372 EP/ELBW and 57/61 term-born children. At 11 years, EP/ELBW-children had fewer exercise events per week, were less engaged in team sports, had lower endurance, lower sports proficiency, and were less vigorous during PA than term-born children (p < 0.05). Low sports proficiency in the healthy EP/ELBW-children at 11 years was predicted (odds ratio; 95% confidence interval) by abnormal MABC-score (3.0; 1.0 to 8.7), and abnormal SDQ-score (4.0; 1.6 to 10.0) at 5 years. Lower endurance at PA was predicted by abnormal MABC-score (2.6; 1.0 to 6.6), abnormal SDQ-score (3.0; 1.4 to 6.5), and borderline intellectual functioning (4.2; 1.8 to 10.1). Conclusions: Eleven-year-old EP/ELBW-children were less physically active than term-born. In healthy EP/ELBW-children, impaired motor coordination, borderline intellectual functioning and behavioral problems at 5 years of age predicted unfavorable PA habits at 11 years.publishedVersio

Reliability of maximum oxygen uptake in cardiopulmonary exercise testing with continuous laryngoscopy

Aims: A cardiopulmonary exercise test (CPET) is the gold standard to evaluate symptom-limiting exercise intolerance, while continuous laryngoscopy performed during exercise (CLE) is required to diagnose exercise-induced laryngeal obstruction. Combining CPET with CLE would save time and resources; however, the CPET data may be distorted by the extra equipment. We therefore aimed to study whether CPET with CLE influences peak oxygen uptake (V′O2peak) and other gas exchange parameters when compared to a regular CPET. Methods: Forty healthy athletes without exercise-related breathing problems, 15–35 years of age, performed CPET to peak exercise with and without an added CLE set-up, in randomised order 2–4 days apart, applying an identical computerised treadmill protocol. Results: At peak exercise, the mean difference (95% confidence interval) between CPET with and without extra CLE set-up for V′O2peak, respiratory exchange ratio (RER), minute ventilation (V′E) and heart rate (HR) was 0.2 (−0.4 to 0.8) mL·kg−1·min−1, 0.01(−0.007 to 0.027) units, 2.6 (−1.3 to 6.5) L·min−1 and 1.4 (−0.8 to 3.5) beats·min−1, respectively. Agreement (95% limits of agreement) for V′O2peak, RER and V′E was 0.2 (±3.7) mL·kg−1·min−1, 0.01 (±0.10) units and 2.6 (±24.0) L·min−1, respectively. No systematic or proportional bias was found except for the completed distance, which was 49 m (95% CI 16 to 82 m) longer during CPET. Conclusion: Parameters of gas exchange, including V′O2peak and RER, obtained from a maximal CPET performed with the extra CLE set-up can be used interchangeably with data obtained from standard CPET, thus preventing unnecessary additional testing.publishedVersio

Reliability of translaryngeal airway resistance measurements during maximal exercise

Objective Exercise-induced laryngeal obstruction is an important cause of exertional dyspnoea. The diagnosis rests on visual judgement of relative changes of the laryngeal inlet during continuous laryngoscopy exercise (CLE) tests, but we lack objective measures that reflect functional consequences. We aimed to investigate repeatability and normal values of translaryngeal airway resistance measured at maximal intensity exercise. Methods 31 healthy nonsmokers without exercise-related breathing problems were recruited. Participants performed two CLE tests with verified positioning of two pressure sensors, one at the tip of the epiglottis (supraglottic) and one by the fifth tracheal ring (subglottic). Airway pressure and flow data were continuously collected breath-by-breath and used to calculate translaryngeal resistance at peak exercise. Laryngeal obstruction was assessed according to a standardised CLE score system. Results Data from 26 participants (16 females) with two successful tests and equal CLE scores on both test sessions were included in the translaryngeal resistance repeatability analyses. The coefficient of repeatability (CR) was 0.62 cmH2O·L−1·s−1, corresponding to a CR% of 21%. Mean±sd translaryngeal airway resistance (cmH2O·L−1·s−1) in participants with no laryngeal obstruction (n=15) was 2.88±0.50 in females and 2.18±0.50 in males. Higher CLE scores correlated with higher translaryngeal resistance in females (r=0.81, p<0.001). Conclusions This study establishes translaryngeal airway resistance obtained during exercise as a reliable parameter in respiratory medicine, opening the door for more informed treatment decisions and future research on the role of the larynx in health and disease.publishedVersio

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

Background: Left vocal cord paralysis (LVCP) is a known complication of patent ductus arteriosus (PDA) surgery in extremely preterm (EP) born neonates; however, consequences of LVCP beyond the first year of life are insufficiently described. Both voice problems and breathing difficulties during physical activity could be expected with an impaired laryngeal inlet. More knowledge may improve the follow-up of EP-born subjects who underwent PDA surgery and prevent confusion between LVCP and other diagnoses. Objectives: Examine the prevalence of LVCP in a nationwide cohort of adults born EP with a history of PDA surgery, and compare symptoms, lung function, and exercise capacity between groups with and without LVCP, and vs. controls born EP and at term. Methods: Adults born EP (<28 weeks' gestation or birth weight <1,000 g) in Norway during 1999–2000 who underwent neonatal PDA surgery and controls born EP and at term were invited to complete questionnaires mapping voice-and respiratory symptoms, and to perform spirometry and maximal treadmill exercise testing. In the PDA-surgery group, exercise tests were performed with a laryngoscope positioned to evaluate laryngeal function. Results: Thirty out of 48 (63%) eligible PDA-surgery subjects were examined at mean (standard deviation) age 19.4 (0.8) years, sixteen (53%) had LVCP. LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, not with lung function or peak oxygen consumption (VO2peak). In the PDA-surgery group, forced expiratory volume in 1 second z-score (z-FEV1) was reduced compared to EP-born controls (n = 30) and term-born controls (n = 36); mean (95% confidence interval) z-FEV1 was −1.8 (−2.3, −1.2), −0.7 (−1.1, −0.3) and −0.3 (−0.5, −0.0), respectively. For VO2peak, corresponding figures were 37.5 (34.9, 40.2), 38.1 (35.1, 41.1), and 43.6 (41.0, 46.5) ml/kg/min, respectively. Conclusions: LVCP was common in EP-born young adults who had undergone neonatal PDA surgery. Within the PDA-surgery group, LVCP was associated with self-reported voice symptoms and laryngeal obstruction during exercise, however we did not find an association with lung function or exercise capacity. Overall, the PDA-surgery group had reduced lung function compared to EP-born and term-born controls, whereas exercise capacity was similarly reduced for both the PDA-surgery and EP-born control groups when compared to term-born controls.publishedVersio

Physical activity and exercise capacity in survivors of preterm birth : A population-based cohort study of long-term consequences of prematurity

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

Validation of a Modified Triage Scale in a Norwegian Pediatric Emergency Department

Objective. Triage is a tool developed to identify patients who need immediate care and those who can safely wait. The aim of this study was to assess the validity and interrater reliability of a modified version of the pediatric South African triage scale (pSATS) in a single-center tertiary pediatric emergency department in Norway. Methods. This prospective, observational study included all patients with medical conditions, referred to the pediatric emergency department of a tertiary hospital in Norway from September 1, 2015, to November 17, 2015. Their assigned triage priority was compared with rate of hospitalization and resource utilization. Validity parameters were sensitivity, specificity, positive and negative predictive value, and percentage of over- and undertriage. Interrater agreement and accuracy of the triage ratings were calculated from triage performed by nurses on written case scenarios. Results. During the study period, 1171 patients arrived at the hospital for emergency assessment. A total of 790 patients (67 %) were triaged and included in the study. The percentage of hospital admission increased with increasing level of urgency, from 30 % of the patients triaged to priority green to 81 % of those triaged to priority red. The sensitivity was 74 %, the specificity was 48 %, the positive predictive value was 52 %, and the negative predictive value was 70 % for predicting hospitalization. The level of over- and undertriage was 52 % and 26 %, respectively. Resource utilization correlated with higher triage priority. The interrater agreement had an intraclass correlation coefficient of 0.99 by Cronbach’s alpha, and the accuracy was 92 %. Conclusions. The modified pSATS had a moderate sensitivity and specificity but showed good correlation with resource utilization. The nurses demonstrated excellent interrater agreement and accuracy when triaging written case scenarios