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Aim: Investigate potential long-term cohort influences on health-related quality of life (HRQoL) in adults born extremely preterm (EP) during the 1980-90s, in view of advancements in neonatal care within that timeframe., Methods: Two cohorts of EP-born adults (82-85 cohort and 91-92 cohort) enrolling matched term controls, were compared. Participants were assessed at 18 years and again in their mid-twenties using the Child Health Questionnaire Children Form-87 (CHQ-CF87) and the Short Form Health Survey (SF-36)., Results: At 18 years, 77 (90%) EP-born and 75 (93%) term controls had data, followed by 67 (78%) EP-born and 66 (82%) term controls in their mid-twenties. At 18 years, there were no differences across the birth decades, and EP-born and term-born reported relatively similar HRQoL scores. In the mid-twenties, birth decade did also not significantly impact HRQoL scores, although the EP-born 82-85 cohort scored numerically poorer than the 91-92 cohort in three domains. Term controls scored similarly across birth decade in all domains. Regarding influence from neonatal factors, postnatal corticosteroids had a negative impact in some domains., Conclusion: No significant differences in HRQoL were observed between EP-born adults from the 82-85 cohort versus the 91-92 cohort, although the EP-born 82-85 cohort tended to score poorer in their mid-twenties., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Extreme preterm (EP) birth, denoting delivery before the onset of the third trimester, interrupts intrauterine development and causes significant early-life pulmonary trauma, thereby posing a lifelong risk to respiratory health. We conducted a systematic review and meta-analysis to investigate adult lung function following EP birth (gestational age <28 weeks); comparing forced expiratory volume in first second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC to reference values. Subgroup differences were explored based on timing of birth relative to surfactant use (1991) and bronchopulmonary dysplasia (BPD) status. Systematic searches were performed in Medline, EMBASE, Web of Science and Cochrane Central. Quality assessments were carried out using a modified Newcastle-Ottawa Scale for cohort studies. Sixteen studies encompassing 1036 EP-born adults were included, with 14 studies (n = 787) reporting data as %predicted, and 11 (n = 879) as z-score (not mutually exclusive). Overall mean [95 % confidence interval (CI)] %FEV 1 was 85.30 (82.51; 88.09), %FVC was 94.33 (91.74; 96.91), and FEV 1 /FVC was 79.54 (77.71 to 81.38), all three with high heterogeneity. Overall mean (95 %CI) zFEV 1 was -1.05 (-1.21; -0.90) and zFVC was. -0.45 (-0.59; -0.31), both with moderate heterogeneity. Subgroup analyses revealed no difference in FEV 1 before versus after widespread use of surfactant, but more impairments after neonatal BPD. This meta-analysis revealed significant airflow limitation in EP-born adults, mostly explained by those with neonatal BPD. FEV 1 was more reduced than FVC, and FEV 1 /FVC was at the lower limit of normal. Although at a group level, most adult EP-born individuals do not meet COPD criteria, these findings are concerning., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To study development trajectories to 34 years of age of health-related quality of life (HRQoL) and subjective health complaints in extremely preterm (EP) born subjects with and without disability, and to compare with term-born controls., Methods: A Norwegian longitudinal population-based cohort of subjects born in 1982-85 at gestational age ≤ 28 weeks or with birth weight ≤ 1000 g and matched term-born controls completed the Norwegian version of the Short Form Health Survey-36 at ages 24 and 34 and the Health Behaviour in School-aged Children-Symptom Checklist at ages 17, 24 and 34 years. Data were analysed by unadjusted and adjusted mixed effects analyses with time by subject group as interaction term., Results: A total of 35/49 (73%) surviving EP-born and 36/46 (78%) term-born controls participated at this third follow-up. EP-born subjects with severe disability reported clinical significant lower mean score in all domains compared to the term-born controls. Healthy EP-born subjects reported significantly lower mean scores for vitality, role emotional and mental health, and significantly higher mean score for total and psychological health complaints compared to term-born controls. There were no significant interactions with age regarding HRQoL and somatic health complaints, while there were significant differences in psychological health complaints; the EP-born scored higher at age 24 and lower at age 34., Conclusions: EP-born adults at age 34 reported inferior HRQoL versus term-born peers, especially in the mental health domains, indicating that the negative differences observed at 24 years remained unchanged., (© 2022. The Author(s).)

Background: Gas exchange in extremely preterm (EP) infants must take place in fetal lungs. Childhood lung diffusing capacity of the lung for carbon monoxide ( D LCO ) is reduced; however, longitudinal development has not been investigated. We describe the growth of D LCO and its subcomponents to adulthood in EP compared with term-born subjects., Methods: Two area-based cohorts born at gestational age ≤28 weeks or birthweight ≤1000 g in 1982-1985 (n=48) and 1991-1992 (n=35) were examined twice, at ages 18 and 25 years and 10 and 18 years, respectively, and compared with matched term-born controls. Single-breath D LCO was measured at two oxygen pressures, with subcomponents (membrane diffusion ( D M ) and pulmonary capillary blood volume ( V C )) calculated using the Roughton-Forster equation., Results: Age-, sex- and height-standardised transfer coefficients for carbon monoxide ( K CO ) and D LCO were reduced in EP compared with term-born subjects, and remained so during puberty and early adulthood (p-values for all time-points and both cohorts ≤0.04), whereas alveolar volume ( V A ) was similar. Development occurred in parallel to term-born controls, with no signs of pubertal catch-up growth nor decline at age 25 years (p-values for lack of parallelism within cohorts 0.99, 0.65, 0.71, 0.94 and 0.44 for z- D LCO , z- V A , z- K CO , D M and V C , respectively). Split by membrane and blood volume components, findings were less clear; however, membrane diffusion seemed most affected., Conclusions: Pulmonary diffusing capacity was reduced in EP compared with term-born subjects, and development from childhood to adulthood tracked in parallel to term-born subjects, with no signs of catch-up growth nor decline at age 25 years., Competing Interests: Conflict of interest: E. Satrell has nothing to disclose. Conflict of interest: H. Clemm has nothing to disclose. Conflict of interest: O.D. Røksund has nothing to disclose. Conflict of interest: K.O. Hufthammer has nothing to disclose. Conflict of interest: E. Thorsen has nothing to disclose. Conflict of interest: T. Halvorsen has nothing to disclose. Conflict of interest: M. Vollsæter has nothing to disclose., (Copyright ©The authors 2022.)

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., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at <32 weeks' gestation) or with very low birthweight (<1501 g) is unknown. We aimed to compare maximal expiratory airflow in these individuals during late adolescence and early adulthood with that of control individuals born with normal birthweight (>2499 g) or at term., Methods: We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV 1 , forced vital capacity [FVC], FEV 1 /FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF 25-75% ]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach., Findings: Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3·4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV 1 (-0·06 [SD 1·03] vs -0·81 [1·33], mean difference -0·78 [95% CI -0·96 to -0·61], p<0·0001), FVC (-0·15 [0·98] vs -0·38 [1·18], -0·25 [-0·40 to -0·10], p=0·0012), FEV 1 /FVC ratio (0·14 [1·10] vs -0·64 [1·35], -0·74 [-0·85 to -0·64], p<0·0001), and FEF 25-75% (-0·04 [1·10] vs -0·95 [1·47], -0·88 [-1·12 to -0·65], p<0·0001). Similar patterns were observed when we compared the proportions of individuals with values below the fifth percentile., Interpretation: Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood., Funding: National Health and Medical Research Council (Australia), University of Bergen, Western Norway Regional Authority, National Institute for Health Research (UK), Stichting Astmabestrijding, St Olav's Hospital's Research Fund, Academy of Finland, European Commission, National Institute of Child Health and Human Development (USA), Victorian Government's Operational Infrastructure Support Program., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Preterm birth and low birth weight are associated with reduced nephron numbers and increased risk of hypertension and kidney disease in later life., Aims: We tested the hypothesis that extremely preterm birth and intrauterine growth restriction is associated with decreased renal function in mid childhood., Methods: At 11 years of age the following measures were obtained in a regional cohort of children born extremely premature (EP, i.e. < 28 weeks gestational age-GA) or with extremely low birth weight (ELBW, i.e. BW < 1000 grams) and in matched controls born at term with appropriate BW (AGA): Height, weight, abdominal circumference, triceps and subscapular skin fold thicknesses, blood pressure, plasma levels of creatinine, cystatin C and symmetric dimethyl arginine (SDMA). Small for gestational age (SGA) was defined as a BW < 10th percentile for GA. Glomerular filtration rate (GFR) was estimated according to the equations by Schwartz, Zappitelli and Gao., Results: Fifty-seven of 61 eligible EP/ELBW children, 20 (35%) born SGA, and 54 controls, were assessed. Estimated GFR decreased while plasma SDMA increased from the children born AGA at term through those born preterm AGA to preterm SGA. Systolic BP was correlated to fat mass indices (p<0.03), but not to renal function (p>0.2) and did not differ between the groups., Conclusions: Children born EP/ELBW, particularly those born SGA, had impaired renal function at age 11 years as judged from estimated GFRs and plasma levels of SDMA. Since reduced renal function is associated with an increased risk of later disease, these children should be followed in order to minimize additional risk factors., Competing Interests: Bevital A/S provided financial support in the form of salaries for KM and ØM, and research materials. This does not alter our adherence to the PLOS ONE policies on sharing data and materials.

Background: Advances in perinatal care have markedly increased the prospects of survival for infants born extremely preterm (EP). The aim of this study was to investigate hospitalisation rates and respiratory morbidity from five to 11 years of age in a prospective national cohort of EP children born in the surfactant era., Methods: This was a national prospective cohort study of all children born in Norway during 1999 and 2000 with gestational age (GA) < 28 weeks or birth weight < 1000 grams, and of individually matched term-born controls recruited for a regional subsample. Data on hospital admissions, respiratory symptoms, and use of asthma medication was obtained by parental questionnaires at 11 years of age., Results: Questionnaires were returned for 232/372 (62%) EP-born and 57/61 (93%) regional term-born controls. Throughout the study period, 67 (29%) EP-born and seven (13%) term-born controls were admitted to hospital (odds ratio (OR) 2.90, 95% confidence interval (CI): 1.25, 6.72). Admissions were mainly due to surgical procedures, with only 12% due to respiratory causes, and were not influenced by neonatal bronchopulmonary dysplasia (BPD) or low GA(≤ 25 weeks). Respiratory symptoms, asthma and use of asthma medication tended to be more common for EP-born, significantly so for medication use and wheeze on exercise. Neonatal BPD was a risk factor for medication use, but not for current wheeze. In multivariate regression models, home oxygen after discharge (OR 4.84, 95% CI: 1.38, 17.06) and parental asthma (OR 4.38, 95% CI: 1.69, 11.38) predicted current asthma, but neither BPD nor low GA were associated with respiratory symptoms at 11 years of age., Conclusions: Hospitalisation rates five to 11 years after EP birth were low, but twice those of term-born controls, and unrelated to neonatal BPD and low GA. Respiratory causes were rare. Respiratory complaints were more common in children born EP, but the burden of symptoms had declined since early childhood.

Rationale: Lifetime respiratory function after extremely preterm birth (gestational age≤28 wk or birth weight≤1,000 g) is unknown., Objectives: To compare changes from 18-25 years of age in respiratory health, lung function, and airway responsiveness in young adults born extremely prematurely to that of term-born control subjects., Methods: Comprehensive lung function investigations and interviews were conducted in a population-based sample of 25-year-old subjects born extremely prematurely in western Norway in 1982-1985, and in matched term-born control subjects. Comparison was made to similar data collected at 18 years of age., Measurements and Main Results: At 25 years of age, 46/51 (90%) eligible subjects born extremely prematurely and 39/46 (85%) control subjects participated. z-Scores for FEV1, forced expiratory flow at 25-75% of vital capacity, and FEV1/FVC were significantly reduced in subjects born extremely prematurely by 1.02, 1.26, and 0.88, respectively, and airway resistance (kPa/L/s) was increased (0.23 versus 0.18). Residual volume to total lung capacity increased with severity of neonatal bronchopulmonary dysplasia. Responsiveness to methacholine (dose-response slope; 3.16 versus 0.85) and bronchial lability index (7.5 versus 4.8%) were increased in subjects born extremely prematurely. Lung function changes from 18 to 25 years and respiratory symptoms were similar in the prematurely born and term-born groups., Conclusions: Lung function in early adult life was in the normal range in the majority of subjects born extremely prematurely, but methacholine responsiveness was more pronounced than in term-born young adults, suggesting a need for ongoing pulmonary monitoring in this population.

Rationale: Extremely preterm (EP) birth is associated with a series of adverse health outcomes, some of which may be alleviated by improved physical fitness. However, EP-born subjects are reportedly less physically active than term-born peers. Exercise capacity is poorly described in this group, and longitudinal data are needed., Objectives: To compare exercise capacity of adults born EP and at term, and to address developmental patterns from adolescence to adulthood., Methods: An area-based cohort of adults, born in 1982-1985 at gestational age 28 weeks or earlier, or with birth weight of 1,000 g or less, originally examined at 18 years of age, were re-examined at 25 years of age together with individually matched term-born control subjects, using an identical maximal cardiopulmonary treadmill exercise test and validated questionnaires., Measurements and Main Results: A total of 34 (76%) eligible preterm and 33 (85%) term control subjects successfully completed the exercise test at age 25 years. In the two groups, average (95% confidence interval) peak oxygen consumption was 40.7 (37.9-43.5) and 44.2 (41.0-47.4) ml ⋅ kg(-1)⋅min(-1), respectively, whereas the distance completed on the treadmill was 910 (827-993) m and 1,020 (927-1,113) m. Peak oxygen consumption was unrelated to neonatal factors and current FEV1, but was positively associated with leisure-time physical activity and negatively associated with age at examination. Values obtained at age 18 and 25 years were strongly correlated and within normal range at both examinations., Conclusions: Exercise capacity was modestly reduced in EP-born adults; however, values were within a normal range, positively associated with self-reported physical activity and unrelated to neonatal factors and current airway obstruction.