Respiratory
Leader of this group:
MD, PhD Maria Vollsæter
During the last 3 to 4 decades, major theoretical, medical and technological advances have been made in the treatment of prematurely born infants.
Immediate and long-term survival has increased considerably. Large cohorts of these tiny infants are growing up and are becoming new fellow citizens of our community, and their public health importance is increasing.
Being born extremely preterm in the second trimester of pregnancy implies that the continuous development and maturation of human organ systems that should have taken place inside a sheltered uterus, now has to take place in a neonatal intensive care unit (NICU).
The full consequences of this remain unknown, particularly for the smallest and most immature infants born at the limits of viability, since their high survival rates are recent history.
All organ systems are immature and vulnerable when born extremely preterm (EPB), and most of these infants require advanced intensive care treatment. Paradoxically, treatment measures required to save their lives in the short-term may also be potentially harmful in the long-term.
As borders of viability move downward, survival increases also for those born most immature. Improved outcomes for “all” preterm born children may thus be counteracted by worse outcomes for the potentially most vulnerable. Repeated studies over decades are needed to address these continuously evolving changes.
In Bergen, we have studied long-term respiratory outcomes in several consecutive population-based cohorts of extremely preterm born (EPB) subjects and matched term-born (TB) controls.
These premature studies form the rootstock in the respiratory group.
Through multiple studies we have illuminated diverse parts of the lungs and the respiratory system in these preterm children, adolecents and adults born prematurely, and compared this to those born at term.
We have looked into respiratory symptoms like cough, wheeze, use of asthma medications and hospital admissions.
We have also performed comprehensive test of lung function, to evaluate bronchial (airway) dimensions, obstruction (airflow hinder due to airway contraction or smaller lumen), hyperreactivity (how the airway reacts to certain stimuli with contraction), physical capacity (oxygen uptake) and the gas exchange in the alveoli (airway pits).
Communicating study results
The work in the respiratory group have led to several dissertations for doctorates or Ph.D’s. The studies have been published in highly ranged international peer-reviewed journals, amongst these, Lancet in 2019 and 2024.
What happens next?
The regional ethical committee for medical research approved new examinations of the regional groups born extremely preterm or at extremely low birthweight, alongside term born control subjects born in 1982-85, 1991-92 and 1999-2000. These examinations were completed in 2020, and we have several international publications of the results.
Currently, there are no ongoing clinical examinations, the plan is to do a new round of assessments of lung function and overall health in these populations 10 years later.
International cooperation
Most studies reporting data from long-term follow-ups after preterm birth, have rather few participants, and hence impaired statistical power. To solve this, international projects have been formed in order to collect data internationally in larger databases. Currently, our group is involved in to such projects, both relevant to the PEP project and the respiratory group:
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Individual patient data analysis of respiratory health and function in adulthood of very low birthweight or very preterm survivors. This projects is leaded by Prof Les Doyle, The Murdoch Children’s Research Institute, Melbourne, Australia, and in collaboration with a larger international group; Adults Born Preterm International Collaboration (APIC), for more information see http://www.apic-preterm.org/.
Specifically, our group will contribute data for lung function from several preterm groups.
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The EU-project “RECAP” from Horizon 2020 “Networking and optimizing the use of population and patient cohorts at EU level”.
Specifically, our group will contribute data from the national PEP 1999-2000 study.
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PELICAN – Prematurity’s Effects on the Lungs In Children and Adults Network. The PELICAN (Prematurity’s Effects on the Lungs in Children and Adults Network) Clinical Research Collaboration was launched by the European Respiratory Society (ERS) in 2020. Although enhanced perinatal care has markedly improved survival outcomes for all preterm infants, there is clear evidence of poorer lung health outcomes in this population. PELICAN has the overarching objective to harmonise cross-sectional and longitudinal datasets globally, to describe the impact of preterm birth on lung health trajectories over its life course, and to determine which neonatal and lifetime exposures contribute to the progression of lung disease in this vulnerable population.
Specifically, our group will contribute data for longitudinal lung function from several preterm groups.
PELICAN – Prematurity’s Effects on the Lungs In Children and Adults Network - ERS - European Respiratory Society (ersnet.org)
These projects are reliable, with strong leadership as well as transparency. Data will be shared in anonymous and de-identified formats, according to Norwegian law and in collaboration with relevant national and local institutions and the person safety representative at Haukeland University Hospital.
Doctorates or Ph.D dissertations emerging from the respiratory group:
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Maria Vollsæter. Long-term respiratory Outcomes of Extreme preterm Birth. A population-based cohort study. University of Bergen 2016.
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Hege Havstad Clemm. Exercise Capacity after extremely preterm birth. Development from childhood to adulthood. University of Bergen 2015.
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Ola Drange Røksund. Larynx in exercising humans. The unexplored bottleneck of the airways. University of Bergen 2012.
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Stein Magnus Aukland. 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. University of Bergen 2011.
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Thomas Halvorsen. Lung sequelae after premature birth: A population based, controlled, long-term cohort study. University of Bergen 2006.
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Emma Satrell: Alveolar function following extremely preterm birth. University of Bergen 2022.
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Mette Engan: Physical activity and exercise capacity in survivors of preterm birth: A population-based cohort study of long-term consequences of prematurity. University of Bergen 2022.
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Merete Salveson Engeset: Outcomes following PDA surgery in extremely preterm born subjects. Focusing on left vocal cord paralysis and associated short- and long-term outcomes. University of Bergen 2022.
Publications
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Halvorsen T, Skadberg BT, Eide GE, Roksund OD, Carlsen KH, Bakke P. Pulmonary outcome in adolescents of extreme preterm birth: a regional cohort study. Acta Paediatr. 2004;93(10):1294-300.
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Skromme, K., et al., Respiratory morbidity through the first decade of life in a national cohort of children born extremely preterm. BMC Pediatr, 2018. 18(1): p. 102.
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Engan, M., et al., Comparison of physical activity and body composition in a cohort of children born extremely preterm or with extremely low birth weight to matched term-born controls: a follow-up study. BMJ Paediatr Open, 2019. 3(1): p. e000481.
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Doyle, L.W., et al., Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight: a meta-analysis of individual participant data. Lancet Respir Med, 2019.
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Clemm HH, Engeseth M, Vollsaeter M, Kotecha S, Halvorsen T. Bronchial hyper-responsiveness after preterm birth. Paediatr Respir Rev. 2017.
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Bentsen MH, Satrell E, Reigstad H, Johnsen SL, Vollsaeter M, Roksund OD, et al. Mid-childhood outcomes after pre-viable preterm premature rupture of membranes. J Perinatol. 2017.
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Roksund OD, Heimdal JH, Clemm H, Vollsaeter M, Halvorsen T. Exercise inducible laryngeal obstruction: diagnostics and management. Paediatr Respir Rev. 2016.
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Bjorke-Monsen AL, Vollsaeter M, Ueland PM, Markestad T, Oymar K, Halvorsen T. Increased Bronchial Hyperresponsiveness and Higher ADMA Levels After Fetal Growth Restriction. American journal of respiratory cell and molecular biology. 2016.
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Andersen T, Sandnes A, Brekka AK, Hilland M, Clemm H, Fondenes O, et al. Laryngeal response patterns influence the efficacy of mechanical assisted cough in amyotrophic lateral sclerosis. Thorax. 2016.
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Halvorsen T CH, Vollsæter M. Langtidskonsekvenser av prematur fødsel. Lungehelse og fysisk arbeidskapasitet. Allergi i praksis. 2015;1:10-8.
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Clemm HH, Vollsaeter M, Roksund OD, Markestad T, Halvorsen T. Adolescents who were born extremely preterm demonstrate modest decreases in exercise capacity. Acta Paediatr. 2015;104(11):1174-81.
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Vollsaeter M, Skromme K, Satrell E, Clemm H, Roksund O, Oymar K, et al. Children Born Preterm at the Turn of the Millennium Had Better Lung Function Than Children Born Similarly Preterm in the Early 1990s. PloS one. 2015;10(12):e0144243.
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Skromme K, Leversen KT, Eide GE, Markestad T, Halvorsen T. Respiratory illness contributed significantly to morbidity in children born extremely premature or with extremely low birth weights in 1999-2000. Acta Paediatr. 2015.
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Vollsaeter M, Clemm HH, Satrell E, Eide GE, Roksund OD, Markestad T, et al. Adult respiratory outcomes of extreme preterm birth. A regional cohort study. Annals of the American Thoracic Society. 2015;12(3):313-22.
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Clemm HH, Vollsaeter M, Roksund OD, Eide GE, Markestad T, Halvorsen T. Exercise Capacity after Extremely Preterm Birth: Development from Adolescence to Adulthood. Annals of the American Thoracic Society. 2014.
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Bjørke-Monsen ALH, Thomas; Midttun, Øivind; Ueland, Per Magne. Increased inflammatory markers in adolescents born extremely preterm and small for gestational age. Journal of Pediatric Biochemistry 2013;Volum 3.((4)):239-46.
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Vollsaeter M, Roksund OD, Eide GE, Markestad T, Halvorsen T. Lung function after preterm birth: development from mid-childhood to adulthood. Thorax. 2013.
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Clemm H, Roksund O, Thorsen E, Eide GE, Markestad T, Halvorsen T. Aerobic capacity and exercise performance in young people born extremely preterm. Pediatrics. 2012;129(1):e97-e105.
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Satrell E, Roksund O, Thorsen E, Halvorsen T. Pulmonary gas transfer in children and adolescents born extremely preterm. Eur Respir J. 2012.
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Roksund OD, Clemm H, Heimdal JH, Aukland SM, Sandvik L, Markestad T, et al. Left vocal cord paralysis after extreme preterm birth, a new clinical scenario in adults. Pediatrics. 2010;126(6):e1569-77.
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Aukland SM, Rosendahl K, Owens CM, Fosse KR, Eide GE, Halvorsen T. Neonatal bronchopulmonary dysplasia predicts abnormal pulmonary HRCT scans in long-term survivors of extreme preterm birth. Thorax. 2009;64(5):405-10.
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Halvorsen T. Lung sequelae after premature birth : A population based, controlled, long-term cohort study [Doctoral thesis]. The University of Bergen, Bergen, Norway: University of Bergen; 2006.
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Aukland SM, Halvorsen T, Fosse KR, Daltveit AK, Rosendahl K. High-resolution CT of the chest in children and young adults who were born prematurely: findings in a population-based study. AJR Am J Roentgenol. 2006;187(4):1012-8.
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Halvorsen T, Skadberg BT, Eide GE, Roksund OD, Markestad T. Better care of immature infants; has it influenced long-term pulmonary outcome? Acta Paediatr. 2006;95(5):547-54.
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Halvorsen T, Skadberg BT, Eide GE, Roksund OD, Bakke P, Thorsen E. Assessment of lung volumes in children and adolescents: comparison of two plethysmographic techniques. Clin Physiol Funct Imaging. 2005;25(1):62-8.
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Halvorsen T, Skadberg BT, Eide GE, Roksund O, Aksnes L, Oymar K. Characteristics of asthma and airway hyper-responsiveness after premature birth. Pediatr Allergy Immunol. 2005;16(6):487-94.
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Expiratory airflow limitation in adults born extremely preterm: A systematic review and meta-analysis
Lillebøe HL, Engeset MS, Clemm HH, Halvorsen T, Røksund OD, Potrebny T, Vollsæter M.
Paediatr Respir Rev. 2024 Feb 16:S1526-0542(24)00019-8. doi: 10.1016/j.prrv.2024.02.002. Online ahead of print.
PMID: 38490917 Review.
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Unravelling the respiratory health path across the lifespan for survivors of preterm birth.
Simpson SJ, Du Berry C, Evans DJ, Gibbons JTD, Vollsæter M, Halvorsen T, Gruber K, Lombardi E, Stanojevic S, Hurst JR, Um-Bergström P, Hallberg J, Doyle LW, Kotecha S; PELICAN.
Lancet Respir Med. 2024 Feb;12(2):167-180. doi: 10.1016/S2213-2600(23)00272-2. Epub 2023 Nov 14.
PMID: 37972623 Review.
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Mechanically assisted cough strategies: user perspectives and cough flows in children with neurodisability.
Hov B, Andersen T, Toussaint M, Mikalsen IB, Vollsæter M, Brunborg C, Hovde M, Hovland V.
ERJ Open Res. 2024 Jan 8;10(1):00274-2023. doi: 10.1183/23120541.00274-2023. eCollection 2024 Jan.
PMID: 38196892 Free PMC article.
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Impaired Lung Function in Extremely Preterm-Born Adults in Their Fourth Decade of Life.
Bårdsen T, Røksund OD, Eagan TML, Hufthammer KO, Benestad MR, Clemm HSH, Halvorsen T, Vollsæter M.
Am J Respir Crit Care Med. 2023 Aug 15;208(4):493-495. doi: 10.1164/rccm.202303-0448LE.
PMID: 37187173 Free PMC article. No abstract available.
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Tracking of lung function from 10 to 35 years after being born extremely preterm or with extremely low birth weight.
Bårdsen T, Røksund OD, Benestad MR, Hufthammer KO, Clemm HH, Mikalsen IB, Øymar K, Markestad T, Halvorsen T, Vollsæter M.
Thorax. 2022 Aug;77(8):790-798. doi: 10.1136/thoraxjnl-2021-218400. Epub 2022 Apr 11.
PMID: 35410959 Free PMC article.
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Prevalence of long-term mechanical insufflation-exsufflation in children with neurological conditions: a population-based study.
Hov B, Andersen T, Toussaint M, Vollsaeter M, Mikalsen IB, Indrekvam S, Hovland V.
Dev Med Child Neurol. 2021 May;63(5):537-544. doi: 10.1111/dmcn.14797. Epub 2021 Jan 3.
PMID: 33393110 Free PMC article.
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Early life growth and associations with lung function and bronchial hyperresponsiveness at 11-years of age.
Mikalsen IB, Halvorsen T, Juliusson PB, Magnus M, Nystad W, Stensrud T, Størdal K, Vollsæter M, Øymar K.
Respir Med. 2021 Feb;177:106305. doi: 10.1016/j.rmed.2021.106305. Epub 2021 Jan 8.
PMID: 33482491
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Voice and Exercise Related Respiratory Symptoms in Extremely Preterm Born Children After Neonatal Patent Ductus Arteriosus.
Engeseth MS, Engan M, Clemm H, Vollsæter M, Nilsen RM, Markestad T, Halvorsen T, Røksund OD.
Front Pediatr. 2020 Apr 8;8:150. doi: 10.3389/fped.2020.00150. eCollection 2020.
PMID: 32322565 Free PMC article.