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Association of prematurity, lung disease and body size with lung volume and ventilation inhomogeneity in unsedated neonates: a multicentre study
  1. G Hülskamp1,2,
  2. S Lum1,
  3. J Stocks1,
  4. A Wade3,
  5. A F Hoo1,
  6. K Costeloe4,
  7. J Hawdon5,
  8. K Deeptha6,
  9. J J Pillow6
  1. 1
    Portex Anaesthesia, Intensive Therapy and Respiratory Medicine Unit, UCL, Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, UK
  2. 2
    Department of Paediatrics, Westfälische Wilhelms-Universität, Münster, Germany
  3. 3
    Paediatric Epidemiology and Biostatistics Unit, UCL, Institute of Child Health, London, UK
  4. 4
    Academic Unit of Paediatrics, Barts and the London School of Medicine and Dentistry, Neonatal Unit, Homerton University Hospital, London, UK
  5. 5
    Neonatal Unit, University College London Hospital, London, UK
  6. 6
    School of Women’s and Infants’ Health, University of Western Australia, Perth, Australia
  1. Dr G Hülskamp, Department of Paediatrics, Universitätsklinikum, Westfälische Wilhelms-Universität and Department of Paediatrics, Clemenshospital Münster, Düesbergweg 124, D-48153 Münster, Germany; g.huelskamp{at}


Background: Previous studies have suggested that preterm birth with or without subsequent chronic lung disease is associated with reduced functional residual capacity (FRC) and increased ventilation inhomogeneity in the neonatal period. We aimed to establish whether such findings are associated with the degree of prematurity, neonatal respiratory illness and disproportionate somatic growth.

Methods: Multiple breath washout measurements using an ultrasonic flowmeter were obtained from 219 infants on 306 test occasions during the first few months of life, at three neonatal units in the UK and Australia. Tests were performed during unsedated sleep in clinically stable infants (assigned to four exclusive diagnostic categories: term controls, preterm controls, respiratory distress syndrome and chronic lung disease). The determinants of neonatal lung function were assessed using multivariable, multilevel modelling.

Results: After adjustment for age and body proportions, the factors gestation, intrauterine growth restriction and days of supplemental oxygen were all significantly associated with a reduced FRC. In contrast, increased ventilation inhomogeneity (elevated lung clearance index) was only significantly associated with duration of supplemental oxygen. After adjusting for continuous variables, diagnostic category made no further contribution to the models. Despite using identical techniques, unexpected inter-centre differences occurred, associated with the equipment used; these did not alter the negative association of preterm delivery and disease severity with lung function outcomes.

Conclusion: Reduction in FRC is independently associated with prematurity, intrauterine growth restriction and severity of neonatal lung disease. Determinants of lung function shortly after birth are highly complex in different disease groups.

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  • Funding: Supported by the Innovative Medizinische Forschung, University of Münster and the Gesellschaft für Pädiatrische Pneumologie, Germany (GH), a Neil Hamilton Fairley NHMRC Postdoctoral Fellowship and NHMRC Career Development Award (JP) and Portex Ltd (JS). Research at the Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust benefits from R&D funding received from the NHS Executive. Research at King Edward Memorial Hospital was supported by grants from the Women & Infants Research Foundation and the Raine Medical Research Foundation.

  • Competing interests: The authors (JS, SL, JP) received some research discount on equipment supplied by EcoMedics in association with undertaking studies contributing to the development of the EcoMedics infant multiple breath washout equipment and software.

  • Ethics approval: The study was approved by the local research ethics committees.

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