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Anne Greenough 1,*, Janet Peacock 2, Sanja Zivanovic 1, Mireia Alcazar-Paris 1, Jessica Lo 2, Neil Marlow 3, Sandy Calvert 4

1 Division of Asthma, Allergy and Lung Biology, Medical Research Council (MRC) Centre for Allergic Mechanisms in Asthma, King’s College London, London, UK
2 Division of Health and Social Care Research, King’s College London, London, UK
3 Institute for Women’s Health, University College London, London, UK
4 Department of Child Health, St George’s Hospital, University of London, London, UK
* Corresponding author Email: anne.greenough@kcl.ac.uk

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Abstract

BACKGROUND

One in 200 infants in the UK is born extremely prematurely, i.e. before 29 weeks of gestation. Seventy-five per cent of such infants survive, but many have long-term respiratory and/or functional problems.

OBJECTIVES

To compare respiratory and functional outcomes of school-age children born extremely prematurely who received either high-frequency oscillation (HFO) or conventional ventilation (CV) immediately after birth to test the hypothesis that the use of HFO would be associated with superior small airway function at school age without adverse effects.

DESIGN

Follow-up of a randomised trial, the United Kingdom Oscillation Study, in which infants were randomised to receive HFO or CV within 1 hour of birth.

SETTING

King's College Hospital NHS Foundation Trust, London, UK.

PARTICIPANTS

Three hundred and nineteen children aged between 11 and 14 years were recruited (160 had received HFO); the planned sample size was 320.

INTERVENTIONS

HFO versus CV.

MAIN OUTCOME MEASURES

The results of comprehensive lung function assessments (primary outcome small airway function), echocardiographic examinations and respiratory, health-related quality of life and functional assessment questionnaires.

RESULTS

Significant baseline differences in maternal and neonatal characteristics between the two groups favoured the CV group, who had a higher mean birthweight (56â g) and were born later (0.3 weeks), and a greater proportion of whom had received surfactant. There were no significant differences between the two groups in their characteristics when assessed at 11-14 years of age. The children who had received HFO had significantly superior small airway function; their forced expiratory flow at 75% vital capacity z-score was 0.23 higher than that of the CV group [95% confidence interval (CI) 0.02 to 0.45]. Thirty-seven per cent of the HFO group and 46% of the CV group had small airway function results that were below the tenth centile. There were significant differences between ventilation groups in favour of HFO for other lung function results as expressed by z-scores {forced expiratory volume at 1 minute (FEV1) [difference 0.35 (95% CI 0.09 to 0.60)], the ratio of FEV1 to forced vital capacity [0.58 (95% CI 0.16 to 0.99)], diffusing capacity of the lung for carbon monoxide [0.31 (95% CI 0.04 to 0.58)], maximum vital capacity [0.31 (95% CI 0.05 to 0.57)]} and expressed as % predicted {peak expiratory flow rate [5.85 (95% CI 2.21 to 9.49)] and respiratory resistance at 5â Hz [-7.13 Hz (95% CI -2.50 to -1.76 Hz)]}. There were no significant differences between ventilation groups with regard to the echocardiographic results, respiratory morbidity in the last 12 months, health problems, Health Utilities Index scores or Strengths and Difficulties Questionnaire (SDQ) scores. When SDQ scores were dichotomised, there was a significant finding for one subscale: a greater proportion of HFO children reported emotional symptoms. This finding was not replicated by parents' or teachers' reports. Two hundred and twenty-four teachers completed questionnaires regarding the children's educational attainment and provision. There were statistically significant differences in attainment in three subjects in favour of HFO: art and design, information technology, and design and technology. The HFO children had lower risk of receiving special education needs support [odds ratio 0.56 (95% CI 0.32 to 1.00)], but the difference was not significant.

CONCLUSIONS

Follow-up at 11-14 years of age of extremely prematurely born infants entered into a randomised trial of HFO versus CV has demonstrated significant differences in lung function in favour of HFO. There was no evidence that this was offset by poorer functional outcomes; indeed, HFO children did better in some school subjects. It will be important to determine whether or not these differences are maintained after puberty as this is the last positive effect on lung function.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN98436149.

Abstract

BACKGROUND

One in 200 infants in the UK is born extremely prematurely, i.e. before 29 weeks of gestation. Seventy-five per cent of such infants survive, but many have long-term respiratory and/or functional problems.

OBJECTIVES

To compare respiratory and functional outcomes of school-age children born extremely prematurely who received either high-frequency oscillation (HFO) or conventional ventilation (CV) immediately after birth to test the hypothesis that the use of HFO would be associated with superior small airway function at school age without adverse effects.

DESIGN

Follow-up of a randomised trial, the United Kingdom Oscillation Study, in which infants were randomised to receive HFO or CV within 1 hour of birth.

SETTING

King's College Hospital NHS Foundation Trust, London, UK.

PARTICIPANTS

Three hundred and nineteen children aged between 11 and 14 years were recruited (160 had received HFO); the planned sample size was 320.

INTERVENTIONS

HFO versus CV.

MAIN OUTCOME MEASURES

The results of comprehensive lung function assessments (primary outcome small airway function), echocardiographic examinations and respiratory, health-related quality of life and functional assessment questionnaires.

RESULTS

Significant baseline differences in maternal and neonatal characteristics between the two groups favoured the CV group, who had a higher mean birthweight (56â g) and were born later (0.3 weeks), and a greater proportion of whom had received surfactant. There were no significant differences between the two groups in their characteristics when assessed at 11-14 years of age. The children who had received HFO had significantly superior small airway function; their forced expiratory flow at 75% vital capacity z-score was 0.23 higher than that of the CV group [95% confidence interval (CI) 0.02 to 0.45]. Thirty-seven per cent of the HFO group and 46% of the CV group had small airway function results that were below the tenth centile. There were significant differences between ventilation groups in favour of HFO for other lung function results as expressed by z-scores {forced expiratory volume at 1 minute (FEV1) [difference 0.35 (95% CI 0.09 to 0.60)], the ratio of FEV1 to forced vital capacity [0.58 (95% CI 0.16 to 0.99)], diffusing capacity of the lung for carbon monoxide [0.31 (95% CI 0.04 to 0.58)], maximum vital capacity [0.31 (95% CI 0.05 to 0.57)]} and expressed as % predicted {peak expiratory flow rate [5.85 (95% CI 2.21 to 9.49)] and respiratory resistance at 5â Hz [-7.13 Hz (95% CI -2.50 to -1.76 Hz)]}. There were no significant differences between ventilation groups with regard to the echocardiographic results, respiratory morbidity in the last 12 months, health problems, Health Utilities Index scores or Strengths and Difficulties Questionnaire (SDQ) scores. When SDQ scores were dichotomised, there was a significant finding for one subscale: a greater proportion of HFO children reported emotional symptoms. This finding was not replicated by parents' or teachers' reports. Two hundred and twenty-four teachers completed questionnaires regarding the children's educational attainment and provision. There were statistically significant differences in attainment in three subjects in favour of HFO: art and design, information technology, and design and technology. The HFO children had lower risk of receiving special education needs support [odds ratio 0.56 (95% CI 0.32 to 1.00)], but the difference was not significant.

CONCLUSIONS

Follow-up at 11-14 years of age of extremely prematurely born infants entered into a randomised trial of HFO versus CV has demonstrated significant differences in lung function in favour of HFO. There was no evidence that this was offset by poorer functional outcomes; indeed, HFO children did better in some school subjects. It will be important to determine whether or not these differences are maintained after puberty as this is the last positive effect on lung function.

TRIAL REGISTRATION

Current Controlled Trials ISRCTN98436149.

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