"Rapid breaths 'protect early babies'," BBC News reports.
One immediate concern when babies are born very premature is their breathing. As their lungs are so tiny, many premature babies require breathing support provided by a ventilator.
Current practice is to set the ventilation to provide oxygen at a rate of around 30 to 60 breaths per minute.
Researchers in the study wanted to see if babies provided with a more rapid method of ventilation, known as high-frequency oscillatory ventilation (HFOV), improved long-term lung development.
HFOV involves keeping the lungs inflated, and then changing the pressure of oxygen by a small enough amount to “breathe”. The frequency of the “breaths” is around 600 per minute. It is believed that this will reduce the chance of damage to very premature lungs from over inflation, which can cause permanent damage to the airways of the lungs.
Children who had been in a randomised controlled trial for the two types of ventilation were invited to have lung function tests and complete questionnaires about their health.
Lung function was significantly better in the HFOV group compared to the conventional ventilation group according to various lung function tests. However the difference was too small to affect the questionnaire responses about the health of the children or any respiratory disease, such as childhood asthma.
The long term effect of HFOV on lung function is better than conventional ventilation but concerns over the initial safety and side effects of the technique warrant further research.
Where did the story come from?
The study was carried out by researchers from King’s College London, Guy’s and St Thomas’ NHS Foundation Trust, University College London and the University of London. It was funded by the National Institute for Health Research and the South London Comprehensive Local Research Network.
The study was published in the peer-reviewed medical journal The New England Journal of Medicine.
BBC News reported the story accurately and provided some useful background information regarding premature births in the UK.
What kind of research was this?
This was an observational follow-up study of children who had been born prematurely who had previously taken part in a randomised controlled trial of two different types of ventilator support. It aimed to see if there were any long term differences in lung function.
Premature babies usually require ventilator support until their lungs mature. Conventional ventilation starts at giving around 60 breaths per minute which can be adjusted. This can cause damage to the delicate lungs, so a technique called high-frequency oscillatory ventilation (HFOV) was proposed.
HFOV provides a constant pressure to the lungs and then fluctuates the pressure by a very small amount, very quickly. This is enough to exchange oxygen and carbon dioxide while keeping the lungs inflated.
The frequency can be varied but was started at 10 cycles per second which is effectively “breathing” 600 times per minute. This prevents overinflation of the lungs.
However, previous research has shown inconsistent results for HFOV – one trial found it caused significant intraventricular haemorrhage (bleeding inside the brain) and periventricular leukomalacia (brain damage) but others did not.
This study aimed to determine whether there was any long term difference between HFOV and conventional ventilation, both in terms of benefits and risks.
What did the research involve?
The researchers followed-up children who had been born very prematurely who had taken part in a randomised controlled trial comparing HFOV with conventional ventilation.
The researchers invited 538 children when they were aged 11 to 14. These children were all born in the UK before 29 weeks gestation.
Parental consent was sought and the children had lung function assessments at King’s College Hospital in London. The researchers conducting the tests were not told which type of ventilation the child had received. Skin prick allergy tests were performed including pollen, cat and dog dander. A urine test for cotinine (a by-product of tobacco exposure) provided evidence of passive or active smoking.
The parents and children were also given questionnaires covering:
- respiratory disorders
- neurological illness
- hospital admissions
- medicine use
- family history of asthma
- health-related quality of life
- ability to function
- household smokers
Their teachers were also given a questionnaire about the children’s academic achievement and behaviour.
The primary outcome was small airway function which was assessed using the forced expiratory flow at 75% of the expired vital capacity (FEF75). This is essentially an assessment of how much air the lungs are capable of breathing out after most of the air has been exhaled. This provides a rough estimate of how efficiently the small airways of the lungs are functioning – those most likely to be damaged in premature neonates.
The researchers calculated z-scores, which are an indication of how different a value is from the mean (average). Z-scores also allow researchers to compare the FEF75 in children of different ages.
What were the basic results?
A total of 319 children participated in the study and 248 of them had the lung function tests.
There were 159 children who had been given conventional ventilation and they had a higher average weight and gestational age at birth than the 160 children who had HFOV. They were also more likely to have had the drug surfactant, which helps prevent the lungs from collapsing. There were no other differences between the two groups in terms of race, maternal smoking during pregnancy, current age, weight and height, active or passive smoking and diagnosis of asthma.
The mean FEF75 z-score was higher in the HFOV group than the conventional ventilation group (-0.97 versus -1.19).
A large proportion of both groups had results below the general population 10th percentile – 37% in the HFOV group and 47% in the conventional ventilation group. Other measures of lung function were also significantly better in the HFOV group including forced expiratory volume in one second (FEV1), forced vital capacity and peak expiratory flow.
There was no significant difference in symptoms, respiratory disorders or the need for medication between the two groups.
Teachers completed questionnaires for 225 children and those in the HFOV group were rated significantly higher in three of eight subjects: art and design, information technology, and design and technology.
How did the researchers interpret the results?
The researchers concluded that the “results suggest that the use of HFOV, as compared with conventional ventilation, immediately after birth in very prematurely born infants was associated with modest improvements in lung function and with no evidence of a poorer functional outcome when the children were 11 to 14 years of age”.
This study shows that children who had been given HFOV had improved lung function tests compared to those who had conventional ventilation. But this difference was not great enough to cause differences in respiratory health.
This was a well-designed observation follow-up study of children from a randomised controlled trial with a reasonable number of participants. This type of trial is able to show that for the premature babies who survived, HFOV improves long term lung function detectable by tests. No difference was found between the groups for respiratory illnesses or health status.
The results of the study are encouraging in that HFOV was effective and caused less lung damage, but it does not further the knowledge of the safety or side effects of HFOV for extremely young neonates.
Importantly, HFOV has been linked to increased risk of bleeding in the brain and brain damage. In the original study, a quarter of the premature babies in both groups did not survive long enough to be discharged from hospital.
This study shows that for the children who survived extreme prematurity of less than 29 weeks HFOV did not cause neurological problems. This study does not show that HFOV is safer than conventional ventilation in the extreme neonatal period.
The long term effect of HFOV on lung function is better than conventional ventilation but initial safety and side effects of the technique warrant further research.
There is no guaranteed way to prevent premature birth, though if you are pregnant, ways you can reduce your risk include quit smoking if you smoke, try to maintain or achieve a healthy weight and eat a healthy balanced diet.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
BBC News, 19 March 2014
Links to the science
The New England Journal of Medicine. Published online March 20 2014