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Follow-up shows no adverse outcomes of CNEP in neonates

BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.332.7544.745 (Published 30 March 2006) Cite this as: BMJ 2006;332:745
  1. Susan Mayor
  1. London

    Long term follow-up of a controversial trial of continuous negative extrathoracic pressure (CNEP) in newborn babies has shown no adverse outcomes, results published in the Lancet this week show (2006;367: 1080-5). The trial had resulted in an inquiry and prolonged suspension of the lead investigators.

    The original study, carried out in the early 1990s, randomised newborn infants with respiratory distress syndrome to continuous negative extrathoracic pressure (pressure applied to the child's chest to help breathing) or standard treatment with supplemental oxygen or positive pressure ventilation, delivering pressurised air to the lungs. At the time, there was concern that positive pressure ventilation via an intratracheal tube might contribute to the high prevalence of chronic lung disease occurring in these children.

    Initial results showed that babies given CNEP improved in overall composite illness score, which was the primary outcome of the study. They needed to be given oxygen for fewer days and developed less chronic lung disease than babies given conventional oxygen treatment. Mortality and the prevalence of abnormal brain scans increased non-significantly, however (Pediatrics 1996;98: 1154-60).

    When the results were published, some of the parents whose children had taken part in the study raised concerns, leading to severe criticism of the study by the media and a series of inquiries into the trial. Members of the research team, including David Southall, who was a consultant paediatrician at the North Staffordshire Hospital Centre, Stoke-on-Trent, were suspended after allegations about consent procedures—which were found to be without foundation in 2001 (BMJ 2001;323: 885).

    In an inquiry commissioned by the Department of Health and published in 2000, Rod Griffiths, who was regional director of public health at the University of Birmingham at the time, called for a review of research governance and long term follow-up of the neonates included in the study (BMJ 2000;320: 1291).

    Results from the recommended long term follow-up, which assessed 133 of the 205 survivors from the original trial assessed at 9-15 years of age, have shown no evidence of poorer outcome after neonatal CNEP. The primary outcome of death or severe disability was equally distributed between the two treatment options (odds ratio for the CNEP group 1.0; 95% confidence interval 0.4 to 2.4). Full IQ did not differ between the two groups, but mean performance IQ was 6.8 (1.5 to 12.1) points higher in the CNEP group than in the conventionally treated group. Results of neuropsychological testing were similar, with scores on language production and visuospatial skills significantly higher in the CNEP group (Lancet 2006;367: 1080-5).

    In a commentary in the Lancet, David Southall and Martin Samuels, two of the researchers from the original trial—who both still work at North Staffordshire Hospital Centre, Stoke-on-Trent—welcomed the absence of harm in the long term neurodevelopment of the preterm infants treated with CNEP.

    Also commenting on the long term follow-up results, Professor Griffiths, now the president of the Faculty of Public Health, said, “We now know that despite what seemed to be an increase in issues related to brain damage when the original trial reported, the longer term study shows that CNEP might, if anything, be kinder on the brain. The paediatric community now has to decide whether CNEP has a place in the care of these babies.” (See Personal View on bmj.com.)

    Footnotes

    • Embedded ImageLonger versions of these articles are on bmj.com

      Report of a Review of the Research Framework in North Staffordshire Hospital NHS Trust is available at www.dh.gov.uk.

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