Jump to comment:

• Re: Conclusions not justified by findings
  Jayesh M Bhatt
  Published on: 23 August 2017
• Conclusions not justified by findings
  Charlotte M Wright
  Published on: 19 January 2017

• Published on: 23 August 2017

  Re: Conclusions not justified by findings

  • Jayesh M Bhatt, Consultant Respiratory Paediatrician Nottingham Children's Hospital, National Paediatric Ataxia Telangiectasia Clinic, QMC, Derby Road, Nottingham NG7 2UH, UK

  Dear Editor,

  We thank Professor Wright for her comments, and we welcome the opportunity to provide some clarification and further analysis. 

  We reported Z-scores rather than percentiles, although some comments on approximate percentiles can be made.  Assuming that Z scores of -1.96 and -3 represent approximately the 2.5^th and 0.2^nd centiles respectively, 36/101 children were below the 2.5^th centile, and 17/101 were below the 0.2^nd centile for weight.  Additionally, our mixed effects model (accounting for multiple measurements) modelling the group trend over time estimated the mean weight Z score at 11 years to be -1.63 (approximately 5^th centile). 

  Despite the overall short stature of the group, 24/101 children had a BMI Z score of less than -1.96.  So, by this approach, their weight was low even after taking into account stature.  We agree that we cannot infer causality from this observational study, but we believe a proportion of the stunted growth is explained by low weight. We are exploring other measures of malnutrition, such as skin-fold thickness. 

  Whilst our patient numbers are small, they do give some weight to the argument that PEG feeding halts the progression of malnutrition.  We investigated the rate of decline of weight after PEG insertion.  In a mixed effects model with a random intercept for individual patients, the rate of wei...

  Show More

  Dear Editor,

  We thank Professor Wright for her comments, and we welcome the opportunity to provide some clarification and further analysis. 

  We reported Z-scores rather than percentiles, although some comments on approximate percentiles can be made.  Assuming that Z scores of -1.96 and -3 represent approximately the 2.5^th and 0.2^nd centiles respectively, 36/101 children were below the 2.5^th centile, and 17/101 were below the 0.2^nd centile for weight.  Additionally, our mixed effects model (accounting for multiple measurements) modelling the group trend over time estimated the mean weight Z score at 11 years to be -1.63 (approximately 5^th centile). 

  Despite the overall short stature of the group, 24/101 children had a BMI Z score of less than -1.96.  So, by this approach, their weight was low even after taking into account stature.  We agree that we cannot infer causality from this observational study, but we believe a proportion of the stunted growth is explained by low weight. We are exploring other measures of malnutrition, such as skin-fold thickness. 

  Whilst our patient numbers are small, they do give some weight to the argument that PEG feeding halts the progression of malnutrition.  We investigated the rate of decline of weight after PEG insertion.  In a mixed effects model with a random intercept for individual patients, the rate of weight Z score decline was 0.01 units per year, in contrast with 0.1 per year in the un-operated population, although low numbers prevent a meaningful statistical comparison.   Given the ultra-rare nature of the disease, a randomised trial is effectively impossible and probably anyway unethical.  

  The multifactorial aetiology of wasting is unique in A-T.  The disease compromises varying components of chronic inflammation, poor feeding ability, and increased calorie consumption due to dystonic and athetoid movements.  The prognosis in A-T is truly appalling, and therefore we aim for the best possible quality of life.  As well as showing that PEG feeding halts the progression of malnutrition (albeit in small numbers of children as compared to controls) and making feeding safer in the presence of possible aspiration, one consistent theme (not reported in our paper but consistently reported by parents in our clinic and previously published by other groups(1)) is significant caregiver satisfaction and reduction in very lengthy meals times. This has a very significant impact in improving the quality of life of carers and patients.

  It is well recognised in other chronic paediatric diseases, such as cystic fibrosis and chronic kidney disease that nutrition is a predictor of overall quality of life.  Currently, we have very little to offer patients with A-T in terms of intervention to prevent the development of malignancy or neurological progression, but we believe by extrapolating from other similar patient groups, we can reduce the risk of death from pulmonary failure.  Key to this is prevention of wasting. 

  All long term invasive medical technologies interfere with the human condition of childhood, and we wholeheartedly agree that a PEG is life-changing and should always be carefully considered on an individual basis.  However, given the poor weight gain in many A-T children, we believe it is important to discuss whether a PEG would be useful early, and consider placement prior to the respiratory deterioration of the child. 

  Yours sincerely

  Emma Stewart1, Andrew P Prayle2, Alison Tooke1, Sara Pasalodos3, Mohnish Suri3, Andy Bush4,5,6, Jayesh M Bhatt1

  Author affiliations:

  1 Nottingham Children's Hospital, National Paediatric Ataxia Telangiectasia Clinic, QMC, Nottingham, UK

  2 University of Nottingham, School of Clinical Science, Queens Medical Centre, Child Health, Nottingham, UK

  3 Nottingham Clinical Genetics Service, National Paediatric Ataxia Telangiectasia Clinic, Clinical Genetics Service, City Hospital Campus, Nottingham, UK

  4 Imperial College, London, UK

  5 National Heart and Lung Institute, London, UK

  6 Royal Brompton & Harefield NHS Foundation Trust, London, UK

   

  1. Lefton-Greif MA, Crawford TO, McGrath-Morrow S, Carson KA, Lederman HM. Safety and caregiver satisfaction with gastrostomy in patients with Ataxia Telangiectasia. Orphanet J Rare Dis. 2011;6:23.

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top
• Published on: 19 January 2017

  Conclusions not justified by findings

  • Charlotte M Wright, Consultant Paediatrician /Professor

  It is encouraging to see a clinical service making an effort to examine the patterns of growth found in their condition. However the conclusions drawn from their data seem greatly overstated. They describe a pattern of 'progressive growth failure' in nearly a quarter of children with ataxia telangiectasia (AT), yet there is an average decline across all children of less than half a centile space over 3 years. These children are...

  Show More

  It is encouraging to see a clinical service making an effort to examine the patterns of growth found in their condition. However the conclusions drawn from their data seem greatly overstated. They describe a pattern of 'progressive growth failure' in nearly a quarter of children with ataxia telangiectasia (AT), yet there is an average decline across all children of less than half a centile space over 3 years. These children are as a group very short, with a majority being below the 2nd centile, but far fewer are thin, making a nutritional origin for this short stature unlikely. Even those children who are thin are not necessarily malnourished. Our experience in a specialist feeding clinic is that children with neurodisability and chronic disorders often have low lean mass due to low muscle mass, which may actually coexist with normal or even high fat levels (1). It is clear from the figure that three of the 12 children who received PEG feeding showed marked weight and some height gain, but others showed no weight acceleration or even a decline, with an overall median annualised gain of less than a third of a centile space. PEG feeding is an invasive, expensive, life changing treatment and to be justified there must be the substantial objective evidence of benefit. It thus seems unreasonable to infer from these findings that more children with AT should be PEG fed at an earlier stage. This should be reserved for individual children where there are clearcut problems with swallowing, or objective evidence of low fat reserves measured using skinfolds or other methods. 1.Wright CM, Smith K, Morrison j. Withdrawing feeds from children on long term enteral feeding: factors associated with success and failure. Arch-Dis-Child 2011 96(5):433-9.

  Conflict of Interest:

  I work in a clinic that specialises in helping children withdraw form or avoid tube feeding

  Show Less

  Conflict of Interest:
  None declared.

  • Back to top