1546 e-Letters

  • The newborn with 2 WD mutations

    The disparity between estimates of the clinical and genetic prevalence of Wilson’s disease (WD) may be due to under-diagnosis or reduced penetrance of ATP7B mutations.
    The widely quoted disease prevalence of 1:30,000 from a 1984 paper is corroborated by 4 recent studies giving estimates from 1:29,000 to 1:40,000 (1). By contrast the calculated frequency amongst 1000 UK control subjects of individuals predicted to carry two mutant pathogenic ATP7B alleles was 1:7026(2). Amongst 14,835 Korean neonatal dried blood spots it was 1:7561 (3).
    Assuming that under-diagnosis is not responsible these data suggest that penetrance in WD is approximately 20%. Interrogating the Genome Aggregation Database (gnomAD) revealed 231 WD-associated ATP7B variants giving an initial estimated population prevalence of around 1 in 2400. Using standardised genetic variant effect prediction algorithms WD-associated ATP7B variants with predicted low penetrance were excluded giving a revised disease estimate of around 1 in 20,000 and a penetrance of 12% (4).
    WD thus resembles alpha-1 antitrypsin deficiency (AAT); only ~10% PiZ individuals develop liver disease. So, what is the prognosis of the newborn found to have the same genotype as a sibling proband with AAT or WD and liver disease - the same risk as the general population or higher? In AAT, if the first PiZ child of PiZ heterozygote parents had unresolved liver disease, there was a 78% chance that a second PiZ child will hav...

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  • Oximetry-detected pulsus paradoxus predicts for severity in paediatric asthma

    We read with interest the paper by Krishnan et al.1 and agree that "pulsus paradoxus" (PP) of the oximetry plethysmogram (pleth) may be useful in assessing severity of acute asthma exacerbations in children. The visual assessment they propose is one of a number of approaches which have been used, with variable success in predicting clinical outcomes2,3,4.

    Rather than pulse amplitude variation associated with respiration, figure 2 in the paper1 shows predominately baseline undulation, at a rate of about 1/5 to 1/6 of pulse rate; no time base nor simultaneous respiratory waveform is included. Can the authors thus be sure that the variation is due to respiration, and if it is, could the baseline variations in fact be associated with respiratory-related changes in peripheral blood volume? As the visual pleth display is dependent on processing by the pulse oximeter, it would be helpful to know more about the oximeter used.

    We have monitored respiration using Respiratory Inductance Plethysmography (RIP) bands simultaneously with oximetry pleth in children with acute wheezing illness using a SOMNOscreen plus recorder (SOMNOmedics GmbH, Germany) with Nonin oximeter module (Nonin Medical Inc., USA). We developed software in MATLAB (The MathWorks Inc., USA) for quantifying pleth pulse amplitude to assess pulsus paradoxus analogous variation. Consistent with Krishnan et al., we found that chil...

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  • Normal infant sleep behaviours

    Dear Editor,

    We note with interest the conclusions made in the longitudinal cohort review published by Cook et al1 linking frequent night wakings in infancy with emotional disorders in later childhood. Our analysis of the paper questions whether the medical profession is overmedicalising normal sleep behaviours without fully identifying what is within normal limits.

    Multiple potential confounders were not adjusted for in the analysis, including but not limited to: method of feeding, neonatal and infant medical history, sleep environment (co-sleeping and bedsharing) or the proportion of parents implementing sleep training methods. Additionally, statistical significance for these conclusions was reached by comparing the babies labelled with with ‘persistent severe sleep problems’ (19.4%) with those classed as ‘settled sleepers’ (23.7%), rather than the 56.0% of babies labelled with ‘moderate sleep problems’. Over half of the cohort were repeatedly waking at night, confirming that this is a common feature of normal infant behaviour. This paper provides a much-needed opportunity to discuss our social expectations of infant sleeping patterns and the increasing risk of overmedicalising normal sleep behaviours.

    Modern western culture necessitates that adults sleep at night in order to function at work during the day. Societal changes over the last century have normalised the idea that babies too should sleep through the night, and this has slipped into the id...

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  • Functional Abdominal Pain

    I read with interest the review on functional abdominal pain and link to anxiety. However, there is no mention of the potential aetiology for anxiety.
    In our school age paediatric neurodevelopmental clinic , children and young people with diagnoses of Autism Spectrum Disorder often present with escalating levels of anxiety in relation to school attendance that is reflected in a range of physical symptoms that may include abdominal pain, headaches and sleep disturbance . Indeed ,they have often been under the care of the acute paediatric service and prescribed a variety of medications. School attendance has often been affected and/or there have been concerns about learning and behaviour leading to referral to the Neurodevelopmental /Community Paediatric clinic
    Once reasonable adjustments and environmental modifications have been implemented to support the individual , anxiety diminishes and physical symptoms improve. This has been most noticeable during the recent lockdown with many young people with ASD flourishing without the incapacitating anxiety that is associated with the busy, complex, social environment of school.
    A detailed psycho - social and neurodevelopmental history and consideration of the possibility of Autism Spectrum Disorder is likely to be helpful for this group of children and young people.

  • Comparisons of febrile infant prediction rules

    Prediction rules to identify young febrile infants with serious bacterial infections (SBI) have been developed by investigators globally. Comparisons of these rules should be conducted by independent parties to avoid conflicts of interest. Two newer prediction rules use procalcitonin (PCT) as an important variable: one rule,[1] created by the authors of the Velasco[2] paper, and the PECARN Febrile Infant Rule[3] created by the authors of this letter. There are important methodological issues which must be considered when evaluating Velasco’s validation of the PECARN study. 1) The Velasco study was a retrospective analysis of a registry at one hospital in Spain, while the PECARN study was prospectively conducted at 20 centers in the United States and analyzed by an independent data center (mitigating investigator bias). 2) The rate of SBI in the Velasco study was 20.5%, much higher than the 9.3% reported by the PECARN study[3] and other investigators.[4] This suggests a different patient population or SBI epidemiology than ours, and/or enrollment bias. 3) Although the PECARN rule (using the urinalysis, absolute neutrophil count [ANC] and PCT) was derived on febrile infants 0-60 days-old, we recommend implementation only on 29-60 day-old infants, as suggested in our article.[3] In the supplement to our article, the PECARN rule using rounded cutoffs (ANC of 4000 cells/mm3 and PCT of 0.5 ng/mL) for simplicity, safety and to decrease the risk of overfitting, performed with simi...

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  • Returning paediatrics to child centred care

    Scott-Jupp et al. recent paper (Effects of consultant residence out-of-hours on acute paediatric admissions1) appeared relevant to myself as a junior doctor at the end of my training. I am interested to know whether there was learning from the resident consultant around discharge behaviour to better understand the differences?

    There were approximately 40% of admissions that stayed less than 12 hours and this group were more likely to be discharged when a consultant was resident. There was no significant difference in discharge rates in children who stayed more than 12 hours1.

    Should the less ill children be attending acute services anyway? Would a service consisting of resident consultants feed into propping up the acute pathway for less ill children?

    A prospective observational study found up to 42.2% of ED presentations over a 14 day period were judged to have been totally avoidable if the family had had better health education2. Studies have previously looked at the appropriateness of paediatric OPD new referrals and suggest that at least 39% of them could be managed by primary care3.

    I wonder whether the expansion of paediatric consultant posts due to increased ED attendance have unwittingly made secondary care reluctant to challenge the status quo of paediatric care delivery despite clear evidence that hospital is not always appropriate? If paediatric ED attendance starts to go down, would the current system become redundant? Other models...

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  • Necrosis of infantile haemangioma is more likely related to natural history rather than to propranolol therapy

    To the editor
    We appreciated the Images in paediatrics ‘Necrosis of infantile haemangioma with propranolol therapy’ by Grech and colleagues1. Nevertheless, we take exception to the Authors’ statement that necrosis is due to propranolol induced-involution for several reasons: first of all, the infant was not receiving a full-dose medication (1.5 mg/kg/day) when propranolol should be given at minimum 2 mg/kg/day. Furthermore, the milestone study by Léauté-Labrèz et al showed that a daily regimen of 3 mg/kg is safe and effective in reducing haemangiomas in a cohort of 456 infants2. We do believe that considering the low dose and the proliferative phase the infant was in3, necrosis was most likely due to natural evolution of the haemangioma than drug-induced involution. The authors do not give precise measurements of the scalp lesion before and during treatment, so it is not clear how much the lesion diminished in size. In view of previous considerations, it is difficult to rule out that the lesion might just have followed its natural course. As a matter of fact, both prematurity and female gender are well known risk factors associated with ulceration4.As the authors properly underline, propranolol therapy is the treatment of choice for infantile haemangioma (IH) and adverse effects as hypoglycemia, hypotension and bradycardia are widely known. Ulceration is the most common complication of IH and so that it could be even considered an indication to continue rather than...

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  • Misuse and alarmist use of the word pandemic

    Sidpra et al1 reported seeing 10 patients with suspected abusive head trauma between 23 March and 23 April 2020, when previously their unit only saw 0.67 cases per month. They concluded that this indicated a pandemic. In support, they cited (providing an incorrect journal name) a published review suggesting an increased risk of family violence2, but in fact the review cited referred to decreasing reports of child abuse and neglect during the Covid-19 pandemic.

    Sidra et al made no mention of the likely explanation for their observations, namely a change in referral patterns. A number of children’s wards in hospitals in London and elsewhere in the UK have been taken over by adult Covid-19 patients, coupled with the closure of some paediatric urgent care centres and emergency departments, resulting in the diversion of ill children to other centres.

    If, as is suggested, the apparent 1493% increase in inflicted head injury cases is indeed the result of adverse psychosocial factors resulting from efforts to reduce Covid-19 transmission, then one would expect paediatric services worldwide to be deluged with other types of inflicted injury, which as yet has not been reported.

    Without other supporting data, and only using information from a single unit, we are not convinced that there is a sound case for the authors' conclusion that these 10 cases represent a ‘pandemic’. The word pandemic means a disease that is prevalent over a whole country or the whole...

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  • Where have all the children gone? Home. Why?

    Dear Editor

    Congratulations and thanks to Isba R et al on documenting the impact of Covid-19 on attendances to UK paediatric emergency departments and assessment units in lockdown [1]. Their data is mirrored by that collected by RCPCH [2] and Italy [3] They ask “Where have all the children gone?”
    As they point out the first concern was that children with serious illness were not being brought to hospital. RCPCH data suggests this is the minority of cases. [2] Other questions we should ask are, “Has the balance of benefit for families tipped in favour of staying away from hospital? Is there any evidence that supports that hypothesis?”
    RCPCH State of Child Health [4] documented a paediatric population with less acute illness but attending hospital more: the “Worried Well”. Furthermore whilst child physical health is improving mental and emotional wellbeing is deteriorating. [4]
    We must watch mortality and morbidity closely. To date there is no data to suggest this has increased in children. If it does not increase then we should ask ourselves the uncomfortable question, “Have we over diagnosed physical illness and contributed to anxiety?” Put another away, “Have UK paediatricians contributed to the anxiety of a population?”
    As we, “Reset, Restore and Recover,” [5] we must not shy away from considering this uncomfortable possibility as we address the secondary affects of the pandemic [6]. We must revaluate the relative risk of all childhood di...

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  • Protect children from Covid-19: the “secondary pandemia”

    Dear Editor,
    Ladhani SN et al (1) underline during the pandemic from Covid-19 the importance of reporting pediatric population surveillance data, and the pediatricians are encouraged to get involved with research and clinical trials to better understand the immunopatho-physiology and identify effective treatments for COVID-19 in children.

    However, as the authors themselves point out, the Covid-19 pandemic has been shown to be much milder as clinical manifestations in the infant and child than in the adult. Bhopal S et al (2) examined mortality data for 0-19 year olds, showing that across France, Germany, Italy, Korea, Spain, the United Kingdom, and the United States there were 44 deaths from covid-19 in 0-19 year olds (total population 135.691.226) up to 19 May 2020. Over a normal three month period, in these countries, published Global Burden of Disease data estimate that more than 13.000 deaths would be expected from all causes in this age group, including over 1000 from unintentional injury and 308 from lower respiratory tract infection including influenza.

    Because of their isolation, children are having documented risks that we are getting used to calling Covid-19 side effects or secondary pandemic (3,4): from delays in diagnosing some clinically relevant diseases (5), to educational deprivation (6), to the care needs of certain categories of children fragile with social and health needs that have interrupted their care project. The deep risk that...

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