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...
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 have similar liver disease (5). Whatever genetic or epigenetic factors caused liver disease to manifest in the PiZ proband may be operative in the younger sibling. If the same is true of WD, then the risk of the newborn sibling developing liver disease is high. This conclusion will be difficult to prove because such infants should be monitored closely and treated early with zinc.
1. Sandahl TD, Laursen TL, Munk DE, Vilstrup H, Weiss KH, Ott P. The Prevalence of Wilson’s Disease: An Update. Hepatology. 2020 Feb 1;71(2):722–32.
2. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, et al. A genetic study of Wilson’s disease in the United Kingdom. Brain. 2013 May;136(5):1476–87.
3. Jang JH, Lee T, Bang S, Kim YE, Cho EH. Carrier frequency of Wilson’s disease in the Korean population: A DNA-based approach. J Hum Genet. 2017 Sep 1;62(9):815–8.
4. Wallace DF, Dooley JS. ATP7B variant penetrance explains differences between genetic and clinical prevalence estimates for Wilson disease. Hum Genet. 2020 Aug 1;139(8):1065–75.
5. Psacharopoulos HT, Mowat AP, Cook PJL, Carlile PA, Portmann B, Rodeck CH. Outcome of liver disease associated with αl antitrypsin deficiency (PiZ): Implications for genetic counselling and antenatal diagnosis. Arch Dis Child. 1983;58(11):882–7.
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...
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 children with visually apparent respiratory modulation of the pleth signal were more likely to require intravenous therapy and high dependency care, and also had longer hospital stay5. We also observed that respiratory modulation of pleth was most evident during regular respiration periods, which could suggest an association with sleep state.
Respiratory modulation of the pleth signal is promising in assessment of acute wheezing illness in children, but its measurement is influenced by physiological and technical factors; these need further exploration before being adopted as a clinical tool.
1. Krishnan SG, Wong HC, Ganapathy S, Ong GY. Oximetry-detected pulsus paradoxus predicts for severity in paediatric asthma. Arch Dis Child. 2020 Jun;105(6):533-538. doi: 10.1136/archdischild-2019-318043.
2. Arnold DH, Jenkins CA, Hartert TV. Noninvasive assessment of asthma severity using pulse oximeter plethysmograph estimate of pulsus paradoxus physiology. BMC Pulm Med. 2010; 29:10:17. doi: 10.1186/1471-2466-10-17.
3. Arnold DH, Wang L, Hartert TV. Pulse Oximeter Plethysmograph Estimate of Pulsus Paradoxus as a Measure of Acute Asthma Exacerbation Severity and Response to Treatment. Acad Emerg Med. 2016; 23:315-322. doi: 10.1111/acem.12886.
4. Uong A, Brandwein A, Crilly C, York T, Avarello J, Gangadharan S. Pleth Variability Index to Assess Course of Illness in Children with Asthma. J Emerg Med. 2018; 55:179-184. doi: 10.1016/j.jemermed.2018.04.058.
5. Wertheim D, Anton O, Olden C and Seddon P. Respiratory modulation of the pulse oximeter plethysmogram amplitude as a marker of severity in acutely wheezy young children. European Respiratory Journal 2020; 56: Suppl. 64, 1206. DOI: 10.1183/13993003.congress-2020.1206
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...
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 idea that a baby who is wakeful at night is somehow abnormal.
The concept that babies should self-settle away from caregivers and sleep through the night, is not the biological norm.2 These ideas, although now mainstream, ignore the fundamental role of the mother-baby dyad and the need for regular physical contact on neonatal development. It is entirely normal for babies to wake overnight, either to feed or for comfort.3
To better support the emotional challenges of early parenthood, the medical profession must appreciate the normal spectrum of neonatal and infant sleep patterns.4 By studying and understanding the social confounders around infant sleep, we can prevent the propagation of potentially unnatural and harmful ideas related to infant behaviour and development.
References
1. Cook F, Conway LJ, Giallo R, et al, Infant sleep and child mental health: a longitudinal investigation. Archives of Disease in Childhood 2020;105:655-660.
2. Bartick, M, Tomori, C & Ball, HL. Babies in boxes and the missing links on safe sleep: Human evolution and cultural revolution. Maternal & Child Nutrition 2017; 14: e12544 doi: 10.1111/mcn.12544.
3. Figueiredo B, Dias CC, Pinto TM, Field T. Exclusive breastfeeding at three months and infant sleep-wake behaviors at two weeks, three and six months. Infant Behav Dev. 2017;49:62-69. doi:10.1016/j.infbeh.2017.06.006
4. Marinelli, K. A., Ball, H. L., McKenna, J. J., & Blair, P. S. (2019). An Integrated Analysis of Maternal-Infant Sleep, Breastfeeding, and Sudden Infant Death Syndrome Research Supporting a Balanced Discourse. Journal of Human Lactation, 35(3), 510–520. https://doi.org/10.1177/0890334419851797
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.
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...
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 similarly high test accuracy. We have validated the PECARN rule using these rounded cutoffs on another 1363 infants with nearly identical test accuracy as the original study.[5] Using these thresholds, we have now analyzed nearly 3200 febrile infants < 60 days-old and have not missed one case of bacterial meningitis. 4) If implemented as we suggest, 4 of the 5 “missed cases” of SBI reported by Velasco would not be missed.
1. Gomez B, Mintegi S, Bressan S, et al. Validation of the "Step-by-Step" approach in the management of young febrile infants. Pediatrics 2016;138:e20154381.
2. Velasco R, Gomez B, Benito J, Mintegi S. Accuracy of PECARN rule for predicting serious bacterial infection in infants with fever without a source. Arch Dis Child 2020;0;1-6.
3. Kuppermann N, Dayan PS, Levine DA, et al. A clinical prediction rule to identify febrile infants 60 days and younger at low risk for serious bacterial infections. JAMA Pediatr 2019;173:342–51.
4. Blaschke AJ, Korgenski EK, Wilkes J, et al. Rhinovirus in febrile infants and risk of bacterial infection. Pediatrics. 2018;141:e20172384.
5. Kuppermann N, Dayan PS, VanBuren JM, et al. Validation of a prediction rule for febrile infants less than or equal to 60 days in a multicenter network. Acad Emerg Med 2020;27:S43.
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...
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 of care such as GP hubs may be a more appropriate area in which to invest. They have already demonstrated high patient satisfaction3.
The coronavirus pandemic has challenged the way we work in many ways. In light of this, the paediatric profession has the opportunity to change our care delivery processes in a way that maximises the benefit for the child. I hope that secondary care can work more creatively with primary care, for example by running more joint clinics with GPs and developing links with community nursing/mental health teams. This will shift focus back to child centred paediatric care.
References
1. Scott-Jupp R, Carter E, Brown N. Effects of consultant residence out-of-hours on acute paediatric admissions. Arch Dis Child. Jul 2020;105(7):661-663. doi:10.1136/archdischild-2019-317553
2. Viner RM, Blackburn F, White F, et al. The impact of out-of-hospital models of care on paediatric emergency department presentations. Arch Dis Child. Feb 2018;103(2):128-136. doi:10.1136/archdischild-2017-313307
3. Montgomery-Taylor S, Watson M, Klaber R. Child Health General Practice Hubs: a service evaluation. Arch Dis Child. Apr 2016;101(4):333-7. doi:10.1136/archdischild-2015-308910
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...
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 to stop treatment.
Best regards,
Francesca Peri, MD
Irene Berti, MD
Egidio Barbi, MD, Professor
1- Grech JA, Calleja T, Soler P, et al. Necrosis of infantile haemangioma with propranolol therapy. Archives of Disease in Childhood 2020;105:608.
2- Léauté-Labrèze C et al. A Randomized, Controlled Trial of Oral Propranolol in Infantile Hemangioma. N Engl J Med. 2015; 372:735-746.
3- Storch CH, Hoeger PH. Propranolol for infantile haemangiomas: insights into the molecular mechanisms of action. Br J Dermatol. 2010;163(2):269-274. doi:10.1111/j.1365-2133.2010.09848.
4- Chang CS, Kang GC. Efficacious Healing of Ulcerated Infantile Hemangiomas Using Topical Timolol. Plast Reconstr Surg Glob Open. 2016;4(2):e621. Published 2016 Feb 16.
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...
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 world. We urge caution in the use of language in these difficult times, when there is already an increased level of public concern about medical problems and medical facilities.
1. Sidpra J, Abomeli D, Hameed B, et al. Arch Dis Child Epub ahead of print: [02 July 2020]. doi:10.1136/archdischild-2020-319872
2. Campbell AM. An increasing risk of family violence during the Covid-19 pandemic: strengthening community collaborations to save lives. Forens Sci Internat Reports Epub ahead of print [12 April 2020] doi.org/10.1016/j.fsir.2020.100089
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...
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 disease.
Yours faithfully
John Furness
References
Isba R, Edge R, Jenner R, et al Where have all the children gone? Decreases in paediatric emergency department attendances at the start of the COVID-19 pandemic of 2020 Archives of Disease in Childhood 2020;105:704. https://www.rcpch.ac.uk/resources/impact-covid-19-child-health-services-... accessed 10th July 2020
Scaramuzza A, Tagliaferri F, Bonetti L, et al Changing admission patterns in paediatric emergency departments during the COVID-19 pandemic Archives of Disease in Childhood 2020;105:704-706 https://stateofchildhealth.rcpch.ac.uk/ accessed 10th July 2020 https://www.rcpch.ac.uk/resources/reset-restore-recover-rcpch-principles... accessed 10th July 2020
Brown N Highlights from this issue Archives of Disease in Childhood 2020;105:i.
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...
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 is being run is that of a passive adaptation that contradicts the very essence of a perspective of well-being and health of childhood. Actions for a concrete safeguard perspective should start now (4). The deep risk that is being run is that of a passive adaptation that contradicts the very essence of a perspective of well-being and health of children. Breaking the current state of indifference is perhaps possible if we stop thinking about the second epidemic wave.
Only when we talk about our concerns and plans for the well-being of children, with the same passion with which we talk about all the extraordinary efforts to save the lives of adults, will those who are bound by the current silence feel able to develop strategies and make investments that will change the prospects of well-being for children.
This represents a priority that has a greater relevance than that of the documentation of clinical problems related to Covid 19 infection in children.
References
1. Ladhani SN, Amin-Chowdhury Z, Amirthalingam G, et al. Prioritising paediatric surveillance during the COVID-19 pandemic. Arch Dis Child 2020;105:613–615.
2. Crawley E, Loades M, Feder G, et al. Wider collateral damage to children in the UK because of the social distancing measures designed to reduce the impact of COVID-19 in adults. BMJ Paediatrics Open 2020, 4:e000701. doi: 10.1136/bmjpo-2020-000701
3. Bhopal SS, Bagaria J, Bhopal R. Risks to children during the Covid-19 pandemic: some essential epidemiology. BMJ 2020;369:m2290 http://dx.doi.org/10.1136/bmj.m229
4. Green P. Risks to children and young people during Covid-19 pandemic. A shift in focus is needed to avoid an irreversible scarring of a generation. BMJ 2020;369:m1669 https://doi.org/10.1136/bmj.m1669
5. Lazzerini M, Barbi E, Apicella A, Marchetti F, Cardinale F, Trobia G. Delayed access or provision of care in Italy resulting from fear of COVID-19. Lancet Child Adolesc Health 2020;4(5):e10-e11. doi: 10.1016/S2352-4642(20)30108-5.
6. Tamburlini G, Marchetti F. Covid-19 pandemia: reasons and indications for reopening education services. Medico e Bambino 2020;39(5):301-304 https://www.medicoebambino.com/?id=2005_301.pdf
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.
Show MoreThe 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...
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...
Show MoreDear 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...
Show MoreI 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.
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...
Show MoreScott-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...
Show MoreTo the editor
Show MoreWe 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...
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...
Show MoreDear 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?”
Show MoreAs 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...
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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