We were delighted to see Lucina highlighted positive data on Community Water Fluoridation (CWF) [1] Has Luciana seen the latest American Academy of Paediatrics (AAP) guideline on the issue? [2] They state that the AAP Standard of Care is Fluoride Varnish. However we have asked them why CWF isn’t the standard of care given the only objection they give for it is that it is a “controversial and highly emotional issue”. In the same paper they make suggestions including that paediatricians should:
1) Apply fluoride varnish
2) Know how to determine the concentration of fluoride in a child’s primary drinking water and determine the need for systemic supplements.
3) Advocate for water fluoridation in their local community.
UK paediatricians cannot apply fluoride varnish. UK paediatricians can identify concentrations of fluoride in the local drinking water using www.onepartpermillion.co.uk. They can prescribe fluoride supplements where there is need.
Until CWF is implemented does Lucina agree that these measures need promoting amongst UK Paediatricians?
References
1. Highlights from the literature Archives of Disease in Childhood 2020;105:1236.
2. Clark MB, Slayton RL for American Academy of Pediatrics Section on Oral Health. Pediatrics 146 (6):e2020034637
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 a 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 h...
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 a 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.
Acute haemorrhagic oedema of infancy, also termed cockade purpura with edema or Finkelstein-Seidlmayer disease, is a rather uncommon small-vessel leukocytoclastic vasculitis. It characteristically affects children 4 weeks to 23 months of age, is skin-limited, spontaneously recovers within 3 weeks, and does not recur. O'Connor C et al [1]. recently documented the distinctive features of acute haemorrhagic oedema in a 23-day-old male infant with fever, rhinorrhoea, conjunctivitis and cough. The authors concluded that acute haemorrhagic oedema has never previously been reported in neonates, with the exception of a female newborn infant noted to have this vasculitis at birth [2].
Stimulated by the fascinating report by O'Connor C et al. [1], we analyzed the data contained in the Acute Hemorrhagic Edema BIbliographic Database AHEBID, which includes all articles on acute haemorrhagic oedema. In the mentioned database, we found 6 further cases (4 males and 2 female patient) of this vasculitis in subjects less than 4 weeks of age, including 4 familial cases [3-5].
It is therefore concluded that acute haemorrhagic oedema has been so far documented in a total of 8 patients (5 males and 3 female patient) less less than 4 weeks of age. In this age group, this vasculitis is uncommon but not exceptional and may affect 2 or more members of the same family.
References
1. O’Connor C, Bux D, O’Connell M. Acute haemorrhagic oedema of infancy: first report...
Acute haemorrhagic oedema of infancy, also termed cockade purpura with edema or Finkelstein-Seidlmayer disease, is a rather uncommon small-vessel leukocytoclastic vasculitis. It characteristically affects children 4 weeks to 23 months of age, is skin-limited, spontaneously recovers within 3 weeks, and does not recur. O'Connor C et al [1]. recently documented the distinctive features of acute haemorrhagic oedema in a 23-day-old male infant with fever, rhinorrhoea, conjunctivitis and cough. The authors concluded that acute haemorrhagic oedema has never previously been reported in neonates, with the exception of a female newborn infant noted to have this vasculitis at birth [2].
Stimulated by the fascinating report by O'Connor C et al. [1], we analyzed the data contained in the Acute Hemorrhagic Edema BIbliographic Database AHEBID, which includes all articles on acute haemorrhagic oedema. In the mentioned database, we found 6 further cases (4 males and 2 female patient) of this vasculitis in subjects less than 4 weeks of age, including 4 familial cases [3-5].
It is therefore concluded that acute haemorrhagic oedema has been so far documented in a total of 8 patients (5 males and 3 female patient) less less than 4 weeks of age. In this age group, this vasculitis is uncommon but not exceptional and may affect 2 or more members of the same family.
References
1. O’Connor C, Bux D, O’Connell M. Acute haemorrhagic oedema of infancy: first report of a rare small vessel vasculitis in the neonatal period. Arch Dis Child 2020: Epub ahead of print. doi:10.1136/archdischild-2020-319739.
2. Cunningham BB, Caro WA, Eramo LR. Neonatal acute hemorrhagic edema of childhood: case report and review of the English-language literature. Pediatr Dermatol 1996;13:39-44.
3. Ballona R. Pápulas purpúricas en récien nacido. Dermatol Peru 2002;12:231-3.
4. Checa Rodríguez R, Carabaño Aguado I, Álvarez Fernández B. Edema agudo hemorrágico en un neonato. Pediatr Aten Primaria 2015;17:151-3.
5. Ostini A, Ramelli GP, Mainetti C, Bianchetti MG, Ferrarini A. Recurrent Finkelstein-Seidlmayer disease in four first-degree relatives. Acta Derm Venereol 2015;95:622-3.
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
Re Functional Abdominal Pain: what clinicians need to know
In their article on the above subject, Andrews et al rightly emphasise that the majority of cases of recurrent abdominal pain in childhood are “functional” ie not associated with structural organic disease.
In placing this large number of potentially differing problems under one large umbrella I feel the authors are ignoring important subdivisions, each requiring a different approach. In particular, they only mention abdominal migraine twice in the whole article, and then only in passing.
The work of the late George Russell put abdominal migraine firmly on the map of UK paediatrics but it seems his message has been lost (1). With a prevalence of 4.1% of the population it seems likely that abdominal migraine is the commonest cause of children presenting with recurrent abdominal pain.
Rather than being a diagnosis of exclusion, abdominal migraine can be regarded as a positive clinical diagnosis based on a clear history. In typical cases the pain is clearly episodic and can come on in any situation. The pain is diffuse and central, and there is associated nausea and even vomiting, often associated with facial pallor and dark rings under the eyes. There is often a past history of travel sickness and usually a positive family history of migraine.
Parents seem to find being given a positive label and an explanation that makes sense to be maximally reassuring. Reassurance and explanation alo...
Re Functional Abdominal Pain: what clinicians need to know
In their article on the above subject, Andrews et al rightly emphasise that the majority of cases of recurrent abdominal pain in childhood are “functional” ie not associated with structural organic disease.
In placing this large number of potentially differing problems under one large umbrella I feel the authors are ignoring important subdivisions, each requiring a different approach. In particular, they only mention abdominal migraine twice in the whole article, and then only in passing.
The work of the late George Russell put abdominal migraine firmly on the map of UK paediatrics but it seems his message has been lost (1). With a prevalence of 4.1% of the population it seems likely that abdominal migraine is the commonest cause of children presenting with recurrent abdominal pain.
Rather than being a diagnosis of exclusion, abdominal migraine can be regarded as a positive clinical diagnosis based on a clear history. In typical cases the pain is clearly episodic and can come on in any situation. The pain is diffuse and central, and there is associated nausea and even vomiting, often associated with facial pallor and dark rings under the eyes. There is often a past history of travel sickness and usually a positive family history of migraine.
Parents seem to find being given a positive label and an explanation that makes sense to be maximally reassuring. Reassurance and explanation alone can result in clinical improvement because of the reduction is stress associated with worry about more serious conditions.
Management is similar to that of cranial migraine, consisting of reduction of stress, avoidance of trigger factors especially dietary ones, and prophylactic drug treatment if necessary (2).
References:
1) Abu-Arafeh I, Russell G “Prevalence and clinical features of abdominal migraine compared with those of migraine headache” Arch Dis Child, 1995;72(5):413-417
2) Symon DN, Russell G “Double blind placebo-controlled trial of Pizotifen syrup in the prophylaxis of abdominal migraine” Arch Dis Child, 1995; 72(1):44-50
In their report “Improving outcomes for children with asthma: role of national audit”(1), Sinha et al highlight the fact that the UK has one of the highest mortality figures from childhood asthma for high-income countries worldwide. They detect complacency regarding childhood asthma, and call for a targeted proactive model to improve matters.
The possible explanation for their observations regarding clinic attendance may be relevant to these wider issues.
The most likely explanation is that parents had not been given adequate safety netting advice regarding how to recognise and treat acute attacks. Such safety netting should have included parent- initiated steroids. Had this safety netting been in place, each of the cases reported would have already been started on oral steroids.
Another possibility is that the parents had not even been told that their child had asthma, or that asthma can kill. Many units seem to make children “earn” a diagnosis of asthma, after several years of being labelled “Viral associated wheeze”.
In my experience working as a locum around the UK, most units stop short of permitting parent- initiated steroids. Parents are simply told to use up to 10 puffs of a beta agonist and if this doesn’t work to “Seek medical advice”. However, this policy fails to recognise that severe attacks can occur in situations where medical help is not close at hand, for instance on holidays in remote places or abroad. Surely we...
In their report “Improving outcomes for children with asthma: role of national audit”(1), Sinha et al highlight the fact that the UK has one of the highest mortality figures from childhood asthma for high-income countries worldwide. They detect complacency regarding childhood asthma, and call for a targeted proactive model to improve matters.
The possible explanation for their observations regarding clinic attendance may be relevant to these wider issues.
The most likely explanation is that parents had not been given adequate safety netting advice regarding how to recognise and treat acute attacks. Such safety netting should have included parent- initiated steroids. Had this safety netting been in place, each of the cases reported would have already been started on oral steroids.
Another possibility is that the parents had not even been told that their child had asthma, or that asthma can kill. Many units seem to make children “earn” a diagnosis of asthma, after several years of being labelled “Viral associated wheeze”.
In my experience working as a locum around the UK, most units stop short of permitting parent- initiated steroids. Parents are simply told to use up to 10 puffs of a beta agonist and if this doesn’t work to “Seek medical advice”. However, this policy fails to recognise that severe attacks can occur in situations where medical help is not close at hand, for instance on holidays in remote places or abroad. Surely we should endeavour to make all families as self-reliant as possible in future emergencies rather than “doctor dependent”?
Parents of children with epilepsy are given advice on how to use buccal midazolam to shorten prolonged convulsions, and children with a risk of anaphylaxis are given adrenaline injectors to enable early life-saving intervention. Why do we not act similarly in all cases of childhood asthma?
Research in the 1980s may still be relevant today. In a study of asthma deaths in children in the Northern region, it was found that 80% of these deaths could have been prevented. The most important factor in these cases was lack of appropriate safety netting.
Perhaps the next audit should be on the content and distribution of safety netting for childhood asthma.
Dr Nigel Speight
Locum consultant
Durham
1) Sinha I et al, Arch Dis Child October Vol 105 No 10
2) “Survey of asthma deaths in the Northern region 1970-85”, H J Fletcher, S A Ibrahim, N Speight, Arch Dis Child 1990; 65: 163-167
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.
Dear Editor
We were delighted to see Lucina highlighted positive data on Community Water Fluoridation (CWF) [1] Has Luciana seen the latest American Academy of Paediatrics (AAP) guideline on the issue? [2] They state that the AAP Standard of Care is Fluoride Varnish. However we have asked them why CWF isn’t the standard of care given the only objection they give for it is that it is a “controversial and highly emotional issue”. In the same paper they make suggestions including that paediatricians should:
1) Apply fluoride varnish
2) Know how to determine the concentration of fluoride in a child’s primary drinking water and determine the need for systemic supplements.
3) Advocate for water fluoridation in their local community.
UK paediatricians cannot apply fluoride varnish. UK paediatricians can identify concentrations of fluoride in the local drinking water using www.onepartpermillion.co.uk. They can prescribe fluoride supplements where there is need.
Until CWF is implemented does Lucina agree that these measures need promoting amongst UK Paediatricians?
References
1. Highlights from the literature Archives of Disease in Childhood 2020;105:1236.
2. Clark MB, Slayton RL for American Academy of Pediatrics Section on Oral Health. Pediatrics 146 (6):e2020034637
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 a 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 h...
Acute haemorrhagic oedema of infancy, also termed cockade purpura with edema or Finkelstein-Seidlmayer disease, is a rather uncommon small-vessel leukocytoclastic vasculitis. It characteristically affects children 4 weeks to 23 months of age, is skin-limited, spontaneously recovers within 3 weeks, and does not recur. O'Connor C et al [1]. recently documented the distinctive features of acute haemorrhagic oedema in a 23-day-old male infant with fever, rhinorrhoea, conjunctivitis and cough. The authors concluded that acute haemorrhagic oedema has never previously been reported in neonates, with the exception of a female newborn infant noted to have this vasculitis at birth [2].
Stimulated by the fascinating report by O'Connor C et al. [1], we analyzed the data contained in the Acute Hemorrhagic Edema BIbliographic Database AHEBID, which includes all articles on acute haemorrhagic oedema. In the mentioned database, we found 6 further cases (4 males and 2 female patient) of this vasculitis in subjects less than 4 weeks of age, including 4 familial cases [3-5].
It is therefore concluded that acute haemorrhagic oedema has been so far documented in a total of 8 patients (5 males and 3 female patient) less less than 4 weeks of age. In this age group, this vasculitis is uncommon but not exceptional and may affect 2 or more members of the same family.
References
Show More1. O’Connor C, Bux D, O’Connell M. Acute haemorrhagic oedema of infancy: first report...
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 MoreRe Functional Abdominal Pain: what clinicians need to know
In their article on the above subject, Andrews et al rightly emphasise that the majority of cases of recurrent abdominal pain in childhood are “functional” ie not associated with structural organic disease.
Show MoreIn placing this large number of potentially differing problems under one large umbrella I feel the authors are ignoring important subdivisions, each requiring a different approach. In particular, they only mention abdominal migraine twice in the whole article, and then only in passing.
The work of the late George Russell put abdominal migraine firmly on the map of UK paediatrics but it seems his message has been lost (1). With a prevalence of 4.1% of the population it seems likely that abdominal migraine is the commonest cause of children presenting with recurrent abdominal pain.
Rather than being a diagnosis of exclusion, abdominal migraine can be regarded as a positive clinical diagnosis based on a clear history. In typical cases the pain is clearly episodic and can come on in any situation. The pain is diffuse and central, and there is associated nausea and even vomiting, often associated with facial pallor and dark rings under the eyes. There is often a past history of travel sickness and usually a positive family history of migraine.
Parents seem to find being given a positive label and an explanation that makes sense to be maximally reassuring. Reassurance and explanation alo...
Dear Editor
In their report “Improving outcomes for children with asthma: role of national audit”(1), Sinha et al highlight the fact that the UK has one of the highest mortality figures from childhood asthma for high-income countries worldwide. They detect complacency regarding childhood asthma, and call for a targeted proactive model to improve matters.
The possible explanation for their observations regarding clinic attendance may be relevant to these wider issues.
The most likely explanation is that parents had not been given adequate safety netting advice regarding how to recognise and treat acute attacks. Such safety netting should have included parent- initiated steroids. Had this safety netting been in place, each of the cases reported would have already been started on oral steroids.
Another possibility is that the parents had not even been told that their child had asthma, or that asthma can kill. Many units seem to make children “earn” a diagnosis of asthma, after several years of being labelled “Viral associated wheeze”.
In my experience working as a locum around the UK, most units stop short of permitting parent- initiated steroids. Parents are simply told to use up to 10 puffs of a beta agonist and if this doesn’t work to “Seek medical advice”. However, this policy fails to recognise that severe attacks can occur in situations where medical help is not close at hand, for instance on holidays in remote places or abroad. Surely we...
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...
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