For the sake of completeness, the account of underlying causes of hypocalcaemia(Table 2)(1) should also include hypoparathyroidism-related hypocalcaemia attributable to magnesium deficiency(2), and coeliac disease-related hypocalcaemia which is not attributable to vitamin D deficiency(3). The role of hypoparathyroidism was documented in a 12 year old patient in whom hypoparathyroidism was thought to be attributable to inhibition of parathyroid hormone(PTH) release as a result of coeliac disease(CD)-related magnesium malabsorption. This patient had been admitted with hypocalcaemia, hypomagnesemia, hyperphosphataemia and subnormal serum vitamin D level of 8 mg/ml(normal 20-45 ng/ml). The plasma parathyroid hormone(PTH) level(14.6 pg/ml; normal > 12 pg/ml) was only minimally elevated, which was inappropriate in relation to the plasma calcium level of 5.1 mg/dl. Sm,all bowel biopsy showed moderate villous atrophy. Despite treatment with gluten free diet(GFD), and replacement therapy comprising vitamin D, calcium, magnesium , and aluminium hydroxide as a phosphate binder, calcium and magnesium levels were initially persistently low and phosphorus levels were persistently high. Furthermore, serum PTH levels also subsequently became undetectable. It was only after magnesium levels and calcium levels rose that phosphorus levels and serum PTH levels normalised. The authors hypothesised that CD had been the underlying cause of both the hypocalcaemia and...
For the sake of completeness, the account of underlying causes of hypocalcaemia(Table 2)(1) should also include hypoparathyroidism-related hypocalcaemia attributable to magnesium deficiency(2), and coeliac disease-related hypocalcaemia which is not attributable to vitamin D deficiency(3). The role of hypoparathyroidism was documented in a 12 year old patient in whom hypoparathyroidism was thought to be attributable to inhibition of parathyroid hormone(PTH) release as a result of coeliac disease(CD)-related magnesium malabsorption. This patient had been admitted with hypocalcaemia, hypomagnesemia, hyperphosphataemia and subnormal serum vitamin D level of 8 mg/ml(normal 20-45 ng/ml). The plasma parathyroid hormone(PTH) level(14.6 pg/ml; normal > 12 pg/ml) was only minimally elevated, which was inappropriate in relation to the plasma calcium level of 5.1 mg/dl. Sm,all bowel biopsy showed moderate villous atrophy. Despite treatment with gluten free diet(GFD), and replacement therapy comprising vitamin D, calcium, magnesium , and aluminium hydroxide as a phosphate binder, calcium and magnesium levels were initially persistently low and phosphorus levels were persistently high. Furthermore, serum PTH levels also subsequently became undetectable. It was only after magnesium levels and calcium levels rose that phosphorus levels and serum PTH levels normalised. The authors hypothesised that CD had been the underlying cause of both the hypocalcaemia and the hypomagnesemia. The latter , in turn, had inhibited PTH release, thereby aggravating the hypocalcaemia. Ultimately, rigorous adherence to GFD led to normalisation of serum magnesium and, hence, normalisation of serum PTH, thereby contributing to GFD-related normalisation of serum calcium levels.(2).
In the adult context coeliac disease(CD) can also manifest as isolated hypocalcaemia in the presence of normal serum magnesium, normal serum phosphorus, normal vitamin D levels, and appropriately elevated serum PTH. This scenario was reported in a 36 year old woman in whom the clinicians hypothesised that hypocalcaemia was solely attributable to CD-related malabsorption of calcium, independent of vitamin D status(3). A similar scenario would be plausible in paediatrics , although hitherto unreported in that context.
I have no funding and no conflict of interest.
References
(1) Nadar R., Shaw N
Investigation and management of hypocalcemia
Arch Dis Child 2020;105:399-405
(2)Yerushalmi B., Lev-Tzion R., Loewenthal N
Refractory hypoparathyroidism in a child with celiac disease
IMAJ 2016;18:58-60
(3)Rickels MR., Mandel SJ
Celiac disease manifesting as isolated hypocalcemia
Endocr Parct 2004;10:203-207
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
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.
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
I welcome this important historical paper emphasising the continued extreme importance of immunisation over more than 2 centuries in effectively preventing avoidable death and disability in children .
I was very surprised though, that the authors omitted a short paper published in the ADC in 2004 which related an 1806 inoculation scare in Northampton UK,. Northampton General Infirmary commenced giving free cowpox inoculations to the poor from 1January 11th 1804. In January 1806 there was an inoculation scare that led to a marked drop in public confidence after rumours of the death of a child Peter Bell. This was thoroughly investigated by the Infirmary Committee and in the Northampton Mercury of 10th January 1806 his parents had published a signed declaration that their son's death was nothing at all to do with the cowpox inoculation.
Public confidence was then restored
Reference
Williams A.N, A Vaccine Scare in 19th Century Northampton Arch Dis Child. 2005 Nov;90(11):1204.
Dear Editor,
We thank Professor Cook et al. for their letter in response to our Archimedes paper. We agree that waveform capnography may have benefit in earlier detection of oesophageal intubation or unplanned extubations in neonates, as has been assumed in adults. However, this assumption will require further study. Following an UK expert panel meeting, we are looking forward to investigating the use of waveform capnography monitoring in neonates.
As previously discussed in correspondence with Dr Whitaker, there are two pertinent questions to answer here for the neonatal population:
1) In neonates (P), does the addition of waveform capnography (I) compared to current methods of detection (colourimetric capnography, ventilator measurements, oxygen saturations and clinical examination) (C) provide an advantage in earlier detection of oesophageal intubation or unplanned extubation (O)?
2) Does the displayed numerical value in waveform capnography correlate with PaCO2 reliably enough to guide ventilator changes?
In our review, we specifically sought to address the second question. Those familiar with contemporary neonatal practice will know that many NICUs use transcutaneous capnography. Question 2 has a particular pertinence in neonates as their physiology is different from the adult and even paediatric population. Neonates are particularly prone to rapid changes in PaCO2, due to their changing lung compliance. Due to their lack of cerebral auto...
Dear Editor,
We thank Professor Cook et al. for their letter in response to our Archimedes paper. We agree that waveform capnography may have benefit in earlier detection of oesophageal intubation or unplanned extubations in neonates, as has been assumed in adults. However, this assumption will require further study. Following an UK expert panel meeting, we are looking forward to investigating the use of waveform capnography monitoring in neonates.
As previously discussed in correspondence with Dr Whitaker, there are two pertinent questions to answer here for the neonatal population:
1) In neonates (P), does the addition of waveform capnography (I) compared to current methods of detection (colourimetric capnography, ventilator measurements, oxygen saturations and clinical examination) (C) provide an advantage in earlier detection of oesophageal intubation or unplanned extubation (O)?
2) Does the displayed numerical value in waveform capnography correlate with PaCO2 reliably enough to guide ventilator changes?
In our review, we specifically sought to address the second question. Those familiar with contemporary neonatal practice will know that many NICUs use transcutaneous capnography. Question 2 has a particular pertinence in neonates as their physiology is different from the adult and even paediatric population. Neonates are particularly prone to rapid changes in PaCO2, due to their changing lung compliance. Due to their lack of cerebral autoregulation, changes in PaCO2 have a direct effect on blood flow to and around the brain. Swings in PaCO2 are known to be associated with poorer long term outcomes, severe neurological complications including intraventricular haemorrhage and potentially death. Thus, whenever a measured value is presented, it is important that staff are trained to interpret the value in the clinical setting to adequately respond, re-evaluate and avoid mistakes.
Despite the PICNIC survey’s merits as a thorough and well carried out national survey, PICNIC was reported by the mainstream media in a manner which may cause undue distress amongst NICU parents. Therefore, we aimed to highlight this problem in our opening paragraph. Regrettably, media misinterpretation is not an infrequent issue.
We are surprised by the comment by Prof. Cook et al. that our review omits the study by Kugelman et al. Their 2016 study on the impact of continuous capnography in ventilated neonates is included, both in the table and as reference number 30 of our paper. This study involved a small number of infants, relied on parameters set by ETCO2 (which has been shown by other studies not to approximate well to PaCO2) and was clearly underpowered to detect differences in neurological outcomes between groups.
To conclude, we feel there may be a role for waveform capnography in neonatal practice providing that concerns about safety (interference with volume guarantee ventilation, auto-triggering of ventilators, etc.) can be alleviated through careful study. If proven effective, waveform capnography must be adopted together with a clear understanding of its benefits and limitations, as well as training for all medical and nursing staff to avoid harm and ensure maximum benefit to patients.
A Scrivens
S Zivanovic
CC Roehr
Infant sleeping, crying and feeding problems can be hugely concerning for parents. As Wolke points out,(1) a growing body of evidence points to a range of poor longer term outcomes for infants who experience persistent, severe, regulatory difficulties. Olsen and colleagues’ study(2) is important because it aims to help our understanding of the early factors that predict persistent regulatory difficulties. If we can identify these early risk factors, perhaps we can better focus our efforts to prevent these difficulties from arising.
There have been several attempts to prevent infant sleeping and crying difficulties via parent education and support programs. Randomized controlled trials of these programs have reported small increases in infant sleep duration, increased likelihood of ‘sleeping through the night’,(3–5) reduced parent depressive symptoms, and less doubt about parenting ability at bedtime.(6) Parent education programs may modestly reduce infant sleep difficulties. Whether these infants are then less likely to develop complex regulatory problems that precede poor childhood outcomes, remains to be tested.
We agree with Wolke’s assertion that ‘there is a major need to educate parents on how to support infants in regulatory adaptation.’ Parenting practices such as having a consistent bedtime routine, and encouraging independent settling, have been shown to improve infant sleep.(7) However, we must consider that some infants’ sleep difficulties may have...
Infant sleeping, crying and feeding problems can be hugely concerning for parents. As Wolke points out,(1) a growing body of evidence points to a range of poor longer term outcomes for infants who experience persistent, severe, regulatory difficulties. Olsen and colleagues’ study(2) is important because it aims to help our understanding of the early factors that predict persistent regulatory difficulties. If we can identify these early risk factors, perhaps we can better focus our efforts to prevent these difficulties from arising.
There have been several attempts to prevent infant sleeping and crying difficulties via parent education and support programs. Randomized controlled trials of these programs have reported small increases in infant sleep duration, increased likelihood of ‘sleeping through the night’,(3–5) reduced parent depressive symptoms, and less doubt about parenting ability at bedtime.(6) Parent education programs may modestly reduce infant sleep difficulties. Whether these infants are then less likely to develop complex regulatory problems that precede poor childhood outcomes, remains to be tested.
We agree with Wolke’s assertion that ‘there is a major need to educate parents on how to support infants in regulatory adaptation.’ Parenting practices such as having a consistent bedtime routine, and encouraging independent settling, have been shown to improve infant sleep.(7) However, we must consider that some infants’ sleep difficulties may have less to do with parenting practices, and more to do with prenatal exposure to stress and other adversities. For these infants, sleep may not be easily improved with typical infant sleep interventions.
Prenatal maternal depression, anxiety, and stress are associated with increased risk for poorer infant health, greater infant stress reactivity and increased risk for preterm birth and low birth weight - factors that are known to contribute to increased regulatory problems.(8,9) Epigenetic influences on NR3C1 gene expression have been suggested to explain the association between heightened stress during pregnancy and later infant neuroendocrine function, behavior regulation and temperament.(10–12) Other research indicates that neurodevelopmental vulnerabilities and prenatal exposure to stress, better predict persistent regulatory difficulties than parenting style.(2,9,13)
While there is strong evidence that parenting practices influence infant sleep and crying behaviors,(7) emerging evidence seems to suggest that prenatal biological factors may also play a critical role. We do not yet know whether the effect of prenatal stress and adversity on later infant sleep can be changed via improved/altered parenting practices. Perhaps this explains why a small proportion of parents who report infant regulation problems insist that nothing helps their infant to sleep better. Instead of asking these parents to keep trying/try harder, it may be more beneficial to consider what other supports can help these families cope.
Further research is necessary to understand how nature and nurture intersect to influence the development of infant regulation. Findings will ultimately inform development of targeted, early prevention strategies that might improve outcomes for all dysregulated infants and their families.
1. Wolke D. Persistence of infant crying, sleeping and feeding problems: Need for prevention. Vol. 104, Archives of Disease in Childhood. 2019. p. 1022–3.
2. Olsen AL, Ammitzbøll J, Olsen EM, Skovgaard AM. Problems of feeding, sleeping and excessive crying in infancy: A general population study. Arch Dis Child. 2019 Jul 3 ;Epub ahead.
3. St James-Roberts I, Sleep J, Morris S, Owen C, Gillham P. Use of a behavioural programme in the first 3 months to prevent infant crying and sleeping problems. J Paediatr Child Health. 2001 Jun;37(3):289–97.
4. Symon BG, Marley JE, Martin AJ, Norman ER. Effect of a consultation teaching behaviour modification on sleep performance in infants: a randomised controlled trial. Med J Aust. 2005 Mar 7;182(5):215–8.
5. Pinilla T, Birch LL. Help me make it through the night: behavioral entrainment of breast-fed infants’ sleep patterns. Pediatrics. 1993 Feb;91(2):436–44.
6. Hiscock H, Cook F, Bayer J, Le HND, Mensah F, Cann W, et al. Preventing Early Infant Sleep and Crying Problems and Postnatal Depression: A Randomized Trial. Pediatrics. 2014 Feb 1;133(2):e346-54.
7. Sadeh A, Tikotzky L, Scher A. Parenting and infant sleep. Sleep Med Rev. 2010 Apr;14(2):89–96.
8. Nazzari S, Fearon P, Rice F, Dottori N, Ciceri F, Molteni M, et al. Beyond the HPA-axis: Exploring maternal prenatal influences on birth outcomes and stress reactivity. Psychoneuroendocrinology. 2019 Mar 14;101:253–62.
9. Bilgin A, Wolke D. Development of comorbid crying, sleeping, feeding problems across infancy: Neurodevelopmental vulnerability and parenting. Early Hum Dev. 2017 Jun;109(March 2017):37–43.
10. Conradt E, Fei M, LaGasse L, Tronick E, Guerin D, Gorman D, et al. Prenatal predictors of infant self-regulation: the contributions of placental DNA methylation of NR3C1 and neuroendocrine activity. Front Behav Neurosci. 2015 May 29;9:130.
11. Glover V, O’Donnell KJ, O’Connor TG, Fisher J. Prenatal maternal stress, fetal programming, and mechanisms underlying later psychopathology—A global perspective. Dev Psychopathol. 2018 Aug 2;30(03):843–54.
12. Van den Bergh BRH, Mulder EJH, Mennes M, Glover V. Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review. Neurosci Biobehav Rev. 2005 Apr;29(2):237–58.
13. Cook F, Conway L, Gartland D, Giallo R, Keys E, Brown S. Profiles and Predictors of Infant Sleep Problems Across the First Year. J Dev Behav Pediatr. 2019 Sep;1.
I read with great interest the article by Haisma et al. that reports on fecal calprotectin instability.(1) The authors are to be commended on their study. However, some points deserve comment.
The authors tested the stability of calprotectin after the stool was homogenized. The clinical relevance of this is unclear since what is important is the stability of calprotectin in stool after collection and before analysis. The studies that have evaluated fecal calprotectin stability in this situation are in alignment; calprotectin is stable in unprocessed stool at room temperature for at least 3 days with some studies suggesting up to a week (for review see D’Amico et al.).(2)
No support is provided for the statement by Haisma et al. that calprotectin instability in stool samples sent by mail may lead to errors in treat-to-target strategies. Indeed, the literature says otherwise.
1. Haisma SM, van Rheenen PF, Wagenmakers L, Muller Kobold A. Calprotectin instability may lead to undertreatment in children with IBD. Arch Dis Child. 2020;105:996-8 doi: 10.1136/archdischild-2018-316584 [published Online First: 2019/01/19].
2. D'Amico F, Rubin DT, Kotze PG, et al. International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases. United European Gastroenterol J. 2021;9:451-60 doi: 10.1002/ueg2.12069 [published Online First: 2021/05/08].
England and Tuthill deserve congratulation for highlighting the need to review the accuracy of drug information on the web. It is encouraging to see an apparent improvement in the quality of online information since we considered this question (Akram et al, 2007) but difficulties in study design would appear to limit the application of these findings. When online information for families is being rated it is important to distinguish between websites geared to the lay reader and those designed for professional reference, which may not be designed specifically to be readable and accessible.
A more ‘lay person’ centred methodology would also suggest that there is more to accuracy of patient information than a ‘correct’ listing of side effects found in a formulary written for prescribers. In line with General Medical Council guidance on consent (GMC, 2020, Para 23), families need information that correctly highlights common side effects and high risk rare events. A website may miss some, less severe, rare side effects and include some side effects that are not recorded in the formulary without necessarily reducing accuracy in a clinically meaningful way.
In this important and topical area for clinical research authors would do well to use established methodologies. For example DISCERN (Charnock et al, 1999) still provides a valuable basis for rating the quality of information.
Akram G, Thomson AH, Boyter A, Morton MJS.
Characterisation and evaluat...
England and Tuthill deserve congratulation for highlighting the need to review the accuracy of drug information on the web. It is encouraging to see an apparent improvement in the quality of online information since we considered this question (Akram et al, 2007) but difficulties in study design would appear to limit the application of these findings. When online information for families is being rated it is important to distinguish between websites geared to the lay reader and those designed for professional reference, which may not be designed specifically to be readable and accessible.
A more ‘lay person’ centred methodology would also suggest that there is more to accuracy of patient information than a ‘correct’ listing of side effects found in a formulary written for prescribers. In line with General Medical Council guidance on consent (GMC, 2020, Para 23), families need information that correctly highlights common side effects and high risk rare events. A website may miss some, less severe, rare side effects and include some side effects that are not recorded in the formulary without necessarily reducing accuracy in a clinically meaningful way.
In this important and topical area for clinical research authors would do well to use established methodologies. For example DISCERN (Charnock et al, 1999) still provides a valuable basis for rating the quality of information.
Akram G, Thomson AH, Boyter A, Morton MJS.
Characterisation and evaluation of UK websites on attention deficit hyperactivity disorder. 2008. Archives of Disease in Childhood 93(8):695-700.
doi:10.1136/adc.2007.130708
Charnock D, Sheppard S, Needham G, et al. DISCERN: an instrument for judging the quality of written consumer health information on treatment choices, 1999. J Epidemiol Community Health 53:105–111
For the sake of completeness, the account of underlying causes of hypocalcaemia(Table 2)(1) should also include hypoparathyroidism-related hypocalcaemia attributable to magnesium deficiency(2), and coeliac disease-related hypocalcaemia which is not attributable to vitamin D deficiency(3). The role of hypoparathyroidism was documented in a 12 year old patient in whom hypoparathyroidism was thought to be attributable to inhibition of parathyroid hormone(PTH) release as a result of coeliac disease(CD)-related magnesium malabsorption. This patient had been admitted with hypocalcaemia, hypomagnesemia, hyperphosphataemia and subnormal serum vitamin D level of 8 mg/ml(normal 20-45 ng/ml). The plasma parathyroid hormone(PTH) level(14.6 pg/ml; normal > 12 pg/ml) was only minimally elevated, which was inappropriate in relation to the plasma calcium level of 5.1 mg/dl. Sm,all bowel biopsy showed moderate villous atrophy. Despite treatment with gluten free diet(GFD), and replacement therapy comprising vitamin D, calcium, magnesium , and aluminium hydroxide as a phosphate binder, calcium and magnesium levels were initially persistently low and phosphorus levels were persistently high. Furthermore, serum PTH levels also subsequently became undetectable. It was only after magnesium levels and calcium levels rose that phosphorus levels and serum PTH levels normalised. The authors hypothesised that CD had been the underlying cause of both the hypocalcaemia and...
Show MoreDear 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 MoreDear 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...
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.
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...
I welcome this important historical paper emphasising the continued extreme importance of immunisation over more than 2 centuries in effectively preventing avoidable death and disability in children .
I was very surprised though, that the authors omitted a short paper published in the ADC in 2004 which related an 1806 inoculation scare in Northampton UK,. Northampton General Infirmary commenced giving free cowpox inoculations to the poor from 1January 11th 1804. In January 1806 there was an inoculation scare that led to a marked drop in public confidence after rumours of the death of a child Peter Bell. This was thoroughly investigated by the Infirmary Committee and in the Northampton Mercury of 10th January 1806 his parents had published a signed declaration that their son's death was nothing at all to do with the cowpox inoculation.
Public confidence was then restored
Reference
Williams A.N, A Vaccine Scare in 19th Century Northampton Arch Dis Child. 2005 Nov;90(11):1204.
Dear Editor,
Show MoreWe thank Professor Cook et al. for their letter in response to our Archimedes paper. We agree that waveform capnography may have benefit in earlier detection of oesophageal intubation or unplanned extubations in neonates, as has been assumed in adults. However, this assumption will require further study. Following an UK expert panel meeting, we are looking forward to investigating the use of waveform capnography monitoring in neonates.
As previously discussed in correspondence with Dr Whitaker, there are two pertinent questions to answer here for the neonatal population:
1) In neonates (P), does the addition of waveform capnography (I) compared to current methods of detection (colourimetric capnography, ventilator measurements, oxygen saturations and clinical examination) (C) provide an advantage in earlier detection of oesophageal intubation or unplanned extubation (O)?
2) Does the displayed numerical value in waveform capnography correlate with PaCO2 reliably enough to guide ventilator changes?
In our review, we specifically sought to address the second question. Those familiar with contemporary neonatal practice will know that many NICUs use transcutaneous capnography. Question 2 has a particular pertinence in neonates as their physiology is different from the adult and even paediatric population. Neonates are particularly prone to rapid changes in PaCO2, due to their changing lung compliance. Due to their lack of cerebral auto...
Infant sleeping, crying and feeding problems can be hugely concerning for parents. As Wolke points out,(1) a growing body of evidence points to a range of poor longer term outcomes for infants who experience persistent, severe, regulatory difficulties. Olsen and colleagues’ study(2) is important because it aims to help our understanding of the early factors that predict persistent regulatory difficulties. If we can identify these early risk factors, perhaps we can better focus our efforts to prevent these difficulties from arising.
There have been several attempts to prevent infant sleeping and crying difficulties via parent education and support programs. Randomized controlled trials of these programs have reported small increases in infant sleep duration, increased likelihood of ‘sleeping through the night’,(3–5) reduced parent depressive symptoms, and less doubt about parenting ability at bedtime.(6) Parent education programs may modestly reduce infant sleep difficulties. Whether these infants are then less likely to develop complex regulatory problems that precede poor childhood outcomes, remains to be tested.
We agree with Wolke’s assertion that ‘there is a major need to educate parents on how to support infants in regulatory adaptation.’ Parenting practices such as having a consistent bedtime routine, and encouraging independent settling, have been shown to improve infant sleep.(7) However, we must consider that some infants’ sleep difficulties may have...
Show MoreI read with great interest the article by Haisma et al. that reports on fecal calprotectin instability.(1) The authors are to be commended on their study. However, some points deserve comment.
The authors tested the stability of calprotectin after the stool was homogenized. The clinical relevance of this is unclear since what is important is the stability of calprotectin in stool after collection and before analysis. The studies that have evaluated fecal calprotectin stability in this situation are in alignment; calprotectin is stable in unprocessed stool at room temperature for at least 3 days with some studies suggesting up to a week (for review see D’Amico et al.).(2)
No support is provided for the statement by Haisma et al. that calprotectin instability in stool samples sent by mail may lead to errors in treat-to-target strategies. Indeed, the literature says otherwise.
1. Haisma SM, van Rheenen PF, Wagenmakers L, Muller Kobold A. Calprotectin instability may lead to undertreatment in children with IBD. Arch Dis Child. 2020;105:996-8 doi: 10.1136/archdischild-2018-316584 [published Online First: 2019/01/19].
2. D'Amico F, Rubin DT, Kotze PG, et al. International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases. United European Gastroenterol J. 2021;9:451-60 doi: 10.1002/ueg2.12069 [published Online First: 2021/05/08].
England and Tuthill deserve congratulation for highlighting the need to review the accuracy of drug information on the web. It is encouraging to see an apparent improvement in the quality of online information since we considered this question (Akram et al, 2007) but difficulties in study design would appear to limit the application of these findings. When online information for families is being rated it is important to distinguish between websites geared to the lay reader and those designed for professional reference, which may not be designed specifically to be readable and accessible.
A more ‘lay person’ centred methodology would also suggest that there is more to accuracy of patient information than a ‘correct’ listing of side effects found in a formulary written for prescribers. In line with General Medical Council guidance on consent (GMC, 2020, Para 23), families need information that correctly highlights common side effects and high risk rare events. A website may miss some, less severe, rare side effects and include some side effects that are not recorded in the formulary without necessarily reducing accuracy in a clinically meaningful way.
In this important and topical area for clinical research authors would do well to use established methodologies. For example DISCERN (Charnock et al, 1999) still provides a valuable basis for rating the quality of information.
Akram G, Thomson AH, Boyter A, Morton MJS.
Show MoreCharacterisation and evaluat...
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