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
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.
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.
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
The question of the safety of ibuprofen in lower respiratory tract infection(LRTI)(1) should be part of a bigger question. That question is the issue of the safety of ibuprofen in a child who is at risk of dehydration. A febrile child with LRTI is at risk of dehydration because of increased insensible fluid loss via the skin. Furthermore, in the presence of LRTI-related tachypnoea, there will be increased insensible fluid loss via the upper respiratory tract . These fluid losses are compounded when the child is too ill to maintain a good oral fluid intake.
In volume depleted states, such as the scenario depicted above, vasodilatory prostaglandins maintain adequate renal blood flow(RBF) and adequate glomerular filtration rate(GFR)(2). Nonsteroidal anti inflammatory drugs(NSAIDs) undermine those compensatory mechanisms by inhibiting prostaglandin synthesis(2). The consequence is the onset of NSAID-related acute kidney injury(AKI), as postulated by Misurac et al(3). These investigators postulated that NSAID-related inhibition of prostaglandin synthesis was the underlying cause of AKI in 21 of their 27 cases of NSAID-related AKI. In the remaining 6 children with AKI, acute interstitial nephritis(also attributable to NSAIDs) was the underlying cause.. Fifteen of the 20 children for whom dosing data were available took NSAID doses in the recommended range. Ibuprofen was the culprit NSAID in 67% of cases. Misurac et al also identified 54 other cases...
The question of the safety of ibuprofen in lower respiratory tract infection(LRTI)(1) should be part of a bigger question. That question is the issue of the safety of ibuprofen in a child who is at risk of dehydration. A febrile child with LRTI is at risk of dehydration because of increased insensible fluid loss via the skin. Furthermore, in the presence of LRTI-related tachypnoea, there will be increased insensible fluid loss via the upper respiratory tract . These fluid losses are compounded when the child is too ill to maintain a good oral fluid intake.
In volume depleted states, such as the scenario depicted above, vasodilatory prostaglandins maintain adequate renal blood flow(RBF) and adequate glomerular filtration rate(GFR)(2). Nonsteroidal anti inflammatory drugs(NSAIDs) undermine those compensatory mechanisms by inhibiting prostaglandin synthesis(2). The consequence is the onset of NSAID-related acute kidney injury(AKI), as postulated by Misurac et al(3). These investigators postulated that NSAID-related inhibition of prostaglandin synthesis was the underlying cause of AKI in 21 of their 27 cases of NSAID-related AKI. In the remaining 6 children with AKI, acute interstitial nephritis(also attributable to NSAIDs) was the underlying cause.. Fifteen of the 20 children for whom dosing data were available took NSAID doses in the recommended range. Ibuprofen was the culprit NSAID in 67% of cases. Misurac et al also identified 54 other cases of NSAID-related AKI in the medical literature during the period 1993 to 2009. Sixty percent of 50 cases for whom dosing data were available took the recommended does of NSAID. Fifty-three percent of the 54 cases were documented as having experienced reduced fluid intake before admission. Ibuprofen was the culprit NSAID in 20 of the 54 cases.
Comment
In the presence of LRTI-related dehydration ibuprofen has the potential to precipitate AKI as a result of NSAID-related inhibition of prostaglandin synthesis.
I have no funding and no conflict of interest
References
(1) Skehin K., Thompson A., Moriarty P
Is use of ibuprofen safe in children with signs and symptoms of lower respiratory tract infection?
Arch Dis Child 2019 Epub ahead of print
(2) Kim G-H
Renal effects of prostaglandins and cyclooxygenase-2 inhibitors
Electrolyte & Bood Disorders 2008;6:35-41
(3)Misurac JM., Knoderer CA., Leiser D et al
Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children
J Pediatr 2013;162:1153-1159
Infant vitamin D supplementation prevents not just rickets but also hypocalcaemic seizures and cardiomyopathy (CMP). The BPSU survey (1) captures rickets incidence which, we feel compelled to highlight, represents only the tip of the iceberg of widespread vitamin D deficiency (VDD) in the population.
In the UK, child surveillance checks are led by general practitioners (GPs). Most GPs do not receive postgraduate paediatric training and have inadequate undergraduate paediatric exposure, as acknowledged by the RCPCH president: “by any stretch of the imagination, GP training in the UK in paediatrics is woefully inadequate” (2). Recognising rickets requires paediatric experience as exemplified by recent cases of VDD induced CMP- one child’s death was preceded by multiple unfruitful visits to GPs and casualty (3). As the BPSU survey reached out only to paediatricians and not GPs, the extent of underreporting and under diagnosis is likely huge, limiting comparison with countries where paediatricians oversee primary care. The conclusion that rickets incidence in the UK is lower than expected downplays the extent of the underlying public health crisis, particularly when a significant number of cases were excluded [table 2 of (1)]. The true disease burden is unravelled when family members of affected children are investigated (3).
Similar to previous studies, rickets incidence here is 90 to 166 fold higher in Asian and Black children compared to wh...
Infant vitamin D supplementation prevents not just rickets but also hypocalcaemic seizures and cardiomyopathy (CMP). The BPSU survey (1) captures rickets incidence which, we feel compelled to highlight, represents only the tip of the iceberg of widespread vitamin D deficiency (VDD) in the population.
In the UK, child surveillance checks are led by general practitioners (GPs). Most GPs do not receive postgraduate paediatric training and have inadequate undergraduate paediatric exposure, as acknowledged by the RCPCH president: “by any stretch of the imagination, GP training in the UK in paediatrics is woefully inadequate” (2). Recognising rickets requires paediatric experience as exemplified by recent cases of VDD induced CMP- one child’s death was preceded by multiple unfruitful visits to GPs and casualty (3). As the BPSU survey reached out only to paediatricians and not GPs, the extent of underreporting and under diagnosis is likely huge, limiting comparison with countries where paediatricians oversee primary care. The conclusion that rickets incidence in the UK is lower than expected downplays the extent of the underlying public health crisis, particularly when a significant number of cases were excluded [table 2 of (1)]. The true disease burden is unravelled when family members of affected children are investigated (3).
Similar to previous studies, rickets incidence here is 90 to 166 fold higher in Asian and Black children compared to white. As the proportion of ethnic minority in the UK continues to rise (14% in 2011 census) those at highest risk of VDD are failed most by inadequate prevention strategies (4).
Shockingly, 77% of reported cases were not on the Department of Health recommended vitamin D supplements demonstrating lack of policy implementation. Whilst we agree with the author’s recommendations on supplementation, vitamin D fortification of flour as a more cost-effective long term strategy should be seriously considered (5).
References:
1. Julies P, Lynn RM, Pall K, Leoni M, Calder A, Mughal Z, et al. Nutritional rickets under 16 years : UK surveillance results. Arch Dis Child. 2020;
2. Modi N, Simon C. Child health care: Adequate training for all UK GPs is long overdue. Br J Gen Pract. 2016;66(646):228–9.
3. Uday S, Fratzl-Zelman N, Roschger P, Klaushofer K, Chikermane A, Saraff V, et al. Cardiac, bone and growth plate manifestations in hypocalcemic infants: revealing the hidden body of the vitamin D deficiency iceberg. BMC Pediatr. 2018 Dec;18(1):183.
4. Uday S, Högler W. Prevention of rickets and osteomalacia in the UK: political action overdue. Arch Dis Child. 2018;103(9):901–6.
5. Aguiar M, Andronis L, Pallan M, Högler W, Frew E. The economic case for prevention of population vitamin D deficiency: a modelling study using data from England and Wales. Eur J Clin Nutr. 2019; DOI:10.1038/s41430-019-0486-x
We write in response to the article "Use of oral corticosteroids in the treatment of alopecia areata" by BJ Cowley and J Dong, published in January's edition of the journal.(1)
In this article, the authors present a summary of their literature search, concluding that oral corticosteroid pulse therapy may be a safe and effective treatment for sufferers of alopecia areata (AA). The authors highlight the risk of avascular necrosis of the hip with the use of corticosteroids, despite none of their cited studies reporting on this complication specifically.
We would argue that iatrogenic adrenal suppression (AS) secondary to exogenous corticosteroid administration is also a noteworthy risk in these patients. Symptomatic AS has been well documented in the asthmatic population receiving daily inhaled corticosteroids, occasionally resulting in adrenal crisis and even sadly death. Whilst there is a good level of awareness of AS amongst some colleagues using high doses of daily steroids, for example in the induction phases of leukaemia treatment, AS is not confined to these children and is as pertinent to those receiving pulsed steroids for AA(2,3).
In our centre we have had personal experience of looking after a child who required intubation and ventilation when they developed a viral illness and presented with hypotension and hypoglycaemia. They had received intralesional steroids to treat AA, which had caused severe adrenal sup...
We write in response to the article "Use of oral corticosteroids in the treatment of alopecia areata" by BJ Cowley and J Dong, published in January's edition of the journal.(1)
In this article, the authors present a summary of their literature search, concluding that oral corticosteroid pulse therapy may be a safe and effective treatment for sufferers of alopecia areata (AA). The authors highlight the risk of avascular necrosis of the hip with the use of corticosteroids, despite none of their cited studies reporting on this complication specifically.
We would argue that iatrogenic adrenal suppression (AS) secondary to exogenous corticosteroid administration is also a noteworthy risk in these patients. Symptomatic AS has been well documented in the asthmatic population receiving daily inhaled corticosteroids, occasionally resulting in adrenal crisis and even sadly death. Whilst there is a good level of awareness of AS amongst some colleagues using high doses of daily steroids, for example in the induction phases of leukaemia treatment, AS is not confined to these children and is as pertinent to those receiving pulsed steroids for AA(2,3).
In our centre we have had personal experience of looking after a child who required intubation and ventilation when they developed a viral illness and presented with hypotension and hypoglycaemia. They had received intralesional steroids to treat AA, which had caused severe adrenal suppression. This took a year to fully recover as evidenced by serial synacthen tests. They had no evidence of any primary adrenal pathology.
We therefore feel strongly that in this education-focused article, it is remiss not to highlight adrenal suppression as a key risk with any corticosteroid regimen.
Dr Elizabeth M Bayman, Dr Louise E Bath, Prof Amanda J Drake
1. Cowley BJ, Dong J. Use of oral corticosteroids in the treatment of alopecia areata. Archives of Disease in Childhood 2020;105:96-98.
2. Goldbloom EB, Mokashi A, Cummings EA, et al. Symptomatic adrenal suppression among children in Canada. Arch Dis Child. 2017 Apr;102(4):340-345.
3. Bayman EM, Drake AJ. Adrenal suppression, still a problem after all these years. Arch Dis Child. 2017 Apr;102(4):338-339.
I read with interest your recent publication “Language in 2-year-old children born preterm and term: a cohort study) in the Archives of Disease in Childhood. I have made certain observations, and would welcome your views on them.
I notice (Figure 1) that you screened 557 preterm infants for eligibility. Ninety three of these were excluded as they were deemed unsuitable by medical staff and another hundred and seventeen were excluded for other reasons. As those numbers are quite substantial, I am curious to know what those factors were, and think that some details on those factors will further enhance the quality of the paper.
Your preterm cohort is defined as <30 weeks gestation. The current evidence shows that mortality and morbidity in preterm babies is associated with degree of prematurity. Therefore, I am wondering that what was the distribution of gestational age in the group and was there any further subgroup analysis attempted.
You mentioned family history having an impact on the likelihood of language delay in the introduction. However, I note that this was not included in list of factors explored. I wonder if there was any particular reason to do so.
I look forward to hearing from you, and would like to thank you in anticipation for your time.
Many thanks,
Dr Anna Howells
Paediatric SPR
Community Paediatrics, Bromley
We enjoyed reading the study by Jaquet-Pilloud et al. 1 examining the role of nebulised 3% hypertonic saline (HS) and bronchiolitis. We thank the authors for this excellent pragmatic non-blinded, randomised controlled trial. Their conclusions support the UK evidence from the SABRE study 2 and their systematic review3 which provides evidence of the futility of adding hypertonic saline to the management of bronchiolitis when compared to standard care alone with length of stay (LOS) or ready for discharge as the primary outcome. The article was well written and easy to follow. The study examined 121 infants with bronchiolitis recruited over three years from one tertiary centre in Switzerland. We felt it illustrated the very important problem of underpowered studies concluding no differences between two treatment regimens. The authors used the Korppi et al 3 study to assume that the mean LOS for infants admitted to hospital with bronchiolitis was 5 days [120 hours] with a standard deviation of 1.2 days [28.8 hours]. Reduction in hospital stay by 1 day was considered clinically significant and based on this a minimum sample size of 120 (with 60 in each group) was arrived. However the data from this paper by Jaquet-Pilloud et al show that the mean LOS was 47 hours (± 8.5) for nebulised hypertonic saline group and 50.4 hours (±11) for standard care group. The LOS at the authors’ hospital was less than half of the assumption used for their power calculation....
We enjoyed reading the study by Jaquet-Pilloud et al. 1 examining the role of nebulised 3% hypertonic saline (HS) and bronchiolitis. We thank the authors for this excellent pragmatic non-blinded, randomised controlled trial. Their conclusions support the UK evidence from the SABRE study 2 and their systematic review3 which provides evidence of the futility of adding hypertonic saline to the management of bronchiolitis when compared to standard care alone with length of stay (LOS) or ready for discharge as the primary outcome. The article was well written and easy to follow. The study examined 121 infants with bronchiolitis recruited over three years from one tertiary centre in Switzerland. We felt it illustrated the very important problem of underpowered studies concluding no differences between two treatment regimens. The authors used the Korppi et al 3 study to assume that the mean LOS for infants admitted to hospital with bronchiolitis was 5 days [120 hours] with a standard deviation of 1.2 days [28.8 hours]. Reduction in hospital stay by 1 day was considered clinically significant and based on this a minimum sample size of 120 (with 60 in each group) was arrived. However the data from this paper by Jaquet-Pilloud et al show that the mean LOS was 47 hours (± 8.5) for nebulised hypertonic saline group and 50.4 hours (±11) for standard care group. The LOS at the authors’ hospital was less than half of the assumption used for their power calculation. Our calculation suggests that based on authors LOS, the minimum sample should be at least 240 subjects. This calculation was similar to the numbers recruited in the SABRE study which used the UK hospital episode statistics that suggested that the average (mean (SD)) time to discharge was 72 (32) hours to power their study and with three years of recruitment and a total of 317 infants in this study with 158 infants randomised to HS and 159 to standard care. There was no difference between the two arms in time to being declared fit for discharge. They showed the median (not mean in this paper) time to being declared fit for discharge was 76 hours from admission in each group, and the time to actual discharge was 89 hours in each group. Essentially Jaquet-Pilloud et al needed twice as many subjects to be sure that there was no type 2 error and to be confident about the accuracy of their conclusions.
Yours sincerely
Dr Muthukumar Sakthivel, Dr Dure Yasrab, Dr Kevin Enright and Professor Colin Powell
Pediatric Emergency Department Sidra Medicine, Doha, Qatar
Dr Whitaker, in a letter in response to our Archimedes review of whether waveform capnography reliably approximates paCO2 in neonates, highlights two important questions which capnography seeks to address: Firstly, whether or not the endotracheal tube (ETT) is patent and correctly positioned in the trachea and secondly, whether the current ventilation strategy provides optimal CO2 clearance for the patient. The two questions are, of course, interlinked.
To date, in our field of neonatal medicine, the ETCO2 provides a valuable adjunct to clinical examination in determining ETT position and patency both at the point of intubation and during ongoing mechanical ventilation. However, for reasons explained in the paper, the numerical approximations to alveolar pCO2 provided by the currently available techniques of wave form capnography in neonates are not accurate enough to guide ventilatory changes. Thus, to guide ventilator changes, many neonatal intensive care units currently use transcutaneous capnometry.
In addition to the physiological properties, the waveform capnography sensors add extra weight and dead space to an infant’s ventilator circuit. This adds further complexity, like their still not fully assessed effect on volume-guarantee ventilation and potential for auto-triggering of ventilators. As volume guarantee is now considered the gold standard for ventilating preterm infants with respiratory distress syndrome, the value of waveform capnography, in addi...
Dr Whitaker, in a letter in response to our Archimedes review of whether waveform capnography reliably approximates paCO2 in neonates, highlights two important questions which capnography seeks to address: Firstly, whether or not the endotracheal tube (ETT) is patent and correctly positioned in the trachea and secondly, whether the current ventilation strategy provides optimal CO2 clearance for the patient. The two questions are, of course, interlinked.
To date, in our field of neonatal medicine, the ETCO2 provides a valuable adjunct to clinical examination in determining ETT position and patency both at the point of intubation and during ongoing mechanical ventilation. However, for reasons explained in the paper, the numerical approximations to alveolar pCO2 provided by the currently available techniques of wave form capnography in neonates are not accurate enough to guide ventilatory changes. Thus, to guide ventilator changes, many neonatal intensive care units currently use transcutaneous capnometry.
In addition to the physiological properties, the waveform capnography sensors add extra weight and dead space to an infant’s ventilator circuit. This adds further complexity, like their still not fully assessed effect on volume-guarantee ventilation and potential for auto-triggering of ventilators. As volume guarantee is now considered the gold standard for ventilating preterm infants with respiratory distress syndrome, the value of waveform capnography, in addition to standard expiratory tidal volume monitoring on volume-guarantee ventilated infants and transcutaneous capnometry, is a topic worthy of further research and discussion.
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 MoreI 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.
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 MoreDear 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...
The question of the safety of ibuprofen in lower respiratory tract infection(LRTI)(1) should be part of a bigger question. That question is the issue of the safety of ibuprofen in a child who is at risk of dehydration. A febrile child with LRTI is at risk of dehydration because of increased insensible fluid loss via the skin. Furthermore, in the presence of LRTI-related tachypnoea, there will be increased insensible fluid loss via the upper respiratory tract . These fluid losses are compounded when the child is too ill to maintain a good oral fluid intake.
Show MoreIn volume depleted states, such as the scenario depicted above, vasodilatory prostaglandins maintain adequate renal blood flow(RBF) and adequate glomerular filtration rate(GFR)(2). Nonsteroidal anti inflammatory drugs(NSAIDs) undermine those compensatory mechanisms by inhibiting prostaglandin synthesis(2). The consequence is the onset of NSAID-related acute kidney injury(AKI), as postulated by Misurac et al(3). These investigators postulated that NSAID-related inhibition of prostaglandin synthesis was the underlying cause of AKI in 21 of their 27 cases of NSAID-related AKI. In the remaining 6 children with AKI, acute interstitial nephritis(also attributable to NSAIDs) was the underlying cause.. Fifteen of the 20 children for whom dosing data were available took NSAID doses in the recommended range. Ibuprofen was the culprit NSAID in 67% of cases. Misurac et al also identified 54 other cases...
Dear Editor
Infant vitamin D supplementation prevents not just rickets but also hypocalcaemic seizures and cardiomyopathy (CMP). The BPSU survey (1) captures rickets incidence which, we feel compelled to highlight, represents only the tip of the iceberg of widespread vitamin D deficiency (VDD) in the population.
In the UK, child surveillance checks are led by general practitioners (GPs). Most GPs do not receive postgraduate paediatric training and have inadequate undergraduate paediatric exposure, as acknowledged by the RCPCH president: “by any stretch of the imagination, GP training in the UK in paediatrics is woefully inadequate” (2). Recognising rickets requires paediatric experience as exemplified by recent cases of VDD induced CMP- one child’s death was preceded by multiple unfruitful visits to GPs and casualty (3). As the BPSU survey reached out only to paediatricians and not GPs, the extent of underreporting and under diagnosis is likely huge, limiting comparison with countries where paediatricians oversee primary care. The conclusion that rickets incidence in the UK is lower than expected downplays the extent of the underlying public health crisis, particularly when a significant number of cases were excluded [table 2 of (1)]. The true disease burden is unravelled when family members of affected children are investigated (3).
Similar to previous studies, rickets incidence here is 90 to 166 fold higher in Asian and Black children compared to wh...
Show MoreDear editor
We write in response to the article "Use of oral corticosteroids in the treatment of alopecia areata" by BJ Cowley and J Dong, published in January's edition of the journal.(1)
In this article, the authors present a summary of their literature search, concluding that oral corticosteroid pulse therapy may be a safe and effective treatment for sufferers of alopecia areata (AA). The authors highlight the risk of avascular necrosis of the hip with the use of corticosteroids, despite none of their cited studies reporting on this complication specifically.
We would argue that iatrogenic adrenal suppression (AS) secondary to exogenous corticosteroid administration is also a noteworthy risk in these patients. Symptomatic AS has been well documented in the asthmatic population receiving daily inhaled corticosteroids, occasionally resulting in adrenal crisis and even sadly death. Whilst there is a good level of awareness of AS amongst some colleagues using high doses of daily steroids, for example in the induction phases of leukaemia treatment, AS is not confined to these children and is as pertinent to those receiving pulsed steroids for AA(2,3).
In our centre we have had personal experience of looking after a child who required intubation and ventilation when they developed a viral illness and presented with hypotension and hypoglycaemia. They had received intralesional steroids to treat AA, which had caused severe adrenal sup...
Show MoreDear Sanchez et al,
I read with interest your recent publication “Language in 2-year-old children born preterm and term: a cohort study) in the Archives of Disease in Childhood. I have made certain observations, and would welcome your views on them.
I notice (Figure 1) that you screened 557 preterm infants for eligibility. Ninety three of these were excluded as they were deemed unsuitable by medical staff and another hundred and seventeen were excluded for other reasons. As those numbers are quite substantial, I am curious to know what those factors were, and think that some details on those factors will further enhance the quality of the paper.
Your preterm cohort is defined as <30 weeks gestation. The current evidence shows that mortality and morbidity in preterm babies is associated with degree of prematurity. Therefore, I am wondering that what was the distribution of gestational age in the group and was there any further subgroup analysis attempted.
You mentioned family history having an impact on the likelihood of language delay in the introduction. However, I note that this was not included in list of factors explored. I wonder if there was any particular reason to do so.
I look forward to hearing from you, and would like to thank you in anticipation for your time.
Many thanks,
Dr Anna Howells
Paediatric SPR
Community Paediatrics, Bromley
Dear Editor
We enjoyed reading the study by Jaquet-Pilloud et al. 1 examining the role of nebulised 3% hypertonic saline (HS) and bronchiolitis. We thank the authors for this excellent pragmatic non-blinded, randomised controlled trial. Their conclusions support the UK evidence from the SABRE study 2 and their systematic review3 which provides evidence of the futility of adding hypertonic saline to the management of bronchiolitis when compared to standard care alone with length of stay (LOS) or ready for discharge as the primary outcome. The article was well written and easy to follow. The study examined 121 infants with bronchiolitis recruited over three years from one tertiary centre in Switzerland. We felt it illustrated the very important problem of underpowered studies concluding no differences between two treatment regimens. The authors used the Korppi et al 3 study to assume that the mean LOS for infants admitted to hospital with bronchiolitis was 5 days [120 hours] with a standard deviation of 1.2 days [28.8 hours]. Reduction in hospital stay by 1 day was considered clinically significant and based on this a minimum sample size of 120 (with 60 in each group) was arrived. However the data from this paper by Jaquet-Pilloud et al show that the mean LOS was 47 hours (± 8.5) for nebulised hypertonic saline group and 50.4 hours (±11) for standard care group. The LOS at the authors’ hospital was less than half of the assumption used for their power calculation....
Show MoreDr Whitaker, in a letter in response to our Archimedes review of whether waveform capnography reliably approximates paCO2 in neonates, highlights two important questions which capnography seeks to address: Firstly, whether or not the endotracheal tube (ETT) is patent and correctly positioned in the trachea and secondly, whether the current ventilation strategy provides optimal CO2 clearance for the patient. The two questions are, of course, interlinked.
Show MoreTo date, in our field of neonatal medicine, the ETCO2 provides a valuable adjunct to clinical examination in determining ETT position and patency both at the point of intubation and during ongoing mechanical ventilation. However, for reasons explained in the paper, the numerical approximations to alveolar pCO2 provided by the currently available techniques of wave form capnography in neonates are not accurate enough to guide ventilatory changes. Thus, to guide ventilator changes, many neonatal intensive care units currently use transcutaneous capnometry.
In addition to the physiological properties, the waveform capnography sensors add extra weight and dead space to an infant’s ventilator circuit. This adds further complexity, like their still not fully assessed effect on volume-guarantee ventilation and potential for auto-triggering of ventilators. As volume guarantee is now considered the gold standard for ventilating preterm infants with respiratory distress syndrome, the value of waveform capnography, in addi...
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