Febrile Infection-Related Epilepsy Syndrome (FIRES)

Cite this article as:
Jessica Archibald and Catherine Murphy. Febrile Infection-Related Epilepsy Syndrome (FIRES), Don't Forget the Bubbles, 2021. Available at:

An 8-year-old presents to the emergency department following a first seizure episode. They had a witnessed generalised tonic-clonic seizure that morning lasting approximately 60 seconds and remain post-ictal. They have a history of being non-specifically unwell yesterday with subjective fever, lethargy and a mild headache. They have no significant past medical history and no family history of seizures. The examination is unremarkable. Whilst in the emergency department they have a further two self-terminating generalised tonic-clonic seizures.

Febrile Infection-Related Epilepsy Syndrome (FIRES) is a rare epileptic encephalopathy that results in prolonged refractory status epilepticus in previously well patients.

Presenting Features

FIRES typically presents in children between the age of 3 to 15 years, with intractable status epilepticus, 2 to 10 days post a febrile illness. The preceding illness is most commonly an upper respiratory tract infection or gastroenteritis. Fevers may have resolved prior to the onset of the acute phase of the condition.

The acute phase of the illness is characterised by frequent seizures, rapidly progressing to status epilepticus. Although the seizures are initially focal in nature, they may evolve into secondary generalised seizures. The acute phase can be prolonged, lasting from weeks to months. An association with rash, liver derangement and arrhythmia has been noted in the literature. There is no latency period.

The chronic phase is denoted by refractory epilepsy, resulting in seizures that may cluster every 2 to 4 weeks. This is often associated with severe neurological impairment and cognitive decline.

FIRES had previously been thought to only occur in children, and New-Onset Refractory Status Epilepticus (NORSE) only in adults, however this theory has been disproven. Although FIRES is more prevalent in children, it has been known to also occur in adults. As such, FIRES is now considered a subtype of NORSE, characterised by a preceding febrile illness. It has previously been known as Acute Encephalitis with Refractory, Bepetitive Partial Seizures (AERRPS) and Devastating Epilepsy in School-age Children (DESC).


The aetiology of FIRES in unknown and as such the pathophysiology remains unclear.

One theory is that FIRES is a form of severe infectious encephalitis, but as yet no infectious agent has been identified, and the refractory nature of the seizures is atypical of encephalitis. Another hypothesis suggests FIRES is the result of an immune response, however, there is not enough evidence to support this theory.

A case identifying anti-GABA A receptor antibodies in the CSF of a patient who presented with severe refractory status epilepticus associated with a fever led to speculation that the condition may be autoimmune-mediated. Again this has not been proven and the case may have been an exception rather than a rule.

Other theories include genetic associations and potential links with metabolic disease, but as yet a cause has not been identified.

Diagnosis and Differentials

The diagnosis of FIRES is essentially clinical, as FIRES is a cryptogenic illness. The work up is initially general, and focused on the exclusion of other treatable causes, such as infectious or autoimmune encephalitis.

A detailed history will identify the preceding febrile illness, and would be focussed on the identification of risk factors for other causes for the presentation, including exposure to animals, drugs and toxins, recent foreign travel and immunosuppression.

Blood sampling will be used to identify an infectious cause for the presentation, through full blood count, blood cultures and a screen for atypical infective agents. Lumbar puncture should be performed for CSF sampling in order to investigate bacterial, viral, fungal or autoimmune causes. CSF may show a mildly elevated white cell count in those with FIRES.

EEGs may show a generalised slowing, in keeping with an encephalopathic picture, but do little in the way of distinguishing between other causes of seizures. However, they are useful in guiding treatment and identifying non-convulsive seizures.

Initial MRI imaging is often normal, however, follow up imaging has been associated with devastating changes. Early MRI, in the first weeks of the acute illness, has shown swelling of the mesial temporal structures and increased T2 weighted signal. Follow up MRI, greater than 6 months after onset, may be associated with bilateral mesial temporal atrophy and increased T2 weighted signal. It should be noted that MRI may be normal in 50% of cases.

Differentials to consider are Dravet Syndrome, which presents with a febrile illness associated with status epilepticus, though this tends to present within the first year of life. Also Alper’s Disease, which presents with refractory seizures in previously well children, and is often associated with liver disease.

The patient is loaded with levetiracetam (40mg/kg) as per hospital guidelines, and admitted under paediatrics locally. A CT head is unremarkable and bloods show mild LFT derangement with normal inflammatory markers. They are treated empirically with intravenous cefotaxime and aciclovir. Later that afternoon they develop a fever of 38.3.

The GCS fluctuates between 11 to 13 with no full recovery to baseline until later that evening. Following two focal seizures the next afternoon, they are transferred to the local tertiary centre for further investigation and management.

Initial Management

Initial management involves treating the seizure, and more often status epilepticus. Local hospitals have their own guideline for managing status epilepticus but the first line is typically benzodiazepines (lorazepam, diazepam, midazolam, clonazepam). Second-line treatment is standard anti-convulsants (levetiracetam, phenytoin, phenobarbitone, sodium valproate), however, FIRES does not typically respond to these medications even in high doses.

The seizure pattern in FIRES is often resistant to multiple anti-epileptics. Alternative treatment options have to be sought although there is limited evidence as to the optimal treatment.

Long-term Management

There is limited data on the treatment of FIRES, however, they all conclude the seizures are very difficult to manage and often require polytherapy. Some of the alternative treatment options include drug-induced burst-suppression comas, immunotherapy, a ketogenic diet, vagus nerve stimulation, therapeutic hypothermia and intravenous magnesium sulfate. The most commonly used and researched options are discussed below.

Burst suppression coma

Burst suppression coma induction is viewed as standard care for refractory status epilepticus. If first and second-line treatments fail the next option involves high doses of anti-convulsants along with anaesthetic agents, for example, an infusion of midazolam, barbiturates or propofol. Unfortunately when the anti-convulsants are weaned the seizures tend to reoccur. Prolonged burst suppression coma has been associated with a significantly worse cognitive outcome and poorer prognosis.


Immunotherapy has been trialled due to the suspected role of inflammation in the pathogenesis of FIRES. High dose steroids, intravenous immunoglobulin and plasmapheresis have all been used. There is limited evidence to suggest a beneficial role in the management of refractory epilepsy. A large-scale Japanese study described 2 out of 12 patients responding to steroids, although there is not enough evidence to support this as a treatment option. Treatment with immunotherapy is often associated with significant side effects

Anakinra is a recombinant and modified human interleukin-1 receptor antagonist protein. Recent evidence has shown it to be an effective and promising treatment option in patients with FIRES, though relapse has been reported after withdrawal. It has been shown to decrease the duration of mechanical ventilation and hospital length of stay, and possibly seizure reduction. Future studies are required to understand the optimum dosing regime and safety of anakinra.

Ketogenic diet

A ketogenic diet is a high fat, adequate protein and low carbohydrate diet aimed at imitating the body’s fasting state. The body, therefore, metabolises fat for energy. The early introduction of the ketogenic diet has shown to be beneficial in the management of FIRES in uncontrolled trials. It has been suggested that the ketogenic diet may have an anti-inflammatory, as well as an anti-convulsant effect. Some reports suggest it may also have a positive effect on long term cognition. Currently, it is one of the only management options shown to be effective. Future controlled studies are needed to prove this efficacy.

Vagus nerve stimulation

Vagus nerve stimulation (VNS) involves the implantation of an electrode that produces intermittent electrical stimulation into the left cervical vagus nerve. Case reports have found benefit from VNS in the cessation of seizures in patients with refractory status epilepticus and NORSE. There is limited evidence of its use in FIRES.

Long term effects

The prognosis of FIRES is poor. The outcome varies with the length of the acute phase with mortality rates up to 30%. Of those patients who survive there is 66-100% chance that they will have long term cognitive impairment due to damage of the frontal and temporal lobe functions. Survivors with a normal cognitive function will present with a spectrum of learning disabilities, behavioural disorders, memory issues and sensory changes. There is a high risk of recurrent status epilepticus. Unfortunately, only a small proportion of survivors will have no neurologic sequelae.

The patient required a lengthy PICU admission where they were managed with a burst suppression coma, ketogenic diet, high dose steroids and intravenous immunoglobulin.

They were later diagnosed with Febrile-Infection Related Epilepsy Syndrome after extensive investigations, including a normal brain MRI and a lumbar puncture which showed a mildly elevated white cell count but was otherwise unremarkable.

They are currently seizure free on a combination of oral phenobarbitone, perampanel and levetiracetam but have some cognitive sequelae.


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The 49th Bubble Wrap

Cite this article as:
Currie, V. The 49th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: The associations between initial serum pH value and outcomes of paediatric out-of-hospital cardiac arrest

Okada A, Okada Y, Kandori K, Nakajima S, Okada N, Matsuyama T, Kitamura T, Hiromichi N, Iiduka R. Associations between initial serum pH value and outcomes of pediatric out-of-hospital cardiac arrest. Am J Emerg Med. 2021 Feb;40:89-95. doi: 10.1016/j.ajem.2020.12.032. Epub 2020 Dec 17. PMID: 33360395.

What’s it about? 

This paper reviewed the association between initial pH, obtained via intra-arrest VBG, and patient outcomes to evaluate if pH can be used to prognosticate in paediatric out of hospital cardiac arrest.

The authors reviewed a large, multicentre, prospective register of out-of-hospital cardiac arrests in 87 hospitals in Japan. They included paediatric out-of-hospital cardiac arrest patients younger than 16 between June 2014- December 2017 (458 patients included in the analysis – however over 35,000 listed in the registry). The primary outcome was 1-month survival. They divided the patients into four groups (based on initial pH on blood gas) and compared this to the patient’s ultimate outcome.

Interestingly, the median age of the patients was one year of age. Just over 6 in 10 of the patients were male. In 7 out of 10 patients, the first monitored rhythm was asystole. Cardiogenic arrest occurred in 4 out of 10 patients.

Mortality, and survival with good neurologic function, were lookd for. The overall survival rate at one month was just over 1 in 10 patients. In the group with pH > 6.82 survival rate was around 4 in 10 patients. However, with a pH< 6.47, thesurvival rate was 1 in 100 patients.

Of particular interest, in the entire study population of 458 patients, there were no patients who survived with good neurological function with a pH <6.8.

Why does it matter? 

Deciding when to stop resuscitation in a paediatric cardiac arrest can be difficult. Guidance is sparse and there are no universally recommended measures to help providers decide when to stop resuscitative measures. This is a stark contrast to adult cardiac arrest management where there are many validated termination of resuscitation rules based on measurements such as end-tidal CO2 s.

This is the first study to assess the association between pH and prognosis in paediatric out-of-hospital cardiac arrest. It presents robust evidence to support an objective, easily obtained measure that can be used to assist decision making around the termination of resuscitation. Important exclusions in this study were patients where resus was not attempted at a hospital, unknown age, traumatic or arrest secondary to hanging and those with no pre-hospital data.

This is an exciting paper providing guidance in an area sorely lacking any previous data. It gives providers a valuable tool that can substantially assist when making a difficult decision.

Clinically Relevant Bottom Line:

In out of hospital paediatric cardiac arrest, according to this study, no patients with a pH <6.8 survived with a neurologically favourable outcome. Survival in general was significantly lower in patients with an initial pH <6.8.

Reviewed by: Sean Croughan

Article 2: Should we be using focused cardiac ultrasound to guide therapy in children with sepsis?

Arnoldi s, Glau CL et al. integrating focused cardiac ultrasound into Pediatric septic shock assessment. Pediatr Crit Care Med. 2021 mar 1;22(3):262-274

What’s it about? 

This paper looks at whether the integration of FCU (focused cardiac ultrasound) in clinical assessment of children with sepsis would alter clinician’s evaluation of their haemodynamic characteristics.

The authors conducted a retrospective, observational study from January 2014 – December 2016 in a large PICU in America. They reviewed 74 PICU patients who received FCU within 72 hours of sepsis pathway initiation. Assessment by clinicians prior to FCU was compared to assessment after FCU in 46 patients, to determine if there was a difference in the haemodynamic characterisation of patients.

They demonstrated that incorporation of FCU changed the clinician characterisation of haemodynamic assessment made prior to FCU in more than 2 out of 3 of cases. The most common new finding identified post-FCU was myocardial dysfunction in (7 out of 22) cases. The most commonly ruled-out physiologies by clinician after FCU performance were obstructive physiology (5 in 8 cases), fluid responsiveness (13 in 26 cases).

Why does it matter? 

Sepsis in children continues to be one of the leading causes of mortality and morbidity worldwide.  Most children who die of sepsis suffer from refractory shock and/or multiple organ dysfunction within the initial 48 -72 hours of treatment, thus demonstrating the need for early and targeted interventions.

The previous method of classifying patients as having either ‘warm shock’ or ‘cold shock’ to guide therapy has been demonstrated to have poor correlation with cardiac function and systemic vascular resistance, and has not led to improved outcomes. It is now recommended that more advanced techniques such as focused cardiac ultrasound (FCU) be used alongside clinical assessment to identify haemodynamic status and direct therapy.  This is already widely the case in adult practice and algorithms have been created for its integration into patient management. 

Although this is a small study, it makes us think about the use of cardiac ultrasound alongside clinical assessment of children with sepsis in order to understand the haemodynamic characterisation of these patients.

This may be particularly useful in relation to fluid responsiveness, as half of the children who were thought to be fluid responsive pre-FCU, were found not to be after a FCU was performed. We know that children with sepsis often receive significantly more fluid per kilogram than adults which is associated with worse outcomes.

Clinically Relevant Bottom Line:

FCU, when incorporated into shock assessment, has the potential to identify myocardial dysfunction earlier and could result in reduced fluid administration as well as more targeted therapy based on haemodynamic status. However, further work is needed to determine how this can be used within paediatric practice.

Reviewed by: Laura Duthie

Article 3: Don’t forget the planet

Di Cicco, M.E., Ferrante, G., Amato, D., Capizzi, A., De Pieri, C., Ferraro, V.A., Furno, M., Tranchino, V., La Grutta, S. (2020) Climate Change and Childhood Respiratory Health: A Call to Action for Paediatricians. Int J Environ Res Public Health, Vol 24;17(15):5344

What’s it all about?

The authors conducted a systematic review looking at papers which examined the connection between respiratory illnesses in children aged 0 – 18 years. Keywords used separately and in combination were (allergic rhinitis, rhinitis, asthma, bronchitis, pneumonia, infections) and key environmental phrases (climate change, pollution, particulate matter, ozone, nitrogen dioxide, allergen, pollen). There was no limitation on the date of paper or country of origin.

Whilst much of the research at this stage is not completely conclusive key points from the review include:

  • Several studies from different countries found a connection between the increased prevalence of rhinitis and asthma, as well as the frequency of symptoms with increased global temperatures, which has changed many plant species’ lifecycles and led to longer pollen seasons
  • Positive correlations between the incidence of pneumonia and other acute respiratory tract infections in the context of increased extreme weather events such as heatwaves, fires and floods
  • Positive associations between the increased relative humidity and increased activity of respiratory viruses such as respiratory syncytial virus

Why does it matter?

Climate change is the long-term shift in weather conditions (temperature, humidity, winds and extreme weather events) and is often talked about in regards to protecting our wildlife or preventing further damage to our oceans and forests. It is less talked about when considering the impact on our own health. A child born in 2020 will live in a world that is more than 4 degrees warmer than the pre-industrial average, and subsequently will be at greater risk of a variety of acute illnesses as well as long term health consequences.

The Bottom Line:

More research needs to be done to accurately define the burden of climate change on our health. In the interim, we can all be environmental champions, from making changes in our own lives to reduce our carbon footprint as well as educating and influencing our colleagues and patients to do the same.

 …And for those with spare time; conducting research into the direct effects of climate change on specific health conditions along with contributing to government policies to create change at a higher level and reducing the carbon footprint of our healthcare systems are excellent places to start! 

Reviewed by: Tina Abi Abdallah

Article 4: Domo arigato, Mr Roboto

Littler BKM, Alessa T, Dimitri P, et al Reducing negative emotions in children using social robots: systematic reviewArchives of Disease in Childhood  Published Online First: 08 March 2021. doi: 10.1136/archdischild-2020-320721

What’s it about?

The paper looks at a number of studies that have used social robots in paediatric outpatient settings to interact and provide multi-sensory experiences to patients. The author postulates that using social robots provides better interaction and distraction for children, thus reducing anxiety and distress during the visit.

This systematic review managed to find ten studies that used social robots ranging from humanoid-based robots to ones simulating toy bears, dinosaurs and seals. The robots interact verbally and physically, and can respond to patient cues and tactile stimulation. They were used before or during the intervention. The studies included randomised controlled trials, exploratory trials, pilot and an observational study, with patient numbers varying from 2 to 73 (320 in total).

Why does it matter?

For lots of children a visit to the hospital can be a stressful and anxiety inducing event. There has been research to suggest that social robots have a positive impact on supporting adults with dementia and in children with autism they have been a useful tool in conducting therapy. The outcomes of this study were measured by observation, and by recording levels of distress, anxiety, pain and emotion using a variety of behavioural questionnaires. Overall, the feedback from the studies showed positive engagement from patients with their robots, reducing negative emotions, distress and pain.

The bottom line

There is promising data to suggest that robots may improve the experience of children in the healthcare environment. However, the evidence is weak due to the nature of the studies, lack of uniformity in the measurements, and low patient numbers. More research is needed on this topic to be able to really change practice but this sci-fi intervention may well become a reality in the not so distant future.

Reviewed by: Laura Riddick

Article 5: Children visiting the Paediatric emergency department during Ramadan

Sawaya,R., Wakil, C., et al (2021) Pediatric emergency department utilisation during Ramadan: a retrospective cross- sectional study. Archives of Disease in Childhood 2021;106:272-275.

What’s it about?

 This study looks to investigate the impact of Ramadan on patient characteristics, diagnoses and metrics in the paediatric emergency department (PED). There is limited data on how Ramadan impacts paediatric ED’s.

Why does it matter?

The authors looked at patient and illness characteristics as well as PED metrics including peak patient load, presentation timings, length of stay, time taken to order tests, receive samples and reporting of results to see how these were affected during the months of Ramadan and those before and after. 

This is a retrospective cross-sectional study on paediatric patients from 0 – 18 years presenting to a PED tertiary centre in Lebanon. Data was collected from all PED visits with any complaint at any time during Ramadan and the months (30days) before and after in 2016 and 2017. A bivariate analysis was performed between the Ramadan and non-Ramadan groups. The main outcomes were illness severity, chief complaints, final diagnoses, PED metrics including peak patient load, presentation timings, length of stay, and PED efficiency metrics such as time to order tests, times to samples being received and reported. 5711 patients were included and 1672 of these presented during Ramadan. There was no significant difference between age, gender or illness severity between the Ramadan or non-Ramadan group. This study found a significant difference in the number of GI complaints during Ramadan (39%) compared with the non-Ramadan group (35%). 

Trauma related complaints increased during Ramadan (3 in 100) vs (2 in 100) in non-Ramadan periods. Especially during the non-fasted periods of Ramadan (4 in 100) vs (2 in 100) during the fasted period of Ramadan. The number of daily visits during Ramadan (28.3) was reduced compared with non-Ramadan attendances (31.5). The Ramadan group did not have to wait longer for tests to be ordered or to have samples collected. 

This study was a single centre- and the charts that were reviewed did not have information on the patients individual fasting status. This would be interesting to see if the patient’s individual status affected diagnosis. The team used months immediately before and after Ramadan to reduce the confounding effects of seasonal bias.

Clinically Relevant Bottom Line:

This study revealed that there were some changes in GI and trauma presentations during the Ramadan period. There was also a reduction in cases presenting in this centre- this could help to influence staffing during this time if the patient population reflected that of the population in this study.

Reviewed by: Vicki Currie

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to.

All articles reviewed and edited by Vicki Currie

Following bronchiolitis guidelines

Cite this article as:
Ben Lawton. Following bronchiolitis guidelines, Don't Forget the Bubbles, 2021. Available at:

In 2016 our friends at PREDICT produced a robust, evidence-based guideline for the management of bronchiolitis. They assembled a diverse team of experts, decided on the key questions we ask ourselves when managing bronchy babies and then did a deep dive of the literature to provide answers to those questions. You can read the guideline here, or the DFTB summary here but the key messages will be familiar to regular readers of DFTB, namely the list of things that do not help babies under 12 months with bronchiolitis includes salbutamol, chest x-ray, antibiotics, nebulised adrenaline and steroids. In the real world, however, these ineffective treatments continue to be used – so what can we do about that? 

The authors of a new PREDICT study released in JAMA Pediatrics on 12 April 2021 sought to demonstrate whether a group of interventions they developed using theories of behaviour change would be effective in reducing the number of ineffective interventions given to bronchiolitic babies. 

Haskell L, Tavender EJ, Wilson CL, et al. Effectiveness of Targeted Interventions on Treatment of Infants With Bronchiolitis: A Randomized Clinical Trial. JAMA Pediatr. Published online April 12, 2021. doi:10.1001/jamapediatrics.2021.0295

Who did they study? 

This was an international multicentre cluster randomised controlled trial (RCT) involving 26 hospitals in Australia and New Zealand. It is described as a “cluster” RCT as randomisation was by hospital rather than by patient. The randomisation was a bit complicated. It was stratified to make sure secondary and tertiary hospitals from each country were represented in each group. Baseline data was collected from 8003 patient records from the three bronchiolitis seasons prior to the start of the intervention period. A further 3727 charts analysed from the season in which the intervention took place. The data from the three prior seasons were used to ensure baseline similarity between groups and to establish patterns of practice change that were already occurring. In short, this was a big study that ensured representation of both specialist children’s hospitals and mixed general hospitals. 

What did they do? 

Hospitals randomised to the intervention group received a package of interventions based on the Theoretical Domains Framework (TDF), developed following an earlier qualitative study that investigated why we do what we do when managing bronchiolitis infants. The TDF is one of the most commonly used frameworks in implementation science and is considered particularly good at identifying interventions to address barriers and facilitators that influence behaviour change. The package included:

  • Appointing clinical leads from medical and nursing streams in both emergency departments and inpatient paediatric units.
  • The study team meeting with those clinical leads to explore the local practice and any anticipated barriers to change.
  • A one day train-the trainer workshop to ensure clinical leads were comfortable using the educational materials provided to train local staff.
  • An education pack including a PowerPoint with scripted messages specifically designed to promote change, a clinician training video, evidence fact sheets, promotional materials and parent/caregiver information sheets.
  • Monthly audits of the first 20 bronchiolitis patients with the results shared and compared to the best performing hospital.

What about the control group?

Hospitals randomised to the control group were just left to their own devices for the year of the intervention period. They had access to the guidelines and were welcome to share that information as they would in any other circumstances. The intervention package was made available to control hospitals in the season following the study period. 

What did they show? 

The primary outcome was the proportion of infants who complied with all five of the Australasian Bronchiolitis Guideline recommendations known to have no benefit (chest x-ray, salbutamol, steroids, adrenaline, antibiotics). There was an 85.1% compliance rate in the intervention group compared to a 73% compliance rate in the control group. In other words, in hospitals that were part of the intervention group, an average of 85.1% of kids received care in line with the guidelines, compared to only 73% receiving guideline compliant care in control hospitals. This was a significant difference.

Secondary outcomes showed improvement was consistent in both the ED and inpatient phases of care. Unsurprisingly, there was no difference in hospital length of stay or admission rates to ICU. 

The DFTB verdict

On the surface this is a robust, well designed study showing that if we put some thought and some resources into supporting our colleagues in doing the right thing then babies with bronchiolitis will get better care in our hospitals. They won’t leave hospital any quicker and they won’t have a lesser chance of needing ICU but they will be exposed to fewer interventions that will not do them any good and may do them some harm. Dig a little deeper though and the big messages in this paper go way beyond the management of bronchiolitis. The implementation science based interventions used in this study can be adapted to anything, and though they have been shown to be effective in getting us to do the right thing here, we haven’t shown that their efficiency has been optimised yet. Great breakthroughs in novel medical science are exciting but there are huge improvements in care to be gained through getting the best care that we do know about to every patient every time. This paper should serve as fuel for the fires lighting implementation science’s journey from the shadows to the centre stage of improvement in clinical care. 

From the authors

The study’s senior author, Prof Stuart Dalziel gave DFTB the following take: 

“The key finding is that we can do better. By using targeted interventions, based on established behaviour change theories and developed from work looking at why clinicians manage patients with bronchiolitis the way they do, we can improve the management of patients with bronchiolitis such that it is more consistent with evidence based guidelines.

In the field of implementation science (IS) and knowledge translation (KT) a 14% improvement in care is a large change.

Changing clinician behaviour is complicated, this is especially so for de-implementation of medical interventions. Many factors influence clinician behaviour and it is thus perhaps naïve to think that a single intervention can cause a significant change to behaviour. For a number of decades the majority of clinical guidelines for bronchiolitis have emphasised that chest x-ray, antibiotics, epinephrine, corticosteroids and salbutamol are low-value care and not evidence based. Yet despite this consistent messaging from guidelines the use of these interventions has remained considerably higher than what it should be. While the interventions delivered in our study were not unique (site based clinical leads, stake holder meetings, train-the-trainer workshops, targeted clinical education, educational material, and audit and feedback) they were specifically developed, using an established framework for behavioural change, following a qualitative study that determined why clinicians managed bronchiolitis they way they do. This prior study, addressing the barriers and enablers to evidence based care, and the subsequent step wise approach to developing the targeted interventions that we used was critical in achieving the change in clinician behaviour observed in our randomised controlled trial”.

The study’s lead author, Libby Haskell, stated:

“Bronchiolitis is the most common reason for children less than one year of age to be admitted to hospital. We can improve the care of these infants, such that they are receiving less low-value care. In order to de-implement low-value care we need to first understand barriers and enablers of care, and then develop targeted interventions, built on robust behavioural change models, to address these. This approach can be used to improve care for other high volume conditions where we see considerable clinical variation in care and with clearly established clinical guidelines on appropriate management.”

Let us know what you think in the comments below 

Forget the Bubbles? Never

Cite this article as:
Neelakshi Ghosh. Forget the Bubbles? Never, Don't Forget the Bubbles, 2021. Available at:

How did we feel when we were told to ‘Forget the bubbles’ and infection control policies binned those slippery soapy solutions and golden rings of plastic? COVID-19 led to innovations in the workplace and we changed practice almost overnight to ensure the safest care was being delivered to our patients. Perhaps the team that demonstrated this to the fullest are the play specialists.

A chat with Maxine Ovens, Play Service Manager at the Royal Brompton Hospital showcased stories of innovation coupled with cycles of constant evolution as the team adjusted to a different way of life. Before COVID-19, Maxine had been the playroom boss for 16 years. She startied with a team of just 2 and is now running a 7-day service with 9 team members.

They have been working on the ward, and in children’s outpatients, supporting not just children and young people, but also their families, ‘to make their hospital experience positive and productive. During the initial surge of the pandemic, PICU beds at the Royal Brompton were allotted to adult ITU services. The playroom on the children’s ward became the storeroom for paediatric equipment as the original storeroom now fell in the ‘red zone’. Play had to be put back on the shelf and staff redeployed. Maxine’s aim was to ‘stay as a team and not be broken up during these difficult times’. The play specialists volunteered at the donning and doffing station at the PICU and actively engaged in boosting staff morale.

Behind the scenes, Maxine continued to push for restoring the playroom services. Working closely with the Infection Control team, she drafted new ‘playroom guidelines’ keeping with national policies and social distancing norms. With relatively fewer admissions, Maxine could arrange for one-to-one play sessions for everyone. These were time-tabled on a daily basis by the play team. The main focus was on the daily cleaning schedule with particular members allotted to be in-charge. All surfaces and toys were cleaned with Chloro-clean solution at the beginning of the day and in between play sessions. All members maintained the daily cleaning logs strictly, signing out for toys used in each session and putting them back after a thorough clean. ‘This was not just to demonstrate to Infection Control that the playroom is hazard-free, but also to reassure parents and carers that it is safe for the children.’ The staff were commended by parents for the clean environment of the playroom. One parent mentioned that ‘such varied activities were not possible even at home with all the recommended hygiene measures’.  And Maxine would quietly remind us of the marathon clean up the team had to do when a young patient decided to start a bit of ‘slime fight’ during a slime time session. Children on respiratory support had their playroom time towards the end of the day. Aerosol generating procedures required the playroom to be closed for an hour after.

Toys and playthings have to be compliant with the new cleaning regime. Staff members laminated books for bed-time stories before cleaning and returning them every day. The Brompton Fountain Charity donated single-use activity packs and colouring sets. Cardboard boxes for the board games were discarded, and playing cards were laminated and stored in plastic containers. All effort was made to ensure traditional play tools were not missed in this ‘new normal’. And, of course, plastic bubble machines appeared on the shelves to replace the old stand by.

Play is about innovation. Just as children grow and learn to explore their environment through play, Maxine and her team invented Covid-safe ‘things to do’. Group play was put on hold. The team used this opportunity to engage more children in one-to-one sessions, exploring their unique ideas. When admission rates started picking up, ‘bay bubbles’ were created so that two children from the same bay could be in the playroom together, using time and space more effectively. Children were engaged in activities like biscuit icing so that they could keep their creations for themselves rather than handing over the products of their labour for cleaning. Over the Christmas period, children made decorations which were then laminated by the team and hung on the ward.


But to Maxine, the biggest challenge was the PPE. During bedside sessions, the team had to adhere to guidelines which made play a little more clinical than they would like. Visors were donned with cut-out tiaras and Mickey Mouse ears. Badges were pinned to uniforms bearing the photo of team members. The smile behind the mask had to be seen. There were picture books of health care staff in PPE explaining to children the new ‘superhero costumes’. The play team helped prepare the young patients for a procedure before junior doctors walked in donned.

So, what does hospital play look like now? Her team has always been creative with new and innovative ideas catering to the varied interests and abilities of her young patients. They have been constantly evolving as a team and will continue to do so.

Take every opportunity to be creative and be flexible. Play doesn’t need to stop. Fight for your service and work closely with the teams that can support you. After all, we all need a little play in our lives.’

Maxine Ovens

The 48th Bubble Wrap

Cite this article as:
Currie, V. The 48th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: An update on PIMS-TS/MIST-C

Flood J, Shingleton J, Bennett E, Walker B, Amin-Chowdhury Z, Oligbu G, Avis J, Lynn RM, Davis P, Bharucha T, Pain CE. Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS): Prospective, national surveillance, United Kingdom and Ireland, 2020. The Lancet Regional Health-Europe. 2021 Apr 1;3:100075.

What’s it about? 

During the first breakout of PIMS-TS, Public Health England (PHE) and the British paediatric surveillance unit (BPSU) requested reports of PIMS-TS, Toxic shock syndrome (TSS) and Kawasaki Disease (KD) to be submitted for prospective national surveillance. This study looks at patients under the age of 16 who presented with symptoms between 1st March and 15th June 2020. The symptoms for the diagnosis of PIMS-TS was set out as per RCPCH guidance (fever >38, CRP>100, no infection proven and evidence of one at least system dysfunction) along with strict criteria for KD and TSS. From these reports, patients were excluded if they did not meet any PIMS-TS resulting in 268 cases of PIMS-TS meeting diagnostic criteria.

Why does it matter? 

Children have made up a small proportion of direct clinical burden due to COVID-19. However, cases all over the world began to appear of PIMS-TS associated with SARS-CoV-2 infection and more information was needed to be able to map this disease process and use clinical data to explain clinical characteristics of PIMS-TS and the epidemiology between these overlapping clinical conditions.

The results of the study showed the median age to be 8 years with PIMS TS/KD subgroup younger (5 years) and PIMS TS/TSS older (8 years) than PIMS TS only cases (7years). 60% of the population were male and patients from the BAME community seem to be disproportionately affected, especially within London.

Patients who exhibited PIMS-TS with features of TSS as well seemed to fair worse with a larger number of interventions, longer hospital stay and severity of illness. 35 cases were felt to be clinically in keeping with PIMS-TS despite not meeting the CRP criteria. Parental occupation was reported in just under half of the cases and more than 2 out of 3 were reported as healthcare workers. Just over 1 in 3 of the children had evidence of current or previous SARS-CoV-2 infection.

Clinically Relevant Bottom Line:

Presentations of PIMS-TS are strongly linked with SARS-CoV-2 infection, and those with features similar to toxic shock syndrome tend to be more unwell. Children in London, and in the BAME population, seem to be disproportionately represented, with the most having severe presentations. The epidemiological links are similar to that of other countries.

Reviewed by: Laura Riddick

Article 2: Screening adolescents for the risk of suicide attempts

Pediatric Emergency Care Applied Research Network (PECARN) King CA, Brent D, Grupp-Phelan J, et al., (2021) Prospective Development and Validation of the Computerized Adaptive Screen for Suicidal Youth. JAMA Psychiatry. 2021 Feb 3:e204576

What’s it about? 

A prospective 2-part study with data collection being undertaken at different ED’s in the United States, which are part of the PECARN network. Introduction of computerised adaptive testing (CAT) which put simply is a tool that takes individuals responses to questions and determines their standing on the measured trait e.g., risk of suicide attempt. This offers the possibility of a more individualised, accurate screening tool.

Two studies ran independently:

Study 1(2015-2016): used CAT to develop a screening tool (computerised adaptive screen for suicidal youth CASSY) that targets items to the individuals personal risk profiles to provide a continuous risk score for the likelihood of suicide attempt (SA) within 3 months.

Study 2 (2017-2018): Prospectively validated CASSY.

In Study 1, adolescents aged 12 – 17 years who presented to ED were offered to complete the Ask Suicide Questions (ASQ) and Columbia Suicide Severity Rating Scale (C-CSSR). Depending on these responses the participants were stratified into low medium/ high risk for suicide attempt. Then a random selection of these were assigned to follow up which was done by interviewers who were blinded to the baseline data were responsible for the 3-month telephone follow up which assessed the number of suicide attempts made by the patient during this time.

CASSY was then developed using questions from these screening tools (questions which were identified to have high suicide attempt predictive value) and was cross validated in Study 1, before it’s use in Study 2. Subsequently, adolescents aged 12 – 17 years who presented to ED were offered to complete CASSY.

The authors have used a multivariate logistic regression model to predict suicide attempt during the 3 months follow up. Based on this, the Receiver Operating Characteristic (ROC) curve demonstrates a sensitivity of 82.4% for predicting suicide attempts using the CASSY score, at a specificity of 80% with an area under the curve (AUC) of 0.87 [95% CI, 0.85-0.89].

For a reminder on these type of stats take a look at this DFTB post.

Some important exclusions in this study population were being a ward of the state (e.g. adolescent in foster care) and non-English speaking participants which from previous studies are shown to be important risk factors for altered mental health.

Why does it matter? 

Data from Australia (and around the world) show that our adolescent population are suffering from increasing levels of mental health issues such as anxiety and depression. With those illnesses often comes suicidal ideation, and when these patients reach crisis point, they present to our emergency departments (ED). One of the biggest challenges to all suicidal risk screening is the accurate identification of young people at risk in a setting that efficiency is required. Existing screening tools such as (ASQ) have shown moderate sensitivity to predicting suicide risk, meaning some individuals at risk were not identified.

Clinically Relevant Bottom Line:

This study shows the CASSY tool has a good sensitivity (ability to pick up) those at risk of suicide attempt. Early and accurate recognition of mental health illnesses and suicidal ideation in primary health care settings and emergency departments is an essential first step in managing these issues.

Reviewed by: Tina Abi Abdallah

Article 3: The use of minimally invasive surfactant therapy

Roberts CT, Halibullah I, Bhatia R, Green EA, Kamlin CO, Davis PG, Manley BJ. Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units. The Journal of Pediatrics. 2021 Feb 1;229:141-6.

What’s it all about?

This 18-month prospective audit collected data on patient demographics and clinical outcomes following the introduction of minimally invasive surfactant therapy (MIST) in two neonatal intensive care units (NICUs) in Australia. Infants were eligible for MIST if they received CPAP support with clinical or radiological diagnosis of respiratory distress syndrome (RDS), and were excluded if they had major congenital anomalies, circulatory compromise, recent apnoeas or a diagnosis other than RDS.

Why does it matter?

MIST is a less invasive method of administering exogenous surfactant for the treatment of RDS in premature infants compared to previous surfactant administration by endotracheal tube. Previous meta analysis highlighted that MIST is associated with reduced need for mechanical ventilation, and adverse events such as bronchopulmonary dysplasia and death compared to endotracheal intubation. However, it is difficult to make clear conclusions about the efficacy of MIST versus endotracheal tubing for surfactant administration, as a range of other factors can affect success rate. These include gestational age, surfactant dose and timing of procedure (as prophylactic after birth versus an early rescue approach within the first 24 hours of life. As MIST and endotracheal intubation require laryngoscopy, the authors stress the continued need to adequately train junior staff and suggest the use of routine video laryngoscopy regularly to allow for second operator confirmation and potentially increased rates of success.

135 MIST procedures were performed. The median gestation was 30 weeks, and median birth weight being 1439 grams. All infants received supplementary oxygen before MIST. The most common adverse event was peripheral oxygen desaturation to <80% which occurred in 3 out of 4 of MIST procedures. Other events included bradycardia <100 beats per minute (13 out of 100) and the need for positive pressure ventilation (1 in 10). Positively, over 2/3rds of infants treated with MIST did not require further intubation and mechanical ventilation and senior clinicians had higher rates of procedural success. Surfactant administration was successful in all but one MIST procedure due to patient apnoea requiring intubation.

The Bottom Line:

The authors determined that MIST can be successfully adopted into clinical practice in such settings where staff have limited prior experience. Rates of adverse events, mentioned above, were comparable to results from previous randomized trials. Over 2/3rd of infants in this study with MIST did not require further intubation and ventilation. 

Reviewed by: Ivy Jiang

Article 4: Can we perform phototherapy at home?

Pettersson M, Eriksson M, Albinsson E, Ohlin A. Home phototherapy for hyperbilirubinemia in term neonates—an unblinded multicentre randomized controlled trial. European Journal of Pediatrics. 2021 Jan 19:1-8.

What’s it about?

Within the first week of life, 60% of term babies and 80% of pre-term babies will have some degree of jaundice. This study looked at well term babies and if delivering phototherapy at home, with daily hospital reviews, would be an acceptable alternative to inpatient phototherapy.

This was an unblinded, randomised control trial of 147 jaundiced neonates across 6 hospitals in Sweden. To be included babies had to be well, >48 hours old, have a gestational age >36+0 and have a raised serum bilirubin (SBR). Parents also had to be capable to perform phototherapy at home and agree to return daily for review and blood tests. Babies were excluded if they had a high bilirubin result (>400µumol/L), weight loss of >10% of birth weight, any ongoing infection or illness, or if there was blood group incompatibility.

Babies were randomly selected to receive home phototherapy (78) vs hospital phototherapy (69). Babies in both groups were reviewed daily in the hospital, and a daily SBR and weight. Home treatment was done by Bilisoft (Bilibed) that was provided with eye protection and clear instructions. This study could not find any statistically significant differences that suggested that either therapy was superior to the other. Only 3 in 78 babies of the home phototherapy neonate were converted to hospital treatment. No one across either group had SBR’s high enough to require IVIG or blood exchange. There was no statistically significant difference regarding the duration of phototherapy, time until discharge, amount of blood tests, weight loss or adverse events.

Why does it matter?

Jaundice is one of the most common reasons for prolonged postnatal hospitalisation and readmissions in the postnatal period. Hospital management of jaundice can negatively impact bonding and attachment, it can be inconvenient for families and is associated with a significant cost to the healthcare system.

The bottom line

This study shows that with daily reviews and monitoring, home phototherapy could be an effective and safe alternative to hospital phototherapy for otherwise healthy, term, neonates. When determining appropriateness for home phototherapy bilirubin levels, geographic location and ability to commute, parental anxiety and the capability of parents/carers must all be considered.

Reviewed by: Phoebe Campbell

Article 5: How is procedural sedation performed in Europe?

Sahyoun C, Cantais A, Gervaix A, Bressan S, Löllgen R, Krauss B. Pediatric procedural sedation and analgesia in the emergency department: surveying the current European practice. European journal of pediatrics. 2021 Jan 28:1-5.

What’s it about?


This cross-sectional study of european paediatric procedural sedation and analgesia (PSA) was endorsed by the Research in European Paediatric Emergency Medicine (REPEM) network, with data collection between November 2019 and March 2020. 

The study aimed to describe PSA practice across europe, perform a needs assessment-like analysis and also identify barriers to PSA implementation.

Online questionnaires were distributed to a target number of either 10 or 5 emergency departments within each country (depending on their population size), via country specific lead research coordinators. The survey included a clinical case scenario with subsequent questions covering 8 key themes. These ranged from the management of a patient requiring PSA, protocols and safety and barriers limiting PSA implementation. The questionnaire was revised several times following input from each country lead, accounting for variations in relevance, language, and grammar between each country, until a consensus was achieved containing 30 questions. Questionnaires were completed by a senior clinician at each site with 171 hospitals contributing data from 19 countries. The UK and Ireland were not included due to a similar project running in these locations simultaneously.

Midazolam (100%) and Ketamine (91%) were the most available PSA medications, followed by propofol (67%), nitrous oxide (56%) and intranasal fentanyl (47%). 8 in 10 of sites reported sedation being performed by general paediatricians. However just over 1 in 3 of sites stated all staff performing PSA were paediatric advanced life support certified and only 1 in 2 required PSA specific course completion. Safety and monitoring guidelines for PSA were present in most  sites (7out of 10) and 1 in 2 had pre-procedural checklists in place, with these sites most likely to perform IV sedation. Capnography was present in just under half of the sites.

Barriers to PSA implementations included lack of physical space (1 in 2 of sites) and shortages of both nurses and clinicians (both more than 2/3rds of sites). Interestingly half of the sites reported nurse-led triage protocols in use for paracetamol and ibuprofen administration, with these sites experiencing the highest number of patient visits per year.

Why does it matter?

PSA is used widely across europe, however there is a large variation in the standard medications and safety measures in use.

Clinically Relevant Bottom Line:

 This study highlights the need for sharing of best-practice amongst sites with the potential for future trials to determine optimal staff training, medication use, procedural checklists and guidelines, nurse-led triage and staff and physical space allocation for PSA. The network generated as a consequence of this study could be used to facilitate such work in the future.

Reviewed by: Joshua Tulley

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to.

All articles reviewed and edited by Vicki Currie

UTI whizzdom – the next steps

Cite this article as:
Felicity Beal. UTI whizzdom – the next steps, Don't Forget the Bubbles, 2021. Available at:

A 4-month-old baby presents with a temperature and urine microscopy suggestive of a urinary tract infection. He appears well and your plan is to discharge home on an oral antibiotic, whilst awaiting culture results. His mother asks you, “Does he need any other tests?”

Why does it matter?

Urinary tract infections (UTIs) are very common in children. Studies suggest that 6-8% of febrile, unwell children presenting to their GP have a UTI. Therefore it is important to carefully select which of these children need further investigations in order to identify those with underlying renal tract problems. It is estimated that up to 15% of children with a first UTI have evidence of scarring on follow up scans. If they are missed, these children may go on to develop hypertension and possible chronic kidney disease later in life.

Which children are more likely to get a UTI?

Before the age of 6 months, UTIs are more prevalent in boys. This is partly due to the increased chance of structural abnormalities within the urinary tract. Uncircumcised boys are particularly at risk, as bacteria on the foreskin are a reservoir for infection.

However, after 6 months of age, girls are at increased risk due to their shorter urethra and its proximity to the anus. This risk is increased again in females when they become sexually active.

Risk factors for UTIs

There are several other risk factors that increase the risk of developing a urinary tract infection. The main risk factor is something we see and manage on a daily basis, another really common presentation…constipation! If you haven’t yet read Chris Dadnam’s Conversations about Constipation post, now would be a great time to have a refresher as these two conditions go hand in hand.

As the colon and rectum fill with stool, the mass effect results in incomplete bladder emptying. This results in stasis of urine. Always ask about, and treat, constipation… If this is left unmanaged UTIs will continue to be a problem. 

After taking a good constipation history and examining the abdomen, it’s important you assess the spine looking for dimples, swellings, birthmarks or hairy patch lesions that can be associated with a neuropathic bladder. This should be followed by a lower limb neurological assessment. I think of this as running a bath after a hard day at work. You are unable to fully empty the tub afterwards but continue to add more bathwater to the tub every time… this will encourage infection to harbour. Recurrent UTIs may be the main presenting complaint in young children and should always prompt a review of the spine.

Foreign bodies such as intermittent or indwelling catheters also pose a risk. But it is essential to remember the last risk factor, not visible to the eye … namely urinary reflux.

Is this the same as vesico-ureteric reflux?

Yes. This is simply a term describing where, anatomically, the reflux occurs – from the bladder (vesico) to the ureters (ureteric). Urine flows back up from the bladder to the ureters causing a bidirectional flow of urine.

VUR can be primary, i.e. within a normal renal tract, or secondary, due to an abnormal renal tract – such as a neuropathic bladder. It is graded from 1 (mild) to 5 (severe.) Most mild to moderate reflux resolves by 5 years of age. However, surgery may be indicated if severe reflux is present, with worsening renal impairment or frequent pyelonephritis.

History and examination

As part of the history taking and examination, it is key to think about whether there could be underlying constipation, VUR or a neuropathic bladder. Asking about a family history of renal problems as well as considering antenatal renal scans is important to risk stratify for structural problems.

Ask about

  1. Constipation
  2. Urine flow
  3. Lower limb/back problems
  4. Antenatal renal abnormalities
  5. Family history of renal problems
  6. History of previous UTI/ fevers

Examine for

  1. Hypertension (complication)
  2. Poor growth
  3. Spine – for any spinal lesions
  4. Lower limb neurology
  5. Faecal masses
  6. Enlarged bladder / abdominal mass

What do we need to consider when further investigating UTIs?

NICE (the National Institute for Health and Care Excellence) ask the following three questions when considering a child’s risk of reflux and scarring:

How old is the child? Age is important. This may be a neonate or infant presenting with an infection as the first indicator of a possible underlying structural abnormality such as posterior urethral valves or VUR.

Is this an atypical UTI? 80% of paediatric UTIs are secondary to E.coli infection. An infection caused by an organism other than E.coli, or not responding within 48 hours of antibiotic therapy, is more unusual. Equally, if a child with a UTI looks unwell, has a palpable bladder, renal impairment or poor urine flow, your index of suspicion should be raised. These are uncharacteristic signs of a urinary tract infection.

Is this child having recurrent infections? Over 30% of children with UTIs will suffer from recurrent infections. Recurrent infections are defined as children who have either 2 or more upper UTIs (affecting the kidneys or ureters), 3 lower urinary tract infections (affecting the bladder or urethra) or 1 upper and 1 lower infection at any point up until the age of 16.

Investigations? Clear as M.U.D.

  • MCUG in 4 – 6 months
  • Ultrasound scan acutely or within 6 weeks
  • DMSA in 4 – 6 months


An MCUG is a Micturating Cystourethrogram, which assesses for urinary reflux or obstruction. A catheter is inserted and radio-opaque contrast is administered via the catheter to fill up the bladder. X-rays are then taken during urination to see if urine is refluxing back towards the kidney.

Normal MCUG. Case courtesy of Dr Aditya Shetty, Radiopaedia.org. From the case rID: 27065
MCUG illustrating marked dilatation of the prostatic portion of the urethra consistent with posterior urethral valves. Case courtesy of Dr Andrew Dixon, Radiopaedia.org. From the case rID: 10432


A DMSA scan is used to assess the function and location of the kidneys. An isotope that emits gamma rays is attached to ‘Dimercaptosuccinic acid’. This is administered via an intravenous cannula and is taken up by the kidneys a few hours later. If performed acutely it can show altered function consistent with pyelonephritis. In the UK, a DMSA scan is undertaken 4-6 months post-infection to assess for scarring.                       

A normal DMSA with equal isotope uptake in both kidneys. Case courtesy of Dr Yusra Sheikh, Radiopaedia.org. From the case rID: 69041

What does the guidance say?

In 2007, NICE published a guideline called “Urinary tract infection in the under 16s: diagnosis and management”, updated in 2018. When it comes to imaging, there are three main highlights.

1. Children under 6 months of age with a first typical UTI should have an ultrasound to assess for a structural cause. An MCUG is considered if this is abnormal.

2. All children with an atypical UTI, regardless of age, should have an ultrasound acutely. A DMSA is also performed if they are under 3 years of age to assess renal parenchyma. Children under 6 months are investigated more fully with an USS, DMSA and MCUG.

3. All recurrent UTIs require a DMSA scan within 4-6 months to assess for scarring.

This traditional approach for investigating children for reflux and scarring is safe yet adopts a different approach to imaging children with UTIs compared with other countries.

Controversial whizzarding….

The decision of who should be investigated further has caused great controversy. Different approaches are adopted around the world. This is due to conflicting evidence with clinicians balancing the risk of radiation, invasive imaging and cost with that of detecting children with an underlying congenital anomaly and preventing the development of chronic kidney disease.

There is conflicting data surrounding the risk factors for VUR in children with their first UTI. Ristola et al (2017) investigated risk factors for children with UTIs, finding the following 3 as the main risk factors for reflux: ultrasound abnormalities, recurrent infections and atypical infections. Interestingly, non-E. coli infections were the only statistically significant risk factor of infection recurrence.

Yılmaz et al (2016) were unable to identify risk factors associated with VUR, although did note that an abnormal renal scan at 6 months after the infection was closely related to the presence of VUR and recurrent UTIs.

In America, Canada, Poland and Italy, children up to 2 -3 years of age with their first UTI would be advised to have an ultrasound. The European Association of Urology advises every child presenting with a first UTI to be investigated with sonography. This is in comparison with the 6 month cut off advised by NICE, which is argued to be a more cost effective and risk stratified approach.

However, the American, Canadian and Italian guidelines do not investigate all children with recurrent UTIs as previously advised by the NICE guidance. Instead of all children with recurrent UTIs undergoing a DMSA scan, recent guidance suggests only performing a DMSA if there were concerns regarding an abnormal ultrasound or alternative diagnosis.

Therefore this makes me wonder, instead of investigating all children with recurrent UTIs, perhaps this decision should be made on an individual basis, using their ultrasound findings and considering risk factors.

How accurate are ultrasound scans in picking up VUR?

An ultrasound cannot exclude all cases of VUR as it is an observer-dependent investigation. Mahant et al (2002) reported low sensitivity of 40% and a specificity of 76% when diagnosing VUR, but the majority of these patients had lower grade reflux. There is now increasing awareness that low-grade reflux and mild scarring are unlikely to cause long term problems, therefore the argument presents itself: is there any benefit in investigating for them? Ultrasound scans are more likely to detect higher grade reflux and hence clinically significant cases, but further evidence is needed to support this approach.

The take homes

Some evidence suggests that children with ultrasound abnormalities or recurrent UTIS are at increased risk of complications from UTIs, regardless of their age or sex. There is no clear consensus on when to request a DMSA or MCUG but the latest evidence suggests that DMSA scans may not be necessary in all children with recurrent infections and a normal ultrasound scan. Clinicians should be aware of this existing controversy, weighing up the benefits and risks in order to make informed clinical decisions.


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Edlin RS, Shapiro DJ, Hersh AL, et al Antibiotic resistance patterns of outpatient pediatric urinary tract infections. J Urol2013;190:222–7.doi:10.1016/j.juro.2013.01.069

Kaufman J, Temple-Smith M, Sanci LUrinary tract infections in children: an overview of diagnosis and management BMJ Paediatrics Open 2019;3:e000487. doi: 10.1136/bmjpo-2019-000487

Mahant S, Friedman J, MacArthur C. Renal ultrasound findings and vesicoureteral reflux in children hospitalised with urinary tract infection. Arch Dis Child. 2002 Jun;86(6):419-20. doi: 10.1136/adc.86.6.419. PMID: 12023172; PMCID: PMC1762998.

Mori R, Lakhanpaul M, Verrier-Kones K. Diagnosis and management of urinary tract infection in children: summary of NICE guidance. Br Med J 2007; 335 (7616): 395–397.G

National Institute for Health and Care Excellence. Urinary tract infection in children: diagnosis, treatment and long-term management. Clinical guideline 54. London: NICE, 2007.

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O’Brien K, Edwards A, Hood K, et al Prevalence of urinary tract infection in acutely unwell children in general practice: a prospective study with systematic urine sampling. Br J Gen Pract2013;63:e156–64. doi:10.3399/bjgp13X663127

Okarska-Napierała M, Wasilewska A, Kuchar E Urinary tract infection in children: Diagnosis, treatment, imaging – Comparison of current guidelines. J Pediatr Urol2017;13:567–73.doi:10.1016/j.jpurol.2017.07.018

Ristola MT, Löyttyniemi E, Hurme T. Factors Associated with Abnormal Imaging and Infection Recurrence after a First Febrile Urinary Tract Infection in Children. Eur J Pediatr Surg. 2017 Apr;27(2):142-149. doi: 10.1055/s-0036-1572418. Epub 2016 Feb 8. PMID: 26855368.

Shaikh N, Craig JC, Rovers MM, et al. Identification of children and adolescents at risk for renal scarring after a first urinary tract infection: a meta-analysis with individual patient data. JAMA Pediatr2014;168:893–900.doi:10.1001/jamapediatrics.2014.637

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Bubble Wrap PLUS – March

Cite this article as:
Anke Raaijmakers. Bubble Wrap PLUS – March, Don't Forget the Bubbles, 2021. Available at:

Can’t get enough of Bubble Wrap? The Bubble Wrap Plus is a monthly paediatric journal club reading list  from Anke Raaijmakers working with Professor Jaan Toelen & his team of the University Hospitals in Leuven. This comprehensive list is developed from 34 journals, including major and subspecialty paediatric journals. We suggest this list can help you discover relevant or interesting articles for your local journal club or simply help you to keep an finger on the pulse of paediatric research.

This month’s list features answers to intriguing questions such as: ‘How long does metronidazole treatment change the gut microbiology?’, ‘Do corticosteroids have a place in the treatment of acute pyelonephritis?’, ‘Is metformin safe for treating obesity in childhood?’, ‘Is it safe to delay antibiotic treatment in respiratory tract infections?’ and ‘Can dried blood spots be used for the detection of congenital CMV infection?’.

You will find the list is broken down into four sections:

1.Reviews and opinion articles

Decision to extubate extremely preterm infants: art, science or gamble?

Shalish W, et al. Arch Dis Child Fetal Neonatal Ed. 2021 Feb 24:fetalneonatal-2020-321282

Ethical Considerations in Pediatricians’ Use of Social Media.

Macauley R, et al. Pediatrics. 2021 Feb 22:e2020049685. 

Review of an episode of racial discrimination in a paediatric ward.

De Rose C, et al. J Paediatr Child Health. 2021 Feb;57(2):293-294. 

Diagnosis and management of neonatal hip dysplasia: a brief history.

Dunn PM, et al. Arch Dis Child. 2021 Feb 17:archdischild-2020-321138. 

Early clinical management of autosomal recessive polycystic kidney disease.

Liebau MC. Pediatr Nephrol. 2021 Feb 17. 

Neonatal acute kidney injury: a case-based approach.

Starr MC, et al. Pediatr Nephrol. 2021 Feb 17

Review: Identification and Management of Circadian Rhythm Sleep Disorders as a Transdiagnostic Feature in Child and Adolescent Psychiatry.

Arns M, et al. J Am Acad Child Adolesc Psychiatry. 2021 Feb 5:S0890-8567(21)00059-9. 

Islamic Beliefs About Milk Kinship and Donor Human Milk in the United States.

Subudhi S, et al. Pediatrics. 2021 Feb;147(2):e20200441

Opening doors: suggested practice for medical professionals for when a child might be close to telling about abuse.

Marchant R, et al. Arch Dis Child. 2021 Feb;106(2):108-110. 

2.Original clinical studies

Impact of Metronidazole Treatment and Dientamoeba Fragilis Colonization on gut Microbiota Diversity.

Gotfred-Rasmussen H, et al. J Pediatr Gastroenterol Nutr. 2021 Feb 24

Maternal Psychological Factors and Onset of Functional Gastrointestinal Disorders in Offspring: A Prospective Study.

Baldassarre ME, et al. J Pediatr Gastroenterol Nutr. 2021 Feb 24. 

Adjuvant corticosteroids for prevention of kidney scarring in children with acute pyelonephritis: a systematic review and meta-analysis.

Meena J, et al. Arch Dis Child. 2021 Feb 25:archdischild-2020-320591. 

Enteral Feeding and Necrotizing Enterocolitis: Does time of First Feeds and Rate of Advancement matter?

Masoli D, et al. J Pediatr Gastroenterol Nutr. 2021 Feb 10. 

A Prevention Program for Insomnia in At-risk Adolescents: A Randomized Controlled Study.

Chan NY, et al. Pediatrics. 2021 Feb 24:e2020006833. 

Hypotension in Preterm Infants (HIP) randomised trial.

Dempsey EM, et al. Arch Dis Child Fetal Neonatal Ed. 2021 Feb 24:fetalneonatal-2020-320241

Clinical implications of thrombocytosis in acute phase Kawasaki disease.

Park JH, et al. Eur J Pediatr. 2021 Feb 1. 

Perinatal risk factors for pediatric onset type 1 diabetes, autoimmune thyroiditis, juvenile idiopathic arthritis, and inflammatory bowel diseases.

Räisänen L, et al. Eur J Pediatr. 2021 Feb 23

Pica, Autism, and Other Disabilities.

Fields VL, et al. Pediatrics. 2021 Feb;147(2):e20200462

Efficacy and Safety of Metformin for Obesity: A Systematic Review.

Masarwa R, et al. Pediatrics. 2021 Feb 19:e20201610. 

Maternal Chronic Conditions and Risk of Cerebral Palsy in Offspring: A National Cohort Study.

Strøm MS, et al. Pediatrics. 2021 Feb 18:e20201137. 

Molecular Diagnostic Yield of Exome Sequencing in Patients With Cerebral Palsy.

Moreno-De-Luca A, et al. JAMA. 2021 Feb 2;325(5):467-475

Augmented Reality-Assisted Video Laryngoscopy and Simulated Neonatal Intubations: A Pilot Study.

Dias PL, et al. Pediatrics. 2021 Feb 18:e2020005009. 

Multisystem inflammatory syndrome in children related to COVID-19: a systematic review.

Hoste L, et al. Eur J Pediatr. 2021 Feb 18:1-16. 

Association between childhood asthma and history of assisted reproduction techniques: a systematic review and meta-analysis.

Tsabouri S, et al. Eur J Pediatr. 2021 Feb 17. 

The intraperitoneal bacteriology and antimicrobial resistance in acute appendicitis among children: a retrospective cohort study between the years 2007-2017.

Dabaja-Younis H, et al. Eur J Pediatr. 2021 Feb 16. 

Adopting otitis media practice guidelines increases adherence within a large primary care network.

Bradley M, et al. J Paediatr Child Health. 2021 Feb 16. 

Bacterial Meningitis in the Absence of Pleocytosis in Children: A Systematic Review.

Zimmermann P, et al. Pediatr Infect Dis J. 2021 Feb 9. 

Association of in utero antibiotic exposure on childhood ear infection trajectories: Results from a national birth cohort study.

Hu YJ, et al. J Paediatr Child Health. 2021 Feb 15

Lack of changes in preterm delivery and stillbirths during COVID-19 lockdown in a European region.

Arnaez J, et al. Eur J Pediatr. 2021 Feb 12:1-6. 

Associations Between Neonatal MRI and Short- and Long-Term Neurodevelopmental Outcomes in a Longitudinal Cohort of Very Preterm Children.

Jansen L, et al. J Pediatr. 2021 Feb 9:S0022-3476(21)00114-1. 

Outcomes following admission to paediatric intensive care: A systematic review.

Procter C, et al. J Paediatr Child Health. 2021 Feb 12. 

Delayed Antibiotic Prescription for Children With Respiratory Infections: A Randomized Trial.

Mas-Dalmau G, et al. Pediatrics. 2021 Feb 11:e20201323. 

Antibiotics for Acute Respiratory Tract Infections: Now, Later, or Never?

Gerber JS, et al. Pediatrics. 2021 Feb 11:e2020046839. 

Diagnosis of celiac disease is being missed in over 80% of children particularly in those from socioeconomically deprived backgrounds.

Whitburn J, et al. Eur J Pediatr. 2021 Feb 10. 

Antibiotic exposure during pregnancy and childhood asthma: a national birth cohort study investigating timing of exposure and mode of delivery.

Uldbjerg CS, et al. Arch Dis Child. 2021 Feb 9:archdischild-2020-319659. 

Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children.

Wang YH, et al. JAMA Pediatr. 2021 Feb 8:e205710. 

Effects of a nudge-based antimicrobial stewardship program in a pediatric primary emergency medical center.

Shishido A, et al. Eur J Pediatr. 2021 Feb 8. 

Comparison of rectal and axillary temperature measurements in preterm newborns.

McCarthy LK, et al. Arch Dis Child Fetal Neonatal Ed. 2021 Feb 8:fetalneonatal-2020-320627. 

Consequences of coronavirus disease-2019 (COVID-19) lockdown on infection-related hospitalizations among the pediatric population in Denmark.

Polcwiartek LB, et al. Eur J Pediatr. 2021 Feb 8:1-9

Mental Wellbeing and General Health in Adolescents with Asthma: The PIAMA Birth Cohort Study.

van der Laan SEI, et al. J Pediatr. 2021 Feb 3:S0022-3476(21)00108-6. 

Neonatal Golden Hour: A survey of Australian and New Zealand Neonatal Network units’ early stabilisation practices for very preterm infants.

Hodgson KA, et al. J Paediatr Child Health. 2021 Feb 5

Perianal streptococcal disease in childhood: systematic literature review.

Gualtieri R, et al. Eur J Pediatr. 2021 Feb 2

Early detection of significant congenital heart disease: The contribution of fetal cardiac ultrasound and newborn pulse oximetry screening.

Menahem S, et al. J Paediatr Child Health. 2021 Feb 2. 

Paediatric appendicitis during the COVID-19 pandemic.

Sheath C, et al. J Paediatr Child Health. 2021 Feb 1

Live attenuated vaccines under immunosuppressive agents or biological agents: survey and clinical data from Japan.

Kamei K, et al. Eur J Pediatr. 2021 Feb 1. 

Sensitivity of Dried Blood Spot Testing for Detection of Congenital Cytomegalovirus Infection.

Dollard SC, et al. JAMA Pediatr. 2021 Feb 1:e205441. 

Newborn Dried Blood Spot Testing for Congenital Cytomegalovirus Screening: The Little Engine That Could.

Demmler-Harrison GJ. JAMA Pediatr. 2021 Feb 1:e205445. 

Early Motor Function of Children With Autism Spectrum Disorder: A Systematic Review.

Lim YH, et al. Pediatrics. 2021 Feb;147(2):e2020011270. 

Use of E-cigarettes and Other Tobacco Products and Progression to Daily Cigarette Smoking.

Pierce JP, et al. Pediatrics. 2021 Feb;147(2):e2020025122. 

Monitoring the recovery time of children after tonsillectomy using commercial activity trackers.

Lambrechtse P, et al. Eur J Pediatr. 2021 Feb;180(2):527-533. 

High flow in children with respiratory failure: A randomised controlled pilot trial – A paediatric acute respiratory intervention study.

Franklin D, et al. J Paediatr Child Health. 2021 Feb;57(2):273-281. 

Pediatric COVID-19 and Appendicitis: A Gut Reaction to SARS-CoV-2?

Malhotra A, et al. Pediatr Infect Dis J. 2021 Feb 1;40(2):e49-e55

Use of probiotics in the treatment of functional abdominal pain in children-systematic review and meta-analysis.

Trivić I, et al. Eur J Pediatr. 2021 Feb;180(2):339-351. 

Evaluation of an educational video providing key messages for doctors to counsel families following a first afebrile seizure.

Ng EWM, et al. J Paediatr Child Health. 2021 Feb;57(2):198-203. 

Sleep, Growth, and Puberty After 2 Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder.

Malow BA, et al. J Am Acad Child Adolesc Psychiatry. 2021 Feb;60(2):252-261.e3. 

Associations of Maternal Cardiovascular Health in Pregnancy With Offspring Cardiovascular Health in Early Adolescence.

Perak AM, et al. JAMA. 2021 Feb 16;325(7):658-668. 

Maternal Cardiovascular Health: A Critical Period for Offspring Lifetime Cardiovascular Health?

Daniels SR. JAMA. 2021 Feb 16;325(7):630-631

Open Schools, Covid-19, and Child and Teacher Morbidity in Sweden.

Ludvigsson JF, et al. N Engl J Med. 2021 Feb 18;384(7):669-671

Predictive Models of Neurodevelopmental Outcomes After Neonatal Hypoxic-Ischemic Encephalopathy.

Peeples ES, et al. Pediatrics. 2021 Feb;147(2):e2020022962. 

3.Guidelines and best evidence

4.Case reports

Not only appendicitis: rare appendix disorders manifesting as surgical emergencies in children.

Samuk I, et al. Eur J Pediatr. 2021 Feb;180(2):407-413. 

Severe movement disorder and psychosis from haloperidol withdrawal in a 7-year-old girl with autism.

Syamkumar S, et al. J Paediatr Child Health. 2021 Feb;57(2):286-288. 

Neonatal systemic lupus erythematosus syndrome presenting as 4 months of ‘persistent ringworm’.

Patel F, et al. Arch Dis Child. 2021 Feb;106(2):153. 

Purpuric, delayed child: Beyond septicaemia and into inborn errors of metabolism.

Hertzog A, et al. J Paediatr Child Health. 2021 Feb 15. 

Use of Cognitive Shortcuts in Decision-making for Children With Severe Neurologic Impairment.

Bogetz JF, et al. Pediatrics. 2021 Feb 11:e20200930. 

Hand sanitiser-associated ocular chemical injury in children.

Rodríguez-Ares MT, et al. J Paediatr Child Health. 2021 Feb 10. 

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

The 47th Bubble Wrap

Cite this article as:
Currie, V. The 47th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: The safety profile of ceftriaxone

Zeng, L., Wang, C., et al., (2020) Safety of ceftriaxone in paediatrics: a systematic review. Archives of Disease in Childhood. Oct;105(10):981-985. doi: 10.1136/archdischild-2019-317950

What’s it about? 

Ceftriaxone is one of the most commonly prescribed antibiotics for children. It is a broad spectrum third generation cephalosporin, used as a first line empirical agent for meningitis, sepsis and useful against many bacterial infections. It has an elimination half-life of 8 hours and can be given once every 24 hours IV or IM, giving us options when that cannula is particularly tricky! Whilst it is well known that using ceftriaxone in the newborn is contraindicated due to biliary sludging, the authors of this paper delved into the literature to identify other adverse reactions (ADRs) to ceftriaxone.

What did they do?

The authors performed systematic searches across several databases looking for studies to evaluate the type of ADR, the incidence of ADRs in patients aged 0 – 18 years old and to identify any potential risk factors for serious ADRs. A total of 112 studies were identified (22 RCTs, 61 case reports, 19 prospective studies, 7 retrospective studies, 2 case series and 1 case control study) which reported on ADRs of ceftriaxone use (although it was not a primary outcome measurement in any of the studies).

Looking at the RCTs, prospective and retrospective studies, gastrointestinal side effects were the most common ADR (specifically, diarrhoea). The second most common ADR identified amongst these studies was hepatobiliary (biliary sludging and cholelithiasis). These ADRs were all transient, and usually self-resolved after cessation of ceftriaxone. The case reports and case studies identified the more serious ADR of immune haemolytic anaemia, which carries a risk of death, especially for patients with an underlying diagnosis of sickle cell disease.

Clinically Relevant Bottom Line:

Transient gastrointestinal side effects are generally tolerable, and we should closely monitor patients for evolving symptoms of gallstones. Most importantly, we should be mindful and cautious when prescribing ceftriaxone in patients with underlying haematological conditions such as sickle cell anaemia, due to the uncommon but significant risk of immune haemolytic anaemia. Ceftriaxone is really a great antibiotic, and as long as we remember the clinical spectrum of ADRs, we will not cause significant patient harm.

Reviewed by: Tina Abi Abdallah

Article 2: Kawasaki Disease vs Septic Shock: Early Differentiating Features Despite Overlapping Clinical Profiles

Power A, Runeckles K, Manlhiot C, Dragulescu A, Guerguerian AM, McCrindle BW. Kawasaki Disease Shock Syndrome Versus Septic Shock: Early Differentiating Features Despite Overlapping Clinical Profiles. J Pediatr. 2020 Dec 5:S0022-3476(20)31482-7. doi: 10.1016/j.jpeds.2020.12.002. Epub ahead of print. PMID: 33290811.

What’s it about? 

According to literature around 6-7% *of patients with Kawasaki disease present with shock and this can provide a challenge in differentiating Kawasaki disease from septic shock. This paper looks to compare clinical features, resuscitative measures and haemodynamic response to treatment between those presenting with Kawasaki disease shock syndrome and children with septic shock.

*Kanegaye JT, Wilder MS, Molkara D, Frazer JR, Pancheri J, Tremoulet AH, et al. Recognition of a Kawasaki Disease Shock Syndrome. Pediatrics 2009;123:e783-9.

What did they do?

This was a retrospective chart review of patients under the age of 18 over a 10-year period admitted to a tertiary centre in the USA. The charts of children who met the criteria for Kawasaki disease shock syndrome (as defined by the American Heart Association) were analysed and children meeting the criteria for septic shock were used as controls. Over the 10-year period >1000 children were admitted to the centre with Kawasaki disease. Of these 9 met the criteria for Kawasaki disease shock syndrome. They were case matched with 18 controls who were admitted with septic shock.

The study found that children with Kawasaki disease shock syndrome were less likely (1 in 9) to have an underlying significant medical illness than the septic shock group (11 in 18). All the patients in the Kawasaki group had at least one of the five classic features of Kawasaki disease at presentation (rash, conjunctivitis, mucous membrane changes, cervical lymphadenopathy and extremity changes). With rash found in 7 of 9 of the patients either at presentation or during the admission. 5 in 9 of the Kawasaki disease cohort had cardiac involvement with zero of the control group with any cardiac involvement.

The length of stay for children in the Kawasaki disease shock syndrome group was a median of 9 days vs 28 days in the septic shock group, with no difference found in ICU length of stay. Biochemical markers were compared, and this study found a lower platelet count (median 140 vs 258) in the Kawasaki group. Interestingly in children with Kawasaki disease shock syndrome the duration of illness prior to admission was much longer (9 days vs 3 days) than the control group.

There have been no studies that directly compare children with Kawasaki disease shock syndrome and septic shock, so this acts as a starting point. However, it is a very small cohort (only 9 patients out of >1000 presentations of Kawasaki disease with Kawasaki shock syndrome); perhaps a multi- centre trial within a network could be done to increase the numbers.

Clinically Relevant Bottom Line:

This study has found that when compared to children with septic shock children with Kawasaki disease shock syndrome are more likely to have a lower platelet count on admission, a longer duration of illness prior to admission, cardiac involvement if an echo is performed and have a longer stay in hospital. All the patients in this study had at least one of the classic features of Kawasaki disease with rash being the most common here. As clinicians who review these children at the front door perhaps a child with a rash and low platelets fever >5 days will continue to make us think about Kawasaki disease.

Reviewed by: Vicki Currie

Article 3: Is it necessary to evaluate urinary tract infection in children with lower respiratory tract infection?

Kim JM, Koo JW, Kim H-B. Is it necessary to evaluate urinary tract infection in children with lower respiratory tract infection? Journal of Paediatrics and Child Health. 2020 Dec;56(12):1924-1928

What’s it all about?

Lower respiratory tract infections (LRTIs) and urinary tract infections (UTIs) are common childhood infections that previous literature has reported to have a concomitance rate of 3 to 10 per 100 children. While LRTIs are often self-limiting viral infections, UTIs are often caused by a bacterial source that can have long term implications if not adequately treated.

What did they do?

This was a retrospective review of 1574 patients’ medical records under 36 months of age who were hospitalised for a LRTI over a 2 year period in a South Korean hospital. 278 of patients had a fever and underwent a subsequent urine evaluation performed either by catheterisation (<24mo) or voided urine (24-36mo).

Patients with a congenital airway or kidney disease, absence of fever at presentation or whose parents refused or failed to undergo a urinalysis were excluded from the analysis.

The overall prevalence rate of a concomitant UTI with LRTI in this population was 1 in 10 in children <36mo and 13 in 100 in children <24mo. Mean age was significantly younger in the UTI group 7 months vs 12 months in the non UTI group. There was a greater prevalence rate of UTIs in boys (n=23) compared to girls (n=7). The most common organism cultured in the UTI group was Escherichia coli which were all treated with a third-generation cephalosporin. The positive rate of virus detection was 93.3% in the UTI group, and 89.9% in the non-UTI group. Most frequently detected co-infections were adenovirus, rhinovirus, and RSV.

The Bottom Line:

LRTIs and UTIs are common childhood infections that have up to a 1 in 10 concomitance rate.  A child presenting with a LRTI and concomitant UTI may present to ED with early respiratory and non-specific symptoms of a UTI (fever, lethargy and irritability), which may lead clinicians to presume a respiratory source of infection and not perform or delay a urinalysis. Hence a diagnosis of an underlying UTI may be missed. Failure to diagnose and promptly treat an underlying UTI can lead to renal morbidity including renal scars, hypertension and chronic kidney disease. Considering the ease of diagnosing and treating a UTI, this study further reiterates the importance of excluding a UTI in children with LRTIs under 36 months of age, especially of male gender. However, given the nature of this single centre study in South Korea, these findings cannot be generalised to a global population and must be taken in context to the population you encounter in clinical practice.

Reviewed by: Emma Chan

Article 4: Why don’t kids get sick with COVID-19?

Zimmermann P, Curtis N., Why is COVID-19 less severe in children? A review of the proposed mechanisms underlying the age-related difference in severity of SARS-CoV-2 infections Arch Dis Child 2020;0 1-11

What’s it about?

A review article analyzing the possible mechanisms for reduced severity of COVID-19 in paediatric patients. The debate about if children have a lower rate of COVID-19 infection continues but it is known that children are less severely affected (in contrast to other respiratory viruses). This appears to be true even in paediatric patients with immune suppression or preexisting conditions e.g. IDDM. What we don’t know is why. The authors look at the evidence for multiple hypotheses but the two they favor are:

1)     Age related endothelial damage and increased coagulability. This fits the clinical profile of COVID-19 which features endotheliitis, micro thrombi, thrombotic complications and vasculitic skin manifestations. It could also explain COVID-19 being more severe in conditions which damage the endothelium e.g. hypertension and diabetes.

2)     Age related changes to the immune system. There is a decline in innate and adaptive immunity in the elderly compared with children who have not gone through this decline. The chronic proinflammatory state (which predisposes to the cytokine storm seen in severe COVID-19) increases with age. Additionally the authors hypothesize that the effect of chronic CMV infection on T-cells may explain the worsening of COVID-19 with age.

The authors concluded that these were the only two hypotheses which fit with the age-gradient in COVID-19 with mortality and morbidity rising steeply after 60-70.

The bottom line

If we could figure the ‘magic formula’ protecting children against severe COVID-19 we could use this to target treatment in adults. However, this paper is very much exploring theories and cannot yet be extended to clinical treatments.

The interplay between a lack of endothelial damage, lack of propensity to hyper-coagulation and their not yet declined immune system are most likely to protect children from severe COVID-19 infection.

Reviewed by: Sarah Reynolds

Article 5: A Gut Feeling: Abdominal Symptoms as an Initial Presentation of EVALI

Christel Wekon-Kemeni, MD, Prathipa Santhanam, MD, Pallav Halani, MD, Lauren Bradford, MD, Ceila E. Loughlin, MD.A Gut Feeling: Abdominal Symptoms as an initial presentation of EVALI, Paediatrics Volume 147, number 1, January 2021.

What’s it about?


Vaping or electronic cigarette use associated lung injury (EVALI) is a syndrome resulting from electronic cigarette use which causes predominantly respiratory symptoms, such as shortness of breath.

This case report describes an American 13-year-old male presenting, on two occasions primarily with abdominal symptoms of pain, nausea and vomiting. Initially, he was managed as a case of gastroenteritis, and had been noted to have borderline saturations. Initial abdominal CT report described bilateral lung pathology (lower lobe consolidation and atelectasis) in addition to mild jejunal loop thickening. However, after a second admission with similar symptoms plus raised inflammatory markers and fever, further workup was commenced. 

Repeat abdominal CT excluded appendicitis and evidence of inflammatory bowel disease. CXR revealed bilateral changes and a Thoracic CT identified multifocal ground-glass changes and infiltrates bilaterally with scattered septal thickening and dependent bibasal opacities.

Following a review of the patient by the respiratory team, a year long history of e -cigarette use preceding this patient’s symptoms was discovered, identifying EVALI as the potential diagnosis.

The patient was started on intravenous methylprednisolone which, following an improvement in all symptoms, was converted to a  course of oral corticosteroids. Repeat thoracic CT one month following discharge showed almost complete resolution of the initial changes. 

Why does it matter?

EVALI is a relatively new syndrome, mostly documented in North America, with the potential to increase in prevalence as we see the popularity of e-cigarette use continuing to rise.

Given this patient’s initial symptoms of nausea and vomiting, detailed smoking history to include e-cigarette use may not have been taken. Thus, a workup for abdominal pathology was justifiably completed. However, considering published case reports of EVALI describing nausea and vomiting as common symptoms, this diagnosis should still be considered in patients presenting without respiratory involvement initially. The data available describing EVALI in the paediatric population is sparse, nevertheless in adult’s progression to respiratory failure requiring invasive ventilatory support is reported.

Clinically Relevant Bottom Line:

 Although challenging, obtaining an accurate smoking history to include e-cigarette use in young people is important for the consideration of EVALI as a diagnosis. We still don’t completely understand the pathophysiology of e-cigarettes, or how much damage they are causing to the young people we see who smoke them, but remembering to ask about this as part of your history is a step we can take to improve knowledge and understanding.

Reviewed by: Joshua Tulley

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to.

High flow therapy – when and how?

Cite this article as:
Padmanabhan Ramnarayan. High flow therapy – when and how?, Don't Forget the Bubbles, 2021. Available at:

Isn’t nasal high flow just a fancy name for plain old high flow oxygen? Or is it CPAP-lite? For a therapy that has become so popular in less than a decade, amazingly, there is more opinion sloshing around than proper scientific evidence…

OK, back up, what is Nasal High Flow therapy?

Nasal high flow therapy (NHF), aka high flow nasal cannula therapy (HFNC), is a non-invasive mode of respiratory support, involving the delivery of heated (to 37° C) and humidified (to nearly 100% relative humidity) gas (oxygen and/or medical air) through nasal cannulae at high gas flow rates. What is a “high” gas flow rate is still not uniformly defined (some studies say >2 L/min and others >4 L/min). In physiological terms, to provide the true benefits of “high flow”, the gas flow rate should exceed the patient’s maximal peak inspiratory flow rate (roughly 8-10 x normal minute ventilation).

Makes sense, but what is a child’s peak inspiratory flow rate?

Short answer – it changes according to the age and the extent of respiratory distress. For example, a 4 kg baby breathing at 40 breaths/min and inhaling a tidal volume of 5 ml/kg (=20 ml) would have a minute ventilation of 0.8 L/min and a peak inspiratory flow (PIF) rate of nearly 3 L/min. However, the same infant would have a much higher PIF in respiratory distress. Matching the maximal PIF rate by aiming for roughly 8-10 x normal minute ventilation (in this case, 8-10 x 0.8 L/min = 7-8 L/min) is the key principle of NHF therapy. NB: Magically, the 8 L/min flow rate in this baby is also 2 L/kg/min (more on that later!)

Got it. But when should I start NHF in the ED?

Case 1. A previously healthy 4-month old infant is seen in the emergency department with a two-day history of coryza and poor feeding. On examination, he has mild/moderate subcostal recession and a respiratory rate of 60 bpm. His oxygen saturation in room air is 89%. Would you start nasal high flow?

This baby most likely has mild viral bronchiolitis and the main question is whether to start standard oxygen therapy (SOT) via nasal cannulae or NHF. The most useful clinical outcomes we are interested in are transfer to paediatric intensive care (PICU) and the need for endotracheal intubation.

What does the evidence say?

A recent systematic review (Lin J et al. Arch Dis Child 2019) is an obvious starting point. For the outcome of transfer to PICU, only two RCTs were included (Franklin et al. NEJM, 2018; Kepreotes et al. Lancet 2017). The overall risk ratio was 1.30 (95% CI 0.98, 1.72) indicating no significant difference between NHF and SOT, although there was a tendency to favour SOT.

Similarly, only two RCTs were included for the outcome of intubation (Franklin et al. NEJM, 2018; Yang et al. Chinese Pediatric Emergency Medicine, 2017). The overall risk ratio was 1.98 (95% CI 0.60, 6.56), again with no significant difference between NHF and SOT. So, not much joy from the systematic review…

Considering that Franklin et al dominated the systematic review in terms of sample size, it is useful to look at this RCT in a bit more detail, from a PICO point of view as well as the flow of patients through the RCT.

Population: Infants <12 months of age with bronchiolitis and needing supplemental oxygen

Intervention: NHF at 2 L/kg/min

Control: Standard oxygen therapy

Outcome: Escalation of care due to treatment failure (composite outcome)

A few reflections on the outcomes of infants in this RCT: although nearly double the number of infants randomised to SOT “failed treatment” compared to NHF, it is notable that over 75% of infants randomised to SOT did not “fail”; the majority of those who did “fail” SOT were rescued by NHF; and since NHF “failure” automatically led to PICU transfer, in effect, more infants were transferred to PICU in the NHF group than in the SOT group (12% vs 9%). Essentially, this RCT could be considered a trial of ‘immediate’ NHF versus ‘rescue’ NHF, as covered by us here previously.

Bottom line: There is no advantage to starting NHF as first-line therapy in an infant with mild bronchiolitis. A more clinically and cost-effective strategy would be to use NHF as ‘rescue’ therapy when standard oxygen therapy has failed.

Case 2. An ex-prem born at 24 weeks gestation, now 4 months old, is seen in the emergency department with a 24-hour history of coryza and cough. On examination, he has moderate/severe subcostal recession and a respiratory rate of 80 bpm. His oxygen saturation in room air is 85%. Would you start nasal high flow?

This baby is much sicker, with significant past medical history, and most likely has moderate/severe bronchiolitis. Would NHF be more useful as first-line therapy in this infant, where previously nasal CPAP would have been an option – can NHF be used as ‘CPAP-lite’? A really useful clinical outcome to focus on is endotracheal intubation.

What does the evidence say?

Lin et al summarise the evidence in their recent systematic review. For the outcome of intubation, 4 RCTs were included, but the total number of patients included were low (n=264). Intubation rates were identical in the NHF and CPAP groups (5.3%), with a risk ratio of 0.96 (95% CI 0.35, 2.61). So, there is not much evidence to support the use of NHF compared to CPAP, although quite notably, the rate of adverse events was lower in the NHF group (8% vs 21%).

Bottom line: There is no clinical advantage to starting NHF as first-line therapy in an infant with moderate to severe bronchiolitis to avoid intubation. However, its adverse event profile and tolerability by infants might make NHF more appealing as first-line therapy.

When should I start NHF in the HDU?

Case 3: A 5-year old boy with cerebral palsy and epilepsy is admitted to the paediatric HDU bed with fever, cough and respiratory distress. On examination, he has moderate subcostal and intercostal recession and a respiratory rate of 45 bpm. His oxygen saturation in room air is 88%. Would you start nasal high flow?

In this older child with a complex past medical history, is starting NHF, compared to either standard oxygen or CPAP, beneficial in terms of avoiding the need for endotracheal intubation?

What does the evidence say?

A recent systematic review (Luo J et al. Journal of Pediatrics, 2019) is an obvious starting point. In the comparison of NHF versus SOT, 5 RCTs were included, although 2 were focussed on bronchiolitis (previously covered – Franklin et al and Kepreotes et al). The other 3 RCTs were small (Chisti et al. Lancet, 2015; Ergul et al. Eur J Pediatrics, 2018; Sittikharnka et al. Indian J Crit Care Med 2018) with just 300 patients in total. The overall risk ratio for intubation from these 3 studies alone (calculated specifically for this post) was 0.72 (95% CI 0.38, 1.36). Similarly, in the comparison of NHF versus CPAP, 4 RCTs were included but 2 were in bronchiolitic infants (covered earlier). The other two RCTs (Ramnarayan et al. Crit Care 2018; Chisti et al. Lancet 2015) included just 187 children. The overall risk ratio for intubation based on these two RCTs (calculated for this post) was 2.14 (95% CI 0.93, 4.92) indicating a tendency for a higher intubation rate with NHF in older children.

Bottom line: In an older child, intubation was not less frequent when NHF was used compared to SOT as first line therapy. There was a tendency for NHF to be associated with a higher intubation rate compared to CPAP.

Great – what is the best way to provide NHF?

Starting gas flow rate

Milesi et al showed in physiological studies in infants aged <6 months with bronchiolitis that the work of breathing is reduced considerably when the gas flow rate is set at nearly 2 L/kg/min. In their cohort of 21 infants (mean weight 4.3 kg), the measured work of breathing was lowest at a flow rate of 7 L/min (compared to 1, 4 and 6 L/min). Similarly, in children up to the age of 3 years with pneumonia, work of breathing was reduced by nearly 20% at a flow rate of 1.5 L/kg/min compared to 0.5 L/kg/min (Weiler et al. Journal of Pediatrics 2017). Usual adult flow rates range from 50-60 L/min.

In summary, the optimal gas flow rate does not increase in a linear fashion with increasing age/weight, instead it goes from nearly 2 L/kg/min in infancy to nearly 1 L/kg/min in young adults.

RCTs of different starting flow rates

There have been two RCTs comparing NHF flow rates in bronchiolitis (Yurtseven A et al. Ped Pulm 2019; Milesi et al. Intens Care Med 2018). In the former, 1 L/kg/min (n=88) was compared to 2 L/kg/min (n=80) in infants <24 months with clinical severe bronchiolitis presenting to the emergency department. The primary outcome was ‘treatment failure’ within 24 hours. There was no significant difference in treatment failure between the two flow rates (1 L/kg/min: 11.4%; 2 L/kg/min: 10%). The second RCT compared 2 L/kg/min (n=142) with 3 L/kg/min (n=144) in infants aged <6 months with moderate/severe bronchiolitis. The primary outcome was treatment failure within 48 hours. There was no significant difference in treatment failure between the two groups (2 L/kg/min: 38.7%; 3 L/kg/min: 38.9%).

A useful chart with suggested starting flow rates based on weight is used in the ongoing FIRST ABC clinical trial of NHF versus CPAP.

Nasal cannula size

There are different nasal cannula sizes available based on the manufacturer. The general rule of thumb is that the cannula prongs should be no more than 50% of the diameter of the nostril to avoid inadvertent occlusion of the nasal passages. It is also advisable to start the gas flow rate at a low rate and then increase gradually over 10-15 min to avoid patient discomfort. Pacifiers may be useful in babies to prevent mouth opening.

Weaning NHF

There are no RCTs comparing weaning strategies for NHF. Clinical practice is also highly variable – in a global survey of practice in over 1000 PICU professionals by Kawaguchi et al, 68% weaned the FiO2 first to a threshold value (e.g. 0.40) and then weaned the flow rate gradually, 11% weaned the FiO2 first to a threshold value (e.g. 0.40) and then stopped NHF, and 4% weaned the flow rate alone without weaning the FiO2. The FIRST ABC RCT algorithm for the weaning of NHF provides a weight-based approach to a one-step weaning process and suggested clinical thresholds for weaning and stopping NHF.

The take homes

  • Nasal high flow is a form of non-invasive respiratory support that sits somewhere between standard oxygen therapy and nasal CPAP.
  • In infants with mild bronchiolitis, there is no clinical (or cost) benefit in starting NHF as first-line treatment – rather, NHF is best used as a ‘rescue’ therapy after standard oxygen.
  • In infants with moderate/severe bronchiolitis, NHF may be a useful first-line therapy owing to its ease of use and since it is better tolerated by infants, however there is no clinical benefit compared to nasal CPAP.
  • In older children with respiratory failure, there is little RCT evidence to guide practice – however, there is no clear benefit of starting NHF over and above standard oxygen. NHF may be associated with a higher intubation rate compared to CPAP in older children.
  • There is no RCT evidence to support either 1, 2 or 3 L/kg/min NHF flow rates in infants with bronchiolitis; however, physiological evidence suggests that nearly 2 L/kg/min is associated with reduction in work of breathing. Suitable flow rates in older children approximate 1.5 L/kg/min and in young adults, 1 L/kg/min.
  • There is no RCT evidence to support one way of weaning over another – the most common practice seems to be to reduce FiO2 to below 0.40, followed by a reduction in the NHF flow rate.
  • Ongoing RCTs such as the FIRST ABC trial will help address the question whether NHF is non-inferior to CPAP in critically ill children.

The 46th Bubble Wrap

Cite this article as:
Currie, V. The 46th Bubble Wrap, Don't Forget the Bubbles, 2021. Available at:

With millions upon millions of journal articles being published every year it is impossible to keep up.  Every month we ask some of our friends from PERUKI (Paediatric Emergency Research in UK and Ireland) to point out something that has caught their eye.

Article 1: Ten Tips for Breaking Bad News

Brouwer, M.A., Maeckelberghe, E.L.M., van der Heide, A., et al., Breaking bad news: what parents would like you to know (2020) Archives of Disease in Childhood Published Online First: 30 October 2020. doi: 10.1136/archdischild-2019-318398

What’s it about? 

Difficult conversations in paediatrics often revolve around conditions which reduce life expectancy, such as oncological, metabolic, cardiac and neurological diagnoses. In the case of new diagnoses, difficult discussions may happen in the emergency department – an environment that is not designed for sensitive and long (ideally interruption free) discussions. 

This article reviews the experiences of parents who were involved in difficult conversations surrounding their child’s care or condition and provides practical advice on how to provide empathic, timely and optimal communication.

Based in the Netherlands, the authors recruited bereaved and non-bereaved parents of children aged between 1 and 12 years with life threatening conditions. Between November 2016 and October 2018, face to face interviews with the parents were conducted and transcribed verbatim.

Using transcripts, key themes and ten clear barriers to the communication of bad news were identified. The authors then reviewed the transcripts at length to identify positive feedback when breaking bad news; with the key aspects being where and when conversations took place, who was present for the conversation, and the honesty and information that was given.

Why does it matter? 

Breaking bad news or caring conversations are part of our every day work. But for the families and children receiving the information, the high emotional and practical significance means that they remember these conversations for a long, long time. The onus on us as professionals is to develop and grow the insight and skill to thoughtfully, effectively and compassionately communicate during these conversations.

Clinically Relevant Bottom Line:

Communication skills remain the cornerstone of medical practice. Feedback from patients and family often revolves around communication with the team caring for them, and whether it was “good” or “bad”. This article highlights some important factors to optimise communication when breaking bad news, which can be (and should be) utilised on a daily basis.

Reviewed by: Tina Abi Abdallah

Article 2: Risk of traumatic intracranial haemorrhage in children with bleeding disorders

Bressan, S., Monagle, P., Dalziel, S.R., Borland, M.L., Phillips, N., Kochar, A., Lyttle, M.D., Cheek, J.A., Neutze, J., Oakley, E., Dalton, S., Gilhotra, Y., Hearps, S., Furyk, J., Babl, F.E. (2020). Risk of traumatic intracranial haemorrhage in children with bleeding disorders. J Paediatr Child Health, 56: 1891-1897.

What’s it about? 

This multi-centre prospective observational study aimed to assess the rate of  CT use and frequency of diagnosing intracranial haemorrhage (ICH) on CT, in children with bleeding disorders presenting with head trauma.

20 137 children were evaluated in Australian and New Zealand EDs for head trauma, with or without bleeding disorders between April 2011 and November 2014. Congenital or acquired bleeding disorders were present in 0.5% of this population. Head CT use was significantly higher in children with bleeding disorders than those without (3 in 10 vs 1 in 10) despite the latter group presenting more frequently with severe mechanisms of head injury. Children with bleeding disorders who received CT were more likely to present with milder mechanisms of injury as well as clinical signs of vomiting and abnormal behaviour reported by parents, compared to children with bleeding disorders who did not receive CT scans . Only one child with a bleeding disorder had an ICH requiring neurosurgical intervention and no children without CT imaging had evidence of ICH on follow-up.

Why does it matter? 

Minor head injuries present frequently to paediatric EDs. Children with bleeding disorders are at increased risk of ICH following a minor head injury than those without bleeding disorders. Patients with severe haemophilia are reported to have the highest risk of traumatic ICH within this heterogenous disease group. It is important to detect ICH early in order to avoid long term disability and potentially fatal outcomes whilst balancing the decision for imaging against the risks of repeated radiation exposure. Previous clinical decision rules have supported ED clinicians in making judgements on CT use for paediatric head injuries but there is little evidence or guidance on its use for children with bleeding disorders.

Clinically Relevant Bottom Line:

The low incidence of ICH in children with bleeding disorders receiving CT imaging suggests that CT scans may not be routinely necessary in children with congenital or acquired bleeding disorder. The authors suggest a more selective approach to CT decision-making, combining a period of clinical observation with the severity of injury mechanism and the underlying bleeding disorder, rather than a “CT all” strategy.

However, the study is limited in its analysis by the low number of children with bleeding disorders. It would also be interesting to note from Bressan et al.’s study whether the rate of CT use varied with patients’ GCS scores or age of presentation, given the wide age window of children < 18 years.

 Nonetheless, current head injury rules such as PECARN were designed with the explicit exclusion of children with bleeding disorders. This study can therefore support the development of targeted neuroimaging guidelines for children with bleeding disorders.

Reviewed by: Ivy Jiang

Article 3: Can we safely send paediatric head injuries home from triage?

Aldridge, P., Castle, H., Phillips, C., Russell, E., Guerrero-Luduena, R., Rout, R. (2020). Head home: a prospective cohort study of a nurse-led paediatric head injury clinical decision tool at a district general hospital. Emergency Medicine Journal.

What’s it all about?

Head injuries are a common presentation to emergency departments internationally. Recent Australian data has shown that in >19,000 attendances with head injury only 3 in 100 had a traumatic brain injury on CT or a clinically important brain injury.

This study group set out to assess whether children under 17 years could safely be discharged by triage nurses following a pre-set clinical decision tool (HIDATq- Head Injury Discharge At Triage questionnaire). HIDATq was developed using PECARN and NICE guidelines. For a recap on Head Injury Decision tools see Anna Ing’s ‘Head Injury- who to scan?’ on DFTB.  HIDATq was implemented over a 6-month period in children who presented with a head or facial injury to a DGH in the UK.

Over 1700 patients were assessed, and data was analysed retrospectively. 61% were HIDATq negative and 1 in 5 of these patients were felt to be safe for discharge from triage without further investigation or management. A further 3 out of 10 children in the HIDATq negative patients were found to be eligible for discharge following minor wound management. 4 % of patients underwent CT scans (only 1 patient from the HIDATq negative group).

Why does it matter?

Head injuries are a common presentation to the paediatric ED. This study has revealed a patient group who might be eligible, using this screening tool, for a safe discharge from triage that would potentially have a large impact on ED crowding and pressures.

Clinically Relevant Bottom Line:

There were no adverse outcomes and the clinical decision tool used produced a high sensitivity and specificity for determining the need for CT after head injury. More than half of the children who had a negative HIDATq were potentially suitable for a safe discharge from triage.

This study did however have a highly selective population- it was not a major trauma centre so by default likely to have had less severe presentations of head injury. A larger multi centre trial is needed to provide validation for the tool. However, this study provides a useful starting point and identifies possible ways to improve patient management and ED departmental pressures.

Reviewed by: Brent Stevenson

Article 4: Should POC blood ketones be used as a triage tool to assess dehydration and predict likely admission?

Durnin, S., Jones, J., Ryan, E., Howard, R., Walsh, S., Dawkins, I., Blackburn, C., O’Donnell, S.M. and Barrett, M.J., 2020. The utility of ketones at triage: a prospective cohort study. Archives of Disease in Childhood105(12), pp.1157-1161.

What’s it about?

This is a small non-blinded prospective cohort study looking at 198 patients aged 1m-5yrs over a 12-month period. The eligibility criteria were presentation with vomiting/diarrhea/decreased fluid intake or clinical concerns of possible hypoglycaemia. Patients had finger prick blood ketones measured at triage, along with a Gorelick 4-point dehydration score. Repeat ketone measurement at 4hrs later or at discharge, clinical assessment and a 10-point Gorelick dehydration score (a Gorelick score is a validated tool to predict significant dehydration for children aged 1 month to 5 years).

The authors found a weak correlation between POC ketone level and the 10-point Gorelick dehydration scale (a more detailed assessment) and no correlation between POC ketones and Gorelick 4-point dehydration scale score.

Ketone level at triage was not predictive of admission however repeat measurement at 4hrs was weakly predictive; meaning, a larger proportion of the discharged cohort showed a reduction in ketones after rehydration compared to the admitted cohort.

Why does it matter?

Assessing dehydration is an inexact science and an accurate POC test for dehydration would simplify and potentially improve patient care. The Gorelick 4-point scale has previously shown to be oversensitive for assessing percentage dehydration but scales are better than unstructured assessment. This study rules out blood ketones as a tool for assessment of degree of dehydration or for predicting admission in this patient group.

The bottom line

Blood ketones are of little use as a triage tool for assessing degree of dehydration or predicting hospital admission in children with reduced fluid intake / D&V. There is no benefit to routine measurement of blood ketones at triage in patients with dehydration who do not have concerns about potential DKA.

Reviewed by: Sarah Reynolds

Article 5: Is loop-mediated isothermal amplification a useful tool for early identification of invasive meningococcal disease?

Waterfield, T., Lyttle, M.D., McKenna, J., Maney, J.A., Roland, D., Corr, M., Woolfall, K., Patenall, B., Shields, M. and Fairley, D., 2020. Loop-mediated isothermal amplification for the early diagnosis of invasive meningococcal disease in children. Archives of Disease in Childhood105(12), pp.1151-1156.

What’s it about?

A point of care test: Loop mediated isothermal amplification (LAMP) is a potential test for early identification of invasive meningococcal disease (MD).  (LAMP) is a form of rapid nucleic acid amplification and a commercially available LAMP test (using oropharyngeal swabs) can test for all serotypes of Neisseria meningitidis. This study looked to evaluate the diagnostic accuracy of LAMP for identifying invasive (MD) in children and to compare LAMP testing with more familiar tests like CRP and white cell counts (WCC).

 263 children under the age 18 with fever and signs or symptoms of meningococcal septicaemia were included over a 2-year period in 3 ED’s across the UK. 97% of participants were appropriately vaccinated as per UK vaccination schedule with over 1 in 2 of these children having had the Men B vaccination and over 2 in 3 children who had received the Men C vaccine.

Less than 2 per 100 children had confirmed cases of invasive MD. There were 14 positive LAMP tests, and all the confirmed cases of invasive MD were within these. In all the children with negative LAMP tests NONE had invasive MD. The LAMP test in this population performed better than other more commonly used tests (CRP, WCC or neutrophil counts).

Why does it matter?

Whilst vaccination programmes have thankfully made invasive MD more uncommon, it is still a significant cause of morbidity and mortality in children when it does occur. 

Early diagnosis is challenging, meaning potential overuse of broad-spectrum antibiotics or false reassurance for the clinician.

A point of care test for N. meningitidis, which is easy to do, with a low false negative rate has the potential to change this. However, false positives, meaning asymptomatic carriage must be considered.  The study included mostly young children and adolescents who are known to have higher asymptomatic carriage rates of N. meningitis, meaning false positive could be higher in this group.  It has the potential to be used as an adjuvant to PCR and blood culture, but the optimum patient group selection is yet to be determined and it could not be used as a rule out test in low prevalence areas like the UK.

Clinically Relevant Bottom Line:

LAMP testing for IMD, is a potentially useful test to identify children with invasive MD rapidly. However, clinical utility is yet to be determined.

Reviewed by: Sarah Kapur

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!

That’s it for this month. Many thanks to all of our reviewers who have taken the time to scour the literature so you don’t have to.

Conversations about constipation

Cite this article as:
Chris Dadnam. Conversations about constipation, Don't Forget the Bubbles, 2021. Available at:

Like most of you I have to deal with the issues of constipation within the ED or CAU environment and most of the time it’s not the reason the child attends the department! This can then lead to a series of awkward questions and issues that parents may ask that we need to consider in order to provide safe, useful and most of all, worthwhile advice! 

So let’s go through these questions ask issues:

1. My child has a UTI, why are you talking to me about constipation? 

This is something I get asked not only when a UTI is diagnosed but other clinical conditions including; appendicitis, bedwetting, incontinence, urinary retention, obstruction, etc…. it is important that parents understand the implications of constipation, not only from a pain and symptoms point of view but also the complications surrounding it. Indeed, many parents also struggle to understand how their child, who is rolling around in agony, is only suffering from constipation (you can literally feel them questioning your medical acumen). 

During these tough times I always mention two key points. Firstly, the fact that your bowel covers the majority of your abdomen. A build up of wind and solid matter in the bowels can bring about severe griping abdominal pain, when pressing against sensitive nerves. As it covers a lot of your abdomen, when full, it will compress other structures like your child’s bladder leading to urinary infections, incontinence and retention. The second point is that stools are like a toxin your body wants to expel, when it remains in your bowels it can get into small structures like your child’s appendix and cause it to become inflamed and that leads to appendicitis.

Also, the longer the stools sit in the colon the more water is absorbed leading to harder, solid stools. This will cause a blockage and lead to vomiting and obstruction which may require surgery. 

Once parents have a better understanding of these points they’re less likely to roll their eyes at constipation! 

2. How are they constipated, they go every day? 

This in fairness is a good question, one that used to throw me quite a bit in my early paediatric years, but let’s break it down. Constipation is not simply the length of time between going to the toilet, rather it is the build up and insufficient clearance of stools in your bowels. With this in mind, a child can go daily and pass small amounts of stool but still have a backlog of faecal matter in their bowels. Therefore also question the time spent on the toilet, straining and pain during defecation. These are all signs of constipation. If you can, ask your young patients too! 

3. They already drink plenty of fluids

Don’t let this answer fool you, explore the parents’ meaning of fluids. When we are saying it, we mean clear liquids like water and squash (preferably sugar-free), but for the parents, it’s anything from water and tea, to milk and hot chocolates. Now there is a myth that milk makes us constipated but that’s simply not the case….well not entirely. Milk is indeed a liquid and it doesn’t make us constipated but it’s thicker and takes longer to digest (hence why in surgery they stress only clear liquids 4hrs before). Milk fills up the child and so reduces their intake of solid food which will be full of fibre. 

Always remember, parents may say they’ve cut out all the milk, but this may have been substituted for milky teas and hot chocolates, so double check! 

In terms of managing the milk, appreciate the difficulty the family is about to face. Wean the milk down slowly, starting with the bottles in the middle of the day, then the morning bottle and finally the night bottle. Milk shouldn’t be stopped entirely, having a 250-500ml glass of milk daily is perfectly fine. 

4. They eat a really good diet 

Whenever I get this response, I immediately think they haven’t and 99% of the time I’m right……says a lot. 

Again, this is either due to a misconception as to what a good diet is, or they don’t think it’s an important issue so they simply brush it off with this generic statement so that they can get to the medication that will actually help. Another quick way to check is to just ask the child. They normally find it much more difficult to turn a blind eye.

I always try to tackle this in one of two ways:

Tell me what they eat?

– it’s surprising how many children don’t have breakfast or any of the three square meals a day. If they do, just add in tips when you can.

Breakfast; dried fruits in cereal (especially raisins), don’t switch the cereal completely but rather mix in an all bran, so they’re still getting their tasty favourites, but now with added fibre. Toast – if it’s white bread, freeze it; it’ll keep longer and by placing it straight into the toaster means that the strands of carbs, fats and protein are bound together and form fibre.

Lunch; Try to include salad into sandwiches. If the parents say they don’t like salad then how do they expect their children too! Encourage healthy eating in the parents as well, to form positive connotations for their kids.

Dinner; any sauce can hide a multitude of veggies if blended or chopped fine enough – so get them cooking and where possible get them to encourage their kids to join in. If they cook it themselves, they’ll appreciate the food and, for some reason, enjoy it more……probably a labour of love! And it’s a great time to leave out and pick on a bowl of fresh berries or grapes, the more accessible things are the more they get eaten.

Do they eat all their fruit and vegetables?

This again leads to a classic ‘Yes’ response – which falsely reassures a lot of healthcare professionals. In truth, it’s a vague and rather inadequate question to ask. If I told you that my child eats peeled apples and pears, has a glass of orange juice and then eats loads of veggies which I boil until soft… It might make you think twice about the goodness they’re actually getting.  So I always ask – Do they eat the skins of the fruit and vegetables? How do you prepare them? The skin of most fruits and vegetables holds the majority of fibre along with different vitamins and minerals required. In all honesty, if you are peeling apples and pears, all you’re left with is sugar and water, so I tell parents to give their child the peel instead! 

Again with veggies, I tend to suggest for microwaving or steaming as people tend to overcook them when they boil them. They need a crunch as that equals fibre. Root vegetables (potatoes, sweet potatoes, carrots, butternut squash, celeriac, parsnips) – all these lovely fibre rich foods – contain most of the fibre in their skins. I tell parents to roast them, long and slow – they’ll taste better (caramelizes the sugars in the veg/skin) so children will prefer them! 

Be mindful of smoothies and fruit juices. Yes, they can count for 1 of our 5 a day (soon to be 10 a day) but they can have little to no fibre, especially with the models that separate out the pulp. The pulp is fibre!! Try to get them to have whole fruits instead or 1 x 250ml glass of fruit smoothie a day with the pulp. 

5. I have tried all this and it doesn’t work 

Before you dismiss this answer make sure you look over the medical background again (cystic fibrosis, hypothyroid disease, Hirschsprung’s). Ask these all-important questions:

  • When did they have their very first poo? It should be within the first 48 hours. Then double-check it was a good amount – small smears don’t count.
  • Have they had issues with weight gain and prolonged issues with chest problems (in cystic fibrosis, LRTIs tend to happen towards the end of their first year of life).
  • Did they have a Guthrie / heel prick test. Any developmental delay? A large soft spot on their head?

In all of these conditions, the child would have always had an issue with constipation since birth, so don’t miss them. 

Once covered, it’s important to go through what they have tried….. most parents will only have been given a packet of Movicol and told to get on with it. Look at the summary section to see how to structure a constructive management plan.

6. I’m scared they’ll starve so I give them what they want. 

How many of us have been told this with little Jonny sitting there looking larger than life?

In general, throughout the developed world, children are unlikely to starve if their parents are trying to feed them a healthy balanced diet. There are caveats to this:-

  • Autistic children or children with textural issues. 
  • Children with a background of eating disorders (bulimia or anorexia). 

These children will need extra support and input from community and nutritional teams. 

All the other children will always put up a fight (normally a good one!) but then their bodies will give in and want food. This is an important step for parents to understand, especially when the child is too young to go out and get food themselves. Make sure you tell the parents this won’t be a simple task, and the main reason children normally win, is that carers will be busy and won’t have time to tackle this problem. It’s a quick fix to give them something just so that they know they’ve eaten…….then the habit starts. I always tell parents, wait until you have a week off and prepare yourself/ yourselves for a bumpy ride. Have a united front, it’s no good if one parent plays the ‘strict/ bad guy’ whilst the other literally feeds the problem behind their back. Prepare meals and hide away the unhealthy processed snacks (or don’t buy them in the first place) and leave fruit out. Again, get the child involved in cooking, build a healthy connection with food and make it fun. Children will most likely throw tantrums at the start, but remind them that eventually their child’s body will give in and they will come for food, most likely with a grumpy face. 

Just make sure they’re hydrated with clear fluids! And NO milky substitutes. Remind the parents they’re not bad people and this will help fix things in the long run.

7. Movicol doesn’t work and I don’t want it to make their bowels lazy 

This age-old answer…..makes you wonder why we bother using Movicol? More often than not they’ve not prepared it correctly, despite the instructions being on the box. Honestly, the ways parents use Movicol; sprinkle on cereal, mix into snacks or food, add to tea….the list goes on!

Movicol is only effective when it is bound with water. After this, the parent can then mix it with a small amount of any other liquid or flavouring. Make sure they don’t add it to a litre bottle of squash as the child will have to drink the whole lot. Also, this means they don’t need the flavoured versions (which taste vile – remember when they made you try them in medical school!). 

Another myth is that “it’ll make their bowels lazy.” Explain that Movicol is not a stimulant, it is an osmotic diuretic and acts to drive the water you mixed it with into the child’s stool to make them softer and easier to pass. With this in mind, even stimulant laxatives won’t make your bowels lazy. I always say, they can be on it for the rest of their lives, it’ll never make their bowels lazy – that tends to reassure parents.

8. I tried laxatives before and they suddenly had diarrhoea so I stopped using it. 

This answer may again throw you into thinking that the laxative has done a great job in under 72 hours and fixed a months worth of constipation… it sounds too good to be true?? Well, it is. The big problem here is, if clinicians don’t pre-warn the carers what might happen after starting a laxative, it can lead to long term mistrust in both the medication and in our advice.

I always start off by setting the day to start. Aim to start the laxative at the end of the week, a Thursday or Friday, to avoid accidents in the school. They will deter the child from ever trying them again.

Once we know when to take them, always triple check they’re using them correctly… mix with water first, then add to a small volume of any other liquid for taste.

Finally, but most importantly, the change in stool. Referring to the Bristol stool chart (the only card I carry around!), I explain the child will start with Type1-3 stools. Then, they’ll have what looks like diarrhoea, brown watery smelly stools, but, of course, it’s overflow. Take the time to talk about why this happens; the Movicol is slowly moving through the hard stools, like rain trickling down a wall, in their child’s bowel. The Movicol/water mix will initially run over it but over time their stools start to soften. 

The next step, again important due to risk of pain, is the big logs. And big means big! I’ve had parents say they’ve used shears to cut up these stools in the toilet. This is essentially the wall slowly being emptied out. 

Once this is over, they will finally have the soft mushy stools. The laxative story should not end there! It is important to mention this ‘wall of stool’ has caused the bowels to stretch. This will lead to a build-up of stools again as the child won’t know when they need to go. This is reservoir constipation. It can take months to revert back to normal so I always advise to continue on with the laxatives and reduce (but not stop) the maintenance daily dose down if the child is passing clear watery liquid. Usually, treatment should continue for at least three months to treat reservoir constipation (although in some children it can be longer).

9. They don’t like my cooking. They’re vegetarian now, I’m not. 

It doesn’t have to be vegetarian, of course, this is just what an angry mum said to me once about her daughter. Parents will mention the difficulties of preparing food they’re not used to cooking, I always suggest ‘get your child involved‘. This is the perfect time to do something together (bonus points as well in tackling mental health and isolation. It gets the family talking). The child will appreciate their intent and willingness to give their lifestyle a try, which will build confidence in the relationship as well. They can get a cookbook, go online (it’s all free and easily accessible these days) and adapt their cooking style. Again. this will make their child feel more involved and interested in cooking and eating healthy foods. 

10. They don’t like fruit and vegetables. 

I think we’ve all suffered from hating vegetables and fruit at some point in our lives. I remember hating tomatoes and peppers, so I feel for any parent tackling this problem. 

There are several factors to contend with here:

  • Their child not liking the fruit because it’s unknown to them or feels texturally unsatisfactory.
  • Having access to other more ‘enjoyable’ foods such as biscuits, chocolates and crisps around the house which they can graze on and avoid these unwanted bags of goodness. 
  • Watching older siblings and parents, and copying them.

To this, I normally offer a number of solutions but be mindful that parents will have busy lives around their child’s eating habits so it has to be a conscious effort at a convenient time, like over the weekend or annual leave.  

Firstly, hide unhealthy snacks or simply reduce the amount you buy, what they don’t see they don’t know…. out of sight, out of mind technique.

Secondly, I always tell carers that they and older siblings are role models. If you’re not eating it, why should they? There should be a united front by the parents. 

Finally, get cooking and get your child involved. Any child who cooks will appreciate the food they’ve made and the sense of achievement, even if it doesn’t taste nice, they’ll love it. It’s a great time to chat over a bowl of fresh berries…

My own enthusiasm then tends to kick in. I like to say “Get creative in the kitchen!” I’ve mentioned simple things for example: make flapjacks and throw in lots of dried fruits; raisins, dates, apricots, prunes – all-natural sweetness with skinned nuts & oats. Freeze smoothies with the pulp into ice-lollies. Fruit crumbles with honey and oats… With vegetables, always remember to steam or microwave them, they need the crunch. Again if kids don’t like them…. Chop them up/ blend them and throw them into sauces, pies and mixed into other dishes. If it’s the taste they don’t like, again mixed into gravy or a tasty sauce will fix that problem! 

It is important to mention the importance of a healthy balanced diet. Food is your best medicine. This is can be true for managing many conditions; anaemia , skin problems, poor immunity, nail and hair problems..you get my point. A varied diet holds the key to a lot of management plans, and it’s important to mention this even when the child is on supplements. A classic example is the parent says we’ve fixed the iron problem with iron tablets, but they fail to realise, without vitamin C your body can’t absorb the iron through the small intestine. Therefore, they’ll be questioning why their child remains anaemic in months to come. 

11. They’ve gone back into nappies as they’re scared of using the toilet. 

This is an important issue. It’ll mean the child will probably have problems with incontinence which may be affecting their social life such as staying over at a friends houses. Yet another reason why it needs tackling. 

Always start with asking what happened? More often than not it’s a series of bad habits and untimely events that have led to a regression in the family’s good practice. It happens to the best of us. Reassure everyone and give them the positive reinforcement that they’ve identified a problem that needs to be solved. Then offer the advice below. Take your time with these parents, it would have taken a lot for them to come into an acute setting to seek advice, so try to give them some. 

A framework for managing constipation.

This is ultimately an important topic that you have or, no doubt, will see at some point in your paediatric career. Knowing how to manage it is a core skill. 

I always frame my management in 3 steps: 

1. Diet and fluid intake – take the points from the above questions. Ultimately, the parents control the diet and food at home. They, and older siblings, are the child’s role models so what they eat will influence the child’s diet too. Remind them that food is their family’s best medicine so they need to get it right. Cancel out the milky drinks, cook smart & healthy and don’t forget clear fluids.

2. Toileting – our constipation module covers this but key points; get them into a routine (20 to 30mins after dinner – to sit on the toilet). Make the toilet a fun place with all their toys and gadgets and don’t forget to get them to blow the bubbles. Optimise positioning with knees above bums when sitting, using a footstool. 

3. Medication – ensure parents are giving them correctly – mixing with water first then adding to any other liquid for taste. Make sure this isn’t a full bottle, as they’ll have to drink the lot!. Movicol doesn’t make your bowels lazy. If they’re on a disimpaction regime, think about the volume they’ll be drinking each time. It may be better to split it into thrice daily doses instead. Briefly touch on the sequence of stool changes to reduce misconceptions of overflow and diarrhoea. Lastly start Movicol towards the end of the week, Thursday or Friday to avoid accidents at school. 

End with: 

  • Referencing the ERIC constipation website. It’s a great tool for constipation and bedwetting. It talks to the parent and child, so easy to understand and explain.
  • It will take time for things to fall into place. There is no quick fix. There will be tantrums, sleepless nights and days you’ll want to give in. Hang in there and once you’re sorted you’ll wish you’d done it sooner!

Bubble Wrap PLUS – January

Cite this article as:
Anke Raaijmakers. Bubble Wrap PLUS – January, Don't Forget the Bubbles, 2021. Available at:

Happy New Year! Most of us have a long list of good intentions for the new year. We hope that keeping up with literature in 2021 is one of them. Here is a new Bubble Wrap Plus, our monthly paediatric Journal Club List provided by Professor Jaan Toelen of the University Hospitals in Leuven (Belgium). This comprehensive list of ‘articles to read’ comes from 34 journals, including Pediatrics, The Journal of Pediatrics, Archives of Disease in Childhood, JAMA Pediatrics, Journal of Paediatrics and Child Health, NEJM, and many more.

This month’s list features answers to intriguing questions such as: ‘Is child abuse more prevalent during the pandemic?’, ‘Can the smartphone replace the Bristol Stool Chart?’, ‘Does ‘one hour’ matter in giving antibiotics in septic shock?’, ‘Does social distancing lead to fewer URTIs?’, ‘Are ketones useful at triage?’ and ‘Should we worry about invasive infections in children with OMA?’.

You will find the list is broken down into four sections:

2. Original clinical studies

Physiological responses to facemask application in newborns immediately after birth.

Gaertner VD, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Dec 9

Kawasaki Disease Shock Syndrome versus Septic Shock: Early Differentiating Features Despite Overlapping Clinical Profiles.

Power A, et al. J Pediatr. 2020 Dec 5:S0022-3476(20)31482-7.

Invasive Bacterial Infections in Afebrile Infants Diagnosed With Acute Otitis Media.

McLaren SH, et al. Pediatrics. 2020 Dec 7:e20201571.

Invasive Bacterial Infections in Afebrile Infants With Otitis Media: Worry Less but Still Worry.

Ravera J, et al. Pediatrics. 2020 Dec 7:e2020039602.

Machine Learning Supports Automated Digital Image Scoring of Stool Consistency in Diapers.

Ludwig T, et al. J Pediatr Gastroenterol Nutr. 2020 Dec 1.

Use of insulin pump therapy is associated with reduced hospital-days in the long-term: a real-world study of 48,756 pediatric patients with type 1 diabetes.

Auzanneau M, et al. Eur J Pediatr. 2020 Dec 1.

Prescription of acid inhibitors in infants: an addiction hard to break.

Levy EI, et al. Eur J Pediatr. 2020 Dec;179(12):1957-1961.

Use of anti-reflux medications in infants under 1 year of age: a retrospective drug utilization study using national prescription reimbursement data.

O’Reilly D, et al. Eur J Pediatr. 2020 Dec;179(12):1963-1967.

Fool me once… treatment exposure to achieve remission in pediatric IBD.

Van Limbergen JE, et al. Eur J Pediatr. 2020 Dec;179(12):1921-1924.

Infliximab in young paediatric IBD patients: it is all about the dosing.

Jongsma MME, et al. Eur J Pediatr. 2020 Dec;179(12):1935-1944.


Diarrheal Deaths After the Introduction of Rotavirus Vaccination in 4 Countries.

Paternina-Caicedo A, et al.Pediatrics. 2020 Dec 30:e20193167.

Emergency Visits and Hospitalizations for Child Abuse During the COVID-19 Pandemic.

Kaiser SV, et al. Pediatrics. 2020 Dec 30:e2020038489.

Association Between Abnormal Fetal Head Growth and Autism Spectrum Disorder.

Regev O, et al. J Am Acad Child Adolesc Psychiatry. 2020 Dec 27:S0890-8567(20)32215-2.

High flow in children with respiratory failure: A randomised controlled pilot trial – A paediatric acute respiratory intervention study.

Franklin D, et al. J Paediatr Child Health. 2020 Dec 30.

Early Skin-to-skin Care with a Polyethylene Bag for Neonatal Hypothermia: A Randomized Clinical Trial.

Travers CP, et al. J Pediatr. 2020 Dec 26:S0022-3476(20)31574-2.

Atypical bartonellosis in children: What do we know?

Lemos AP, et al. J Paediatr Child Health. 2020 Dec 10.

Alternative Cerebral Fuels in the First Five Days in Healthy Term Infants: The Glucose in Well Babies (GLOW) Study.

Harris DL, et al. J Pediatr. 2020 Dec 26:S0022-3476(20)31573-0.

Improving Toddlers’ Healthy Eating Habits and Self-regulation: A Randomized Controlled Trial.

Nix RL, et al. Pediatrics. 2020 Dec 28:e20193326.

Bench-top comparison of thermometers used in newborn infants.

Dunne EA, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Dec 28:fetalneonatal-2020-320123.

Pediatric Emergency Department Visits at US Children’s Hospitals During the COVID-19 Pandemic.

DeLaroche AM, et al. Pediatrics. 2020 Dec 23:e2020039628.

Sustained Lung Inflations During Neonatal Resuscitation at Birth: A Meta-analysis.

Kapadia VS, et al. Pediatrics. 2020 Dec 23:e2020021204.

Association between Baseline Cortisol Serum Concentrations and the Effect of Prophylactic Hydrocortisone in Extremely Preterm Infants.

Renolleau C, et al. J Pediatr. 2020 Dec 23:S0022-3476(20)31567-5.

Delayed Administration of Antibiotics beyond the First Hour of Recognition is Associated with Increased Mortality Rates in Children with Sepsis/Severe Sepsis and Septic Shock.

Sankar J, et al. J Pediatr. 2020 Dec 23:S0022-3476(20)31545-6.

Association of Cesarean Delivery with Childhood Hospitalization for Infections before 13 Years of Age.

Auger N, et al. J Pediatr. 2020 Dec 21:S0022-3476(20)31546-8.

Effect of a Sepsis Screening Algorithm on Care of Children with False-Positive Sepsis Alerts.

Baker AH, et al. J Pediatr. 2020 Dec 21:S0022-3476(20)31543-2.

Rates of Presentation, Treatments and Serious Neurologic Disorders Among Children and Young Adults Presenting to US Emergency Departments With Headache.

Ramgopal S, et al. J Child Neurol. 2020 Dec 24:883073820979137.

COVID-19 in children treated with immunosuppressive medication for kidney diseases.

Marlais M, et al. Arch Dis Child. 2020 Dec 21:archdischild-2020-320616.

Audit on awake anorectal manometry: tolerability in children.

Athanasakos E, et al. Arch Dis Child. 2020 Dec 21:archdischild-2020-321083.

A Graded Approach to Intravenous Dextrose for Neonatal Hypoglycemia Decreases Blood Glucose Variability, Time in the Neonatal Intensive Care Unit, and Cost of Stay.

Sen S, et al. J Pediatr. 2020 Dec 15:S0022-3476(20)31507-9.

Association of Childhood Growth Hormone Treatment With Long-term Cardiovascular Morbidity.

Tidblad A, et al. JAMA Pediatr. 2020 Dec 21:e205199.

Cardiovascular Disease in Former Pediatric Recipients of Growth Hormone: Another Look at Growth Hormone Safety.

Grimberg A. JAMA Pediatr. 2020 Dec 21:e205232.

Deamidated Gliadin Antibodies: Do They Add to Tissue Transglutaminase-IgA Assay in Screening For Celiac Disease?

Abdulrahim A, et al. J Pediatr Gastroenterol Nutr. 2020 Dec 16;Publish Ahead of Print.

Acute Kidney Injury Associated with Late-Onset Neonatal Sepsis: A Matched Cohort Study.

Coggins SA, et al. J Pediatr. 2020 Dec 16:S0022-3476(20)31505-5.

Autism spectrum disorder and kidney disease.

Clothier J, et al. Pediatr Nephrol. 2020 Dec 19.

Bronchopulmonary dysplasia and postnatal growth following extremely preterm birth.

Dassios T, et al. Arch Dis Child Fetal Neonatal Ed. 2020 Dec 17:fetalneonatal-2020-320816.

Long-Term Survival and Causes of Death in Children with Trisomy 21 After Congenital Heart Surgery.

Peterson JK, et al. J Pediatr. 2020 Dec 23:S0022-3476(20)31568-7.

Follow-up Blood Cultures in Children With Staphylococcus aureus Bacteremia.

Cardenas-Comfort C, et al. Pediatrics. 2020 Dec;146(6):e20201821.

Motor Impairment in Children With Congenital Heart Defects: A Systematic Review.

Bolduc ME, et al. Pediatrics. 2020 Dec;146(6):e20200083.

Hospitalised infants due to falls aged less 12 months in New South Wales from 2002 to 2013.

Cooray N, et al. J Paediatr Child Health. 2020 Dec;56(12):1885-1890.

Risk of traumatic intracranial haemorrhage in children with bleeding disorders.

Bressan S, et al. J Paediatr Child Health. 2020 Dec;56(12):1891-1897.

Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome – Is It Related to Ethnicity? An Israeli Multicenter Cohort Study.

Amarilyo G, et al. J Pediatr. 2020 Dec;227:268-273.

Association Between Fat Mass in Early Life and Later Fat Mass Trajectories.

de Fluiter KS, et al. AMA Pediatr. 2020 Dec 1;174(12):1141-1148.

Complementary and Alternative Medicine Use in Pediatric Functional Abdominal Pain Disorders at a Large Academic Center.

Ciciora SL, et al. J Pediatr. 2020 Dec;227:53-59.e1.

Effect of Social Distancing Due to the COVID-19 Pandemic on the Incidence of Viral Respiratory Tract Infections in Children in Finland During Early 2020.

Kuitunen I, et al. Pediatr Infect Dis J. 2020 Dec;39(12):e423-e427.

Universal screening of high-risk neonates, parents, and staff at a neonatal intensive care unit during the SARS-CoV-2 pandemic.

Cavicchiolo ME, et al. Eur J Pediatr. 2020 Dec;179(12):1949-1955.

Risk Factors for Orthostatic Hypertension in Children.

Hu Y, et al. J Pediatr. 2020 Dec;227:212-217.e1.

Neurodevelopmental outcomes after moderate to severe neonatal hypoglycemia.

Rasmussen AH, et al. Eur J Pediatr. 2020 Dec;179(12):1981-1991.

The utility of ketones at triage: a prospective cohort study.

Durnin S, et al. Arch Dis Child. 2020 Dec;105(12):1157-1161.

Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.

Walsh EE, et al. N Engl J Med. 2020 Dec 17;383(25):2439-2450.

Does detection of fetal growth restriction improve neonatal outcomes?

Selvaratnam RJ, et al. J Paediatr Child Health. 2020 Dec 14.

Children and young adults with spinal muscular atrophy treated with nusinersen.

Osredkar D, et al. Eur J Paediatr Neurol. 2020 Dec 4;30:1-8.

Effect of Early Targeted Treatment of Ductus Arteriosus with Ibuprofen on Survival Without Cerebral Palsy at 2 years in Infants with Extreme Prematurity: A Randomized Clinical Trial.

Rozé JC, et al. J Pediatr. 2020 Dec 8:S0022-3476(20)31488-8.

Time Course of Coronary Artery Aneurysms in Kawasaki Disease.

Tsuda E, et al. J Pediatr. 2020 Dec 7:S0022-3476(20)31484-0.

4. Case reports

Chewing gum bezoar as an unexpected cause of acute intestinal obstruction.

Sinopidis X, et al. J Paediatr Child Health. 2020 Dec 29.

Unusual presentation of coeliac disease with idiopathic intracranial hypertension.

Pathmanandavel K, et al. J Paediatr Child Health. 2020 Dec 21.

Case 39-2020: A 29-Month-Old Boy with Seizure and Hypocalcemia.

Virkud YV, et al. N Engl J Med. 2020 Dec 17;383(25):2462-2470.

A Gut Feeling: Abdominal Symptoms as an Initial Presentation of EVALI.

Wekon-Kemeni C, et al. Pediatrics. 2020 Dec 30:e20193834.

Sequential Retinal Hemorrhages in an Asymptomatic Child.

Ho DK, et al. J Pediatr. 2020 Dec;227:319-320.

If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments!