The Paediatric Papers are summaries of important journal articles for paediatric staff. They aim to provide concise, easily read clinical advice from high-impact publications.

Background

The Paediatric literature is constantly evolving and at such a rapid pace that it is difficult to keep up-to-date with the evidence base. Paediatric Papers aims to help by distilling the wisdom gained from journal articles into written, audio or multimedia summaries that can be consumed within two minutes.

Get involved

If you are interested in creating, or want to suggest, an article for a Paediatric Papers summary, please email education.hub@rch.org.au

A summary of how to make a Paediatric Papers summary can be found here.

Editors

Jye Gard, Amy Gray

Contributors

John Doan, Julian Dascalu, Jye Gard

Article

Parker CM, Cooper MN. Prednisolone versus dexamethasone for croup: a randomized controlled trial. Pediatrics. 2019 Sep 1; 144(3):e20183772.

How it helps

Use steroids in children with croup and stridor at rest to reduce the severity of symptoms, risk of a readmission or ICU admission. Steroids also decrease the length of hospital and emergency department stays. The type of steroid doesn't matter.

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Study type

Prospective, double-blind, non-inferiority randomised controlled trial at a single site (two hospitals linked to a tertiary paediatric emergency department Perth).

Major findings

  • A single dose of high-dose dexamethasone (0.6mg/kg/dose), low-dose dexamethasone (<0.15mg/kg/dose) and prednisolone (1mg/kg/dose) were found to be equally efficacious in reducing hospital representations and symptom severity 1-hour post drug administration (Westley Croup Score).
  • Children with prednisolone were more likely to be given a second dose on re-presentation.
  • Some children given low-dose dexamethasone had poor symptoms scores at 3 hours. There may be a small population where low-dose dexamethasone has a delayed effect.

Where next

  • The study looked at non-inferiority, not superiority. New studies are needed to determine which steroid is best.
  • The study population was limited to one site and did not include atypical croup presentations (children <6 months, >20kgs).

Additional resources

  • Learn more about the Westley Croup Score here

Summary by Jye Gard, April 2020

Article

Peters RL, Koplin JJ, Gurrin LC, Dharmage SC, Wake M, Ponsonby AL, et al. The prevalence of food allergy and other allergic diseases in early childhood in a population-based study: HealthNuts age 4-year follow-up. The Journal of allergy and clinical immunology. 2017; 140(1):145-53.e8.

How it helps

The HealthNuts group provide the first longitudinal estimate of food allergy prevalence in Australian infants.

Children may ‘grow out’ of previously confirmed challenge-confirmed food allergies – they are more prevalent in 1 year old than 4 year olds.

Prevalence of allergy among children in Melbourne, Australia is remarkably high compared to the rest of the world.

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Study type

Population-based, longitudinal cohort study of children in Melbourne, Australia reporting prevalence of food allergy (egg, peanut, sesame). Initial prevalence data had been described previously in 5,276 12-month-old infants (Allen 2015). Follow-up data was collected from the participants at 4 years of age.

Challenge-confirmed food allergy was defined by:

  • Positive test of sensitisation (skin prick testing wheal above cut-off for age and/or elevated specific IgE ³35 kU/L), and
  • Positive oral food challenge.

Major findings

  • Prevalence of challenge-confirmed food allergy was less at 4 years of age (3.8%) compared to 12 months of age (11.0%).
  • Between 12 months and 4 years of age, the most marked decrease in prevalence was seen with egg allergy (see below).
  • 5% of children experienced symptoms of an allergic disease (food allergy, asthma, eczema and/or allergic rhinitis) in the first 4 years of life.
  • International data reports much lower prevalence of food allergy than described by HealthNuts.
Prevalence of Allergic Outcomes
  1 year prevalence % (95% CI) 4 years prevalence % (95% CI)
Peanut allergy 3.1 (2.7-3.6) 1.9 (1.6-2.3)
Egg allergy 9.5 (8.7-10.3) 1.2 (0.9-1.6)
Sesame allergy 0.6 (0.5-0.9 0.4 (0.3-0.6)
Any challenge-confirmed food allergy 11.0 (10.1-11.9) 3.8 (3.3-4.4)

 

Where next

  • Some participants from the original cohort were lost to follow-up at 4 years of age (18.7%), and others declined to undergo a food challenge at 4 years.
  • Not all allergens were tested in the follow-up period, e.g. IgE-mediated cow’s milk allergy.
  • Further follow-up is planned for the HealthNuts participants at 6 and 10 years of age, with repeat questionnaires and formal allergy testing.

Additional resources

Summary by John Doan, May 2020

Article

Mitre E, Susi A, Kropp LE, Schwartz DJ, Gorman GH, Nylund CM. Association between use of acid-suppressive medications and antibiotics during infancy and allergic diseases in early childhood. JAMA pediatrics. 2018 Jun 1;172(6):e180315-.

How it helps

Infants (<6months) who are prescribed acid-suppressant medicines are more likely to be prescribed antibiotics before they turn 12 years old.

Infants who are prescribed acid-suppressant medicines are more likely to develop allergies. Even if they only take a short course (<60 days).

Children (<12 years old) who are prescribed antibiotics are more likely to develop allergies.

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Study type

A retrospective cohort study of 792, 130 children of parents who work or worked for the United States Department of Defence.

The researchers used the Military Health System (MHS); defence workers and their families are provided with subsidised healthcare and the MHS is a database that records their medical billing data (inpatient and outpatient). Akin to our PBS.

The study expressed most of their findings using Hazard Ratios.

Major findings

  • Infants who received acid-suppressants (either H2RAs or PPIs) have significantly higher risk of every type of allergic disease. Infants given PPIs a little more so than those given H2RAs.
  • The risk is dose-dependent. Infants who took long courses of acid-suppressants (>60 days) were at higher risk, than those who had shorter courses. But even children who had short courses had significantly increased risk!
  • The most common allergic disease children given acid-suppressants as infants developed was food allergies. Especially cow’s milk allergy (their risk increased from 2/100 to 4/100 – a 52% jump in risk). There was also a marked increase in their risk of childhood asthma, allergic conjunctivitis, and urticaria.
  • Infants given antibiotic also had an increased risk of all allergic diseases, especially asthma (a greater than 2-fold risk!). There was also a marked increase in their risk of food allergies (cow’s milk and egg), anaphylaxis, allergic conjunctivitis and medication. As well as atopic dermatitis, allergic rhinitis, contact dermatitis and urticarial.
  • Unlike acid-suppressive medications, antibiotics did not demonstrate a dose-dependent risk for the development of allergies.
  • Children who were prescribed antibiotics during infancy, were more likely to also be prescribed acid-suppressants. And vice-versa.
  • The study recorded interesting data about how US doctor prescribing preferences differ from ours

Where next

  • Are there prescriber biases at play? If so, what are they?
  • Is there other protective or risk factors to consider? Is it safer to prescribe these medicines to certain cohorts?
  • Can the risk be mitigated?

Additional resources

Summary by Jye Gard, May 2020

Article

Leigh J, Rickard M, Sanger S, Petropoulos J, Braga LH, Chanchlani R. Antibiotic prophylaxis for prevention of urinary tract infections in the first year of life in children with vesicoureteral reflux diagnosed in the workup of antenatal hydronephrosis: a systematic review. Pediatric Nephrology. 2020 Apr 30:1-8.

How it helps

Currently there is no strong evidence for either the use or disuse of prophylactic daily antibiotics for children <1y found to have vesicoureteric reflux

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Study type

A literature review (18 studies were included from 6895 found across four databases) where the researchers used software to exclude irrelevant articles based on their titles and abstracts.  Two researchers then read the full texts of the remaining articles (or 3 in a tie-break) to decide if they met the inclusion criteria.

Major findings

  • Daily prophylactic antibiotics are often empirically prescribed for infants with vesicoureteric reflux (VUR) with the aim of reducing their rate of urinary tract infections (UTIs) in the first year of life
  • Whilst there is some evidence that this may hold true for infants with symptomatic VUR (e.g. those who have already had a UTI), there is a paucity of evidence to start them for infants with asymptomatic VUR (i.e. as prophylaxis for infants who have yet to have a UTI)
  • The authors intended to perform a meta-analysis to test the hypothesis that infants with asymptomatic VUR would benefit from prophylactic antibiotics.
  • However, what they actually found was that the meta-analysis could not be completed – the current pool of available studies are of low-quality, retrospective and most do not include a comparison control group (i.e. researchers only report on the findings of children who took prophylactic antibiotics). Those that did used tiny sample sizes.
  • Without good data, very little could be concluded. There was some evidence that 15% of infants on prophylactic antibiotics will still develop at least one UTI anyway. Most were female.

Where next

  • This is a good example of the role of a literature review – to help identify a gap in research

Additional resources

  • Learn more about research tools like
    • Guidelines for how to conduct a systematic review or meta-analysis PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)
    • Guidelines on how to assess non-randomised studies (The Newcastle-Ottawa Scale)
    • Software you can use to help with Cochrane style reviews
  • The benefit of prophylactic antibiotics in infant with symptomatic vesicoureteric reflux

Summary by Jye Gard, May 2020

Article

Franklin D, Shellshear D, Babl FE, Schlapbach LJ, Oakley E, Borland ML, Hoeppner T, George S, Craig S, Neutze J, Williams A. Multicentre, randomised trial to investigate early nasal high—flow therapy in paediatric acute hypoxaemic respiratory failure: a protocol for a randomised controlled trial—a Paediatric Acute Respiratory Intervention Study (PARIS 2). BMJ open. 2019 Dec 1; 9(12).

How it helps

Using high-flow reduces the need to transfer children with bronchiolitis to a PICU, but the number needed to treat (NNT) is 9.

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Study type

Prospective, non-blinded, randomised controlled trial at multiple centres (Australian & New Zealand hospitals).

Major findings

  • High-flow is safe to use. Adverse events were low in both the low-flow and high-flow groups (both had 1 child each that developed a pneumothorax that didn't need draining). This means children on high-flow treatment don't necessarily need extra nursing cares.
  • Starting high-flow doesn't change how long a child stays in hospital (ward or ICU) or needs oxygen.
  • In bronchiolitis, high-flow improves a child's observations (heart rate, respiratory rate and oxygen saturations) and thus reduces MET calls.

Where next

  • The treatment failure rates were lower at hospitals without a PICU. Is this because these hospitals have a higher threshold to start high-flow? Is this appropriate?
  • 1/3 escalations from low-flow to high-flow treatment was made at a doctor's request, not because their observations had changed. What are the factors that make us choose to escalate care, even if a child's observations are the same? Are there other bedside observations we should measure or account for?

Additional resources

  • Check out the first PARIS trial here.

Summary by Jye Gard, April 2020

Article

O’Brien S, Craig S, Babl FE, Borland ML, Oakley E, Dalziel SR; Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network, Rational use of high-flow therapy in infants with bronchiolitis. What do the latest trials tell us?’ A Paediatric Research in Emergency Departments International Collaborative perspective, J Paediatr Child Health. 2019 Jul; 55(7):746-752.

How it helps

Hypoxaemia (<91%) in bronchiolitis should be treated initially with low flow O2 via nasal prongs, up to 2L/min.

High flow should be used as rescue therapy if no improvement over 4 hours on low flow.

Early use of high flow O2 for work of breathing in the absence of hypoxaemia is not supported by evidence

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Study type

Systematic review of the evidence base comparing immediate high flow O2 therapy to rescue high flow O2 therapy. Analysing systematic reviews and randomised controlled trials of HFNC therapy in infants with bronchiolitis from 1 January 2000 to 27 June 2018.

Major findings

  • Early use of high flow O2 did not reduce the rate of ICU admission, rate of intubation, duration of oxygen therapy or duration of stay.
  • Children who will benefit from high-flow, will do so within 4 hours. Their heart rate & respiratory rate will begin to normalise and their Paediatric Early Warning Score will reduce.
  • High flow is an effective rescue therapy for those failing to improve with low flow therapy with ~60% avoiding further escalation to CPAP and admission to ICU.
  • Initial use of high flow O2 did not provide a cost benefit.
  • High flow therapy is considered safe with no significant increase in adverse effects compared to low flow.

Gaps in the literature

  • Significant variability exists in the literature when comparing target saturations, criteria to escalate care, and flow rates and FiO2 for O2 therapy.
  • No studies exist comparing treatment of bronchiolitis with high flow, vs treatment of bronchiolitis with NO high flow.

Additional resources

Summary by Julian Dascalu, April 2020

Article

Foster SJ, Cooper MN, Oosterhof S, Borland ML. Oral prednisolone in preschool children with virus-associated wheeze: a prospective, randomised, double-blind, placebo-controlled trial. The Lancet Respiratory Medicine. 2018 Feb 1;6(2):97-106.

How it helps

Prednisolone reduces the time preschool aged children with viral-associated wheeze spend in-hospital to <7hours. Especially pre-schoolers who present with a severe wheeze, previous diagnosis of asthma or who use salbutamol at home. Personal and family history of atopy are not good indicators of prednisolone effect.

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Study type

A non-inferiority randomised, double-blind, placebo-controlled trial at a single-site (Emergency Department of Princess Margaret Hospital in Perth, Australia). Testing that placebo was non-inferior to prednisolone.

After this was finished, the researchers then used the data to perform a post-hoc superiority study.

Major findings

  • The “time in-hospital” was calculated from when the child was given prednisolone given until the time they were ready for discharge. Prednisolone reduced the incidence of children who stayed >7hours in-hospital
  • Steroids did not reduce the incidence of short (<4hours) hospital stays
  • Other secondary health outcomes were reduced: hospital admission, emergency re-presentations, general practitioner consultations, and use of salbutamol within 7 of the initial presentation to the ED.
  • The study used children aged 24-72 months so as not to confuse pre-wheeze with bronchiolitis. This hasn’t been done in many other studies!
  • No serious steroid related side-effects were reported (one child had a rash and two became hyperactive – one of the two was from the placebo group)

Where next

  • Further studies are needed to determine the impact oral prednisolone has on pre-school wheezers’ short, medium and long-term health outcomes
  • What is the role of prednisolone in treating children in the ‘sticky’ age range of 9 months to 2 years old?
  • Children who used steroids within 14 days of presentation were excluded – further studies regarding repeat or prolonged steroid therapy are needed

Additional resources

Summary by Jye Gard, May 2020

Article

Morris R, Jones S, Banerjee S, Collinson A, Hagan H, Walsh H, Thornton G, Barnard I, Warren C, Reid J, Busfield A. Comparison of the management recommendations of the Kaiser Permanente neonatal early-onset sepsis risk calculator (SRC) with NICE guideline CG149 in infants≥ 34 weeks’ gestation who developed early-onset sepsis. Archives of Disease in Childhood-Fetal and Neonatal Edition. 2020 Mar 13.

How it helps

For infants >34 weeks gestation, the National Institute for Health and Care Excellence (NICE) guidelines and Kaiser Permanente neonatal Sepsis Risk Calculator (SRC) are good at detecting early onset neonatal sepsis.

The NICE guidelines are superior at detecting the 1 in 5 cases that are asymptomatic at 4 hours of life.

Neither NICE or SRC are good at detecting sepsis <4 hours of life. Hourly patient reviews are.

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Study type

Retrospective analysis of five maternity centres in the UK – their clinical notes, blood and CSF cultures results. The researchers analysed the sensitivity of two different tools in detecting neonatal sepsis.

Out of a birth population of 142,333 babies born >34 weeks, 72 were found to have positive cultures. Only 70 were included in the study, as records for 2 babies were incomplete or couldn’t be found.

All 70 received antibiotics, however only 43/70 were given antibiotics early (within 4 hours of life). The remaining 27/40 culture-positive babies became symptomatic >4 hours of life and were started on antibiotics when these symptoms were seen.

The researchers then applied both the NICE and SRC tools to the cases to see if they recommended starting antibiotics, and if so, when.

Major findings

  • The NICE guidelines picked up 39/43 babies that needed antibiotics vs the SRC that picked up 27/43. The extra 4 cases that were missed by both tools were started on antibiotics because of changes to other clinical observations.
  • The 12 cases caught by the NICE guidelines but not the SRC were clinically well babies whose mother had a fever or had received (adequate) intrapartum antibiotics. The SRC didn’t pick up any cases the NICE guidelines did not.
  • The researchers found that the trade off for prophylactically treating 12 asymptomatic infants with suspected early onset sepsis was the unnecessary treatment of approximately 11386-16852 infants. It also noted that reasons commonly given for not following the tools were only using parts of the tools (and ignoring others) and “clinical nervousness”.

Where next

  • The study recommended that a new trial should assess the efficacy of using the NICE guidelines first (given their increased sensitivity) and then the SRC for positive cases (given its more comprehensive suggestions for follow-up observations) – to see if this works better
  • Are there other factors to consider regarding the detection of? Like the rate of false-negative blood cultures due to inadequate volumes of blood collected in the culture bottle (contentious) or other test collection issues

Additional resources

  • Check out the Kaiser Permanente Neonatal Early-Onset Sepsis calculator here
  • Check out the NICE interactive flowchart here and full guideline here
  • Proof that it is safe and feasible to implement at tertiary Australian hospitals

Summary by Jye Gard, June 2020