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, Emer Ryan, Nelson Wang, Ary Sudarmana, Caitlin Richardson

Article

Twilhaar ES, de Kieviet JF, van Elburg RM, Oosterlaan J. Academic trajectories of very preterm born children at school age. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2019;104F419-F423

How it helps

This is the first longitudinal analysis of how very preterm (VP) children perform academically during their primary school years compared to their peers born at term. VP children frequently have problems in arithmetic, reading comprehension and spelling that persist throughout primary school. However, they show a similar rate of academic progression to term-born children, which suggests that with early intervention VP children can 'catch up' to their peers. 

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Study type

A longitudinal analysis of Dutch children using a national educational measurement (in Amsterdam, primary school children undergo a variety of standardised tests over grades 1 - 6).  

A selection of VP children (GA <32/40, many of whom also had very low birth weights <1500gthat had participated in a different study whilst cared for in an Amsterdam NICU from 2001- 2003 were recruited. 52/102 eligible children agreed to participate in the new study. 

58 classmates and students from neighbouring schools who were born at term and free of developmental, behavioural and learning disorderswere used as study controls. All children were tested in arithmetic, spelling and reading comprehension at multiple points between grades 1 - 6.  

Major findings

  • VP children scored lower in all three subjects over the course of their primary school education. 0.53 SD lower in arithmetic, 0.31 SD lower in reading comprehension and 0.21 SD lower in spelling. i.e. Between 2 to 5 letter grades lower than their peers. 
  • One in three VP children repeated a grade. 
  • VP children showed the same academic growth over time compared to controls though were generally unable to reach the same performance levels by the end of the study. i.e. even with early intervention, six years was too short for VP children to achieve grades similar to the ex-term peers 
  • VP children were more likely to require educational assistance and have a lower education level at the end of study  

Where next

  • Further studies are needed to investigate which learning skills and neurocognitive functions can be targeted to utilise the learning potential in VP children to allow them to reach similar education levels as their term-born peers 

Additional resources

Summary by Aryanto Sudarmana, August 2020

Article

Wang ME, Biondi EA, McCulloh RJ, Garber MD, Natt BC, Lucas BP, Schroeder AR. Testing for meningitis in febrile well-appearing young infants with a positive urinalysis. Pediatrics. 2019 Sep 1;144(3).

How it helps

In America, there remains wide variation in practice - which infants with a positive urinalysis undergo LP Infants <30 days old with raised inflammatory markers are more likely to have an LP. Hospitals who see lots of febrile infants (>10 cases of fever of unknown origin per day) are more likely to do LPs Infants >30 days old with a positive urinalysis who "appear well" do not need LP

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Study type

The researchers performed a secondary retrospective analysis on data that had already been collected and used for a different quality improvement project (Reducing Excessive Variability in Infant Sepsis Evaluation - REVISE) The data included 20,570 "well looking" infants (7 - 60 days old) that attended one of 124 American hospitals between September 2015 to November 2017 for fever (T >38oC) of unknown origin. Infants who were "unwell looking" or at increased risk of bacterial infection were excluded:
  • Assessed as either: toxic, ill-appearing, lethargic, sick-appearing
  • Comorbidities including genetic, neuromuscular and developmental disease
  • Diagnosed as having bronchiolitis
So unwell that they needed to be transferred to different hospital

Major findings

  • Positive urinalysis = dipstick positive (including trace) for either leucocyte esterase or nitrates, or urinalysis showed >5 WCC per high-power field
  • Abnormal inflammatory markers = >1 of WCC <5000 or >15000m3, absolute band count >1500 cells mm3 per band-to-neutrophil count >0.2, elevated CRP or procalcitonin
  • 9/10 had urinalysis before discharge from ED. Of these, 2/10 had positive urinalyses. 90% had collection either via SPA or in-out catheter
  • 70% of children with positive urinalyses underwent LP. Most children who underwent LP were started on empirical antibiotics, regardless of a positive or negative urinalysis.
  • Infants <30 days with abnormal inflammatory markers and a positive urinalysis who attended a hospital that saw >10 infants with PUO each day, were more than 4 times more likely to have an LP
  • Of the 1061 infants with positive urinalysis who did not have LP, 70 received a 'full course' of antibiotics
  • There were no cases of delayed diagnosis of meningitis (representation to the same hospital within 7 days of discharge from ED or inpatient admission)
  • No infants >30 days old who had a positive urinalysis but no LP, returned to the same hospital within 7 days of discharge

Where next

  • The study builds on previous research regarding the prevalence of concomitant meningitis in children with UTIs - found to be 0.8 - 1.2% in the first month of life, 0 - 0.3% in the second
  • Are practitioners really that good at selecting out patients who are at higher risk of meningitis and require LP?
  • Care should be taken with interpretation of the results:
    • Infants may have presented to different institution
    • LPs may have been declined by the family or unsuccessful (9 infants without LP had stays >14 days but we don't get more details about them)
    • Short course of antibiotics may have been enough to treat undiagnosed meningitis

Additional resources

Summary by Jye Gard, June 2020

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

Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, Ramnarayan P, Fraisse A, Miller O, Davies P, Kucera F. Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. 2020 Jun 8.

How it helps

Children with evidence of previous SARS-CoV-2 infection were found to develop signs and symptoms of Kawasaki’s disease (KD), including: Fever for 3 or more days, mucocutaneous signs (rash, conjunctival injection), high inflammatory markers, cardiogenic and/or distributive shock ("KD shock syndrome") and coronary aneurysms.

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Study type

A case series of 58 children from 8 different hospitals in England who:
  1. Met criteria for Pediatric Inflammatory Multisystem Syndrome temporarily associated with SARS-CoV-2 (PIMS-TS)
AND
  1. Either SARS-CoV 2 PCR or IgG positive (using Epitope Diagnostic Inc ELISA kits)
The clinical symptoms, signs, laboratory and imaging results of children with PIMS-TS were compared to those of children who suffered from other paediatric inflammatory disorders such as KD, KD shock syndrome and toxic shock syndrome with the aim to help clinicians "pattern recognise" PIMS-TS and distinguish it from similar illnesses.

Major findings

Clinical features
  • Children were investigated for PIMS-TS if they had fevers that persisted for at least 3 days. Some untreated patients had fevers that persisted for as long as 19 days!
  • The next most common features were abdominal pain (53%), erythematous rash (52%), conjunctival injection (45%) and red cracked lips (29%). Rarer features were lymphadenopathy (16%), headache (26%), swollen hands and feet (16%), sore throat (10%)
  • Half of the patient were admitted to ICU for at least one of either inotropic support (47%), mechanical ventilation (43%) or treatment of acute kidney injury (22%)
Laboratory features
  • Most (40/46 children tested) were IgG positive, fewer (15/58) were PCR positive. It didn't matter whether children tested IgG or PCR positive, the clinical features were the same.
  • Many had very high inflammatory markers including CRP >220mg/L, Neutrophilia >13x109/L and Ferritin >610µg/L
  • Two thirds also had raised troponin levels and most (83%) has raised pro-B-type-BNP.
  • Only 2 patients had evidence of a new second virus (both adenovirus and enterovirus, EBV)
Clinical course features
  • Children fit one of three clinical patterns
    1. Persistent fever and raised inflammatory markers only
    2. Shock with left ventricular dysfunction, raised cardiac markers +/- dysrhythmias
    3. Kawasaki's disease or atypical Kawasaki’s disease
  • Children from all three groups developed coronary aneurysms!
How to "pick" a PIMS-TS case
  • Blood count: Compared to 'regular' KD cases, children with PIMS-TS had a higher WCC, neutrophilia, CRP and more profound anaemias and lymphopenias. Children with PIMS-TS also had mild thrombocytopaenia (unlike in KD where we often see thrombocytosis).
  • Biochemistry: higher troponins, fibrinogen levels.
  • Age: PIMS-TS children tended to be older

Where next

  • Prospective trials/data collection
  • Standardised methods for detecting SARS-CoV-2 so like can be compared to like

Additional resources

  • Read the World Health Organisation (WHO) definition of PIMS-TS here
  • Check out a similar study done in New York
  • A helpful image of the features of PIMS-TS from Don't Forget The Bubbles
Summary by Jye Gard, June 2020

Article

Ibrahim L, Babl, F, Hopper S, et al Cellulitis: Oral versus intravenous and homer versus hospital-what makes clinicians decide Archives of Disease in Childhood. 2020;105: 413-415

How it helps

This study describes physicians embedded decision-making rules about route and locations of antimicrobial therapy for cellulitis. The purpose of this study was to understand barriers to changing practice.

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Study type

Web-based anonymous staff survey including a clinical scenario.

Major findings

  • There was a wide variation in perceived risk of bacteraemia in the clinical scenario.
  • There was a 50:50 split in terms of preference for treating intravenously as either an inpatient or outpatient.
  • Lymphangitis, fever, having already received 24hrs of oral antibiotics, and the size of the affected area were among the reasons included in choosing IV over oral treatment. These clinical features made physicians were more likely, however, to choose inpatient over outpatient IV antibiotics.
  • 96% of physicians prefer children under 6 months to be treated as inpatients.
  • 46% of physicians prefer children aged 6 months to 1 year to be treated as inpatients.
  • Clinical features such as rash and fever deter 50% of physicians from using outpatient based IV treatment.
  • Fear of complications such as a deterioration going unnoticed, needing to re-present, or missing complications were reasons to prefer inpatient therapy 20-25% of the time.

Where next

  • Clinicians are receptive to home treatment with IV antibiotic therapy. Barriers to choosing home therapy should be addressed with education.

Additional resources

Summary by Emer Ryan, May 2020

Article

Biondi EA, Mischler M, Jerardi KE, et al. Blood Culture Time to Positivity in Febrile Infants With Bacteremia. JAMA Pediatr. 2014;168(9):844-849.doi:10.1001/jamapediatrics.2014.895 

How it helps

  • The febrile infant is a common presentation, however bacteraemia is uncommon in otherwise well infants. 
  • In febrile infants, most pathogens will be identified via blood culture within 24 hours, in previously well (non-ICU/non-surgical) patients. 
  • Duration of observation and empiric treatment vary widely amongst institutions. 

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Study type/population

Multi-centre, retrospective cross-sectional evaluation of blood culture time to positivity in febrile infants (< 90 days age), with bacteraemia and no surgical/ICU history. 

Major findings

  • 5332 positive blood cultures were initially identified. 3129 were excluded from ICU and surgical patients and a further 1447 from those not treated for pathogenic organisms (common contaminants) were also excluded.
  • 392 blood cultures for which patient were treated with a full course of antibiotics were used in the analysis.
  • By 24 hours, 355 of the 392 blood culture results (91%; 95% CI, 88-93) were positive. By 36 & 48 hours, 378 (96%) and 386 (99%) were positive
  • E.coli was the most common organism identified (41%). Group B strep had the shortest median time to positive culture – 10.5 hours.

Where next

  • This study looked at 17 paediatric centres in the US. This may not translate to all other settings, including low resource settings. 
  • A study must include negative culture results and clinical outcomes (e.g. clinical deterioration) to comment on overall risk for serious bacterial infections in infants. 

Additional resources

Summary by Julian Dascalu, July 2020 

Article

Hoberman A, Paradise JL, Rockette HE, Kearney DH, Bhatnagar S, Shope TR, Martin JM, Kurs-Lasky M, Copelli SJ, Colborn DK, Block SL. Shortened antimicrobial treatment for acute otitis media in young children. New England Journal of Medicine. 2016 Dec 22;375(25):2446-56. 

How it helps

  • Reducing the duration of treatment for acute otitis media in children less than 2 years old with amoxicillin-clavulanate from 10 days to 5 days was more likely to result in treatment failure.
  • There was no change to the rate of adverse events or emergence of resistance.

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Study type

A non-inferiority randomized, placebo-controlled trial across multiple sites (Children’s Hospital of Pittsburgh, paediatric practices and Kentucky Paediatric and Adult Research in Bardstown, Kentucky). 

Major findings

  • Acute Otitis Media (AOM) was diagnosed based on the AOM-Severity of Symptoms (AOM-SOS) scale, middle-ear effusion and appearance on otoscopy.
  • 520 children, 6 to 23 months of age with AOM received standard-dose amoxicillin-clavulanate for either 10 days, or for 5 days followed by placebo for 5 days.
  • Children who were treated for 5 days were more likely to have clinical treatment failure (77 of 229, 34% vs. 39 of 238, 16% - a difference of 17 percentage points between groups, 95% Cl of 9 to 25).
  • Clinical treatment failure included those with persistent and worsening clinical symptoms or signs at the end of treatment and was more likely with high initial AOM-SOS or recent antibiotics.
  • No significant between-group differences in rates of recurrence, adverse events or nasopharyngeal colonization with resistant pathogens.

Where next

  • Many guidelines such as the RCH CPG still recommend 5 days of amoxicillin if we are going to treat and no contraindications. Be aware some children will benefit from longer treatment 
  • This study does not tell us what we should do about older children, or in other low resource settings. 

Additional resources

Summary by Nelson Wang, July 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

Article

Rivas-Fernández M, Izquierdo AD, Cassanello P, Balaguer A. Do probiotics help babies with infantile colic?. Archives of disease in childhood. 2019 Sep 1;104(9):919-23. 

How it helps

Use of a specific probiotic culture called Lactobacillus reuteri strain Deutsche Sammlung von Microorganismen (LR DSM) 17938 may reduce crying and fussing times in babies that are predominantly breastfed.  

LR DSM 17938 is usually found in different body sites including the skin, breast tissue, gastrointestinal and urinary tracts. Other sources include dairy and meat products. It is also sold commercially. 

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Study type

Literature review using seven different databases revealed 29 primary papers and 4 meta-analyses that examined the use of probiotics in children with colic. The review was limited to articles published in English or European languages. 

Major findings

Rigorous trials have yet to return a clear cause or treatment for colic. One leading hypothesis is that colic may be caused by dysbiosis (microbial imbalance).   

Positive finding were only found in infants who were  >50% breastfed. Infants who were mostly formula fed did not show any change in behaviour.  

In studies that showed positive findings, mostly breastfed babies who used LR DSM 17938 for 21 days halved their crying and/or fussing timesIn some studies this was a decrease in crying time of about 25 minutes per day. Importantly, other studies showed no benefits from LR DSM 17938 use.  

There have not been any reported adverse effects of LR DSM 17938 in healthy infants to date.  

Other strains of pro-biotics have not been well studied. 

Where next

There are currently 9 active randomised control trials also analysing the use of LR DSM 17938 in infantile colic.  

It is important that these studies: 

  • Clarify the recommended dose of LR DSM 17938 infants may trial – the dose used by different studies was highly variable, from 1x10^8 colony-forming units orally/day to 5x10^8 CFU/day to 1x10^10 CFU/day for 21 days.  
  • Review the cost effectiveness of using a daily probiotic, given that the natural course of infantile colic is self-limiting and benign. This study estimates that only 1 out of 8 infants with colic will gain benefit from using this probiotic (NNT = 8).  

Additional resources

Summary by Caitlin Richardson, August 2020

Article

Phelan PD, Robertson CF, Olinsky A. The Melbourne Asthma Study: 1964-1999. The Journal of Allergy and Clinical Immunology. 2002 Feb;109(2):189-94 

How it helps

Children with mild wheezing episodes associated with respiratory tract infections (RTI) generally do not develop asthma in adolescence or adulthood and usually cease to have symptoms by early adolescence. Whereas, children with wheezing not associated with RTIs and those with severe asthma are more likely to have asthma symptoms that persist into adolescence and adulthood. 

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Study type

Cohort study to assess the long-term outcomes of childhood wheezing in Melbourne school children randomly selected at 7-years-old during routine school medical examination. 

Participants were cohorted based on severity of asthma symptoms (none; <5 episodes associated with RTIs; >5 episodes associated with RTIs; wheezing without RTIs; severe symptoms) then followed up at 10, 14, 21, 28, 35 and 42 years of age. 

Major findings

  • Children in the milder groups, particularly those with wheezing episodes associated with RTIs, typically had resolution of symptoms by early adolescence and did not go on to develop asthma symptoms in adulthood.
  • The severity of childhood symptoms correlated to the severity of symptoms in adulthood. At 21yr of age, 95% of those in the most severe cohort continued to have symptoms.
  • The severe group showed reduced lung function (FEV1 and FEV1/FVC) by the age of 14, though this did not worsen over time. This early loss in function was measured at a time before anti-inflammatory agents were routinely used.
  • There was no difference in lung function between in the milder groups and the control group on long term follow up, leading the authors to postulate that children in these groups do not require therapy at preventing progressive disease or loss of lung function (eg. steroids).
  • Atopic disease in childhood increased the risk of more severe asthma in adulthood.

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 Ary Sudarmana, August 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

Florin TA, Ambroggio L, Brokamp C, Zhang Y, Rattan M, Crotty E, Belsky MA, Krueger S, Epperson TN, Kachelmeyer A, Ruddy R. Biomarkers and Disease Severity in Children With Community-Acquired Pneumonia. Pediatrics. 2020 Jun 1;145(6). 

How it helps

FEB, neutrophil counts, CRP and procalcitonin  on admission were similar between cases of mild, moderate and severe pneumonia.  CRP and procalcitonin levels may be helpful in determining which children with severe pneumonia will need extra help (IV fluids, positive pressure ventilation, broad spectrum antibiotics, vasopressors and/or ICU admission). 

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Study type

Single site (Cincinnati Children’s Hospital Medical Center Emergency Department) prospective cohort study of 477 children aged 3 months to 18 years old who presented between July 2013 and December 2017.  In order to be included, the children has to have: 
  1. One or more symptoms or signs of a LRTI (new or different cough, sputum production, chest pain, dyspnoea, tachypnoea or abnormal findings on auscultation) AND 
  2. A chest X-ray that showed focal opacity AND 
  3. Blood investigations
Note that in the US, X-rays and blood tests are more commonly done in children who have signs or symptoms of a LRTI. In Australia, we advocate that for clear-cut clinical pneumonia, there is no need to do them!  The researchers excluded children who had already been to hospital in the last fortnight or had underlying conditions that increased their risk of pneumonia (i.e. a history of aspiration pneumonia, immunodeficiency or other chronic diseases like neuromuscular disorders)   Severity of pneumonia was determined by the type of hospital treatment received (eg mild – discharged, mild-moderated – admitted, moderate-severe – admitted plus other therapy eg IV fluid, oxygen and severe – ICU) 

Major findings

  • The inflammatory marker values were very similar between pneumonia of different severity.
  • CRP and procalcitonin however seemed to be slightly higher in children who developed an empyema that required a chest drain and/or sepsis requiring vasopressors.
  • Some things that made interpretation of results a little sticky:
    • The researchers analysed composite outcomes (i.e. “moderate-severe pneumonia” were lumped together - all cases where children either received an IV fluid bolus, >12 hours of continuous IV fluid support, oxygen, antibiotics broader than just penicillin presumed complications or sepsis, were looked at all together) 
    • The blood results analysed were those taken when they first presented to hospital. As we know, markers such as CRP change with time and this does not account for different length of illness at time of testing.  
  • As an aside, 1142 children had a chest X-ray even though they had signs and symptoms of pneumonia! 477/1142 had blood tests!   

Where next

  • This is a single study in a single context.
  • Pneumonia complications take time to develop. Are they better at predicting severity or treatment needs when a child has been unwell for a certain period of timeOr when looked at as a trend alongside clinical progress to anticipate treatment needs? 

Additional resources

  • Check out this podcast with A/Prof Ed Oakley about avoiding unnecessary tests 
Summary by Jye Gard, September 2020