Bumper Bubble Wrap PLUS – October/November 2019

Cite this article as:
Anke Raaijmakers. Bumper Bubble Wrap PLUS – October/November 2019, Don't Forget the Bubbles, 2019. Available at:

Here is our latest Bumper BubbleWrap Plus, combining October and November’s paediatric Journal Club Lists provided by Professor Jaan Toelen & his team of the University Hospitals in Leuven (Belgium). This comprehensive list of ‘articles to read’ from the last two months 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 bumper list features answers to intriguing questions such as: ‘What are the outcomes for oral immunotherapy for peanut allergy?’, ‘Is lung ultrasound a useful investigation in preterms with RDS?’, ‘Does a gluten-free diet lead to improved headache in children with celiac disease?’,  ‘ Which mental health conditions are associated with hyperthyroidism?’, ‘Do commonly available round facemasks fit near-term and term infants?’, ‘Does formula feeding increases the risk of antibiotic prescriptions?’, ‘Is foot-length growth a good early marker for puberty?’ and ‘Is chocolate consumption good for your telomeres?’

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

1.Reviews and opinion articles

Clinical Approach to Lactose Intolerance.

Micic D, et al. JAMA. 2019 Sep 26.

Challenges and controversies in childhood tuberculosis.

Reuter A, et al. Lancet. 2019 Sep 14;394(10202):967-978.

Neonatal Hypoglycemia: A Review.

Alsaleem M, et al. Clin Pediatr (Phila). 2019 Sep 26:9922819875540.

School-aged Children Who Are Not Progressing Academically: Considerations for Pediatricians.

Rey-Casserly C, et al. Pediatrics. 2019 Sep 23.

A perfect storm: fetal inflammation and the developing immune system.

Sabic D, et al. Pediatr Res. 2019 Sep 19.

What I Learned From the Antivaccine Movement.

Ju AC. Pediatrics. 2019 Sep 16.

A brief history of rickets.

Friedman A. Pediatr Nephrol. 2019 Oct 25.

Review of bilirubin neurotoxicity I: molecular biology and neuropathology of disease.

Riordan SM, et al. Pediatr Res. 2019 Oct 10.

Review of bilirubin neurotoxicity II: preventing and treating acute bilirubin encephalopathy and kernicterus spectrum disorders.

Shapiro SM, et al. Pediatr Res. 2019 Oct 3.

Kawasaki disease: origins and evolution.

Kainth R, et al. Arch Dis Child. 2019 Oct 18.

The Spartacus Problem: Diagnostic Inefficiency of Neonatal Sepsis.

Cantey JB. Pediatrics. 2019 Nov;144(5).

The promise of a prophylactic Epstein-Barr virus vaccine.

Balfour HH Jr, et al. Pediatr Res. 2019 Oct 3.

Imaging surveillance for children with predisposition to renal tumors.

Srinivasan AS, et al. Pediatr Radiol. 2019 Oct;49(11):1453-1462.

Clinical Features of Tourette Syndrome.

Gill CE, Kompoliti K. J Child Neurol. 2019 Oct 14:883073819877335.

Seeking a Second Opinion on Social Media.

Caruso Brown AE, et al. Pediatrics. 2019 Nov;144(5).

Early childhood caries epidemiology, aetiology, risk assessment, societal burden, management, education, and policy: Global perspective.

Tinanoff N, et al. Int J Paediatr Dent. 2019 May;29(3):238-248.

Soccer Injuries in Children and Adolescents.

Watson A, et al. Pediatrics. 2019 Nov;144(5).

2. Original clinical studies

Step-Up Therapy in Black Children and Adults with Poorly Controlled Asthma.

Wechsler ME, et al. N Engl J Med. 2019 Sep 26;381(13):1227-1239.

Sustained outcomes in oral immunotherapy for peanut allergy (POISED study): a large, randomised, double-blind, placebo-controlled, phase 2 study.

Chinthrajah RS, et al. Lancet. 2019 Sep 12.

Sustained unresponsiveness in peanut oral immunotherapy.

van Ree R. Lancet. 2019 Sep 12.

Can children predict psychological recovery after injury?

Alisic E, et al. Arch Dis Child. 2019 Sep 26.

Depression, Anxiety, and Emergency Department Use for Asthma.

Bardach NS, et al. Pediatrics. 2019 Sep 25.

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled trial.

Stahl A, et al. Lancet. 2019 Sep 12.

A Randomized Trial of Prenatal n-3 Fatty Acid Supplementation and Preterm Delivery.

Makrides M, et al. N Engl J Med. 2019 Sep 12;381(11):1035-1045.

Risk stratification to improve Pediatric Early Warning Systems: it is all about the context.

Teheux L, et al. Eur J Pediatr. 2019 Oct;178(10):1589-1596.

Pediatric Hemoptysis without Bronchiectasis or Cardiac Disease: Etiology, Recurrence, and Mortality.

Chiel L, et al. J Pediatr. 2019 Sep 17.

Probiotics for paediatric functional abdominal pain disorders: A rapid review.

Ding FCL, et al. Paediatr Child Health. 2019 Sep;24(6):383-394.

Accuracy of Autism Screening in a Large Pediatric Network.

Guthrie W, et al. Pediatrics. 2019 Sep 27.

Adverse Events of Antibiotics Used to Treat Acute Otitis Media in Children: A Systematic Meta-Analysis.

Hum SW, et al. J Pediatr. 2019 Sep 24.

Human Milk Use in the Preoperative Period Is Associated with a Lower Risk for Necrotizing Enterocolitis in Neonates with Complex Congenital Heart Disease.

Cognata A, et al. J Pediatr. 2019 Sep 24.

Nutrition, Growth, Brain Volume, and Neurodevelopment in Very Preterm Children.

Power VA, et al. J Pediatr. 2019 Sep 24.

Diversity of Serotype Replacement After Pneumococcal Conjugate Vaccine Implementation in Europe.

Levy C, et al. J Pediatr. 2019 Oct;213:252-253.e3.

Short-Term High-Flow Nasal Cannula for Moderate to Severe Bronchiolitis Is Effective in a General Pediatric Ward.

Sachs N, et al. Clin Pediatr (Phila). 2019 Sep 26:9922819877881

The Impact of Physical Activity on Brain Structure and Function in Youth: A Systematic Review.

Valkenborghs SR, et al. Pediatrics. 2019 Sep 25. pii: e20184032.

A Single Institution’s Experience of Primary Headache in Children With Celiac Disease.

Hom GL, et al. J Child Neurol. 2019 Sep 25:883073819873751.

The Importance of Language-Learning Environments to Child Language Outcomes.

Feldman HM. Pediatrics. 2019 Sep 24.

Parenting Behavior and Child Language: A Meta-analysis.

Madigan S, et al. Pediatrics. 2019 Sep 24.

Association Between Screen Media Use and Academic Performance Among Children and Adolescents: A Systematic Review and Meta-analysis.

Adelantado-Renau M, et al. JAMA Pediatr. 2019 Sep 23.

Do commonly available round facemasks fit near-term and term infants?

Haase B, et al. Arch Dis Child Fetal Neonatal Ed. 2019 Sep 21

Increase of body mass index is a useful predictor of childhood obesity.

Ichikawa G, et al. J Pediatr. 2019 Sep 18.

Acute Management of Pediatric Cyclic Vomiting Syndrome: A Systematic Review.

Gui S, et al. J Pediatr. 2019 Sep 17.

Pneumonia Prevention Strategies for Children With Neurologic Impairment.

Lin JL, et al. Pediatrics. 2019 Sep 19.

Efficacy of oral midazolam for minimal and moderate sedation in pediatric patients: a systematic review.

Manso MA, et al. Paediatr Anaesth. 2019 Sep 20.

Feasibility and Accuracy of Fast MRI Versus CT for Traumatic Brain Injury in Young Children.

Lindberg DM, et al. Pediatrics. 2019 Sep 18.

The Feasibility of Fast MRI to Reduce CT Radiation Exposure With Acute Traumatic Head Injuries.

Burstein B, et al. Pediatrics. 2019 Sep 18.

Chronotype, Social Jet Lag, and Cardiometabolic Risk Factors in Early Adolescence.

Cespedes Feliciano EM, et al. JAMA Pediatr. 2019 Sep 16.

Prelacteal and early formula feeding increase risk of infant hospitalisation: a prospective cohort study.

Nguyen P, et al. Arch Dis Child. 2019 Sep 15.

Formula feeding increases the risk of antibiotic prescriptions in children up to 2 years: results from a cohort study.

Di Mario S, et al. Eur J Pediatr. 2019 Sep 6.

Foot Length Growth as a Novel Marker of Early Puberty.

Balzer BWR, et al. Clin Pediatr (Phila). 2019 Sep 14:9922819875531.

The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants: A Randomized Controlled Trial.

Lam R, et al. J Pediatr. 2019 Sep 10.

Reducing Streptococcal Testing in Patients <3 Years Old in an Emergency Department.

Ahluwalia T, et al. Pediatrics. 2019 Sep 11.

Effectiveness Oral Theophylline, Piracetam, and Iron Treatments in Children With Simple Breath-Holding Spells.

Dai AI, et al. J Child Neurol. 2019 Sep 10:883073819871854.

Predicting Long-Term Survival Without Major Disability for Infants Born Preterm.

Bourke J, et al. J Pediatr. 2019 Sep 4.

Celiac Disease Autoimmunity and Emotional and Behavioral Problems in Childhood.

Wahab RJ, et al. Pediatrics. 2019 Sep 6.

Further Support for Psychological Symptoms in Pediatric Celiac Disease.

Smith LB, et al. Pediatrics. 2019 Sep 6.

Mycoplasma pneumoniae Carriage With De Novo Macrolide-Resistance and Breakthrough Pneumonia.

Alishlash AS, et al. Pediatrics. 2019 Sep 5.

Changes in the Management of Children With Brief Resolved Unexplained Events (BRUEs).

Ramgopal S, et al. Pediatrics. 2019 Sep 5

Nebulised hypertonic saline in moderate-to-severe bronchiolitis: a randomised clinical trial.

Jaquet-Pilloud R, et al. Arch Dis Child. 2019 Sep 5.

Lung function evolution in children with old and new type bronchopulmonary dysplasia: a retrospective cohort analysis.

Cardoen F, et al. Eur J Pediatr. 2019 Sep 5.

Appendicitis or non-specific abdominal pain in pre-school children: When to request abdominal ultrasound?

Prada-Arias M, et al. J Paediatr Child Health. 2019 Sep 4.

Bacterial meningitis in febrile young infants acutely assessed for presumed urinary tract infection: a systematic review.

Poletto E, et al. Eur J Pediatr. 2019 Oct;178(10):1577-1587.

Flavored E-cigarette Use and Progression of Vaping in Adolescents.

Leventhal AM, et al. Pediatrics. 2019 Nov;144(5).

Use of Intraosseous Needles in Neonates: A Systematic Review.

Scrivens A, , et al. Neonatology. 2019 Oct 28:1-10.

Lung ultrasound in preterm infants with respiratory distress: experience in a neonatal intensive care unit.

Gregorio-Hernández R, et al. Eur J Pediatr. 2019 Oct 26.

Use of clinician-performed ultrasound in the assessment of safe umbilical venous catheter tip placement.

Seigel A, et al. J Paediatr Child Health. 2019 Oct 26.

Strengthening Diagnosis of Pulmonary Tuberculosis in Children: The Role of Xpert MTB/RIF Ultra.

Zar HJ, et al. Pediatrics. 2019 Nov;144(5).

A Test for More Accurate Diagnosis of Pulmonary Tuberculosis.

Sun L, et al. Pediatrics. 2019 Nov;144(5).

Accelerating diagnosis for childhood brain tumours: an analysis of the HeadSmart UK population data.

Shanmugavadivel D, et al. Arch Dis Child. 2019 Oct 25.

Predicting intestinal recovery after necrotizing enterocolitis in preterm infants.

Kuik SJ, et al. Pediatr Res. 2019 Oct 24.

Nutritional interventions to reduce rates of infection, necrotizing enterocolitis and mortality in very preterm infants.

Bührer C, et al. Pediatr Res. 2019 Oct 23.

Newborn Antibiotic Exposures and Association With Proven Bloodstream Infection.

Schulman J, et al. Pediatrics. 2019 Nov;144(5).

Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?

Parga JJ, et al. Pediatr Res. 2019 Oct 4.

Prevalence and Factors Associated With Safe Infant Sleep Practices.

Hirai AH, et al. Pediatrics. 2019 Nov;144(5).

Duration of initial antibiotic course is associated with recurrent relapse in protracted bacterial bronchitis.

Gross-Hodge E, et al. Arch Dis Child. 2019 Oct 17.

Factors Associated With Fast Recovery of Bell Palsy in Children.

Lee Y, et al. J Child Neurol. 2019 Oct 17:883073819877098

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017.

Burstein R, et al. Nature. 2019 Oct;574(7778):353-358.

Diagnostic and Clinical Utility of Clinical Exome Sequencing in Children With Moderate and Severe Global Developmental Delay / Intellectual Disability.

Stojanovic JR, et al. J Child Neurol. 2019 Oct 17:883073819879835.

Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing.

Homma TK, et al. J Pediatr. 2019 Oct 17.

Predictors and Outcomes of Early Intubation in Infants Born at 28-36 Weeks of Gestation Receiving Noninvasive Respiratory Support.

Roberts CT, et al. J Pediatr. 2019 Oct 11

Pain and Sedation Scales for Neonatal and Pediatric Patients in a Preverbal Stage of Development: A Systematic Review.

Giordano V, et al. JAMA Pediatr. 2019 Oct 14.

Effect of Exercise Recommendation on Adolescents With Concussion.

Stumph J, et al. J Child Neurol. 2019 Oct 10:883073819877790.

Endotracheal suctioning for prevention of meconium aspiration syndrome: a randomized controlled trial.

Kumar A, et al. Eur J Pediatr. 2019 Oct 7.

Bronchiolitis severity is related to recurrent wheezing by age 3 years in a prospective, multicenter cohort.

Mansbach JM, et al. Pediatr Res. 2019 Oct 4.

Mental Health Conditions and Hyperthyroidism.

Zader SJ, et al. Pediatrics. 2019 Nov;144(5).

Head circumference at birth and intellectual disability: a nationwide cohort study.

Aagaard K, et al. Pediatr Res. 2019 Oct 2.

Unintentional Symptom Intensification by Doctors.

Schechter NL, et al. Pediatrics. 2019 Nov;144(5).

Higher chocolate intake is associated with longer telomere length among adolescents.

Chen L, et al. Pediatr Res. 2019 Oct 1.

20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia.

Luirink IK, et al. N Engl J Med. 2019 Oct 17;381(16):1547-1556.

Controlled Trial of Two Incremental Milk-Feeding Rates in Preterm Infants.

Dorling J, et al. N Engl J Med. 2019 Oct 10;381(15):1434-1443.

3. Guidelines and Best Evidence

Digital media: Promoting healthy screen use in school-aged children and adolescents.

Canadian Paediatric Society Paediatr Child Health. 2019 Sep;24(6):402-417

Debate: Are Stimulant Medications for Attention-Deficit/Hyperactivity Disorder Effective in the Long Term? (Against).

Swanson JM. J Am Acad Child Adolesc Psychiatry. 2019 Oct;58(10):936-938.

Debate: Are Stimulant Medications for Attention-Deficit/Hyperactivity Disorder Effective in the Long Term? (For).

Coghill D. J Am Acad Child Adolesc Psychiatry. 2019 Oct;58(10):938-939

Overtesting and overtreatment-statement from the European Academy of Paediatrics (EAP).

Størdal K, et al. Eur J Pediatr. 2019 Sep 10

Reaffirming that every poke counts! Higher repeated pain exposure in early life linked with greater short- and long-lasting alteration of the nociceptive system.

Campbell-Yeo ML. Pediatr Res. 2019 Sep 6.

The Use of Nonnutritive Sweeteners in Children.

Baker-Smith CM, et al. Pediatrics. 2019 Nov;144(5).

What clinical practice strategies have been shown to decrease incidence rates of intraventricular haemorrhage in preterm infants?

Howes A, et al. J Paediatr Child Health. 2019 Oct;55(10):1269-1278.

Concussion Management for Children Has Changed: New Pediatric Protocols Using the Latest Evidence.

DeMatteo C, et al. Clin Pediatr (Phila). 2019 Oct 18:9922819879457.

Post-traumatic Headache After Pediatric Traumatic Brain Injury: Prevalence, Risk Factors, and Association With Neurocognitive Outcomes.

McConnell B, et al. J Child Neurol. 2019 Oct 4:883073819876473.

Postnatally acquired cytomegalovirus infection in extremely premature infants: how best to manage?

Kadambari S, et al. Arch Dis Child Fetal Neonatal Ed. 2019 Oct 15.

Diagnostic values of the femoral pulse palpation test.

Khammari Nystrom F, et al. Arch Dis Child Fetal Neonatal Ed. 2019 Oct 9.

Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents.

Wolraich ML, et al. Pediatrics. 2019 Oct;144(4).

Canadian Paediatric Society clinical practice recommendations for assessment of children and youth with autism spectrum disorder.

Zwaigenbaum L, et al.  Paediatr Child Health. 2019 Nov;24(7):421-423.

Acute Treatment of Migraine in Children and Adolescents.

Pediatrics. 2019 Nov;144(5).  (AAP endorsement of: https://www.aan.com/Guidelines/Home/GetGuidelineContent/970 and https://www.aan.com/Guidelines/Home/GuidelineDetail/967)

4. Case Reports

Di Lorenzo C, et al. N Engl J Med. 2019 Sep 19;381(12):1159-1167.

A Rare Case of Fetal Onset, Food Protein-Induced Enterocolitis Syndrome.

Ichimura S, et al. Neonatology. 2019 Sep 25:1-4.

A 5-year-old girl with recurrent fever.

Uruthirakumar R, et al. Paediatr Child Health. 2019 Sep;24(6):368-370.

12-Year-old Female with Mucocutaneous Lesions.

Marujo F, et al. Pediatr Infect Dis J. 2019 Nov;38(11):1159.

Three-year-old girl with progressive leg pain, weakness and refusal to ambulate.

Gallagher J, et al. J Paediatr Child Health. 2019 Oct 17.

A 15-Year-Old Girl with a Squint.

Tan GH. J Pediatr. 2019 Oct 11.

The Case of a Twitchy Tongue: An Uncommon Presentation of a Common Childhood Epilepsy.

Khalid R, et al.  J Pediatr. 2019 Oct 9.


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

The 34th Bubble Wrap

Cite this article as:
Grace Leo. The 34th Bubble Wrap, Don't Forget the Bubbles, 2019. Available at:

Article 1: Implementation of the neonatal sepsis calculator

Akangire G et al. Implementation of the Neonatal Sepsis Calculator in Early-Onset Sepsis and Maternal Chorioamnionitis. Advances in Neonatal Care. September 2019; Publish Ahead-of-Print: doi: 10.1097/ANC.0000000000000668 (accessed 20 October 2019)

What’s it about?

This quality improvement project aimed to develop guidelines and education materials for implementing the neonatal sepsis calculator published by Kaiser Permanente in 2017 in a neonatal intensive care unit (NICU). The calculator predicts the probability of neonatal early-onset sepsis (EOS) in babies ≥34 weeks gestation, based on maternal risk factors for chorioamnionitis and the baby’s clinical presentation.

The calculator then makes a clinical recommendation (no blood culture or antibiotics, blood culture but no antibiotics, or blood culture and antibiotics), and recommends the frequency of recording vital signs for the baby. The calculator relies on users knowing the incidence of early- onset sepsis for their particular hospital/neonatal unit. The calculator is gaining in popularity (certainly in my recent experience), but guidelines for its implementation in individual neonatal units are lacking. One of the concerns is that the calculator will take the place of clinical judgement. The researchers were based at a Level III NICU in the USA. They evaluated current blood culture collection and antibiotic use for suspected EOS in their unit, then developed guidelines and education materials for implementing the neonatal sepsis calculator, and then re-evaluated rates of blood culture collection and antibiotic use.

Why does it matter?

Neonatal early-onset sepsis (EOS) is culture-positive invasive infection that presents in the first 72 hours of life, with Group B streptococcus (GBS or S. agalactiae) the main culprit. Guidelines for screening for and treating suspected neonatal EOS vary, with the conventional wisdom suggesting at least 48 hours of empirical antibiotics for treatment of suspected EOS due to maternal chorioamnionitis. The definition of maternal chorioamnionitis also varies based on maternal symptoms, including intrapartum and postpartum fever and clinical instability. EOS guidelines vary for and within each state and territory in Australia, with some units implementing the neonatal sepsis calculator, and others using stricter guidelines for evaluation and treatment of suspected neonatal EOS. NICE Guidelines from the UK do not refer to the calculator, but use risk factors, clinical indicators, and red flags to guide antibiotic management decisions (https://pathways.nice.org.uk/pathways/early-onset-neonatal-infection).

In the study, in the 4 months prior to implementing the neonatal sepsis calculator, antibiotic use for suspected EOS was 11%, and blood culture was done on 14.8% of live births. The calculator was subsequently implemented for 6 months. In the 4 months post-implementation, neonatal sepsis calculator use was more than 95%, antibiotic use decreased significantly to 5%, and blood culture use dropped to 7.6%.

Importantly, the researchers considered the management of asymptomatic neonates, for whom the implementation of the neonatal sepsis calculator represented the greatest change in practice. The calculator uses the highest antepartum maternal temperature to indicate chorioamnionitis. In asymptomatic infants, if there is no maternal fever, but a clinical diagnosis of chorioamnionitis is made, the neonatal sepsis calculator may recommend observation only, with no blood culture or antibiotics. By contrast, the neonatologists in the study agreed that in these cases, a full blood count and blood culture should be done, with antibiotics withheld.

The researchers did not advocate blanket implementation of the neonatal sepsis calculator in the absence of clinical reasoning. Indeed, part of their research required clinicians to document the recommendations from the calculator, and then document their reason/s for accepting or rejecting the recommendations.

What’s the bottom line?

In this quality improvement project around implementation of the neonatal sepsis calculator, high uptake was achieved (>95%). In comparision at 4 months pre and post implementation, there was an associated reduction in antibiotic use from 11% to 5%, with blood cultures taken dropping from 14.8% to 7.6% of live births. The neonatal sepsis calculator provides objective data that can be used along with clinical judgement to make decisions about investigations and treatment of EOS. 

Reviewed by: Katie Nash


Article 2: To scan or not to scan?

Why does it matter?

With increasing availability and use of imaging over the past 10 years there has been a growing concern regarding the risks of diagnostic ionizing radiation. Previously our data regarding this has been based on studies of atomic bomb survivors from Hirsoshima & Nagasaki. A previous UK cohort study of 170,000 children under 10 undergoing head CT scans showed 1 excess case of leukaemia and 1 excess case of brain cancer for every 10,000 scans performed (Pence 2012).

What’s it about?

This was a retrospective population based cohort study of South Korean children (under 19 years of age) who had had a claim made via the National Health Insurance System. From 2006-2015 there were 12,068,821 individuals include. Of these 1,275,829 (10.6%) were exposed to low-dose ionizing radiation (defined as CT and other modalities such as IV urography but not plain X-Rays) with 92% being CT. Any scans performed 2 years before a diagnosis of cancer was excluded as these may well have been performed in the diagnostic evaluation for malignancy.
Amongst the entire cohort there were 21,912 cancers detected and this included 1444 cancers amongst those exposed to radiation (0.1%). In the group exposed to low-dose ionizing radiation there was in increased in overall cancer incidence than in the non-exposed group. (Incidence Rate Ratio of 1.64 [95% CI 1.56-173] p<0.001).

What’s the bottom line?

This study adds to the evidence that diagnostic ionizing radiation such as CT does increase the risk of cancer. It is import to recognise this risk is small compared to the lifetime risk of cancer but medical practioners should judge carefully the risks and benefits of performing any scan and adhere to the “as low as reasonably achievable” (ALARA) principles (RCR guidelines 2012).
Reviewed by: Jamie Pope


Article 3: Rotavirus Vaccine Effectiveness in NSW

Maguire J.E et al.  Rotavirus Epidemiology and Monovalent Rotavirus Vaccine Effectiveness in Australia: 2010 – 2017, Pediatrics[Internet]. 2019 Oct;144(4). pii: e20191024. doi: 10.1542/peds.2019-1024. Epub 2019 Sep 17 [cited 2019 Oct 29].

Why does it matter?

Rotavirus gastroenteritis is a frequently encountered and unpleasant illness. In 2007, a monovalent live attenuated vaccine covering for several G1 strains was introduced into the Australian Immunization schedule. Vaccine effectiveness (VE) is the percentage reduction of disease when comparing immunized and unimmunized patients. 3 years after the introduction, hospitalization in children less than 5 years due to rotavirus gastro declined by 71% – so just how effective is the vaccine?

What’s it about?

A retrospective cross-sectional study looked at laboratory confirmed cases of rotavirus in NSW from January 1 st 2010 to December 31 st 2017. A total of 9517 cases were identified, and age, gender, ATSI status, immunization status and rotavirus genotype recorded. VE was calculated based on the 2017 dataset, a year where there was a significant rotavirus gastro outbreak, and looked at children aged 0 – 16 years, born after 2008. It appears that 2 doses of Rotarix are effective, with VE estimates of 88% for the 6 – 11month age group, 83% for the 1 – 3 year old age group and 78% for the 4 – 9 year old age group. It is notable that VE significantly reduced from 89.5% at 1 year post vaccination to 77% at 5-10 years post vaccination.

What’s the clinically relevant bottom line?

The vaccine (Rotarix) appears to be effective, especially in children under 12 months who are exposed to those G1 strains, however the emergence of new strains and the waning immunity with age raises 2 questions: should a new and improved vaccine be developed and do adults (particularly those who work in healthcare) need booster doses?

Reviewed by: Tina Abi Abdallah


Article 4:  How well do you know your inhaler technique?

Spaggiari S, Gehri M, Di Benedetto et al. Inhalation technique practical skills and knowledge among physicians and nurses in two pediatric emergency settings. J  Asthma [Internet]. 2019 Oct 17 [cited 2019 Nov 1]. doi: 10.1080/02770903.2019.1674329. [Epub ahead of print]

Why does it matter?

Effective treatment of wheeze requires an appropriate inhalation technique but inhalers are often used incorrectly. Such errors can hinder deposition of the active compound into the lungs, thus diminishing treatment efficiency, which can lead to inadequate treatment or control of the disease. To overcome this problem, the Global Initiative for Asthma report recommend that patients be asked to demonstrate their inhaler device technique at every visit to enable improper use to be corrected and ongoing use technique to be monitored. Unfortunately, many healthcare professionals who are charged with providing instruction and monitoring aimed at optimizing inhaler use are not well versed with the use of these devices themselves.

What’s it about?

The aim of the study was to assess the ability and knowledge of physicians and nurses to use a pMDI with a masked VHC in paediatric emergency units. They conducted a 2 centre observational study, in Switzerland, with a total of 100 participants (50 nurses and 50 physicians). Their inhaler technique instructions were checked using a manikin and were video recorded. Using a 9 point operational checklist the recordings were reviewed and marked by 3 experts in aerosol therapy. The second part of the study evaluated health care professionals inhaler user knowledge by using a semi-structured questionnaire.

49% of the healthcare professionals performed all nine steps of the inhalation technique perfectly, with about a third performing eights steps correctly, and less than a fifth performing five, six, or seven steps correctly. The most frequent errors were forgetting to shake the pMDI before the second dose and incorrect patient or VHC positioning.


Site 1 (Lausanne)

Site 2 (Geneva)



Mean Sore










Only 18% of physicians and 64% of nurses reported having had specific training on inhalation technique. A notable portion of the healthcare professionals lacked practical knowledge about pMDI and VHC use. Differences between sites, professions and grades were statistically significant but probably not clinically relevant. The mean score being 8.3 (out of 9) and differences between groups being no more than 0.6 (Nurses performed better than  Doctors, Registered Nurses better than  nurses with a diploma in emergency care but there was no difference between junior and senior doctors)

This study has several limitations. Participants were recruited during their work time. Thus, it is possible that their inhalation technique and survey responses were influenced by stress. On the other hand, the participants may have exhibited better performance because they knew that the study was underway and that they were being observed (Hawthorne effect).

Healthcare professionals’ practical skills and knowledge related to inhalation therapy were not completely mastered. In light of their results, they provided information to participating healthcare professionals to help them observe good practices and provide suitable inhalation technique support.

What’s the bottom line?

Overall this study demonstrates that some professionals lack knowledge on inhaler technique which could lead to ineffective administration of medication to children with wheeze. It is recommended that health care professionals receive brief repeated training programmes on inhaler technique to provide optimal advice to patients. Do you know how good your unit’s education of inhaler technique is?

Reviewed by: Suzannah Johnson


Article 5: Is there a link between shorter sleep in infancy and becoming more overweight later?

Tuohino T et al. Short Sleep Duration and Later Overweight in Infants. J Paediatr [Internet]. 2019 Sep [cited 2019 Nov 4];212:13-19. doi: 10.1016/j.jpeds.2019.05.041. 

What’s it about?

The longitudinal study examined the relationship between sleep duration and excess weight gain in infants. Sleep data (N=1679) was reported by parents at 3, 8, 18 and 24 months of age in Finland from 2011 to 2017. In 3-month-old infants, short sleep is associated with lower weight-for-length/height (p≤0.026) and body mass index (p≤0.038). Short sleep duration in 3-month-old infants was associated with greater risk for excess weight-for-length/height at 24-month-old (aOR 1.56; 95% CI 1.02- 2.38) and a predisposition to gain excess weight between 3 and 24-month-old (aOR 2.61; 95% CI 1.75-3.91). Short night-time sleep duration in 8-month-old infants was associated with greater weight-for-length at 24-month-old (aOR 1.51; 95% CI 1.02-2.33)

Why does it matter?

Numerous factors contribute to the obesity epidemic in children, such as sedentary behaviour and the increasing use of electronic devices. Previous studies have explored potential mechanisms for infant weight gain, which include parental obesity and feeding practices. Studies have associated short sleep with a heavier weight profile in older children and adults, although negative results also have been reported.

What’s the bottom line?

Short total sleep duration at 3 months and short night-time sleep duration at 8 months are associated with the risk of gaining excess weight at 24 months. Sleep is important for child growth and development. To prevent the childhood obesity epidemic in the future, parents are encouraged to be aware of their child’s circadian rhythm, bedtime routines and sleep hygiene.

Reviewed by: Jessica Wong


If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments! We are also looking to expand the Bubble Wrap team so please contact us if you’re interested in this! 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. 

Wheeze. It’s all in the timing…

Cite this article as:
Patrick Aldridge. Wheeze. It’s all in the timing…, Don't Forget the Bubbles, 2019. Available at:
You’ve just treated a 5 year old with their second episode of wheeze this year. They’ve had burst therapy,  and are now one hourr post treatment with no work of breathing, scattered wheeze on auscultation and oxygen saturations of 95%. You contemplate giving them steroids and decide against it.

Bubble Wrap PLUS – September 2019

Cite this article as:
Anke Raaijmakers. Bubble Wrap PLUS – September 2019, Don't Forget the Bubbles, 2019. Available at:

Here is September’s Bubble Wrap Plus, our monthly paediatric Journal Club List provided by Professor Jaan Toelen & his team 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: ‘When may influenza lead to severe pneumonia?’, ‘Do IVF babies have an abnormal vascular health?’, ‘Should we have a talk with our anesthesiologists about prolonged fasting in pediatric anesthesia?’, ‘Is there an association between UTIs and renal scarring?’ and ‘Prednisolone or Dexamethasone, which one is best for Croup?’.

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

1.Reviews and opinion articles

Social media and children: what is the paediatrician’s role?

Hadjipanayis A, et al. Eur J Pediatr. 2019 Aug 30.

Ultrafine particles and children’s health: Literature review.

da Costa E Oliveira JR, et al. Paediatr Respir Rev. 2019 Jun 26.

An introduction to clinical trial design.

Schultz A, et al. Paediatr Respir Rev. 2019 Jun 26.

Janus looks both ways: How do the upper and lower airways interact?

de Benedictis FM, et al. Paediatr Respir Rev. 2019 Jun 26.

Decision-making for pediatric allergy immunotherapy for aeroallergens: a narrative review.

Tortajada-Girbés M, et al. Eur J Pediatr. 2019 Aug 14.

Leaving me speechless: how an early encounter with a doctor influenced my work as a paediatrician.

[No authors listed] Arch Dis Child. 2019 Aug 13.

Does It Matter if This Baby Is 22 or 23 Weeks?

Janvier A, et al. Pediatrics. 2019 Sep;144(3).

Walking on Eggshells With Trainees in the Clinical Learning Environment-Avoiding the Eggshells Is Not the Answer.

Gold MA, et al. JAMA Pediatr. 2019 Aug 5.

Abdominal ultrasound should become part of standard care for early diagnosis and management of necrotising enterocolitis: a narrative review.

van Druten J, et al. Arch Dis Child Fetal Neonatal Ed. 2019 Sep;104(5):F551-F559.

2. Original clinical studies

Risk Factors for Influenza Virus Related Severe Lower Respiratory Tract Infection in Children.

Eşki A, et al. Pediatr Infect Dis J. 2019 Aug 27.

Timing of voiding cystourethrography after febrile urinary tract infection in children: a systematic review.

Mazzi S, et al. Arch Dis Child. 2019 Aug 29.

Physical activity, fatigue and sleep quality at least 6 months after mild traumatic brain injury in adolescents and young adults: A comparison with orthopedic injury controls.

van Markus-Doornbosch F, et al. Eur J Paediatr Neurol. 2019 Aug 9.

Incidence of epilepsy in children born prematurely and small for gestational age at term gestation: A population-based cohort study.

Chou IC, et al. J Paediatr Child Health. 2019 Aug 28.

Prenatal Opioid Exposure: Neurodevelopmental Consequences and Future Research Priorities.

Conradt E, et al. Pediatrics. 2019 Sep;144(3).

Enterovirus, parechovirus, adenovirus and herpes virus type 6 viraemia in fever without source.

L’Huillier AG, et al. Arch Dis Child. 2019 Aug 28.

Frequency of urinary tract infection in children with antenatal diagnosis of urinary tract dilatation.

Pennesi M, et al. Arch Dis Child. 2019 Aug 28.

Electronic Nicotine Delivery Systems Marketing and Initiation Among Youth and Young Adults.

Loukas A, et al. Pediatrics. 2019 Sep;144(3).

Prenatal paracetamol exposure and neurodevelopmental outcomes in preschool-aged children.

Trønnes JN, et al. Paediatr Perinat Epidemiol. 2019 Aug 25.

Two new chest compression methods might challenge the standard in a simulated infant model.

Rodriguez-Ruiz E, et al. Eur J Pediatr. 2019 Aug 24.

Can intussusceptions of small bowel and colon be transient? A prospective study.

Wang Q, et al. Eur J Pediatr. 2019 Aug 24.

Effects of Childhood and Adult Persistent Attention-Deficit/Hyperactivity Disorder on Risk of Motor Vehicle Crashes: Results From the Multimodal Treatment Study of ADHD.

Roy A, et al. J Am Acad Child Adolesc Psychiatry. 2019 Aug 22.

Should we look for Hirschsprung disease in all children with meconium plug syndrome?

Buonpane C, et al. J Pediatr Surg. 2019 Jun;54(6):1164-1167.

Necrotizing enterocolitis in term neonates: A different disease process?

Overman RE Jr, et al. J Pediatr Surg. 2019 Jun;54(6):1143-1146.

Digital Phenotyping With Mobile and Wearable Devices: Advanced Symptom Measurement in Child and Adolescent Depression.

Sequeira L, et al. J Am Acad Child Adolesc Psychiatry. 2019 Sep;58(9):841-845.

Vascular Health of Children Conceived via In Vitro Fertilization.

Zhang WY, et al. J Pediatr. 2019 Aug 20. pii: S0022-3476(19)30885-6.

Symptom Burden and Quality of Life Over Time in Pediatric Eosinophilic Esophagitis.

Klinnert MD, et al. J Pediatr Gastroenterol Nutr. 2019 Aug 20.

Real fasting times and incidence of pulmonary aspiration in children: Results of a German prospective multicenter observational study.

Beck CE, et al. Paediatr Anaesth. 2019 Aug 22.

Reducing Variability in the Infant Sepsis Evaluation (REVISE): A National Quality Initiative.

Biondi EA, et al. Pediatrics. 2019 Sep;144(3).

An End in Sight: Shorter Duration of Parenteral Antibiotics in Neonates.

Leva NV, et al. Pediatrics. 2019 Sep;144(3).

Parenteral Antibiotic Therapy Duration in Young Infants With Bacteremic Urinary Tract Infections.

Desai S, et al. Pediatrics. 2019 Sep;144(3).

Impact of an Antibiotic Stewardship Program on Antibiotic Prescription for Acute Respiratory Tract Infections in Children: A Prospective Before-After Study.

Aoybamroong N, et al. Clin Pediatr (Phila). 2019 Aug 20:9922819870248.

Long-term vs. recent-onset obesity: their contribution to cardiometabolic risk in adolescence.

Burrows R, et al. Pediatr Res. 2019 Aug 19.

Environmental determinants associated with acute otitis media in children: a longitudinal study.

van Ingen G, et al. Pediatr Res. 2019 Aug 17.

Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial.

Parker CM, et al. Pediatrics. 2019 Sep;144(3).

Maternal Voice and Infant Sleep in the Neonatal Intensive Care Unit.

Shellhaas RA, et al. Pediatrics. 2019 Sep;144(3).

Childhood Facial Palsy: Etiologic Factors and Clinical Findings, an Observational Retrospective Study.

Hanci F, et al. J Child Neurol. 2019 Aug 13:883073819865682.

Association Between Electronic Cigarette Use and Marijuana Use Among Adolescents and Young Adults: A Systematic Review and Meta-analysis.

Chadi N, et al. JAMA Pediatr. 2019 Aug 12:e192574.

Association of Cereal, Gluten, and Dietary Fiber Intake With Islet Autoimmunity and Type 1 Diabetes.

Hakola L, et al. JAMA Pediatr. 2019 Aug 12.

Shared Reading at Age 1 Year and Later Vocabulary: A Gene-Environment Study.

Jimenez ME, et al. J Pediatr. 2019 Aug 8.

Cost-Effectiveness of Screening Ultrasound after a First, Febrile Urinary Tract Infection in Children Age 2-24 Months.

Gaither TW, et al. J Pediatr. 2019 Aug 8.

Use of paediatric early warning scores in intermediate care units.

Lampin ME, et al. Arch Dis Child. 2019 Aug 10.

How Much Is Too Much? Examining the Relationship Between Digital Screen Engagement and Psychosocial Functioning in a Confirmatory Cohort Study.

Przybylski AK, et al. J Am Acad Child Adolesc Psychiatry. 2019 Aug 7.

Delivery Room Continuous Positive Airway Pressure and Pneumothorax.

Smithhart W, et al. Pediatrics. 2019 Sep;144(3). pii: e20190756.

Understanding the Risks and Benefits of Delivery Room CPAP for Term Infants.

Claassen CC, et al. Pediatrics. 2019 Sep;144(3).

Quality of Life in Children with Functional Constipation: A Systematic Review and Meta-Analysis.

Vriesman MH, et al. J Pediatr. 2019 Aug 6.

Testing for Meningitis in Febrile Well-Appearing Young Infants With a Positive Urinalysis.

Wang ME, et al. Pediatrics. 2019 Sep;144(3).

Undifferentiated Abdominal Pain in Children Presenting to the Pediatric Emergency Department.

Harris BR, et al. Clin Pediatr (Phila). 2019 Aug 6:9922819867459.

Association Between Recurrent Febrile Urinary Tract Infections and Renal Scarring: From Unquestioned Answers to Unanswered Questions.

Roberts KB. JAMA Pediatr. 2019 Aug 5.

Association of Renal Scarring With Number of Febrile Urinary Tract Infections in Children.

Shaikh N, et al. JAMA Pediatr. 2019 Aug 5.

Use of high-flow nasal cannula in infants with viral bronchiolitis outside pediatric intensive care units.

Panciatici M, et al. Eur J Pediatr. 2019 Aug 1.

Association of Gluten Intake During the First 5 Years of Life With Incidence of Celiac Disease Autoimmunity and Celiac Disease Among Children at Increased Risk.

Andrén Aronsson C, et al. JAMA. 2019 Aug 13;322(6):514-523.

4. Case reports

Superior mesenteric artery syndrome mimicking cyclic vomiting syndrome in a healthy 12-year-old boy.

Dimopoulou A, et al. J Paediatr Child Health. 2019 Aug 13.

An 8-year-old boy with ataxia and abnormal movements.

Hanes I, et al. Paediatr Child Health. 2019 Aug;24(5):297-298.

A 10-year-old boy with fever, arthritis, and a painful rash.

Erdle SC, et al. Paediatr Child Health. 2019 Aug;24(5):295-296.

Abdominal Pain and Intermittent Fevers in a 16-Year-Old Girl.

Penberthy K, et al. Pediatrics. 2019 Sep;144(3).

Case 27-2019: A 16-Year-Old Girl with Head Trauma during a Sailboat Race.

Iaccarino MA, et al. N Engl J Med. 2019 Aug 29;381(9):863-871.

Mittens and Booties Syndrome: A Unique Manifestation of Human Parechovirus Infection in Infants.

Ristagno EH, et al. Pediatr Infect Dis J. 2019 Sep;38(9):e223-e225.


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

The 33rd Bubble Wrap

Cite this article as:
Grace Leo. The 33rd Bubble Wrap, Don't Forget the Bubbles, 2019. Available at:

Article 1: More evidence for lower dexamethasone dosing in croup

Parker C, Cooper M. Prednisolone Versus Dexamethasone for Croup: a Randomized Controlled Trial. Pediatrics. 2019; 144(3):e20183772 

Why does it matter?

There is a lack of data comparing prednisolone and low-dose dexamethasone for the treatment of childhood croup. Early trials have shown the safety and efficacy of 0.6mg/kg of oral dexamethasone and there have been some studies showing potential efficacy of 0.3mg/kg and 0.15mg/kg dosing. These  studies however have not been adequately powered to detect clinical significance.  It is known that 1mg/kg of prednisolone is effective in croup patients requiring intubation and shortens the time to extubation for patients with croup in intensive care1.

What’s it about?

A prospective, double-blind, noninferiority randomised controlled trial was conducted over two urban emergency centres in Perth, Australia. 1252 children >6 months old, and <20kg with croup were randomised to oral dexamethasone (0.6mg/kg; n=410), low-dose dexamethasone (0.15mg/kg; n=410), or oral prednisolone (1mg/kg; n= 411).  

The Westley Croup Score (WCS), a clinical score based on stridor, retractions, air entry and level of consciousness was assessed at baseline, and then hourly up to 6 hours, and again at 12 hours, if the patients were not yet discharged.  Results showed no statistically significant difference between the 3 groups for the WCS at the 1-hour assessment: 0.03 (95% CI- 0.09 to 0.15; p=0.62) for low-dose dexamethasone and 0.05 (95% CI -0.07 to 0.17; p=0.40) for prednisolone.  Both of these groups fell within the prescribed noninferiority margin of 0.5.  Interestingly, WCS for low-dose dexamethasone was 0.11 higher at 2 hours and 0.23 higher at 3 hours compared to 0.6mg/kg dexamethasone group.  The difference was significant at 3 hours (p=0.04), however, the upper limit of 95% CI (0.45) was within the noninferiority margin. Authors propose that the “ceiling effect,”theory, where steroid effect above a certain threshold does not have additional benefit, may be at a dose higher than 0.15mg/kg for a minority of patients. 

Re-attendance rates (to GP and ED) within 7 days after treatment were 17.8% for 0.6mg/kg dexamethasone, 19.5% (p=0.59) for low-dose dexamethasone and 21.7% (p=0.19) for prednisolone. 

Clinically Relevant Bottom Line

Noninferiority was demonstrated for both low-dose dexamethasone (0.15mg/kg) and single dose prednisolone (1mg/kg) compared with 0.6mg/kg dexamethasone. There was no clinically significant difference on efficacy in the acute period, as well as re-attendance rates to both GP and ED.  

Reviewed by: Lorraine Cheung

1.   Tibballs J, Shann FA, Landau LI. Placebo-controlled trial of prednisolone in children intubated for croup. Lancet. 1992:340 (8822): 745-748

2.   Geelhoed GC, Macdonald WB. Oral dexamethasone in the treatment of croup: 0.15mg/kg versus 0.3mg/kg versus 0.6mg/kg. Paediatric Pulmonology. 1995;20(6):362-368 


Article 2: The dangers of VALI (not the son of Loki)  

Ween MP, Hamon R, Macowan MG, Thredgold L, Reynolds PR, Hodge SJ. Effects of E cigarette E liquid components on bronchial epithelial cells: Demonstration of dysfunctional efferocytosis, Respirology. 2019 Sep 22. doi: 10.1111/resp.13696 [Epub ahead of print]

Why does it matter?

The e-cigarette was released in 2003, being marketed as safer for smokers and everyone around them. The use and popularity amongst adolescents continues to rise, despite new information about Vaping Associated Lung Injury (VALI), as well as injuries related to malfunctioning devices. In Australia, e-cigarettes containing nicotine liquid have been banned, but the base composition of a fruit flavour, vegetable glycerine (VG) and propylene glycol (PG) may still have harmful effects.

What’s it about?

An in vitro study which compared the effects of cigarette smoke extract to apple flavoured E liquid and nicotine (in a VG and PG base). The authors looked at cytokine release, cell necrosis, apoptosis and efferocytosis in healthy bronchial epithelial cells.

The results show that all individually (glycol bases alone, apple flavouring alone, nicotine alone) and combination (apple + nicotine) had significant toxic effects, when compared with the control of cigarette smoke extract. E cigarette components caused apoptosis and necrosis, reduced efferocytosis by down regulation of receptors, and reduced the production of certain inflammatory cytokines.

Clinically Relevant Bottom Line

To the surprise of nobody, e-cigarettes are not harmless. Ongoing research into the effects of first hand and second hand E- Cigarettes vapour, both containing nicotine and nicotine free, will be crucial in determining new policies and regulations, especially to curb the rise of use amongst our young population.

Reviewed by: Tina Abi Abdallah


Article 3:  Optimal fasting regimens – what does the evidence suggest?

Real fasting times and incidence of pulmonary aspiration in children: Results of a German prospective multicenter observational study. Beck et al. Paediatr Anaesth. 2019 Aug 22.

What’s it about?

Unfortunately, prolonged fasting times before a general anaesthesia is still common in paediatrics. The authors of this article hypothesised that shortened fasting times could improve the child’s condition during induction of anaesthesia and improve children’s and parental satisfaction. This prospective observational study in Germany looked at real fasting times and proposed reduced fasting times, but an (adapted) national guideline is lacking. Over 3000 children were included at 10 paediatric centres in Germany. Surprisingly, the real fasting times were 14 hours for large meals, 9 hours for light meals, 6 hours for formula, 5 hours breast milk and 3 hours for clear fluids. The authors report a prolonged fasting (defined as over 2 hours deviation from guideline) for large meals in 88%, for light meals in 55%, for formula milk in 44%, for breast milk in 26% and for clear fluids in 34%.

Eleven cases (0.33%) of regurgitation, four cases (0.12%) of suspected pulmonary aspiration and two cases (0.06%) of confirmed pulmonary aspiration were reported, without any prolonged anaesthetic.

Why does it matter?

Children having an anaesthetic should not be fasted longer than necessary as this negatively impacts tolerability of the child, the parents and their environment. This study shows that prolonged fasting is very common, from large meals to clear fluids. All cases could be extubated after the end of the procedure and recovered without any incidents which may suggest we are too strict with our fasting times.

Clinically Relevant Bottom Line

This study shows that prolonged fasting is still common in paediatric anaesthesia and that complications related to not fasting are rare and that improvements to current local fasting regimens and national fasting guidelines are urgently needed. Short fasting guidelines for children could potentially improve anaesthetic tolerance and satisfaction.

Reviewed by: Anke Raaijmakers


Article 4:  Family Chaos and Asthma Control

Weinstein SM, Pugach O, Rosales G, Mosnaim GS, Walton SM, Marin MA. Family Chaos and Asthma Control. Paediatrics. 2019. Aug;144(2). doi: 10.1542/peds.2018-2758. Epub 2019 Jul 9.

What’s it about?

This cohort study focused on 223 children (5 to 16 years-old) of low-income minority background with poorly-controlled asthma in the United States.  The study explored the relationship between asthma severity and psychosocial factors such as parental and child depression, post-traumatic stress disorder (PTSD) symptoms and family functioning.    Both parents and children showed higher rates of depression and PTSD symptoms compared to the general population. Parental and child depression symptoms were associated with poor asthma control, asthma severity and limitations of activity (P<0.001). PTSD symptoms were unrelated to child asthma outcomes. Family chaos serve as a predictor of poor asthma outcomes and a mediator for the relationship between parental depression and child asthma (P<0.05).  

Why does it matter?

Previous studies have shown a high prevalence of poorly-controlled asthma among school-aged children (6 to 17 years old). Studies have found increased rates of parental depression and anxiety, associated with poor child asthma outcome. Child depression and anxiety symptoms are predictors of poor asthma outcomes, including increased functional impairment, asthma severity and frequency of emotional triggers.

Clinically Relevant Bottom Line

Child and parent depression and family chaos are predictors of uncontrolled asthma. Family chaos also serves as the mediator between parent depression and asthma outcomes. To optimise asthma care, measures to screen youth and parent depression in community settings should be made aware and become part of the clinical guideline.

Reviewed by: Jessica Wong


Article 5:  Mother knows best?

Vanderkooi OG, Xie J, Lee BE, Pang X, Chui L, Payne DC et al. on behalf of Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) and Pediatric Emergency Research Canada (PERC). A prospective comparative study of children with gastroenteritis: emergency department compared with symptomatic care at home . Eur J Clin Microbiol Infect Dis. 2019 Sep 9. doi: 10.1007/s10096-019-03688-8. [Epub ahead of print]

What’s it about?

The “apple juice” paper highlighted that treatment of gastroenteritis can be simple but led many to question why some of the children recruited needed any formal fluid trials at all. This study by the same author (Stephen Freedman) was designed to compare the treatment and outcomes of children with gastroenteritis seen in the Emergency Department with those who were managed at home.

The recruitment strategy was dependent on a national helpline, those in the UK will know this as similar to 111, which triages and directs parents to call to either self-care at home or suggest onward referral.

A cohort of patients presenting to the Emergency Department with gastroenteritis (1317 children, median age 20.8 months) were compared with those who were managed at home (296 children, median age 17.4 months). The groups were essentially similar (both had a high rate of having a rectal swab for bacteria.viruses performed, in the ‘at home’ cohort this was taken by the parents).

Isolated vomiting was higher in the ED group but isolated diarrhea more frequent at the home cohort. While the median dehydration scores in the ED (3 IQR 2-4) were significantly different from at home (1 IQR 0-2) the clinical significance is not clear as both would rank as ‘some dehydration’ and the scale goes up to 8.

Why does it matter?

This could have been a ‘so-what’ study. You would expect that a group of children presenting to an ED with symptoms of gastroenteritis would vomit more than those staying at home and would be more clinically dehydrated. However this study again shows how minor dehydration generally is with gastroenteritis and how isolated vomiting causes concern in parents. Of most interest was over 35% of the at home group had norvovirus. This means if we can direct public health efforts to further educating parents on managing gastroenteritis it is possible we can further safely reduce ED attendance.

Clinically Relevant Bottom Line

Children are more unwell with gastroenteritis if their parents choose to bring them to hospital. But not by a massive amount and they do successfully look after children with infections often associated with need for admission.

Reviewed by: Damian Roland


If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments! We are also looking to expand the Bubble Wrap team so please contact us if you’re interested in this! 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. 

Change against the grain: Shweta Gidwani at DFTB19

Cite this article as:
Team DFTB. Change against the grain: Shweta Gidwani at DFTB19, Don't Forget the Bubbles, 2019. Available at:

Shweta Gidwani graduated from Seth G.S. Medical College, Mumbai, India in 2002. S. She has been involved in the development of emergency care service delivery and training programs in India for several years and was invited to join the International Emergency Medicine section at George Washington University as Adjunct Asst Professor in 2013 where she works on the India programs.

This talk, the opening talk proper after Mary set the scene, is a stark reminder of just how the world really works.


©Ian Summers



This talk was recorded live at DFTB19 in London, England. With the theme of  “The Journey” we wanted to consider the journeys our patients and their families go on, both metaphorical and literal. DFTB20 will be held in Brisbane, Australia.

If you want our podcasts delivered straight to your listening device then subscribe to our iTunes feed or check out the RSS feed. If you are more a fan of the visual medium then subscribe to our YouTube channel. Please embrace the spirit of FOAMed and spread the word.

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Blood Lactate: Freshly Squeezed

Cite this article as:
Alasdair Munro. Blood Lactate: Freshly Squeezed, Don't Forget the Bubbles, 2019. Available at:

Hermione is a 15-day old baby girl brought in for prolonged jaundice. She is breastfed and has no other risk factors. Her examination is normal other than being a bit on the yellow side. You ask the nurse to perform a blood gas to check her bilirubin, which is below 200. You notice the lactate on the gas is 4, but the nurse reports it was a “squeezed sample” which she suggests could explain the result?

BRUE v ALTE – have the new guidelines made a difference?

Cite this article as:
Roland D, Davis T. BRUE v ALTE – have the new guidelines made a difference?, Don't Forget the Bubbles, 2019. Available at:

This week sees the publication of a new paper in Pediatrics by the team at the Children’s Hospital of Pittsburgh and the University of Pittsburgh.

Ramgopal SR, Noorbakhsh KA, Callaway CQ, Wilson PM, Pitetti RD. Changes in the management of children with brief unresolved unexplained events (BRUEs). Pediatrics.

Why was this study needed?

In 2016, the American Academy of Pediatrics published a guideline which renamed and redefined ALTEs (acute life-threatening event). The new term was BRUE (brief resolved unexplained event).

ALTE was initially coined in 1986 and the definition was:

an episode that is frightening to the observer and that is characterised by some combination of apnoea (central or occasionally obstructive), colour change…marked change in muscle tone (usually marked limpness), choking, or gagging. In some cases, the observer fears that the infant has died.

This was a broad definition and caused some difficulties for those of us assessing babies in hospitals. Although an ALTE could indicate a serious underlying problem – NAI, infection, seizure – commonly the infant was completely well. ALTEs by definition were subjective and this made the management of them tricky. Often these babies had overnight admissions to hospital for observation.

The new definition for BRUE is:

A BRUE has occurred if the observer reports a sudden, brief, and now resolved, unexplained episode of ≥1 of the following:

  • cyanosis or pallor
  • absent, decreased, or irregular breathing
  • marked change in tone (hyper- or hypotonia)
  • altered level of responsiveness

As well as the new definition, the guideline also stratifies patients and recommends management for those in the low-risk group.

Read our DFTB summary of the change in guidance here.

It has now been three years since the change from ALTE to BRUE. The aim of this study was to see whether the new guidance has affected rates of admission, investigations, or outcomes.

The objectives of the study were cleared stated and relevant to paediatric emergency medicine.

Who were the patients?

Patients were taken from the Pediatric Health Information System, which is a database with all information from presentations and admissions in hospitals across 26 states in the USA.

Patients were included if they were under 1 year old and had a diagnosis coded of either ALTE or BRUE between 2015 and 2017.

Exclusions were if patients had been transferred from another hospital, or had ambulatory surgery.

A control cohort was also used from all ED presentations of children under one year old during the inclusion period with no diagnosis of ALTE and BRUE (same exclusion criteria). The aim of the cohort group was to check whether there were any confounding trends in admissions/investigations during that time period.

This was an appropriate choice of patient group and the use of control cohort was beneficial. Sample size estimates were not stated explicitly but were alluded to.

The limitation here is the reliance on coding. However, additionally the authors were unable to determine if the diagnosis was correct, or if the patient could be classified as a low-risk BRUE as these assessments require a history and examination.

9,501 patients were used for the cohort analysis (5508 patients 0-60 days old, and 3993 who were 60 days to 1 year old). This group was split into a 2015 cohort (i.e. before the new guidelines) and a 2017 cohort (after the introduction of the new guidelines)

A second analysis was an interrupted time series analysis to look at trends in admissions over time. 13,977 patients were included in this group.

1.4 million patients were in the control cohort.

What analysis was carried out on these groups?

The cohort analysis looked at the rate of admissions as the primary outcome. Secondary outcomes included revisits and investigations performed. A comparison was also conducted by using the control cohort.

The interrupted time series analysis looked at whether admission rates changed over time following the introduction of the guideline. Admission rates were analysed in one-week batches throughout the three year time period.

The subjects were all accounted for and appropriate outcomes were considered.

What were the findings?

Admissions: the proportion of admissions in the 61-365 day old group was 86.2% in the 2015 cohort and 68.2% in the 2017 cohort. The admissions were also significantly lower in the 0-60 days group – 89.9% in the 2015 group and 84.1% in the 2017 group.

Investigations: the 2017 group had significantly lower rates of EEG, MRI, CXR, FBC, U+Es, LFT, and urinalysis. Those in the 0-60 day old group (2017) had significantly lower rates of blood gas measurement, blood sugar testing, head CT, metabolic studies, and lumbar puncture.

Revisits: in the 0-60 day old group, revisits within 3 days were significantly lower in the 2017 group (3.7%) than in the 2015 group (5.2%). The rest of the revisit rates were similar.

Analysis of the control cohort here suggested that the decreased rates of these outcomes were independent of other trends over time.

Interrupted time series analysis: in the 0-60 day old group the introduction of the guideline did not affect trends in admissions rates. However, in the 61-365 day old group, the admission rates decreased each week after the guideline was published.

The authors were clear on what was measured and how it was measured. Follow up was for a 30 day period so should have picked up most complications. The measurements were reliable, valid, and the basic data was adequately described.

What did the authors conclude?

Between 2015 and 2017 there has been a significant reduction in the rates of admission and investigations for patients with ALTE/BRUE. This rate decreased steadily following the guideline publication.

The authors note that this reduction is seen in the 0-60 day old group, even though that age group would be stratified as higher risk in the new guidelines. The fact that BRUE is a diagnosis of exclusion, whereas ALTE was all-encompassing may mean that this diagnosis is being applied to a smaller, safer group over time, which might explain the findings. There were less patients diagnosed with ALTE/BRUE in 2017 compared to 2015.

The results are discussed in relation to existing knowledge and the discussion seems balanced and not biased. The conclusions are justified by the data.

Will this paper change my practice?

Changing practice is challenging, changing a definition is a little easier.

This study is a great example of how to review the impact of guideline change and determine whether the outcomes have improved for patients without unintended consequences. At face value the BRUE approach has had beneficial clinical impact. We see an overall decline in admission and investigations with no obvious harm (returns don’t increase).

There are a few caveats that are important to consider though. This study was from a chain of hospitals likely working with similar cultures and convergent working practices. A random selection of children’s hospitals may have interpreted the AAP guideline with a greater degree of variance (and therefore application). With this in mind the relevance of quite a profound change in coding should be highlighted. In a similar timescale 25% of patients with a prior diagnosis of ALTE are no longer coded as such and it appears that these patients are not replaced with a BRUE code (as there was a 25% reduction overall in either code). This means that either the guidance has been successful in making staff think hard about about the underlying reason for the infant’s presentation or that perhaps initial coding was not as precise as it could have been (“I’m not sure what happening here so I’ll just call it an ALTE“). Of note the return rate isn’t supplied for those not coded as BRUE or ALTE so we don’t know if the cohort of patients now coded as something else have actually come to increased harm. It is also interesting to note the significant fall in admissions for those less than 60 days old. This wasn’t the intention of the initial guidance and while this group’s re-admission rates didn’t increase this study wasn’t powered (or designed) to look at whether the re-admission changes would be significant or not. The fact that it appears safer is a statistical construct, not a clinical one. This means a type II error is possible (there is actually a problem but we aren’t seeing it).  

Ultimately, while these risks are real, and do need investigation in future study, it is likely that altering to using BRUE will effectively rationalize your investigation and management pathways without causing additional harm. The challenge for those outside the United States is whether national organizations are happy to formally endorse the BRUE concept as staff may feel uncomfortable applying new rules without official sanction. Locally certainly, we use the BRUE criteria in our risk assessment and this study only further endorses that approach.

Post-publication commentary from one of the authors

This is a really wonderful summary and analysis of the study. The findings do suggest that patients in the low risk cohort identified by the AAP BRUE guidelines are being discharged safely without an increase in return visits. It is important to note that this narrower definition of BRUE has not excluded all high acuity conditions, as patients with high acuity co-diagnoses were identified in both age groups after the practice guideline publication.
Overall, I think our findings support continued clinical application of the BRUE definition and guidelines. While not within the scope of our study, the results did make us wonder about the impact of guidelines published by a national medical organization. How much of the change we saw in a three-year period were due to influence by the AAP and how much was because the medical community was ready for a change in ALTE management? Finally, we hope that our findings are able to support further research into management of both low-risk and high-risk BRUE and into understanding what has changed in the management of infants who are now excluded from the BRUE diagnosis.
Katie Noorbakhsh (author)

Here’s a printable A4 summary of the paper & our thoughts:

Changes in the management of children with Brief resolved unexplained events (BRUEs)

The 32nd Bubble Wrap

Cite this article as:
Grace Leo. The 32nd Bubble Wrap, Don't Forget the Bubbles, 2019. Available at:


Article 1: Should we worry about fever after Meningococcal B immunisations?

Campbell G, Bland RM, Hendry SJ. Fever after meningococcal B immunisation: A case series. J Paediatr Child Health. 2019; 55: 932-937. doi:10.1111/jpc.14315

Why does it matter?

Meningococcal meningitis and septicaemia remain is one of the most serious bacterial infections (SBI). In Australia, the government subsidised vaccine schedule includes Meningococcal ACWY however Meningococcal B vaccine (Bexsero) can be purchased ($250-$500) for children 6 weeks to 11 years. It is an immunogenic vaccine, and paracetamol is recommended on the day of immunisation, but how can we be sure the fever is due to the infection and not something more sinister?

What’s it about?

A prospective case series from the ED at Royal Hospital for Children, Glasgow was performed on patients presenting between 2016-17. They identified 92 eligible infants under 3 months presenting with fever within 72 hours of Bexsero immunisations. The youngest infant was 7 weeks old.

Of these patients, 76 infants were discharged within 24 hours with majority undergoing at least one investigation (FBC, CRP, Urine MCS, NPA). Only 16 children of the 66 admitted remained in hospital for > 24 hours, with 12 undergoing an LP and completing 48 hours of IV antibiotics.

In this study, 26 children had an NPA performed with 12 positive for at least 1 virus, and one child represented with bronchiolitis.

Only one child in the cohort had SBI with an E.coli UTI. This infant also had a significantly elevated CRP and WCC compared with the other patients, and their fever started 54 hours after immunisation. The remainder had negative CSF, urine and blood cultures.

Clinically Relevant Bottom Line

Fever in the first 24 hours following the 2 month Meningococcal B vaccine is expected, and depending on the clinical exam and partial septic work up results, may be discharged home with reassurance. The key is to always be weary of the unwell looking infant and those whose fevers persist, as a full septic work up and IV antibiotics should be considered.

Reviewed by: Tina Abi Abdallah


Article 2:  Does iron fortified formula for Infants make a difference?

Gahagan S, et al. Randomized Controlled Trial of Iron-Fortified versus Low-Iron Infant Formula: Developmental Outcomes at 16 Years. The Journal of Pediatrics. 2019 June [epub] doi: 10.1016/j.jpeds.2019.05.030

Why does it matter?

Iron deficiency anaemia in infancy has long-term effects on the developing brain.  It is the most common nutrition disorder in the world.  Therefore, many countries routinely supplement infant formula with iron.  Recommendations for iron concentrations in infant formulas differ between guidelines, ranging from 4-12mg/L.Australian formulas generally contain between 6.7-9 mg/L.  There has been no study comparing the effects of iron-fortified formula vs low-iron formula on cognitive outcomes. 

What’s it about? 

Six-month old infants who did not have iron deficiency anaemia, were recruited from community clinics in Santiago, Chile.  They were randomised to iron-fortified (12mg/L) or low-iron (2.3mg/L) formula for 6 months and were followed-up at 16 years of age.  Of the 405 participants, those who randomised to iron-fortified formula (n=216) had lower scores than those randomised to low-iron formula (n=189) in 8 of the 9 tests.  Three of the 8 were statistically significant, and were in the domains of visual memory (p=0.02), arithmetic achievement (p=0.02) and reading comprehension achievement (p=0.02).  For visual motor integration, it was found that those with low haemoglobin at 6-months of age who received iron-fortified formula, outperformed those with low-iron formula.  The opposite was also true, with those with high haemoglobin at 6 months, receiving iron-fortification underperforming those with low-iron formula.  Animal studies have shown concern regarding the possibility of iron neurotoxicity in the growing infant, as well as the effects of iron exposure in early life on brain aging and neurodegenerative disease outcomes.

Clinically Relevant Bottom Line

This study from Chile suggests that  adolescents who received iron-fortified formula as infants from 6 to 12 months of age had poorer cognitive outcomes compared with those who received a low-iron formula. This could be related to iron neurotoxicity and there is a need for further studies to investigate the optimal level of iron supplementation in infancy.  Although on a public health level it may not be feasible, it may be ideal to individualise the optimal amount of iron for supplementation based on baseline haemoglobin or iron measures. 

Reviewed by: Lorraine Cheung

  1. American Academy of Pediatrics Committee on Nutrition recommends 10-12mg/L from birth. European Society of Pediatric Gastroenterology, Hepatology and Nutrition recommends 4-7 mg/L.


Article 3: Introducing paediatric procedural sedation in low-resource countries

Schultz, M & Niescierenko, M. Guidance for Implementing Pediatric Procedural Sedation in Resource-Limited Settings. Clinical Pediatric Emergency Medicine, 2019 In Press; doi: 10.1016/j.cpem.2019.06.004

Why does it matter?

Since its introduction, much research has demonstrated the safety and benefit of paediatric procedural sedation (when used with the proper monitoring). The benefits of procedural sedation include reduced procedure time and error rates; increased comfort of patients, parents and health care professionals; and reduced need for general anaesthesia for minor procedures. While paediatric procedural sedation is part of routine practice in high-income countries (HIC), it is almost non-existent in low- and middle-income countries (LMIC). The paper claims this is mainly due to a lack of skilled providers, not for lack of need. Providing proper clinical training to health providers in LMIC would help provide safe and adequate analgesia for children undergoing minor procedures.

What’s it about?

The authors of the paper have devised a paediatric procedural sedation curriculum, which was piloted at John F. Kennedy Hospital in Monrovia, Liberia. The pilot curriculum focuses solely on the use of ketamine, as it is cheap, widely available in Africa, has multiple routes of administration and is safe for use in children. The curriculum also allows for a single-practitioner method of procedural sedation, which is key in LMIC where there are limited number of health providers compared to the patient load. The curriculum is divided in three 2-hour sessions which consist of (1) introduction to procedural sedation, (2) resuscitation and management of adverse effect, and (3) monitoring and conclusion. All required teaching supplies were restricted to printed handouts, poster paper, markers and low-fidelity simulation equipment, thus eliminating the need for computers, software and electricity. Participants of this curriculum were 15 paediatric and surgical residents.

Clinically relevant bottom line

I was  fascinated with how the authors came up with this pilot curriculum for the Liberian hospital. Not only did they have to think about the costs of the individual piece of equipment in the sedation kit, but they also took into consideration the variable availability of electricity, the type of possible monitoring during sedation, and the scarcity of personnel. Too often we forget how lucky we are to have access to so many resources! The rollout of safe and routine paediatric procedural sedation is ongoing in Liberia and this is an initial step toward enabling safe procedural sedation for children living in LMIC.

Reviewed by: Jennifer Moon


Article 4: Supporting parents to CEASE smoking

Nabi-Burza E, Drehmer JE, Hipple Walters B, et al. Treating Parents for Tobacco Use in the Pediatric Setting: The Clinical Effort Against Secondhand Smoke Exposure Cluster Randomized Clinical Trial. JAMA Pediatr. Published online August 12, 2019. doi:10.1001/jamapediatrics.2019.2639

Why does it matter?

Exposure of children to secondhand and even thirdhand smoke (from toxins absorbed in clothing, carseats) is a serious public health issue. Smoke from cigarette smoke contains about 4000 chemicals, over 50 of which are known carcinogens. Second hand smoke increases the risk of children having SIDS, ear and respiratory infections, asthma exacerbations and teeth problems.

What’s it about?
The CEASE intervention (Clinical Effort Against Secondhand Smoke Exposure Cluster Randomized Clinical Trial) was developed between the AAP  and Massachusetts Tobacco Cessation and Prevention Program, and the Massachusetts General Hospital Center for Child and Adolescent Health Research and Policy. It focuses on 3 of the 5 As of tobacco cessation – Ask, Assist and Arrange Follow Up.

In this cluster RCT study run by the AAP, the CEASE intervention was delivered in paediatric clinics in 5 American states. The CEASE intervention included a smart tablet questionnaire, educational pamphlets and aids and training for staff to help screen for tobacco use and offer treatment to parents. Treatments were referral to a Quitline and/or provision of nicotine replacement therapy.
The study looked at the effectiveness and sustainability of this CEASE intervention 2 weeks and 2 years post start of intervention.

In a population of 8184 parents screened, 27.1% in the intervention group and 23.9% in the control group were smokers. Engagement in a treatment practice was 44.3% in the group vs 0.1% in the control. In the 2 year follow up of 9794 parents screened, 24.4% and   of the parents were smoking in the intervention and control practices respectively. There was a reduction in smoking prevalence in the intervention practices of 2.7% compared to an increase of 1.1% in the usual care control group. The NNT to treat to reduce one smoker was 27 individuals. For confirmed cessation (saliva tested, at least quit for 1 week), the NNT was 18.

The bottom line

We might take a smoking history routinely, but how often do we reach the next step of advising or assisting parents to quit? This trial shows that simple interventions can help improve uptake of treatment. Every parent who quits is one less child exposed to dangerous chemicals from tobacco smoke. The CEASE resources are freely available for use and adaptation https://www.massgeneral.org/children/cease-tobacco So why not move from contemplation to action and take the time to adopt a meaningful change in your own practice? There’s help on hand and it may be easier than you think to start!

Reviewed by: Grace Leo


If we have missed out on something useful or you think other articles are absolutely worth sharing, please add them in the comments! We are also looking to expand the Bubble Wrap team so please contact us if you’re interested in this! 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. 

An approach to obesity: Matt Sabin at DFTB18

Cite this article as:
Team DFTB. An approach to obesity: Matt Sabin at DFTB18, Don't Forget the Bubbles, 2019. Available at:

Associate Professor Matt Sabin is the Chief Medical Officer of the Royal Children’s Hospital in Melbourne. It was not in this role that we asked him to speak but rather in his clinical role as a paediatric endocrinologist running the largest tertiary hospital obesity service in Australia.

Move over Melatonin: Harriet Hiscock at DFTB18

Cite this article as:
Team DFTB. Move over Melatonin: Harriet Hiscock at DFTB18, Don't Forget the Bubbles, 2019. Available at:

Professor Harriet Hiscock is a consultant paediatrician and post-doctoral research fellow. Amongst other roles she is co-director of the Unsettled Babies Clinic and it is with this role in mind that we asked her to speak at DFTB18.