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The 36th Bubble Wrap


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

Article 1: When to ultrasound for appendicitis in pre-school children?

Prada-Araias M, Gomez-Veiras J, Vazquez J, Salgado-Barreira A, Montero-Sanches M, Fernandez-Lorenzo J. Appendicitis or non-specific abdominal pain in pre-school children: When to request abdominal ultrasound?  J Paediatr Child Health. 2019 Sept 4. doi: 10.1111/jpc.14617.

What’s it about?

The study examined the most useful diagnostic tools in differentiating appendicitis from non-specific abdominal pain (NSAP) in pre-school children. A prospective observational study of 82 children under 5 years old with suspected appendicitis (27 NSAP, 55 appendicitis) was performed.  Symptoms, signs and laboratory tests, including anorexia, nausea or vomiting, diarrhoea, tenderness, temperature, white blood cell (WBC), absolute neutrophil count (ANC), C-reactive protein (CRP) were analyzed.  There was no symptom or sign with a high power of discrimination to distinguish between NSAP and appendicitis.  The study found that complicated cases of appendicitis (perforated or gangrenous) were had symptom duration exceeding 12 hours.  Diarrhoea was also associated with complicated appendicitis (28.9%).   Among the laboratory tests, it was found that a CRP of >34 mg/L had the greatest association with appendicitis (odds ratio 9.8). Male gender had an odds ratio of 4.7, whereas the presence of anorexia had an odds ratio of 4.7.  Temperature, WBC, and ANC had moderate diagnosis accuracy. The study found that the diagnostic accuracy of abdominal ultrasounds improved when symptoms exceeded 12-hour duration.

Why does it matter?

Up to 50% of pre-school children with appendicitis are misdiagnosed,1 leading to perforation or unnecessary appendectomy.  The Paediatric Appendicitis Score is a tool that helps stratify patients into risk groups, but it has not been validated in pre-school children.  Although abdominal ultrasounds had a high sensitivity (74-100%) and specificity (88-99%),2 there are no clear indications for when to ultrasound a pre-school child with abdominal tenderness.

Clinically Relevant Bottom Line:

This single-centre study, with 82 patients, recommends that in pre-school children with right lower quadrant tenderness, an ultrasound is indicated if the child has abdominal pain lasting longer than 12 hours, or CRP value >34 mg/L.


  1. Sakellaris G, Tilemis S, Charissis G. Acute appendicitis in preschool-age children. Eur. J. Pediatr. 2005; 164:80-3
  2. Ross M, Lui H, Netherton S et al. Outcomes of children with suspected appendicitis and incompletely visualized appendix on ultrasound. Acad. Emerg. Med. 2014; 21:538-42

Reviewed by: Lorraine Cheung


Article 2: Magic Eight Balls – Automated Algorithms in Acute Paediatrics

Dewan M & Sanchez-Pinto LN. Crystal Balls and Magic Eight Balls: The Art of Developing and Implementing Automated Algorithms in Acute Care Pediatrics.Pediatr Crit Care Med. 2019 Dec;20(12):1197-1199. doi: 10.1097/PCC.0000000000002147.

What’s it about?

Crystal Balls?? Magic Eight Balls? Don’t let the mixed metaphor in the title fool you, this brief article provides a scything insight into the current state (and barriers to) the use of automated algorithms in acute paediatrics. Automated algorithms are one of the many facets of Artificial Intelligence that are beginning to augment the way we care for kids. Such examples include the alerts you receive when a patient meets an ‘Early Warning Score’ threshold, or when you miscalculate a dose.

Clinically Relevant Bottom Line:

Drs Dewan and Sanchez-Pinto surmise that there are three main areas to tackle this challenge. Firstly, to improve the accuracy of algorithms to an acceptable level, utilizing better data and specific definitions. Secondly, effective clinical decision support, that is fast, reliable, usable. Thirdly, a plan to monitor and improve the system. The paper also introduced me to the concept of NNA (Number Needed to Alert) and flagging the importance of understanding this as we become increasingly reliant on EWS (and other algorithms) of all kinds.

Reviewed by: Henry Goldstein


Article 3: Does supplementation with Cow’s Milk Formula affect risks of sensitization to food allergies?

Urashima M, Mezawa, H, Okuyama M, Urashima T, Hirano, D, Gocho, N, Tachimoto, H. Primary Prevention of Cow’s Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow’s Milk Formula at Birth: A Randomized Clinical Trial. JAMA Pediatrics 2019;173:1137-1145. 

Why does it matter?

IgE-mediated food allergy is increasing in prevalence and severity worldwide. Cow’s milk formula is commonly used to supplement breastfeeding at birth but its association with the risk of developing cow’s milk allergy is still controversial. Furthermore, vitamin D deficiency has been associated with food allergy, but the results have not been conclusive.

In terms of recent research in this area, it appears that there are mixed results on whether early exposure to cows milk formula early in life reduces or increases your subsequent risk of having a cows milk food allergy.  A cohort study from Israel in 2010 by Katz et al. showed that the frequency of IgE-mediated cow’s milk allergy was lower in infants who began receiving cow’s milk formula within the first 14 days of life (with or without breastfeeding). Similarly, an observational study (HealthNuts) in Victoria, Australia involving >5000 infants, showed that the introduction of cow’s milk protein before 3 months of age was associated with significantly reduced risk for cow’s milk sensitization and allergy at 12 months of age. In contrast, a recent retrospective study by Kelly et al.  in Ireland demonstrated that breastfed infants are at significantly increased risk of cow’s milk allergy by receiving supplemental formula in the first 24 hours of life.

What’s it about?

The Atopy Induced by Breastfeeding or Cow’s Milk Formula (ABC) trial was a single centre, randomized, nonblinded clinical trial.  330 newborns at risk for atopy were recruited; of these, 312 were included in the analysis. Immediately after birth, newborns were randomized (1:1 ratio) to breastfeeding (BF) with or without amino acid-based elemental formula (EF) for at least the first 3 days of life (BF/EF group) or BF supplemented with cow’s milk formula (CMF, at least 5 mL/d) from the first day of life to 5 months of age (BF plus CMF group). The infants were followed up until their second birthday.

Sensitization to cow’s milk (as defined as IgE level ≥0.35 allergen units [UA]/mL) occurred in 24 infants (16.8%) in the BF/EF group, which was significantly fewer than the 46 infants (32.2%) in the BF plus CMF group (relative risk, 0.52; 95%CI, 0.34-0.81). The prevalence of food allergy at the second birthday was significantly lower in the BF/EF than in the BF plus CMF groups for immediate (4 [2.6%] vs 20 [13.2%]) and anaphylactic (1 [0.7%] vs 13 [8.6%]) types.

Clinically Relevant Bottom Line:

This study had an unfortunate overlap between the randomized group and the control group which make the findings difficult to interpret – for example, after 3 days of life, most infants in the BF/EF group were switched from  BF/EF to BF plus CMF, whereas all infants in the BF plus CMF group remained in the same group, which may cause differential misclassification. However, it was still a promising study attempting to show that sensitization to cow’s milk and other food allergies may be primarily preventable by avoiding CMF at birth. Further studies are required to validate and build on these findings.

Reviewed by: Jennifer Moon


Article 4: Children with cerebral palsy who present to ED with feeding tube complications

Wong A-L, Meehan E, Babl F E, et al. Paediatric emergency department presentations due to feeding tube complications in children with cerebral palsy. J PaediatrChild Health. 2019; 55: 1230-1236

What’s it about?

Triage comment: “feeding tube dislodged”. It’s such a common paediatric ED presentation. This paper reports that approximately 10% of children with cerebral palsy have a gastrostomy or gastrojejunal tube for feeding, and the prevalence increases to 1 in 3 children with severe gross motor impairment. Complications with feeding tubes are a common reason for children with CP to present to the ED. The researchers aimed to describe the characteristics of ED presentations due to feeding tube complications in children with CP. They also aimed to determine the complexity of the complications, and how they were managed. They performed a retrospective review of the medical records of children with CP who presented with feeding tube-related complaints to two tertiary paediatric EDs in Victoria over a 5-year period.

Why does it matter?

Feeding tube-related complaints, including dislodgement, are common presentations to both tertiary and non-tertiary EDs. This study clarifies issues relating to feeding tube complaints and hence may help to empower non-tertiary EDs and even parents to manage these complications, which will decrease presentations to tertiary EDs. The researchers report that the biggest risk of gastrointestinal tract closure occurs in the first 8 weeks after a gastrostomy tube is placed; the initial tube is replaced by a low-profile gastrostomy tube (primarily a balloon retention device) after about 6 months, and then is usually replaced every 6-12 months.

Clinically-relevant bottom line?

The majority of children with CP who attended tertiary EDs with feeding tube-related complaints had severe gross motor impairment (GMFCS IV or V). 46% were triaged as low urgency (category 4 or 5), and 68% occurred during daylight hours. Most complaints were due to gastrostomy tube complications, and most of these complications were in low-profile gastrostomy tubes. Dislodgement was the most common presenting complaint. In almost 90% of these children, the tube was replaced in ED, with the majority replaced by an ED physician. Most of these children did not require hospital admission. More than half had traveled to the tertiary centre from an outer metropolitan or regional/rural area.

The researchers suggest that children with CP who have dislodged gastrostomy tubes could be managed in non-tertiary EDs or other community health clinics. They recommend further research to assess the competency of ED physicians in these areas, as well as education and training for parents and community healthcare providers.

Reviewed by: Katie Nash


Article 5: Medical conditions revealed in fairytales and folklore

Massie J. Medical conditions revealed in fairy tales, folklore and literature. J Paediatr Child Health. 2019 Nov;55(11):1295-1298. doi: 10.1111/jpc.14615. Epub 2019 Sep 4.

Once upon a time, in a faraway kingdom, there were writers who transport readers to a timeless realm where fairy godmothers, evil witches, beautiful princesses, and handsome princes have magical adventures.

What’s it about?

This paper illustrates the myriad of medical conditions found in fairy tales, folklore, and literature. They suggest that Sleeping Beauty’s slumber may have been caused by the protozoa Trypanosoma brucei. Snow White, a princess who has “skin white as snow, lips red as blood and hair black as ebony,” is suggested to have suffered from albinism. Pinnochio, (the living wooden puppet whose nose grew when he told a lie), may have been a reference to treeman syndrome, a rare disorder characterized by skin lesions that resemble bark. Interestingly, these tales also exert influences and lend the name to modern medical conditions. For example, the Peter Pan Syndrome, an inability to grow up or the Alice in Wonderland Syndrome, a neurological disorder in which a person experiences distorted perception of space, time, distance and dimension.

Why does it matter?

Through the lens of science, these fairy tales and folklores not only entertain and teaches us life lessons, but also uncover the relationship between literature and medicine, and in doing so, reveal essential truths about human nature.

Clinically Relevant Bottom Line:

For centuries, writers weaved stories of magic and monsters, capturing the imaginations of children and stimulating their emotional, physical and mental development. With a bit of magic, we may be able to uncover the various medical conditions and treasures buried within these stories…and may the fairy godmothers, evil witches, beautiful princesses, and handsome princes live happily ever after.

Reviewed by: Jessica Win See Wong



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

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


  • Grace is a Registrar at Sydney Children's Hospital. She loves innovative medical education and paediatrics. She is on the organising committee for the DFTB18 and SMACC conference. Grace is a former internal director of the AMSJ. She enjoys board games, cooking and graphic design.


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