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The 27th 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 UK and Ireland) to point out something that has caught their eye.

Article 1: Assessing pain in children with cognitive difficulties

Cascella M et al. The challenge of pain assessment in children with cognitive disabilities: Features and clinical applicability of different observational tools. Journal of Paediatrics and Child Health 55 (2019) 129–135.

What’s it about?

This paper reviews several pain assessment tools for their usefulness in evaluating pain in children with cognitive difficulties, including intellectual disabilities, developmental delay, developmental disability, learning disabilities, and cognitive impairment secondary to acquired brain injuries or neurodegenerative diseases.

The reviewers evaluated self-report tools, including a faces scale, stating that reliability depends on the degree of intellectual disability. They also reviewed several observational tools that assess physiological changes and pain behaviours, including the Face, Legs, Activity, Cry and Consolability (FLACC) scale, the revised FLACC scale (more flexible; allows caregivers to describe behaviours specific to their child), and the Paediatric Pain Profile (PPP), among others. For each tool, the reviewers identified advantages, disadvantages, and available validation studies.

According to the reviewers, “A very effective strategy, adopted by several observational tools, requires parents to assess their child’s pain. Parents are more familiar with their child’s normal behaviour than clinicians, who often have no previous experience with the child.”

The reviewers also outlined features of the ideal tool for assessing pain in children with cognitive difficulties, which they believe does not yet exist.

Why does it matter?

Children with cognitive disabilities are at greater risk of experiencing pain than children without cognitive disabilities. Assessment and management of pain in this patient population are challenging due to communication difficulties, which can lead to inadequate management of pain.

Clinically-relevant bottom line?

The reviewers conclude that children with mild cognitive impairment should be given the opportunity to use a self-report pain scale if the medical professional feels they can understand and use the scale. Otherwise, observational pain assessment tools should be used to identify pain in cognitively impaired children. The ideal tool does not exist, so selecting the appropriate tool will depend on the patient, and several tools may be used in combination. The reviewers recommend that healthcare providers and families be trained in the use of these tools.

Reviewed by: Katie Nash

Article 2: What should we feed our infants to reduce the risk of allergies?

Joshi PA, Smith J, Vale S, Campbell DE. The Australasian Society of Clinical Immunology and Allergy infant feeding for allergy prevention guidelines. Medical Journal of Australia doi:10.5694/mja2.12102 Published online 14/01/2019

What’s it about?

The Australasian Society of Clinical Immunology and Allergy (ASCIA) have developed primary prevention guidelines aimed at reducing eczema and food allergy. Parents are often bombarded with conflicting advice about what they should feed their offspring and when, a situation not helped by the medical profession changing its mind in less than a generation. When I was a kid (and even a young adult) the standard line was that certain allergenic foods should be avoided in early childhood. The observation that Israeli children (who are typically fed peanuts from 6-7 months) have a rate of peanut allergy one-tenth the rate of their British counterparts led to an RCT which found the early introduction of peanuts was helpful, especially in kids with severe eczema and/or egg allergy. ASCIA has looked at all the evidence and put it into some helpful guidelines which can reasonably be considered the gold standard for providing advice to parents on food choices to reduce the risk of allergic disease.

Why does it matter?

Allergic disease places a burden on Australian children with 15-20% affected by eczema and up to 10% of infants under 1 year of age having a challenge-proven food allergy. Egg has the dubious honour of topping the allergen leaderboard with 8.9% of infants affected and up to 30% of these continuing to suffer into adulthood. Emergency department presentations and fatalities due to anaphylaxis are both increasing with peanut and cow’s milk protein as the leading triggers for anaphylactic death in Australia and the UK respectively.

Clinically Relevant Bottom Line

Mothers don’t need to exclude anything from their diet in pregnancy or during breastfeeding (remember these guidelines are about reducing the risk of allergy so anything they might exclude for other reasons is not covered). Probiotics and up to 3 serves a week of oily fish may help but there is conflicting evidence. Cow’s milk-based formula can be used if breastfeeding is not possible and there is no evidence soy or goat’s milk formula have any advantage in preventing allergic disease. Partially or extensively hydrolysed formulas are not recommended for primary prevention of allergic disease, this is at odds with previous Cochrane reviews (one outdated, one withdrawn) and persisting national guidelines in some countries including the US. Introduction of solid food is recommended around 6 months but not before 4 months, ideally while still breastfeeding. Peanuts and eggs should be introduced before 12 months of age and guidance is provided on how to do this. Recommendations are not made for other allergens due to lack of specific evidence though there is no suggestion to withhold these.

Reviewed by: Ben Lawton

Article 3: Caffeine and the Baby Brain

Lodha A, Entz R. et al. (2019) Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants, Paediatrics Vol 143, Issue 1

Why does it matter?

Caffeine is a well-studied pharmacological option for helping manage apnoeas of prematurity. The safety of caffeine has not been as well studied, and the Canadian Neonatal Network has attempted to determine any associations between caffeine exposure and neurodevelopmental outcomes in premature neonates.

What’s it about?

The study is a retrospective analysis of neonates born < 29 weeks, divided into two groups: early caffeine administration (within 48 hours of birth) or late (48 hours after birth). Of the 2108 neonates who were eligible (exclusion criteria: congenital anomalies, deceased between day 0 – 3 of life, extremely unstable), 1545 were in the early-caffeine group and 563 were in the late-caffeine group.

The Canadian Neonatal Follow-up Network used their routine follows up of ex-prems at 18 and 24 months, with development assessment made using the Bayley III scales. The primary outcome was significant neurodevelopmental impairment such as cerebral palsy, and hearing or visual impairment.

Based on the data, they found that severe neurologic injury and significant neurodevelopmental impairment were lower in the early-caffeine group, compared to the late-caffeine group across all measured fields. However, the odds ratio was only significant in the significant neurodevelopmental impairment group and after post hoc analysis with propensity score matching to account for variables such as gestational age, sex and steroid use; the result was not statistically significant.

Clinically Relevant Bottom Line

Caffeine is delicious and has neuroprotective and anti-inflammatory properties which is the proposed mechanism for improved neurodevelopmental outcomes in premature babies. Whilst the study appears to favour the early introduction of caffeine in the < 29-week population, post hoc analysis was not statistically significant so it is difficult to draw confident conclusions. This study is a stepping stone for future studies with more study groups i.e. gestational age, comorbidities, and delivery method. It would also be worth looking into whether it is the timing of the first dose of caffeine and/or the duration of caffeine administration that reduces neurological impairment.

Reviewed by: Tina Abi Abdallah

Article 4: How successful are we in preventing GBS disease in neonates?

Nanduri et al. Epidemiology of Invasive Early-Onset and Late-Onset Group B Streptococcal Disease in the United States, 2006 to 2015: Multistate Laboratory and Population-Based Surveillance. JAMA Pediatr. 2019 Jan 14.

What’s it all about?

Due to a rise in the use of intrapartum antibiotics (IAP), the rates of early-onset Group B Streptococcal Disease (GBS) have decreased significantly, but GBS disease in newborns is still one of the major causes of infant morbidity and mortality. This study reports the findings of a population and laboratory-based surveillance study across 10 states in the USA. Infants younger than 90 days of age were included who had a positive (invasive) GBS culture. They were classified as early onset GBS ( within one week after birth) and late-onset GBS disease (7-89 days of age).

The investigators found 1277 cases of early GBS and 1387 cases of late GBS. During the study period, early-onset GBS incidence declined significantly (0.37 to 0.23 per 1000 live births), however, late-onset GBS rates remained the same. Interestingly, among 1277 early onset GBS infants, half of their mothers (48%) had no indication for IAP and did not receive antibiotics, but even more surprisingly, over one in five mothers (22%) with indications for IAP did not receive antibiotics. The authors also commented on serotypes, with serotype III being most common (56%) in late onset GBS with an increased incidence over time. Of note, no β-lactam resistance was identified during the study period (but 21% showed clindamycin resistance).

Why does it matter?

GBS is still one of the most common causes of infant morbidity and mortality. Whereas IAP is very effective in preventing early-onset GBS, there is room for improvement based on this study. However, as stressed by the authors, there is currently no effective preventative measure for late-onset GBS. The authors have suggested that a vaccine with the six most prevalent serotypes (Ia, Ib, II, III, IV, and V) could potentially prevent 99% of invasive GBS infections.

Clinical Relevant Bottom Line

Intrapartum antibiotics help prevent early-onset GBS disease but do not appear to prevent late-onset GBS disease. In the future, it is worth exploring additional strategies such as a GBS vaccine to help prevent late-onset GBS disease.

Reviewed by: Anke Raaijmakers


Article 5: Human Factors in Prescribing Errors

Sutherland A, Ashcroft DM, Phipps DL. Exploring the human factors of prescribing errors in paediatric intensive care units. Arch Dis Child: Epub ahead of print: 8th Feb 2019. doi:10.1136/ archdischild-2018-315981

Why does it matter?

Children are twice as likely as adults to suffer harm as a result of medication errors and it is estimated that 11-18% of prescriptions in PICU have prescribing errors. This study investigated human factors which contribute to prescribing errors in order that they may be targeted to improve outcomes.

What’s it about?

The authors performed eleven semistructured interviews with junior and senior medical staff and nurse practitioners involved in prescribing in the PICU. The interviewees all worked in an environment using handwritten medication charts. They used three case vignettes around prescribing errors to analyse the subtasks of prescribing in PICU as well as to assess for different human factors that were contributing to the outcomes.

The three cases were based on actual errors from the patient safety incident database at one site and were chosen to represent active failures from Reason’s hotel of human errors; that is skill-based errors, rules-based mistakes and knowledge-based problems.

Across the interviews, the team identified 5 different key factors contributing to medication prescription errors.

Individual Factors – Inexperience or lack of skills/knowledge
Organisational Factors – Different protocols between consultants and departments
Task-related Factors – Reliance on memory, difficulty locating guidelines or guidelines not covering non-routine situations
Team Related Factors – Verbal communication, lack of handover
Work-Related Factors – Interruption, prioritisation

They also found that of the human factors, cognitive burden, both physical and psychological was the main contributory factor to prescribing error. Whilst physical burdens such as interruption or distraction often led to errors of omission or selection; psychological issues such as inexperience, lack of support information or workload factors tended to lead to errors related to lack of awareness. Nursing staff were also identified as an important part of social control to help mitigate prescription errors but more layers of control such as formalising communication about medications, using computerised standardised order sets and organisational standardising may help mitigate further errors being made.

The bottom line

Medication errors are a serious issue and whilst multiple factors contribute, cognitive burden is one of the primary issues that need to be addressed. Medication prescribing should be considered a high-priority and high-risk task. Interventions which may help reduce error include reducing fatigue, improving skill mix, handover of information and standardisation of procedures.

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! 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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