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The 44th 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: Neurodevelopmental outcomes at the edge of viability.

Watkins PL, Dagle JM, Bell EF, Colaizy TT. Outcomes at 18 to 22 months of corrected age for infants born at 22 to 25 weeks of gestation in a center practicing active management. The Journal of Pediatrics. 2020 Feb; 217:52-8.

What’s it about? 

This is a retrospective study assessing the survival and neurodevelopmental outcomes of infants born at 22-23 weeks compared with those born at 24-25 weeks of gestation in a single site which provides antenatal steroids and active resuscitation when desired by parents.  The study focused on 255 infants born at 22-25 weeks of gestation between 2006 and 2015, of which 7 infants were excluded because of a congenital anomaly, death in delivery room, or parental request for palliation. The cohort was stratified into 22-23 weeks gestation (n=70) and those born at 24-25 weeks gestation (n = 178).

Both groups received antenatal steroids, intubation, surfactant replacement therapy, and high-frequency ventilation as the primary mode of ventilation. The survival and neurological outcomes were assessed at 18-22 months of corrected age in both groups. Survival to hospital discharge of those surviving to NICU admission was 78% at 22-23 weeks and 89% at 24-25 weeks or gestational age (P=0.02).

More than 10,000 primary tracheal intubations were performed, with about 1 in 3 utilising ketamine as an induction agent. Ketamine was used in 41.4% of children for whom haemodynamic instability was the primary indication for intubation, as opposed to only 35% of cases where a procedure was the indication and 17.1% of neurological indications. The majority of children receiving ketamine were intubated for respiratory indications, reflective of respiratory compromise being the predominant cause for intubation in the paediatric population.

Bayley Scales of Infant-Toddler Development (BSID-III) and neurologic examination was performed for 169 of the 214 survivors at 18-22 months of corrected age. In the surviving infants, no or mild neurodevelopmental impairment in surviving infants was approximately 2 of 3 infants at 22-23 weeks and 3 of 4 infants at 24-25 weeks; this difference was not statistically significant.

Why does it matter? 

Clinicians consider many factors when deciding to initiate active treatment in infants born at 22-25 weeks. Generally, active intervention for infants born before 22 weeks of gestation is not recommended. However, the approach for infants born at 22-25 weeks of gestation varies due to concerns for treatment effectiveness or poor outcomes.

Clinically Relevant Bottom Line:

The survival and neurodevelopmental outcomes for a cohort of extremely preterm infants born are favourable due to active resuscitation management by both obstetricians and neonatologists and high rates of antenatal steroid administration.

Reviewed by: Jessica Win See Wong

Article 2: Bacterial Meningitis – amenable to a clinical prediction tool?

Mintegi S, Garcia S, Martin MJ, et al. Clinical Prediction Rule for Distinguishing Bacterial from Aseptic Meningitis. Pediatrics. 2020;146(3):e20201126

What’s it about? 

Santiago Mintegi is the Basque master of clinical prediction rules; bringing us Step by Step approach to febrile infants, back in 2014. This study aimed to develop and validate a ‘meningitis score for emergencies’ (MSE) to distinguish bacterial versus aseptic meningitis in pediatric patients presenting to the Emergency Department with CSF pleocytosis. Secondary objective was to compare the performance of the MSE to the BMS (bacterial meningitis score), another clinical prediction tool, in guiding the initial clinical decision making of children with CSF pleocytosis. Inclusion criteria included the presence of CSF pleocytosis AND blood and CSF bacterial cultures, WBC count, serum CRP, procalcitonin.

This study recruited 1009 patients aged 29 days to 14 years old with meningitis (917 cases of aseptic meningitis and 92 cases of bacterial meningitis) admitted to 25 different Spanish Emergency Departments. A retrospective cohort including 819 patients admitted between 2011 and 2016 was used as the derivation set to develop the MSE criteria. A prospective cohort including 190 patients admitted between 2017 and 2018 was used as the validation set to assess the validity of the MSE. After critically analyzing data of the derivation set, four variables for the MSE were selected and each assigned points depending on their magnitude of effect: procalcitonin >1.2ng/mL (3 points), CSF protein >80mg/dL (2 points), CSF absolute neutrophil count >1000 cells per mm3 (1 point), and CRP >40mg/L (1 point).

The utility of the MSE was tested on the validation set. An MSE score ≥1 predicted bacterial meningitis with a sensitivity of 100%, specificity 83.2, and negative predictive value of 100%. There were no patients diagnosed with bacterial meningitis in the derivation or validation sets had an MSE <2. Comparing the MSE versus the BMS, the BMS clinical tool missed 2 patients with a BMS score 0 that ended up with a diagnosis of bacterial meningitis. Overall, the MSE clinical prediction tool identified pediatric patients aged 29 days to 14 years old with CSF pleocytosis as having either having bacterial or aseptic meningitis, without misclassifying any patients.

Why does it matter? 

Paediatric bacterial meningitis is a potentially life-threatening illness that warrants urgent intervention given its high mortality and morbidity rate. Most cases of pediatric meningitis are aseptic, with viruses remaining the most common cause, and thus only require supportive cares. Conversely, bacterial meningitis can lead to dire consequences if not promptly acted on with IV antibiotics.  No single variable thus far has been identified to fully distinguish bacterial versus aseptic meningitis.

Often children with CSF pleocytosis are admitted to hospital to receive antibiotics while bacterial culture results are pending. The utility of the MSE is that children with a negative MSE score can avoid unnecessary interventions such as IV antibiotics and hospital admission, as well as being financially beneficial for hospitals and reducing the antibiotic burden on antimicrobial resistance.

Clinically Relevant Bottom Line:

This study suggests utilization of the MSE clinical decision tool can accurately distinguish bacterial or aseptic meningitis in pediatric patients with CSF pleocytosis. Addition of CRP and procalcitonin as clinical predictors in the MSE greatly improves its performance compared to existing decision tools. The authors recommends physicians should admit and give antibiotics to all febrile children with CSF pleocytosis and any MSE score ≥1. Interestingly, this is the second clinical prediction tool for bacterial infection from this group with a strong emphasis on procalcitonin.

Reviewed by: Emma Chan

Article 3: Use of probiotics in the treatment of functional abdominal pain in children

Trivić, I., Niseteo, T., Jadrešin, O., & Hojsak, I. (2020). Use of probiotics in the treatment of functional abdominal pain in children – systematic review and meta-analysis. Eur J Pediatr

What’s it all about?

This systematic review and meta-analysis evaluating strain-specific probiotic interventions for paediatric functional abdominal pain (FAP) includes nine randomised controlled trials published up to April 2020. The authors evaluated the outcomes of the number of children with the cessation of pain symptoms following intervention, intensity of pain after intervention, patient-reported frequency of pain, number of days missed from school, and number of pain-free days. 

Two probiotic strains were investigated in the RCTs, including Lactobacillus rhamnosus GG and Lactobacillus reuteri DSM 17938. L. reuteri was associated with a significant reduction in pain intensity and number of pain-free days. There was no significant reduction in pain frequency or school absenteeism. Further, no studies reported the authors’ primary outcome which was the number of children with the cessation of pain symptoms after intervention.

Why does it matter?

Chronic abdominal pain is a common functional gastrointestinal disorder in childhood and can disrupt the quality of life, school attendance, and family activities of children experiencing it. In over 90% of cases, an organic cause for the pain cannot be identified and are therefore considered functional.

While the pathophysiology underlying functional pain remains unclear, the current school of thought involves the gut-brain axis that has been altered by psychosocial factors such as stress, as well as physiological factors such as gut dysbiosis and sensitised gut motility. Probiotics have been studied to target the gut-brain axis, and are considered safe and therapeutic for children with FAP. Previous reviews have limited data on the particular strains that may confer benefit in children with FAP and are limited in the range of different outcomes assessed.

Clinically Relevant Bottom Line:

This systematic review and meta-analysis hoped to inform clinicians of beneficial probiotic strains for children with FAP based on clinically relevant outcomes. Trivić et al. suggest that L. reuteri can effectively reduce pain intensity and increase the number of pain-free days in children with FAP. However, the doses and formulations of probiotic strains used in individual studies were heterogeneous. Moreover, inadequate sample sizes and wide confidence intervals, as well as a diverse range of outcomes and study duration were reported, making it difficult to interpret and therefore draw accurate conclusions. Longer study interventions and follow-up are also still in need. For more reading, here is Szajewska’s 2016 review of the evidence for probiotics in other indications.

Reviewed by: Ivy Wei Jiang

Article 4: Ten years on – have your experiences changed your opinion?

Truog, R.D (2010) Is it always wrong to perform futile CPR?  New England Journal of Medicine, Vol 362 (6), pp 477-479

What’s it about?

The ethical, moral and clinical questions surrounding paediatric resuscitation continue to challenge us. The author reflects on the case of a 2-year-old boy with a large frontal encephalocele who had significant neurological impairment, and although extensive discussions had been made regarding palliation, his parents wanted full resuscitation measures.

The time came when the boy required resuscitation. On arrival to ICU, it was evident from a clinical point of view that CPR would not be successful. As there was no NFR in place, the consultant directed the team to attempt futile CPR for 15 minutes before ceasing and pronouncing time of death. The psychological impact on the people involved varied – the parents were grateful the team “had really tried” and “didn’t just give up and let him die” whilst one of the nursing staff told the consultant the resuscitation “had been so upsetting, she had to fight the urge to vomit”.

Why does it matter?

In the heat of the moment, it can be difficult to make a well-reasoned and ethical argument as to the appropriateness of resuscitation in the patient in front of us. This article highlights how essential it is for the treating team to have a strong relationship with the patient and their parents/carers, and for the goals of life and death to be discussed regularly, so when the time comes, the team’s knowledge of the patient and family can help guide a medical and carer decision regarding CPR.

There is no way to truly know whether a patient is “beyond physiological suffering” at the various terminal stages of life. Our Hippocratic Oath states to do no harm, and our duty of care is primarily to the patient. In paediatrics, this duty of care often extends to the carers, and as such we have to consider how our actions may harm them as well.  We will inevitably be involved in cases where the treating team’s opinion about resuscitation status differs markedly from that of the family. When making decisions about commencing resuscitation, our focus should always be on what is best for the patient; the family’s wishes should come second.

The bottom line

Each patient’s needs, and those of their parents/carers, are uniquely different – not only from a medical, personal and psychological perspective, but also from a cultural, spiritual and religious aspect. Some carers want a peaceful and comfortable death for their loved ones, while others want to believe they fought until the very end. The treating team’s goal is to minimize pain and suffering while doing no harm. Given the complexities each case may present, creating guidelines for managing futile CPR may not really be helpful.

Our focus should be on education about end of life planning and resuscitation discussions, and ensuring our clinical staff have appropriate debriefing and psychological support after unsuccessful resuscitation attempts.

Reviewed by: Tina Abi Abdallah

Article 5: Australia’s Children in 2020

Australian Institute of Health and Welfare 2020. Australia’s children. Cat. no. CWS 69. Canberra: AIHW.

What’s it about?

This 389-page report is the Australian Institute of Health and Welfare’s (AIHW) cross-sectional analysis of the population level of health for Australia’s children. Better, it places much of the numbers, figures and information in a time-based context, observing changes and trends since data began being reasonably and reliably recorded.

Why does it matter?

Big data gets a bad rap most days of the week. It’s hard to collect accurately, and the uses of big data can be perceived as imprecise and occasionally nefarious. The AIHW is seeking to measure, understand, analyse and share an understanding of the current status of children’s health in Australia. These data identify where we can focus our domestic efforts, as well as providing the opportunity to appropriate international benchmarking.

And, if you’re a budding researcher in population health, the report clearly outlines the gaps in existing data reporting. Strikingly, these data gaps include FASD, the impact of device and social media on health, and medical technology and devices used by children with health conditions.

Clinically Relevant Bottom Line:

If you want to gain an insight into the best population numbers for the health of Australian kids, dive into the executive summary. If you’re reading from beyond Australian shores, this report provides an additional example of how to share well-worked, well presented and, in the main, well-demonstrated data. Full disclosure; I haven’t yet read every page of this report.

Reviewed by: Henry Goldstein

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.


  • The house-elves are still hard at work, copying, pasting, and occasionally weaving a little magic!


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