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The 32nd Bubble Wrap



Article 1:  Should you worry if a child develops a fever after their vaccine?

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 among the most serious bacterial infections (SBI). In Australia, the government-subsidised vaccine schedule includes Meningococcal ACWY; however, the Meningococcal B vaccine (Bexsero) can be purchased ($250-$500) for children six 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 the 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 one 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 workup results, they may be discharged home with reassurance. The key is always to be weary of the unwell-looking infant and those whose fevers persist, as a full septic workup and IV antibiotics should be considered.

Reviewed by: Tina Abi Abdallah

Article 2:  Does iron-fortified formula 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 an iron-fortified formula vs a 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 six months and were followed up at 16 years of age. 

Of the 405 participants, those who were randomised to the iron-fortified formula (n=216) had lower scores than those randomised to the low-iron formula (n=189) in 8 of the nine 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 six months of age who received an iron-fortified formula outperformed those with a low-iron formula.  The opposite was also true, with those with high haemoglobin at six 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 ageing 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 an LMIC, where there is a limited number of health providers compared to the patient load.

The curriculum is divided into three 2-hour sessions, which consist of

  • (1) introduction to procedural sedation,
  • (2) resuscitation and management of adverse effects, 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 developed 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, car seats) 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 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 two weeks and two 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 two-year follow-up of 9794 parents screened, 24.4% 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 one 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 the 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. 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. 


  • 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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