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Bubble Wrap PLUS – March ’24


Can’t get enough of Bubble Wrap? The Bubble Wrap Plus is a monthly Paediatric Journal Club reading list from Professor Jaan Toelen (University Hospitals Leuven) and Dr Anke Raaijmakers (Sydney Children’s Hospital). 

This comprehensive list is developed from 34 journals, including major and subspecialty paediatric journals. We suggest this list can help you discover relevant or interesting articles for your local journal club or allow you to keep a finger on the pulse of paediatric research.

This month’s list includes many interesting studies, but as always, we have highlighted a few.

In a prospective cohort study in the J Pediatr Gastroenterol Nutr, researchers examined the growth patterns of children who were given rice hydrolyzed formula. Although formulas made from hydrolyzed rice proteins have been developed and marketed over the last two decades, several studies have evaluated them with conflicting results, often with small cohorts or limited follow-up periods.

This study included 66 non-breastfed children (aged 2-24 months) with suspected IgE—or non-IgE-mediated cow’s milk protein allergy. It switched them to rice hydrolyzed formula and followed them up for twelve months. The outcomes were anthropometry, adherence to the formula, and adverse event occurrence.

The growth pattern for the entire cohort remained within the normal WHO growth reference range. The formula was well tolerated, adherence optimal, and no adverse events were reported. However, this study does not address lingering concerns such as arsenic content, effects on bone mineralization, or the acquisition of immune tolerance. One could state that ‘more research is needed’.

Acute appendicitis is a common surgical emergency in children, categorized into simple appendicitis (SA) or perforated appendicitis (PA), with the latter carrying higher mortality. Appendectomy is the standard treatment, but alternatives like antibiotics exist for simple appendicitis. Management of PA includes conservative approaches or drainage before surgery. Diagnosis relies on clinical evaluation, scoring systems, and imaging, though none are perfect. Blood-based biomarkers, including those identified through machine learning, are being explored.

A study in JAMA Pediatrics explored a potential gene expression signature in the peripheral blood of a pediatric patient with appendicitis. The study suggests a dysregulated immune response akin to sepsis in patients with perforation, hinting at some genetic involvement.

While promising, the study has limitations. It focuses solely on inflammation and needs to be validated in larger studies. Practical considerations like cost and time also need to be addressed before clinical application is possible.

The Lancet published two excellent studies on important vaccines for global healthcare (malaria and typhoid fever).

The malaria vaccine was tested in over 4800 children across four African countries. Children aged 5-36 months were randomly assigned to receive either the vaccine or a control. The vaccine was well-tolerated, with mild adverse effects such as injection site pain and fever. Importantly, there were no treatment-related deaths.

Vaccine efficacy remained high, with a 12-month efficacy of 75% at seasonal sites and 68% at standard sites in preventing the first clinical malaria episode. There was also a reduction in malaria cases per 1000 children years. Vaccine-induced antibodies correlated with efficacy. The vaccine’s efficacy decreased slightly over the first year but remained substantial.

This vaccine could significantly contribute to malaria control efforts in sub-Saharan Africa. Its low cost, high efficacy, and WHO prequalification promise widespread availability, potentially alleviating the malaria burden in the region.

Looking at the typhoid fever vaccine, the final analysis of a randomized controlled trial in Malawi evaluated efficacy over more than 4 years of follow-up. Healthy children aged 9 months to 12 years were randomly assigned to receive the typhoid or meningococcal vaccine.

After a median follow-up of 4.3 years, the typhoid vaccine showed durable efficacy, with a 78.3% reduction in blood culture-confirmed typhoid fever compared to the control group. Despite the high number needed to vaccinate (163), this result is important given the rise in multidrug-resistant strains and healthcare challenges in many endemic regions. The findings support WHO recommendations for mass vaccination campaigns targeting children in typhoid-endemic regions and ongoing improvements in water, sanitation, and hygiene (WASH) practices.

You will find the list of interesting papers broken down into four sections:

1.Reviews and opinion articles

Terminology for discussing chronic pain: Using metaphors to educate families on chronic pediatric pain.

Borucki AN, et al. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):169-173. 

Management of well-appearing febrile young infants aged ≤90 days.

Burstein B, et al. Paediatr Child Health. 2024 Feb 6;29(1):50-66. 

Neonatal point-of-care lung ultrasound: what should be known and done out of the NICU?

Alonso-Ojembarrena A, et al. Eur J Pediatr. 2024 Feb 5. 

Diagnostic evaluation of the hypertensive child.

Stabouli S, et al. Pediatr Nephrol. 2024 Feb;39(2):339-343. 

Fluid management in children with volume depletion.

Zieg J, et al. Pediatr Nephrol. 2024 Feb;39(2):423-434.

2.Original clinical studies

Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates.

Johnson MD, et al. Arch Dis Child Fetal Neonatal Ed. 2024 Feb 28:fetalneonatal-2023-326501. 

Prophylactic Oropharyngeal Surfactant for Preterm Newborns at Birth: A Randomized Clinical Trial.

Murphy MC, et al. JAMA Pediatr. 2024 Feb 1;178(2):117-124. 

Lack of Effect for Oropharyngeal Surfactant for Preterm Neonates-Method or Timing?

Rub DM, et al. JAMA Pediatr. 2024 Feb 1;178(2):113-114. 

Immunophenotypes of Newborns From SARS-CoV-2-infected Mothers.

Stracuzzi M, et al. Pediatr Infect Dis J. 2024 Feb 22

Birth weight and head circumference discordance and outcome in preterms: results from the EPIPAGE-2 cohort.

Guellec I, et al. Arch Dis Child. 2024 Feb 26:archdischild-2023-326336. 

Fluids and body composition during anesthesia in children and adolescents: A pilot study.

Betti C, et al. Eur J Pediatr. 2024 Feb 26. 

Childhood Predictors of Nonsuicidal Self-Injury in Adolescence: A Birth Cohort Study.

Wickstrom T, et al. J Am Acad Child Adolesc Psychiatry. 2024 Feb 21:S0890-8567(24)00073-X. 

Use of the “Sepsis Risk Calculator” in Belgian Newborns: A Retrospective Cohort Study.

Langer BI, et al. Pediatr Infect Dis J. 2024 Feb 21. 

Atopic dermatitis in early life and pain at 10 years of age: An exploratory study.

Gorito V, et al. Eur J Pediatr. 2024 Feb 24. 

Gingival bleeding is a useful clinical feature in the diagnosis of hereditary bleeding disorders in children.

Edme E, et al. Eur J Pediatr. 2024 Feb 22. 

Drawing the abdominal pain: A powerful tool to distinguish between organic and functional abdominal pain.

Opp J, et al. J Pediatr Gastroenterol Nutr. 2024 Feb 22. 

Impact of newborn screening for fatty acid oxidation disorders on neurological outcome: A Belgian retrospective and multicentric study.

Everard E, et al. Eur J Paediatr Neurol. 2024 Feb 7;49:60-65. 

Growth pattern of paediatric patients affected by cow milk protein allergy fed with rice hydrolyzed formula.

Nocerino R, et al. J Pediatr Gastroenterol Nutr. 2024 Feb 20. 

Faster discharge with lactated ringers than normal saline in first 72 h of acute pancreatitis: A multicenter randomized trial.

Farrell PR, et al. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):360-368

Gene Expression Profiling in Pediatric Appendicitis.

Dhillon BK, et al. JAMA Pediatr. 2024 Feb 19:e236721

New Genetic Biomarkers to Diagnose Pediatric Appendicitis.

Pacilli M, et al. JAMA Pediatr. 2024 Feb 19

Exposure to Paracetamol in Early Pregnancy and the Risk of Developing Cerebral Palsy: A Case-Control Study Using Serum Samples.

Thacher JD, et al. J Pediatr. 2024 Feb 16:113959. 

Trends in Apgar scores and umbilical artery pH: a population-based cohort study on 10,696,831 live births in Germany, 2008-2022.

Boos V, et al. Eur J Pediatr. 2024 Feb 17. 

Evaluation of Continuous Infusion Vancomycin in a Pediatric Hematology/Oncology Population.

King MA, et al. Pediatr Infect Dis J. 2024 Feb 12

Clinical Picture and Risk Factors for Poor Outcome in Streptococcus pneumoniae Meningitis of Childhood on Three Continents.

Mbakwe PL, et al. Pediatr Infect Dis J. 2024 Feb 7. 

Association between co-sleeping in the first year of life and preschoolers´ sleep patterns.

Garrido F, et al. Eur J Pediatr. 2024 Feb 14. 

Estimated C-reactive protein (CRP) velocity for rapidly distinguishing bacterial from other etiologies in children presenting to emergency department with remarkably elevated CRP levels.

Cohen N, et al. Eur J Pediatr. 2024 Feb 12. 

Valganciclovir in Infants with Hearing Loss and Clinically Inapparent Congenital Cytomegalovirus Infection: A Nonrandomized Controlled Trial.

Chung PK, et al. J Pediatr. 2024 Feb 7:113945. 

Oral Valganciclovir Initiated Beyond 1 Month of Age as Treatment of Sensorineural Hearing Loss Caused by Congenital Cytomegalovirus Infection: A Randomized Clinical Trial.

Kimberlin DW, et al. J Pediatr. 2024 Feb 2;268:113934. 

Safety and efficacy of malaria vaccine candidate R21/Matrix-M in African children: a multicentre, double-blind, randomised, phase 3 trial.

Datoo MS, et al. Lancet. 2024 Feb 10;403(10426):533-544. 

Efficacy of typhoid conjugate vaccine: final analysis of a 4-year, phase 3, randomised controlled trial in Malawian children.

Patel PD, et al. Lancet. 2024 Feb 3;403(10425):459-468. 

3.Guidelines and best evidence

An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow’s Milk Allergy.

Vandenplas Y, et al. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386-413

Admissions to paediatric medical wards with a primary mental health diagnosis: a systematic review of the literature.

Vázquez-Vázquez A, et al. Arch Dis Child. 2024 Feb 19:archdischild-2023-326593. 

Management of Food Allergies and Food-Related Anaphylaxis.

Iglesia EGA, et al. JAMA. 2024 Feb 13;331(6):510-521

International Consensus Criteria for Pediatric Sepsis and Septic Shock.

Schlapbach , et al. JAMA. 2024 Feb 27;331(8):665-674.

4.Case reports

Clubbing and hypoxia in an adolescent male.

Bradford J, et al. Arch Dis Child. 2024 Feb 26:archdischild-2024-326882. 

An exceptional cause of polyuria-polydipsia syndrome in a 10-year-old boy.

Boussetta A, et al. Pediatr Nephrol. 2024 Feb;39(2):451-453. 

The Intersection of Autism Spectrum Disorder, Food Allergy, and Avoidant/Restrictive Food Intake Disorder: A Clinical Case Study.

Proctor KB, et al. J Pediatr. 2024 Feb 16:113965

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


  • Anke Raaijmakers is a paediatric nephrologist, currently working as clinician and researcher in Sydney (Sydney Children’s Hospital, Australia). She did her training in Belgium and Australia and previously worked as general paediatrician and paediatric nephrologist in Antwerp (ZNA Jan Palfijn, Belgium). She is passionate about education, teaching, and research and has completed a PhD on health outcomes of preterm infants. Anke strongly believes in the importance of evidence-based medicine, helping to run journal clubs everywhere she works and the BubbleWrapPlus. In her free time, she loves to play hockey and hike with her husband and three kids.


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