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The 31st Bubble Wrap


Article 1: An egg a day keeps the doctor away? (Ecuador)

Ianotti LL, et al. Eggs in Early Complementary Feeding and Child Growth: A Randomized Controlled Trial. Pediatrics; 2017 July [epub] doi: 10.1542/peds.2016-3459

What’s it about?

Childhood stunting is contributed to by both biological factors and environmental factors such as poverty. The World Health Assembly has set a global target to reduce childhood stunting by 40% by 2025. Previous interventions to improve growth have included fortification of food and dietary supplementation. Utilising locally available nutritious food is an important step improving outcomes. Eggs have high nutritional value and contain high concentrations of choline, a nutrient previously found to promote growth in animal models.  There has been no previous study investigating the use of eggs as a complementary nutrition source for infants.

Why does it matter?

The study was completed in Cotopaxi Providence, a rural, indigenous population in Ecuador. This population is estimated to have a baseline prevalence of stunting of 38%. Children aged 6 to 9 months were randomised to treatment (1 egg per day for 6 months [n=83], and control (no intervention [n=80]). Children were excluded if they had a medical condition, severe malnutrition or egg allergy. Eggs were delivered on a weekly basis and a log report egg consumption, morbidities, and anthropometric measures were taken after 6 months. Egg intervention increased length-for-age z score by 0.63 (93% CI, 0.38-0.88, p<0.001), and weight-for-age z score by 0.61 (95% CI 0.45-0.77, p<0.001).  There was a reduced prevalence of stunting by 47% (prevalence ratio, 0.53; 95% CI, 0.37-0.77).  Children in the treatment group also had reduced intake of sugar-sweetened foods compared with control (PR, 0.71; 95% CI, 0.51-0.97 p=0.032). 

Clinically Relevant Bottom Line:

This study found that supplementing the diet 6 to 9-month-olds with an egg a day significantly improves linear growth and reduces stunting within a population from a developing country with a high prevalence of stunting (38%). There were no reports of allergic reactions. Care must be taken in applying this study to different contexts and cultural backgrounds.

Reviewed by: Lorraine Cheung

Article 2: Maternal influenza immunisation to improve infant outcome (Nepal)

Steinhoff MC, et al. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial. Lancet Infect Dis. 2017 Sep;17(9):981-989

Why does it matter?

Influenza can cause serious illness in children, especially infants younger than 6 months of age. Immunisations are strongly recommended to pregnant woman and any child over 6 months of age. Maternal immunisation during pregnancy induces high levels of maternal antibodies that can be transferred to the foetus and prevents influenza virus infection both in pregnant women and their infants during their first few months of life.

What’s it about?

This randomised controlled trial assessed the safety and efficacy of maternal influenza immunisations in mothers and infants in Nepal, where Influenza viruses circulate perennially.  They recruited 3693 women in 17 to 34 weeks of gestation between 2011 to 2013. Maternal influenza immunisations were offered throughout the year, with 3629 infants included in the immunisation efficacy analysis.

The study found that influenza immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1-34).  Among infants followed from birth to six months of age, immunisation had an overall efficacy of 30% (95% CI 5-48. There was also a 42g increase in birth weight (95% CI: 8-76) among infants born to immunised mothers (with an overall decrease in low birth weight infants by 15%). There were no differences noted in the rates of small for gestational age infants or preterm birth. Both groups had a similar number of adverse events.

Clinically Relevant Bottom Line:

Maternal influenza immunisation reduced maternal influenza-like illness, influenza in infants and rates of low birth weight in Nepal. Maternal immunisation should be considered in subtropical regions where the virus is present for many months.

Reviewed by: Jessica Win See Wong

Article 3: Comparing infusion rates of fluid boluses in septic shock (India)

Sankar J et al. Fluid Bolus Over 15-20 Versus 5-10 Minutes Each in the First Hour of Resuscitation in Children With Septic Shock: A Randomized Controlled Trial. Pediatric Critical Care Medicine. 2017 Oct; 18(10)

What’s it about?

This was a randomised controlled trial where the researchers identified children with septic shock in paediatric ED and ICU in a tertiary hospital in northern India, and compared intravenous fluid boluses of 40-60mL/kg per hour in 20mL/kg aliquots delivered over 15-20 minutes versus over 5-10 minutes. Primary outcomes were the need for mechanical ventilation and/or impaired oxygenation. There were several other secondary objectives.

Subjects were aged 9 months to 12 years and included children with suspected infection with two or more clinical signs of decreased perfusion. They excluded children with dengue, malaria, severe anaemia, severe malnutrition, primary cardiac illness, those on non-invasive ventilation before developing shock, those who had already received fluids or inotropes, and those with contraindications to central line insertion.

This was a small RCT, with only 96 children randomised. The study was terminated after about 50% enrolment after interim analysis suggested harm in the 5-10 minute group. They found that children who received fluid boluses over 5-10 minutes were at higher risk of intubation and mechanical ventilation, had higher rates of intubation due to fluid overload, and had higher percentages of fluid overload in 24 hours. There was no difference in the mortality rate.

Why does it matter?

Recognition and treatment of sepsis is huge in acute paediatrics. Guidelines around the world recommend treating septic shock with fluid resuscitation of up to 60mL/kg as boluses, although the 2011 FEAST trial highlighted the potential harms of fluid boluses, suggesting a cautious approach to fluid bolus administration.

Instead of looking at different fluid volumes or types of fluid, this study compared infusion times. Unlike in the FEAST study, they excluded children vulnerable to the effects of fluid overload, allowing for more broad applicability of the results. Both groups of children received almost identical volumes of fluid as boluses; it was only the infusion times that differed.

The researchers suggested that rapid fluid bolus administration is difficult in developing countries due to a shortage of staff to administer the boluses, and fear of fluid overload and need for ventilation, which is not easy to achieve in resource-restricted settings.

The Bottom Line

Research is yet to identify the optimal fluid management of septic shock in developing and developed countries, so in the meantime caution is prudent.

Reviewed by: Katie Nash

Article 4: Think zinc! (India)

Negi K et al. Serum zinc, copper and iron status of children with coeliac disease on three months of gluten-free diet with or without four weeks of zinc supplements: a randomised controlled trial. Trop Doct. 2018; 48(2): 112-116. Doi: 10.1177/0049475517740312.

Why does it matter?

Coeliac disease is characterised by gluten intolerance which leads to damage to the small bowel mucosa via an autoimmune process in genetically susceptible individuals. Partial or total villous atrophy affects the maintenance of nutrients. Zinc is implicated in the improvement of mucosal healing and faster normalisation of micronutrient status in susceptible patients. Therefore, zinc supplementation may prove to be beneficial in patients with coeliac disease.

What’s it about?

This study compares the serum zinc, iron and copper status in paediatric patients following a gluten-free diet with or without zinc supplementation. All children aged <18 years with newly diagnosed coeliac disease were randomised to either the gluten-free diet (GFD) group or the glute-free diet + zinc supplementation (GFD+Zn) group via computer-generated random sequences. Patients were assessed with clinical history, examination and blood tests at baseline and various follow-up review up to 3 months. Unsurprisingly, iron, zinc and copper levels were below the normal range at baseline in all patients. The rise in haemoglobin, serum iron and ferritin levels was better in the GFD+Zn group than the GFD alone group. Otherwise, there was no significant difference in the rise of zinc, copper and weight gain in the two groups.

Clinically Relevant Bottom Line:

The study has shown that zinc supplementation significantly improves iron status but does not affect serum zinc or copper levels. The authors speculate this may be secondary to the contributory effect of zinc towards mucosal healing and improvement of intestinal absorption. Although interesting, it would have been helpful to couple these biochemical results with endoscopic findings with zinc supplementation. Nevertheless, the mainstay of treatment for coeliac disease remains the gluten-free diet and you may think of supplementing zinc if you want a faster improvement in iron status

Reviewed by: Jennifer Moon

Article 5: The power of playtime (Ethiopia)

Worku, B.N., et al  Effects of home-based play-assisted stimulation on developmental performances of children living in extreme poverty: a randomized single-blind controlled trial. BMC Paediatrics. 2018 Vol 18. doi: 10.1186/s12887-018-1023-0.

Why does it matter?

The study looked at foster children aged between 3 and 59 months, living with foster mothers in Jimma, a town in Ethiopia. The children were randomly assigned to intervention and control groups at a 1:1 ratio. The intervention group received home-based play stimulation once a week for 6 months, which focused on activities to promote developmental skills and mother-child interactions. The therapy was provided by a trained nurse, however, they also spent time teaching the foster mothers, so they could provide ongoing play therapy at home.

The assessors, who were blinded to the children’s allocations, used culturally specific and standardized developmental screening tools, at baseline, 3 months and 6 months. The study found that intervention was beneficial for language, social-emotional and personal-social performances (statistically significant for language [P = 0.0014], personal-social [P = 0.0087] and social-emotional [P < 0.0001] performances).


Clinically Relevant Bottom Line:

The study showed positive effects on multiple domains of development in the 6 months of follow up for children who received home-based play therapy. This approach is highly sustainable, as the foster mother’s acquired skills means they can continue to provide play therapy and hopefully, continue to have positive effects on children living in resource-limited settings.

Reviewed by: Tina Abi Abdallah

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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