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The 74th Bubble Wrap X PRAM


With millions of journal articles published yearly, it is impossible to keep up.  

Paediatric Research Across the Midlands (PRAM) is a trainee-led research collaborative across the West Midlands, networking since 2016. Learn more about past and future projects on our website . Join our mailing list by contacting and following us on Twitter @PramNetwork.

PRAM’s Neonatal, Community Paediatrics and Acute Paediatrics/ Paediatric Emergency Medicine Subgroups would like to share interesting articles in this month’s Bubble Wrap.

Article 1: How often do we stumble across an underlying condition in a child with low blood sugar?

Rosenfeld E, Alzahrani O, De León DD. Undiagnosed hypoglycaemia disorders in children detected when hypoglycaemia occurs in the setting of illness: a retrospective study. BMJ Paediatrics Open 2023;7:e001842. doi: 10.1136/bmjpo-2022-001842

What’s it about? 

This American single-centre retrospective review of 145 previously-well children referred to endocrinology to evaluate hypoglycaemia (<3.9 mmol/L) with acute illness between 2013 and 2018. In this group, a hypoglycaemic disorder was identified in 12 patients (8%) – seven hyperinsulinism, three inborn errors of metabolism, one growth hormone deficiency and one impaired hepatic insulin clearance due to acute hepatic insufficiency. The high proportion of hyperinsulinism may have been influenced by including neonates in the study population. The study highlights the importance of obtaining a ‘critical sample’ (hypoglycaemia screen) or assays for bicarbonate and beta-hydroxybutyrate at a minimum.

Limitations of this study are being a single centre and a retrospective review that introduces multiple biases. A threshold of 3.9mmol was used, higher than that used in UK practice. Could this have resulted in more children being picked up than if a cut-off of 2.6mmol had been used? Many patients met the criteria (1410), which was reduced to 145 due to exclusion criteria.

Underlying disorders were only found in patients who went on to have a diagnostic fast. This was conducted in just under half of patients, emphasising the need for correct workup in these children.

Why does it matter?

Younger age, higher bicarbonate levels and lower ketones in children with acute illness and hypoglycaemia on presentation to ED are potential predictors of establishing a hypoglycaemia diagnosis. The reported prevalence of undiagnosed hypoglycaemia disorders among children seen in the emergency department (ED) for any reason ranges between 10% and 28%. Previously well children presenting with acute illness are often thought hypoglycaemic due to prolonged fasting. There is a lack of data to indicate whether these children require endocrine evaluation.

Clinically Relevant Bottom Line

All children presenting to ED with an acute illness and hypoglycaemia should have a diagnostic evaluation (with endocrinology guidance).

Reviewed by Dr. Anandini Arumugam and Dr. Anandi Singh

Article 2:   Does quality of life differ for adults born premature or with a very low birth weight?

Selman C, Mainzer R, Lee K, et al. Health-related quality of life in adults born extremely preterm or with extremely low birth weight in the post-surfactant era: a longitudinal cohort studyArchives of Disease in Childhood – Fetal and Neonatal Edition Published Online First: 30 March 2023. doi: 10.1136/archdischild-2022-325230

What’s it about? 

This cohort study compared the health-related quality of life (HRQoL) in all survivors born extremely premature or with extremely low birth weight (EP/ELBW) (n=297) in Victoria, Australia, between 1991 and 1992, with their peers who were born at term and with normal birth weight (n=251). Self-reported HRQoL was examined at 18 and 25 years of age, using a validated tool assessing various domains, giving an overall score (0 to 1). The overall HRQoL at 18 years of age was lower for those born EP/ELBW than term-born peers (0.92 vs 0.94, median difference -0.016, 95% -0.061 to 0.02, p=0.47). At 25 years of age, this difference grew (0.89 vs 0.93, median difference -0.040, 95% CI -0.088 to 0.008, p= 0.10) with increasing divergence in speech and dexterity domains. Other attributes (vision, hearing, pain and emotion) were similar between groups.

Limitations of this study include large confidence intervals indicating substantial uncertainty as to whether there is an actual difference in health-related quality of life between the two groups.

Why does it matter? 

With significant increases in survival of EP/ELBW infants, it has become apparent that survivors may have ongoing reductions in HRQoL. In this study this was reported to be more at 25 than 18 years.

Clinically Relevant Bottom Line

This study highlights how the disparity in the HRQoL between those born EP/ELBW and those born at term and normal birth weight may increase in adulthood with increasing life demands. More work is needed in this area, especially with the ever-increasing viability margins of extreme prematurity.

Reviewed by: Dr Nikitha Rajaram and Dr Tim van Hasselt

Article 3: Fragility and resilience: parental and family perspectives on the impacts of extreme prematurity

Janvier A, Bourque CJ, Pearce R, et al.Fragility and resilience: parental and family perspectives on the impacts of extreme prematurity. Archives of Disease in Childhood – Fetal and Neonatal Edition Published Online First: 30 March 2023. doi: 10.1136/archdischild-2022-325011

What’s it about?

In this study from a large neonatal intensive care unit in Canada, parents of extremely preterm babies were asked about the impact preterm birth had on their lives. This was a mixed methods study, with a quantitive question and then open-ended questions asking families to talk about their own experiences.  

There were 285 responses in total. The mean gestational age of families’ babies at birth was 26.6 weeks (range 22 to 28). 74% of parents reported positive and negative impacts on their family life, 18% reported only positive and 8% only negative impacts.

The most common positive impacts included an improved outlook on life, such as gratitude and change of perspective, stronger family relationships, and the gift of the child. The most common negative ones were stress and fear, loss of equilibrium due to the child’s medical fragility, concerns about developmental outcomes and the child’s vulnerability.

One of the study’s other major findings was that there was no correlation between the positive or negative responses and the child’s neurodevelopmental impairment (NDI). This raises an interesting point about using NDI as an important outcome in neonatal research.

One of this study’s limitations is that the responses were taken from parents from a publicly funded healthcare system with one year of guaranteed parental leave. This might provide very different responses for families with less financial pressures due to this. The study did not get responses from parents whose children did not survive (although some of the responses were from parents of multiples who had lost one of the babies). The majority of responses were from only one parent- therefore, they may not reflect the views of the whole family unit.

Why does it matter?

Most families of preterm babies report having some positive experiences, an aspect of neonatal care that is not explored as often as the negative impacts.

Clinically Relevant Bottom Line

The study suggests that family-centred neonatal care can allow families to have positive experiences following preterm birth. This should be considered when healthcare professionals are counselling parents, alongside the adverse outcomes.

Reviewed by: Dr. Eileen Foster and Dr. Tim van Hasselt

Article 4: How much do babies sleep?

O Sullivan MP, Livingstone V, Korotchikova I, et al Reference centiles for infant sleep parameters from 4 to 16 weeks of age: findings from an Irish cohort Archives of Disease in Childhood 2023;108:481-485.

What’s it about?

This longitudinal study aimed to define normal sleep parameters for healthy term infants. This data was taken from the non-intervention arm of the BabySMART trial (RTC looking at massage therapy, sleep and neurodevelopment). Term babies with no NICU admission, no congenital or metabolic abnormalities and singleton pregnancy were eligible.  

Parents of 106 infants completed sleep diaries capturing the duration and timing of each sleep episode from 4 to 16 weeks of age. Parental questionnaires assessed sociodemographics, sleeping arrangement, feeding status and parents’ perceptions of infant sleep. Total sleep time, day-time sleep (from 07:00-18:59), night-time sleep (from 19:00-06:59) and longest sleep in 24 hours were measured. Reference centiles for these parameters were created using multilevel linear mixed modelling and plotted against the infants’ ages.

Results showed variability between infants. From 4 to 16 weeks, total sleep increased by under 1 hour, daytime sleep decreased by nearly 2 hours, night-time sleep increased by 2.5 hours, and the longest sleep period increased by 3 hours.

By four weeks, 49% of infants were exclusively breastfed – this had dropped to 31% by 16 weeks. There was no difference in sleep patterns between infants exclusively breastfed, mixed feeding or receiving formula.

Most parents (80%) did not feel their child’s sleep pattern was problematic. This study relies on parental recall, which may be an underestimate or overestimate. This study also had a very specific demographic – white Irish babies. It is unclear if this can be extrapolated to a population of different ethnicities and cultures. It is important, too, that this data was taken from an RCT. Therefore, the initial plan for this data was not what this study looked at (good to think of as a spin-off series – good but not the intended initial outcome!).

Why does it matter?

Sleep is essential for early brain development. Many parents worry about ‘normal’ sleep patterns in babies.

Clinically Relevant Bottom Line

Parents can be reassured there is variability in sleep patterns between infants in the first few months. Shorter sleep episodes and mixed circadian rhythms evolve to more rhythmic day-night trends over this period. The feeding method does not appear to influence infants’ sleep.

Reviewed by: Dr. Bethany Davies and Dr. Hannah Cooney

Article 5: Does living in an area with better air quality improve your lung function?

Yu Z, Merid SK, Bellander T, et al. Associations of improved air quality with lung function growth from childhood to adulthood: the BAMSE study. Eur Respir J 2023; 61: 2201783[DOI:10.1183/13993003.01783-2022].

What’s it about?

This prospective cohort study investigated associations between changes in ambient air pollution levels and lung function from childhood to adulthood. Spirometry measurements were performed at 8-year, 16-year and 24-year intervals for 1509 participants in Sweden. These measurements were compared to the preceding year’s air pollution exposure assessed by calculating particulate matter, black carbon and nitrogen oxide levels for each participant’s address.

Reduced levels of air pollution were associated with an increased growth rate of FEV1 and FVC. This was irrespective of factors such as asthma, being overweight, smoking, allergic sensitisation, dietary antioxidant intake and early life exposures.

The study also showed relocating to areas of lower air pollution improved lung function. The mean growth rate in FEV1 increased by 4.63ml/year and FVC by 9.38ml/year for each unit reduction in particulate matter, black carbon, and nitrogen oxide. There was a substantially larger effect observed from childhood (8 years) to adolescence (16 years) than from adolescence to young adulthood (24 years).

Potential limitations were using different spirometers at the 8, 16, and 24 marks. This could potentially account for some of the changes at these points. Other environmental factors could act as confounders, such as noise and surrounding green spaces – although less is known about these in relation to lung function. This data was taken from a population with a lower area of air pollution than many major cities and countries. More research looking at differing baselines of pollution would be useful.

Why does it matter?

The adverse effects of air pollution on children’s respiratory health are well understood. However, less is known about the benefits of improved air quality on lung function.

Clinically Relevant Bottom Line

Long-term reduction of air pollution correlates with improved lung function, and this change is greatest in the years from childhood to adolescence. These results support public health policymakers and paediatricians advocating for climate change strategies.

Reviewed by: Dr. Isabel Cowling and Dr. Bethany Davies

If we missed something useful or you think other articles are 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.

All articles were reviewed and edited by Vicki Currie.


  • Vicki is a Paediatric Registrar in the West Midlands in the UK , starting PEM in September 2021. Vicki is passionate about good communication in teams and with patients along with teaching at undergraduate and postgraduate level. When not editing Bubble wrap Vicki can be found running with her cocker spaniel Scramble or endlessly chatting with friends.


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