Category: Paediatrics

Delaying Lumbar Puncture Cuts Relapse in Childhood Leukaemia

Commencing chemotherapy several days before the first lumbar puncture for diagnosis and treatment of acute lymphoblastic leukaemia (ALL) may lower the risk of central nervous system (CNS) relapse in children, according to a study from St Jude Children’s Research Hospital and collaborators in China. 

“This study identified factors to help us predict and better manage the risk of CNS relapse that will be useful for treating ALL patients worldwide, in both resource-rich and resource-limited countries,” said corresponding author Ching-Hon Pui, MD, chair of the St. Jude Department of Oncology. Dr Pui pioneered paediatric ALL treatment that has achieved 94% long-term survival for St. Jude patients that did not receive brain irradiation.

Using an adapted paediatric protocol from St Jude Hospital, 7640 children and adolescents across 20 Chinese hospitals were enrolled in the trial. However, there was a great disparity across the hospital settings. For example, just three of the hospitals offered total intravenous anaesthesia for children undergoing spinal taps, while only two had flow cytometry for the diagnosis of leukaemia cells in cerebrospinal fluid.

The five-year overall survival rate was 91% for study patients, and the cancer-free survival rate was 80%, which is a dramatic improvement over previous clinical trials in China. But 1.9% of patients relapsed in the CNS alone, and in another 2.7% of patients the relapse involved the CNS. In comparison, a Canadian study reported a 6.6% rate for CNS-involved relapse in paediatric ALL patients followed over 10 years.

According to Dr Piu, in order to increase the survival rate of paediatric ALL patients requires identifying those at risk for CNS relapse, along with increasing their quality of life. Three factors reduced the risk of CNS relapse. First, commencing dexamethasone a few days before the spinal tap, prevents leukaemia cells entering the cerebrospinal fluid (CSF). Second, intravenous anaesthesia reduced bleeding risk during lumbar punctures, and improved  intrathecal therapy. Third, flow cytometry enables more accurate diagnosis of leukaemia cells in CSF, and reduced CNS relapse.

Source: Medical Xpress

Journal information: Jingyan Tang et al. Prognostic Factors for CNS Control in Children with Acute Lymphoblastic Leukemia Treated Without Cranial Irradiation, Blood (2021). DOI: 10.1182/blood.2020010438

Early Interventions May Improve Infant Brain Health

Image by Raman Oza from Pixabay

At the Cognitive Neuroscience Society’s (CNS) annual meeting, researchers from the University of Minnesota presented their work on early interventions to ameliorate negative effects on infant brain health.

Their two interventions consist of using engineered gut microbes for antibiotic-exposed infants and the other is a choline supplement to treat infants exposed to alcohol in the womb.

Dr Gale’s new research shows that infants with different compositions of gut bacteria process auditory and visual stimuli differently during memory tasks. “These results raise the possibility that gut bacteria are involved in the development of brain function,” she said.

The study compared the brain activity of infants who received antibiotics within their first month of life to those who did not. Using EEG, the researchers recorded a type of electrical activity called event related potentials (ERPs) in the infants’ brains in response to either their mother’s voice or a stranger’s voice – a “recognition memory” that can be assessed in preverbal infants before any behavioral changes are apparent. This has been shown to be an effective assessment of many aspects of cognitive development.

“Recognition memory is one of the earliest types of explicit memory to develop and is known to be dependent on medial temporal lobe structures, including the hippocampus, the brain region affected by microbiome perturbation in animal models,” explained Dr Cheryl Gale, of the University of Minnesota.

The ERP measurements of infants exposed to antibiotics showed an abnormal response to their mother’s voices compared to those unexposed.
While antibiotics were associated with impact on brain function, a causal relationship could not be established. “We don’t yet know if there is a definitive cause and effect relationship between microbes and brain function in human infants, but future research will hopefully be able to shed light on this,” Gale says.

The work raises the prospect of creating engineered microbes as an early life intervention. “Infancy is a critical time window for brain development, when therapeutic interventions can have effects for the life-course,” Gale said.

The other study was on foetal alcohol exposure, which is still a widespread problem, involved in some 8 in 1000 births worldwide, resulting in serious cognitive consequences. Dr Jeff Wozniak became aware of a lack of neural imaging studies in this very high-need population.

“So I became interested in using some of the tools that we had available here at the University of Minnesota to do high-quality imaging of brain structure and function in this understudied population to learn something about how the brain is altered by prenatal alcohol exposure at the earliest stages of development,” he said.

Together with colleagues, they identified a number of pathways by which alcohol impacts the foetus, such as interfering with the myelination of nerves. The researchers came up with a treatment: choline, an essential nutrient. This has been used in a number of double-blind, placebo-controlled clinical trials in 2-5 year olds with foetal alcohol exposure.
Children receiving choline early in life showed higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder (ADHD) than those in the placebo group.

“The further back you go and do your intervention, the more leverage you have to alter the developmental trajectory of that particular child,” Dr Wozniak said. “So that was the exciting thing about bringing those children back and looking at their development and seeing much larger choline versus placebo effects in cognitive functions like working memory and even behavioural differences in terms of ADHD.”

Source: News-Medical.Net

Playing with Ultra-thin Dolls Skews Girls’ Ideal Body Size

A small-scale study led by Durham University in the UK, has shown that play with ultra-thin dolls may negatively affect body image in girls as young as five years old.

The researchers warn that the dolls, combined with exposure to ‘thin ideals’ in the media, could lead to body dissatisfaction in young girls, which has been shown to be a factor in the development of eating disorders. A Dutch study showed that girls randomised to receive an ultra-thin doll to play with ate less than those who received a realistic adult doll.

The study had 30 girls aged between 5-9 years old play with an ultra-thin doll, a realistic childlike doll or a car. Before and after each play session, the girls were asked about their perceived own body size and ideal body size via an interactive computer test using pictures.

Playing with the ultra-thin dolls reduced girls’ ideal body size immediately after play. There was no improvement even when they subsequently played with the childlike dolls or cars afterwards, demonstrating that playing with other toys cannot quickly counteract the effects. The realistic children’s dolls had a neutral effect on body ideals.

Lead author Professor Lynda Boothroyd, from Durham University’s Department of Psychology, said: “Body dissatisfaction is a huge problem, particularly amongst young girls. It can have serious consequences for girls’ wellbeing and lead to eating disorders and depression.

“The results from our study indicate that playing with ultra-thin dolls, which are sold in the millions each year, could have a real negative impact on girls’ body image. This is on top of all the images of unrealistic body sizes they see on TV, in films and on social media. This is something that needs to be addressed in order to reduce the pressure on girls and women to aspire to a ‘thin ideal body’.”

The psychologists had found in previous research that the more TV we watch, the more we prefer thinner female bodies. Of the girls who took part in the study, 80% said they had ultra-thin dolls at home or with their friends, and nearly all watched films which tend to portray very thin female bodies. Dolls available in shops tend to have a projected BMI of 10 to 16 (underweight). The study used realistically proportioned dolls resembling healthy children of 7 and 9.

Dr Elizabeth Evans, from Newcastle University’s School of Psychology, said: “This study isn’t intended to make parents feel guilty about what’s in their child’s toy box, and it certainly isn’t trying to suggest that ultra-thin dolls are ‘bad’.

“What our study provides is useful information that parents can take into account when making decisions about toys. Ultra-thin dolls are part of a bigger picture of body pressures that young children experience, and awareness of these pressures is really important to help support and encourage positive body image in our children.”

The study, though small, tested the children before and after doll play, an unusual approach which nevertheless adds to growing evidence that doll play affects young girls’ beauty ideals.

Professor Martin Tovee, from Northumbria University’s Department of Psychology, said: “Our study shows how perception of ideal body size and shape is moulded from our earliest years to expect unrealistic ideals. This creates an inevitable body image dissatisfaction which is already known to lead towards disordered eating.”

Source: Medical Xpress

Journal information: Can realistic dolls protect body satisfaction in young girls?, Boothroyd et al, Body Image, 11 March 2021.

20% of Healthy Children May Have Benign Bone Tumours

Around 20% of healthy children may possess benign tumours, according to a review of radiographs taken nearly a century ago.

Although it sounds alarming, non-ossifying fibromas and other common benign bone tumours in symptom-free children are not dangerous. Such bone tumours are often discovered on x-rays taken for other causes, such as a fracture. 

“Understandably, these tumours cause a lot of anxiety for patients and families as they await confirmation that the tumour is benign,” said Christopher Collier, MD, Indiana University School of Medicine, Indiana University. “They need reassurance and often ask how common these tumours are, when did they first appear, and whether they will resolve over time? We don’t have much evidence to date to address these questions.”

To address these questions, the researchers analysed annual x-rays taken of children’s bones as they grew, however such studies today are not feasible today due to ethical concerns over sensitivity of children to ionising radiation. Therefore, they drew on a unique collection of radiographs from the Brush Inquiry, a study in which a series of healthy, ‘normal’ children in Ohio, underwent annual radiographs from 1926 to 1942.

Dr Collier’s team analysed a total of 25 555 digitised radiographs of 262 children, followed from infancy to adolescence, finding a high prevalence of bone tumours. A total of 35 benign bone tumors were found in 33 children – an overall rate of 18.9 percent when considering that only the left side of the children was radiographed.

Over half of the tumours were non-ossifying fibromas, which are connective tissue masses that have not hardened into bone. Generally, these fibromas appeared around age five, and again around the time of skeletal maturation, possibly linked to growth spurts. Of 19 non-ossifying fibromas detected, seven disappeared over time. Others may have resolved some time after the annual radiographs stopped.

Rarer benign bone tumoors included enostoses, sometimes called ‘bone islands’; and osteochondromas or enchondromas (tumours in cartilage). In patients with these tumours, they persisted to the last available radiograph.

The findings are similar to the rates of benign bone tumours in healthy adults. Dr Collier noted: “Despite the inherent limitations of our historical study, it may provide the best available evidence regarding the natural history of asymptomatic benign childhood bone tumors.”

Source: News-Medical.Net

Researchers Say New Vaccines Needed for Childhood Pneumonia


Research in Australia on new pneumonia vaccines show that while pneumonia in children is being suppressed,  empyaema is increased.

The research, which was led by the University of New South Wales (UNSW), examined the impact of the new 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyaema.
Empyaema, which is the collection of pus in the lungs, occurs in about 1% of children with pneumonia. In children, empyaema is far less fatal than it is in adults, but it does extend hospitalisation, requiring antibiotics and surgery or installation of a drain.
The findings of the study showed that while 13vPCV resulted in a 21% drop in childhood pneumonia hospitalisations, there was a contemporaneous 25% rise in empyaema hospitalisations.

According to senior author Professor Adam Jaffe, Head of the School of Women’s and Children’s Health at UNSW Medicine & Health, said the findings suggested an emergence of non-vaccine serotypes—those which 13vPCV does not cover.

13vPCV was introduced to cover the 13 most common serotypes that cause invasive pneumococcal infection, adding six more serotypes over the seven serotypes covered by its predecessor, 7cPCV.

Prof Jaffe said: “Although we found a substantial reduction in serotype 1, serotype 3 is now the predominant organism which causes childhood empyema—in 76% of cases—so, efforts must be made to create a vaccine which is more effective against serotype 3.

“In fact, Australia recently changed the vaccination dosage schedule to try and improve the effectiveness of 13vPCV against serotype 3, but we need to continue monitoring patients using molecular techniques to see if this change has had an impact.

“Childhood bacterial pneumonia and empyema are potentially preventable diseases through vaccination. So, if Australia can develop an effective vaccine, we could prevent children from being hospitalized with pneumonia and empyema.”

The researchers conducted a similar study over four years during the 7vPCV era.   

“Our new study had two parts,” Prof Jaffe said. “We analysed national hospitalisations for childhood empyaema and childhood pneumonia, then we conducted an enhanced surveillance study on children with empyaema.”

The first part of the research used publicly available hospitalisations data to find out if the introduction of 13vPCV changed how many children were admitted to hospital with pneumonia and empyaema.

The enhanced surveillance study involved the collection of blood and lung fluid samples from 401 children  with empyaema, followed by molecular testing on these samples and comparing the results to their previous study undertaken during the period of 7vPCV.

Prof Jaffe said research with a larger sample was ongoing, and 13vPCV monitoring was needed.

Source: Medical Xpress

Journal information: Roxanne Strachan et al. Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia, Thorax (2021). DOI: 10.1136/thoraxjnl-2020-216032

Regular Sleep Patterns in Toddlers Important for BMI

Although getting regular sleep patterns in toddlers has long been a priority for parents, researchers have shown it is important for toddlers’ BMI.

The researchers, led by Lauren Covington, an assistant professor in the University of Delaware School of Nursing, investigated the link between poverty, regular sleep patterns and BMI in toddlers. According to The National Sleep Foundation, toddlers 1- to 3-years-old should have 12 to 14 hours of sleep in a 24-hour period.

“We’ve known for a while that physical activity and diet quality are very strong predictors of weight and BMI,” said Prof Covington, the lead author of the article. “I think it’s really highlighting that sleep may be playing a bigger role here than it’s been given credit for.”

The researchers aimed to investigate the relationship between poverty and BMI in toddlers, and wanted to see whether sleep behaviour, activity or food intake could provide the explanation.

Using data from families in an obesity prevention trial, 70% of whom were below the poverty line, and all eligible for nutritional supplementation grants, Toddlers were given accelerometers to wear to measure physical activity and parents filled out food diaries.

The researchers found that children from households with greater poverty were more likely to have greater inconsistent bedtimes, and those with more inconsistent bedtimes had higher BMI percentages.

Prof Covington said this is likely to be a bidirectional relationship. “There’s a lot of teasing out the relationships of the mechanisms that are at play here, which is really difficult to do because I think they’re all influencing each other,” she said.

Having consistent bedtimes where children go to bed within one hour of the normal time is a recommended guideline, but for families in poverty this may be impossible for a variety of reasons. Single parent households and juggling multiple jobs are part of the challenges they face.

“Implementing a consistent bedtime could be one behavioural change that a family could potentially do,” said Prof Covington. “It’s more attainable than maybe getting healthy food at the grocery store or playing outside on the playground, especially now with the cold weather. Just having a consistent bedtime can help provide some sense of structure, but then maybe have better implications for health and BMI as well.”

Source: Medical Xpress

Journal information: Lauren Covington et al. Longitudinal Associations Among Diet Quality, Physical Activity and Sleep Onset Consistency With Body Mass Index z-Score Among Toddlers in Low-income Families, Annals of Behavioral Medicine (2020). DOI: 10.1093/abm/kaaa100

Novel Transplant Technique Yields More Donor Hearts for Children

Two hospitals in the UK have reported great success in a new heart transplant technique, resulting in a record number of children receiving heart transplants in 2020.

Royal Papworth Hospital in Cambridge and Great Ormond Street Hospital (GOSH) have collaborated on a new procedure which has enabled a much larger supply of donor hearts for children, who have had to wait two and a half times as long as adults for a donation.

Royal Papworth Hospital was the first in Europe to harvest non-beating hearts from adult patients whose life support had been withdrawn, and then been restarted for transplantation, instead of waiting for brain death with a still-beating heart.

By using a special device called the organ care system, surgeons can effectively restart the heart and keep it healthy until transplantation. The first non-beating heart transplant was performed in Australia in 2014. Since February last year, the two hospitals have been offering the service to children.

The use of non-beating hearts had previously been ruled out for transplantation until recently, due to tissue damage from lack of oxygen. The new organ care system, which supplies the heart with oxygenated blood and nutrients, can be used to keep the heart alive and pumping outside the body for up to 12 hours. This is long enough for checks to be performed prior to the transplant procedure, or even transferred to another hospital.

GOSH and Freeman Hospital are the only two centres in the UK with paediatric heart transplant units. In the past five years, 39 children died while waiting for donors.

“Some patients will just not survive the wait,” said Jacob Simmonds, a transplant surgeon at GOSH. “There is also a risk that while waiting they could damage other organs, particularly the lungs.” 

Last year, six paediatric heart transplants were carried out in the UK using the new procedure, and only four elsewhere in the world. The organs came from adult donors, as the organ care system is designed to accommodate hearts from people weighing over 50kg. Development is being carried out on a system which could allow harvesting organs from children. This would increase the available transplants for infants and babies, who have a critical lack of donors.

Source: BBC News

Study Reveals More Sugar in Breakfast Products Aimed at Children

Breakfast products that are aimed at children contain significantly more sugar than those aimed at adults, a Spanish study has revealed.

The researchers analysed a 355 advertisements from 117 different products from 2015 to 2019, and found that the average amount of sugar in the breakfast products analysed and advertised for adults was 10.25%, while for children it was 36.20%.

“Although much of the adult population still adhere to the Mediterranean diet, it is a practice that is waning among children and young people, who are increasingly opting to eat processed industrial products with a high sugar content for breakfast,” explained Mireia Montaña, UOC Faculty of Information and Communication Sciences professor and researcher.

Mònika Jiménez, professor of Advertising and Public Relations at Pompeu Fabra University (UPF) and co-author of another study on breakfast food advertising involving Prof Montaña, warned of persuasive advertising for foods with little nutritional value.

She said, “The less closely a product correlates to that which would be deemed healthy nutritional parameters, the greater the tendency for the advertising discourse to focus on hedonism or happiness and tend towards persuasion.” As Jiménez explained, when such discourse alludes to positive feelings, it stimulates certain areas of the brain that lead us to consume, a strategy which “is especially harmful in relation to certain audiences, such as minors, because they are very susceptible to these kinds of stimuli.”

Profs Montaña and Jiménez found that low nutritional quality breakfast foods were advertised mostly through television (39%), followed by radio (28%), the internet (18%), newspapers (6%), magazines (5%), outdoor advertising (2%) and cinema (0.56%). “TV is the most effective medium when it comes to persuading children. And when is it that children are going to the supermarket with their parents and end up imposing their preferences with regard to what goes into the shopping trolley? Precisely when they are younger, up until preadolescence,” Prof Jiménez pointed out.

Though there are regulations in Spain preventing advertisers from targeting children directly, there are no such restrictions for products which can be aimed at any age group, such as hot chocolate. Advertising aimed at children to use ‘pester power’ on their parents results in food being bought which is then consumed by the entire family. 

Their recommendations included more stringent regulatory frameworks, better nutritional education aimed at parents and children, and added taxes on certain products such as soft drinks.

Source: News-Medical.Net

Journal information: Blasco, M.M., et al. (2021) Breakfast Food Advertisements in Mediterranean Countries: Products’ Sugar Content in the Adverts from 2015 to 2019. Children. doi.org/10.3390/children8010014.

No Evidence for Strep Exacerbating Chronic Tics in Kids

A new study has found that children with chronic tic disorders, mainly Tourette syndrome, do not have tic exacerbations when exposed to group A Streptococcus.

No significant association with tic exacerbations emerged across four definitions of pharyngeal strep exposure with a mean follow-up of 16 months, though a weak link was observed in trend, reported Davide Martino, MD, PhD, of the University of Calgary, and co-authors.

Strep was however significantly associated with longitudinal changes in hyperactivity-impulsivity symptom severity of 17% to 21%.
“The link between Streptococcus and tics in children is still a matter of intense debate,” Martino stated. “We wanted to look at that question, as well as a possible link between strep and behavioral symptoms like obsessive-compulsive disorder and attention deficit hyperactivity disorder.

“While our findings suggest that strep is not likely to be one of the main triggers for making tics worse, more research is needed into other possible explanations. For example, the social stress of having this disorder could be implicated in making tics worse more than infections. It’s also possible another pathogen might be triggering an immune response associated with tic worsening.”

In an invited editorial, Andrea Cavanna, MD, PhD, of the University of Birmingham, and Keith Coffman, MD, of Children’s Mercy Hospital in Kansas City, observed that group A Streptococcus had been posited as a potential environmental factor in tic disorders for the past two decades.

The editorialists noted that, on the basis of isolated clinical observations, tic disorders should be included as a collateral feature in conditions which are known as pediatric autoimmune neuropsychiatric disorders associated with Streptococcus (PANDAS) infections. However, the results of longitudinal clinical studies were inconclusive, with a case control study even arguing against the association.

Drawing data from the EMTICS study, recruiting children with chronic tic disorders from 2013 to 2016, one arm of the study prospectively examined associations between new group A Streptococcus throat exposures and tic exacerbations, obsessive-compulsive disorder (OCD), and attention deficit hyperactivity disorder (ADHD) symptoms.

Four definitions of strep exposure were used: new definite (newly positive throat swab regardless of serological results), new possible (elevated anti-streptolysin O [ASOT] or anti-DNAseB [ADB] titers with negative or no throat swab), ongoing definite, and ongoing possible.

Initially, 59 children had a positive throat swab; as the study progressed, 103 children had new definite strep exposure. During follow-up, 308 children (43%) had tic exacerbations. The proportion of exacerbations temporally associated with strep exposure ranged from 5.5% to 12.9%, depending on exposure definition. No association between OCD symptoms and strep exposure was seen.

“Our study of the largest prospective cohort of youth with chronic tic disorders ever documented to date provides evidence against a temporal association between group A Streptococcus exposure and clinically relevant tic exacerbations,” the researchers wrote.

“This result indicates that specific diagnostic work-up or active management of group A Streptococcus infections in the context of worsening of tic severity in patients with chronic tic disorders is not warranted,” the researchers added.

The researchers noted that limitations included the data being collected from specialist centres in different countries, and that some cases of strep may have been missed.

Source: MedPage Today

Journal information (article): Martino D, et al “Association of Group A Streptococcus Exposure and Exacerbations of Chronic Tic Disorders: A Multinational Prospective Cohort Study” Neurology 2021; DOI: 10.1212/WNL.0000000000011610.

Journal information (editorial): Cavanna A, Coffman K “Streptococcus and Tics: Another Brick in the Wall?” Neurology 2021. DOI: 10.1212/WNL.0000000000011608.

Caffeine Shown to Alter Brain Pathways in Utero

Caffeine consumption during pregnancy could change key brain pathways, resulting in children having significant behavioural problems in later life. 

“These are sort of small effects and it’s not causing horrendous psychiatric conditions, but it is causing minimal but noticeable behavioural issues that should make us consider long term effects of caffeine intake during pregnancy,” said John Foxe, PhD, director of the Del Monte Institute for Neuroscience. “I suppose the outcome of this study will be a recommendation that any caffeine during pregnancy is probably not such a good idea.” Foxe also pointed out that this was a retrospective study, reliant on mothers’ recall of caffeine consumption.

Studies had already linked caffeine to other outcomes, such as a meta-review which found a nearly linear link between caffeine consumption and low birth weight. It is known that foetuses do not possess the enzyme necessary to break down caffeine, which crosses the placenta into the foetal bloodstream.

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester Medical Center (URMC) analysed brain scans of thousands of children. The researchers observed increased behavioural and attention problems along with hyperactivity in these children. They observed distinct changes in how the white matter tracks (which connect brain regions) were organised in children of mothers who reported caffeine consumption during pregnancy.

“What makes this unique is that we have a biological pathway that looks different when you consume caffeine through pregnancy,” said first author Zachary Christensen, an MD/PhD candidate in the Medical Science Training Program. “Previous studies have shown that children perform differently on IQ tests, or they have different psychopathology, but that could also be related to demographics, so it’s hard to parse that out until you have something like a biomarker. This gives us a place to start future research to try to learn exactly when the change is occurring in the brain.”

At this stage it is not known what the relationship between amounts of caffeine are, or what effects arise in each trimester.

“Current clinical guidelines already suggest limiting caffeine intake during pregnancy—no more than two normal cups of coffee a day,” added Christensen. “In the long term, we hope to develop better guidance for mothers, but in the meantime, they should ask their doctor as concerns arise.”

Source: Medical Xpress

Journal information: Zachary P. Christensen et al, Caffeine exposure in utero is associated with structural brain alterations and deleterious neurocognitive outcomes in 9–10 year old children, Neuropharmacology (2021). DOI: 10.1016/j.neuropharm.2021.108479