Children around the world are spending more and more time with screens, which is a great concern for parents and physicians alike. New research from Japan indicates that more screen time at age 2 is associated with poorer communication and daily living skills at age 4 – but playing outdoor seems to reduce some of the negative effects.
For their study, published in JAMA Pediatrics, the researchers followed 885 children from 18 months to 4 years of age. They looked at the relationship between three key features: average amount of screen time per day at age 2, amount of outdoor play at age 2 years 8 months, and neurodevelopmental outcomes at age 4: communication, daily living skills, and socialization scores according to a standardised assessment tool called Vineland Adaptive Behavior Scale-II.
“Although both communication and daily living skills were worse in 4-year-old children who had had more screen time at aged 2, outdoor play time had very different effects on these two neurodevelopmental outcomes,” explains Kenji J. Tsuchiya, Professor at Osaka University and lead author of the study. “We were surprised to find that outdoor play didn’t really alter the negative effects of screen time on communication – but it did have an effect on daily living skills.”
Specifically, almost one-fifth of the effects of screen time on daily living skills were mediated by outdoor play, meaning that increasing outdoor play time could reduce the negative effects of screen time on daily living skills by almost 20%. The researchers also found that, although it was not linked to screen time, socialisation was better in 4-year-olds who had spent more time playing outside at 2 years 8 months of age.
“Taken together, our findings indicate that optimizing screen time in young children is really important for appropriate neurodevelopment,” says Tomoko Nishimura, senior author of the study. “We also found that screen time is not related to social outcomes, and that even if screen time is relatively high, encouraging more outdoor play time might help to keep kids healthy and developing appropriately.”
These results are particularly important given the recent COVID-related lockdowns around the world, which have generally led to more screen time and less outdoor time for children. Because the use of digital devices is difficult to avoid even in very young children, further research looking at how to balance the risks and benefits of screen time in young children is eagerly awaited.
A cohort study on the prescription of antipsychotics to children and adolescents in the UK has found that they have doubled over the past two decades. The findings, published in The Lancet Psychiatry, depict a concerning tendency for more, longer prescriptions of antipsychotics for a wider array of indications, many of them off-label, and which may be influenced by US and European approvals.
Studies around the world have reported an increase in the prescription of antipsychotics for children and adolescents. While this may reflect actual changing clinical needs, most antipsychotics are not approved for use in under-18s due to lacking safety data, especially in the long term. There is also little evidence on indications for, and doses of, antipsychotic prescribing in children and adolescents.
The study used a cohort of over 7 million children and adolescents (age 3–18 years) assembled from a large English primary care database, and found a doubling in the proportion of prescribed antipsychotics between 2000 and 2019.
This increase resulted from the accumulation of repeated prescriptions to the same individuals combined with an increase in new prescriptions. The researchers found that antipsychotic prescribing was more frequent for children in more deprived areas, which reflected a previous UK study on adults.
The study also revealed multiple clinical indications for antipsychotics beyond their initial approvals, most commonly for anxiety and depression. Risperidone was the most prescribed antipsychotic for all indications apart from depression, for which the most prescribed antipsychotic was quetiapine, and eating disorders, for which it was olanzapine.
Prescribing trends for certain disorders could be though to reflect prevalence. The authors noted however that “the most common indications for antipsychotics were ASD, ADHD, anxiety, and depression. It could be the increasing prevalence of these disorders that causes higher prescribing rates. However, increasing ASD prevalence results primarily from patients with less severe ASD, who are unlikely to receive antipsychotics.”
They also observed that increases in prescribing appeared to be linked to new US and European approvals.
Limitations included the database not identifying whether a prescription was for a first time, and not tying indications directly to prescriptions. Dosage regimen information was also only available for a third of prescriptions. The database was also not necessarily nationally representative, and only reflected prescriptions issued in secondary care – referral to primary care means that the rate of prescribing may be underestimated.
In October last year, the National Institute for Communicable Diseases (NICD) alerted the public to a measles outbreak in Limpopo. Since then, four more provinces have reported outbreaks, and the number of positive cases in the country has climbed rapidly.
Last week’s measles report from the NICD indicated that between the first week of October 2022 and mid-week in the second week of January 2023, a total of 397 cases of measles were identified across the country. Of those, 382 cases were detected in five provinces – Limpopo 145, North West 125, Mpumalanga 79, Gauteng 18, and the Free State 15. These five provinces have all met the criteria for a measles outbreak (three or more cases in a district within a month).
The remaining 15 cases are spread around KwaZulu-Natal, Northern Cape, the Eastern Cape, and the Western Cape – none of which have so far met the criteria for an outbreak.
‘Biggest outbreak in 11 years’
Dr Kerrigan McCarthy, a pathologist from the Centre for Vaccines and Immunology at the NICD, tells Spotlight that this is the biggest outbreak in 11 years, surpassing the outbreak in 2017 when around 280 cases of measles were identified.
According to the NICD report, the total number of laboratory-confirmed measles cases and the total number of samples submitted for testing has decreased for the third consecutive week. However, McCarthy cautions that this apparent decline might actually be due to a decrease in the number of specimens sent to the NICD for testing, and not to the outbreak actually slowing down.
“The fact that we have seen a decrease in the number of positive cases could be attributed to the decrease in number of specimens that have been submitted, but there is a small possibility that it could represent a turnaround in the outbreak. However, a consensus amongst us in public health is that it is the former problem,” says McCarthy.
She adds that the true extent of this outbreak – and whether new cases have really declined or not – may only become clear in the next few weeks, as schools across the country resume activities.
While it isn’t possible to predict exactly where the outbreak is going, McCarthy says at the moment it is following a similar trend to the widespread measles outbreak that occurred just over a decade ago. “In 2009 to 2011 we had an outbreak of over 22 000 measles cases… and in fact, in that outbreak, we saw a similar pattern. The outbreak was declared in late 2009 and cases started increasing into December and then when the schools closed and December holidays happened, there was a lull in cases and then when the schools returned there was a massive increase in cases,” she says.
Fears of much larger outbreaks
In a Spotlight article published in July last year, Dr Haroon Saloojee, Professor and Head of the Division of Community Paediatrics at the University of the Witwatersrand, and other experts warned that low vaccination rates may lead to measles outbreaks of the type we are now seeing. Now they are concerned that things might get worse.
Saloojee agrees that it isn’t possible to predict exactly how this outbreak will behave. “There are obviously three possible outcomes,” he says, “An increase, levelling off, or decline. My fear and expectation [are] that the outbreak will continue to expand. There are more than a million unvaccinated children under five, and possibly about 2.5 million unvaccinated under 15 years.
“We should be greatly concerned. It is highly likely that the outbreak will extend beyond the five provinces and affect all provinces in the country,” he says.
He adds that children are protected from measles through vaccination and if 95% of children are vaccinated against measles, then this herd immunity will protect the 5% who are not vaccinated. But in South Africa, measles coverage is not at 95%.
“In South Africa, at best, about 80% of children are vaccinated [against measles]. The proportion is lower in some provinces. Thus, all children, but particularly unvaccinated children, are at risk of acquiring measles,” he says. “We haven’t had a serious problem [with] measles in South Africa for at least the last 20 years. But in other low- and middle-income countries, it is still one of the five major causes of child mortality.”
Mass measles immunisation campaign needed
Saloojee tells Spotlight the only way to curtail the outbreak at this point is through a national supplementary mass measles immunisation campaign.
“There is only one option at this stage, as we are facing a crisis. A national supplementary immunisation campaign is warranted, despite its high cost and resource demands,” he says. “Such activities have already commenced in the affected provinces and will be extended to other provinces if the outbreak continues to spread. The aim of the campaign is to boost measles vaccine coverage to the 95% mark in the short term, so that herd immunity can kick in.”
How did we get here?
While such an immunisation campaign should help mitigate the current spread of measles, the question remains how a widespread outbreak could occur in the first place given South Africa’s well-established childhood immunisation programme.
“The outbreak was entirely predictable and preventable,” says Saloojee. “We have had similar outbreaks [about] every five years since 2000. Paradoxically, COVID delayed this outbreak, which should have happened in 2020 because the isolation measures protected against measles spread too.”
“However, we cannot run away from the fact that too few children receive all their routine vaccinations, and there is little being done to systematically change this such as stopping vaccine stockouts, and clinics and hospitals reducing missed opportunities to vaccinate eligible children,” he says. “If nothing is done, we can count on another outbreak in 2028.”
Countries across the world are reporting measles outbreaks, according to the CDC, which is being attributed to a disruption in services like routine immunisation because of the COVID pandemic. However, according to Saloojee, South Africa’s outbreak cannot be attributed exclusively to the pandemic disrupting services, instead, it is also due to years of suboptimal measles vaccine coverage.
Spotlight previously reported in-depth on results from the 2019 Expanded Programme on Immunisation (EPI) National Coverage survey, which showed that only around 77% (76.8%) of the children surveyed had received all fourteen age-appropriate vaccines from birth to 18 months. This includes the two doses of the measles vaccine.
Dr Lesley Bamford, a child health specialist in youth and school health at the National Department of Health, provided Spotlight with a table showing measles vaccination coverage per province between 2017 and 2022.
Note that the data only includes vaccinations provided in the public sector, whilst the denominator includes all children in South Africa. Graph courtesy of Dr Lesley Bamford, National Department of Health
According to the figures provided by Bamford, national coverage for the first dose of the measles vaccine has improved from 80% in 2017-2018 to 88% in 2021-2022. However, coverage for the second measles dose remained stuck in a narrow band from 77% to 80%, until 2021-2022, when it improved to 84% – still well below the 95% coverage required for herd immunity.
Expanded vaccination campaign
The NICD report shows the highest number of measles cases so far have been in the five to nine-year age group, which represents 40% of cases. 29% of cases were in the one to four age group and 17% in the 10 to 14-year age group. The remaining cases occurred in children younger than one year and those aged 15 and older.
According to McCarthy, based on the distribution of cases in these age groups, the NICD recommended to the National Department of Health that it extend its planned mass measles vaccination campaign to include children between six months and 15 years of age – which the Department has agreed to do.
Bamford tells Spotlight that a mass measles immunisation campaign had already been planned across all provinces for February 2023. But for the five provinces experiencing outbreaks, the timeline has since moved up. The four remaining provinces will still start their campaigns in February as planned.
“The target age group for that campaign has been extended. So, the initial plan was targeting children under 5 years of age and now in most provinces, it has been extended to include all children six months to 15 years of age,” she says.
Spokesperson for the National Department of Health, Foster Mohale confirms that all children between the ages of six months and 15 years, regardless of documentation, are eligible to receive their measles vaccination in the catch-up drive. “Most provinces have been vaccinating all children between 6 months and 15 years, with [or] without documents because diseases have no discrimination. So, we haven’t received any concern or report about non-vaccination of children without documentation,” he says.
Bamford adds that a measles incident management team has been established by the National Department of Health, which meets with the NICD and the provinces on a weekly basis.
She says Limpopo started its campaign in November, Mpumalanga and North West started in December, and Gauteng and the Free State started in January. The campaigns have so far been conducted mainly at primary healthcare clinics and outreach to ECD centres but now that the school year has resumed, children will also be vaccinated at schools.
Because the provinces all started at different times, there is no specific timeline for the vaccination campaign to be completed, according to Bamford, but the expectation from the National Department is that all provinces will wrap up their campaigns by mid-February when the HPV vaccination campaign kicks off.
“We know that measles coverage is suboptimal, and that is why we were planning to run a campaign, but of course, that is the single biggest reason why we are now experiencing these outbreaks,” she says. “The only way really to stop measles outbreaks is to improve immunisation coverage.”
A study of 104 children wearing pedometers to monitor daily activity showed that higher levels of physical activity are associated with reduced susceptibility to upper respiratory tract infections such as the common cold. Reporting the findings in Pediatric Research, the researchers suggest reduced inflammatory cytokines and improved immune responses as a possible mechanism.
Wojciech Feleszko, Katarzyna Ostrzyżek-Przeździecka and colleagues measured the physical activity levels and symptoms of upper respiratory tract infections of children aged between four and seven years in the Warsaw city region between 2018 and 2019. Participants wore a pedometer armband 24 hours a day for 40 days to measure their activity levels and sleep duration. For 60 days, parents used daily questionnaires to report their children’s symptoms of upper respiratory tract infections, such as coughing or sneezing. On a second questionnaire, parents reported their children’s vaccinations, participation in sport, whether they had siblings, and their exposure to smoking and pet hair.
The authors found that as the average daily number of steps taken by children throughout the study period increased by 1000, the number of days that they experienced symptoms of upper respiratory tract infections decreased by an average of 4.1 days. Additionally, children participating in three or more hours of sport per week tended to experience fewer days with respiratory tract infection symptoms than those not regularly participating in sports.
Higher activity levels at the beginning of the study were associated with fewer days with respiratory tract infection symptoms during the following six weeks. Among 47 children, with 5668 average daily steps during the first two weeks of the study period, the combined number of days during the following six weeks that these children experienced upper respiratory tract infection symptoms was 947. However, among 47 children whose initial average daily steps numbered 9368, the combined number of days during the following six weeks that these children experienced respiratory symptoms for was 724. Upper respiratory tract infection symptoms were not associated with sleep duration, siblings, vaccinations, or exposure to pet hair or smoking.
The authors speculate that higher physical activity levels could help reduce infection risk in children by reducing levels of inflammatory cytokines and by promoting immune responses involving T-helper cells. They also suggest that skeletal muscles could release small extracellular vesicles that modulate immune responses following exercise. However, they caution that future research is needed to investigate these potential mechanisms in children. In addition, since this was an observational study, causality could not be established.
Contrary to popular belief, rest may not always be the best treatment after a concussion, according to the results of a large multi-centre study published in JAMA Network Open. In fact, an early return to school may be associated with a lower symptom burden after suffering a concussion and, ultimately, faster recovery.
“We know that absence from school can be detrimental to youth in many ways and for many reasons,” says study lead author Christopher Vaughan, PsyD, neuropsychologist at Children’s National Hospital. “The results of this study found that, in general, an earlier return to school after a concussion was associated with better outcomes. This helps us feel reassured that returning to some normal activities after a concussion – like going to school – is ultimately beneficial.”
In this cohort study, data from over 1600 youths aged five to 18 were collected across nine paediatric emergency departments in Canada. Because of the large sample size, many factors associated with greater symptom burden and prolonged recovery were first accounted for through the complex statistical approach used to examine the data. The authors found that an early return to school was associated with a lower symptom burden 14 days post-injury in the 8 to 12 and 13 to 18-year-old age groups.
“Clinicians can now confidently inform families that missing at least some school after a concussion is common, often between 2 and 5 days, with older kids typically missing more school,” Dr Vaughan says. “But the earlier a child can return to school with good symptom management strategies and with appropriate academic supports, the better that we think that their recovery will be.”
The results suggest a possible mechanism of therapeutic benefit to the early return to school. This could be due to:
Socialisation (or avoiding the deleterious effects of isolation).
Reduced stress from not missing too much school.
Maintaining or returning to a normal sleep/wake schedule.
Returning to light-to-moderate physical activity sooner (also consistent with previous literature).
New clinical guidelines from the American Academy of Pediatrics (AAP) advise “immediate, intensive obesity treatment to each patient” upon diagnosis of childhood obesity. Published in the journal Pediatrics, these recommendations stands in marked contrast from other, previous guidelines.
The guidelines are summarised in key action statements, some of which recommend children ages 6 and up (and sometimes 2 to 5) with overweight or obesity to intensive health behaviour and lifestyle therapy.
In children 12 and older, the guidelines advise consideration of weight-loss pharmacotherapy. In case of severe obesity (BMI ≥35 or 120% of the 95th percentile for age and sex, whichever is lower) for adolescents 13 and older, clinicians should offer referrals for evaluation for metabolic and bariatric surgery.
Author Sarah Armstrong, MD, co-director of the Duke Center for Childhood Obesity Research told Medpage Today that “This is one of the most important messages that differentiates our current clinical practice guidelines from the prior recommendations, and that is to say 15 years of data have taught us that ‘watchful waiting’ only leads to greater increase in child BMI, accumulation of comorbidities, and more challenges in trying to reverse some of this.”
The guidelines also recommend regularly screening children ages 2 years and up for obesity, and comprehensively evaluating children and adolescents with overweight and obesity for related comorbidities.
Clinicians are also advised to treat children and adolescents for overweight/obesity and comorbidities concurrently, in line with principles of the chronic care model, using a non-stigmatising approach centred around the family.
The guidelines are based on a comprehensive evidence review of controlled and comparative effectiveness trials and high-quality longitudinal and epidemiologic studies. In a pair of accompanying technical reports, the authors give detailed descriptions of the evidence review behind the development of the guidelines.
An explanatory model presented in a thesis from University of Gothenburg may make simplify the understanding of autism development. It provides new insights into how various risk factors give rise to autism and why there is such great variability between individuals.
Autism, a neurodevelopmental condition, affects how people perceive the world around them and how they interact and communicate with others. Among individuals with autism, there are major differences in terms of personal traits and manifestations alike. The disorder is therefore usually described as a spectrum, with numerous subtle variations.
While theoretical, the new explanatory model is also practical in application, since its various components are quantifiable through testing. The model describes various contributing factors and how they combine to prompt an autism diagnosis and cause other neurodevelopmental conditions.
Three contributing factors
The model links three contributing factors. Together, these result in a pattern of behaviour that meets the criteria for an autism diagnosis:
Autistic personality – hereditary common genetic variants that give rise to an autistic personality.
Cognitive compensation – intelligence and executive functions, such as the capacity to learn, understand others, and adapt to social interactions.
Exposure to risk factors – for example, harmful genetic variants, infections, and other random events during gestation and early childhood that adversely affect cognitive ability.
“The autistic personality is associated with both strengths and difficulties in cognition but does not, as such, mean that diagnostic criteria are fulfilled. Still, exposure to risk factors that inhibit people’s cognitive ability may affect their capacity to tackle difficulties, which contributes to individuals being diagnosed with autism,” says Darko Sarovic, physician and postdoctoral researcher at Sahlgrenska Academy, University of Gothenburg, who wrote the thesis.
The model makes it clear that it is the many different risk factors combined that bring about the major differences among individuals on the spectrum. The various components of the model are supported by results from previous research.
Adaptive ability
High executive functioning skills may let people cover up their impairment, reducing their risk of meeting the diagnostic criteria for autism. This may explain why a lower degree of intelligence is observed among people diagnosed with autism, as well as other neurodevelopmental conditions. It also affords an understanding of why intellectual disability is more common among these groups. Thus, the model indicates that low cognitive ability is not part of the autistic personality but, rather, a risk factor that leads to diagnostic criteria being met.
“The autistic personality is associated with various strengths. For example, parents of children with autism are overrepresented among engineers and mathematicians. The parents themselves have probably been able to compensate for their own autistic personality traits and thus not met the criteria for an autism diagnosis. The impact of the disorder has then become more noticeable in their children owing, for instance, to an exposure to risk factors and relatively low cognitive ability,” Sarovic says.
Gender differences affect diagnosis
The diagnosis of autism is more common among boys than girls, and girls often get their diagnosis later in life. Some girls reach adulthood before being diagnosed, after many years of diffuse personal difficulties.
“Girls’ symptoms are often less evident to other people. It’s well known that girls generally have more advanced social skills, which probably means that they’re better at compensating for their own difficulties. Girls also tend to have fewer autistic traits and be less susceptible to the effects of risk factors. Accordingly, the model can help to answer questions about the gender gap,” Sarovic says.
Research and diagnostics
The model also proposes ways of estimating and measuring the three factors, enabling use of the model in research studies. Diagnostics is another conceivable area of use. In a pilot study in which 24 participants had been diagnosed with autism and 22 controls had not, measuring the three factors of the model enabled more than 93% to be correctly assigned to the right category. The model can also be used to explain the inception of other neurodevelopmental disorders, such as schizophrenia.
Analysing magnetic resonance imaging (MRI) brain scans of nearly 2000 children, researchers found children who played video games for three or more hours a day did better in cognitive skills tests involving impulse control and working memory compared to children who had never played video games. Published in JAMA Network Open, this study analysed data from the ongoing Adolescent Brain Cognitive Development (ABCD) Study, which is supported by the and other entities of the National Institutes of Health.
“This study adds to our growing understanding of the associations between playing video games and brain development,” said National Institute on Drug Abuse (NIDA) Director Nora Volkow, MD. “Numerous studies have linked video gaming to behaviour and mental health problems. This study suggests that there may also be cognitive benefits associated with this popular pastime, which are worthy of further investigation.”
Although a number of studies have investigated the relationship between video gaming and cognitive behaviour, the neurobiological mechanisms underlying the associations are not well understood. Only a handful of neuroimaging studies have addressed this topic, and the sample sizes for those studies have been small, with fewer than 80 participants.
To address this research gap, scientists at the University of Vermont, Burlington, analysed data obtained when children entered the ABCD Study at ages 9 and 10 years old. The research team examined survey, cognitive, and brain imaging data from nearly 2000 participants from within the bigger study cohort, comparing those who reported playing no video games at all and those who reported playing video games for three hours per day or more. This threshold was selected as it exceeds the American Academy of Paediatrics screen time guidelines, which recommend limiting videogames to one to two hours per day for older children. Researchers assessed their performance in two tasks that reflected the children’s ability to control impulsive behaviour and to memorise information, as well as brain activity while performing the tasks.
The researchers found that the children who reported playing video games for three or more hours per day were faster and more accurate on both cognitive tasks than those who never played. They also observed that the differences in cognitive function observed between the two groups was accompanied by differences in brain activity. Functional MRI brain scans found that children who played video games for three or more hours per day showed higher brain activity in regions of the brain associated with attention and memory than in never-gamers. At the same time, those children who played at least three hours of videogames per day showed more brain activity in frontal brain regions that are associated with more cognitively demanding tasks and less brain activity in brain regions related to vision.
The researchers think these patterns may stem from practicing tasks related to impulse control and memory while playing videogames, which can be cognitively demanding, and that these changes may lead to improved performance on related tasks. Furthermore, the comparatively low activity in visual areas among children who reported playing video games may reflect that this area of the brain may become more efficient at visual processing as a result of repeated practice through video games.
While prior studies have reported associations between video gaming and increases in depression, violence, and aggressive behaviour, this study did not find that to be the case. The three hours or more group tended to report higher mental health and behavioural issues compared to the non-gaming children, but was not statistically significant. The researchers note that this will be an important measure to continue to track and understand as the children mature.
Further, the researchers stress that this cross-sectional study does not allow for cause-and-effect analyses, and that it could be that children who are good at these types of cognitive tasks may choose to play video games. The authors also emphasise that their findings do not mean that children should spend unlimited time on their computers, mobile phones, or TVs, and that the outcomes likely depend largely on the specific activities children engage in. For instance, they hypothesise that the specific genre of video games, such as action-adventure, puzzle solving, sports, or shooting games, may have different effects for neurocognitive development, and this level of specificity on the type of video game played was not assessed by the study.
“While we cannot say whether playing video games regularly caused superior neurocognitive performance, it is an encouraging finding, and one that we must continue to investigate in these children as they transition into adolescence and young adulthood,” said Bader Chaarani, PhD, assistant professor of psychiatry at the University of Vermont and the lead author on the study. “Many parents today are concerned about the effects of video games on their children’s health and development, and as these games continue to proliferate among young people, it is crucial that we better understand both the positive and negative impact that such games may have.”
Through the ABCD Study, researchers will be able to track these children into young adulthood, looking for gaming-related changes in cognitive skills, brain activity, behaviour, and mental health.
Giving three years of chemotherapy to children with acute lymphoblastic leukaemia (ALL) instead of two years lowers the risk of their disease coming back after treatment by three times. The survival rate of all children with ALL, the most common form of childhood cancer, together has further increased to 94%. Less intensive therapy proved safe for three groups of children, resulting in a better quality of life. These findings on a large Dutch study into ALL were reported at the annual conference of the American Society of Hematology (ASH).
Many children with ALL have good outcomes. After two years of chemotherapy treatment, nine out of ten children are cured. But some children have a more aggressive disease, such as having the Ikaros mutation in their leukaemia cells, have a greater risk of recurrence after treatment. In order to improve the chances of survival and quality of life of all children with leukaemia, the treatment protocol has been continuously adapted over the years, based on the latest scientific insights.
Prof Rob Pieters, medical director and paediatric oncologist at the Princess Máxima Center for paediatric oncology in the Netherlands, presented the outcomes of the ALL-11 treatment protocol. The Dutch researchers tested the benefit of an adapted treatment in specific groups of children with leukaemia, including children with the Ikaros mutation. More than 800 children in the Netherlands were treated with this protocol between April 2012 and July 2020.
Threefold lower risk of recurrence
Children with Ikaros leukaemia received an extra year of chemotherapy in the ‘maintenance phase’ on top of the first two years of treatment. This change lowered the risk of their cancer coming back by threefold: this happened in only 9% of them, compared to 26% of the children in the previous treatment protocol.
87% of children with Ikaros leukaemia survived their disease for five years without their cancer coming back, an improvement on the 72% in the previous protocol. Because of the extra year of chemotherapy, this group of children had a slightly higher risk of infection, but these were treatable. The extended therapy did not lead to any additional side effects.
Analysis of data from all children with ALL, regardless of subtype, showed that the five-year survival rate has improved stepwise over the past 30 years from 80% to 94% under the ALL-11 protocol.
Safe reduction of treatment
In the ALL-11 protocol, doctors and researchers also looked at the benefit of a less intensive treatment plan for three groups of children. This included children with a leukaemia mutation linked to a very high chance of recovery, and children with Down syndrome who experience more severe side effects. These children received treatment without or with a lower dose of anthracyclines, a type of leukaemia drug that increases the risk of heart damage and infections. The reduced treatment proved successful: children had the same or even a better chance of survival, while their quality of life improved due to a lower risk of infections and damage to the heart.
Global interest
Globally, there is much interest in the Dutch research as it has been unclear how to improve therapy for children with Ikaros leukaemia. The results have now been presented for the first time at the largest blood cancer conference, and could lead to changes in treatment protocols for these children worldwide.
In the Netherlands, there are about 15 children with ALL each year for whom existing treatments stop working. Since 2019, they have been eligible for treatment with CAR T-cell therapy, a promising form of immunotherapy that now leads to a cure in 40% of these children.
Making a difference
Prof Monique den Boer, medical biologist and group leader at the Princess Máxima Center, played an important role in the adapted therapy for children with the Ikaros gene change. She says: ‘The Ikaros mutation was first discovered about 15 years ago in children with leukaemia who had a poor prognosis, partly thanks to the emergence of new DNA technologies. We saw that the cancer came back in many of these children shortly after the end of the two-year treatment plan. I am very proud that our lab findings have now found their way into the clinic and can make such a big difference for children with leukaemia.”
More cure with fewer side effects
Prof Pieters concludes: The five-year survival rate for children with acute lymphoblastic leukaemia has increased enormously since the 1960s, from zero to 94%, but the last steps are the most difficult. We are now one step closer to curing all children with ALL. We have also largely been able to remove a drug that poses a risk of heart damage from the treatment of children with a less aggressive form of the disease. The latest results for children with leukaemia therefore fit in perfectly with our mission: curing more children with cancer, with fewer side effects.”
The presence of food-specific IgA antibodies in the gut does not prevent peanut or egg allergies from developing in children, according to a Northwestern Medicine study published in Science Translational Medicine.
Scientists examined stool samples from more than 500 infants across the country and found that the presence of Immunoglobulin A, the most common antibody found in mucous membranes in the digestive tract, does not prevent peanut or egg allergies from developing later in life.
This discovery calls into question the role of Immunoglobulin A, or IgA, which was previously thought to be a protective factor against the development of food allergies.
While prior research had shown IgA could bind to and neutralide toxins and bacteria in the body, there was inconclusive evidence that IgA could do the same for food allergens, said Stephanie Eisenbarth, MD, PhD, senior author of the study.
“We were able to collaborate with different groups around the country to look at a number of different cohorts of children and young adults to ask: ‘Does the presence of IgA to peanut tell us that the person is tolerant to peanut?’,” said Eisenbarth. “We found that there really was no difference between kids who had peanut allergies and children who didn’t, and the same is true with egg allergies.”
The findings come as rates of allergies in children continue to climb: According to data from the Centers for Disease Control and Prevention, the number of children with allergies has more than doubled in the last 20 years.
Future directions for research will center on understanding the role IgA plays in people who have undergone immunotherapy and developed a tolerance to food allergens, Eisenbarth said.