Category: Paediatrics

Chinese Study Finds Children More Likely to Spread COVID

Photo by Kelly Sikkema on Unsplash

By gaining access to a high quality COVID transmission data from a northern Chinese city which enforced stringent lockdowns, scientists concluded that young people were most responsible for an increase in direct and secondary infections, and also determined that county-wide lockdowns proved effective in limiting the virus’s spread.

The research study, led by Professor of Sociology Zai Liang at University of Albany, was given rare access to patient profiles and contact tracing data from every case accompanying the outbreak of the virus in Shijiazhuang from January to February in 2021. “Because of universal testing and digital tracing, the data are of high quality,” said Prof Liang, who was assisted by Sociology PhD student and lecturer Han Liu. Liu is from Shijiazhuang and has connections with that city’s CDC research centre, which enabled them to get the data.

The two UAlbany researchers, joined by two colleagues from China, published their findings in the Journal of Urban Health.

Prof Liang wrote that while individual-level contact tracing studies on the virus’s transmission and mitigation efforts have been growing, “because of limited testing capacities and risks of infringing on privacy, surveillance data used in individual-level research usually have limited representativeness.” His Shijiazhuang study, whose analysis included 99.52 percent (1028 of 1133) of the transmitted cases in Shijiazhuang, is designed “to fill this gap in the literature.”

The research examined sociodemographic factors including age, gender and socioeconomic status, postulating that “certain sociodemographic characteristics may facilitate the spread of germs by exposing the host to more social contacts.” This would include children interacting in the classroom, females having more contact with their relatives than do males, and less affluent workers working or living in overcrowded settings.

Among the study’s results are:

  • Children 0–17 years old had fewer close contacts than adults, but these led to more secondary infections: 32.1% infected children, 67.9% adults
  • Close contacts of children were 81% more likely to be infected than the contacts of those 18–49
  • Peasant workers, compared to non-manual workers, had 40% more secondary cases from the same neighbourhoods.

Prof Liang wrote, “While children have a low probability of having severe symptoms after being infected by COVID, they can seed the spread in the larger society by infecting their household members and other adults living in their neighbourhoods. These adults can then transmit the disease to their own social contacts. Future studies on how to control within-school infections are therefore urgently needed.”

Another major conclusion of the Shijiazhuang study is that timely non-pharmaceutical interventions, including restrictions on gatherings and school closures, effectively contained further infections via contact reduction, especially when implemented in small areas with the highest caseloads. Liang acknowledged that school closures did have negative ramifications for children’s education and socialisation.

Serendipitous data collection

How did Prof Liang and colleagues obtain comprehensive data not yet publicly available to others? “We heard of this COVID outbreak in this part of northern China early last year, when I was working on a proposal to study COVID. I asked Han Liu if we had connections in that city. It turned out that he is originally from Shijiazhuang and has connections with that city’s CDC research centre.

“The two researchers who collected the data agreed to join us in this effort. I am lucky to ask the right question at the right time.”

Source: University at Albany

Paediatric Kidney Transplants without Immunosuppressive Drugs

Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Stanford Medicine physicians have developed a way to provide paediatric kidney transplants without immunosuppressive drugs. Their key innovation is a safe method to transplant the donor’s immune system to the patient before surgeons implant the kidney.

The medical team has dubbed the two-transplant combination a “dual immune/solid organ transplant,” or DISOT. The first three DISOT cases, all performed at Lucile Packard Children’s Hospital Stanford were described in the New England Journal of Medicine, accompanied by an an editorial about the research.

The Stanford innovation removes the possibility that the recipient will experience immune rejection of their transplanted organ, the most common reason for a second organ transplant The new procedure also rids recipients of the substantial side effects of a lifetime of immune-suppressing medications, including increased risks for cancer, diabetes, infections and hypertension.

“Safely freeing patients from lifelong immunosuppression after a kidney transplant is possible.”

Alice Bertaina, MD, PhD, report’s lead author, associate professor of paediatrics, Stanford University

The first three DISOT patients were children with a rare immune disease, but the team is expanding the types of patients who could benefit. The protocol received FDA approval on May 27, 2022, for treating patients with a variety of conditions that affect the kidneys. Dr Bertaina anticipates that the protocol will eventually be available to many people needing kidney transplants, starting with children and young adults, and later expanding to older adults. The researchers also plan to investigate DISOT’s utility for other types of solid-organ transplants.

The scientific innovation from Dr Bertaina’s team has another important benefit: It enables safe transplantation between a donor and recipient whose immune systems are genetically half-matched, meaning children can receive stem cell and kidney donations from a parent.

The advance is especially meaningful for Jessica and Kyle Davenport of Muscle Shoals, Alabama. Their two children, both born with a rare and potentially deadly immune disease, are among the first recipients of DISOT: 8-year-old Kruz received transplants from Jessica, while his 7-year-old sister, Paizlee, received transplants from Kyle.

“They’ve healed and recovered, and are doing things we never thought would be possible,” said Jessica Davenport. After years of helping Kruz and Paizlee cope with severe immune deficiency and its attendant infection riskk as well as kidney dialysis, she and her husband are thrilled that their children have more normal lives.

The idea of transplanting a patient with their organ donor’s immune system has been around for decades, but it has been difficult to implement. Transplants of stem cells from bone marrow provide the patient with a genetically new immune system, as some of the bone marrow stem cells mature into immune cells in the blood. First developed for people with blood cancers, stem cell transplants carry the risk of the new immune cells attacking the recipient’s body, a potentially lethal complication called graft-versus-host disease.

Source: Stanford Medicine

Early Intervention in Spinal Muscular Atrophy is Key

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According to the results of a new study published in Developmental Medicine & Child Neurology, early identification and treatment of patients with spinal muscular atrophy (SMA) can greatly reduce the total financial costs associated with the condition. 

A genetic disorder, SMA is characterised by progressive muscle weakness, reduced tone with associated destruction of alpha motor units. There are four main subtypes of spinal muscular atrophy defined by the age of onset and severity with type 0 presenting in utero and causing death within the first months of life and type 4 in adulthood, causing mild weakness and no effect on lifespan. Understanding the underlying pathophysiology, subtypes, and emerging treatments is key to treating patients with spinal muscular atrophy effectively.

Analysing the data of 149 SMA patients, (93 untreated, 42 treated after symptoms arose, and 14 treated after early diagnosis), the total societal cost was lower in untreated patients (due to high drug costs in treated patients), but costs were lower for treated patients who were identified by newborn screening than for treated patients identified due to the development of symptoms. 

“These data are important as they are issued from a real-life prospective collection. They demonstrate clearly that as long as the decision to reimburse treatments for SMA has been made, newborn screening becomes a no-brainer—not only because it gives patients a much better future, but also because it saves a significant amount of money for the taxpayer,” said senior author Laurent Servais, PhD, of the University of Liege, in Belgium and the University of Oxford, in the UK. “Using these data issued from the real world, we are working currently on a model that estimates the lifetime cost of the different strategies.” 

Source: Wiley

Older Siblings Confer Healthy Development

Children
Photo by Ben Wicks on Unsplash

Being a younger sibling in a family can have more benefits than simply being spoiled by the parents. A new study, published in BMC Public Health, reveals that older siblings confer a protective effect on the behaviours of their younger brothers and sisters.

Exposure environmental stressors during critical periods of life, especially to maternal stress while in the womb, can have negative long-term consequences for children’s development.

In a new study, researchers used longitudinal data from the LINA cohort (Lifestyle and environmental factors and their Influence on the Newborn Allergy risk) to test 373 German mother-child pairs, from pregnancy until 10 years of age. 

Mothers were asked to fill in three validated questionnaires, to assess their stress levels and their child’s behavioural problems. First, the researchers assessed which social and environmental factors were linked to an increase in maternal stress levels during pregnancy, and the long-term consequences of maternal stress on the occurrence of child behavioural problems. Second, the researchers assessed whether the presence of siblings had a positive effect on the occurrence of child behavioural problems, by directly reducing stress levels and increasing children’s psychological well-being, or by indirectly buffering the negative consequences of maternal stress. 

Prenatal stress can cause behavioural problems in the child

The results of the study showed that socio-environmental stressors, like the lack of sufficient social areas in the neighbourhood, were clearly linked to an increase in maternal stress levels during pregnancy. Moreover, mothers who had experienced high stress levels, like worries, loss of joy or tension, during pregnancy were also more likely to report the occurrence of behavioural problems when their children were 7, 8 or 10 years old. “These results confirm previous findings about the negative impact that even mild forms of prenatal stress might have on child behaviour, even after several years, and highlight the importance of early intervention policies that increase maternal wellbeing and reduce the risks of maternal stress already during pregnancy,” explained Federica Amici, one of the researchers involved in the project.

On a more positive note, the study also found a lower occurrence of behavioural problems in children with older siblings. “Children who have older brothers or sisters in their households are less likely to develop problems, which suggests that siblings are crucial to promote a healthy child development,” explained Gunda Herberth, coordinator of the LINA study. 

Higher social competence thanks to older siblings?

This study further suggests that the presence of older siblings directly reduced the risk of developing behavioural problems, but did not affect negative effects of maternal stress on child behaviour. How could older siblings reduce the occurrence of behavioural problems in children? By interacting with their older siblings, children may develop better emotional, perspective taking and problem solving skills, which are linked to higher social competence and emotion understanding. Moreover, the presence of older siblings may provide learning opportunities for parents, who might thus develop different expectations and better parental skills. 

“We were especially impressed by the important role that siblings appear to play for a healthy child development,” concluded researcher Anja Widdig. “We hope that our findings will draw attention to the importance of public health policies that directly target children and their siblings, and promote a healthy environment for their well-being and the development of high-quality sibling relationships”.

Source: Helmholtz Centre for Environmental Research

The Process of Remission from Peanut Allergy Mapped Out

Credit: NIH

An Australian study published in Allergy, has identified the key immunological changes that support the remission of peanut allergy in children, a discovery that could pave the way to new, more targeted treatments.

The research showed, for the first-time, that specific gene networks are rewired to drive the transition from peanut allergy to clinical remission following a combination treatment of a probiotic and peanut oral immunotherapy.

The study found that this network reprogramming essentially shuts down the allergic immune response that was responsible for causing a food allergy.

Lead researcher, Professor Mimi Tang of Murdoch Children’s Research Institute, said this was the first study to map the complex gene to gene communication and connectivity underlying clinical remission of peanut allergy.

“The immunological changes leading to remission of peanut allergy were largely unknown,” she said. Previous studies had mostly focused on examining the levels of gene expression, without also exploring how genes interact with each other. But genes don’t work in isolation; instead, biological responses are controlled by large numbers of genes communicating with each other, so it made sense to look at these interactions more closely.

“What we found was profound differences in network connectivity patterns between children who were allergic and those who were in remission. These same changes were also seen when we compared gene networks before and after immunotherapy in the children who achieved remission following immunotherapy.”

The randomised controlled trial involved 62 peanut allergic children, ages 1–10, who received a combination treatment of a probiotic and oral immunotherapy (gradual introduction of the allergen) or a placebo. Following 18 months of treatment, 74% taking the combination treatment achieved remission compared with 4% in the placebo group.

The peanut oral immunotherapy that was used in combination with the probiotic in the trial was PRT120, a lead candidate from biotech company Prota Therapeutics.

The team led by Professor Tang also recently showed in a separate trial that two treatments — the combination probiotic and peanut oral immunotherapy treatment and the peanut oral immunotherapy alone — were highly effective at inducing remission and desensitisation. About half of the treated children achieved remission, which allowed them to stop treatment and safely eat peanut freely.

Murdoch Children’s Dr Sarah Ashley said while oral immunotherapy could successfully induce desensitisation and remission, desensitisation often waned after treatment ended or even during ongoing maintenance dosing.

“Certain changes in the allergen-specific immune cells, called Th2 cells, are critical to achieving lasting remission,” she said. Th2 cells are essential for generating allergen-specific antibodies and the development of food allergy. We found that the Th2 signalling that drives allergy is ‘turned off’ in children in remission.”

Food allergy is a global public health concern, affecting 10% of infants and 5–8% of children.

Source: Murdoch Children’s Research Institute

New Ambulatory BP Monitoring Guidance for Children and Adolescents

Boys running
Photo by Margaret Weir on Unsplash

An American Heart Association scientific statement reviewing new evidence and guidance on ambulatory blood pressure monitoring (ABPM) of children and adolescents published in the journal Hypertension.

The statement provides simplified classifications for ABPM in children and adolescents. ABPM is designed to evaluate a person’s blood pressure during daily living activities, including times of physical activity, sleep and stress.

Key points of the statement:

  • The statement provides simplified classifications for ambulatory blood pressure monitoring (ABPM) in children and adolescents. ABPM is designed to evaluate a person’s blood pressure during daily living activities, including times of physical activity, sleep and stress.
  • The new classifications come with guidance on when ABPM is appropriate and how to interpret monitoring results.
  • Children who have medical diagnoses, such as kidney disease, may have normal office blood pressure but significant abnormalities noted on ABPM. Without taking ABPM into account, this can lead to a more benign prognosis.
  • Elevated childhood blood pressure is linked to heart and kidney damage during youth and adulthood, as well as brain changes associated with worse cognitive function.
  • ABPM helps ease concern of spikes in blood pressure caused by measurement anxiety, known as white coat hypertension, and helps assess daily blood pressure patterns.
  • ABPM is used to confirm whether a child or adolescent with high blood pressure during a clinic measurement truly has hypertension.

Source: American Heart Association

Analysis Finds that Early Interventions in Autism are Effective

Children
n Photo by Ben Wicks on Unsplash

In a Cochrane analysis of therapeutic or educational interventions for very young children with or at high likelihood for autism, researchers found that certain types of interventions were beneficial. The analysis, published in Developmental Medicine & Child Neurology, included seven reviews which summarised the results of 63 studies from 2009 to 2020.

The analysis found that naturalistic developmental behavioural interventions, developmental interventions, and behavioural interventions were effective.

Heterogeneity in design, intervention and control group, dose, delivery agent, and measurement approach was noted. Inconsistent methodological quality and potential biases were identified.

“We have a growing evidence base that supports the importance of early intervention and its ability to promote communication, adaptive behavior, and facilitate social interactions and relationships. However, there are limitations to this evidence base, which leaves families with some work to do in order to understand which approach is the best fit for themselves, their child, or their family,” said lead author Lauren Franz, MBChB, MPH, of Duke University Medical Center.

Source: Wiley

A Tangled Web of Brain Damage from Concussions in Children

Boy hanging from tree
Photo by Annie Spratt on Pexels

Concussion may cause different types of brain damage which lead to similar symptoms in children, according to research published in eLife. A new way of studying concussions could help inform the development of future treatments.

While most children fully recover after a concussion, some will have lasting symptoms. The findings help explain the complex relationships that exist between symptoms and the damage caused by the injury.

The researchers found that certain combinations of brain damage were associated with specific symptoms such as attention difficulties. Other symptoms, such as sleep problems, occurred in children with multiple types of injuries. For example, damage to areas of the brain that are essential for controlling sleep and wakefulness could cause challenges with sleeping, as could damage to brain regions that control mood.

The brain’s white matter holds clues

To do this, they examined how damage to the brain resulting from concussion affected its structural connection network, known as white matter. They then used statistical modelling techniques to see how these changes related to 19 different symptoms reported by the children or their caregivers.

Analysing symptoms may advance treatment

“Despite decades of research, no new treatment targets and therapies for concussions have been identified in recent years,” said lead author Guido Guberman, a Vanier Scholar and MDCM Candidate at McGill University. “This is likely because damage to the brain caused by concussions, and the symptoms that result from it, can vary widely across individuals. In our study, we wanted to explore the relationships that exist between the symptoms of concussion and the nature of the injury in more detail.”

Guberman and his colleagues analysed data collected from 306 children, aged nine to 10 years old, who had previously had a concussion. The children were all participants in the Adolescent Brain Cognitive Development (ABCD) Study.

“The methods used in our study provide a novel way of conceptualising and studying concussions,” says senior author Maxime Descoteaux, a Professor of Computer Science at Université de Sherbrooke. “Once our results are validated and better understood, they could be used to explore potential new treatment targets for individual patients. More broadly, it would be interesting to see if our methods could also be used to gather new insights on neurological diseases that likewise cause varied symptoms among patients.”

Source: McGill University

How Do You Do, Fellow Kids? Making Anti-vaping Messaging Work

Vaping with an e-cigarette
Photo by Toan Nguyen on Unsplash

Effective anti-vaping advertisements geared to teens have the greatest impact when they emphasise the adverse consequences and harms of vaping e-cigarettes, use negative imagery, and avoid memes, hashtags and other ‘teen-centric’ communication styles, according to a first-of-its-kind study by researchers in the journal Tobacco Control.

The researchers also found that certain messaging content currently being used, especially sweets and flavour-related imagery, increases the appeal of vaping and should be avoided when designing prevention messages.

“E-cigarettes and vaping have become a major public health concern, with nicotine addiction and other harmful outcomes looming large for youth,” said Seth M. Noar, PhD, the paper’s corresponding author and UNC Lineberger professor. “The percentage of teens vaping increased from about 5% in 2011 to over 25% in 2019,” Prof Noar said. “That is an alarming trend, making an understanding of effective vaping prevention messages especially urgent.”

Since the introduction of e-cigarettes, numerous US health departments have created their own anti-vaping messaging geared to teens, as have national health organisations such as the US Food and Drug Administration and Centers for Disease Control and Prevention.

The online study asked 1501 teens to rate seven randomly selected vaping prevention ads from a pool of more than 200 ads. Vaping prevention ads that clearly communicated the health harms of vaping, or compared vaping to cigarette smoking, were comparatively more effective. Neutral or less personally relevant content, such as referencing the environmental impact of vaping or the targeting of youth by the tobacco industry, was less impactful.

“Although we anticipated that vaping prevention ads with neutral or pleasant imagery would not be as effective, we were alarmed to find that flavour-related messages actually heightened the attractiveness of vaping,” said Marcella H. Boynton, PhD, first author

“In retrospect, it stands to reason that by reminding teens about pleasurable aspects of e-cigarettes, even within the context of a prevention ad, we run the risk of doing harm. Notably, we found that flavour-related prevention ad content was associated with vaping appeal among both users and non-users of e-cigarettes, which is a good reminder of how much candy and fruit flavours in e-cigarettes have driven the youth vaping epidemic.”

The researchers hope to next investigate the effects of other types of anti-vaping ads on a wide range of audiences. They also are developing a series of messages and a companion website to test the ability of a text message-driven intervention to reduce youth vaping. In that regard, Prof Noar noted that “We have been developing our own evidence-based messages based on the latest science about the harms of vaping. Our messaging approach has been greatly influenced by the insights generated by this study.”

The study used UNC’s Vaping Prevention Resource, a website designed to provide practitioners, researchers and communities with vaping prevention media content from around the world, as well as strategies and resources for youth vaping prevention. It is the largest repository of free, open-access vaping prevention materials, all available for download at https://vapingprevention.org/.

Source: UNC Lineberger Comprehensive Cancer Center

PFAS and Phthalates Linked to Reduced Bone Density in Teen Boys

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Per- and polyfluoroalkyl substances (PFAS) and phthalates (two types of endocrine-disrupting chemicals) may be associated with lower areal bone mineral density (aBMD) in teenage boys, according to a new study published in the Journal of Clinical Endocrinology and Metabolism.

Endocrine disrupting chemicals (EDCs) and potential EDCs are mostly man-made found in various materials. By interfering with the body’s endocrine system, endocrine disruptors produce adverse developmental, reproductive, neurological, and immune effects in humans, abnormal growth patterns and neurodevelopmental delays in children. These include per- and polyfluoroalkyl substances (PFAS) are used in non-stick pots and pans, clothing and food packaging, and are increasingly being found in US water supplies. Phthalates are used in medical devices, personal care products, food processing and children’s toys.

“Adolescence is an important time when our bodies build up bone. Almost all US children and adolescents are exposed to PFAS and phthalates, but few studies have looked at how these chemicals could be impacting our bone health,” said Abby F. Fleisch, MD, MPH, of the Maine Medical Center Research Institute and Maine Medical Center. “Our research found an association between certain PFAS and phthalates and reduced bone mineral density in adolescent males. Because bone accrual primarily occurs during adolescence, if replicated, this finding may have implications for lifelong bone health.”

The researchers accessed data on urine and blood samples from 453 boys and 395 girls from the National Health and Nutrition Examination Survey (NHANES). Participants were on average 15.1 years old, and found that higher levels of PFAS and phthalates may be associated with lower aBMD in adolescent males. The same effect was not found in girls; rather a slight increase in aBMD was observed for certain PFAS and phthalates.

The researchers noted that bone mineral density tracks across a lifetime, so if the same results are seen in longitudinal cohorts, this finding may have implications for lifelong skeletal health.

Source: The Endocrine Society