Category: Paediatrics

Categories : PaediatricsTags :

Female Blood Donors Better for Very-low-birthweight Transfusions

On By ModernMedia
Photo by Hush Naidoo on Unsplash

The sex of adult blood donors may affect the risk of common complications in transfusions of red blood cells (RBCs) to premature or very-low-birthweight infants while in the neonatal intensive care unit (NICU), according to new research.

Anaemia is common in premature or very-low-birthweight infants, often requiring an RBC transfusion. Common negative outcomes that can occur with very low birth weight infants include necrotising enterocolitis, lung damage or retinopathy of prematurity. Studies provided conflicting evidence of transfusions being a risk factor.

The study was led by Dr Ravi Patel is director of neonatal research in the Department of Pediatrics at Emory University School of Medicine and Children’s Healthcare of Atlanta. Dr Patel and colleagues followed 181 very-low-birth-weight infants at three hospitals from 2010 to 2014. The infants were selected who received RBC transfusions from only male donors or only female donors.\

The study, published in JAMA Network Open, found that a typical very-low-birth-weight infant who received red blood cell transfusion from only female donors had a three times lower risk of negative outcomes than one who received red blood cells from only male donors.

Increasing donor age increased the protective effect of female donors. Some potential explanations for the protective effect could be reduced breakdown during storage of RBCs from female donors, along with less inflammation and more antioxidant capacity, the authors wrote.

RBC transfusion is common, according to Dr Patel, with about half of very low birth infants receiving at least one RBC transfusion while in the NICU. RBC transfusion is necessary to treat anaemia related to prematurity. In rare circumstances, this can lead to an infection or transfusion reaction. It is uncertain whether RBC transfusion increases the risks of some adverse clinical outcomes.
  Is it correct to say that the suspected mechanism for the difference in risk has to do with the characteristics of the RBCs, rather than immune differences, the suspected reason for the reverse effect in adults?

Future research should investigate inflammation or antioxidant capacity of red blood cells since these mechanisms may differ from adults, Dr Patel suggested.
Should their findings that age and sex have an effect on transfusion outcomes be confirmed, the next step would be transfusing blood from only males or only females, which could inform changes in practice.
Source: Emory University

Categories : Cancer PaediatricsTags :

Existing Drug Could Target Childhood Leukaemia

On By ModernMedia
Existing Drug Could Target Childhood Leukaemia

A new study published in PNAS has shown that the tumour-inhibiting gene TET2 is silenced in a large fraction of cases of acute lymphoblastic leukaemia (ALL) in children. The scientists show that the gene can be reactivated by an existing drug, 5-azacytidine, suggesting that it could be used a as targeted therapy for ALL in children.

“T-cell acute lymphoblastic leukaemia (T-ALL) is a devastating disease for the affected children and their families. One of five children affected do not survive the disease. The ultimate goal of my research is to ensure that all children can be cured. Our discovery may pave the way for clinical studies of 5-azacytidine as a new therapy for this poorly understood disease. The more treatment options we have for T-ALL the more chance we have of beating this aggressive cancer,” explained study leader Colm Nestor, senior lecturer in the Department of Biomedical and Clinical Sciences .

One of the characteristics of cancer cells is that they lose their cellular identity. One of the reasons for this is certain genes being silenced while others are activated. Switching genes on and off is controlled by epigenetic modification, where small chemical groups are attached to and removed from DNA, such as DNA methylation. The pattern of DNA-methylation is often altered in cancer cells, making them attractive targets for cancer drug research.

In the recently published study, the researchers were interested in an enzyme, TET2, that removes methyl groups from DNA. The gene that codes for TET2 is often affected by mutations in adult leukaemias. In children however, harmful mutations in TET2 are very rare, which led the researchers to speculate whether TET2 function is affected differently in child leukaemias. They analysed the gene expression patterns in cancer cells from more than 300 patients with T-ALL, and found that in many cases the TET2 gene was silenced.

It turned out that  methylation often silenced the TET2 gene. The scientists therefore decided to treat tumour cells in culture with a drug, 5-azacytidine, that removes methyl groups from DNA. This drug is used to treat certain leukaemias in adults.

“We found that one type of T-ALL cell, whose DNA seems to be highly methylated, is more sensitive to azacytidine than other cells that are not highly methylated. The drug actually turns silenced TET2 back on by demethylating it, so this might be a targeted therapy for a subset of cases. We suggest that azacytidine may have a doubled effect in these cells, since both the drug itself and TET2 kill cancer cells by demethylating the genome,” explained Colm Nestor.

Since 5-azacytidine is an approved drug, the researchers hope that it will be a much quicker path to treatment than when developing a novel drug.

“Chemotherapy agents have a broad effect and can be used for many patients, but they also kill healthy cells and can give rise to serious undesired effects. Targeted treatment, on the other hand, only works for a small fraction of patients, but is extremely specific. We need an arsenal of drugs to use for patients who experience relapses, and for those whose cancer does not respond to chemotherapy,” said Colm Nestor.

The researchers will continue with experiments to determine the effects of activating TET2 in these cancer cells, and to see if 5-azacytidine can function as targeted therapy in other types of cancer.

“The fact that we can target the loss of TET2 using the drug 5-azacytidine makes me hopeful that this treatment can help T-ALL patients in the future,” said researcher Maike Bensberg, PhD student at Linköping University.

Source: Linköping University

Categories : Cancer PaediatricsTags :

A Brief Window of Opportunity to Halt Certain Paediatric Gliomas

On By ModernMedia
Photo by Jeffrey Riley on Unsplash

In a pre-clinical study, investigators identified a vulnerability in a developmental signaling pathway that can be hijacked to drive paediatric low-grade glioma (pLGG) formation.

The study, published in Developmental Cell, demonstrated that targeted treatment prevents tumor formation, long before irreversible damage to the optic nerve can cause permanent loss of vision. This finding will inform chemo-prevention therapeutic trials in the future.

Brain tumours are the most common solid tumours in children, the most prevalent of which are pLGGs, of which 10 to 15% arise in patients with the familial cancer predisposition syndrome known as neurofibromatosis type 1 (NF1). Thi increases risks of developing tumours along the nerves and in the brain.

Almost 20% of children with NF1 develop pLGGs along the optic pathway, also known as NF1-associated optic pathway glioma (NF1-OPG). Despite many advances in cancer therapy, there are no definitive therapies available that prevent or alleviate the neurological deficits (i.e. vision loss) and that could improve the quality of life.

“The evidence presented can inform chemoprevention therapeutic trials for children with NF1-OPG. This therapeutic strategy may also be applicable to children with the developmental disorders that are at high risk of developing pediatric tumors, such as other RASopathies,” said Yuan Zhu, PhD, scientific director and Gilbert Family Endowed professor at the Gilbert Family Neurofibromatosis Institute and associate director of the Center for Cancer and Immunology Research.

The mechanism of vulnerability to pLGGs during development is not fully understood. It could be that the cell population of origin for this debilitating tumour is transiently proliferative during development. The NF1 gene produces a protein that inhibits MEK/ERK signalling, thereby helping regulate normal cell proliferation, survival and differentiation. With loss of NF1 function, it abnormally activates the MEK/ERK signalling pathway, leading to tumour formation.

Certain transient cells present during development of the brain and optic nerve are vulnerable to tumour formation because they depend on MEK/ERK signalling. Researchers identified cells dependent on the pathway and grew during a transient developmental window as the lineage-of-origin for NF1-OPG in the optic nerve. They then used a genetically engineered pre-clinical model to design a transient, low-dose chemo-preventative strategy, which prevented these tumours entirely.

“When we provided a dose-dependent inhibition of MEK/ERK signaling, it rescued the emergence and increase of brain lipid binding protein-expressing (BLBP+) migrating GPs glial progenitors, preventing NF1-OPG formation,” the researchers wrote. “Equally importantly, the degree of ERK inhibition required for preventing NF1-OPG formation also greatly improved the health and survival of the NF1-deficient model.”

Clinical trials using MEK inhibitors (MEKi) are underway for children as young as 1 month old, making the design of a chemo-preventative trial using a MEKi to treat children with NF1 more feasible. This treatment approach might not only prevent OPG formation, but also other NF1-associated and RASopathies-associated developmental defects and tumours.

Source: Children’s National Hospital

Categories : PaediatricsTags :

Only 10% of Children Completely ‘Outgrow’ ADHD

On By ModernMedia
Photo by Scott Webb on Unsplash

In contrast to popular belief, most children diagnosed with attention deficit hyperactive disorder (ADHD) do not in fact outgrow the disorder according to a new study in the American Journal of Psychiatry. Instead, it manifests itself in adulthood in different ways over a lifetime, increasing and decreasing.

“It’s important for people diagnosed with ADHD to understand that it’s normal to have times in your life where things maybe more unmanageable and other times when things feel more under control,” said lead researcher Margaret Sibley, associate professor of psychiatry and behavioral sciences at the University of Washington School of Medicine and a researcher at Seattle Children’s Research Institute.

Decades of research characterise ADHD as a neurobiological disorder typically first detected in childhood that persists into adulthood in approximately 50% of cases, but this study found that only 10% of children completely outgrow it.

“Although intermittent periods of remission can be expected in most cases, 90% of children with ADHD in the Multimodal Treatment Study of ADHD continued to experience residual symptoms into young adulthood,” they wrote.

ADHD is characterised by two main clusters of symptoms: inattentive symptoms which look like disorganisation and forgetfulness, and also the hyperactive, impulsive symptoms. In children, those symptoms look like having a lot of energy, such as running around and climbing on things. In adults, it manifests more as verbal impulsivity, difficulty with decision-making, and not thinking before acting. The disorder affects people differently and looks different depending on the phase of life.

Some people with ADHD also report a unique ability to hyper-focus, as in some Olympic athletes. While many people may experience symptoms similar to ADHD, it is estimated the disorder roughly affects 5% to 10% of the population, said Sibley.

This study followed a group of 558 children with ADHD from 8-years old to 25 years-old. Every two years, the cohort had assessments to determine whether they had symptoms of ADHD. Family members and teachers were also asked about their symptoms.

According to Prof Sibley, the belief that 50% of children outgrow ADHD was first put forward in the mid-1990s. Most studies, she said, only re-connected once when the kids reached adulthood and weren’t able to see if the ADHD had really gone away.

Coping with ADHD
Researchers have yet to find what causes ADHD to flare. Prof Sibley said it could be stress, the wrong environment, and not having a healthy lifestyle of proper sleep, healthy eating, and regular exercise. Also, if a person is not taking the time to manage symptoms and really understand what works best for them, then the symptoms are probably going to get more out of control, she said.

The two main treatments for ADHD are medication and therapy, though people can pursue their own healthy coping skills as well, said Prof Sibley.

Researchers found that most people who technically no longer meet criteria for ADHD in adulthood still retained traces though they were coping well.

“The key is finding a job or a life passion that ADHD does not interfere with,” Prof Sibley said. “You are going to see a lot of creative people have ADHD because they’re able to be successful in their creative endeavors despite having ADHD, whereas people who might be required to do very detail-oriented work at a computer all day—that could be a really hard combination for a person with ADHD.”

Prof Sibley said the time to seek professional help is when the symptoms cause problems in life, including not performing at one’s best, interpersonal problems, and inability to complete basic daily tasks.

Source: Medical Xpress

Categories : COVID PaediatricsTags :

Infant with COVID Airlifted Out as Texas Hospitals Fill Up

On By ModernMedia
Photo by Fas Khan on Unsplash
Photo by Fas Khan on Unsplash

An 11-month-old girl in Houston, Texas, had to be airlifted to a hospital in a different city because no paediatric hospitals in Houston would accept her as a transfer patient.

“She needed to be intubated immediately because she was having seizures,” said Patricia Darnauer, the administrator for LBJ Hospital. “We looked at all five major paediatric hospital groups and none [had beds] available.”

The little girl will be receiving treatment at Baylor Scott & White McLane Children’s Medical Center some 220 kilometres away.

The situation is sad but not surprising for Dr Christina Propst, who is one of the most outspoken pediatricians in Houston. Ever since the pandemic began in the US, Dr Propst has encouraged masking, social distancing, and being cautious to anyone who would listen.

“The emergency rooms at the major children’s hospitals here in Houston, the largest medical center in the world, are extremely crowded,” said Dr Propst. “They are filling, if not full, as are the hospitals and intensive care units.”

Delta variant infecting more children
Dr Propst and other clinicians ascribed the scarcity of paediatric beds, to the delta variant of COVID noticeably affecting more children, as well as being more transmissible. Texas Children’s Hospital has 30 children and adolescents hospitalised with COVID, compared to their January peak of 40.

However, the problem is worsened by widespread cases of Respiratory Syncytial Virus (RSV) in children. This is all taking place during the summer break for US schools, where doctors are used to injuries from playing outdoors.

Darnauer spoke of high numbers of patients at her hospital. “We are back beyond our pre-pandemic volumes at LBJ.”

Dr Propst advises mask wearing for those children not old enough for the vaccine, and she would also like to see Texas once again allow public schools to mandate masks. Unlike many other countries, COVID health regulations are largely up to individual states.

“If children are not masking in schools, it will be a major problem,” said Dr Propst.

She added that, even in normal times, the start of the school year generally causes a lot of germs to spread.

“It is typical that two weeks after school we see a great surge of strep and other sources of infection. We are bracing ourselves, not a question of when, it will be bad,” she said.

Source: ABC13

Categories : Metabolic Disorders PaediatricsTags :

A Restful Sleep for Diabetic Children with New Glucagon Administration

On By ModernMedia


A new treatment has been developed that promises a way to prevent potentially lethal hypoglycaemic episodes in children.

For children with Type 1 diabetes, the risk of experiencing a severe hypoglycaemic episode can be quite high. Undetected drops in blood sugar overnight can result in coma and death — an event known as ‘dead in bed syndrome’. As well as being a threat to the child, parents also suffer psychological stress worrying about the situation and often losing sleep.

In severe situations, glucagon injections can stabilise blood glucose levels long enough for parents to get their child medical attention. But in a new study, published in the Journal of the American Chemical Society, Matthew Webber, associate professor of chemical and biomolecular engineering at the University of Notre Dame, is rethinking the traditional use of glucagon as an emergency response by administering it as a preventive measure.

The study describes how Prof Webber and his team successfully developed hydrogels that remain intact in the presence of glucose but slowly destabilise as levels drop, releasing glucagon into the system and raising glucose levels.

“In the field of glucose-responsive materials, the focus has typically been on managing insulin delivery to control spikes in blood sugar,” Prof Webber said. “There are two elements to blood glucose control. You don’t want your blood sugar to be too high and you don’t want it to be too low. We’ve essentially engineered a control cycle using a hydrogel that breaks down when glucose levels drop to release glucagon as needed.”

The water-based gels a three-dimensional structure. Prof Webber describes them as having a mesh-like architecture resembling a pile of spaghetti noodles with glucagon “sprinkled” throughout. In animal models the gels dissolved as glucose levels dropped, releasing their glucagon.

Ideally in future applications, the gels would be administered each night before bed, Webber explained. “If a hypoglycaemic episode arose later on, three or five hours later while the child is sleeping, then the technology would be there ready to deploy the therapeutic, correct the glucose imbalance and prevent a severe episode.”

Since research is in extremely early stages, parents and individuals living with Type 1 diabetes should not expect a therapy available anytime soon, Prof Webber cautioned.

“One of the big challenges was engineering the hydrogel to be stable enough in the presence of glucose and responsive enough in the absence of it,” he said. Another challenge was preventing the glucagon from leaking out of the hydrogel’s mesh-like structure. Though the team was successful in this regard, Prof Webber said he hopes to improve stability and responsiveness with further study.

Source: EurekAlert!

Categories : Neurology PaediatricsTags :

Internal Body Sensing Ability Varies with Age

On By ModernMedia
Photo by Daniil Kuželev on Unsplash

A Chinese study has found that the ability to sense nervous signals such as heartbeat varies with age, peaking in young adulthood, but does not seem to be associated with autism.

Interoception is the ability to process and integrate internal signals originating from one’s body, such as heartbeats and breathing patterns. This ability is important for maintaining homeostasis. Recent findings have suggested that autism spectrum disorders are associated with a wide range of sensory integration impairments including interoceptive accuracy.

However, it is still not clear whether individuals with subclinical features of autism, which only moderately impact daily life, also exhibit similar impairments in interoceptive accuracy. It is also not clear how interoceptive ability and its association with autistic traits varies with age.

In order to address this issue, Dr Raymond Chan’s team from the Institute of Psychology of the Chinese Academy of Sciences (CAS) has developed an innovative paradigm involving eye-tracking measures to examine the multidimensional interoception and autistic traits in different age groups.

In so doing, they recruited 114 healthy university students aged 19–22 and explored the correlations among autistic traits and interoceptive accuracy using an “Eye-tracking Interoceptive Accuracy Task” (EIAT), which presents two bouncing shapes and requires participants to look at the one whiches bounces in time with their heartbeat.

Since this task requires no verbal report or button-pressing, it enables the exploration of interoceptive accuracy in preschool children and individuals with psychiatric disorders or speech impairments.

However, while autistic traits correlated significantly with the ability to describe and express emotion (alexithymia) but not with the different dimensions of interoception such as interoceptive accuracy (performance of interoceptive ability on behavioural tests), interoceptive sensibility (subjective sensitivity to internal sensations on self-report questionnaires) and interoceptive awareness (personal insight into interoceptive aptitude).

They then recruited 52 preschool children aged four to six, 50 adolescents aged 12–16 and 50 adults aged 23–54 to specifically examine the relationship of autistic traits and interoceptive accuracy across these three age groups. The researchers found that interoceptive accuracy evolves from childhood to early adulthood, and then declines with age. The highest average accuracy was seen in 12-16 year olds. The dataset showed that the developmental trajectory of interoceptive accuracy has a reverted U-shape trend peaking around early adulthood.

The findings suggest that interoceptive accuracy significantly differs between typically-developing preschool children, adolescents and adults. The study also highlights the need for future study into preschool children with suspected autism spectrum disorders.

Source: Medical Xpress

Categories : COVID PaediatricsTags :

Child Mask Study Which Reported High CO2 Levels Retracted

On By ModernMedia
Photo by Kelly Sikkema on Unsplash

A study which generated controversy by suggesting that masks may harm children through exposure to high carbon dioxide levels was retracted on Friday.

The research letter released in JAMA Pediatrics on June 30 had reported finding in a lab environment unacceptably high levels of CO2 by German standards in air inside masks worn by children.

The journal editors cited “numerous scientific issues” in the retraction notice, which also included questions over the applicability of the CO2 measurement device and the validity of the study’s conclusions.

“In their invited responses to these and other concerns, the authors did not provide sufficiently convincing evidence to resolve these issues, as determined by editorial evaluation and additional scientific review,” the notice read. “Given fundamental concerns about the study methodology, uncertainty regarding the validity of the findings and conclusions, and the potential public health implications, the editors have retracted this Research Letter.”

The study drew prompt criticism following its publication. Joseph Allen, MPH, DSc, who studies the impact of carbon dioxide on human health at Harvard School of Public Health in Boston, described the study as “terribly flawed”, predicting its retraction on Twitter. He pointed out that the study made no account of the flood of air taken in when children inhale, his key complaint.

The US Centers for Disease Control do not list any known risk wearing facing masks poses to children, and in fact, recently recommended that unvaccinated children wear masks when school reopen later this year. A previous study with adult volunteers had shown short-term but acceptable rises in CO2 when wearing masks,

While many areas of the US have dropped mask mandates, Los Angeles is reinstating its indoor mask mandate regardless of vaccination status as COVID cases and hospitalisations rise, presumably due to the spread of the Delta variant.

Source: MedPage Today

Categories : Injury & Trauma Mental Health PaediatricsTags :

Self-inflicted Firearm Injuries Among Rural Youth Three Times Urban Rates

On By ModernMedia
Photo by Annie Spratt on Unsplash
Photo by Annie Spratt on Unsplash

Emergency Department visits by youth for self-inflicted firearm injuries were three times more common in rural areas compared to urban ones, a national study has found.
The study, published in the Journal of Pediatrics found that Emergency Department (ED) visits by youth for self-harm were nearly 40 percent higher in rural areas compared to urban settings. Youth from rural areas presenting to the ED for suicidal ideation or self-harm also were more likely to need to be transferred to another hospital for care, which underscores the insufficient mental health resources in rural hospitals.

“Our study used pre-pandemic data, and we know that increased attention to youth mental health is even more pressing now everywhere, but especially in rural settings to prevent self-harm in youth,” said lead author Jennifer Hoffmann, MD, pediatric emergency medicine physician at Ann & Robert H. Lurie Children’s Hospital of Chicago and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “We need universal screening for suicidal ideation for all children and adolescents age 10 and up who present in the ED to identify youth at risk and intervene before tragedy occurs.”

The study drew on national data on suicidal ideation or self-harm in youth (ages 5-19 years) from a sample of EDs across the country, including those in general hospitals and children’s hospitals. The researchers extrapolated the results to arrive at national estimates.

Dr Hoffmann explained that a number of factors contribute to higher suicide rates and self-harm in rural youth. One of these is access to mental healthcare, which she said is a huge challenge. A lack of paediatric mental health professionals in rural areas is another factor, forcing patients to travel long distances for help. In addition, poor insurance coverage resulting from lower family income and unemployment. Small towns also have anonymity concerns, possibly delaying seeking care until a crisis brings the child to the ED. Firearm ownership is higher in rural firearms, so increased access to firearms may account for the high degree of disparity in self-inflicted firearm injuries.

“We need to improve mental health training for ED providers, allocate more resources and implement policies in rural hospitals on managing young patients who present with suicidal ideation or self-harm,” said Dr Hoffmann. “More widespread use of tele-psychiatry also might help prevent unnecessary transfers to other hospitals. But even more importantly, we need to train primary care providers to help diagnose and treat mental health issues earlier, so we can prevent self-inflicted injuries and death.”

Source: Ann & Robert H. Lurie Children’s Hospital of Chicago

Categories : Antibiotics Obstetrics & Gynaecology PaediatricsTags :

In Utero or Neonatal Antibiotic Exposure Could Lead to Brain Disorders

On By ModernMedia
Image by Ahmad Ardity from Pixabay
Image by Ahmad Ardity from Pixabay

According to a new study, antibiotic exposure early in life could alter human brain development in areas responsible for cognitive and emotional functions.

The study suggests that penicillin alters the body’s microbiome as well as gene expression, which allows cells to respond to its changing environment, in key areas of the developing brain. The findings, published in the journal iScience, suggest reducing widespread antibiotic use or using alternatives when possible to prevent neurodevelopment problems.
Penicillin and related medicines, such as ampicillin and amoxicillin, are the most widely used antibiotics in children worldwide. In the United States, the average child receives nearly three courses of antibiotics before age 2, and similar or greater exposure rates occur elsewhere.

“Our previous work has shown that exposing young animals to antibiotics changes their metabolism and immunity. The third important development in early life involves the brain. This study is preliminary but shows a correlation between altering the microbiome and  changes in the brain that should be further explored,” said lead author Martin Blaser, director of the Center for Advanced Biotechnology and Medicine at Rutgers.

In the study, mice were exposed to low-dose penicillin in utero or immediately after birth. Researchers found that, compared to the unexposed controls, mice given penicillin had large changes in their intestinal microbiota, with altered gene expression in the frontal cortex and amygdala. These two key brain areas are responsible for the development of memory as well as fear and stress responses.

Increasing evidence links conditions in the intestine to the brain in the ‘gut-brain axis‘. If this pathway is disturbed, it can lead to permanent altering of the brain’s structure and function and possibly lead to neuropsychiatric or neurodegenerative disorders in later childhood or adulthood.

“Early life is a critical period for neurodevelopment,” Blaser said. “In recent decades, there has been a rise in the incidence of childhood neurodevelopmental disorders, including autism spectrum disorder, attention deficit/hyperactivity disorder and learning disabilities. Although increased awareness and diagnosis are likely contributing factors, disruptions in cerebral gene expression early in development also could be responsible.”

Whether it is antibiotics directly affecting brain development or if molecules from the microbiome travelling to the brain, disturbing gene activity and causing cognitive deficits needs to be determined by future studies.

Source: Rutgers University-New Brunswick