Tag: paediatrics

Categories : Paediatrics Respiratory DiseasesTags :

Surprising Finding Links Asthma Risk to Meat Consumption as Infants

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Researchers looking for post-breastfeeding dietary patterns in two prospective birth cohorts, were surprised to discover meat consumption as a predictive factor.

Alexander Hose, MA, MPH, of Ludwig Maximilian University in Munich presented the study’s findings at the virtual European Respiratory Society annual meeting. 

After switching from breast milk, babies up to age 1 whose protein intake came largely from meat products, rather than dairy, fish, or egg proteins, had a more than eight-fold greater chance of developing asthma by age 6 versus non-meat protein consumption. Asthma prevalence reached 30% in some subgroups.

Wheezing was more common in this diet pattern, which Hose and colleagues termed “unbalanced meat consumption” (UMC); this continued up to age 10, with a five times higher odds.

The duration of breastfeeding was an important factor, likely because switching to baby foods prolonged the exposure. Odds of developing asthma by age 6 increased nearly 12-fold in UMC-fed infants whose breastfeeding stopped by week 19, versus about four-fold in those continuing longer on breast milk.

In addition, UMC was also linked to a certain intestinal microbiome profile featuring unusually high levels of Lactococcus, Granulicatella, and Acinetobacter species.

This type of microbiome scavenges iron in the gut, Hose said, which could explain why the children became especially susceptible to asthma. Additionally, milk proteins may exert an opposite effect on asthma risk by generating a type of “nutritional immunity.”

While the mechanism connecting the gut microbiome to respiratory disease is unknown, the existence of a ‘gut-lung axis‘ is well established; a recent trial showed that probiotics can prevent coughs and wheezing in older adults. The phenomenon has also been considered for COVID’s gastrointestinal symptoms.

A pair of European birth cohort studies, PASTURE and LUKAS2, provided the data for the study. In these, about 1400 infants were followed through age 10 and parents kept detailed records of their infants’ feeding, and other environmental factors, and children’s medical records were accessed as well.

However, a key limitation is the cohorts being from rural areas since investigating asthma’s relationship to animal exposure was a key goal for the studies. Partly because of this, Hose and colleagues were able to separate out ‘industrial’ meat, milk, and yoghurt from that produced at home. A trend toward greater asthma risk was observed with store-bought protein products.

Source: MedPage Today

Categories : Gender PaediatricsTags :

Study Highlights Role of Sex Hormones in Behavioural Development

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A new study shows that sex hormones are important for developing gender role behaviours in boys, such as active play.

In laboratory animals, sex differences in behaviour arise from different hormone levels produced by males and females influence patterns of gene expression in the developing brain. However, the origins of sex differences in human behaviour are not as well understood.

“In the lab, you can do experiments on how these hormones affect animal brains and perform other experimental manipulations. We can’t do those things to people, so we looked to a natural experiment,” explained study leader David Puts, associate professor of anthropology.

Prof Puts and his collaborators made use of a natural experiment called isolated GnRH deficiency (IGD), a rare endocrine disorder. Individuals with IGD lack sex hormones from the second trimester of development right through until they begin hormone replacement therapy to induce puberty. However, as the external genitals develop earlier, during the first trimester, people with IGD are clearly male or female at birth, and are raised according to their sex. 

IGD therefore presents the chance to study the behaviour of those raised as boys but exposed to low testicular hormones, or raised as girls but exposed to low ovarian hormones.

The researchers compared 97 individuals with IGD (a small number due to its rarity) to 1665 individuals with typical hormonal development. Differences in behaviour were investigated; boys being encouraged toward active play, girls pushed to more passive pursuits. The researchers asked subjects to recall behaviours they had as children.

“We asked them, ‘When you read a book, were you the male or female in the story?’, ‘Where your friends boys or girls?’, ‘Did you play with dolls or trucks?’,” said Talia N Shirazi, doctoral recipient in anthropology now working in the reproductive health industry.

These childhood gender role behaviours are among the largest differences in behaviour between sexes, Prof Puts said. Typically, males will say they were the male character, played with other boys and preferred trucks, while females will say they were the female character, played with other girls and preferred dolls.

However, males with IGD reported more gender non-conforming in this regard. The researchers found in that men with IGD recalled a higher level of childhood gender non-conformity than typical men, while women with IGD did not differ from typical women in childhood gender conformity.

‘”We don’t see this effect in the women with IGD,” said Shirazi, indicating that low levels of ovarian hormones does not significantly impact childhood gender role behaviours.

“Our results suggest that in humans, androgens, such as testosterone produced by the testes, influence male brain development directly as they do in other mammals, rather than only indirectly by influencing external appearance and consequently gender socialisation,” said Prof Puts. “Both the direct influence of androgens on the developing brain and gender socialisation probably play important roles in producing sex differences in childhood behaviour.”

Prof Puts and Shirazi agree that despite their modest sample of participants with IGD, they are encouraged that the results were very similar in subjects who came from a clinical setting and those recruited from support groups.

“It would be nice to be able to identify people with IGD when they are younger, before they reach what should be puberty,” said Shirazi. “We need to focus on recruitment for our studies because there is a lot that can be learned about the cause of gender behaviours.”

Source: Penn State

Categories : PaediatricsTags :

Glasses Boosts Academic Performance for Students Who Need Them

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Students receiving eyeglasses through a school-based initiative scored higher on reading and math tests, found in the largest clinical study of the impact of glasses on education ever conducted in the US. Students struggling the most academically showed the greatest improvement.

The study by Johns Hopkins researchers from the Wilmer Eye Institute and School of Education is published in JAMA Ophthalmology.

“We rigorously demonstrated that giving kids the glasses they need helps them succeed in school,” said senior author Megan Collins, a paediatric ophthalmologist at the Wilmer Eye Institute. “This collaborative project with Johns Hopkins, Baltimore City and its partners has major implications for advancing health and educational equity all across the country.”

The team studied students who received eye examinations and glasses through the Vision for Baltimore program. The effort was launched in 2016 after an acute need for vision care among the city’s public school students was identified: as many as 15 000 of the city’s 60 000 pre-K (age 2 to 4) through 8th-grade (age 13 to 14) students likely needed glasses though many were unaware or were unable to get them.

Over five years, Vision for Baltimore has tested the vision of more than 64 000 students and distributed more than 8000 pairs of glasses. The Johns Hopkins study represents the most robust work thus far evaluating whether having glasses affects a child’s performance in school.

The three-year randomised clinical trial, conducted from 2016 to 2019, analysed the performance of 2304 students in grades 3 to 7 who received screenings, eye examinations and eyeglasses from Vision for Baltimore. The team looked at their scores on standardised reading and math tests, measuring both 1-year and 2-year impact.

After one year, reading scores increased significantly for students who got glasses, compared to those getting glasses later. There was also significant improvement in maths for students in primary grades.

There were particularly striking improvements for girls, special education students, and students who had been among the lowest performing.

Megan Collins, senior author said, “The glasses offered the biggest benefit to the very kids who needed it the most – the ones who were really struggling in school.”

The gains were about the same as two to four months of extra education compared to students with glasses, said lead author Amanda J Neitzel, deputy director of evidence research at the Johns Hopkins Center for Research and Reform in Education. For students performing in the lowest quartile and students in special education, wearing glasses equated to four to six months of additional learning.

“This is how you close gaps,” Neitzel said.

However, the academic improvements seen after one year were not sustained over two years. Researchers suspect this could be a result of students starting to wear their glasses less, perhaps from loss or breakage.

To keep up the academic achievement boost, the researchers recommend that school-based vision initiatives should also try to ensure children are wearing the glasses and to replace them if needed.

Source: Johns Hopkins University

Categories : PaediatricsTags :

Female Blood Donors Better for Very-low-birthweight Transfusions

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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

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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

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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 : COVID PaediatricsTags :

Infant with COVID Airlifted Out as Texas Hospitals Fill Up

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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 : Cancer GeneticsTags :

Comprehensive Genome Sequencing Can Improve Cancer Outcomes

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Image source: National Cancer Institute

Researchers from St Jude Children’s Research Hospital have demonstrated the feasibility of comprehensive genomic sequencing for all paediatric cancer patients, which maximises the lifesaving potential of precision medicine.

All 309 patients who enrolled in the study were offered whole genome and whole exome sequencing of germline DNA. For the 253 patients for whom adequate tumour samples were available, whole genome, whole exome and RNA sequencing of tumour DNA was carried out.

Overall, 86% of patients had at least one clinically significant variation in tumour or germline DNA. Those included variants related to diagnosis, prognosis, therapy or cancer predisposition. An estimated 1 in 5 patients had clinically relevant mutations that would not have been picked up with standard sequencing methods.

“Some of the most clinically relevant findings were only possible because the study combined whole genome sequencing with whole exome and RNA sequencing,” said Jinghui Zhang, PhD, St Jude Department of Computational Biology chair and co-corresponding author of the study.

While such comprehensive clinical sequencing is not widely available, as the technology becomes less expensive and accessible to more patients, comprehensive sequencing will become an important addition to paediatric cancer care.

“We want to change the thinking in the field,” said David Wheeler, PhD, St Jude Precision Genomics team director and a co-author of the study. “We showed the potential to use genomic data at the patient level. Even in common pediatric cancers, every tumor is unique, every patient is unique.

“This study showed the feasibility of identifying tumour vulnerabilities and learning to exploit them to improve patient care,” he said.

Tumour sequencing resulted in a change in treatment for 12 of the 78 study patients for whom standard of care was unsuccessful. In four of the 12 patients, the treatment changes stabilised disease and extended patient lives. Another patient, one with acute myeloid leukaemia, went into remission and was cured by blood stem cell transplantation.

“Through the comprehensive genomic testing in this study, we were able to clearly identify tumor variations that could be treated with targeted agents, opening doors for how oncologists manage their patients,” said co-corresponding author Kim Nichols, MD, St Jude Cancer Predisposition Division director.

The results of the study were published online in the journal Cancer Discovery.

Source: St. Jude Children’s Research Hospital

Journal information: Newman, S., et al (2021) Genomes for Kids: The scope of pathogenic mutations in pediatric cancer revealed by comprehensive DNA and RNA sequencing. Cancer Discovery. doi.org/10.1158/2159-8290.CD-20-1631.

Categories : Metabolic Disorders PaediatricsTags :

A Restful Sleep for Diabetic Children with New Glucagon Administration

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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

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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