Category: Paediatrics

COVID is Turning Some Children into ‘Fussy Eaters’

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More and more children could be turning into ‘fussy eaters’ after a bout of COVID, according to smell experts at the University of East Anglia and Fifth Sense, a charity for people affected by smell and taste disorders.

This is because they may be suffering parosmia – a symptom where people experience strange and often unpleasant smell distortions. Once-loved foods like chicken may taste like petrol, for example, making it hard for children to eat those foods and maintain a healthy diet – or even take in enough calories to maintain their weight.

Together, Fifth Sense and leading smell expert Professor Carl Philpott from University of East Anglia, are launching guidance to help parents and healthcare professionals better recognise the disorder.

Prof Carl Philpott said: ”Parosmia is thought to be a product of having less smell receptors working which leads to only being able to pick up some of the components of a smell mixture. It’s a bit like Eric Morecambe famously said to Andre Previn – ‘it’s all the right notes but not necessarily in the right order’.

He said that as COVID swept through classrooms in the UK, there has been a growing awareness that it is affecting children too. “In many cases the condition is putting children off their food, and many may be finding it difficult to eat at all.

“It’s something that until now hasn’t really been recognised by medical professionals, who just think the kids are being difficult eaters without realising the underlying problem. For Prof Philpott, he is seeing teenage patients with parosmia for the first time in his career.

Fifth Sense Chair and founder Duncan Boak said: “We’re hearing anecdotal evidence that children are really struggling with their food after covid.

“If children are suffering smell distortions – and food smells and tastes disgusting – it’s going to be really hard for them to eat the foods they once loved.

“We’ve heard from some parents whose children are suffering nutritional problems and have lost weight, but doctors have put this down to just fussy eating. We’re really keen to share more information on this issue with the healthcare profession so they’re aware that there is a wider problem here.”

Together with Prof Philpott, Fifth Sense have put together guidance for parents and healthcare providers to help recognition and understanding of the problem.

The guidance shows that children should be listened to and believed. Parents can help by keeping a food diary noting those that are safe and those that are triggers.

“Establishing what the triggers are and what tastes ok is really important,” said Prof Philpott.

“There are lots of common triggers – for example cooking meat and onions or garlic and the smell of fresh coffee brewing, but these can vary from child to child.

“Parents and healthcare professionals should encourage children to try different foods with less strong flavours such as pasta, bananas, or mild cheese – to see what they can cope with or enjoy.

“Vanilla or flavour-free protein and vitamin milkshakes can help children get the nutrients they need without the taste. And it may sound obvious, but children could use a soft nose clip or hold their nose while eating to help them block out the flavours.”

Smell training’ has emerged as a simple and side-effect free treatment option for various causes of smell loss, and is a final option to consider.

Prof Philpott said: “Smell training involves sniffing at least four different odours – for example eucalyptus, lemon, rose, cinnamon, chocolate, coffee, or lavender – twice a day every day for several months.

“Children should use smells that they are familiar with and are not parosmia triggers. In younger children this might not be helpful, but in teenagers this might be something they can tolerate.”

Source: University of East Anglia

Trial Shows Dupilumab is Safe and Effective for Asthma in Children

Source: PIxabay/CC0

In a late-stage clinical trial, the biologic agent dupilumab reduced the rate of severe asthma attacks and improved lung function and asthma control for children ages 6 to 11, adding to the treatment options for children with moderate-to-severe asthma. 

The findings of the international multicentre Liberty Asthma VOYAGE trial, appeared in the New England Journal of Medicine, and informed the agent’s approval in this age group by the Food and Drug Administration.

“This is a really important advance for children with moderate-to-severe asthma and their families,” said Leonard Bacharier, MD, an asthma specialist at Monroe Carell Jr. Children’s Hospital at Vanderbilt and the international lead investigator for the trial.

Asthma is the most common chronic disorder of childhood, according to the Centers for Disease Control and Prevention. It is a leading cause of hospitalisation for children, and children with moderate-to-severe asthma may have reduced lung function and be at greater risk for lung diseases in adulthood, said Dr Bacharier.

“As asthma gets increasingly severe, the burden becomes substantial, impacting the child and the entire family,” he said. “While we have very good asthma therapies available, none of them are perfect in eliminating severe exacerbations.”

Dupilumab, a monoclonal antibody that targets type 2 inflammation, has been approved for the treatment of asthma in adults and adolescents for several years. Based on its established safety and efficacy, the investigators conducted a Phase III clinical trial in 408 children aged 6 to 11 who had uncontrolled moderate-to-severe asthma.

In a double-blind trial, children received either a subcutaneous injection of dupilumab or placebo in addition to their standard therapy every two weeks for a year.

Most participants had markers of type 2 inflammation, namely elevated levels of immune cells called eosinophils and/or elevated levels of nitric oxide in exhaled air. In patients with these markers, dupilumab significantly reduced the rate of severe exacerbations – symptoms requiring systemic steroid treatment, need for emergency care or hospitalisation – by nearly 60%. Additionally, dupilumab improved lung function, measured by forced exhalation, and improved asthma control.

“This is the first study of its kind in children ages 6 to 11 that has demonstrated that a biologic improves asthma exacerbations, lung function and asthma control,” Dr Bacharier said. “We were not surprised, because dupilumab was very effective in clinical trials in adults and adolescents, but we were delighted with the results and the hope they bring to children and their families.”

The trial demonstrated that dupilumab was safe. Some children in the treatment  arm had increases in blood eosinophil levels or mild but manageable parasitic infections (type 2 immunity fights parasites), but very few discontinued dupilumab because of adverse reactions.

Limited ethnic diversity was noted as a weakness in the trial, especially in light of the disproportionate asthma burden among Black people. Trial participants were invited to participate in a trial extension to determine long-term safety and efficacy.

While two other biologic medicines targeting type 2 inflammation have been approved for asthma treatment in children, neither has shown improvements in all three key clinical endpoints – asthma exacerbations, lung function and asthma control – in a controlled clinical trial, Dr Bacharier said.

Bacharier plans to explore the potential for dupilumab to modify asthma development. “Can we use this agent earlier in life to change how the disease develops? I think that’s the next frontier,” he said.

Source: EurekAlert!

Scientists Find Epilepsy Biomarker in Autistic Children

Photo by Ben Wicks on Unsplash

Scientists have discovered that an important brain protein that quiets overactive brain cells and is abnormally low in children with autism, which may explain why so many children with autism also have epilepsy. The findings were published in Neuron.

This protein can be detected in the cerebrospinal fluid, making it a promising marker to diagnose autism and potentially treat the epilepsy that accompanies the disorder.

Mutated versions of this gene were known to cause autism combined with epilepsy, and epilepsy appears in 30% to 50% of children with autism. Autism, which is 90% genetic, affects 1/58 children in the US.

Appropriately nicknamed ‘catnap2’, the protein, CNTNAP2, is produced by the brain cells when they become overactive. Because the brains of children with autism and epilepsy lack sufficient CNTNAP2, scientists found, their brains become overactive, leading to seizures.

For the study, the researchers analysed the cerebrospinal fluid in individuals with autism and epilepsy, and in mouse models. Though, cerebrospinal fluid has been used in researching disorders such as Parkinson’s, this is the first study showing it is an important biomarker in autism.

The new finding about CNTNAP2’s role in calming the brain in autism and epilepsy may lead to new treatments.

“We can replace CNTNAP2,” said lead study author Peter Penzes, the director of the Center for Autism and Neurodevelopment at Northwestern University Feinberg School of Medicine. “We can make it in a test tube and should be able to inject it into children’s spinal fluid, which will go back into their brain.”

Penzes’ lab is currently working on this technique in preclinical research.

The level in the spinal cord is proxy for the level in the brain, explained Penzes. When brain cells are too active because of overstimulation, they produce more CNTNAP2, which floats away and binds to other brain cells to calm them. The protein also leaks into the cerebrospinal fluid, where scientists were able to measure it, giving them a clue for how much is produced in the brain.

Source: EurekAlert!

Delayed Umbilical Clamping in Preterm Babies Saves Lives

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A study following the effects of delayed umbilical cord clamping in preterm babies has found significant reduction in subsequent mortality and disability. The findings were published in The Lancet Child and Adolescent Health.

The study was a two-year follow up of the Australian Placental Transfusion Study, the award-winning and largest-ever clinical trial of delayed cord clamping of babies born before 30 weeks. Infants born preterm (before 37 weeks’ gestation) have poorer outcomes than infants at term, especially if born before 32 weeks.

The new study compared outcomes for over 1500 babies from the initial study, 767 with caregivers aiming for 60 second delay in clamping and 764 with caregivers aiming for cord clamping before 10 seconds after delivery.

Researchers found that delaying clamping reduces a child’s relative risk of death or major disability in early childhood by 17%. This included a 30% reduction in mortality  before age two. In addition, 15% fewer infants in the delayed-clamping group needed blood transfusions after birth.

The leader of the study, Professor William Tarnow-Mordi, said the simple process of aiming to wait a minute before clamping will have significant global impact.

“It’s very rare to find an intervention with this sort of impact that is free and requires nothing more sophisticated than a clock. This could significantly contribute to the UN’s Sustainable Development goal to end preventable deaths in newborns and children under five – a goal which has really suffered during the pandemic,” he said.

“Applied consistently worldwide, aiming to wait a minute before cord clamping in very preterm babies who do not require immediate resuscitation could ensure that an extra 50 000 survive without major disability in the next decade,” said biostatistician Dr Kristy Robledo from the University of Sydney who led the two-year follow-up analysis.

“In other words, for every 20 very preterm babies who get delayed instead of immediate clamping, one more will survive without major disability.”

Delayed umbilical cord clamping is routine in full term babies to allow the newborn time to adapt to life outside the womb, however, until recently, clinicians generally cut the cord of preterm babies immediately so urgent medical care could be given.

“Ten years ago, umbilical cords were routinely clamped quickly after a very preterm birth and the baby was passed to a paediatrician in case the child needed urgent help with breathing,” said Professor Tarnow-Mordi.

“But we now know that almost all very preterm babies will start breathing by themselves in the first minute, if they are given that time.”

“We think that, after delaying cord clamping, babies get extra red and white blood cells and stem cells from the placenta, helping to achieve healthy oxygen levels, control infection and repair injured tissue.”

The childhood follow-up to the Australian Placental Transfusion Study is the largest world-wide two-year follow up of preterm cord clamping providing the best evidence so far on positive outcomes at two years of age.

In 2017, a systematic review of randomised trials in nearly 3000 preterm babies provided the first evidence indicating that delayed umbilical cord clamping might have benefits for preterm infants and their mothers.
While the World Health Organization recommends that newborns, including preterm babies who do not require positive pressure ventilation should not have their cord clamped earlier than one minute after birth this has not always been consistently applied.

“Moving forward it’s vital that perinatal professionals record the time of first breath and cord clamping to the second during births to allow for robust, large-scale data to further our work in this area,” said co-author Professor Jonathan Morris.

“Intensive staff training in the new protocols will also be vital as it can be daunting to delay treatment in very early and sick babies, but the evidence suggests this results in the best outcomes for these children.”

Source: University of Sydney

One-sixth of Patients in PICUs Harmed by Medications

One-sixth of children in paediatric intensive care units (PICUs) were harmed by medications, of which most cases were preventable, according to a new study published in the British Journal of Clinical Pharmacology.

Researchers conducted an observational study across three PICUs in England over a three-month period in 2019.

The study included 302 patients and 62 adverse drug events were confirmed. The estimated incidence of adverse drug events were 20.5 per 100 patients, and most were preventable as judged by the expert panel. ADEs were commonly involved with medicines prescribing (46.8%) and caused temporary patient harm (67.7%). 

Medications for the central nervous system (22.6%), infections (20.9%), and the cardiovascular system (19.4%) were commonly implicated with adverse drug events. Analysis revealed that patients who stayed in PICU for seven or more days were more likely to experience an adverse event compared to patients with a shorter stay. 

“This multicentre study is the first of its kind in the UK hospitals, and its findings can guide future remedial interventions to reduce avoidable medication-related harm in this vulnerable patient population,” said lead author Anwar A. Alghamdi, PhD, of the University of Manchester.

Source: Wiley

Cholesterol Screening Recommended for Children with Autism

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Physicians have recommended that children with autism spectrum disorder (ASD) receive screening for abnormally high or low cholesterol levels at least once during their childhood, since ASD is a risk factor for cardiovascular disease in both children and adults.

The recommendation stemmed from a recent study, published in Translational Psychiatry, that found reduced levels of high density lipoprotein cholesterol (HDL-C) in individuals from families with two or more children with ASD. Additionally, they found reduced or elevated levels of other lipids, apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB). Individuals with low HDL-C levels or ApoA1 levels had lower adaptive functioning than other individuals with ASD.

“This latest research is part of our ongoing work to understand some of the co-occurring conditions with ASD,” said Elaine Tierney, MD, a child and adolescent psychiatrist with Kennedy Krieger Institute. “Our work indicates that lipids are abnormal in many individuals with ASD. Our findings, in addition to studies that show an increase in heart disease in individuals with ASD, lead us to recommend that children with ASD be screened for abnormal total and HDL cholesterol levels. We hope our work underscores the importance of cholesterol screening and raises awareness for families in the ASD community.”

Previously, Dr Tierney and colleagues identified that Smith-Lemli-Opitz Syndrome (SLOS), a genetic condition of impaired cholesterol biosynthesis, is associated with autism. This led to a recommendation that all children with ASD be screened for SLOS if they exhibit some of its characteristics, such as slow growth, microcephaly, mental retardation and other birth defects, although the severity of this rare disease can vary.

Source: Kennedy Krieger Institute

Is Milk Allergy Being Overdiagnosed in Infants?

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Current guidelines could be causing cow’s milk allergy to be over-diagnosed in infants, according to a new study. 

Researchers analysed data on 1303 healthy infants who were exclusively breastfed until at least three months of age, and found that 38% and 74% of infants had multiple mild-to-moderate milk allergy symptoms – as defined by current allergy guidelines – at three months and 12 months old, respectively. By comparison, non-IgE-mediated cow’s milk allergy has a prevalence of less than 1% in children.

The researchers’ findings, which are published in Clinical & Experimental Allergy, suggest that following current guidelines may lead to over-diagnoses in infants by labelling normal infant symptoms as possible milk allergies.

“There is an assumption that the existence of a guideline is more beneficial than no guideline. However, well-meaning guidelines need to be supported by robust data to avoid harms from over-diagnosis that exceed the damage of missed and delayed cow’s milk allergy diagnoses that they are seeking to prevent,” the researchers wrote.

Source: Wiley

Too Few Children with HIV are Virally Suppressed

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Globally, less than two thirds of children and adolescents living with HIV who are receiving treatment are virally suppressed, according to new research published in The Lancet HIV.

Viral suppression [PDF] for HIV means that treatments are protecting health and preventing the transmission of HIV to others. UNAIDS has set a target of achieving 95% viral suppression among all people living with HIV on treatment by 2030.

“We estimate viral suppression one, two and three years after people start taking antiviral treatment, so that we can understand how well the treatments are working over time,” said Professor Matthew Law from the Kirby Institute.

“The data among adults on treatment in our studies show that viral suppression was achieved in an estimated 79% of adults at one year, and 65% at three years. However, viral suppression is poorer among children, at an estimated 64% at one year and 59% at three years.”

Senior study author, Dr Azar Kariminia from the Kirby Institute, said there are unique barriers to achieving viral suppression for children and adolescents. “It can be challenging for them to take treatment regularly, and children rely on caregivers who are often having to manage their own medical needs. There are also a range of factors that stem from stigma and discrimination, including a fear of disclosing the child’s HIV status.”

For this study, the researchers analysed data from 21 594 children/adolescents and 255 662 adults from 148 sites in 31 countries who initiated treatment between 2010 and 2019.

Dr Annette Sohn, from amfAR’s TREAT Asia program, is Co Principal Investigator for IeDEA Asia-Pacific (along with Prof. Law). She says that “while there has been substantial progress in the global response to HIV, the needs of children and adolescents often fall behind those of adults. Our efforts must extend beyond ensuring access to paediatric medicines to address the social and developmental challenges they face in growing up with HIV if we are to achieve the WHO targets by 2030.”

Viral load testing is essential to find out whether HIV treatments are working effectively. It is recommended by WHO at six and 12 months following the initiation of treatment, and then every 12 months thereafter. While viral load testing is common in high-income countries, scaling up accessible viral load testing in resource-limited settings remains a challenge.

With Australian government funding, the Kirby Institute and the Papua New Guinea Institute of Medical Research (PNGIMR) are partnering with the PNG government and a consortium of partners are implementing a program called ‘ACT-UP PNG’ which will scale up HIV viral load testing in two provinces with high HIV rates.

“Our work is ensuring that infants and children are afforded the same access to testing and treatment as other people with HIV,” says Dr Janet Gare from the PNGIMR and a Co-Principal Investigator on ACT-UP-PNG.

Instead of doing viral load testing in distant laboratories, ACT-UP PNG provides same-day molecular point-of-care testing in HIV clinics.

“This brings HIV viral load testing closer to patients, which currently includes children aged 10 and older, and adolescents,” says Dr Gare. “However, we are also pioneering the implementation of a diagnostic platform that will allow the same access to timely HIV viral load testing and results for infants six to eight weeks of age, and children up to nine years, who are currently unable to be included in point-of-care methods.”

Scientia Associate Professor Angela Kelly-Hanku says that these technologies will make testing for viral suppression in infants and children easier.

“We cannot end AIDS without addressing the inequalities that exist between paediatric and adult HIV programs. Projects like ACT-UP make a real difference and bring us closer to achieving the UNAIDS targets.”

Source: University of New South Wales

Kids’ Spit Could be a Great COVID Test

Photo by CDC

Saliva samples are easy to obtain and useful for measuring antibodies to SARS-CoV-2 in children, which could improve epidemiological surveillance in school settings. The study followed over 1500 children who went to summer schools in Barcelona last year. The results were published in BMC Medicine.

One of the pressing questions during this pandemic has been to understand children’s susceptibility to SARS-CoV-2 infection and how they infect others. An obstacle to answer this question is that most infections in children are mild or asymptomatic, and are therefore missed. To establish whether an individual has been exposed to SARS-CoV-2 in the past, virus-specific antibodies in blood need to be detected. Measuring antibody prevalence over time in a cohort of children can provide very valuable epidemiological information. However, this requires techniques that are both sensitive and minimally invasive.

In this study, performed through the Kids Corona platform, the team led by Carlota Dobaño, from the Barcelona Institute for Global Health (ISGlobal), and Iolanda Jordan, from Hospital Sant Joan de Déu (HSJD), used saliva instead of blood to measure virus-specific antibodies in over 1500 children who attended different summer schools in Barcelona in 2020, as well as around 400 adult staff. Two saliva samples per participant were analysed, one at the beginning and one at the end of the camp stay, and different antibody types (IgG, IgA and IgM) targeting different viral antigens were measured.

The study found that 3.2% of the participants developed antibodies between the first and second sample, indicating new infections. This is six times higher than the infection rate estimated by weekly PCR screening. “It has been reported that some children can be positive for antibodies despite being negative by PCR, which suggests that they can generate an immune response that prevents the establishment of SARS-CoV-2 infection,” explained Dobaño, first author of the study. It could also be because asymptomatic children have lower viral loads or that their viral clearance is faster.

Furthermore, the analysis shows that the percentage of new infections was higher in adults (2.94%) than in children (1.3%), suggesting differences in infection and transmission dynamics. Finally, contrary to blood tests, asymptomatic people had higher levels of anti-Spike antibodies in saliva, suggesting these antibodies play a protective role in respiratory mucosae. “This means that anti-Spike antibodies in saliva could be used to measure protective immunity upon vaccination, especially in the case of intranasal vaccines,” said senior study co-author Gemma Moncunill.

“We previously demonstrated in other Kids Corona studies that saliva is useful for detecting virus by PCR. With this study, we demonstrate that it’s also an effective and much friendlier way to measure antibodies, making it the ideal sample for children, instead of the more invasive nasal swab,” said Jordan.

Source: EurekAlert!

Is That A Girl’s Voice or A Boy’s?

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Researchers have found that it is possible to distinguish a girl’s voice from a boy’s from as young as five years old, but identification requires the listener to perceive the size of the speaker, providing a clue to their likely age. 

Perceiving gender in children’s voices is of special interest to researchers, because in children, a girl’s voice and a boy’s are very similar before the age of puberty. Adult male and female voices are fairly easy to distinguish due to acoustic differences.

With children, gender perception is much more complicated because gender differences in speech may emerge before sex-related anatomical differences between speakers. This suggests listeners may need to consider speaker age when guessing speaker gender and the perception of gender may depend on acoustic information besides anatomical differences between boys and girls.

In the Journal of the Acoustical Society of America, researchers reported developing a database of speech samples from children ages five to 18 to answer two questions: What types of changes occur in children’s voices as they become adults, and how do listeners adjust to the enormous variability in acoustic patterns across speakers?

Listeners assess a speaker’s gender, age, height, and other physical characteristics based primarily on the speaker’s voice pitch and on the resonance (formant frequencies) of their voice.

“Resonance is related to speaker height — think violin versus cello — and is a reliable indicator of overall body size,” said co-author Santiago Barreda, from the University of California, Davis. “Apart from these basic cues, there are other more subtle cues related to behaviour and the way a person ‘chooses’ to speak, rather than strictly depending on the speaker’s anatomy.”
When co-authors Barreda and Peter Assmann presented listeners with both syllables and sentences from different speakers, gender identification improved for sentences. They said this supports the stylistic elements of speech that highlight gender differences and are better conveyed in sentences.

They made two other important findings. First, listeners can reliably identify the gender of individual children as young as five.

“This is well before there are any anatomical differences between speakers and before there are any reliable differences in pitch or resonance,” said Barreda. “Based on this, we conclude that when the gender of individual children can be readily identified, it is because of differences in their behavior, in their manner of speaking, rather than because of their anatomy.”

Second, they found identification of gender of speakers must take place along with the identification of age and likely physical size.

“Essentially, there is too much uncertainty in the speech signal to treat age, gender, and size as independent decisions,” he said. “One way to resolve this is to consider, for example, what do 11-year-old boys sound like, rather than what do males sound like and what do 11-year-olds sound like, as if these were independent questions.”

Their findings suggest that “perception of gender can depend on subtle cues based on behaviour and not anatomy,” said Barreda. “In other words, gender information in speech can be largely based on performance rather than on physical differences between male and female speakers. If gendered speech followed necessarily from speaker anatomy, there would be no basis to reliably identify the gender of little girls and boys.”

This study supports the notion that gender (as opposed to sex) is largely performative in nature, which has long been argued on theoretical grounds.

Source: American Institute of Physics