Hypoxic-ischaemic encephalopathy (HIE) is one of the leading causes of newborn mortality and morbidity worldwide, and therapeutic hypothermia is often used as a treatment. A review in Developmental Medicine and Child Neurology highlights additional therapies for HIE that are being tested with and without concomitant therapeutic hypothermia.
Neonatal HIE is characterised by neurological dysfunction resulting from inadequate oxygen and blood flow to the brain near the time of birth. Therapeutic hypothermia is an established therapy in high-income countries, but many infants still die or experience neurodevelopmental consequences after treatment. Moreover, in low- and middle-income countries, where the burden of HIE is the highest, therapeutic hypothermia was recently shown to be ineffective.
The new review notes that investigational therapies for HIE include agents that block excessive activation of glutamate receptors, drugs that act as antioxidants or anti-inflammatories, and products that target multiple neuroprotective pathways.
“Therapeutic hypothermia for moderate-to-severe neonatal HIE is one of the success stories in newborn care, but there is an urgent need to identify additional therapies that are effective both with and without therapeutic hypothermia,” said corresponding author Natalie H. Chan, MD, MPH, of the University of California, San Francisco. “Our paper reviews the promising therapies being evaluated in clinical studies that could close the remaining gap in optimising outcomes in all babies with HIE.”
More than six sedentary hours per day from childhood through young adulthood may cause an excess increase of 4mmHg in systolic blood pressure, a new study shows. Continuously engaging in light physical activity (LPA) significantly mitigated the rise in blood pressure – while longer bouts of more vigorous exercise . The results were published in the prestigiousJournal of Cachexia, Sarcopenia and Muscle.
In the present study, a collaboration between the Universities of Bristol and Exeter, and the University of Eastern Finland, 2513 children drawn from the Children of the 90s cohort were followed up from age 11 until 24 years. At baseline, the children spent six hours per day sedentary, six hours per day engaging in LPA, and approximately 55 minutes per day in moderate-to-vigorous physical activity (MVPA). At follow-up in young adulthood, nine hours per day were spent sedentary, three hours per day in LPA, and approximately 50 minutes per day in MVPA.
The average blood pressure in childhood was 106/56mmHg which increased to 117/67mmHg in young adulthood, partly due to normal physiological development. Persistent increase in sedentary time from age 11 through 24 years was associated with an average of 4mmHg excess increase in systolic blood pressure. Participating in LPA from childhood lowered the final level by 3mmHg, but engaging in MVPA had no blood pressure-lowering effect.
“Furthermore, when 10 minutes out of every hour spent sedentary was replaced with an equal amount of LPA from childhood through young adulthood in a simulation model, systolic blood pressure decreased by 3mmHg and diastolic blood pressure by 2mmHg. This is significant, as it has been reported in adults that a systolic blood pressure reduction of 5mmHg decreases the risk of heart attack and stroke by ten percent,” says Andrew Agbaje, an award-winning physician and associate professor (docent) of Clinical Epidemiology and Child Health at the University of Eastern Finland.
The current study is the largest and the longest follow-up of accelerometer-measured movement behaviour and blood pressure progression in youth in the world. Measurements of blood pressure, sedentary time, LPA and, MVPA were taken at ages 11, 15, and 24 years. The children’s fasting blood samples were also repeatedly measured for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, glucose, insulin, and high-sensitivity C-reactive protein. Heart rate, socio-economic status, family history of cardiovascular disease, smoking status as well as dual-energy X-ray absorptiometry measured fat mass and lean mass were accounted for in the analyses.
“We have earlier shown that elevated blood pressure and hypertension in adolescence increase the risk of premature cardiac damage in young adulthood. The identification of childhood sedentariness as a potential cause of elevated blood pressure and hypertension with LPA as an effective antidote is of clinical and public health significance. Several MVPA-based randomised controlled trials in the young population have been unsuccessful in lowering blood pressure. We noted an MVPA-induced increase in muscle mass enhanced a physiologic increase in blood pressure explaining why earlier MVPA-based randomised clinical trials were unsuccessful,” says Agbaje.
Adolescents who meet the recommended guidelines of nine to 11 hours of sleep per day were shown to have a significantly lower risk of hypertension, according to a new study from UTHealth Houston.
Recently published in the Journal of the American Heart Association, the research revealed that adolescents had a 37% lower risk of developing incidents of high blood pressure by meeting healthy sleep patterns, and underscoring the importance of adequate sleep behaviour. The research further explored the impact of environmental factors potentially impacting sleep.
“Disrupted sleep can lead to changes in the body’s stress response, including elevated levels of stress hormones like cortisol, which in turn can increase blood pressure,” said first author Augusto César Ferreira De Moraes, PhD, assistant professor in the Department of Epidemiology at UTHealth Houston School of Public Health.
De Moraes and his team analysed data from 3320 adolescents across the US to investigate incidents of high blood pressure during nighttime sleep cycles. Scientists identified a rise in hypertension incidents over two data periods, 2018-2020 and 2020-2022, showing an increase from 1.7% to 2.9%. The data included blood pressure readings and Fitbit assessments, which measured total sleep time and REM sleep duration at night. The study’s design analysed covariates such as Fitbit-tracked sleep, blood pressure, and neighbourhood noise by residential geocodes, allowing for a thorough examination of environmental noise exposure for each participant.
Neighbourhood/community noise was not significantly associated with the incidence of hypertension. Environmental factors, such as neighbourhood noise, point to the need for longer-term studies to investigate the relationship between sleep health and hypertension, particularly in relation to socioeconomic status, stress levels, and genetic predispositions.
The study emphasises the importance of improved sleep behaviours and meeting recommendations. “Consistent sleep schedules, minimising screen time before bed, and creating a calm, quiet sleep environment can all contribute to better sleep quality,” advises Martin Ma, MPH, second author of the study and recent graduate of the school. “Although environmental noise didn’t directly affect hypertension in this study, maintaining a quiet and restful sleep environment is still important for overall well-being.”
More than a quarter of new mothers have fallen asleep recently while feeding their babies, putting the infants at increased risk of sudden infant death syndrome (SIDS), research published in Pediatrics reveals.
More than 80% had not intended to fall asleep, and many had chosen to feed in chairs or on sofas rather than in a bed. Unfortunately, the cushions and confines of those locations can be very unsafe for babies, raising the risk of death by 49 to 67 times.
The researchers, with UVA Health and UVA Health Children’s, are urging care providers to provide additional guidance for new parents on safe feeding practices, such as informing new moms that a hormone naturally released during breastfeeding will make them feel sleepy.
“While falling asleep while feeding young infants is not in itself too surprising, what is very alarming is that the majority of mothers did not plan to fall asleep, so the sleep space was potentially unsafe for the baby while both slept,” said researcher Fern Hauck, MD, MS, a safe-sleep expert at UVA Health and the UVA School of Medicine. “This highlights the need for parents to be educated about the potential risk of falling asleep while feeding and to plan for that possibility by making the space around the baby as safe as possible. That would include removing pillows and blankets to ensure an open airway for the baby.”
Safe infant feeding
Hauck and her collaborators, including UVA’s Ann Kellams, MD, and Rachel Moon, MD, analysed survey results collected from more than 1250 new mothers as part of the Social Media and Risk-reduction Training (SMART) study conducted at 16 US hospitals in 2015 and 2016. Most respondents completed the survey when their infant was between 2 and 3 months of age.
Among the respondents, more than 28% said they had “usually” or “sometimes” fallen asleep during feeding in the prior two weeks. Of those, a whopping 83.4% said falling asleep was unplanned.
Women who fed in bed were more likely to fall asleep (33.6%) than those who fed on a chair or couch (16.8%). The American Academy of Pediatrics (AAP) recommends mothers at risk of falling asleep while breastfeeding should do so in an adult bed rather than a chair or couch.
Many of the women who fell asleep on chairs or sofas said they chose those locations specifically to avoid falling asleep, to avoid locations (such as a bed) they had been told were unsafe or to avoid disturbing someone else. (The AAP warns moms against sharing a bed or other sleep space with an infant because of the risk the parent might accidentally roll over and smother the child, or that the child could become tangled in bedding. But the group also says that beds are safer than chairs and sofas if falling asleep while feeding is a possibility.)
“We need to meet families where they are and come up with a nighttime plan for sleeping and feeding their baby that works for them and is as safe as possible,” said Kellams, a paediatrician and breastfeeding and lactation medicine specialist at UVA Health Children’s. “Our data suggest that too many of these falling asleep incidents are not planned, so discussions about how to plan for feeding your baby when you are very tired are important.”
The researchers note that providing parents with information about safe sleep and feeding has been shown to reduce risk of unexpected death significantly. But this educational outreach needs to be expanded, they say. Care providers should acknowledge that moms face a very real risk of falling asleep while feeding, even if they are trying not to, and provide practical advice on how to reduce that risk. Further, the researchers are urging additional studies to find ways to assist parents in both safe-sleep practices and breastfeeding.
“We hope that parents of young infants will think proactively about what might happen in the middle of the night,” said Moon, a paediatrician and safe-sleep expert at UVA Health Children’s. “Feeding your baby in your bed is safer than feeding on a couch or armchair if you might fall asleep.”
A University of Minnesota Medical School research team has found that giving iron supplements to children living with human immunodeficiency virus (HIV) in sub-Saharan Africa could be an important first step in optimising brain development.
The study, published in Lancet HIV, demonstrates that iron, while often withheld from children with HIV due to fear of increasing infection risk, is in fact beneficial. This finding paves the way for future research examining iron’s role in neurodevelopmental outcomes in children with HIV.
“With the success and widespread availability of antiretroviral therapy (ART), children with HIV in sub-Saharan Africa are living longer, and optimising their brain development is a new public health imperative,” said Sarah Cusick, PhD, associate professor at the U of M Medical School and a member of the Masonic Institute for the Developing Brain.
Between May 2018 and November 2019, researchers enrolled 200 children with HIV and anaemia who had received ART for at least six months. The study participants were randomly chosen to receive either iron supplements or a placebo for three months. Children who received iron had higher haemoglobin concentrations and better markers of iron nutrition than those who received the placebo. There also was no evidence of increased risk of infection.
According to Dr Cusick, further research is needed to assess brain development and infection risk over a longer period of time.
Maternal antibodies passed across the placenta can interfere with the response to the malaria vaccine, which would explain its lower efficacy in infants under five months of age, according to research led by the Barcelona Institute for Global Health (ISGlobal), in collaboration with seven African centers (CISM-Mozambique, IHI-Tanzania, CRUN-Burkina Faso, KHRC-Ghana, NNIMR-Ghana, CERMEL-Gabon, KEMRI-Kenya).
The findings, published in Lancet Infectious Diseases, suggest that children younger than currently recommended by the WHO may benefit from the RTS,S and R21 malaria vaccines if they live in areas with low malaria transmission, where mothers have less antibodies to the parasite.
The world has reached an incredible milestone: the deployment of the first two malaria vaccines –RTS,S/AS01E and the more recent R21/Matrix-M– to protect African children against malaria caused by Plasmodium falciparum. Both vaccines target a portion of the parasite protein called circumsporozoite (CSP) and are recommended for children aged 5 months or more at the moment of the first dose.
“We know that the RTS,S/AS01E malaria vaccine is less effective in infants under five months of age, but the reason for this difference is still debated,” says Carlota Dobaño, who leads the Malaria Immunology group at ISGlobal, a centre supported by “la Caixa” Foundation.
To investigate this, Dobaño and her team analysed blood samples from more than 600 children (age 5-17 months) and infants (age 6-12 weeks) who participated in the phase 3 clinical trial of RTS,S/AS01E. Using protein microarrays, they measured antibodies against 1000 P. falciparum antigens before vaccination to determine if and how malaria exposure and age affected IgG antibody responses to the malaria vaccine.
“This microarray approach allowed us to accurately measure malaria exposure at the individual level, including maternal exposure for infants and past infections for older children,” says Didac Maciá, ISGlobal researcher and first author of the study.
The role of maternal antibodies
The analysis of antibodies to P. falciparum in children who had received a control vaccine instead of RTS,S/AS01E revealed a typical “exposure” signature, with high levels in the first three months of life due to the passive transfer of maternal antibodies through the placenta, a decline during the first year of life, and then a gradual increase as a result of naturally acquired infections.
In children vaccinated with RTS,S/AS01E, antibodies induced by natural infections did not affect the vaccine response. However, in infants, high levels of antibodies to P. falciparum, presumably passed from their mothers during pregnancy, correlated with reduced vaccine responses. This effect was particularly strong for maternal anti-CSP antibodies targeting the central region of the protein. Conversely, infants with very low or undetectable maternal anti-CSP IgGs exhibited similar vaccine responses as those observed in children.
The molecular mechanisms underlying this interference by maternal antibodies are not fully understood, but the same phenomenon has been observed with other vaccines such as measles.
Overall, these findings confirm something that was already suspected but not clearly demonstrated: despite their protective function, maternal anti-CSP antibodies, which decline within the first three to six months of life, may interfere with vaccine effectiveness. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. These findings further suggest that infants below five months of age may benefit from RTS,S or R21 vaccination in low malaria transmission settings, during outbreaks in malaria-free regions, or in populations migrating from low to high transmission settings.
“Our study highlights the need to consider timing and maternal malaria antibody levels to improve vaccine efficacy for the youngest and most vulnerable infants,” says Gemma Moncunill, ISGlobal researcher and co-senior author of the study, together with Dobaño.
New research published in Acta Paediatrica suggests that children who engage in outdoor play during their preschool years have a lower risk of developing obesity later in childhood.
The study included children born in Japan during two weeks in January and July 2001. Of 53 575 children born, 42 812 had data on outdoor play habits at age 2.5 years. In a survey, parents were asked, “Where do your children usually play (excluding home residences and daycare centres attended)?” Available options for answers included “in my garden or on the grounds of my apartment complex,” “in parks,” “in natural areas such as fields, forests, and beaches,” “on the street,” “in shrines and temples,” “in playgrounds in department stores and supermarkets,” “other,” and “don’t play anywhere but inside my home.” If one or more of the first five items were chosen, a child was considered to have exposure to outdoor play—this was the case for 91% of the children.
In follow-up surveys when the children were seven years old, 31 743 of 42 812 (74%) children had height and weight data, with 10% classified as overweight or obese.
Compared with children without exposure to outdoor play, children with outdoor play habits had 15% lower odds of being overweight or obese, after adjusting for other influencing factors.
“We suggest that parents and caregivers encourage outdoor play habits in their children at an early age, as this may help prevent obesity later in life,” said corresponding author Takahiro Tsuge, MPH, of Kurashiki Medical Center.
The foundation for healthy eating behaviour starts in infancy. Young children learn to regulate their appetite through a combination of biological, psychological, and sociological factors. In a new paper published in Social Science & Medicine, researchers at the University of Illinois Urbana-Champaign propose a model that explores these factors and their interactions, providing guidelines for better understanding childhood appetite self-regulation.
Appetite self-regulation is related to general self-regulation, but it specifically concerns an individual’s ability to regulate food intake, which affects healthy development and obesity risk. Children are born with a capacity to regulate appetite based on hunger and satiety signals, but with increased exposure to environmental factors, their eating is increasingly guided by psychological reasoning and motivations. Therefore, it is important to take a developmental perspective to trace changes in eating behaviours over time, Ju stated.
Ju and her colleagues provide a comprehensive framework based on the biopsychosocial pathways model, which outlines three interacting categories: Biological factors, including sensory experience, physiological hunger and satiety signals, brain-gut interaction, and the influence of the gut microbiome; psychological factors, including emotional self-regulation, cognitive control, stress regulation, and reward processing;and social factors, such as parental behaviour and feeding practices, culture, geographic location, and food insecurity.
The researchers combine this framework with temperamental theory to explore how the pathways are modified by individual temperament.
Children react differently to stimuli based on their psychological and emotional make up, Ju explained. For example, openness to novelty and positive anticipation can affect whether a child is willing to try new foods. If a parent pressures their child to eat, it could be counter-productive for a child with heightened sensitivity to negative affect, causing the child to consume less.
The model also takes children’s developmental stages into account. Infants have basic appetite regulation based on physiological cues. They gradually become more susceptible to external influences and by age 3-5, children begin to exhibit greater self-control and emotional regulation.
“By analysing the pathways outlined in our model, we can better understand the combined influences of multiple factors on children’s appetite self-regulation and their motivations to approach food,” Ju said. “For example, the presence of palatable food may not generate similar responses in everyone. Children could approach food as a reward, for pleasure-seeking, or to regulate emotions. The underlying motivations can be diverse, and they are influenced by external factors as well as temperamental characteristics.”
Socio-environmental influences include parent-child interactions around food, as well as non-food-related caregiver practices that can impact the child’s emotional regulation. The household food environment, cultural value of food intake, and food availability are also important factors, the researchers stated.
“If we understand the differential susceptibility to various factors, we can identify and modify the environmental influences that are particularly obesogenic based on children’s temperamental characteristics. Then we will be able to provide more refined approaches to support children’s healthy eating behaviour,” Ju explained.
Respiratory syncytial virus (RSV) is the leading cause of hospitalisation in young children due to respiratory complications such as bronchiolitis and pneumonia. Yet little is understood about why some children develop only mild symptoms while others develop severe disease.
To better understand what happens in these cases, clinician-scientists from Brigham and Women’s Hospital, and Boston Children’s Hospital analysed samples from patients’ airways and blood, finding distinct changes in children with severe cases of RSV, including an increase in the number of natural killer (NK) cells in their airways.
The descriptive study, which focuses on understanding the underpinnings of severe disease, may help to lay groundwork for identifying new targets for future treatments. Results are published in Science Translational Medicine.
“As a physician, I help to care for children who have the most severe symptoms, and as a researcher, I’m driven to understand why they become so sick,” said corresponding author Melody G. Duvall, MD, PhD, of the Division of Pulmonary and Critical Care Medicine at Brigham and Women’s Hospital (BWH) and the Division of Critical Care Medicine at Boston Children’s Hospital. “NK cells are important first responders during viral infection – but they can also contribute to lung inflammation. Interestingly, our findings fit with data from some studies in COVID-19, which reported that patients with the most severe symptoms also had increased NK cells in their airways. Together with previous studies, our data link NK cells with serious viral illness, suggesting that these cellular pathways merit additional investigation.”
Duvall and colleagues, including lead author Roisin B. Reilly of the Division of Pulmonary and Critical Care Medicine at BWH, looked at samples from 47 children critically ill with RSV, analysing immune cells found in their airways and peripheral blood. Compared to uninfected children, those with severe illness had elevated levels of NK cells in their airways and decreased NK cells in their blood. In addition, they found that the cells themselves were altered, both in appearance and in their ability to perform their immunological function of killing diseased cells.
Duvall and co-authors have previously described a post-pandemic surge in paediatric RSV infections. While clinicians can only provide supportive care to the most severely sick children, vaccines to prevent RSV are now available for children 19 months and younger, adults 60 years and over, and people who are pregnant.
Discoid lateral meniscus and osteochondritis dissecans in adolescent patients. The black arrow represents DLM and the white arrow represents osteochondritis dissecans. Credit: Osaka Metropolitan University
Growing pains are common in maturing children, but sometimes this growth can be irregular and cause injury. Discoid lateral meniscus (DLM), a misshapen knee cartilage, is one such occurrence that can degenerate into osteochondritis dissecans, a joint disorder where the bone and joint begin to separate from the rest of the bones. It has been reported that osteochondritis dissecans of the femoral condyle occurs in approximately 14.5% of cases of DLM, but there has been little analysis of its treatment to date.
Dr Ken Iida and Specially Appointed Professor Yusuke Hashimoto’s team at Osaka Metropolitan University’s Graduate School of Medicine analysed the incidence of post-surgery osteochondritis dissecans. This analysis consisted of two groups, a pre-osteochondritis group with DLM and osteochondritis dissecans of the outer femoral epicondyle, and a non-osteochondritis dissecans DLM group. They studied 95 cases of DLM patients under the age of 15 who underwent surgery between 2003 and 2017 and had five years of post-surgery records. There were 15 cases in the pre-osteochondritis dissecans group and 80 non-osteochondritis dissecans cases.
Their analysis found that the surgical results for osteochondritis dissecans were good in pre-osteochondritis cases, but 28.5% had a recurrence of the joint disorder. In the non-osteochondritis dissecans group, 8.8% were diagnosed with the disorder after surgery. Additionally, age was found to be a risk factor for relapse or post-surgical osteochondritis dissecans, and surgery on patients ages 9 and under was also involved in the occurrence of osteochondritis dissecans.
“Patients with DLM accompanied by osteochondritis dissecans of the femoral condyle often have difficulty in deciding on a treatment method,” Dr Iida explained. “Based on the results of this study, we believe for patients ages 9 years or younger, it is necessary to consider conservative treatment methods rather than immediate surgery.”
