Researchers at Children’s Hospital of Philadelphia (CHOP) found that combining a specialised diet with an approved medication interrupts the growth of high-risk neuroblastoma, a deadly paediatric cancer, by reprogramming tumour behaviour. The findings were published in the journal Nature.
Neuroblastoma originates from primitive cells meant to form nerve tissues but that remain “undifferentiated,” indicating cancer cells that haven’t specialized, often suggesting a more aggressive and unfavourable prognosis. These tumours rely on a steady supply of chemicals called polyamines that are essential for rapid cell growth and tumour progression. A medicine called difluoromethylornithine (DFMO) was approved by the Food and Drug Administration (FDA) to treat children with high-risk neuroblastoma, as DFMO blocks polyamine production. However, researchers sought to improve the effectiveness of the drug by using it at high doses and combining it with a diet that is depleted of the nutrients used by the body to make polyamines (arginine). This two-step approach was anticipated to lower polyamines substantially more than low dose DFMO alone.
“Our findings show that this treatment reduced polyamines in tumours to roughly 10% of their usual levels. This reduction greatly slowed tumour growth, and in many cases, completely eliminated the tumours,” said Michael D. Hogarty, MD, a lead author and an Attending Physician in the Division of Oncology at Children’s Hospital of Philadelphia. “Notably, the treatment altered the way the tumour cells make proteins, making it harder for them to grow and easier for them to mature, or differentiate.”
Hogarty and his team used a preclinical model to mimic MYCN-driven neuroblastoma, directly addressing the strong association between extra MYCN gene copies and aggressive neuroblastoma with poor prognosis. Animal models with tumours were divided into groups: one fed a normal diet and the other lacking amino acids for polyamine production. Each group either received DFMO in their drinking water or did not. The special diet or DFMO alone partially lowered polyamines and extended survival, but the combination had the most significant impact on tumours due to the profound polyamine depletion it caused.
The researchers plan to conduct additional preclinical studies, followed hopefully by clinical trials in children to determine the safety and efficacy of targeting this specific metabolic dependency of neuroblastoma cells. By complementing existing treatments, they hope to substantially improve patient outcomes, and because the therapy targets polyamines it may be effective in many other types of cancer that have frequent MYC gene activation.
Researchers are calling for an urgent overhaul of diagnostic and treatment guidelines for infections in newborn babies, after a University of Sydney-led study revealed frontline treatments for sepsis are no longer effective to treat the majority of bacterial infections.
The study, published in The Lancet Regional Health – Western Pacific, analysed almost 15 000 blood samples collected from sick babies in 2019 and 2020 at 10 hospitals across five countries in Southeast Asia, including Indonesia and the Philippines.
It found that most infections were caused by bacteria unlikely to respond to the currently applied WHO recommended treatments. These were developed using data from high-income countries, instead of using localised data which could be more accurate and therefore effective.
“Our study highlights the causes of serious infections in babies in countries across Southeast Asia with high rates of neonatal sepsis, and reveals an alarming burden of AMR that renders many currently available therapies ineffective for newborns,” said senior author Associate Professor Phoebe Williams, a Senior Lecturer and NHMRC Fellow in the Sydney School of Public Health.
“Guidelines must be updated to reflect local bacterial profiles and known resistance patterns. Otherwise, mortality rates are only going to keep climbing.”
The problem is further compounded by a lack of new antimicrobial medications in development for infants and babies, added co-author Michelle Harrison, PhD candidate and Project Coordinator of NeoSEAP in the Sydney School of Public Health.
“It takes about 10 years for a new antibiotic to be trialled and approved for babies,” Harrison said.
“With so few new drug candidates in the first place, we need a significant investment in antibiotic development.”
Gram-negative bacteria responsible for 80% of infections
For the samples which tested positive for fungal or bacterial infections, the team analysed whether they were caused by gram-positive or gram-negative bacteria – referring to the structure of the bacteria’s cell wall which influences how likely it is to develop and acquire antibiotic resistance.
Gram-negative bacteria like E. coli, Klebsiella and Acinetobacter were responsible for nearly 80% of infections and are more likely to develop (and spread) antibiotic resistance.
“These bugs have long been considered to only cause infections in older babies, but are now infecting babies in their first days of life,” said Associate Professor Williams.
When treating babies, doctors don’t have time to wait for lab tests to confirm the exact cause of the infection, and often make an educated guess from published data, most often based on high-income populations, to guide treatment. These tests are also frequently delayed or falsely negative due to the difficulty of collecting blood samples.
Harrison explained that the findings showcase the importance of locally relevant data to guide routine medical decision-making.
“We need more region-specific surveillance to guide treatment decisions. Otherwise, we risk reversing decades of progress in reducing child mortality rates,” she said.
“Our results also revealed fungal infections caused nearly one in 10 serious infections in babies – a much higher rate than in high-income countries.
“We need to ensure doctors are prescribing treatments that have the best chance at saving a baby’s life.”
Study of nearly 4 million children and adolescents finds that 10% of paediatric blood and bone marrow cancers may have stemmed from radiation exposure.
Credit: Pixabay CC0
A study led by UC San Francisco and UC Davis has concluded that radiation from medical imaging is associated with a higher risk of blood cancers in children.
For the study, which appears in NEJM, the researchers examined data from nearly 4 million children and estimated that 1 in 10 blood cancers – some 3000 cancers in all – may be attributable to radiation exposure from medical imaging. The risk increased proportionally based on the cumulative amount of radiation the children received.
The investigation is the first comprehensive assessment using data from children and adolescents in North America that quantifies the association between radiation exposure from medical imaging and blood and bone marrow cancers, such as leukaemia and lymphoma, which are the most common forms of cancer in children and adolescents.
Medical imaging saves lives by enabling timely diagnosis and effective treatment, but it also exposes patients to ionizing radiation, a known carcinogen, particularly through computed tomography (CT).
The authors caution that doctors and parents should avoid excessive radiation doses and minimize exposure when clinically feasible.
“Children are particularly vulnerable to radiation-induced cancer due to their heightened radiosensitivity and longer life expectancy,” said Rebecca Smith-Bindman, MD, a radiologist and professor of Epidemiology and Biostatistics, as well as Obstetrics, Gynecology and Reproductive Sciences at UCSF and the first author of the paper.
“While medical imaging can be lifesaving, our findings underscore the critical need to carefully evaluate and minimise radiation exposure during paediatric imaging to safeguard children’s long-term health,” said Smith-Bindman, who is also a member of the Philip R. Lee Institute for Health Policy Studies. “This involves ensuring that imaging is performed only when it provides essential information for the child’s care and, in cases such as CT scans, using the lowest possible radiation doses.”
Documenting risks in children
The study uses a retrospective cohort design, looking back at the complete imaging histories of 3.7 million children who were born between 1996 and 2016. The children were treated at six health care systems in the U.S. and Ontario, Canada. Investigators found a significant relationship between cumulative radiation dose and the risk of a hematologic malignancy, which includes tumours affecting the blood, bone marrow, lymph, and lymphatic system.
The risk of developing cancer varied significantly by imaging modality. CT, which is used to detect many abnormalities such as tumours, heart disease, and injuries of the spinal cord and brain, entails significant radiation exposure. But radiographs, which are used to diagnose both broken bones and pneumonia, expose children to much lower doses.
Among all the forms of medical imaging, the study found that chest radiography was the most common imaging exam that doctors performed. The most common form of CT was of the head and brain.
For children who underwent a head CT, the researchers attributed about a quarter of the children’s subsequent hematologic malignancies to radiation exposure. For those who had radiographs, by contrast, they estimated that only a small fraction of the children’s subsequent cancers were associated with radiation exposure.
Getting one or two head CTs was associated with a 1.8-fold increased risk of a cancer diagnosis, and this rose to 3.5 times for children who received more scans and were therefore exposed to more radiation.
Altogether, 2961 haematologic malignancies were diagnosed during the study period. Lymphoid malignancies accounted for 79.3%, while myeloid malignancies and acute leukaemia together accounted for 15.5%. About 58% of cancers occurred in males, and about half were diagnosed in children under 5.
The authors said that up to 10% of haematologic malignancies in children and adolescents could be prevented by reducing unnecessary imaging and optimising radiation doses. In many cases, the authors said, substituting non-ionising imaging modalities like ultrasound or MRI may be feasible without compromising diagnostic accuracy.
Benefits vs risks
The authors emphasised that while medical imaging remains an invaluable tool in paediatric care, their findings highlight the need to carefully balance its diagnostic benefits with potential long-term risks.
“This study provides robust, directly observed evidence of a clear dose–response relationship between radiation from medical imaging and hematologic malignancy risk in children and adolescents,” said Diana Miglioretti, PhD, UC Davis Health professor and chief of the Division of Biostatistics.
“Our findings align with international research highlighting that children are especially radiosensitive,” Miglioretti added. “It’s crucial for clinicians to weigh the immediate benefits of imaging against potential long-term health risks and to optimise imaging protocols to minimize radiation exposure.”
It is not only premature babies and children with underlying diseases who suffer from serious respiratory syncytial virus (RSV) infections. Even healthy, full-term babies are at significant risk of intensive care or prolonged hospitalisation – especially during the first three months of life. This is according to a comprehensive registry study from Karolinska Institutet published in The Lancet Regional Health – Europe.
RSV is a common cause of respiratory infections in young children and accounts for around 245,000 hospital admissions annually in Europe. Researchers have now analysed data from over 2.3 million children born in Sweden between 2001 and 2022 to find out who is at greatest risk of suffering serious complications or dying from an RSV infection.
Preventive treatment available
It is well-known that premature babies and children with chronic diseases are at increased risk of developing severe illness when infected with RSV. It is also known that children under three months of age are particularly vulnerable, but it has not been entirely clear how common severe disease is among previously healthy children. The study shows that the largest group among the children who needed intensive care or were hospitalised for a long period of time were under three months of age, previously healthy and born at full term.
“When shaping treatment strategies, it is important to take into account that even healthy infants can be severely affected by RSV,” says the study’s first author, Giulia Dallagiacoma, a physician and doctoral student at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “The good news is that there is now preventive treatment that can be given to newborns, and a vaccine that can be given to pregnant women.”
Starting September 10, 2025, all newborns in Sweden are being offered preventive treatment with antibodies during the RSV season. The drug works much like a vaccine and protects against severe RSV infection for about six months.
Several risk factors identified
A total of 1.7 per cent of the children in the study were diagnosed with RSV infection. Among those, just under 12 per cent (4,621 children) had a severe course of illness. The median age of children who needed intensive care was just under two months, and the majority of them had no underlying disease.
The researchers identified several factors that were linked to an increased risk of needing intensive care or dying. Children who were born in the winter, or had siblings aged 0–3 years or a twin, had approximately a threefold increased risk, while children who were small at birth had an almost fourfold increased risk. Children with underlying medical conditions had more than a fourfold increased risk of severe illness or death.
“We know that several underlying diseases increase the risk of severe RSV infection, and it is these children who have so far been targeted for protection with the preventive treatment that has been available,” says the study’s last author, Samuel Rhedin, resident physician at Sachs’ Children and Youth Hospital and associate professor at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “However, the study highlights that a large proportion of children who require intensive care due to their RSV infection were previously healthy. Now that better preventive medicines are available, it is therefore positive that the definition of risk groups is being broadened to offer protection during the RSV season to previously healthy infants as well.”
A Stanford University-led study has found that young children with attention deficit/hyperactivity disorder (ADHD) often receive medication just after being diagnosed, which contravenes treatment guidelines endorsed by the American Academy of Pediatrics.
The findings, from published JAMA Network Open, highlight a gap in medical care for 4- and 5-year-olds with ADHD. Treatment guidelines recommend that these young children and their families try six months of behaviour therapy before starting ADHD medication.
But paediatricians often prescribe medication immediately upon diagnosis, according to an analysis of medical records from nearly 10 000 young children with ADHD who received care in eight paediatric health networks in the United States.
“We found that many young children are being prescribed medications very soon after their diagnosis of ADHD is documented,” said the study’s lead author, Yair Bannett, MD, assistant professor of paediatrics. “That’s concerning, because we know starting ADHD treatment with a behavioural approach is beneficial; it has a big positive effect on the child as well as on the family.”
Medications not appropriate to under-6s
In addition, stimulant medications prescribed for the condition cause more side effects in young patients than they do in older children, Bannett said. Before age 6, children’s bodies don’t fully metabolise the drugs.
“We don’t have concerns about the toxicity of the medications for 4- and 5-year-olds, but we do know that there is a high likelihood of treatment failure, because many families decide the side effects outweigh the benefits,” he said. Stimulant medication can make young children more irritable, emotional, and aggressive.
ADHD is a developmental disorder characterised by hyperactivity, difficulty paying attention, and impulsive behaviour.
“It’s important to catch it early because we know these kids are at higher risk for having academic problems and not completing school,” Bannett said. Early identification and effective treatment for ADHD improve children’s academic performance. Research has shown that good treatment also helps prepare individuals with ADHD for many aspects of adulthood, such as maintaining employment, having successful relationships, and avoiding trouble with the law.
Complementary treatments
Behavioral therapy and medication, the two mainstays of ADHD treatment, have different purposes.
“Behavioral treatment works on the child’s surroundings: the parents’ actions and the routine the child has,” Bannett said. The therapy helps parents and kids build skills and establish habits compatible with how the child’s brain works.
The evidence-based behavioral treatment recommended by the American Academy of Pediatrics is called parent training in behavior management. The training helps parents build strong, positive relationships with their children; offers guidance in rewarding a child’s good behaviors and ignoring negative behaviors; and recommends tools that help kids with ADHD, such as making visual schedules to help them stay organized.
In contrast, medication relieves ADHD symptoms such as hyperactivity and inattentiveness, with effects that wear off as the body breaks down each dose of the drug.
Both approaches are needed for most kids with ADHD to do well. But previous studies of preschoolers diagnosed at age 4 or 5 show that it’s best to start with six months of behavioural treatment before prescribing any medication.
Rapid prescriptions
The researchers analysed data from electronic health records for children seen at primary care practices affiliated with eight US academic medical centres. They began with 712 478 records from children aged 3, 4, or 5 years old and were seen by their primary care physician at least twice, over a period of at least six months, between 2016 and 2023.
From these records, the scientists identified 9708 children who received an ADHD diagnosis, representing 1.4% of the children in the initial sample. They found that 42.2% were prescribed medication within a month of their ADHD diagnosis. Only 14.1% of children with ADHD first received medication more than six months after diagnosis. The researchers did not have access to data on referrals to behavioural therapy, but since young children are supposed to try the therapy alone for six months before receiving medication, any who were prescribed medication sooner were likely not being treated according to academy guidelines. A smaller study of recommendations for behaviour therapy, published in 2021, found only 11% of families got the therapy in line with guidelines.
Children who were initially given a formal diagnosis of ADHD were more likely to get medication within the first 30 days than those whose medical charts initially noted some ADHD symptoms, with a diagnosis at a later time. But even among preschoolers who did not initially meet full criteria for the condition, 22.9% received medication within 30 days.
Barriers to behavioural treatment?
Because the study was based on an analysis of electronic medical records, the researchers could not ask why physicians made the treatment decisions they did. But in informal conversations with physicians, outside the scope of the study, the researchers asked why they prescribed medication.
“One important point that always comes up is access to behavioural treatment,” Bannett said. Some locales have few or no therapists who offer the treatment, or patients’ insurance may not cover it. “Doctors tell us, ‘We don’t have anywhere to send these families for behavioural management training, so, weighing the benefits and risks, we think it’s better to give medication than not to offer any treatment at all.’”
Bannett said he hopes to educate primary care paediatricians on how to bridge this gap. For example, free or low-cost online resources are available for parents who want to learn principles of the behavioural approach.
And while the study focused on the youngest ADHD patients, behavioural management therapy also helps older children with the diagnosis.
“For kids six and above, the recommendation is both treatments, because behavioural therapy teaches the child and family long-term skills that will help them in life,” Bannett said. “Medication will not do that, so we never think of medication as the only solution for ADHD.”
Blood pressure matters at all ages. Children with higher blood pressure at age 7 may be at an increased risk of dying of cardiovascular disease by their mid-50s, according to preliminary research presented at the American Heart Association’s Hypertension Scientific Sessions 2025. The study is simultaneously published in JAMA.
“We were surprised to find that high blood pressure in childhood was linked to serious health conditions many years later. Specifically, having hypertension or elevated blood pressure as a child may increase the risk of death by 40% to 50% over the next five decades of an individual’s life,” said Alexa Freedman, Ph.D., lead author of the study and an assistant professor in the department of preventive medicine at the Northwestern University’s Feinberg School of Medicine in Chicago. “Our results highlight the importance of screening for blood pressure in childhood and focusing on strategies to promote optimal cardiovascular health beginning in childhood.”
Previous research has shown that childhood blood pressure is associated with an increased risk of cardiovascular disease in adulthood, and a 2022 study found that elevated blood pressure in older children (average age of 12 years) increased the risk of cardiovascular death by middle age (average age of 46 years). The current study is the first to investigate the impact of both systolic (top number) and diastolic (bottom number) blood pressure in childhood on long-term cardiovascular death risk in a diverse group of children. Clinical practice guidelines from the American Academy of Pediatrics recommend checking blood pressure at annual well-child pediatric appointments starting at age 3 years.
“The results of this study support monitoring blood pressure as an important metric of cardiovascular health in childhood,” said Bonita Falkner, MD, FAHA, an American Heart Association volunteer expert. “Moreover, the results of this study and other older child cohort studies with potential follow-up in adulthood will contribute to a more accurate definition of abnormal blood pressure and hypertension in childhood.” Falkner, who was not involved in this study, is emeritus professor of paediatrics and medicine at Thomas Jefferson University.
The researchers used the National Death Index to follow up on the survival or cause of death as of 2016 for approximately 38,000 children who had their blood pressures taken at age 7 years as part of the Collaborative Perinatal Project (CPP), the largest US study to document the influence of pregnancy and post-natal factors on the health of children. Blood pressure measured in the children at age 7 years were converted to age-, sex-, and height-specific percentiles according to the American Academy of Pediatrics clinical practice guidelines. The analysis accounted for demographic factors as well as for childhood body mass index, to ensure that the findings were related to childhood blood pressure itself rather than a reflection of children who were overweight or had obesity.
After follow-up through an average age of 54 years, the analysis found:
Children who had higher blood pressure (age-, sex-, and height-specific systolic or diastolic blood pressure percentile) at age 7 were more likely to die early from cardiovascular disease as adults by their mid-50s. The risk was highest for children whose blood pressure measurements were in the top 10% for their age, sex and height.
By 2016, a total of 2,837 participants died, with 504 of those deaths attributed to cardiovascular disease.
Both elevated blood pressure (90-94th percentile) and hypertension (≥ 95th percentile) were linked with about a 40% to 50% higher risk of early cardiovascular death in adulthood.
Moderate elevations in blood pressure were also important, even among children whose blood pressure was still within the normal range. Children who had blood pressures that were moderately higher than average had a 13% (for systolic) and 18% (for diastolic) higher risk of premature cardiovascular death.
Analysis of the 150 clusters of siblings in the CPP found that children with the higher blood pressure at age 7 had similar increases in risk of cardiovascular death when compared to their siblings with the lower blood pressure readings (15% increase for systolic and 19% for diastolic), indicating that their shared family and early childhood environment could not fully explain the impact of blood pressure.
“Even in childhood, blood pressure numbers are important because high blood pressure in children can have serious consequences throughout their lives. It is crucial to be aware of your child’s blood pressure readings,” Freedman said.
The study has several limitations, primarily that the analysis included one, single blood pressure measurement for the children at age seven, which may not capture variability or long-term patterns in childhood blood pressure. In addition, participants in the CPP were primarily Black or white, therefore the study’s findings may not be generalisable to children of other racial or ethnic groups. Also, children today are likely to have different lifestyles and environmental exposures than the children who participated in the CPP in the 1960s and 1970s.
Study details, background and design:
38 252 children born to mothers enrolled at one of 12 sites across the U.S. as part of the Collaborative Perinatal Project between 1959-1965. 50.7% of participants were male; 49.4% of mothers self-identified as Black, 46.4% reported as white; and 4.2% of participants were Hispanic, Asian or other groups.
This analysis reviewed blood pressure taken at age 7, and these measures were converted to age-, sex-, and height-specific percentiles according to the American Academy of Pediatrics Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents.
Survival through 2016 and the cause of death for the offspring of CPP participants in adulthood were retrieved through the National Death Index.
Survival analysis was used to estimate the association between childhood blood pressure and cardiovascular death, adjusted for childhood body mass index, study site, and mother’s race, education and marital status.
In addition, the sample included 150 groups of siblings, and the researchers examined whether the sibling with higher blood pressure was more likely to die of cardiovascular disease than the sibling with lower blood pressure. This sibling analysis allowed researchers to ask how much shared family and early childhood factors might account for the mortality risk related to blood pressure.
Korean children with early life exposure to antibiotics were not diagnosed with autoimmune diseases at higher rates
Photo by Chayene Rafaela on Unsplash
The global incidence of autoimmune diseases among children has increased over the past few decades. A study published August 21st in the open-access journal PLOS Medicine by Ju-Young Shin at Sungkyunkwan University, Republic of Korea, and colleagues suggests that early life antibiotic exposure is not associated with an increased risk of autoimmune diseases in children.
Previous research has suggested that exposure to antibiotics as a foetus or infant may contribute to the development of autoimmune diseases among children. However, confounding variables limit the validity of prior studies and the association of antibiotics to autoimmune disease remains poorly understood.
In order to investigate whether antibiotics may increase risk of autoimmune diseases, researchers conducted a retrospective cohort study comprised of over 4 million children born in the Republic of Korea between April 1, 2009, and December 31, 2020. They accessed a mother-child linked insurance claims database from the South Korea National Health Insurance Service-National Health Insurance Database (NHIS-NHID) to identify children whose mothers had received antibiotic prescriptions during pregnancy or while breastfeeding their infant. The researchers then retrospectively analysed the health outcomes of each cohort for a period of over 7 years, tracking all diagnoses of Type 1 diabetes, Juvenile idiopathic arthritis, Inflammatory bowel disease (ulcerative colitis, Crohn’s disease), Systemic lupus erythematosus, and Hashimoto’s thyroiditis.
The researchers found no relationship between antibiotic exposure during pregnancy or early infancy and the overall incidence of autoimmune diseases in children. Future research is needed, however, to replicate the outcomes in other populations and to further investigate potential effects on subgroups.
According to the authors, “Our findings suggest no association between antibiotic exposure during the prenatal period or early infancy and the development of autoimmune diseases in children. This observation contrasts with several previous studies reporting increased risks and underscores the importance of carefully considering the underlying indications for antibiotic use and genetic susceptibility when interpreting such associations. While the potential benefits of antibiotic treatment in managing infections during pregnancy or early infancy likely outweigh the minimal risk of autoimmune outcomes, our findings also highlight the need for cautious and clinically appropriate use of antibiotics during these critical developmental periods in specific subgroups.”
The authors note, “Exposure to antibiotics during pregnancy or early infancy was not associated with an increased risk of autoimmune diseases in children. Nevertheless, the importance of follow-up studies to confirm and extend these findings cannot be overstated.”
Colourised transmission electron micrograph of an HIV-1 virus particle (yellow/gold) budding from the plasma membrane of an infected H9 T cell (purple/green).
A new study in Nature shows that delivering a single injection of gene therapy at birth may offer years-long protection against HIV, taking advantage of a critical window in early life that could reshape the fight against paediatric infections in high-risk regions.
This study is among the first to show that the first weeks of life, when the immune system is naturally more tolerant, may be the optimal window for delivering gene therapies that would otherwise be rejected at older ages.
“Nearly 300 children are infected with HIV each day,” said first author Amir Ardeshir, associate professor of microbiology and immunology at the Tulane National Primate Research Center, who conducted the study alongside fellow researchers at the California National Primate Research Center. “This approach could help protect newborns in high-risk areas during the most vulnerable period of their lives.”
“This is a one-and-done treatment that fits the critical time when these mothers with HIV in resource-limited areas are most likely to see a doctor.”
Amir Ardeshir
In the study, nonhuman primates received a gene therapy that programs cells to continuously produce HIV-fighting antibodies. Timing proved critical to the one-time treatment offering long-term protection.
Those that received the treatment within their first month of life were protected from infection for at least three years with no need for a booster, potentially signifying coverage into adolescence in humans. In contrast, those treated at 8–12 weeks showed a more developed, less tolerant immune system that did not accept the treatment as effectively.
“This is a one-and-done treatment that fits the critical time when these mothers with HIV in resource-limited areas are most likely to see a doctor,” Ardeshir said. “As long as the treatment is delivered close to birth, the baby’s immune system will accept it and believe it’s part of itself.”
More than 100 000 children acquire HIV annually, primarily through mother-to-child transmission after birth from breastfeeding. Antiretroviral treatments have shown success in suppressing the virus and limiting transmission. However, adherence to treatment and access to doctors both decline after childbirth, particularly in areas with limited access to healthcare.
To deliver the treatment, researchers used an adeno-associated virus (AAV), a harmless virus that can act as a cargo truck to deliver genetic code to cells. The virus was sent to muscle cells, unique in their longevity, and delivered instructions to produce broadly neutralising antibodies, or bNAbs, which are capable of neutralising multiple strains of HIV.
This approach solved a longstanding problem with bNAbs. Previous studies found them effective at fighting HIV, but they required repeated infusions, which are costly and pose logistical challenges in low-resource settings.
“Instead, we turn these muscle cells – which are long-lived – into micro factories that just keep producing these antibodies,” Ardeshir said.
Newborns showed greater tolerance and expressed high levels of bNAbs, which successfully prevented infection, while older infants and juveniles were more likely to have produced anti-drug antibodies that shut down the treatment.
Researchers also found that exposing fetuses to the antibodies before birth helped older infants accept the gene therapy later, avoiding the immune rejection that often occurs with age.
Still, Ardeshir said a one-time injection at birth offered a more cost-effective and feasible real-world solution, while putting less burden on the mother for a follow-up visit.
Questions remain as to how the results translate to human infants and children, who may be less susceptible to AAV-delivered treatments. The study also used one strain of simian–human immunodeficiency virus, which doesn’t reflect the variety of HIV strains.
If successful, however, this treatment could dramatically reduce mother-to-child HIV transmission rates in high-risk regions such as sub-Saharan Africa, where 90% of paediatric HIV cases can be found. It may also be adapted to protect against other infectious diseases like malaria, which disproportionately affects young children in low-income countries.
“Nothing like this was possible to achieve even 10 years ago,” Ardeshir said. “This was a huge result, and now we have all the ingredients to take on HIV.”
Preterm babies with very low birth weight who received a probiotic alongside antibiotics had fewer multidrug resistant bacteria and a more typical gut microbiome, a new study shows.
The paper published in Nature Communications is the result of a trial testing probiotics among a group of 34 pre-term babies born with a very low birth weight, under 1500g representing around 1-1.5% of babies born around the world. The study sequenced gut bacteria from the babies during the first three weeks after birth.
The collaborative study led by Professor Lindsay Hall and Dr Raymond Kiu from the University of Birmingham found that among babies who received a probiotic treatment of a certain strain including Bifidobacterium alongside antibiotics, levels of typical bacterial strains associated with early-life gut microbiota were at levels typical among full-term babies, reducing both the abundance of antibiotic resistance genes and the number of multi-drug resistant bacteria in the gut.
In the context of the global AMR crisis, this is a major finding, especially for NICUs where preterm infants are especially vulnerable. Probiotics are now used in many neonatal ICUs around the UK, and the WHO have recommended probiotic supplementation in preterm babies. Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold.Professor Lindsay Hall – University of Birmingham
There were lower levels of drug-resistant pathogens including Enterococcus associated with risks of infections and longer hospital stays. Babies who received probiotics also saw higher levels of certain positive bacteria found naturally in the gut.
Among babies who didn’t receive probiotics, analysis of the gut bacteria found that while some differences occurred between those receiving antibiotics or not, both groups saw a dominant microbiome develop that included key bacteria (pathobionts) that can cause health problems including life-threatening infections during the crucial period after birth, as well as in later life.
Professor Lindsay Hall from the University of Birmingham and a group leader at Quadram Institute Bioscience, and senior corresponding author of the study said: “We have already shown that probiotics are highly effective in protecting vulnerable preterm babies from serious infections, and this study now reveals that these probiotics also significantly reduce the presence of antibiotic resistance genes and multidrug-resistant bacteria in the infant gut. Crucially, they seem to do so selectively – targeting resistant strains without disrupting non-resistant strains that might be beneficial.
“In the context of the global AMR crisis, this is a major finding, especially for NICUs where preterm infants are especially vulnerable. Probiotics are now used in many neonatal ICUs around the UK, and the WHO have recommended probiotic supplementation in preterm babies.
“Our paper shows how beneficial this intervention can be for babies born prematurely to help them give their gut a kickstart, and reduce the impact of concerning pathogens taking hold.”
Dr Raymond Kiu from the University of Birmingham, first and co-corresponding author of the paper said: “Sequencing technology has now confirmed that probiotic Bifidobacterium rapidly replicates in the preterm gut during the first three weeks of life. Importantly, this successful colonisation drives the maturation of the gut microbiota and is linked to a noticeable reduction in multi-drug-resistant pathogens – pointing to its pivotal role in improving neonatal health. Our findings also shed light on the complex interactions between antibiotics, probiotics, and horizontal gene transfer (HGT) in shaping the early-life microbiome.
“We believe this research lays the groundwork for future studies exploring the role of probiotics in antimicrobial stewardship and infection control among preterm populations.”
Dr Saul Kaplan (left) stands next to Dr Kenny Beck, with mother Zukiswa Panyaza as her baby receives a full leg cast at the clubfoot clinic in Tygerberg Hospital’s Division of Orthopedic Surgery, while medical students observe. (Photo: Sue Segar/Spotlight)
By Sue Segar
When Karen Mara Moss’s son was diagnosed with clubfoot, she travelled to the US in search of a life-changing treatment. She made a promise to bring it home and two decades on, her non-profit is at the heart of a remarkable success story.
“I looked at those tiny feet. They were turned over and rigidly pointing inwards,” recalls Karen Mara Moss about the day her son Alex was born in 2003.
For her, the memory is as vivid today as it was then. Within moments of his birth, a concerned obstetrician commented on Alex’s feet. Then the paediatrician diagnosed Alex with bilateral clubfoot, a condition in which a baby is born with one or both feet twisted inward and downward.
“I remember thinking: Will he walk with a limp? Will people mock him?” Moss tells Spotlight. “It was a traumatic time.”
She says the paediatrician told her not to worry. “He said they’d have to cut his feet and straighten them, and it would all be perfect,” says Moss.
Despite having several prenatal scans and tests, the condition had not been picked up before birth.
The most common form of clubfoot present at birth is idiopathic clubfoot, medically known as talipes equinovarus. It is when a baby’s foot is pointed in and down because the tissues connecting the muscles to the bone are shorter than usual, leading to pain and reduced mobility if left untreated, according to a review study published in The Lancet medical journal. In most cases, the cause of this congenital anomaly which ranges from mild to severe, is unknown, baby boys are twice as likely to be born with clubfoot as baby girls, and about half of children with clubfoot have it in both feet. Globally, an estimated 176 000 babies are born with the condition every year.
Eight days after Alex was born, Moss says she met with a paediatric orthopaedic surgeon. She says he told her he’d fixed many clubfeet using the Kite method and even had one patient playing first-team rugby. The Kite method was developed in the 1930s and uses manipulations and castings to achieve a sequential and gradual full correction of the forefoot, then the hindfoot, and finally, the ankle. After the casting is done, the baby wears a special splint to keep the feet pointing slightly outward and upward, but, critically, many would also require further surgery.
Back then, the standard of care for clubfoot was surgical management, says Dr Pieter Maré, an orthopaedic surgeon who heads up the clubfoot clinic at Greys Hospital in Pietermaritzburg, Kwazulu-Natal. “The reality was that a large number of children required extensive surgery before the Ponseti method,” he says.
Moss followed the doctor’s advice, and during that first appointment, she says he began applying casts up to Alex’s knees. “He started wrenching Alex’s foot, holding the back, whilst pushing the front of the foot, and plastering the foot. Alex was blue in the face from screaming. I was crying while holding him down,” she says.
Another way
But after two months and seven casts, she says there was little improvement in Alex’s feet. That is when Moss began searching for answers herself. Doing research on the internet, she discovered the University of Iowa Children’s Hospital website, where she read about a technique developed by Dr Ignacio Ponseti, which he claimed could help children have pain-free, functional feet without surgery.
The Ponseti method was developed in the 1950s but only became more widely used in the United States in the 1990s, and later in much of the rest of the world. The technique uses gentle manipulations and plaster casts to correct the midfoot, hindfoot, and forefoot simultaneously, while the ankle is treated afterwards. In some cases, before the last cast is applied, it may require a percutaneous tenotomy which is a minimally invasive procedure to cut the heel cord that is resistant to stretching. A brace is then fitted the same day as the last cast is taken off.
“The Kite method was developed to correct clubfoot but over time it was realised that this method was using the wrong anatomical methods,” explains Professor Anria Horn, a consultant orthopaedic surgeon at the Red Cross Children’s Hospital in Cape Town.
“There are multiple joints in the foot and the Kite method was, effectively, manipulating the wrong joint in an attempt to bring about the correction in the foot. Ponseti discovered that the manipulation should occur at a different joint,” she says.
Back in 2003, Moss emailed Ponseti, and a few days later called his office. “I was put through to a man with a Spanish accent. He said he’d read my email, and that he’d seen the photos I sent of my son’s feet; that what we’d done was not the way his method worked. He suggested I go to Iowa because nobody in South Africa was practising his method,” she says.
Not long after this, Moss and her husband travelled with ten-week-old Alex for 10 000 miles from sunny South Africa to an unseasonable snowstorm in Iowa.
The idea of travelling to a foreign country to see a “special” doctor that one read about on the internet, with a treatment carrying his name, may raise red flags for some. There are after all no shortage of quacks out there exploiting vulnerable people with just this type of story of an underutilised treatment. Ponseti, however, was a serious scientist and, even by 2003, his method had performed well in several studies and had been quite widely adopted by doctors in the United States.
Moss says in that first visit, Ponseti eventually did a cast all the way up Alex’s leg. “He looked like a little turtle with his legs sticking out. By the time he’d done the second cast, Alex was asleep,” Moss recalls.
“Dr Ponseti’s normal protocol was to remove the cast every week, then re-manipulate the foot into a different position, and reapply the cast. For out-of-town patients, he accelerated the treatment and changed the cast every five days,” she adds.
After just one cast, Alex’s foot looked different, says Moss. “They did another cast, and five days later, it was time for the third cast. Dr Ponseti took the second cast off and then did the percutaneous tenotomy, as well as the third and final cast.”
After this procedure and with Alex now in his final casts, they were told they could return to South Africa and take the casts off three weeks later. Moss said an orthotist measured Alex’s feet before the tenotomy and gave her instructions on how to fit the clubfoot brace he would wear for four years while sleeping.
Three weeks later, back home, Moss soaked the casts off and started to put the brace on at night. She says Alex’s feet were straight.
‘A parting gift’
On her final day in Iowa, Moss recalls Ponseti telling her: “You’re the first South African that’s ever been here. Please go back home and tell the doctors not to operate on clubfoot”. He gave her his book, copies of his research papers, and CDs demonstrating his casting method – a parting gift that would shape the course of her life.
Determined to share her what she had learnt, Moss created a website to provide information on clubfoot. The website gained traction and soon she started getting requests from parents across southern Africa for help to access the Ponseti method.
At the time, Moss says she knew of only one doctor using the method, whom she recommended parents consult. “I’d met him soon after my return to South Africa in 2003 and had lent him Dr Ponseti’s book and papers. He’d then gone to the US to attend a Ponseti training workshop and started using the method. I was sending everyone to him.”
The founding of STEPS
Moss realised the best solution was to bring the training directly to South Africa. In 2005, despite having no experience in running a non-profit organisation, she founded STEPS, driven by her commitment to introduce the Ponseti method across the country.
Moss says STEPS held its first two-day Ponseti training course in 2006, with about 60 paediatric orthopaedic surgeons attending. “Three Ponseti experts came from Canada, Brazil and the UK to give the training. They taught a lot of theory and used bone models to demonstrate the method,” she says.
The second STEPS Ponseti workshop in 2007 focused on public health facilities. Moss says the training took place at the Charlotte Maxeke Johannesburg Academic Hospital.
Partly due to the workshops, partly due to the strength of the accumulating scientific evidence, the method caught on in the country. In 2012, the South African Paediatric Orthopaedic Society officially endorsed the method. A Cochrane Review published in the same year found that, while the available evidence was far from complete, it did indicate that the method works well. Cochrane Reviews are a highly regarded type of study that attempts to assess evidence from all randomised clinical trials relating to a specific medical question.
“The Ponseti method has become the gold standard for the treatment of idiopathic clubfoot,” stated an article published in the World Journal of Orthopedics in 2014. And according to the Lancet study cited earlier, “the Ponseti method is widely recognised as an effective conservative treatment approach for clubfoot that avoids corrective surgery in over 90% of cases”.
Today, Horn says the Kite method isn’t used in South Africa any more, having been replaced by the Ponseti method. “STEPS has played a big part in promoting the Ponseti method in South Africa, as well as providing training, workshops and conferences and supporting clubfoot clinics across the country. Our job would have been much harder without the support that STEPS provides,” she adds.
Ponseti in the public sector
Given the equipment and know-how involved, making the Ponseti method available in South Africa’s public sector was a challenge. In 2013, Moss launched a support programme to help government clinics offer the treatment. STEPS began by partnering with just six clinics. With support from donors, they recruited staff to visit each clinic weekly to guide families or trained someone on-site to do so. They also provided educational materials to help raise awareness. Over time, this led to STEPS helping develop standard systems and processes for running the clinics, making care more consistent and accessible. When some clinics couldn’t provide braces, STEPS arranged for it to be donated.
Today, STEPS has 48 partner clinics across South Africa, ranging from a tiny rural clinic in Lusikisiki in the Eastern Cape to bigger clinics in Gauteng and the Western Cape. “Lusikisiki might see three patients a week, and Chris Hani Baragwanath Academic Hospital could see 80. They all open once a week, except for some small, rural clinics,” Moss says.
Based on stats that STEPS collected, Moss estimates that at least 2 000 children are born every year with clubfoot in South Africa. Through the help of her organisation, she says: “More than 20 500 children have accessed effective treatment. We’ve … distributed 22 628 clubfoot braces. In 2024, we supported 4 592 children at partner clinics in different stages of the four-year treatment protocol.”
Moss adds that STEPS has conducted over 20 training sessions across South Africa, Namibia, Botswana, and the Seychelles, with more than 2 000 healthcare professionals. “Parents were bringing their children over the border as they couldn’t access treatment back home. We worked with the ministries of health in those countries to teach the Ponseti method there,” she says.
Though separated by an ocean, Moss says she stayed in close contact with Ponseti. She says the last time they saw each other was at a clubfoot symposium in Iowa in 2007. Two years later, he passed away at the age of 95.
“I felt as if I’d lost a member of my family,” Moss says. “He was the master, and he inspired me in my work to improve the lives of children born with clubfoot.” She said she would always carry the ache of missing him, but bringing his method to South Africa, just as she had promised, was something that gave her a deep sense of purpose and peace.
That promise, purpose and peace started with Alex who is today in his final year of a Bachelor of Commerce degree and who, in his own words, “enjoys being active outdoors with my friends”, likes playing padel, and going on hikes.
*This article is part of Spotlight’s 2025 Women in Health series, featuring the remarkable contributions of women to healthcare and science.
