A rare disorder which causes babies to be born with extra fingers and toes and a range of birth defects has been identified in new research published in the American Journal of Human Genetics. The disorder, which has not yet been named, is caused by a genetic mutation in a gene called MAX.
As well as extra digits – polydactyly — it leads to a range of symptoms relating to ongoing brain growth, such as autism. The research marks the first time this genetic link has been identified. It has also found a molecule that could potentially be used to treat some of the neurological symptoms and prevent any worsening of their condition. However, more research is needed to test this molecule before it can be used as a treatment.
Co-led by the University of Leeds, the study focuses on three individuals with a rare combination of physical traits, namely polydactyly, and a much larger than average head circumference – known as macrocephaly.
The individuals share some other characteristics, including delayed development of their eyes which results in problems with their vision early in life.
The researchers compared the DNA of these individuals and found they all carried the shared genetic mutation causing their birth defects.
The latest research was co-led by Dr James Poulter from the University of Leeds; Dr Pierre Lavigne at Université de Sherbrooke in Québec and Professor Helen Firth at Cambridge University.
As with many rare disorders, the disorder currently has no treatments – but in this case, the researchers identified one already undergoing clinical trials which might reverse some of the mutation’s effects.
The study team has highlighted the importance of interdisciplinary research into rare diseases in giving understanding and hope of a treatment to families who often face many years of uncertainty about their child’s condition and prognosis.
The researchers now plan to look for additional patients with mutations in MAX to better understand the disorder and investigate whether the potential treatment improves the symptoms caused by the mutation.
Asthma and cystic fibrosis are diseases which affect the lungs of children and adults. Previous research has shown that genetic and environmental factors during pregnancy and early childhood can contribute to the way children and young adults are affected by these lung diseases.
In her thesis, Emma Caffrey Osvald, PhD student at Karolinska Institutet looked for new factors that may influence the development and outcomes of asthma and cystic fibrosis. In the four included studies, Emma used data from a clinical cohort and national health and demographic registers and a quality register on individuals born in Sweden to shed light on potential factors which impact the course of asthma and cystic fibrosis. Her findings should be useful when creating clinical guidelines and policies for the prevention and management of respiratory disease in children and young adults.
What are the most important results in your thesis?
“In my first study, we show that mothers with asthma have an increased likelihood of having a child with asthma and that higher lung function in pregnancy is associated with a decreased likelihood of having a child with asthma. However, asthma or lung function in the mother does not impact childhood growth. In the second study, we see that parental social standing (socioeconomic status, measured as parents’ education and income) is associated with the onset of asthma in childhood. By comparing the social standing and onset of asthma among first cousins we see that parental education may be directly linked to the onset of asthma. In the third study, we also show that there is a connection between having asthma in childhood or young adulthood and death between 1 to 25 years of age. The likelihood of death between 1 to 25 years of age is higher if the person also has a life-limiting disease but not altered by the parents social standing at the child’s birth. In the final study, we see some association between low parental social standing and severe disease and lung function decline among persons with cystic fibrosis, however low parental social standing does not impact growth. So we found that there are factors in the parents (including during the pregnancy and social standing) which impacts the onset of asthma. Asthma increases the risk of mortality between 1 to 25 years and low parental social standing is shown to be associated with severe disease and lung function decline in persons with cystic fibrosis.”
Why did you become interested in this topic?
“I have wanted to learn more about epidemiology ever since my ex-job project as a medical student and these PhD projects have allowed me, as a paediatric pulmonologist, to explore the factors which influence onset and outcomes for children and young adults with respiratory disease. Asthma and CF are two chronic diseases which we meet as part of our routine clinical practice and for me it has been really interesting to avail of both clinical data and national register data and a variety of statistical methods to further our understanding of these diseases.“
What do you think should be done in future research?
“Areas which will interest me in my future research continues to be the determinants and outcomes of respiratory disease in childhood. For me, the future of register-based research lies in the combining of clinical data with register data. There is more to explore in regards to risk factors for acute respiratory disease such as severe pneumonia and empyema, but also the outcomes for persons with asthma and CF, such as presence of comorbidity or educational attainment.”
A state witness in the trial of murder accused Dr Peter Beale has testified that colleagues advised him against a procedure which led to the death of a three year old patient.
Paediatric surgeon Beale is charged with three counts of murder, as a result of deaths from unnecessary surgeries over 2012 to 2019. He is also charged with two counts of fraud. He was first arrested in 2019, with his trial date postponed multiple times and only getting underway this week Monday in Johannesburg. His co-accused, anaesthetist Dr Abdulhay Munshi, was shot dead in 2020. As a result of the case, some have voiced concerns over what could lead to criminalisation over deaths resulting from unavoidable errors and systemic failures.
Two of the three deaths stemmed from laparoscopic Nissen fundoplication, a complex and costly procedure that is usually used to treat GERD by tightening the junction of the oesophagus and stomach.
According to the indictment, Beale is accused of “unlawfully and intentionally” causing the deaths of a three-year-old boy in 2012, a 21-month-old girl in 2016 and a 10-year-old boy in 2019 after he had operated on the children.
The state contends that Beale performed these unnecessary procedures as he needed money to recover from heavy financial losses incurred in a failed investment in the 1990s.
News24 reports that, based on a rectal biopsy, Beale believed that the three year old boy had Hirschsprung’s Disease, requiring surgical intervention. As reported in Beeld, Beale said in his plea explanation that he “misread” the patient’s biopsy results and did not deliberately misrepresent the biopsy results to the parents.
The parents sought a second opinion, the state alleges, and the second doctor was hesitant about carrying out the procedure. Beale was able to convince the other doctor that the procedure was necessary based on the biopsy results. Beale also explained in his plea deal that there was a variant of the disease, and the treatment was the same. His counsel, Advocate Ian Greene, also pointed out that the pathologist testified at a disciplinary hearing that the biopsy did not exclude the variant even if it did not exclude Hirschsprung’s Disease.
According to News24, a state witness, who is another paediatric surgeon who remains anonymous at the court’s order, stated that Beale had tried to recruit him to a Ponzi scheme. The scheme had a joining fee of R1 million.
The witness, who had know Beale since 1996, said that in 2009, the accused had also confided in him at a conference that he had suffered significant losses in an investment. The witness was also on the committee at the Healthcare Practitioners’ Council of South Africa disciplinary hearing over the three-year-old’s death. Beale has since been struck from the HPCSA.
The South African Medical Association released a statement urging that, while tragic, the case highlights laws that criminalise and punish individuals instead of taking into account the various organisational failings that can lead to patient deaths and can in no way prevent “unavoidable errors”.
Note: this article has been updated to correct the number of laparoscopic Nissen fundoplication procedures and to add more information about the Hirschsprung’s Disease diagnosis.
Sickle cell disease. Credit: National Institutes of Health
A clinical trial in Uganda has revealed that hydroxyurea significantly reduces infections in children with sickle cell anaemia. Their latest findings enhance strong evidence of hydroxyurea’s effectiveness and could ultimately reduce death in children in Africa, the continent most burdened by the disease.
The group’s research, appearing in the journal Blood, revealed that hydroxyurea treatment resulted in a remarkable 60% reduction in severe or invasive infections, including malaria, bacteraemia, respiratory tract infections and gastroenteritis, among Ugandan children with sickle cell anaemia.
“Our investigation provides powerful justifications for hydroxyurea’s use in children with sickle cell anaemia in Africa,” said Dr Chandy John, paediatrics professor at IU School of Medicine and co-lead investigator of the latest study.
“Given the high rates of infection in this region, we hope our evidence will encourage ministries of health to continue supporting and expanding access to hydroxyurea for young patients who can greatly benefit from the treatment.”
Sickle cell anaemia is a genetic blood disorder that alters the structure of red blood cells and affects oxygen distribution throughout the body, increasing susceptibility to serious health complications and life-threatening infections.
According to the World Health Organization, more than 300 000 children worldwide are born with sickle cell disease each year, with a high prevalence found in African countries.
While hydroxyurea has had U.S. Food and Drug Administration approval as a sickle cell disease treatment for children since 2017, its accessibility and acceptance in Africa have been comparatively limited.
As hydroxyurea has become more recognised in African countries for its effectiveness in treating sickle-cell-related complications, John and his colleagues noticed a knowledge gap about the treatment’s effect on infections.
This led the research group to incorporate hydroxyurea treatment and analysis into their established clinical trial, Zinc for Infection Prevention in Sickle Cell Anemia, led by Indiana University School of Medicine and collaborators in Uganda.
During the study, the researchers examined the effects of hydroxyurea on 117 children in Uganda and focused on a range of infections. After hydroxyurea treatment, results showed a substantial decrease in the incidence of these infections.
Additionally, eight of the nine deaths that occurred in the trial were children whose parents declined hydroxyurea treatment. The only death in a child on hydroxyurea treatment occurred four days after starting treatment, providing insufficient time for hydroxyurea to have an effect.
Of the five children for whom a cause of death was known, all five died of infectious causes.
The high death rate in the study, despite expert clinical care by study personnel, provides further evidence of the urgent need for additional interventions to decrease mortality in children with sickle cell disease in Africa.
“Infections commonly precede other complications related to sickle cell anaemia and often result in hospitalizations that can lead to death,” said Dr Ruth Namazzi, site principal investigator, first author and a lecturer in the Department of Pediatrics and Child Health at Makerere University in Uganda.
“We believe incorporating hydroxyurea treatment as the standard of care for sickle cell anaemia across Africa will not only reduce infections but will more importantly save countless lives.”
A new study co-led by investigators from Mass Eye and Ear, a member of Mass General Brigham, demonstrated the effectiveness of a gene therapy towards restoring hearing function for children suffering from hereditary deafness.
In a trial of six children taking place at the Eye & ENT Hospital of Fudan University in Shanghai, China, the researchers found the novel gene therapy to be an effective treatment for patients with a specific form of autosomal recessive deafness caused by mutations of the OTOF (otoferlin) gene, called DFNB9. With its first patient treated in December 2022, this research represents the first human clinical trial to administer gene therapy for treating this condition, with the most patients treated and longest follow-up to date. Their results are published in The Lancet.
“If children are unable to hear, their brains can develop abnormally without intervention,” said Zheng-Yi Chen, DPhil, an associate scientist in the Eaton-Peabody Laboratories at Mass Eye and Ear and associate professor of Otolaryngology–Head and Neck Surgery at Harvard Medical School. “The results from this study are truly remarkable. We saw the hearing ability of children improve dramatically week by week, as well as the regaining of their speech.”
Hearing loss affects more than 1.5 billion people worldwide, with congenital deafness making up about 26 million of those individuals. For hearing loss in children, more than 60% stem from genetic reasons. DFNB9 for example, is a hereditary disease caused by mutations of the OTOF gene and a failure to produce a functioning otoferlin protein, which is necessary for the transmission of the sound signals from the ear to the brain. There are currently no FDA-approved drugs to help with hereditary deafness, which has opened the door for new solutions like gene therapies.
In order to test this novel treatment, six children with DFNB9 were observed over a 26-week period at the Eye & ENT Hospital of Fudan University. The Mass Eye and Ear collaborators utilised an adeno-associated virus (AAV) carrying a version of the human OTOF gene to carefully introduce the gene into the inner ears of the patients through a special surgical procedure. Differing doses of the single injection of the viral vector were used.
All six children in the study had total deafness, as indicated by an average auditory brainstem response (ABR) threshold of over 95 decibels. After 26 weeks, five children demonstrated hearing recovery, showing a 40-57 decibel reduction in ABR testing, dramatic improvements in speech perception and the restored ability to conduct normal conversation. Overall, no dose-limiting toxicity was observed. While following up on the patients, 48 adverse events were observed, with a significant majority (96%) being low grade, and the rest being transitory with no long-term impact.
This study provides evidence towards the safety and effectiveness of gene therapies in treating DFNB9, as well as their potential for other forms of genetic hearing loss. Moreover, the results contribute to an understanding of the safety of AAV insertion into the human inner ear. In regard to the usage of AAVs, the success of a dual-AAV vector carrying two pieces of the OTOF gene is notable. Typically, AAVs have a gene size limit, and so for a gene like OTOF that exceeds that limit, the achievement with a dual viral vector opens the door for AAV’s use with other large genes that are typically too big for the vector.
“We are the first to initiate the clinical trial of OTOF gene therapy. It is thrilling that our team translated the work from basic research in animal model of DFNB9 to hearing restoration in children with DFNB9,” said lead study author Yilai Shu, MD, of the Eye & ENT Hospital of Fudan University at Fudan University. Shu previously served as a postdoctoral fellow in Chen’s lab at Mass Eye and Ear. “I am truly excited about our future work on other forms of genetic hearing loss to bring treatments to more patients.”
The researchers plan to expand the trial to a larger sample size as well as track their outcomes over a longer timeline.
“Not since cochlear implants were invented 60 years ago, has there been an effective treatment for deafness,” said Chen. “This is a huge milestone that symbolises a new era in the fight against all types of hearing loss.”
Healthy children in Malawi participating in study to test efficacy of typhoid conjugate vaccine. Credit: TyVAC/Madalitso Mvula
A single dose of the typhoid conjugate vaccine, Typbar TCV®, provides lasting efficacy in preventing typhoid fever in children ages 9 months to 12 years old, according to a new phase 3 clinical study published in The Lancet.
The study conducted by researchers at University of Maryland School of Medicine’s (UMSOM) Center for Vaccine Development and Global Health (CVD) and led by in-country partners at the Malawi-Liverpool Wellcome Trust (MLW) Clinical Research Programme.
The research team enrolled more than 28 000 healthy children in Malawi and randomly assigned about half the group to receive the TCV and the other half to receive a meningococcal capsular group A conjugate (MenA) control vaccine. During the more than four years of follow-up, 24 children in the TCV group and 110 in the MenA group developed typhoid fever, which was confirmed via blood culture. That resulted in an efficacy of 78.3% in the TCV group, with one case of typhoid prevented for every 163 children vaccinated. TCV was effective in all age groups and over the study period – which ended in 2022 – vaccine efficacy remained strong, decreasing by only 1.3% per year.
Typhoid fever causes more than 9 million illnesses and at least 110,000 deaths worldwide every year, mostly in sub-Saharan Africa and southeast Asia. It is a contagious bacterial infection that occurs from consuming contaminated food or beverages. Symptoms include nausea, fever, and abdominal pain that, if left untreated, can be deadly.
“These findings have significant implications for identification of the contribution of TCVs in the control and potential elimination of typhoid fever in endemic settings,” wrote the authors of a commentary published in The Lancet alongside the study.
In May 2023, the Malawi government launched a national rollout of the TCV in children under 15 years. Going forward, all children in Malawi will receive TCV at 9 months of age as part of the routine immunisation schedule.
“The newly published study supports the long-lasting impacts of a single shot of TCV, even in the youngest children, and offers hope of preventing typhoid in the most vulnerable children,” said Kathleen Neuzil, MD, MPH, CVD Director, the Myron M. Levine, MD, DTPH, Professor in Vaccinology at UMSOM and coauthor of the current study. “We could not have had a better partner in this endeavor than MLW, whose long-standing excellence in typhoid research and strong surveillance infrastructure made this study possible.”
“The CVD’s outstanding record of generating data to accelerate public health decisions continues with this landmark study,” said UMSOM Dean Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor. “The research could not come at a more critical time when Malawi and other African countries are struggling with climate change, extreme weather events and increased urbanisation patterns, which are likely to contribute to increases in enteric diseases, including typhoid.”
One in three children who fall ill from bacterial meningitis go on to live with permanent neurological disabilities due to the infection. This is according to a new epidemiological study led by Karolinska Institutet and published in JAMA Network Open. This marks the first time that researchers have identified the long-term health burden of bacterial meningitis.
The bacterial infection can currently be cured with antibiotics, but it often leads to permanent neurological impairment. And since children are often affected, the consequences are significant.
“When children are affected, the whole family is affected. If a three-year-old child has impaired cognition, a motor disability, impaired or lost vision or hearing, it has a major impact. These are lifelong disabilities that become a major burden for both the individual and society, as those affected need health care support for the rest of their lives,” says Federico Iovino, associate professor in Medical Microbiology at the Department of Neuroscience, Karolinska Institutet, and one of the authors of the current study.
By analyzing data from the Swedish quality register on bacterial meningitis between 1987 and 2021, the researchers have been able to compare just over 3500 people who contracted bacterial meningitis as children with just over 32 000 matched controls from the general population, with an average follow-up time of over 23 years.
The results show that those diagnosed with bacterial meningitis consistently have a higher prevalence of neurological disabilities such as cognitive impairment, seizures, visual or hearing impairment, motor impairment, behavioural disorders, or structural damage to the head.
The risk was highest for structural head injuries – 26 times greater, hearing impairment – almost eight times greater, and motor impairment almost five times greater.
About one in three people affected by bacterial meningitis had at least one neurological impairment compared to one in ten among controls.
“This shows that even if the bacterial infection is cured, many people suffer from neurological impairment afterwards,” says Federico Iovino.
With the long-term effects of bacterial meningitis identified, Federico Iovino and his colleagues will now move forward with their research.
“We are trying to develop treatments that can protect neurons in the brain during the window of a few days it takes for antibiotics to take full effect. We now have very promising data from human neurons and are just entering a preclinical phase with animal models. Eventually, we hope to present this in the clinic within the next few years,” says Federico Iovino.
Babies and toddlers exposed to television or video viewing may be more likely to exhibit atypical sensory behaviours, such as being disengaged and disinterested in activities, seeking more intense stimulation in an environment, or being overwhelmed by sensations like loud sounds or bright lights, according to data from researchers at Drexel’s College of Medicine published in the journal JAMA Pediatrics.
According to the researchers, children exposed to greater TV viewing by their second birthday were more likely to develop atypical sensory processing behaviours, such as “sensation seeking” and “sensation avoiding,” as well as “low registration” – being less sensitive or slower to respond to stimuli, such as their name being called, by 33 months old.
Sensory processing skills reflect the body’s ability to respond efficiently and appropriately to information and stimuli received by its sensory systems, such as what the toddler hears, sees, touches, and tastes.
The team pulled 2011-2014 data on television or DVD-watching by babies and toddlers at 12- 18- and 24-months from the National Children’s Study of 1471 children (50% male) nationwide.
Sensory processing outcomes were assessed at 33 months using the Infant/Toddler Sensory Profile (ITSP), a questionnaire completed by parents/caregivers, designed to give insights on how children process what they see, hear and smell, etc.
ITSP subscales examine children’s patterns of low registration, sensation seeking, such as excessively touching or smelling objects; sensory sensitivity, such as being overly upset or irritated by lights and noise; and sensation avoiding – actively trying to control their environment to avoid things like having their teeth brushed. Children score in “typical,” “high” or “low” groups based on how often they display various sensory-related behaviours. Scores were considered “typical” if they were within one standard deviation from the average of the ITSP norm.
Measurements of screen exposure at 12-months were based on caregiver responses to the question: “Does your child watch TV and/or DVDs? (yes/no),” and at 18- and 24- months based on the question: “Over the past 30 days, on average, how many hours per day did your child watch TV and/or DVDs?”
The findings suggest:
At 12 months, any screen exposure compared to no screen viewing was associated with a 105% greater likelihood of exhibiting “high” sensory behaviours instead of “typical” sensory behaviours related to low registration at 33 months
At 18 months, each additional hour of daily screen time was associated with 23% increased odds of exhibiting “high” sensory behaviours related to later sensation avoiding and low registration.
At 24 months, each additional hour of daily screen time was associated with a 20% increased odds of “high” sensation seeking, sensory sensitivity, and sensation avoiding at 33 months.
The researchers adjusted for age, whether the child was born prematurely, caregiver education, race/ethnicity and other factors, such as how often the child engages in play or walks with the caregiver.
The findings add to a growing list of concerning health and developmental outcomes linked to screen time in infants and toddlers, including language delay, autism spectrum disorder, behavioural issues, sleep struggles, attention problems and problem-solving delays.
“This association could have important implications for attention deficit hyperactivity disorder and autism, as atypical sensory processing is much more prevalent in these populations,” said lead author Karen Heffler, MD, an associate professor of Psychiatry in Drexel’s College of Medicine. “Repetitive behaviour, such as that seen in autism spectrum disorder, is highly correlated with atypical sensory processing. Future work may determine whether early life screen time could fuel the sensory brain hyperconnectivity seen in autism spectrum disorders, such as heightened brain responses to sensory stimulation.”
Atypical sensory processing in kids with autism spectrum disorder (ASD) and ADHD manifests in a range of detrimental behaviours. In children with ASD, greater sensation seeking or sensation avoiding, heightened sensory sensitivity and low registration have been associated with irritability, hyperactivity, eating and sleeping struggles, as well as social problems. In kids with ADHD, atypical sensory processing is linked to trouble with executive function, anxiety and lower quality of life.
“Considering this link between high screen time and a growing list of developmental and behavioural problems, it may be beneficial for toddlers exhibiting these symptoms to undergo a period of screen time reduction, along with sensory processing practices delivered by occupational therapists,” said Heffler.
The American Academy of Pediatrics (AAP) discourages screen time for babies under 18–24 months. Live video chat is considered by the AAP to be okay, as there may be benefit from the interaction that takes place. AAP recommends time limitations on digital media use for children ages two to five years to typically no more than one hour per day.
“Parent training and education are key to minimising, or hopefully even avoiding, screen time in children younger than two years,” said senior author David Bennett, PhD, a professor of Psychiatry in Drexel’s College of Medicine.
In a study designed to better understand sudden, unexpected deaths in young children, which usually occur during sleep, researchers have identified brief seizures, accompanied by muscle convulsions, as a potential cause.
Experts estimate in excess of 3000 families each year in the US lose a baby or young child unexpectedly and without explanation. Most are infants in what is referred to as sudden infant death syndrome, or SIDS, but 400 or more cases involve children aged 1 and older, and in what is called sudden unexplained death in children (SUDC). Over half of these children are toddlers.
The study, published in the journal Neurology, used a registry of more than 300 SUDC cases, set up a decade ago by researchers at NYU Grossman School of Medicine. Researchers used extensive medical record analysis and video evidence donated by families to document the inexplicable deaths of seven toddlers between the ages of 1 and 3 that were potentially attributable to seizures. These seizures lasted less than 60 seconds and occurred within 30 minutes immediately prior to each child’s death, say the study authors.
For decades, researchers have sought an explanation to sudden death events in children, noticing a link between those with a history of febrile seizures (seizures accompanied by fever). Earlier research had reported that children who died suddenly and unexpectedly were 10 times more likely to have had febrile seizures than children who did not die suddenly and unexpectedly. Febrile seizures are also noted in one-third of SUDC cases registered at NYU Langone Health.
The new study involved an analysis by a team of eight physicians of the rare SUDC cases for which there were also home video recordings, from either security systems or commercial crib cameras, made while each child was sleeping on the night or afternoon of their death.
Five of seven recordings were running nonstop at the time and showed direct sound and visible motion indicative of a seizure happening. The remaining two recordings were triggered by sound or motion, but only one suggested that a muscle convulsion, a sign of seizure, had occurred. As well, only one toddler had a documented previous history of febrile seizures. All children in the study had previously undergone an autopsy that revealed no definitive cause of death.
“Our study, although small, offers the first direct evidence that seizures may be responsible for some sudden deaths in children, which are usually unwitnessed during sleep,” said study lead investigator Laura Gould, a research assistant professor at NYU Langone. Gould lost her daughter, Maria, to SUDC at the age of 15 months in 1997, a tragedy that prompted her successful lobby for establishment of the NYU SUDC Registry and Research Collaborative. Gould points out that if not for the video evidence, the death investigations would not have implicated a seizure.
“These study findings show that seizures are much more common than patients’ medical histories suggest, and that further research is needed to determine if seizures are frequent occurrences in sleep-related deaths in toddlers, and potentially in infants, older children, and adults,” said study senior investigator and neurologist Orrin Devinsky, MD.
Devinsky, a professor in the Departments of Neurology, Neurosurgery, and Psychiatry at NYU Langone, as well as chief of its epilepsy service, adds that “convulsive seizures may be the ‘smoking gun’ that medical science has been looking for to understand why these children die.
“Studying this phenomenon may also provide critical insight into many other deaths, including those from SIDS and epilepsy,” said Devinsky, who cofounded the SUDC Registry and Research Collaborative at NYU Langone with Gould.
Further research, Devinsky notes, is also needed to determine precisely how seizures with or without fever may induce sudden death. Previous research in epilepsy patients, he says, points to difficulty breathing that is known to occur immediately after a seizure and that can lead to death. This has been found to happen more frequently in epilepsy patients, as it does in the children involved in the study, while they are sleeping face down on the stomach and without anyone witnessing the death.
Continuous monitoring of child deaths and improvements in health records to track how often these convulsive seizures precede death, he explains, will be needed for this to be confirmed. Seizure-related deaths are underreported in people with and without epilepsy.
For the study, experts in forensic pathology, neurology, and sleep medicine analysed each recording for video quality, sound, and motion. From this, they were able to determine which toddlers showed signs of muscle convulsions as a sign of seizures prior to their death and when. Access to the videos was and remains strictly limited to the researchers involved in the study.
Infants born extremely prematurely need enrichment in addition to breast milk, but it wasn’t clear as to whether enrichments were made from breast milk or cow’s milk had an effect on the risk of severe complications. This has been investigated by a large clinical study led by Linköping University, Sweden, published in eClinicalMedicine.
Infants born extremely prematurely, between weeks 22 and 27 of pregnancy, are among the most vulnerable patients in healthcare, at high risk of serious complications and mortality.
There is strong research support for giving breast milk to these children rather than formula made from cow’s milk. Formula based on cow’s milk is known to increase severe the risks for intestinal inflammation and sepsis.
“In Sweden, all extremely preterm infants receive breast milk from their mother or donated breast milk. Despite this, almost one in ten children get a severe inflammation of the intestine called necrotising enterocolitis. It’s one of the worst diseases you can have. At least three out of ten children die and those who survive often have neurological problems afterwards,” says Thomas Abrahamsson, professor at Linköping University and senior physician at the neonatal department at the University Hospital in Linköping, who led the current study.
Historically, there have been very few studies on extremely preterm infants where treatments have been compared against each other.
Therefore, there is a great need for clinical studies that can provide scientific support for how these children should be treated to have better chances of survival and a good life.
In some countries, such as Sweden, infants are fed exclusively with either their mother’s breast milk or donated breast milk.
However, in order for extremely preterm infants to grow as well as possible, they need more nutrition than breast milk contains. This is why breast milk is supplemented with extra protein, so-called enrichment.
The enrichment has previously been made from cow’s milk. But there have been suspicions that cow’s milk-based enrichment increases the risk of severe complications. Today, there is enrichment that is based on donated breast milk, and which has begun to be used in healthcare in some places.
The big question is whether it can reduce the risk of diseases in extremely preterm infants.
The current study, called N-Forte (the Nordic study on human milk fortification in extremely preterm infants), is the largest that has been carried out to seek answers to this question.
The results have been eagerly awaited by paediatricians and others caring for these fragile infants.
“We concluded that it doesn’t matter whether extremely preterm infants get enrichment made from cow’s milk or made from donated breast milk,” says Thomas Abrahamsson.
Although the study indicates that there was no difference between the two options, its results can be useful – the breast milk enrichment is fairly expensive.
“On the one hand, we’re disappointed that we didn’t find a positive effect of enrichment based on breast milk. On the other hand, it’s a large and well-done study and we can now say with great certainty that it doesn’t have an effect in this patient group. This is also important knowledge, so that we don’t invest in expensive products that don’t have the desired effect,” says Thomas Abrahamsson.
The N-Forte study included 228 extremely preterm infants, randomised 1:1 to receive enrichment made from breast milk and cow’s milk respectively.
The researchers examined whether the two groups differed in the incidence of necrotising enterocolitis, sepsis and death.
Of the children treated with breast milk-based enrichment, 35.7% had these complications, while the corresponding proportion was 34.5% in the group receiving cow’s milk-based enrichment, which means that there was no difference between the groups.
The results of the study are in line with a smaller study from Canada published in 2018, where researchers also saw no difference between the two types of enrichment on necrotising enterocolitis and severe sepsis.
