A new study published in Nature Communications suggests that use of antidepressants can impact early post-natal brain development, potentially contributing to the development of mental health disorders. The study, led by researchers at the University of Colorado Anschutz Medical Campus, focused on the effect of fluoxetine, commonly used in medications such as Prozac and Sarafem for treating depression and perinatal depression, on the developing prefrontal cortex of mice.
Since fluoxetine works by increasing the levels of serotonin in the brain, the researchers looked at the impact serotonin has on prefrontal cortex development.
“While it is known that serotonin plays a role in the brain development, the mechanisms responsible for this influence, specifically in the prefrontal cortex, have been unclear, ” said lead author Won Chan Oh, PhD, assistant professor in the Department of Pharmacology at CU Anschutz.
Changes in gestational and early postnatal serotonin levels can arise from many causes including maternal deprivation or abuse, diets high or low in tryptophan, or the use of medications such as selective serotonin reuptake inhibitors (SSRIs) that can readily cross the placenta or be passed to offspring through breast feeding. Disbalances of 5-HT during brain development are associated with increased risk of neurodevelopmental disorders such as autism spectrum disorder and long-lasting behavioural deficits, but the underlying mechanisms remain elusive.
Oh and his student, Roberto Ogelman, a neuroscience PhD candidate, found serotonin directly influences nascent and immature excitatory synaptic connections in the prefrontal cortex, which if disrupted or dysregulated during early development can contribute to various mental health disorders.
“Our research uncovers the specific processes at the synaptic level that explain how serotonin contributes to the development of this important brain region during early-life fluoxetine exposure,” adds Oh. “We are the first to provide experimental evidence of the direct impact of serotonin on the developing prefrontal cortex in mice.”
To study the effect, the researchers looked at the impact of deficiency and surplus of serotonin on brain development in mice. They discovered that serotonin is not just involved in overall brain function but also has a specific role in influencing how individual connections between neurons change and adapt, contributing to the brain’s ability to learn and adjust.
“Understanding this correlation has the potential to help with early intervention and the development of new therapeutics for neurodevelopmental disorders involving serotonin dysregulation,” said Oh.
The researchers plan to continue studying the impact of fluoxetine, next examining its impact on a developing brain later in life.
An unexpectedly high percentage of children, who were born with HIV and started treatment within 48 hours of life, exhibit biomarkers by two years of age that may make them eligible to test for medication-free remission, according to a multinational study published in The Lancet HIV.
“Moving away from reliance on daily antiretroviral therapy (ART) to control HIV would be a huge improvement to the quality of life of these children,” said Protocol Co-Chair and senior author Ellen Chadwick, MD, at Ann & Robert H. Lurie Children’s Hospital.
Conducted in 11 countries including South Africa, the proof-of-concept study was charged with replicating the case of HIV remission as seen in the “Mississippi baby” that was reported in 2013. In that case, the infant started ART at 30 hours of life, was treated for 18 months, and achieved 27 months of ART-free remission before the virus rebounded. Typically, if ART is stopped, the virus rebounds within a month.
The study included a three-drug ART regimen initiated within 48 hours of life, with the fourth drug added within 2-4 weeks. This is very early treatment compared to the standard of care where three-drug ART may not begin until 2-3 months of age.
In the US, however, based on earlier findings from this study, very early treatment is now the norm for infants at high risk of acquiring HIV infection from their mother.
“With earlier treatment, we hope to limit or prevent the establishment of viral reservoirs in the body. These viral reservoirs hold small amounts of hidden virus which are hard to reach with ART. By shrinking these reservoirs, we expect to increase the amount of time that patients can be in remission, without needing daily ART,” said co-author and Protocol Co-Chair Jennifer Jao, MD, MPH, from Lurie Children’s.
Dr Chadwick adds: “Another benefit of smaller viral reservoirs might be that newer treatments such as long-acting antibody therapies or therapeutic vaccines could potentially be used instead of daily ART.”
“Our results show a higher percentage of children might be eligible to interrupt therapy than we expected, and the next step is to stop ART and see how many children actually achieve remission,” said Dr Chadwick.
“If even one child achieves remission, that would be considered a success. Today, newer more effective and better tolerated HIV medications are available for infants than when the study began, strengthening the prospect of limiting viral reservoirs and testing for possible remission in infants and children with HIV. Overall, this is an exciting advancement and an opportunity to change the course of pediatric HIV infection.”
The study was conducted in 11 countries – Brazil, Haiti, Kenya, Malawi, South Africa, Tanzania, Thailand, Uganda, USA, Zambia and Zimbabwe.
A UK nurse has been sentenced to life in prison for murdering seven babies in a neonatal unit. In what is the longest murder trial in recent UK history, 33-year old Lucy Letby was also convicted of attempting to kill six other babies, and further investigation by the BBC has also revealed how hospital management at the time deflected concerns by doctors and actively silenced them.
Between June 2015 and June 2016, Letby deliberately injected air into babies’ parenteral nutrition lines, force-fed milk to others and administered huge doses of insulin to two others. In the years before, less than three death per year had been recorded at Countess of Chester Hospital at the neonatal unit where she worked.
According to The Guardian, Mr Justice Goss said during her sentencing: “This was a cruel, calculated, and cynical campaign of child murder involving the smallest and most vulnerable of children, knowing that your actions were causing significant physical suffering and would cause untold mental suffering.”
She was found not guilty of two other counts of attempted murder, but the jury consisting of four men and seven women were unable to reach a verdict on six additional attempted murder charges. The court will consider whether to attempt to retry these six charges.
Dr Stephen Brearey, lead consultant at the neonatal unit where Letby worked told the BBC he first raised concerns about the nurse in October 2015, but not no action was taken and she went on to attack five more babies.
He that hospital management failed to investigate allegations against her and also tried to silence doctors. An investigation by BBC Panorama BBC News revealed just how Letby was able to get away with murdering and harming the babies for so long.
The hospital’s top manager ordered doctors to make written apologies to to Letby, and two consultants had to undertake mediation with the nurse, despite their suspecting she had killed babies. Efforts to bring in the police were also quashed by senior management, who said in an email “This is absolutely being treated with the same degree of urgency … All emails cease forthwith”.
Dr Ravi Jayaram, a consultant paediatrician at the hospital, wrote on social media that he felt relief at the oft-maligned justice system working “this time”.
But he continued there were “things that need to come out about why it took several months from concerns being raised to the top brass before any action was taken to protect babies”.
He also added: “And why from that time it then took almost a year for those highly-paid senior managers to allow the police to be involved.”
Ten percent of babies born before 32 weeks will develop cerebral palsy resulting from infections that damage white matter, nerve fibres deep in the brain. While it’s known that the white matter loss will lead to neurological deficits, there is currently no treatment to avoid this.
Now, researchers at Duke Health have conducted experiments using neonatal mice and identified a fatty molecule in breast milk that triggers a process in which stem cells in the brain produce cells that create new white matter, reversing the injury.
The study appears in the journal Cell Stem Cell. Corresponding author Eric Benner, MD, PhD, said that further study in a clinical trial is needed, but the finding is promising.
“Developing therapies for children – especially such medically fragile children – is very difficult to do because there are justifiably strict safety concerns,” Benner said. “The fact that this molecule is already found in something that is safe for premature babies – breast milk – is extremely encouraging.
“It’s been known that fats in breast milk benefit a child’s brain development, but there are many types of fats in breast milk,” Benner said. “This work has identified a lipid molecule in breast milk that promotes white matter development. Now, we can begin to develop a therapy that isolates and delivers this lipid in a way that is safe for the unique challenges of these infants.”
Benner is a neonatologist at Duke University and one of the co-founders of Tellus Therapeutics, a Duke spinout company developed with the help of the Duke University Office for Translation & Commercialization to bring this therapy from the bench into the neonatal intensive care unit.
The fatty molecule identified in the study will be administered intravenously to patients in an upcoming clinical trial. This is significant because many of the infants who are part of this vulnerable population also have gastrointestinal issues and cannot safely be given milk or medication by mouth.
The lipid molecule enters the brain and binds with stem cells there, encouraging the stem cells to become or produce a type of cell called oligodendrocytes.
The oligodendrocytes are like a hub that allow for the production of white matter in the central nervous system. This newly produced white matter in pre-term infants prevents the neurological damage that would otherwise impact the child’s ability to move – the hallmarks of cerebral palsy.
“The timing of brain injury is extremely difficult to predict, thus a treatment that could be safely given to all preterm babies at risk would be revolutionary,” said Agnes Chao, MD, a former fellow in the Division of Neonatology and first author of the paper.
“As a neonatologist, I’m so excited that I may be able to offer a treatment to families with babies that are affected by preterm brain injury who would otherwise have no other options,” Chao said.
“The death of a child affects us all. Witnessing the loss of a newborn baby who has sepsis is terribly traumatic, especially so when antibiotics used to treat the child are ineffective,” says neonatologist Professor Sithembiso Velaphi.
“It’s very heavy for a mother to carry her baby, give birth, watch as her newborn gets seriously sick from infection, suffers while being pricked with drips and pumped with drugs to try and save the child – only for her to leave the hospital empty handed. It’s painful,” says Velaphi, who is the head of Paediatrics at Chris Hani Baragwanath Academic Hospital in Johannesburg.
Professor Sithembiso Velaphi, head of Paediatrics at Chris Hani Baragwanath Academic Hospital in Johannesburg. PHOTO: Kim Cloete for GARDP
Nurses and doctors feel sad and crushed too when they cannot save a newborn’s life because of antibiotic resistance to bacterial infections. “We need to prioritise the development of antibiotics to treat these babies. For us, success is seeing a baby get better and going home,” he says.
Velaphi was speaking to Spotlight about a landmark global observational study published in the journal Plos Medicine (June 8) which found that many neonates (within 60 days of birth) get life-threatening bloodstream infections, or sepsis, and are dying because the antibiotics used to treat them are not effective. This is the first global overview to assess the extent of the problem. Spotlight last year reported on interim findings from the same study.
The study, called NeoOBS, led by the Global Antibiotic Research and Development Partnership (GARDP) recruited more than 3 200 babies in 19 hospitals in 11 countries – South Africa, Kenya, Uganda, Thailand, Vietnam, India, Greece, Italy, Bangladesh, Brazil, and China.
The researchers reported great variability in mortality rates of babies with sepsis across the 19 hospitals, ranging from 1% to 27.3%.
Sepsis affects up to 3 million babies a year globally. Importantly, the study’s 80 authors estimate that 214 000 newborns die every year from sepsis that has become antibiotic resistant, and this is mostly in low- to middle-income countries (LMIC). Many survivors suffer from neurodevelopmental problems. Treatment options have become increasingly limited as about 40% of infections are reported to be resistant to standard antibiotic treatments.
Many infections acquired in hospital
Almost 60% of infection-related deaths were due to infections acquired at the 19 hospitals under review. Klebsiella pneumoniae was the most common pathogen isolated.
Of the 40 antibiotics approved for use in adults since 2000, only four have included dosing information for neonates in their labelling. Currently, 43 adult antibiotic clinical trials are recruiting patients, compared to only six trials recruiting neonates, researchers say.
New antibiotic treatments are urgently needed, especially in LMICs where almost 1 in 5 babies with sepsis died. Premature babies are particularly vulnerable to infections because of their immature immune systems.
More than 200 different antibiotic combinations were used by hospitals included in the NeoOBS study, with repeated switching of antibiotics due to high resistance to treatments. This showed a pattern of limited use of the World Health Organization’s recommended first-line treatment.
Many doctors have had to opt for last-line antibiotics such as carbapenems because of the high degree of antibiotic resistance in their units or because they were the only treatment available.
Outlining various challenges, Velaphi says the risk of infections is very high in hospital settings where there is often a shortage of nurses, beds, and space between patients making it difficult to stop the spread of infection. Chris Hani Baragwanath has an 18-bed Intensive Care Unit (ICU) that is almost always full and when the situation is desperate there is a spillover of patients into the high-care area. The pressure on the facility is huge and the influx of people from other countries has made it even more challenging, he says.
“There is a major problem of infection control, specifically related to high-risk babies – sick babies with complications who need interventions such as drips and even surgery. This increases the chances of infection. “More than 70% of all deaths ascribed to prematurity at the hospital were due to hospital-acquired multi-drug resistant infections,” he says.
The NeoSep 1 trial
The authors say the NeoOBS study has yielded “a wealth of high-quality data” needed to design trials for much-needed and appropriate treatments for sepsis in babies. Encouragingly, and building on from the observational study the first global hospital-based neonatal sepsis trial called NeoSep 1 is underway in Kenya and South Africa. Chris Hani Baragwanath is taking part in the trial together with Tygerberg Hospital in Cape Town and KEMRI, Kilifi County Hospital in Kenya. It’s planned that the trial will be expanded to other countries and regions in 2024 with the aim of recruiting 3 000 newborns.
A Personalised Randomised Controlled Trial (PRACTical) design will be used. According to GARDP and partners the design is a new way of comparing antibiotic treatments for neonatal sepsis. In addition, doctors can choose treatment regimens that are likely to work well for newborns in their specific hospital settings.
Researchers say the development pipeline for new antibiotic treatments is limited and the lack of a universal, effective standard of care creates huge challenges in conducting research to tackle neonatal sepsis. The PRACTical design has been specifically developed to address these challenges in important public health emergencies such as neonatal sepsis. (You can read more about how this type of trial works in the Lancet.)
The trial will compare the safety and efficacy of three new combinations of older antibiotics (fosfomycin-amikacin, flomoxef-amikacin, and flomoxef-fosfomycin) against the current standard of care. It will also assess and validate the doses of two antibiotics (fosfomycin and flomoxef) for use in newborns. The trial will also evaluate new combinations of generic antibiotics.
“We are hoping the trial will provide robust evidence that the antibiotic combinations are safe and effective and that this will lead to a change in both WHO and local treatment guidelines,” says Christina Obiero, Principal Investigator for the NeoSep1 trial for KEMRI at Kilifi County Hospital in a statement.
Severity and recovery scores
Principal Investigator for the NeoSep1 trial at Tygerberg Hospital, Professor Adrie Bekker tells Spotlight, “We have so few antibiotics that work effectively against these very sick babies. And even for those that we have, we are still not 100% sure how to dose these drugs to get accurate concentrations in the blood and to also make sure that the outcomes in these babies are as good as can be. This trial will help give us confidence that we are delivering more effective treatment.”
Bekker who is also Professor in the Division of Neonatology, Department of Paediatrics and Child Health at Stellenbosch University says a positive outcome of the NeoOBS study is the development of two important tools which can be used in ICUs globally.
The first is the NeoSep Severity Score which is a compilation of common symptoms and signs that can occur in a baby with clinical sepsis. The second is the NeoSep Recovery Score, which will assist clinicians in deciding if they can stop antibiotics earlier.
The tools are expected to help prevent the often excessive and inappropriate use of antibiotics for over too long a period, which compounds the problem of antibiotic resistance globally.
Diagnosis in older age groups, children, and adults, is generally easier.
“It’s sometimes difficult for a clinician to know whether a baby actually has neonatal sepsis because it can present very subtly and not always with the same symptoms,” Bekker explains.
The blood culture is the gold standard for diagnosing neonatal sepsis, but Bekker says only around 10% of blood cultures will grow an organism even if the baby has sepsis, making it very difficult to get a diagnosis. “And because it’s such an aggressive disease and a baby can die very quickly from it, clinicians tend to rather over-treat than under-treat. That is correct but, just as important as it is to start antibiotics quickly, it’s important to stop them if they are not necessary. The NeoSeps Severity score will help doctors identify babies that are at very high risk from sepsis and those that would need treatment immediately.
Velaphi says a major challenge is the time it takes for an outcome of the blood culture and the general protocol is to start antibiotics immediately. Waiting between 24 to 48 hours can be too late for a child who may have sepsis and could die. On the other hand, antibiotics may be given to children who do not have sepsis and this adds to the frequency of antibiotic resistance. “So, you are damned if you do and you are damned if you don’t.”
He says we need new diagnostic tests that are reliable and that have a high degree of sensitivity and specificity. “We need antibiotics that work to reduce mortality,” he adds.
For newborns, caregivers have to identify and evaluate any pain they may be in. Until the turn of this century, many clinicians did not even recognise that neonates could even experience pain, resulting in infrequent, nonstandard training for medical workers. The COVID pandemic also disrupted opportunities for training. Now, researchers are reporting that a flexible e-learning program improves neonate pain management knowledge and skills for nurses.
They published the results of their randomised, controlled study in Pain Management Nursing.
“Continuing education is essential to maintain and increase nurses’ proficiency in neonatal pain assessment and treatment,” said corresponding author Mio Ozawa, associate professor in the Graduate School of Biomedical and Health Science at Hiroshima University. “Our results showed that e-learning programs were more effective as compared to no training.”
The researchers randomly divided recruited certified neonatal intensive care nurses from across Japan into two groups. One group received four weeks of online training in pain measurement, using structured scales designed for pre-term newborns, called the e-Pain Management of Neonates program. The other group did not receive training. Both groups took pre- and post-tests. While the pre-test results were the same across both groups, the e-learning group scored higher for both knowledge and skill.
The research builds on a prior pilot study, in which 52 nurses completed the e-learning program and improved their test scores. However, without a control group for comparison, the evidence was not sufficient to illustrate the intervention’s effectiveness, according to Prof Ozawa.
“In the current study, we tested the e-learning program with a randomised control trial, a more powerful research design than used with the pilot study,” Prof Ozawa said. “To the best of our knowledge, this is the first such trial that investigates the effects of e-learning on the knowledge and skill in neonatal pain measurement for certified nurses across NICUs across multiple hospitals.”
The e-learning program consists of four modules, each of which takes about 15 minutes to complete. Participants could save their progress and return at any point, as well as review as many times as they wanted. While more nurses were more likely to access the program in the middle of the day or late at night on a weekday, participants still accessed the program at odd hours and over the weekend.
“An e-learning program may be a more efficient method as nurses can participate in the program at their own convenience,” Prof Ozawa said. “In comparison with other health care professionals, NICU nurses stay at the bedside of newborns for the longest time to provide care, including invasive procedures. It is vital for nurses to be educated and train in using the neonatal pain management scale.”
Prof Ozawa stressed that while this study did not demonstrate e-learning’s superiority as a learning method compared to traditional approaches, such as in-person training, it does indicate that e-learning can improve skills and knowledge.
“Learning in this program would allow nurses to acquire knowledge and skills concerning newborn pain, which is preferred over no education,” Prof Ozawa said. “Further research is needed to determine how nurses’ training through e-learning programs is related to patient outcomes, such as more frequent pain assessment of infants by nurses and improved pain management.”
In the century since it was first used in humans, the Bacille Calmette-Guérin (BCG) vaccine against tuberculosis has become one of the world’s most widely used vaccines. Administered in countries with endemic TB, it has surprisingly been found to protect newborns and young infants against multiple bacterial and viral infections unrelated to TB. Some evidence even suggests that it can reduce severity of COVID. Now, a new study in Cell Reports sheds light on the mechanisms behind its extra protective effects.
Surprisingly little is known about how BCG exerts its many side benefits. To better understand its mechanism of action, researchers collected and comprehensively profile blood samples from newborns vaccinated with BCG, using a powerful ‘big data’ approach analysing lipid and metabolite biomarkers.
Their study found that the BCG vaccine induces specific changes in metabolites and lipids that correlate with innate immune system responses. The findings provide clues toward making other vaccines more effective in vulnerable populations with distinct immune systems, such as newborns.
First author Dr Joann Diray Arce and her colleagues started off with blood samples from low-birthweight newborns in Guinea Bissau who were enrolled in a randomised clinical trial to receive BCG either at birth or after a delay of six weeks. Blood samples were taken at four weeks for both groups (after BCG was given to the first group, and before it was given to the second group).
The researchers comprehensively profiled the impact of BCG immunisation on the newborns’ blood plasma. They found that BCG vaccines given at birth changed metabolite and lipid profiles in newborns’ blood plasma in a pattern distinct from those in the delayed-vaccine group. The changes were associated with changes in cytokine production, a key feature of innate immunity.
The researchers had parallel findings when they tested BCG in cord blood samples from a cohort of Boston newborns and samples from a separate study of newborns in The Gambia and Papua New Guinea.
“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said Dr Arce. “We studied three different BCG formulations and showed that they converge on similar pathways of interest. Reshaping of the metabolome by BCG may contribute to the molecular mechanisms of a newborn’s immune response.”
“A growing number of studies show that BCG vaccine protects against unrelated infections,” said Ofer Levy, MD, PhD, the study’s senior investigator. “It’s critical that we learn from BCG to better understand how to protect newborns. BCG is an ‘old school’ vaccine – it’s made from a live, weakened germ – but live vaccines like BCG seem to activate the immune system in a very different way in early life, providing broad protection against a range of bacterial and viral infections. There’s much work ahead to better understand that and use that information to build better vaccines for infants.”
Long-term brain damage resulting from neonatal hypoglycaemia can be warded off with proper treatment such as later education and dextrose gel after birth, new studies have found.
The study is the first of its kind to show that stabilising blood sugar levels in neonatal hypoglycaemia prevents brain damage.
Hypoglycaemia is very common, affecting more than one in six babies. Since glucose is the main energy source for the brain and the body, untreated low blood sugar can cause adverse effects on a child’s neurodevelopment up to the age of 4.5 years old.
While hypoglycaemia is known to alter early development, there has been a significant gap in our understanding of how hypoglycaemia can alter a child’s development after early childhood. A study in JAMA investigated the long-term impact on brain development in mid-childhood – ages 9 to 10 – and found that, compared to peers, there was no significant difference in academic outcomes for children exposed to hypoglycaemia as newborns.
“Rich pre-school and school experiences may help a child’s brain to re-organise and improve their academic abilities up to the developmental milestones of their peers,” said Professor Ben Thompson, who is part of the research team.
Following 480 children born at risk of neonatal hypoglycaemia, researchers assessed each child at aged nine to 10 in five key areas: academic achievement, executive function, visual-motor function, psychosocial adaptation, and general health. All child participants were involved in previous studies, providing researchers with information on their neuro-development outcomes at two and 4.5 years old.
This ability to catch-up in neuro-cognitive function could be because of the brain’s plasticity, the researchers suggest.
“It’s a big relief to know that babies who are born with and treated for a condition as common as hypoglycaemia are not likely to suffer long-term brain damage,” Prof Thompson said.
The researchers have also continued studying the efficacy of dextrose gel to treat low blood sugar in the first 48-hours of a newborn’s life, avoiding the need for babies to go to newborn intensive care units immediately after delivery.
In an additional study published in JAMA, the team assessed the later risks of dextrose gel as a treatment for hypoglycaemia in infancy, and found change to the risk of neuro-sensory impairment at age two. This treatment continues to be widely used in a growing number of countries, including Canada, Australia, the United Kingdom and the United States.
A new study indicates that for newborns in respiratory failure supported by ECMO, the greater volume of the red blood cell (RBC) transfusions that the babies receive, the higher their mortality rate.
“In order for the baby to survive on ECMO, they need red blood cells, they need platelets, they need plasma,” said Dr Brian Stansfield, neonatologist at the Medical College of Georgia and Children’s Hospital of Georgia (CHOG) “You have to have sufficient blood volume to make the whole system work. But there is also increasing evidence that if you can get by with less, that is probably more.”
“We think this supports the overall trend of being more restrictive in transfusion practices and being even more mindful about when you give transfusions and when you don’t while a child is on ECMO,” said Dr Jessica Gancar, neonatology fellow at MCG and CHOG.
The clinicians are the most confident this holds true for ECMO with babies in respiratory failure, while the relationship is more tentative for other causes. Respiratory failure makes up the largest population of newborns needing ECMO. The findings are another good reason for ECMO centres to reexamine when they transfuse babies, the clinicians point out. Haematocrit levels (red blood cells to volume ratio) are a key measure typically used to determine whether to transfuse.
“Our transfusion practice is when the haematocrit hits 35% we will transfuse,” said Dr Stansfield. “Most ECMO centres still have a threshold of 40%, which means they are transfusing more. Others transfuse at 30%. So in our program we also have to ask the question if we are accepting some unnecessary risks. Could we get by with less?” They looked at 248 newborns treated from 2002-19 at CHOG with an overall survival rate of 93%.
They analysed their medical records for any relationship between blood product transfusion and death and complication rates in these babies.
“We identified a clear linear relationship between mortality and red blood cell transfusion volume. Specifically, for every transfusion of red cells while on ECMO, a baby’s chances of survival decreased by 14%,” said Dr Gancar.
Plasma or platelet transfusions did not correlate with increased mortality. The findings are being presented during the Southern Society for Pediatric Research meeting.
“While blood product transfusions are necessary for critically ill newborns on ECMO, transfusions are given in response to ‘understudied, arbitrary thresholds and may be associated with significant morbidity and mortality,’” they write in their abstract.
“I think we are getting to the point, with neonatal ECMO in particular, where we are transitioning from how do we prevent death by intervening with ECMO – for a long time that was the question – to asking questions like once you are on ECMO, how do we make outcomes better,” said Dr Stansfield. “We already know that going on ECMO is a risk, that all the blood and other products we are giving at the start of ECMO is a risk, but could we limit some of the additional risk?”
ECMO requires essentially doubling the baby’s blood volume, said Dr Gancar. Just priming the pump typically requires two packs of red blood cells along with other select additives like albumin and heparin. Typically two more packs of platelets as well as fresh frozen plasma are given once the baby is on ECMO. Other blood product transfusions may follow over their course on ECMO, which averages three to seven days at CHOG.
At CHOG, the neonatal specialists work hard to give as few transfusions as possible and some babies, typically those on ECMO five days or less, may not require any exposures beyond the pump priming; others, typically the sickest babies, may be given five to 10 transfusions over their treatment course. They note that their study adjusted for sickness severity so that could not explain the increased mortality they found associated with more red blood cell transfusions.
Blood transfusion is known to increase mortality risk in essentially any disease process, Dr Gancar said, as they can prompt problems like increased inflammation, despite modern typing procedures to help ensure a good match between donor and recipient.
In these babies that risk seems linked to red blood cells, which have to be separated from factors they normally circulate with, be exposed to preservatives and may have a protracted storage time before they are transfused.
Decades of success with ECMO has the CHOG team confident about its value in helping babies overcome potentially deadly but also potentially reversible problems like meconium aspiration, but they still have a “healthy respect” for the technique, Dr Stansfield said.
They rule out traditional therapies first like using a ventilator to support breathing and nitric oxide to dilate the lungs and blood vessels. Dr Stansfield notes that the number of babies needing ECMO has fallen over the years as neonatal teams like theirs have improved.
But sometimes: “We run out of options unfortunately and that is when we bring in ECMO,” said Stansfield. While the team has one of the longest and best track records in the nation with ECMO, the facts remain that it requires surgery on the baby’s neck to place a small cannula in their internal jugular vein and sometimes a second one placed in the carotid artery to return the warmed and oxygenated blood back to the baby. Both those blood vessels no longer function afterward.
Approaches like ventilators are more straightforward and less invasive, Dr Stansfield said. “But the realisation is that we know there is a small percentage of kids that need more intensive therapy,” he said.
