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.
