A treatment to protect premature babies from blood poisoning does not work according to new research, which has been highlighted in the media.
“A treatment thought to improve a premature baby's chance of fighting infection does not actually provide any benefit,” BBC online reports. The news service says that a protein given to premature babies to boost their immune system does not improve their chances of survival, as was previously thought.
The story comes from research into protecting premature babies from blood poisoning by giving them a protein known as GM-CSF. Blood poisoning, or septicaemia, is a major cause of newborn deaths, and babies born prematurely are particularly at risk. Researchers studied 280 babies born before 32 weeks of pregnancy, and found that while GM-CSF boosted numbers of infection-fighting white blood cells, it did not improve the babies’ survival rates.
The results were disappointing for neonatal specialists who had hoped that GM-CSF might work for newborns in the same way it does for adults with damaged immune systems. These results show that premature babies are not simply small adults, and researchers may have to find alternative treatments to improve the survival rates of babies born early.
This study was conducted by Dr Robert Carr, a haematologist from Guy’s and St Thomas’ Hospital, King’s College London, and colleagues from other universities in the UK. The study was funded by Action Medical Research and published in the Lancet , a peer-reviewed medical journal.
This was a multicentre, randomised controlled trial, which was single-blind, meaning that the clinicians administering the drug knew whether it was the active drug or not.
The researchers were interested in potential treatments for systemic sepsis, an infection that is a major cause of death in the early life of premature babies. They were specifically interested in the drug GM-CSF, which is already used in adults. Previous research suggests that it could potentially be a preventive treatment, which could help protect babies at high risk of blood poisoning.
The authors offer good reasons why treatment with GM-CSF might reduce sepsis and improve outcomes, but they also warn that these agents are being used in neonatal medicine without adequate evidence of their effectiveness.
The researcher assessed the rates of sepsis (infection), mortality (death), and morbidity (other illness) in 280 babies born at 26 centres over five years (2000 to 2006). Babies included in this study were born before the 32nd week of pregnancy, and were in the lightest 10% of expected birthweight for their pregnancy duration. These “small-for-dates babies” were selected because they are at the highest risk of infection.
After enrollment, the babies were randomised within 72 hours of birth to receive either standard management or a dose of GM-CSF (10 ?g/kg each day) by injection for five days. The clinicians filled in a detailed, daily clinical record form for the first 28 days. Blood tests were taken as usual to record the number of white cells (neutophils) in the blood, as these are the cells that are stimulated by GM-CSF.
During the first 11 days, white cell count rose significantly faster in the babies treated with the GM-CSF than in control infants receiving standard treatment. Between these two groups, there was no significant difference in the rates of children who survived without infection.
The researchers report that 93 of 139 GM-CSF treated infants (66.9%) survived, and 105 of 141 control infants (74.5%) survived. This is a difference of around -8% (95% confidence interval, –18% to +3%), suggesting that there was a trend towards better survival in the control group, although this trend did not reach statistical significance.
The authors also carried out a meta-analysis to combine the data from this trial with previous published prevention trials. This showed no overall survival benefit with GM-CSF.
The researchers say that the early, preventive use of GM-CSF in extremely “preterm neonates” corrects low white cell counts, but the drug does not reduce infection or improve survival and short-term outcomes.
They also say that knowledge of the immune system in premature babies is limited and needs continued research.
This is a reliable study with an important conclusion for those practising in the area.
The two small studies prior to this one had shown small (but non-significant) benefits individually, and when combined they indicated a possible overall improvement in survival. This was the reason for conducting this slightly larger trial.
Meta-analysis is an important statistical technique for combining the results of small trials, and it proved useful in this trial. Meta-analysis was used both to justify the current trial in the first place, and to show the overall effect of GM-CSF by pooling these new results with those from previous studies.
The authors say that “successful future stratagems will need a wider view of [the premature baby’s] antibacterial defences”. This means that although this result may be prove disappointing, there is always further research to be done.
Negative research results are at least as important as positive results, although the researchers and editors of journals don’t like them as much.