Saving the lives of preterm babies with rapid genome sequencing

Worldwide, around 15 million babies are born preterm every year. Typically, these newborns can suffer from complications, including cerebral palsy, developmental issues, but also infection from bacteria.    

These infections can cause serious issues with preterm babies as their immune systems are not fully developed. With the growing problem of antibiotic resistant bacteria, the situation is only expected to get worse.

By developing a diagnostic test that not only gives results within a matter of hours as to which bacteria are causing the infections, but even which specific antibiotic genes they are harbouring, researchers are hopeful that they can increase the survival rate of preterm babies.

Dr Matt Clark is a Research Leader at the Museum, who has been working on using new technology, specifically using nanopore sequencers, to rapidly decode the genomes of bacteria in samples taken from preterm babies.

'Typically, if doctors are worried that a baby might have an infection then they send a sample off, which can take one or two days for the results to come back,' explains Matt. 'We show that with the nanopore sequencers, you can do all this within five hours.'

The results of these tests, conducting in conjunction with Quadram Institute and the Earlham Institute (EI), have been published in the journal Nature Microbiology. 

Compounding factors

Preterm babies are any babies which are born at fewer than 37 weeks of gestation. Prematurity is the leading cause of neonatal death, in addition to the increased risk of developing serious chronic health problems.  

One of the major issues that doctors face when caring for premature babies is that of bacterial infections.

Our guts are full of beneficial bacteria that not only help break down the food we eat, but also prevent harmful bacteria from getting a foothold and producing dangerous toxins. The womb is a sterile environment, which means that new born babies need to get these good gut bacteria from somewhere.

During vaginal birth, as the baby passes through the birth canal it will pick up the bacteria needed to seed its gut from the mother. As preterm babies are born via a caesarean, they do not get exposed to these beneficial microorganisms.

'This means that the preterm babies don't have either a properly developed immune system or gut because they were born early, and that they didn't get the good bacteria from their mothers,' explains Matt. 'And then they are often given antibiotics, and bacteria that might do well in that environment are those which are already resistant to these drugs.'

As a result, some preterm babies end up developing necrotising enterocolitis. This is when harmful bacteria become established in the babies' gut, and the toxins they produce start to kill sections of it. If left untreated, the gut begins to rot.

At this stage the only treatment is for surgeons to operate on the young patients and remove the section of gut that has died, compounding the problems by increasing the risk of infection.

Speed is of the essence

With babies that are so young and immunocompromised, the need for a rapid diagnosis is essential.

'The babies can go downhill inside of even half a day, so this is the time frame that you want to get the results within,' says Matt. 'If we can tell the clinician what sort of bacteria are within the baby, and even work out which antibiotic resistance genes are present in just five hours, it means the doctors can figure out which drugs to give to the babies much quicker.'

The test uses what are called nanopore sequencers. These are devices into which a sample of the gut bacteria derived from the patients' poop is placed. The sequencer then reads the strands of DNA, generating the data in real time.

The team of researchers then developed their own software to rapidly analyses this data in order to not only identify which species of bacteria were present in the sample, but even which specific genes that might be resistant to antibiotics could also be found.

By doing this, they were able to identify which babies were healthy and which of those had been diagnosed with either necrotising enterocolitis or sepsis. While the test may not be ready to be put into practice immediately, the results showed clear proof of concept and a lot of potential for use across hospitals.

'To roll out any clinical tests requires a lot more work because you need to demonstrate success with a much bigger sample size to show that it is really clinically robust,' says Matt. 'This is one of the things we will be looking at next.'