Necrotising enterocolitis (NEC)

NEC is a disease of the premature gut and one of the most common causes of death in the one in 10 Australian babies born prematurely. For babies who survive, NEC can also have long-term impacts on the developing brain. NEC is a major health challenge because of its insidious onset and rapid progression. Currently there is no effective drug available to prevent or treat NEC.

The story of baby Charlie and the researchers aiming to improve the prospects of babies with necrotising enterocolitis.

View Video | The story of baby Charlie and the researchers aiming to improve the prospects of children with NEC.

What is NEC?

Bacteria invades the wall of the baby’s delicate intestinal tissue, causing inflammation and tissue damage to set in. Unchecked, the inflammation creates a hole or gap which allows the contents of the intestine to leak into the baby’s abdomen and cause overwhelming bacterial infection (sepsis), and sometimes multi-organ failure and death.

Necrotising enterocolitis (NEC) is one of the most common cause of surgical emergency and death in premature babies between days 15 and 60 of life.
Up to a third (between 20-30 per cent) of babies who develop NEC die – a number that has changed little over the past 50 years.

Who is at risk?

NEC is more common in premature infants, but also in very sick babies that are born with a heart disease. Babies at risk include those who are

Born before 32 weeks
Weigh less 1,500 grams
Fed through a tube in the stomach
Fed formula, by mouth or tube
Have had a difficult delivery
Have lowered oxygen levels
Have too many red blood cellsin circulation
Gastrointestinal infections.

Full-term but who other health problems, like a heart defect.

What causes NEC?

The cause NEC is not yet known. The contributing factors include babies who have

Weaker immune systems
Underdeveloped intestines and lungs
Difficulties moving oxygen carrying blood around their body, including to immature intestinal tissues
Difficulties breaking down food – formula fed babies are at a higher risk of NEC than breast fed babies
Dysbiosis of the gut – decreased beneficial microbiota and increased pathogenic bacteria in the gut
Infection.

NEC sometimes affects several infants who are in the same area. While NEC does not spread between babies, a virus or bacteria that causes it can. As a result, hospitals have strict precautions to help prevent the spread of infections.

What are NEC symptoms?

NEC can progress very quickly. Getting immediate treatment is vital to stop the condition taking hold. Symptoms include general signs like

Trouble feeding
Swollen, red or tender stomach
Vomiting bile (green)
Bloody stools as a result of infection in the bowel wall.

If these signs are not acted on, the following may develop

Trouble breathing
Unstable body temperature
Slow heart rate
Red, swollen or tender abdomen
Diarrhea
Lethargy, less active
Shock (decreased blood pressure).

How is NEC diagnosed?

NEC is difficult to diagnose, tests used include

X-rays – to show gas or air bubbles in the intestinal wall, indicating a damaged bowel
Blood – to check for bacteria and infection. A low white blood counts shows that the baby’s ability to fight infection is reduced
Faecal – to check for blood that may not be visible
Insertion of needle into the abdomen – the presence of fluid is a sign there’s a hole in the intestine.

How is NEC treated?

Current treatment is offers basic support to rest the intestines by using intravenous fluids to keep the baby nourished and hydrated and antibiotics to fight infection. This includes the insertion of a tube through the nose into the stomach to remove fluid and keep the stomach empty.

Other supports include extra oxygen or a ventilator if the stomach is too swollen for breathing, and regular X-rays are used to monitor the condition.

If the baby does not respond, and a hole develops, surgery is needed to remove injured and dead intestine. Some infants who have surgery may not be able to absorb nutrients normally and may need a bowel transplant to live. Sadly, there is high fatality rate.

How medical research is helping babies with necrotising enterocolitis

Hudson Institute scientists are shedding light on how NEC develops and working on promising new anti-inflammatory treatment approaches. By revealing valuable new insights into the pathways involved in the disease progression, our scientists have identified promising opportunities for medications.

Necrotising enterocolitis research projects

Novel anti-inflammatory approaches for the preterm baby

Molecular studies. New treatments. Inflammation is known to play a central role in the pathogenesis of NEC. After establishing the underlying disease mechanism in NEC, Professor Marcel Nold, Professor Claudia Nold, Dr Steven Cho and Dr Nadia Deen are now setting out to translate their knowledge into novel treatment strategies.

The team’s studies have already show promise that an effective NEC treatment will be found through repurposing existing anti-inflammatory medications such as interleukin 1 receptor antagonist, or through the development of novel potent anti-inflammatory molecules such as interleukin 37.

Team | Professor Marcel Nold, Professor Claudia Nold, Dr Nadia Deen

Patient derived organoids for pre-clinical drug testing in NEC

Molecular studies. New treatments. The team have established three-dimensional cell culture models of the neonatal intestine called organoids to study underlying mechanism of NEC. Organoids largely resemble the organ they originate from and are an excellent preclinical model to support drug development for this difficult to treat neonatal disease.

Combining these sophisticated models with cutting edge drug and CRISPR/genetic screening technologies, this project will streamline the identification and progression of new therapies.

Team | Professor Ron Firestein, Professor Claudia Nold, Dr Marius Dannappel

Finding the best microbiome for every baby

Microbiome studies. New microbiota treatments. From the moment of birth, the microbial life in and on a newborn’s body begins to establish. Termed the microbiome, the exact microbes and even the order they arrive can have immense impacts on health throughout an entire life. Despite this importance, very little is known about the effect of microbial communities in health or disease.

By gaining a deeper understanding of the role of the microbiome in neonatal health, particularly intestinal diseases such as NEC, this project will shed light on the importance of commensal bacteria and how probiotic treatment might confer a health benefit to the child.

Team | Professor Claudia Nold, Associate Professor Samuel Forster, Professor Marcel Nold