We asked NEC UK families what questions they wanted answered by our medical advisory panel. we are extremely grateful to our MAP Members who have answered them below:
Dr Nicholas Embleton
Consultant Neonatal Paediatrician and Professor of Neonatal Medicine Read More...
Dr Janet Berrington
Consultant Neonatal Paediatrician in Newcastle and Honorary Clinical Senior Lecturer in Neonatal Medicine, Newcastle University, UK.
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Dr Christopher Stewart
Has researched the early life microbiome in health and disease for the past decade, specializing on infants born premature (<32 weeks gestation). Read More...
Jutta Koeglmeier
Jutta Koeglmeier is a paediatric Gastroenterologist at Great Ormond Street Hospital for Children in London, where she is clinical lead for the Unit of Nutrition and Intestinal Failure Rehabilitation.
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Nigel Hall
Nigel Hall is a Paediatric Surgeon in Southampton and a researcher at the University of Southampton
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1.How can we spot the signs quicker? I understand there are many and they are very hard to spot but is there a specific sign to look for?
Nick Embleton: Unfortunately, there are no specific signs that are always associated with NEC. In many cases the early signs are incredibly difficult to spot. Looking back, people will often comment that they thought ‘things were not right’ but at the time it was difficult. I have worked as a consultant for more than 20 years, and have probably looked after hundreds of babies with NEC - I still find it difficult to know for sure which babies have NEC, especially in the early stages. However, there is some good news - research studies are starting to use new techniques that can look at the patterns of chemicals or other markers in the stool (poo). This might provide an early warning signal. It is also possible that newer techniques of scanning the baby’s tummy or looking at changes in blood flow may help. But sadly, at present, it is still really difficult to spot the early signs in many babies.
2.Are there tests in early stages if a parent suspects their child may have NEC but their symptoms are similar to other conditions. Eg my son was on suppositories for 3 days for having no bowel movements, was being fussy with feeds, he had a bloated belly which was all veiny, he was having problems with blood sugars and they put it down to constipation and being new to feeds. 8 hours later he was ventilated, we were told he had NEC and just hours later he passed away. For 3 days I raised my concerns for staff to brush it off
Nigel Hall: An X-ray of the abdomen is usually the first test that is done to see if there is any evidence of NEC. If the X-ray doesn't show this but there are still concerns that a baby may have NEC, then an ultrasound of the baby’s tummy can also be helpful. Not all units have the appropriate expertise to use ultrasound for a baby who may have NEC. Unfortunately we do not have a single test that can tell for certain if a baby has NEC or not. The diagnosis is made on the combination of clinical features (the baby’s observations and examination findings), blood test results and the X-ray or ultrasound findings. Increasing awareness of NEC (such as through NEC-UK) is certainly something that may help with earlier identification.
3.Is there guidance on feeding premature infants. For example, how often should their feeds be increased? How many hours should be between feeds, how many mls should feeds be increased by?
Why does this vary so much between professionals.
Nick Embleton: Doctors have often worried about when to start milk feeds, how quickly to increase the volume and whether there should be long gaps (3 hours) between feeds, short gaps (1 hour) or continuous. This is a really complicated area of research, but UK researchers have contributed to one of the largest ever trials in this area (SIFT) of more than 2,800 preterm babies (by the way, thank you to all the parents who took part !). What this study shows quite convincingly is that for most preterm babies it really does not matter how quickly you increase feeds within a certain range - so faster increases at 30ml/kg/day versus slower increases of 18ml/kg had no effect on whether babies got NEC. Of course it is possible that feed increases much quicker than that could be a problem, but most doctors are happy that anything in the range 18-30ml/kg seems safe.
We still do not know when is the best time to start milk feeds, but most of us are confident that it is safe to provide small amounts of colostrum in the first hours of life. We need more studies to be absolutely sure if early colostrum really makes a positive difference, but we are not worried that it is dangerous or increases the risk of NEC. However, early feeds of formula milk may behave differently so our own practice is only to use mother’s milk in the first 2-3 days.
There have been a few studies of bolus versus continuous feeds. None of those have been large enough to conclusively determine an effect on NEC, however, there are no data to suggest that the risk of NEC is affected by bolus or continuous. Different hospitals practice in different ways, and do what seems to work for them. We understand that it can be difficult for parents when every NICU does something different. But this might be a good thing! It means everyone is still thinking rather than blindly following a single way of doing things, which might not always be the best!
4. Is there a guideline for surgery or extreme cases of NEC (my son was refused transfer to another hospital until he perforated his bowel?)
Nigel Hall: the decision of which babies will benefit from an operation and the timing of surgery is often difficult and we know there is variation between different units and different surgeons regarding this. This area is certainly the subject of ongoing research as earlier surgery has the possibility of improving outcomes from NEC.
As such no written guidelines exist. If a baby has a perforation in their intestine from NEC then that is generally accepted as an indication for surgery. If there is no perforation then the decision is usually made based on the general clinical condition of the baby.
Because not all neonatal units have neonatal surgeons on site the decision to transfer a baby to a surgical unit can sometimes be difficult. Surgeons rely on the discretion of the team at the referring hospital to help them decide which babies need transfer to be seen by a surgeon.
5.What is being done to help prevent cases of NEC in premature infants?
Nick Embleton: Every year more data is coming out of research studies. We have been involved in large trials recruiting thousands of premature babies, and every year we learn more. Researchers are looking actively at things like probiotics, and other things that could be added to milk feeds (oligosaccharides). Overall, we are getting better. Whilst it is true that the rate of NEC has not changed a lot, we are looking after smaller and smaller babies, who have a higher risk of NEC. So even though we still see NEC, we see it less frequently in the bigger babies than we did 10 years ago. We are also getting better at supporting mother’s provide their own breast milk - that has a large effect on reducing the rate of NEC.
6.What has been achieved in the last 10 years since my daughter had NEC?
Chris Stewart: Using samples collected from preterm infants, researchers have learnt a huge amount about how microbes and the babies own cells interact, which is thought to be a critical part in the NEC disease pathway. We know some microbes are generally lower or absent from babies that develop NEC, giving rise to potential for preventative therapy. We also know certain sugars in mothers breast milk are associated with reduced risk of NEC, which could be used to assess disease risk in the clinic and to supplement infant diet. While exciting, more work is needed to prove if these results are cause or effect, and what the underlying biological mechanisms are. So from a research prospective, huge gains have been made in our understanding of NEC, but we still have a long way to go. Translation of research into the clinic can often be slow, and rightly so, due to the requirement to prove safety and effectiveness of an intervention. NEC remains relatively understudied, but passionate researchers around the world are doing all they can, and that's why it is vital we have initiatives such as those driven by NEC UK to raise awareness and understanding!
7. Does a blood transfusion help if so how?
Janet Berrington: Once a baby is unwell with NEC they may benefit from a blood transfusion as part of their supportive care, or during an operation if one is needed. Not all babies with NEC are anaemic or need surgery though and so not all babies will benefit from a blood transfusion.
There are lots of studies looking at the link between anaemia and developing NEC - it is quite hard to separate this data from data on receiving transfusions, but we think that leaving babies very anaemic for significant time might not be good for protecting them against NEC.
8. NEC has caused my daughter to have SBS. She already had cloaca and IA. Can NEC cause problems with fertility or whilst pregnant?
Nigel Hall: Any baby or child that has had significant infection in the tummy cavity and particularly if there has been a perforation of the bowel may be at risk of having problems with fertility. This is because the reproductive organs in the pelvis, particularly the fallopian tubes, may be kinked or scarred by the way the body responds to the infection and/or surgery. However it’s not a problem that is just related to NEC, other illnesses can cause this too. For instance, one of the most common is perforated appendicitis.
9. Does NEC increase the risk of cerebral Palsy? If so why and is there anything that can be done to prevent it
Nick Embleton: unfortunately, there does seem to be a strong association between NEC and the later risk of cerebral palsy (CP) or other developmental problems. We are not sure exactly why, and it is important to remember that many babies with NEC do not get CP.
When a baby gets NEC or septic, their own immune system releases hundreds of chemicals (cytokines) and proteins that try to fight the infections and inflammation. This has been called the ‘cytokine storm’ and probably happens in every baby with NEC. It is part of being very sick and represents the immune system trying to ‘save’ the baby - without it babies might simply die from overwhelming blood poisoning.
Unfortunately these cytokines also seem to damage the immature brain, and particular the white matter of the brain - the connections between the different brain areas. We don’t really know why it damages the brain in this way and it seems specific to premature babies. Research studies are working to see whether other treatments could help - either drugs that could ‘block’ the cytokine effects in the brain, or cooling treatments that might slow down brain metabolism. But at present there are no drugs that can safely treat this problem.
Furthermore, babies with NEC often also don’t get as much nutrition as they need to grow normally. Either they are too sick and already have too much fluid in them, or sometimes because their body metabolism can’t “use” the nutrients normally, even if they get them. There are some data, and more research is underway, that show ‘extra’ nutrition or nutrients might help recovery, and it seems likely that breast milk has components that might help. Some babies with NEC may also have problems with blood pressure and oxygen which also increases the risk of CP. Careful management of babies with NEC reduces these problems.
CP is, of course, associated with life-long challenges, and sadly some babies are severely affected. However, many children with CP lead happy and fulfilling lives even though this can require huge efforts from families. Of course, no one would want their baby to get CP, but it is important to remember that there are many children living with CP and other disabilities who have happy family lives. Being told your baby might develop CP, or that your child has CP, must feel very scary. Ask your doctors what it means, and look to get more information and support from groups and therapists.
10. Does fortifier increase the risk of NEC? Is human milk fortifier better than bovine and if so why don’t units use it?
Nick Embleton: This is a really tricky question! None of the published studies so far conclusively show that the fortifier is associated with NEC. Many people are concerned, but the data we have is not conclusive by any means. Sadly, most babies in the UK (and perhaps elsewhere) develop NEC only ever having had their own mothers milk, and never having had a fortifier at all. A research study that was designed to definitely prove that fortifiers caused NEC would need to recruit more than 1000-2000 premature babies. That study has never been done, so we simply do not know. But we agree that a research study to explore this question is needed. Such a study would probably cost around £5 million.
Furthermore, we know that babies' brain outcomes (i.e. how intelligent they are when they grow up) are closely related to how they are fed when on the NICU. Without using a fortifier, babies may not grow effectively, which increases the risk of cerebral palsy and learning difficulties. Most doctors therefore feel that using fortifiers is the best practice in small babies.
Newer human milk fortifiers are available both in the US and the UK. Whilst there is some evidence that they may cause less NEC than cow milk based fortifiers many clinicians in Europe and the UK remain sceptical. The studies conducted so far have been too small to show a definite decrease in NEC. Babies on human milk based fortifiers may also grow more slowly. Milk that is used to make these fortifiers is also not available to be used as donor milk. So there could be issues with supply. Furthermore, use of human milk fortifiers would cost around £3-5,000 per baby - for a large NICU that would mean spending ¼ million pounds extra per year. We completely agree that the cost would be entirely justified if we knew for definite that human fortifiers were better, but we need more research studies to be sure.
11.I would like to ask about the long term implications of NEC. My daughter had 3 areas of bowel removed and a stoma. She is 8 now and is struggling with constant constipation and impaction. The GP also believes she has adhesions. She often complains of pain across her scar. We were warned when she had the initial surgery that a lot of her bowel was ‘sick’. Is this common and any advice on management would be gratefully received?
Jutta Koeglmeier: To give you the best possible answer it would be important to understand what areas of bowel your daughter had removed and what type of stoma she had. As she is complaining about constipation and faecal impaction I assume she had sections of small bowel removed but has an intact large bowel (colon). There is very little data regarding the gastrointestinal sequela of NEC with the exception of short bowel syndrome (SBS) and/or intestinal failure (the need for parenteral nutrition). The 7 year follow up ORACLE study on children has shown that those who had NEC had a 3.6 fold increased likelihood of suffering from long term bowel problems.
Children who had medical NEC – so no surgery - are four times more likely to have feeding difficulties between the ages of 6 to 12 months compared to children without NEC, but by 24-36 months feeding difficulties are not more common compared to those who did not have NEC. Infants who had surgery for NEC are much more at risk of experiencing feeding problems at 6 to 12 months of age (11 times more likely) and still 4 times more at risk by the age of 24 to 36 months. Little is known about malabsorption in children with medical NEC but those with surgical NEC are much more likely to have problems with nutrient (and fluid) absorption. At Great Ormond Street Hospital (GOSH) we follow all children up long term who had a surgical resection, even if they did not need parenteral nutrition. We monitor their growth and blood vitamin and trace metal levels and urine electrolytes to make sure they have enough body salt.
Strictures are a relatively common complication of NEC but the reported frequency varies widely. Studies report that 3 to 37 % of children with medical NEC develop strictures and 24 to 65% of those who had surgical NEC. Children who had a severely inflamed ‘sick’ bowel are much more at risk of developing strictures. Adhesions can form following surgery and can cause partial or total bowel obstruction reported to occur in 10 to 25 % of children who had surgery for NEC. It is unusual for children with SBS to become constipated – most have diarrhoea. As your daughter had a stoma when she was younger and lost 3 areas of bowel, which were joined together, I share your GP’s concern that she may have adhesions/strictures. A plain abdominal X-ray would show areas of dilated bowel. In case of a stricture the bowel before the anastomosis can become dilated. A contrast study would also help. A badly inflamed gut can lead to altered motility. Even if a stricture or adhesions have been ruled out your daughter’s bowel may be sluggish. A good fluid intake and diet are important. The GP may want to use laxative medication such as Movicol. Should simple measures not make a difference your GP should consider a referral to a Paediatrician, if you do no longer have follow up. The Paediatrician may want to send some blood tests to exclude other causes for constipation like coeliac disease or an underactive thyroid gland. At GOSH children like your daughter sometimes have what is called a pellet marker study – a special X-ray to understand how the colon is contracting. Your Paediatrician may want to involve a paediatric Gastroenterologist if your child is not getting better. As you do not mention parenteral nutrition, I assume your daughter did not need home PN but for completion I also wanted to mention it here. Short bowel syndrome due to NEC is the most common cause of intestinal failure in children.
However, children who need long term parenteral nutrition have a good chance of being weaned off parenteral support. Long term survival and quality of life on home parenteral nutrition have improved dramatically in the last decade and are now considered good. Even children with ultrashort bowel syndrome, who have lost a massive amount of gut (less than 10 cm of bowel or less than 10% of expected bowel length for age remaining) do have a much better outcome and only a small proportion develops irreversible complications of long term parenteral nutrition.
12. Anything around the science in America linked to proteins being emitted by the gut when ill going up to protect the developing brain and any links with this to global developmental delay etc.
Nigel Hall: There is some research that suggests that there may be a link between the inflammation in the intestine that happens during the NEC and damage to the developing brain. The nature of this link is unclear though.
Certainly, we know that babies who develop NEC are at increased risk of neurodevelopmental problems and those babies who have more advanced NEC (typically those who get surgery) may be at higher risk. What we do not yet understand is whether there is anything that can be done to protect the brain in this situation.
13. Are there any links with term NEC and Hirschsprung disease?
Nigel Hall: NEC is typically a problem that affects preterm babies. Whilst Hirschsprung disease can affect babies of any gestation, it is actually quite uncommon in preterm babies.
Babies born with Hirschsprung disease can get another type of intestinal infection similar to NEC but specific to Hirschsprung disease, called Hirschsprung related enterocolitis.
14. I have read that NEC causes delays in development. Is this true? If so to what extent, is it a case that they have behavioural needs, learning needs etc. We weren’t told of possible implications of this sort when our twin had it. Is there research into this area and what is being done to minimise this?
Janet Berrington; there is overlap between this and Q 12 and 9. We know that if we adjust for how preterm a baby was and then compare their development for babies with NEC, meningitis or neither, then babies with NEC will generally have less good development than those with meningitis or neither. So this suggests that having NEC is associated with delayed development. Some of this is behavioural and some learning. It can also affect physical development (cerebral palsy). Because some babies with NEC are very sick and have low blood pressure some of the problems may be caused by just being sick, but we also know that some chemicals (inflammatory cytokines) are produced during NEC and they can harm a developing brain. There may also be a link between changes in the poo bacteria (microbiome) and NEC and brain outcomes as we know the gut and brain ‘talk’ to each other.
15. Why is there such a difference in the timing of stoma closure in different units and even the same unit with different surgeons? Why isn’t there a guideline of best practice?
Nigel Hall: this is a topic that is the subject of an ongoing research project called ToSCiN. We know there is variation between surgeons and units about this and the project is trying to find out if we can do research to find out when the BEST time to close a baby’s stoma is.
At the moment the decision to close a stoma is based on a lot of factors, some related to the condition of the baby, some related to how well the baby can tolerate or absorb feeds (and therefore how well the baby is gaining weight) and some logistical factors as well. It can often be a difficult balancing act!
Thank you to our Map members for taking the time to answer our family questions.
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