Feeding and NEC

Necrotizing Enterocolitis remains a devastating disease. One of the major causes of mortality in Very Low Birth Weight Infants, it often strikes when babies are starting to do well. Because it is relatively unpredictable, observational studies are potentially useful, but can easily be misleading. In particular, observational studies which are performed as a result of a perceived change in incidence might easily be biased.

One recent study that was published has received some publicity, I myself received some links on Linked-In pointing to this study, which at first sight seems to show that advancing feeds slowly might decrease NEC. Lets examine the data a bit more carefully.

In 2009 a hospital changed their feeding policies. A paper published in 2014 reported their data from 2009 to 2012. According to the published article the paper was received on July 24th 2014, and accepted on August the 5th. Which immediately makes me wonder two things, why the authors decided to perform this study, and how do they get a paper accepted so quickly? If the authors performed the study because they saw a decrease in NEC, and then decided to do the analysis, that immediately creates a bias, many other hospitals could possibly have made a similar change and not noted any change in NEC, and therefore not looked at their data. Studies such as this are more likely to be reliable if the decision to prospectively collect and try to publish their data is made at the time that the change in therapy is introduced. But then a similar study showing no effect on NEC would be very difficult to publish, and probably not be accepted in under 2 weeks!

There are a couple of concerning things in their findings, one is that after the change in the protocol there was not actually statistically any less NEC overall than before the change in protocol. Only by a subgroup analysis, was the group of babies under 750g significant, and then they did not report the p-value of the interaction, which is really essential. They showed much less NEC in the babies under 750 g birth weight than those between 750 and 1000g. Which really strongly suggests to me that this is just the result of the random nature of NEC incidence, I don’t know any large study that has ever found more NEC in the larger babies.

More worryingly, the new protocol led to babies having later commencement of feeds, longer use of intravenous nutrition, longer use of picc lines, and really horrendous nutritional outcomes, with over half of the babies being under the 10th percentile at discharge (admittedly that was better than the 75% with their older protocol).  The feeding protocol that they introduced is entirely non-evidence based, as I have noted before here, there is no evidence from controlled trials that varying the advancement of feeds has any effect at all on the incidence of NEC.

A slightly older study (from 2009) provides interesting data from the German Neonatal Network, and is, I think, much more reliable. They compared the outcomes of babies from centers where it took on average less than 12.5 days to get their VLBW babies on full feeds, to centers where it took on average more than 12.5 days to get the babies to full feeds.


You can see here the clinical outcomes from the study. The only things that were different between the groups were the late-onset sepsis, which was much higher in the babies with slower feeding. Surgical NEC was slightly (non-significantly) more frequent with slower feeding, and severe retinopathy was also higher, which is entirely consistent with the recent information linking retinopathy with poorer nutrition.


About Keith Barrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , . Bookmark the permalink.

4 Responses to Feeding and NEC

  1. Richard Taylor says:

    Another confounder in the American groups analysis is that there was significantly more use of human milk in their second cohort. They agree that human milk reduces NEC but they dont seem to admit to the possibility that it was this that led to less NEC, rather than delaying/slowing feeds. Also their NEC rate in the recent cohort remained too high -over 5% -which is nothing to be proud of.

  2. Sreekanth Viswanathan says:

    I have to respectfully disagree with some of the comments about our study mentioned here

    This was my neonatology fellowship project and we designed this feeding protocol based on evidence from an observational study (Pietz J, Pediatrics, 2007) and study data was indeed collected prospectively. While designing our feeding protocol in 2009, there was very limited high quality RCT evidence/consensus on what is the best way to feed ELBW infants.

    According to the largest NEC study cohort study published using the Vermont Oxford Network database, 2006-10 (Hull MA, 2014), the incidence of NEC in VLBW infants was 9% with 28% mortality rate. Infants with birth weight < 750 with NEC had a mortality rate of 40-50%. In our study, the subgroups (Babies with birth weight < 750 and 750-1000g) were pre-specified and they had separate feeding protocols based on the same hypothesis (slow and standardized will reduce NEC). We had to combine them as we felt it is hard to reach the sample size requirements in a single center study during the 3 year fellowship period.

    However, the feeding protocol was remarkably effective in NEC prevention in < 750g infants (Our NEC rate 2.1% compared to VON US NICU 2011-12 rate, 9.1-9.6%). In 750-1000g group, our NEC rate (7.7%) was similar to VON (2011-12, 6.8-7.1%). No infant < 750 g, either developed surgical NEC or died from NEC since the protocol was implemented. The IRB approval for this study is still in place and we plan to publish our 5 year data for infants with birth weight < 750 in the next year or so.

    Regarding nutritional outcomes, I agree that over half of the babies were under the 10th percentile at discharge (57%). However, it was better than our control group and was similar to VON database during the same study period (2010-12, 55%). There is definitely a room for further improvement, but the feeding protocol may not necessary be the only culprit here.

    Re: Dr Taylor’s comments: We agree that the rate of human milk initiation was higher in our slow feeding group, compared to controls. However, we added this into our propensity model and the adjusted effect was not significant. The purpose of propensity score matching was to reduce the bias from important confounding variables like human milk use.

    • Thanks for the response to my post. I appreciate that evaluating practice as objectively as possible and writing an article about your experience is much preferable to changing practice and not evaluating the response, so congratulations for having done that.

      I must reiterate however, that your protocol is absolutely non-evidence based, and contains many features which are potentially very damaging and against best practice. Leaving a baby npo for 14 days flies in the face of any evidence that exists, why would you do that? Taking 44 to 52 days to reach full feeds is outrageous. Most babies, including those below 750g can be fed on day one and advanced at 30 mL/kg/d. That way you can give them much more mothers milk, much better overall nutrition, you can prevent postnatal growth restriction, get their lines out faster and do that without any evidence that it affects NEC. As I noted the fact that your experience showed less NEC below 750 g than above it is bizarre, and strongly suggests a random change in NEC incidence, rather than an effect of your protocol. Maybe in the future there will be some evidence that an approach such as yours is appropriate, for now there is none, and I worry that babies will suffer from very poor nutrition as a result of following restrictive practices such as yours.

  3. Jeffrey Pietz says:

    Dr Barrington; With regards to your comments about Dr. Vishwanathan’s paper. You are incorrect in suggesting that his protocol is not evidence based. I would respond that no feeding protocol is as evidence based as the one in this paper. They at least based their protocol on our protocol at Fairview. We documented a 20 year experience with over 1200 VLBW babies with an overall NEC rate of < 0.5%. I can also tell you that that rate held up for another 5 years past the time of the study when I left that unit. The babies in that unit had very good outcomes. I only spent 10 years there but having little NEC and no short gut to worry about made the lives of our patients a lot easier. You can look at the paper for the details but our patients were very comparable to the VON network except for the better outcomes. It is unfair and unreasonable to criticize Dr. Vishwanathan for taking the promising observations in the Fairview paper and adding to the paltry level on evidence available.

    Evaluating any study on NEC is hampered by the fact that NEC tends to come in epidemics so when a short term study shows improvement after an intervention one can always argue that the new intervention was instituted after the epidemic was over. You inferred as much in your comments. That is why the Fairview paper is interesting. If you do not want to believe that slow feeding matters how do you explain the absence of an epidemic in the Fairview unit for a quarter of a century?

    I would suggest that before you accuse Dr. Vishwanathan of not being evidence based you might explain the evidence for how you feed babies. Your German data is very poor evidence since it does not address the value of what I would call slow feeding. 12.5 days to full feeds is fast in my book. Based on the lack of supporting evidence one might suggest it is bizarre.

    One case of NEC and short gut will lower the average growth and development of a cohort of babies far more than uniform slow feeding. I am not sure that having fatter babies who were fed quickly and did not get NEC are any batter off than a slowly fed baby who did not get NEC. I am sure that any baby with NEC is going to do worse than the former or the latter.

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