I’m still not absolutely sure about TANEC, as it now seems to be called. It is certainly possible that transfusions could trigger gut injury in very preterm babies, but how to prove it? Even if the temporal association was absolutely clear, does the transfusion just change the timing of NEC rather than increasing incidence? And then what do you do about it?
The 2 RCTs of differing blood transfusion thresholds that I recall, Ed Bell’s study, and the PINT trial did not report any difference in NEC. There was no mention in Bell’s study, and the frequency of NEC was actually slightly lower in the high transfusion threshold PINT group (not significant) who got transfused more frequently as a result of their assigned group.
A recent systematic review of observational studies illustrates to me the difficulties in figuring this all out, their first question was ‘Are neonates who develop NEC more
likely to be exposed to PRBC transfusion within previous 48 hours compared
with those who do not develop NEC?’. My question is, for those who do not develop NEC, which 48 hours do you mean?
One study from the CNN (the database not the news channel) used a case control design, the controls were all patients who did not develop NEC at all, the controls had a transfusion within 2 days before their diagnosis. For the controls they examined the 2 days before the median age of developing NEC in the same birth weight stratum. According to this study 9% of cases of NEC occur within the 2 days after a transfusion. Of course, babies who get NEC as well as babies who have transfusions are smaller, more immature and sicker. You can try and correct for such things, but it is hard to convince me that you can eliminate all the confounding.
Even if it does exist what do you do about it? I have written on this blog on numerous occasions that there is no evidence that feeding patterns affect NEC. You can advance feeds fast or slow, feed trophically or advance immediately, or whatever you want to do, don’t expect any effect on NEC. Probably the only thing that you should not do is keep babies nil by mouth, to be honest there isn’t much evidence that this affects NEC, but it does affect growth, subsequent feeding tolerance and the duration of TPN and central catheter use.
Despite this, several individuals have suggested putting babies npo, to use the usual english-latin abbreviation. One stopped feeds during the transfusion and then started them again immediately afterward. They had a decrease in NEC from 9 cases of 171 LBW, to 2 out of 155. Which of course is a far bigger decrease than you could get from just preventing TANEC.
The most recent study, and the one which triggered this post, showed something quite similar. The authors instituted a policy of withholding feeds for 4 hours before and after the transfusion, and then half the previous volume for 12 hours, then advanced to the previous volume. They showed a reduction in NEC after introducing this (from 12% of VLBWs to 7%). However, they showed just as much reduction in NEC not related to transfusion as in TANEC, and the actual reduction in TANEC was not significant. So clearly the change in the policy of withholding of feeds was just coincidental with something else that happened (I don’t know what, they don’t seem to either).
And to come back to the overall feeding management issue. As I understand the data, and Bill McGuire, who does many of these Cochrane reviews, can correct me if I am wrong, early commencement of trophic feeds has a number of advantages over keeping babies npo, but in terms of the most clinically important outcomes of death or NEC there is no proof of benefit. Many of the studies actually had 2 or 3 days of being npo even in the trophic group, though, so good data about starting feeds immediately after birth are lacking. Secondly, the data compare trophic feeds to no feeds. I don’t think there are good trials comparing trophic feeds, initiated early, to immediately starting to increase feed volume. That is a trial that I think we do need, infants would be randomized shortly after birth to a schedule which gives 3 or 4 days of trophic feeds, or would start at the same volume for the first feed, but immediately be on a schedule of increasing by 20 to 30 mL/kg/day.
Wasn’t NEC also increased in the babies in the low oxygen arm of the BOOST II trial? And the only apparent reason for the increased mortality in that group?
There were more deaths from sepsis and from bronchopulmonary dysplasia as well, but the biggest difference was in NEC deaths, 23 vs 14. There wasn’t a big difference in diagnosis of NEC, 11.9% vs 10.8%, just in mortality from NEC.
Its also interesting that in the new article I discussed the babies that seemed to have TANEC had lower hemoglobins before the transfusion, maybe their intestines were hypoxic from their anemia? The NEC might be a manifestation of re-oxygenation injury.