The Proprems study that I have referred to a couple of times before has now been published. This was a multicenter RCT of a probiotic preparation in 1100 very preterm infants less than 1500 grams and less than 32 weeks. The primary outcome of the trial was late onset sepsis. We now have good evidence from a large number of randomized trials that probiotics have no effect on late onset sepsis, I guess when this trial was being planned that wasn’t so clear. The babies were enrolled before 72 hours of age, and received their probiotics whenever they were getting more than 1 mL of milk every 4 hours. The preparation contained 2 bifidobacteria (infantis and lactis) and a probiotic streptococcus, S thermophilus.
The results showed a reduction of necrotizing enterocolitis from 4.4% in the control arm to 2% in the probiotic group, which was statistically significant. So even in a low risk group, with high breast feeding rates (over 96%) and very high quality NICU care, probiotics do exactly what they have done in the other studies: a reduction of 50 to 60% in the frequency of stage 2 NEC.
In fact, and in contrast to what I said in the first paragraph, there was a small effect on late onset sepsis, a reduction which could have been due to chance, (p=0.16). I await the next Cochrane review to see if that changes the overall conclusion of no effect, but, if there is an effect, it is certainly not huge.
Interestingly the incidence of NEC in the ANZNN annual report, among babies less than 28 weeks in 2010 was 10.4%. This is very similar to the CNN annual report (we don’t divide up the GA exactly the same way, but NEC under 29 weeks in the new 2012 CNN report was 8.1%). So the babies enrolled in the Proprems study were a lower risk group, mostly by design I think, with a range up to 32 weeks GA, but it would be interesting to know the risk profile of the non-enrolled infants, perhaps in the next version of CONSORT a report of some basic summary characteristics of non-enrolled patients could be added.
The published trials of probiotics now include over 5000 preterm babies. There is not one report of an adverse event among the 2500 or so randomized to probiotics. We don’t have that sort of safety information for anything else we do in neonatology.
Another fascinating detail, the probiotic preparation used was ABCDophilus, which is manufactured in New Jersey by Solgar. Yes, made in the USA. (www.solgar.com).