I have had several communications from people interested in starting the use of probiotics in their nurseries. There are often roadblocks, and some reluctance from either infection control, or pharmacy and therapeutics committees (or both).
I will recount what we went through at Sainte-Justine to get probiotics to our babies.
When I arrived here 4 1/2 years ago (time flies) I was already convinced that probiotics were the way to go. My first inquiries about using probiotics were not fruitful, but I worked with one of our NICU pharmacists to produce a document formally applying for the addition of a probiotic mixture to the hospital formulary. I investigated the different preparations available and at that time got into contact with someone who works with a probiotic manufacturer (Harmonium International) who have their facility not far from Montreal. He is the one who really got me informed about the Health Canada Natural Products Directorate, what an NPN (natural product number) means, the DNA registration database for probiotics (there are several) and the different preparations available. After the document was prepared I went with the pharmacist to the pharmacy committee, they were very reluctant, wanted some time to consider, wanted to confer with the infection control docs, and asked me to consider how we would evaluate the effects. I was hopeful, however: it wasn’t an outright no.
At about the same time, we had a mother in our NICU whose baby was born about 24 1/2 weeks gestation, the baby had a ‘NEC scare’ and subsequently the mother came to me, telling me she had read about probiotics on the internet, that she already gave probiotics to her other children, and she would like her baby to have them.
Now we had previously had some parents want to give their baby herbal medicines, and, if we were able to be fairly sure that the preparation was safe, then we have facilitated this. So in this new situation, and my pre-existing desire to give probiotics anyway, I told the mother that if she wanted to go and buy a preparation with a Health Canada NPN, that had a lactobacilllus and at least one bifidobacterium in it, (and I gave her 2 choices of mixtures that I thought were appropriate) and bring it to the NICU, then we would give it to her baby.
From then it snowballed, several parents wanted to give their babies probiotics, when they asked me about it I told them about the evidence, (at the time there were ‘only’ 17 RCTs with ‘only’ 3,000 babies randomized; showing no adverse effects, no infections with probiotic organisms, a reduction in NEC and a reduction in mortality). It was, and still is, the only intervention, other than breast milk, which is proven to prevent NEC. A number of parents decided to buy their own probiotics. By now it seemed a little random who was getting probiotics and who was not, so I wrote an information letter for the parents, to be given on admission. Applying the ethical principle of justice, I didn’t want some parents to be informed but not others.
By this time the hospital was a bit unhappy with me, and asked me to go back to the Pharmacy committee, so the pharmacist (Josianne Malo) and I re-applied to the pharmacy committee, by this time our infectious disease people had confirmed, by taking a sample from one of the tubs that a parent had brought to the hospital, that they can grow the organisms in our lab, and that they didn’t find any pathogens.
The pharmacy committee asked me to perform an objective prospective evaluation of the effects of introducing probiotics into our NICU, we developed a standing order form to be completed on admission, and wrote a protocol to control how they were used.
The current protocol:
All babies under 32 weeks gestation admitted to the NICU within the first 3 days of life are eligible.
Babies with congenital GI anomalies are excluded
Starting with the first feed 0.5g of florababy(TM) are given mixed with 1 ml of water, once a day just before a feed.
Florababy is continued to 34 weeks post-menstrual age, and then stopped (unless the parents ask us to continue, which has been rare).
If the baby is put npo the florababy is also stopped, and then restarted with the feeds.
As we were unwilling to perform a randomized trial with untreated controls, the pharmacy committee agreed that a prospective cohort study would be acceptable. We obtained permission from the research ethics board to perform the cohort study, and a retrospective chart review to get some historical controls. We planned an 18 month collection period to get a sample size of about 300 per group.
I think we have been successful because
1. there was a conjunction of circumstances, including the particular mother involved in our first ‘case’.
2. I was bloody minded enough to keep pushing.
3. My colleagues were supportive, especially Annie who helped to push this through.
4. Our NICU pharmacist was very helpful, to write the documents in a way that would work with the committee.
5. Discussions with Infection Control focused on the risk/benefit balance and not just on the risks, and they were receptive. (In fact the risks are tiny, no adverse effects despite over 5000 babies in the trials)
6. The pharmacy committee were open to the initiative.
I must emphasize that the Health Canada NPN does not mean that probiotics are approved by Health Canada for the prevention of NEC. It does mean that the manufacturers follow GMP, and that there is adequate quality control in inspected factories. It means for probiotics that the DNA of the strains is registered. So it basically means that you are getting what you think you are getting. It also means that any health claims on the label have been approved, (I think this label says ‘maintains intestinal health’ or something equally vague).
I think the key to getting over the objections here was really the infection control groups understanding of the importance of NEC prevention in the face of a lack of documented risks. Once you get them on-side, or at least not in the opposition camp, then you can probably win.
Or rather, it is the babies that win.
Thanks for this. We had less of a business getting probiotics approved for use in our hospital. We simply went to the “drug and therapeutics committe” with the evidence. The fact it wasn’t a drug didn’t seem to make it more complicated. We give them to a similar group, but do still give them to babies who arrive at more than a few days of age.
I see that originally you had a groundswell of parental interest. We have been gaining assent for probiotic use, but plan to move to a leaflet once the hospital has approved it. This process has taken longer than getting probiotics approved for use. Are you using a leaflet to inform parents, or not even that?
Always enjoy the blog.
Wonderful! Would like to see if Dr. Barrington is available to lecture on the topic.
Terri Slagle, MD California