Neonatology recently published a commentary asking the following question about routine probiotic supplementation, ‘what will it take to change practice?‘
This was immediately followed by another commentary, from Neena Modi, explaining why she is still reluctant. Although I have a great deal of respect for Neena, I must say, on this issue, she is wrong.
She reports her unit’s use of fresh colostrum, and the extensive use of fresh breast milk. Now at the risk of receiving howls of protest from the breast milk police (I am one of them myself!) there are stronger data for the efficacy of probiotics than for fresh breast milk, when it comes to prevention of NEC. Indeed one of the mechanisms for the activity of breast milk is probably the frequent ‘contamination’ of breast milk with probiotic organisms, as she mentions herself. I certainly agree that there are also theoretical advantages of other components breast milk, such as the fucosylated oligosaccharides, lactoferrin, and lysozyme. Also secretory antibodies (Rogier EW, et al: Secretory antibodies in breast milk promote long-term intestinal homeostasis by regulating the gut microbiota and host gene expression. PNAS 2014 a new study in a mouse model showing the probably beneficial effects of sIgA on promotion of a normal microbiome).
One place where I disagree with her are the examples she uses that ‘some therapies initially embraced enthusiastically and widely believed to be safe – for example routine oxygen administration at resuscitation, and antenatal antibiotics for women in spontaneous preterm labour with intact membranes – were ultimately shown to be of no benefit or to have harmful long-term consequences’. As I pointed out during my recent presentation in Scottsdale (which you can download if you wish), therapies which fall into that category have a common feature, that they were adopted without much, or without any, evidence from randomized controlled trials. They were adopted based on ‘expert opinion’ or, more commonly, based on fashion.
Which is actually the opposite of what we see with probiotics. In this instance we have extensive evidence from RCTs, of efficacy and of safety, and yet they have not been ’embraced enthusiastically’.
As mentioned, breast milk contains probiotic organisms, so if you use fresh breast milk you are usually giving probiotics anyway, you won’t be giving very many in the first few days, and you have no idea which strains you are administering. There are also, of course, frequently pathogens in breast milk, and mothers who have received antibiotics have a very different microbiome of their breast milk. A new review article (Latuga MS, Stuebe A, Seed PC: A review of the source and function of microbiota in breast milk. Semin Reprod Med 2014, 32(1):68-73) is a fairly brief read, and summarizes the data about the germs that are commonly in breast milk, and how they get there, including the idea of entero-mammary trafficking, meaning that they might be specifically transported to the breast tissue from the GI tract.
In a new study published on-line in JPGEN the frequency of finding lactobacilli and bifidobacteria in breast milk was lower than in some other studies, and importantly was substantially decreased by giving antibiotics to the woman. (Soto A, Martin V, Jimenez E, Mader I, Rodriguez JM, Fernandez L: Lactobacilli and bifidobacteria in human breast milk: Influence of antibiotherapy and other host and clinical factors. Journal of pediatric gastroenterology and nutrition 2014). Many mothers who deliver extremely preterm have received antibiotics, this study demonstrates, as we would suspect, that the women who received antibiotics had much lower probiotic counts in their breast milk.
And finally another study showing that antibiotics given to preterm infants do actually kill probiotic organisms, promote the growth of resistant pathogens, and increase the later risk of NEC. (Greenwood C, et al: Early empiric antibiotic use in preterm infants is associated with lower bacterial diversity and higher relative abundance of enterobacter. Journal of Pediatrics 2014).
So if you give breast milk to very preterm infants, you administer an unreliable source of the same organisms as if you actually give a probiotic preparation. You may not give any probiotics if the mother received antibiotics, and if the baby is on antibiotics you really screw up their intestinal microbiome and kill any good bugs that they are getting from the breast milk.
The best way to be certain that the baby receives a source of these protective organisms is by giving them a verified source of probiotics, which will decrease the rate of NEC, even among babies with a high rate of breast feeding.
Well, I don’t see why you couldn’t simply have both – fresh breastmilk plus probiotic supplement. And not just for the baby, but for the mother too, as it is the same entero-mammary pathway that can ensure that mom’s supplementation will enrich the microbiom in her breastmilk and help restore healthy levels of the desired strains in her milk after an antibiotic treatment.
I absolutely agree. Breast milk has many advantages in addition to reducing NEC. We should be promoting its use vigorously. The only concern about fresh, rather than frozen and thawed, breast milk is the frequent presence of CMV. I don’t know the best answer to what we should do about that.