Breast milk is certainly a hot topic these days. Allergies in childhood are almost equally hot in the media as food allergies seem to be on the rise (not my specialty by a long shot) as well as rates of other atopic illness. Given what is known about the modifiable risks in terms of a number of conditions such as NEC and late onset sepsis in preterm infants it wouldn’t be a stretch to wonder what impact avoidance of cow’s milk exposure could have in the term newborn.
A Landmark Japanese Study
Urashima et al just published in JAMA Pediatrics the following paper Primary Prevention of Cow’s Milk Sensitization and Food Allergy by Avoiding Supplementation With Cow’s Milk Formula at Birth: A Randomized Clinical Trial . This paper looked at 312 infants (≥ 36 weeks at birth) who were randomized to either receive breastfeeding plus an elemental formula if needed vs breastfeeding plus intact protein cow’s milk formula with a volume of at least 5 mL/kg per day. In order to have a group of infants truly at risk of atopic disease, all infants had to have at least one immediate relative with atopic disease. In each arm of the study, infants were followed with blood IgE levels at 5 and 24 months of age to detect a level of CM-IgE ≥ allergen units/mL. This was the primary outcome on which the power calculation was based for the study. Using an estimated incidence of 10% in the breastmilk group vs 25% in the exposed group the authors needed 300 patients to detect a difference. Secondary outcomes included detection of other allergens aside from allergy to cow’s milk.
Given that I called this a landmark study it might not be surprising to know that they found a difference favoring protection with human milk.
Also curious is the relationship to vitamin D levels. Previous research has documented an inverse relationship between vitamin D levels in children and risk of atopy. Why only the middle tertile in this study but not the higher tertile had less IgE response is unknown.
Perhaps even more surprising (at least to me) was that the risk of allergy at age 2 for other allergens was also lower.
Included in this lower risk was food allergy in general, risk of anaphylaxis and cow’s milk allergy that I presume manifested as rectal bleeding.
What Impact Could This Have
It is important to point out here that all these infants were ≥ 36 weeks so although I would love to infer that this strategy would have a huge impact on our preterm population I can’t say that yet (until a study is done). We certainly do see a fair bit of cow’s milk protein intolerance though that often leads to infants being placed NPO and on occasion worked up for NEC with a week or so of antibiotics. If this study is to be trusted, the rate of cow’s milk allergy was reduced from 6.6% to 0.7% in at risk infants (based on an immediate relative with atopy) and I would expect the risk in those without relatives to be less.
What might the impact be if we were to supplement with donor breast milk all term newborns who didn’t have enough maternal milk and take the elemental formula out of the equation entirely? If a 4 kg infant exclusively breastfed on day 1 and was give a couple ounces of supplement followed by full supplementation to 80 mL/kg/d on day 2 and then 100 mL/kg/d on day 3 that would total 26 ounces of donor milk in a worst case scenario assuming no maternal milk production during that time. At $4 per ounce we are looking at a cost to the system of about $100 a baby. Multiple that by the number of term infants in your centre to get an overall cost. In my own centre with about 12000 term deliveries a year that would come to 1.2 million dollars a year (again assuming no maternal milk at all). Is it worth the expense? I am not a health economist but I suspect if you were to add up the costs of workups/office visits etc for rectal bleeding, ED visits for asthma and anaphylaxis and the cost to families for food alleriges (let alone all the epi pens that need to be bought) it is worth it.
At the very least it does raise the question on post partum wards everywhere as to whether provision of cow’s milk formula should be one that someone has to consent to. With the publication of this study it certainly seems that it should be!
Exclusive human milk (EHM) diets using either mother’s own milk or donor milk plus a human based human milk fortifier have been the subject of many papers over the last few years. Such papers have demonstrated reductions is such outcomes as NEC, length of stay, days of TPN and number of times feedings are held due to feeding intolerance to name just a few outcomes. There is little argument that a diet for a human child composed of human milk makes a great deal of sense. Although we have come to rely on bovine sources of both milk and fortifier when human milk is unavailable I am often reminded that bovine or cow’s milk is for baby cows.
Challenges with using an exclusive human milk diet.
While it makes intuitive sense to strive for an exclusive human milk diet, there are barriers to the same. Low rates of maternal breastfeeding coupled with limited or no exposure to donor breast milk programs are a clear impediment. Even if you have those first two issues minimized through excellent rates of breast milk provision, there remains the issue of whether one has access to a human based fortifier to achieve the “exclusive” human milk diet.
The “exclusive” approach is one that in the perfect world we would all strive for but in times of fiscal constraint there is no question that any and all programs will be questioned from a cost-benefit standpoint. The issue of cost has been addressed previously by Ganapathy et al in their paper Costs of Necrotizing Enterocolitis and Cost-Effectiveness of Exclusively Human Milk-Based Products in Feeding Extremely Premature Infants. The authors were able to demonstrate that choosing an exclusive human milk diet is cost effective in addition to the benefits observed clinically from such a diet. In Canada where direct costs are more difficult to visualize and a reduction in nursing staff per shift brings about the most direct savings, such an argument becomes more difficult to achieve.
Detractors from the EHM diet argue that we have been using bovine fortification from many years and the vast majority of infants regardless of gestational age have little challenge with it. Growth rates of 15-20 g/kg/d are achievable using such fortification so why would you need to treat all patients with an EHM diet?
A Rescue Approach
In our own centre we were faced with these exact questions and developed a rescue approach. The rescue was designed to identify those infants who seemed to have a clear intolerance to bovine fortifier as all of the patients we care for under 1250g receive either mother’s own or donor milk. The approach used was as follows:
A. < 27 weeks 0 days or < 1250 g i. 2 episode of intolerance to HMF ii. Continue for 2 weeks
This month we published our results from using this targeted rescue approach in Winnipeg, Human Based Human Milk Fortifier as Rescue Therapy in Very Low Birth Weight Infants Demonstrating Intolerance to Bovine Based Human Milk Fortifier with Dr. Sandhu being the primary author (who wrote this as a medical student with myself and others. We are thrilled to share our experience and describe the cases we have experienced in detail in the paper. Suffice to say though that we have identified value in such an approach and have now modified our current approach based on this experience to the following protocol for using human derived human milk fortifier in our centre to the current: A. < 27 weeks 0 days or < 1250 g i. 1 episode of intolerance to HMF ii. Continue for 4 weeks B. ≥ 27 week 0 days or ≥ 750g i. 2 episodes of intolerance to HMF ii. Continue for 4 weeks or to 32 weeks 0 days whichever comes sooner
We believe given our current contraints, this approach will reduce the risk of NEC, feeding intolerance and ultimately length of stay while being fiscally prudent in these challenging times. Given the interest at least in Canada with what we have been doing here in Winnipeg and with the publication of our results it seemed like the right time to share this with you. Whether this approach or one that is based on providing human based human milk fortifier to all infants <1250g is a matter of choice for each institution that chooses to use a product such as Prolacta. In no way is this meant to be a promotional piece but rather to provide an option for those centres that would like to use such products to offer an EHM diet but for a variety of reasons have opted not to provide it to all.