Simple Strategy Prevents Cow’s Milk Protein Allergy.

Simple Strategy Prevents Cow’s Milk Protein Allergy.

by | Dec 19, 2019 | Breastfeeding

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.

The Findings

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!

Simple Strategy Prevents Cow’s Milk Protein Allergy.

Is it better to be a tortoise or hare when advancing feedings in preemies?

by | Dec 5, 2019 | nutrition

I presented this topic as a fellow many years ago after a paper came on the scene suggesting better outcomes with a faster approach. The paper Randomized trial of “slow” versus “fast” feed advancements on the incidence of necrotizing enterocolitis in very low birth weight infants. was plagued by the same issue as others created around those years which was a small number of patients at the lowest gestational ages. Any differences in sub analyses were difficult to really believe as the outcomes could have easily been explained by chance. Having said that, many centres began advancing feeds a little faster than the typical 20 ml/kg/d in favour of 30 ml/kg/d. It would take some time to coordinate a trial large enough to really answer questions about relevant issues such as time to developmental outcomes, time to full feedings and rates of NEC and the time appears to be now.

The SIFT trial

This trial (Controlled Trial of Two Incremental Milk-Feeding Rates in Preterm Infants) was the result of a great deal of coordination between 55 different centres. For inclusion, infants had to be <1500g and <32 weeks gestational age at birth. Once the decision was made to advance feeds, babies were randomized to receive increases of 18 mL/kg/d vs 30 ml/kg/d. The primary outcome was survival without mod-erate or severe neurodevelopmental disability at 24 months CGA. What is striking about the study is its size. The number of babies in the fast arm was 1394 while 1399 in the slower group. In terms of having sufficient numbers of infants who were at the earliest gestational ages they were able to accomplish this as shown in this table.

Importantly when looking at the primary outcome 87.4% of infants in the faster group vs 88.7% in the slower group were followed up for assessment. It is also worth mentioning that this is even more impressive in terms of retention when one considers that about 6% in both arms died before assessment.

What were the findings then?

There was no difference in the primary outcome or for that matter each of its’ competing parts.

The authors in a secondary analysis did show a very marginal significant finding favouring slow feeds with respect to motor outcome. I concur with the authors though that given the small effect size and the “fishing” for results this likely is simply a chance finding. I can’t think of any reason why that would be the case either from a biological standpoint.

Not surprisingly another significant finding was shorter durations to reach full feeds (10 vs 7 days) and days on TPN at 11 vs 9 in the slow vs fast groups. In spite of having less need for central venous access, the authors were unable to show a reductoin in late onset sepsis or NEC.

Does it change your management?

I suppose that depends on what your management currently is. If you are like our centre and already advancing feedings by 30 ml/kg/d then I suspect not much. If you are in a slow centre one can take away from this study that at the very least you can lessen your patient’s need for central venous access and TPN. Based on this study and my suspicion that there will be no bigger trial forthcoming, whatever you decide to do this is about the best data that you will be getting.