It is not infrequent in the neonatal unit to be faced with an infant who has rectal bleeding. In some places the tendency has been to assume that the infant has cows milk protein intolerance (even among those who are breast fed!) and place the infants on a hydrolysed protein diet or even on an amino acid based diet. What is the evidence for the diagnosis and treatment of cows milk protein intolerance in the preterm, or term newborn?
There are very few reports of cow’s milk protein intolerance in the preterm infant. Even those that have reported have not usually confirmed the diagnosis, but how to do that? There are two methods which have been reported as being reliable, although their reliability is uncertain as we do not have a gold-standard. The most commonly used is response to exclusion of cow’s milk protein, but this must be followed by a challenge; the re-introduction of cow’s milk to see if the signs return and, if they do, the re-exclusion to make sure they go away again. If you don’t do the challenge then any case of transient clinical signs will be mis-diagnosed as cow’s milk protein intolerance.
One study in older infants found 2 things, (Xanthakos SA, Schwimmer JB, Melin-Aldana H, Rothenberg ME, Witte DP, Cohen MB: Prevalence and Outcome of Allergic Colitis in Healthy Infants with Rectal Bleeding: A Prospective Cohort Study. Journal of Pediatric Gastroenterology & Nutrition 2005, 41(1):16-22) firstly, most pediatric gastroenterologists don’t follow their own societies guidelines, and don’t do a challenge if a child presents with rectal bleeding that improves after exclusion. Which means that many infants end up with a diagnosis that has not been confirmed. Secondly, they also showed that using the other method of diagnosis, that is doing a rectal biopsy, less than half of the infants with rectal bleeding actually had evidence of allergic colitis. Another study, (Arvola T, Ruuska T, Keränen J, Hyöty H, Salminen S, Isolauri E: Rectal Bleeding in Infancy: Clinical, Allergological, and Microbiological Examination. Pediatrics 2006, 117(4):e760-e768) also in infants, noted that rectal bleeding was benign and self-limited, and despite rectal biopsies etc, were able to confirm the diagnosis in only 7 of 40 consecutive cases of rectal bleeding. Interestingly they noted a low number of bifidobacteria in the stools of the infants, suggesting that an imbalance in the microbiota may play a rôle.
Even a test as invasive as a biopsy is not certain, the findings of patchy eosinophilic colitis is supposed to be diagnostic, but the cause of the allergic colitis cannot be determined from the biopsy. As it may be found in infants who are exclusively breast-fed, even among those whose mother is on a cows milk free diet, the diagnosis of human milk protein allergy has been created. Which I find very doubtful! What is the evidence that human milk may contain cows milk proteins if the mother consumes them? Well the most common protein implicated is bovine beta lactoglobulin, in one older study one third of mothers consuming cows milk based products had detectable traces of bovine BLG in their breast milk. So it is possible that these trace amounts might trigger symptoms. That study also found that breast fed babies with signs of cows milk protein intolerance had all received supplements with a cows milk based formula in the neonatal period.
For full term infants does it matter if they have a diagnosis of cows milk protein intolerance which is not correct? It is actually pretty straight forward to find nutritionally adequate hydrolyzed protein formulae for the full term infant. (Not soy protein based formulae; a lot of infants proven to be intolerant of bovine proteins are also intolerant of soy proteins). On the other hand they are more expensive, and not all kids will tolerate even them; but amino acid based mixtures are much more expensive. Also bovine protein exclusion diets are a real pain for mothers who are breast feeding, and some of them are inappropriately discouraged from breast feeding. Having a diagnostic label that is incorrect is not the best situation, but some parents are happy to buy hydrolysed protein formulae, accept that the diagnosis is not certain, and live with that uncertainty for a few months, (more than half of proven cows milk protein intolerance disappears in the first year).
For preterm infants the situation is different, there are no artificial milk formulae which are nutritionally adequate for the preterm and yet are free of bovine proteins. So a diagnosis in the preterm has other implications for their nutrition. In addition all approved and appropriate fortifiers which are required to add protein, calories and minerals to human milk are based on cow’s milk.
So going back to the diagnosis of bloody stools, and now looking at the neonatal period, a recent study using new microarray methods found that newborn infants with rectal bleeding did not have findings consistent with allergy. (Ohtsuka Y, Jimbo K, Inage E, Mori M, Yamakawa Y, Aoyagi Y, Suzuki M, Kudo T, Suzuki R, Shimizu T: Microarray analysis of mucosal biopsy specimens in neonates with rectal bleeding: Is it really an allergic disease? Journal of Allergy and Clinical Immunology 2012, 129(6):1676-1678.) Other studies have found weird viruses in the stools of such babies (Chappé C, Minjolle S, Dabadie A, Morel L, Colimon R, Pladys P: Astrovirus and digestive disorders in neonatal units. Acta Paediatrica 2012, 101(5):e208-e212). I have certainly seen rectal bleeding associated with rotavirus in more than one preterm infant.
Rectal bleeding may also occur in the setting of strictures, either congenital strictures or post enterocolitis. This is probably the most common cause of rectal bleeding in the preterm after NEC, and is often misdiagnosed, often as cows milk protein intolerance.
In fact there is evidence that the pre-term period is a time when exposure to foreign proteins is more likely to lead to tolerance than to allergy. There is certainly no evidence of an increase in allergic diseases among preterm infants. There are a couple of large cohort studies showing a similar, and relatively low rate of allergic diseases, and specifically cows milk protein intolerance, among preterm infants to term infants. (Zachariassen G, Faerk J, Esberg BH, Fenger-Gron J, Mortensen S, Christesen HT, Halken S: Allergic diseases among very preterm infants according to nutrition after hospital discharge. Pediatric allergy and immunology 2011, 22(5):515-520.)
In general then a baby in the NICU who has rectal bleeding is more likely to have something other than cows milk protein intolerance, and it becomes even less likely to be that diagnosis if the infant is preterm, and very much less likely if they are breast fed.
That is why protect,promote and support breastfeeding practically to lessen the burden of rectal bleeding in neonates.Breast milk substitutes (tinned milk) is another problem giving rise to bleeding p/r ,we encounter.
Dear Keith, May I ask you for some advice please? At 24 hrs of age, a baby girl born in good condition by vaginal delivery with a b.wt of 3kg, (IM vit K given), (breast fed baby) developed bloody stool. The blood in the stool nearly looked fresh with some small areas looking the colour of beetroot. Was quiet, tachypnoeic with intercostal recessions. First abdo X-ray revealed a gasless abdomen, stomach bubble ok, NGT tip in stomach. No acidosis on bld gas, INR 1.87, CRP max 10, 12 hrs later 16. 2 more doses of Vit K given, 1 IV and 1 IM. Started on IV abx, no more blood in stool even after the 1st dose of abx, good response clinically, activity better, after 48hrs of abx, crying well. NBM for 48 hrs. Feeds re-started. Grateful for any advice as to what this could be.
In terms of likelihood, the most likely diagnosis would be swallowed maternal blood. In healthy appearing full term babies at this age, swallowed maternal blood can appear in the stools almost unchanged, bright red or as apparent clots. The first test to do would be an Apt test. Many labs are reluctant to do Apt tests, due to a lack of experience and lack of standardisation, but the results can be very obvious, if you just compare to a sample of adult human blood. A much more expensive alternative test would be analysis of the type of hemoglobin in the stool.
Other possibilities are much less likely; I have seen rotavirus presenting like this, but not at 24 hours of age, and usually in ex-preterm infants. Cows’ milk protein intolerance is a possibility, from maternal ingestion of cows milk protein, but to get frank blood at 24 hours of age is unusual. A Meckel’s diverticulum does not usually bleed frankly at this age, but if it was recurrent, might need eliminating.
Your babies moderately prolonged PT INR is a concern though, so I would also suggest a hematologic work-up. In a newborn girl, Hemophilias a re not likely, and Von Willebrand doesn’t affect the INR, so it would be something rarer if the INR remains elevated.
Hope this helps
How about milk allergy ? My son was born full term. They found blood stool at very beginning then kept him in hospital with feeding formula. His condition got worse and worse. After 10 days, he was placed at NICU and they replaced formula feeding with IV feeding. 30 days he was discharged and given prescription formula neocate.
Later, IgE test showed his very strong milk allergy.
I think the very early blood stool might be swallowed maternal blood — but later blood stool was caused by milk formula allergy — continuing feeding made it worse.
I wanted to share my own experience. My daughter had on and off mucousy stools, occasionally bloody streaks in them. I have been put on no milk, egg or soy diet (1 month). To me her stools looked the same, and i never felt there was any correlation to what i ate ( kept a detailed food journal, i am a biologist) We went to the dr numerous times whem my daughter was between 2.5 months and 6 months.. And nothing. Mucous and blood didnt stop.
then came solid food! With my mum insisting i add a bit of yogurt to her meals..
Ps. She was breastfed
And viola! She never had mucus again!