Infant Milk Allergy Guidelines Promote Overdiagnosis, Study Says

Marcia Frellick

December 09, 2021

International guidelines developed to help nonspecialists diagnose cow's milk allergy (CMA) lead providers to attribute normal infant symptoms to CMA and result in overdiagnosis, say authors of a study published online this week in Clinical & Experimental Allergy.

Dr Rosie Vincent

Lead author Rosie Vincent, MBChB, with Population Health Sciences at University of Bristol in Bristol, United Kingdom, told Medscape Medical News their study shows that symptoms listed in the international Milk Allergy in Primary Care (iMAP) guidelines as indicative of non-immunoglobulin E (IgE)-mediated milk allergy are very common in a baby's first year. Examples include vomiting, regurgitating milk, loose or more frequent stools, colic, and irritability.

Findings come from performing a secondary analysis of data from 1303 infants from the EAT study, a population-based, randomized controlled trial in the UK that looked at whether introducing allergenic foods into an infant's diet reduced the risk of developing an allergy to that food.

It's not just about reflux, it's not just about a baby spitting up. Happy babies spit up and there's nothing that needs to be done because they will eventually grow out of it. Heather Cassell, MD, University of Arizona College of Medicine

In an indication of how common the symptoms in the guidelines (published in 2017 and 2019) are found in all infants, nearly three fourths (74%) of participants reported at least two mild-to-moderate symptoms and 9% reported at least two severe symptoms in at least one month between 3 and 12 months of age. Data were not available for younger infants.

However, the prevalence of non-IgE-mediated CMA is thought to be less than 1% in infants in European countries, the study states.

In the study, two or more non-IgE CMA mild to moderate symptoms were reported by 25% of families and 1.4% reported severe symptoms each month between ages 3 and 12 months.

"These symptoms peaked at 38% with at least two mild to moderate symptoms and 4.3% with at least two severe symptoms at 3 months, when participants were not directly consuming cow's milk," Vincent said.

Researchers write that at 6 months there was no significant difference in the proportion of children with at least two symptoms between those consuming and not consuming cow's milk.

Consequences of Misdiagnosis

Overdiagnosing milk allergy can lead to additional costs, unnecessary tests, and less breastfeeding, she said.

Cow's milk protein is commonly found in standard infant formula or in milk-containing foods.

The authors note that "small levels of lactoglobulin are found in breastmilk; however, the quantities are below the threshold likely to trigger a reaction in more than 99% of infants with IgE-mediated cow's milk allergy."

Misdiagnosis is likely to result in increasing prescriptions of unwarranted specialized formula, with increased cost to patients and healthcare systems, and use of unvalidated allergy tests, Vincent said.

Vincent added that even the suggestion that cow's milk protein delivered through breast milk might be inducing symptoms could lead a mother to stop breastfeeding.

The authors also note that in reviewing recent CMA guidelines, "three of nine CMA guidelines were directly supported by formula manufacturers or marketing consultants, and 81% of all guideline authors reported a conflict of interest with formula manufacturers."

Dr Heather Cassell

Heather Cassell, MD, a pediatric allergy and immunology specialist with Banner Health and a clinical associate professor of pediatrics at the University of Arizona College of Medicine in Tucson, told Medscape Medical News the conflicts of interest in milk allergy research and guidelines have been a long-standing problem.

She said historically there has been a big push "that people who can afford formula should be paying for formula. That was 100% marketed by the formula companies."

"We have formula companies bringing us samples to encourage pediatricians to use the formula early if we're concerned about a milk protein allergy," Cassell said.

As for the overdiagnosis of milk allergy, she said reintroduction of cow's milk later is one way to improve diagnosis to see if the child no longer has a reaction. However, she points out that in this study, only 21% of parents reintroduced cow's milk.

"Really, it should be closer to 100%, with the exception of the babies who are having severe symptoms," Cassell said. "You don't want to keep a baby from progressing with their diet."

She said families and providers need to look at several contextual clues before they land on a milk allergy label.

"It's not just about reflux, it's not just about a baby spitting up. Happy babies spit up and there's nothing that needs to be done because they will eventually grow out of it," Cassell stressed.

She said significant irritability with blood in the stool might warrant more concern. "I think the [emphasis] needs to be on retrying the food another time," she suggested.

Vincent pointed out that there is no quick or easy test to diagnose non-IgE mediated cow's milk allergy.

"We need further research to identify what symptoms are much more likely to point to a diagnosis," she said.

Although the researchers used iMAP guidelines, they write that results are likely to apply to other CMA guidelines, because they list similar symptoms and signs.

The study was funded by the International Society of Atopic Dermatitis. Vincent reports receiving a 3-month research fellowship award from Pfizer and support from the NIHR School for Primary Care Research, Other authors' financial disclosures are available with the full text. Cassell reports that the University of Arizona School of Medicine is a trial site for testing a patch to help with diagnosing milk protein allergy in infants.

Clin Exp Allergy. Published online December 7, 2021. Abstract  

Marcia Frellick is a freelance journalist based in Chicago. She has previously written for the Chicago Tribune, Science News, and, and was an editor at the Chicago Sun-Times, the Cincinnati Enquirer, and the St. Cloud (Minnesota) Times. Follow her on Twitter at @mfrellick

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