CMPA, Soy and CPS Statement about concerns around Soy


This is intended for assistance in counseling around soy and CMPA

Concerns around using soy based formulas arose due to phytoestrogens and the findings in in vitro animal studies. They have not been substantiated in humans as yet, but there have been some findings that raise concern in some groups. Studies have mostly been performed in children 6 months or older, decreasing the applicability in non IgE mediated CMPA which also tends to present younger than this.


  1. Congenital hypothyroidism, as animal studies suggest phytoestrogens can inhibit thyroid peroxidase, potentially lowering free thyroxine concentrations, which could lead to abormal thyroid function (not a concern if normal thyroid function). Therefore, infants with congenital hypothyroidism who are fed soy-based infant formulas should have their thyroxine levels monitored.
  2. Prematurity: inadequate growth promotion
  3. non IgE mediated CMPA – due to cross reactivity between soy bean protein and bovine casein

So when can we recommend it?

  1. Galactosemia
  2. Cultural or religious practices restrict dairy-based products (veganism)
  3. IgE mediated CMPA

Animal studies have shown that consumption of phytoestrogens can result in infertility.

Exposure of neonatal animals to the isoflavones present in soy-based formula can cause subtle alterations in sex organ development, brain maturation and immune system function, and can also stimulate cancer development.

Currently available soy-based formulas support normal growth and nutritional status for the first year of life, with no overt toxicities observed in normal infants.

Limited long term safety data. Over 40 years of use support the safety of currently available formulations. The Committee on Toxicity (United Kingdom) released a report in 2003 titled “Phytoestrogens and Health”, which identified infants who were fed soy-based formulas as the population subgroup with exposure to the highest concentrations of isoflavones. Although this committee did not identify definitive evidence of adverse health effects in their review, they believed that the potential risks were a concern. The Committee on Toxicity also sought consultation with the United Kingdom’s Scientific Advisory Committee on Nutrition, who suggested that there was no substantive medical need for, nor health benefit arising from, the use of soy-based infant formulas.


  • the commonest food allergy in infants with incidence of approximately 2.5% among infants <1year
  • IgE mediated vs. non IgE mediated is difficult to distinguish but most commonly it is done based on signs/symptoms and confirmed with SPT and specific/nonspecific serum IgE. Some signs have been used to differentiate between the two but they lack sensitivity and specificity.

screen-shot-2016-11-12-at-12-08-52-pmAbove figure taken from:

screen-shot-2016-11-12-at-2-31-09-pmTable above taken from: Diagnostic Approach and Management of Cow’s-Milk Protein Allergy in Infants and Children: ESPGHAN GI Committee Practical Guidelines. JPGN Volume 55, Number 2, Aug 2012.

To differentiate between IgE mediated and non IgE mediated:

History should include symptoms particularly related to skin and gut with some respiratory consideration, and family atopic history.

“acute onset” IgE mediated (traditionally, anaphylaxis type symptoms):

  • urticaria+/- pruritis
  • angioedema
  • respiratory symtpoms
  • GI symptoms
  • eczema may be present

“delayed onset” non IgE mediated (which usually presents under six months of age):

  • gastrointestinal symptoms, and most commonly blood +/- mucus in stool, in the event of colitis
  • colic, reflux, loose/frequent stools, food aversion.

Why do we recommend soy-based formula?

  • cost (reduced compared to hydrolyzed formulas)
  • comparative palatability

However, there is cross-reactivity with cows milk protein, and therefore the use of soy-based formulas is only contraindicated for non IgE-mediated CMPA

NASPAGHAN Recommendation:

  1. hydrolyzed protein formula (HPF) as first line –> Nutramigen
  2. amino acid formula (AAF) if hydrolyzed formula not tolerated–> Neocate

ESPGHAN Recommendation:

  1. soy based formulas should not be used in infants under 6 months due to higher reported rate of adverse reactions to soy protein in the population.

Before soy based formulas are started – tolerance to soy protein should first be established by clinical challenge.

screen-shot-2016-11-12-at-1-58-10-pmFigure above taken from: Diagnostic Approach and Management of Cow’s-Milk Protein Allergy in Infants and Children: ESPGHAN GI Committee Practical Guidelines. JPGN Volume 55, Number 2, Aug 2012.


The gold standard is the double-blind, placebo-controlled food challenge, which, if the patient is clinically stable, with no concern with possible anaphylaxis, can be done in the community setting, but personally, I would leave that to an allergy expert.

If non IgE mediated is suspected, elimination diet ideally recommended for 2-4 weeks with planned slow re- introduction.

If IgE mediated suspected – SPT, specific IgE assay, consideration of food challenge in a hospital/controlled (non community) setting.

screen-shot-2016-11-12-at-3-06-41-pmDiagnosis and management of non-IgE-mediated cow’s milk allergy in infancy – a UK primary care practical guide. Clinical and translational Allergy. Vater et al. 2013.

If there are ongoing difficulties in differentiating the two types, consider consult with Allergist, although not always practical.

MANAGEMENT once CMPA is diagnosed:

  1. Firstly, breast is best.
  2. If this is not tolerated, treat with HPF which is the safest and most appropriate from a public health standpoint
  3. Soy is acceptable in IgE mediated (in non IgE mediated, there is cross reactivity with soy)
  4. Our job is then to: To counsel families about the importance of breastfeeding; to inform families about alternative formulas and to advocate on the behalf of families to the government for assisted coverage of HPF for CMPA.

When to consider re-introduction?

No ideal time. If proven CMPA, keep off at least until 6 months and up to 9-12 months of age.
screen-shot-2016-11-12-at-3-18-26-pm screen-shot-2016-11-12-at-3-18-36-pm

The above advice and flowcharts are from: Diagnosis and management of non-IgE-mediated cow’s milk allergy in infancy – A UK primary care practical guide. Available from:’s_milk_allergy_in_infancy_-_A_UK_primary_care_practical_guide [accessed Nov 12, 2016].

Here is a link to the CPS statement used:

Leave a Reply

Your email address will not be published. Required fields are marked *