Extensively hydrolyzed and amino acid infant formulas

Does my baby need infant formula for allergic babies?

Some babies cannot tolerate regular infant formula based on cow’s milk. They may need extensively hydrolyzed infant formula (EHF) or even amino acid infant formula (AAF). These do not contain milk sugar (lactose) or intact cow’s milk protein. EHF is considered low-allergy and AAF is considered non-allergenic. Both have a strong smell and bitter taste, causing some older babies to reject them. Babies who need EHF or AAF should be under the care of a health-care provider who can help decide which type to use and for how long. Most allergic babies tolerate EHF but some need AAF, including those who still have allergic symptoms when given EHF or are growing poorly on EHF. EHF has been advertised as being able to prevent allergies and reduce the risk of diabetes, but there is a lack of evidence supporting these claims.

A) Describing extensively hydrolyzed and amino acid infant formulas

This specialty type of infant formula (formula) does not intact cow’s milk protein. There are two main sub-types:

  1. Extensively hydrolyzed formula (EHF) has protein that is broken down (hydrolyzed) into little pieces. It is considered hypoallergenic, or low-allergy.
  2. Amino acid formula (AAF), also called elemental formula, has protein that has been further broken down into amino acids. It is considered non-allergenic.

Neither EHF nor AAF contain lactose and instead use other sugars, such as corn syrup or sucrose, to provide energy.

Both EHF and AAF have a strong smell and bitter taste, causing some older babies to dislike or reject them (Menella 1996; Menella 2005).  

AAF is more expensive than EHF, and both cost much more than regular cow’s milk-based formula.

EHF and AAF are not the same as partially hydrolyzed formula, which is a regular cow's milk-based formula

B) When to use extensively hydrolyzed and amino acid infant formulas

Some babies cannot tolerate ingredients found in regular cow’s milk-based infant formula (formula). These include babies who:

  • Are missing a part of their bowel (short-bowel syndrome).
  • Are switching from receiving all nutrition through a vein (parenteral nutrition) to taking food by mouth.
  • Have galactosemia, a disorder that affects how the body uses the sugar galactose.
  • Have congenital lactase deficiency, a disorder the prevents the digestion of lactose.

Those babies with a confirmed allergy to cow’s milk or other protein should continue breastfeeding if the allergic item is removed from the mother’s diet. Sometimes this is not possible because:

  • The mother cannot make the necessary changes.
  • The allergic item cannot be identified.
  • The baby is very ill and an immediate intervention is required.

In this situation, mothers may undertake a trial of EHF or AAF while maintaining their milk supply by expressing. If the symptoms do not quickly clear with specialty formula, the baby's diagnosis should be reconsidered and the mother may wish to resume breastfeeding. 

C) Choosing extensively hydrolyzed and amino acid formulas

Babies who need EHF or AAF should be under the care of a health-care provider who can help decide which type of formula to use and for how long.

Most allergic babies can tolerate EHF, but some need AAF (Meyer 2017; Vanderhoof 2016). This includes babies who:

  • Still have allergic symptoms when given EHF.
  • Are growing poorly on EHF.
  • Have multiple food, complex, or severe allergies, including FPIES, a rare protein allergy.
  • Have eosinophilic esophagitis, an allergic inflammation of the swallowing tube.
  • Have severe eczema, an itchy skin condition.

D) Promotion of extensively hydrolyzed and amino acid formulas

Recently AAF and EHF sales have increased dramatically. For example, In the United Kingdom (U.K.), there was a 10-fold increase in AAF prescription between 2005 and 2018 (Munblit 2020). In 2016 alone, this cost the National Health Service over £60 million (roughly USD 82,000,000) (van Tulleken 2018). Most of these prescriptions were written for cow's milk protein allergies yet actual rates of such allergies have not risen during this time (Munblit 2020). Researchers have tied this increase to the close relationship between formula manufacturers and doctors, experts, and professional associations (Munblit 2020; van Tulleken 2018).

EHF has been advertised as being able to prevent allergic diseases (allergy, asthma, eczema). However, independent studies and reviews have shown this may not be the case (Boyle 2016; Greer 2018; Osborn 2018).

EHF use was suggested to reduce the risk of type 1 diabetes, but this has been disproven (Knip 2014; Writing Group for the TRIGR Study Group 2018). One study found that EHF, when compared to regular formula, may even increase the risk of type 1 diabetes in some babies (Hummel 2017).

References

Boyle RJ, Ierodiakonou D, Khan T, et al. Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis. BMJ 2016 Mar 8;352:i974
 
Greer FR, Sicherer SH, Burks AW; COMMITTEE ON NUTRITION, SECTION ON ALLERGY AND IMMUNOLOGY. The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods. Pediatrics 2019; 143(4)
 
Hummel S, Beyerlein A, Tamura R, et al. First Infant Formula Type and Risk of Islet Autoimmunity in The Environmental Determinants of Diabetes in the Young (TEDDY) Study. Diabetes Care. 2017 Mar;40(3):398-404
 
Knip M, Åkerblom HK, Becker D, et al.; TRIGR Study Group. Hydrolyzed infant formula and early β-cell autoimmunity: a randomized clinical trial. JAMA. 2014 Jun 11;311(22):2279-87
 
Meyer R, Groetch M, Venter C. When Should Infants with Cow's Milk Protein Allergy Use an Amino Acid Formula? A Practical Guide. J Allergy Clin Immunol Pract. 2017 Nov 3. pii: S2213-2198(17)30727-4
  
Munblit D, Perkin MR, Palmer DJ, et al. Assessment of Evidence About Common Infant Symptoms and Cow's Milk Allergy. JAMA Pediatr. 2020 Apr 13 

Osborn DA, Sinn JK, Jones LJ. Infant formulas containing hydrolysed protein for prevention of allergic disease. Cochrane Database Syst Rev. 2018 Oct 19;10:CD003664
 
Vandenplas Y, De Greef E, Hauser B; Paradice Study Group. Safety and tolerance of a new extensively hydrolyzed rice protein-based formula in the management of infants with cow's milk protein allergy. European Journal of Pediatrics. 2014;173(9):1209-1216
 
van Tulleken C. Overdiagnosis and industry influence: how cow’s milk protein allergy is extending the reach of infant formula manufacturers. BMJ 2018;363:k5056
 
Vanderhoof J, Moore N, de Boissieu D. Evaluation of an Amino Acid-Based Formula in Infants Not Responding to Extensively Hydrolyzed Protein Formula. J Pediatr Gastroenterol Nutr. 2016 Nov;63(5):531-533
 
Writing Group for the TRIGR Study Group, Knip M, Åkerblom HK, Al Taji E, et al. Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial. JAMA. 2018 Jan 2;319(1):38-48