CMPA 
Q&A

The first year of life is a period of heightened vulnerability for all infants as their immune system matures.^1-5 However, infants with a food allergy or those formula fed, are at a heightened risk of developing infections compared to healthy breastfed infants.^6-9 Exclusively formula-fed infants have a higher incidence of gastrointestinal and upper and lower respiratory tract infections compared to exclusively breastfed infants⁹. This is because infants are born with an immature immune system and rely on a maternal supply of antibodies as defense against pathogens.^10,11 These breastmilk antibodies are highly targeted against infectious agents and other exogenous antigens, likely to be encountered by the infant.¹¹ It has also been shown that infants with CMPA have increased gut permeability¹² and altered gut microbiota composition,^13,14 which can affect immune system maturation and can result in long-term negative health consequences.¹⁵ Finally, infants with CMPA are also at a higher risk of developing allergies in the future, such as respiratory and atopic dermatitis.⁷

<sup>1.Robertson RC, et al. Trends Microbiol 2019;27(2):131-47. 
2. Agosti M, et al. Pediatr Med Chir 2017;39(2):157. 
3. Dzidic M, et al. Med Sci (Basel) 2018;6(3):56. 
4. Holt PG, and Jones CA. Allergy 2000;55(8):688-97. 
5. Chin AM, et al. Semin Cell Dev Biol 2017;66:81-93. 
6. Juntti H, et al. Acta Otolaryngol 1999;119(8):867-73. 
7. Tikkanen S, et al. Acta Paediatr 2000; 89(10):1174-80. 
8. Woicka-Kolejwa K, et al. Postepy Dermatol Alergol 2016;33(2):109-13. 
9. Duijts E, et al. Pediatrics 2010;126(1):e18-25. 
10. Andreas NJ, et al. Early Hum Dev 2015;91(11):629-35. 
11.Brandtzaeg P. J pediatr 2010; 156(2 Suppl):S8–15. 
12. Jalonen T. J Allergy Clin Immunol 1991;88(5):737-42. 
13. Azad MB, et al. Clin Exp Allergy 2015;45(3):632-43. 
14. Thompson-Chagoyan OC, et al. Int Arch Allergy Immunol 2011;156(3):325-32. 
15. Tanaka M, and Nakayama J. Allergol Int 2017;66(4):515-22.</sup>

When it comes to bowel movements in infants, "normal" can vary depending on several factors, including the age of the infant and their diet.  As babies start eating solid foods, their bowel movements may change. The frequency and consistency can vary depending on the type of foods introduced.  General guidance on what is considered “normal” includes:

Frequency:

• For newborn infants, it is normal for them to have several bowel movements in a day, sometimes even after every feed. As infants grow, the frequency of bowel movements often decrease.^1,2

Color and consistency:

• Breastfed infants typically have loose, mustard-yellow or seedy stools, which is considered normal.¹ Formula-fed babies may have slightly firmer brown or tan-colored stools compared to breastfed babies, but they should still be soft and easily passed.² Stool consistency can vary among infants, and changes in consistency within the normal range are generally not a cause for concern.^1,2
• It has also been noted that in infants consuming extensively hydrolyzed or amino acid-based formula they can have a change in stool color (e.g. green stools). This has been linked to the iron format and amount³ as well as the modified protein in these formulas.

Parents should monitor changes in their infants’ stool pattern (frequency and consistency).  In the case of diarrhea, a record should be kept of the number of bowel movements, frequency, and consistency.  Diarrhea can lead to fluid loss and dehydration, therefore parents should be advised to monitor hydration status, behavior and energy levels. Parents might also want pay attention to their baby's behavior during bowel movements e.g., excessive straining, crying, or signs of discomfort could be an indicator of constipation.

1. Stool charts can help a parent understand if their infant’s stool falls within the normal range for color or consistency.  An example tool is the Brussels Infant and Toddler Stool Scale (BITSS).⁴

<sup>1.Gustin J, et al. Journal of Parenteral and Enteral Nutrition 2018; 42 Suppl 1:S5-S11.
2. Gatzinsky C, et al. Acta Paediatr. 2023;112(6):1341– 1350.
3. Children’s Hospital UnityPoint Health. 2014; https://www.unitypoint.org/blankchildrens/article.aspx?id=40567710-74c7-4ef2-a040-847be9fbd35a. Accessed October 20, 2022.
4. Vandenplas Y, et al. BMJ Open 2017;7:e014620.</sup>
 

When CMPA is the cause, the time frame needed to see resolution of skin symptoms depends on the immunological mechanism involved. Resolution can range from 3 to 5 days in children with immediate clinical reactions (e.g., urticarial rashes), to 1 to 2 weeks in those with delayed reactions to cow’s milk/dairy (e.g., atopic dermatitis).¹ The National Institute for Health and Care Excellence (NICE) guidelines recommend a 6-to-8-week trial of an eHF or AAF in bottle-fed infants <6 months with moderate or severe atopic eczema when uncontrolled following emollient treatments, or following mild topical corticosteroids.² In cases of severe atopic dermatitis, the diagnostic elimination diet may take up to 6 weeks before improvements are seen.³  Lemale and colleagues (2022) showed that a whey-based eHF improved atopic eczema with complete resolution of urticarial rashes after 3- 5 weeks intervention.⁴

<sup>1.Koletzko S, et al. J Pediatr Gastroenterol Nutr. 2012;55(2):221-9.
2. National Institute for Health and Care Excellence (NICE). 2007, updated March 2021.
https://www.nice.org.uk/guidance/cg57/chapter/Recommendations#treatment-2
3. Katta R, & Schlichte M. J Clin Aesthet Dermatol. 2014;7(3):30-6.
4. Lemale J, et al. Nutrients. 2022;14(6):1203.</sup>
 

The nutrient composition of Althéra® HMO, Alfaré® HMO and Alfamino® HMO fulfils the requirements of foods for special medical purposes (FSMP). Althéra® HMO, Alfaré® HMO and Alfamino® HMO are suitable as a sole source of nutrition up to 12 months of age. From 6 months of age they are also suitable as supplementary feeding in combination with age-appropriate foods (i.e., complementary feeding). Children with CMPA who continue to require supplementary feeding beyond 12 months of age need to receive an individualized nutritional assessment from an HCP. This is to ensure they have sufficient nutrient intakes, especially protein, calcium, vitamin D and vitamin E, which was recommended by ESPGHAN due to their often restricted diets.¹

NOTE: If a child requires a formula as the sole source of nutrition over 6 months of age, it is extremely important that they are assessed by an HCP to ensure nutrient adequacy of the diet and optimal growth.

^{1.Koletzko S, et al. J Pediatr Gastroenterol Nutr. 2012;55(2):221-9.}

To ensure that a baby is taking enough formula parents can be advised to consider the following:

• Weight gain and growth: Consistent weight gain and appropriate growth (achieving weight for age and length for age z-scores) are positive signs that a baby is receiving enough nutrition. Regular growth monitoring is essential to compare an infant’s growth against the standard growth charts for their age.¹
• Wet and dirty nappies: Another way to assess if a baby is getting enough formula is by monitoring their nappies. Babies should have a sufficient number of wet nappies (around 6-8 per day) and bowel movements that are of normal consistency.  Nappies should be soaked through with clear or pale-yellow urine, or feel heavy.¹
• Feeding frequency: Newborns generally feed every 2 to 3 hours and may have around 8 to 12 feeds per day.  As babies grow, the number of feeds may decrease as they start spacing out their feeds every 3 – 4 hours and consume larger amounts during each feed.²
• Volume of feeds: The amount of formula consumed per feed can vary depending on the baby’s age, weight, and individual needs. In general, newborns may start with smaller amounts, around 30 – 60 ml, gradually increasing as they grow.²

^{1.National Health Service (NHS). 2019.
https://www.nhs.uk/conditions/baby/breastfeeding-and-bottle-feeding/bottle-feeding/formula-milk-questions/
2.    Centers for Disease Control and Prevention (CDC). 2022.
https://www.cdc.gov/nutrition/infantandtoddlernutrition/formula-feeding/how-much-how-often.html}