Cow's Milk Allergy (CMA)
What is Cow’s Milk Allergy?
Cow’s milk allergy (CMA), also known as Cow’s Milk Protein Allergy (CMPA), is one of the most common food allergies in infants and young children.
It is defined as: a reproducible adverse reaction to one or more milk proteins (usually caseins or whey beta-lactoglobulin) mediated through immunoglobulin (Ig) E and/or non-IgE mechanisms1. An allergic reaction to a food always involves food proteins.
- Hill DJ & Hosking CS. The cow milk allergy complex: overlapping disease profiles in infancy. Eur J Clin Nutr. 1995 Sep;49 Suppl 1:S1-12. PMID: 8647057.
What is the cause of Cow’s Milk Allergy?
Cow’s milk allergy (CMA) occurs when an infant’s immune system reacts abnormally to proteins found in milk and dairy products (e.g., milk, cheese, yogurt).
Due to structural similarities between proteins, most children with CMA also react to the milk of other ruminants; therefore, alternatives such as goat’s milk1 and sheep’s milk2 are not recommended.
This response by the immune system triggers an allergic reaction that causes a range of symptoms.
Normally, the immune system is on the lookout for pathogens that are genuinely harmful to the child, like viruses or certain ‘’unhealthy’’ bacteria. Why this happens is still not well understood, but it has been linked to genetic as well as environmental factors3.
- Vandenplas Y, Broekaert I, Domellöf M, et al. An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy. J Pediatr Gastroenterol Nutr. 2024;78(2):386–413.
- Restani P, Beretta B, Fiocchi A, et al. Cross-reactivity between milk proteins from different animal species. Clin Exp Allergy. 1999;29(7):997–1004.
- Lack G. Update on risk factors for food allergy. J Allergy Clin Immunol. 2012 May;129(5):1187–97.
What are the different types of Cow’s Milk Allergy?
Cow’s milk allergy (CMA) manifests in various complex ways and is generally classified into two distinct types based on the immune mechanisms involved. The key difference lies in the presence or absence of allergen-specific antibodies (IgE):
This type involves an immediate hypersensitivity reaction triggered by the production of cow’s milk protein-specific IgE antibodies. Symptoms typically appear within minutes to up to 2 hours after exposure to cow’s milk proteins and are often referred to as early-phase reactions1,2.
In this form, the immune response is cell-mediated, without detectable allergen-specific IgE. Symptoms are delayed or chronic, often appearing several hours to days after exposure. These reactions primarily affect the gastrointestinal (GI) tract and are sometimes more difficult to diagnose3,4.
Mixed allergic reactions (IgE and non-IgE-mediated)
There can also be a combination of the two (sometimes called mixed CMA)
Some infants present with a combination of immediate and delayed symptoms, involving both IgE- and non-IgE-mediated mechanisms—referred to as mixed CMA. These mixed allergic reactions can involve multiple systems and are increasingly recognized in clinical practice2,3.
| IgE | Non-IgE | |
|---|---|---|
| Symptoms | ||
| Respiratory | Very common | Rarely seen | 
| Skin | Common | Seen in early onset (e.g. AD) 5 | 
| Gastrointestinal/digestive | As a late phase response | In almost all cases5 | 
| Circulatory | In cases of anaphylaxis | Hypotension in FPIES3,6 | 
| General symptoms | In some cases irritability/crying | Commonly irritability/crying, back arching, abdominal pain etc.6 | 
| Timing of onset | Minutes - <2 hours | >2 hours to weeks | 
| Age of onset | Mostly seen <1 year (can be any age) | Early infancy (can be any age) | 
FPIES, Food protein-induced enterocolitis syndrome; AD, Atopic Dermatitis.
- Ulfman LH, Tsuang A, Sprikkelman AB, et al. Relevance of early introduction of cow’s milk proteins for prevention of cow’s milk allergy. Nutrients. 2022;14(13):2659. doi:10.3390/nu14132659
- Vandenplas Y, Broekaert I, Domellöf M, et al. An ESPGHAN position paper on the diagnosis, management, and prevention of cow’s milk allergy. J Pediatr Gastroenterol Nutr. 2024;78(2):386–413.
- Nowak-Wegrzyn A, Chehade M, Groetch M, et al. International consensus guidelines for the diagnosis and management of food protein–induced enterocolitis syndrome: Executive summary. J Allergy Clin Immunol. 2015;135(5):1114–24.
- Labrosse R, Graham F, Caubet JC. Non-IgE-mediated gastrointestinal food allergies in children: An update. Nutrients. 2020;12(7):2086.
- Groetch M, Venter C, Meyer R. Clinical presentation and nutrition management of non-IgE-mediated food allergy in children. Clin Exp Allergy. 2025;55(3):213–25.
- Nowak-Wegrzyn A. Food protein–induced enterocolitis syndrome (FPIES). UpToDate [Internet]. Waltham (MA): UpToDate Inc.; c2023 [updated 2023; cited 2025 Jul 2]. Available from: https://www.uptodate.com/contents/food-protein-induced-enterocolitis-syndrome-fpies
What are the signs and symptoms of Cow’s Milk Protein Allergy?
The signs and symptoms associated with cow’s milk allergy (CMA) are highly variable, which can make diagnosis challenging.
CMA can affect multiple organ systems, either alone or in combination. Commonly involved systems include the skin, gastrointestinal tract, and respiratory tract. In more severe cases, particularly in IgE-mediated reactions, the circulatory system may be involved (e.g., in anaphylaxis). In non-IgE-mediated forms such as FPIES, circulatory symptoms like hypotension can also occur.
CMA is also frequently associated with general symptoms, such as irritability, excessive crying, and back arching, which may reflect discomfort or gastrointestinal distress.
Diagnosis is not based on isolated symptoms. Instead, it often requires a combination of symptoms affecting at least two organ systems, alongside a careful clinical assessment and evaluation of the child’s response to elimination and reintroduction of cow’s milk protein1.
Therefore, it is essential to consider the entire clinical picture, rather than evaluating symptoms in isolation, when suspecting CMA.
How common is Cow’s Milk Allergy?
The reported prevalence of cow’s milk allergy (CMA) varies between regions/countries.
One recent report from the World Allergy Organisation (WAO) suggested it affects between 2 - 4.5% of infants1. Meanwhile, in Europe, the reported prevalence was closer to 1% of those <2 years2. ESPGHAN reported that the prevalence of authenticated CMA in infants and children was <1%3.
- Brozek JL, Firmino RT, Bognanni A, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) Guideline update - XIV - Recommendations on CMA immunotherapy. World Allergy Organ J. 2022 Apr 23;15(4):100646.
- Schoemaker AA, Sprikkelman AB, Grimshaw KE, et al. Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort. Allergy. 2015 Aug;70(8):963-72.
- Vandenplas Y, Broekaert I, Domellöf M, et al. An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386-413.
How is Cow’s Milk Allergy diagnosed?
The following steps have been proposed to accurately diagnose Cow's Milk Allergy (CMA)1,2,3:
Take an allergy-focused history
An allergy-focused clinical history is a fundamental first step to the establishment of a diagnosis of any food allergy, including CMA1-3.
The standardised diet history tool provides a starting point for a structured approach to history-taking1.
Perform supportive IgE tests
IgE tests are used to support the diagnosis of IgE-mediated (and in some cases mixed) CMA and also to determine outgrowth. However, they do not confirm CMA when used in isolation.
Interpretation of the data:
Specific IGE (sIgE) and skin prick tests (SPT) can be useful tools when suspecting IgE mediated CMA, however, a positive SPT or elevated sIgE can demonstrate sensitization to cow's milk, but do not confirm diagnosis when used in isolation2.
Young infants may initially have a negative SPT and absence of cow's milk-specific serum IgE2. The test results must be interpreted together with the allergy specific clinical history and clinical presentation. In most cases, the diagnosis should be confirmed by cow's milk elimination and a supervised oral food challenge (OFC)2.
For more detail refer to the ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy2.
Cow’s Milk-related Symptom Score (CoMiSS)
This tool was developed by a group of international experts in 2015 as an awareness tool to support healthcare professionals when evaluating symptoms in infants related to cow’s milk.
It is especially useful to support the diagnosis of non-IgE-mediated CMA. The CoMiSS® scoring form is not intended to be used as a diagnostic tool and should not replace an oral food challenge (OFC)4.
Elimination of suspected food followed by food reintroduction (food challenge)
The elimination of the implicated food/s (now called the diagnostic elimination diet2) should be followed by a challenge to the food/s (re-exposure) and is considered the gold standard method to establish if a child has CMA or not.
The proposed elimination period for the diagnosis of CMA varies between 1-4 weeks depending on whether IgE-mediated and/or non-IgE-mediated allergy is suspected4.
The elimination diet plus challenge helps to confirm, or refute, a food allergic reaction. It is used in practice when the IgE tests and/or the food allergic history is not 100% clear, or to determine if a child has outgrown their food allergy.
If the infant is exclusively breastfed and CMA is suspected, maternal elimination of cow’s milk/dairy products is recommended for a period is 2-4 weeks2,5.
When the child is formula fed and IgE-mediated CMA is suspected from the allergy focused history, the recommended elimination period is 1-2 weeks2.
While when suspicion of non-IgE-mediated CMA the recommended elimination period is 2-4 weeks2.
However, it can take 6-8 weeks in those with atopic dermatitis2.
In each case it should be followed by the reintroduction of cow's milk/dairy to the diet to determine if symptoms return on re-exposure (except in those who have had a well-defined severe reaction).
Once CMA has been confirmed a therapeutic elimination diet, entirely free from cow’s milk/dairy and all ruminant milk products is required2.
Important Note: if a child has had a well-defined anaphylactic reaction to cow’s milk/dairy, they should not be exposed to these food/s until it is clear that they have outgrown their allergy!
- Skypala IJ, Venter C, Meyer R, et al; Allergy-focussed Diet History Task Force of the European Academy of Allergy and Clinical Immunology. The development of a standardised diet history tool to support the diagnosis of food allergy. Clin Transl Allergy. 2015 Feb 19;5:7.
- Vandenplas Y, Broekaert I, Domellöf M, et al. An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386-413.
- Santos AF, Riggioni C, Agache I, et al. EAACI guidelines on the diagnosis of IgE-mediated food allergy. Allergy. 2023;78:3057-3076
- Vandenplas Y, Dupont C, Eigenmann P, et al. A workshop report on the development of the Cow’s Milk related Symptom Score awareness tool for young children. Acta Paediatr. 2015 Apr;104(4):334-9
- McWilliam V, Netting MJ, Volders E; WAO DRACMA Guideline Group. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update - X - Breastfeeding a baby with cow's milk allergy. World Allergy Organ J. 2023 Nov 3;16(11):100830.
How is Cow’s Milk Allergy managed?
Managing Cow's Milk Allergy (CMA) effectively is achievable when the diagnosis is made early and accurately.
Following diagnosis, infants and young children with CMA need ongoing, structured support to ensure optimal care.
The dietary management/treatment phase of CMA is also known as the therapeutic elimination diet1. It has been recommended that this phase lasts for 6 months or up to 9 -12 months of age (whichever arrives first)1.
Managing the breastfed infant with Cow’s Milk Allergy
Breast milk is rich in a variety of bioactive components, providing essential maternal immune support to infants through compounds such as human milk oligosaccharides (HMOs), secretory immunoglobulin A (IgA), lactoferrin, antimicrobial peptides (AMPs) and probably many other compounds2,3. The unique composition of human milk, therefore, plays a vital role in supporting the health of infants, including those with CMA.
It is also known that exclusively breastfed babies rarely develop CMA1,4.
If CMA is suspected, maternal elimination of cow’s milk/dairy products is recommended for a period is 2-4 weeks1 for a trial period.
This should be followed by the reintroduction of milk/dairy to the maternal diet (while monitoring symptoms) to determine if the symptoms return1.
Removing foods from the mother’s diet unnecessarily puts the mother’s nutritional health at risk, particularly when removing food groups such as dairy, wheat and eggs, for example. Healthcare professionals should be cautious not to undermine breastfeeding.
When CMA has been confirmed in a breastfed infant, it is advised that maternal exclusion of cow’s milk/dairy continues for 6 months or 9 to 12 months - whichever arrives first1,4.
When the maternal elimination diet is prolonged, supplementation with calcium, vitamin D and possibly vitamin B12 and iodine is recommended1.
Managing the formula-fed infant with Cow’s Milk Allergy
When infants with confirmed CMA are not exclusively breastfed (for whatever reason), then a hypoallergenic CMA formula is necessary to ensure they receive all the nutrients required for growth and development.
These CMA formulas can be based on extensively hydrolysed (extensively broken down) cow’s milk proteins, such as whey and casein, or plant-based, such as hydrolysed rice formula (HRF) or soy formula (non-hydrolysed). They can also be based on 100% free amino acids.
Extensively hydrolysed cow’s milk-based formulas (eHFs) or HRF with proven efficacy in children with CMA are considered the first line choice during the therapeutic elimination period for majority of infants1,5-7 .
- Vandenplas Y, Broekaert I, Domellöf M, et al. An ESPGHAN position paper on the diagnosis, management, and prevention of cow's milk allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386–413.
- Field CJ. The immunological components of human milk and their effect on immune development in infants. J Nutr. 2005 Jan;135(1):1–4.
- Cederlund A, Kai-Larsen Y, Printz G, et al. Lactose in human breast milk: an inducer of innate immunity with implications for a role in intestinal homeostasis. PLoS One. 2013;8(1):e53876.
- Muraro A, Worm M, Alviani C, et al. EAACI guidelines: Anaphylaxis (2021 update). Allergy. 2022 Feb;77(2):357–377.
- Bognanni A, Fiocchi A, Arasi S, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XII – Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA. World Allergy Organ J. 2024 Mar 26;17(4):100888.
- Meyer R, Venter C, Bognanni A, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – VII – Milk elimination and reintroduction in the diagnostic process of cow's milk allergy. World Allergy Organ J. 2023;16(7):100785.
- Venter C, Meyer R, Groetch M, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update – XVI – Nutritional management of cow's milk allergy. World Allergy Organ J. 2024 Aug 12;17(8):100931.
Types of CMA formulas
- First line choice for the majority of CMA infants is an extensively hydrolysed cow’s milk-based (whey/casein) formula (eHF) or a hydrolysed rice formula (HRF)1,2,3.
- Soy formula is generally not recommended <6 months of age1. DRAMCA2 suggests that soy formula can be used when CM-based eHF is not a success in non-IgE patients such as patients with food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP).
- Amino-acid based formula (AAF) are based on free amino acids (100% hypoallergenic) and are recommended for children with severe forms of CMA or those not responding to an eHF or HRF1,2,3. According to ESPGHAN due to severity of symptoms and failure of the CM-based eHF, AAF may be required in a subset of children when there is (i) anaphylaxis; (ii) faltering growth; (iii) multiple and severe complex gastrointestinal food allergies; (iv) acute and chronic severe food protein-induced enterocolitis syndrome; (v) eosinophilic oesophagitis not responding to an extended exclusion diet; (vi) any risk of sensitization; (vii) symptom persistence on an eHF (even partial)1.
Summary of key allergic conditions
Atypical food protein-induced enterocolitis syndrome (aFPIES)
Children with aFPIES are more likely to develop IgE-mediated food allergies even though FPIES is considered a non-IgE-mediated form of CMA5.
Food Protein-Induced Allergic Proctocolitis (FPIAP)
This condition is typically caused by an allergic reaction to cow’s milk or soy in infants. The diagnosis of FPIAP is primarily based on clinical symptoms.
Atopic Dermatitis (AD)
Atopic dermatitis or eczema is linked to food allergens like egg, dairy, wheat, and nuts, with both IgE and non-IgE pathways involved. The most common food allergen reported in those with atopic dermatitis was cow’s milk (44.5%); and both IgE and non-IgE mediators were involved6. The dietary management of infants with AD is not universally agreed. Therefore, it depends on the symptoms and diagnosis as well as the status of the infant, for example when faltering growth manifests along with food allergies then an AAF might be recommended.
Eosinophilic Oesophagitis (EoE)
Although EoE is considered a non-IgE-mediated condition, some children with EoE can also have IgE-mediated reactions.
For example, food-specific IgE levels can indicate sensitisation and the higher the IgE for a given food, the more likely it was that the patient is clinically allergic7. In this study they found the most commonly implicated food to be cow’s milk7.
ESPGHAN recommended a step‐up elimination approach (starting with 2, then 4 and finally 6 food elimination diet (6FED) as needed)8.
AAF are generally reserved for patients who do not respond the SFED and/or medical options, where further food allergen causes need to be investigated, or in selected patients fed via gastrostomy tube.
- Vandenplas Y, Broekaert I, Domellöf M, et al. An ESPGHAN position paper on the diagnosis, management, and prevention of cow's milk allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386–413.
- Bognanni A, Fiocchi A, Arasi S, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – XII – Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA. World Allergy Organ J. 2024 Mar 26;17(4):100888.
- Meyer R, Venter C, Bognanni A, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update – VII – Milk elimination and reintroduction in the diagnostic process of cow's milk allergy. World Allergy Organ J. 2023;16(7):100785.
- Venter C, Meyer R, Groetch M, et al. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update – XVI – Nutritional management of cow's milk allergy. World Allergy Organ J. 2024 Aug 12;17(8):100931.
- Groetch M, Venter C, Meyer R. Clinical presentation and nutrition management of non-IgE-mediated food allergy in children. Clin Exp Allergy. 2025 Mar;55(3):213–225.
- Pourpak Z, Farhoudi A, Mahmoudi M, et al. The role of cow milk allergy in increasing the severity of atopic dermatitis. Immunol Invest. 2004 Feb;33(1):69–79.
- Gómez Torrijos E, Moreno Lozano L, Extremera Ortega AM, et al. Eosinophilic esophagitis: personalized treatment with an elimination diet based on IgE levels in children aged <16 years. J Investig Allergol Clin Immunol. 2019 Apr;29(2):155–157.
- Amil-Dias J, Oliva S, Papadopoulou A, et al. Diagnosis and management of eosinophilic esophagitis in children: an update from the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). J Pediatr Gastroenterol Nutr. 2024 Aug;79(2):394–437.
How long should children remain on the CMPA therapeutic elimination diet?
The exclusion of milk and dairy for children on a CMPA diet should be continued for a period of 6 months or up to 9-12 months of age (whichever arrives first)1.
- Vandenplas Y, Broekaert I, Domellöf M, et al. An ESPGHAN Position Paper on the Diagnosis, Management, and Prevention of Cow's Milk Allergy. J Pediatr Gastroenterol Nutr. 2024 Feb;78(2):386-413.
When do children with Cow’s Milk Allergy become tolerant to cow’s milk?
Around 80% of children outgrow their allergy to cow’s milk/dairy by the age of three to five years1.
However, allergy testing and/or an oral food challenge (OFC) may also be necessary to reconfirm. Depending on the initial reaction, these may be performed in the clinical setting and supervised by an allergy specialist or at home.
If the child has had an immediate-type reaction (IgE or mixed), then the OFC would be performed in a supervised clinical setting. A child who has had a non-IgE-mediated allergic reaction to cow’s milk/dairy can usually start (supervised) reintroductions at home.
- Australian Society of Clinical Immunology and Allergy (ASCIA): FAQ – Q10. for Parents and Carers. https://www.allergy.org.au/patients/food-allergy/cows-milk-dairy-allergy; Online data - accessed 2025.
Complementary feeding in Cow’s Milk Allergy
The World Health Organisation (WHO) and other experts define complementary feeding (CF) as the process of starting additional foods and liquids when breast milk alone is no longer sufficient to meet the nutritional requirements of infants1,2.
In the non-breastfed infant, it is when the replacement infant formula alone no longer meets nutritional needs. As infants grow and develop, their needs for energy and nutrients exceed what is provided by breast milk or hypoallergenic formula, and this is when CF should start.
How do you use the CMA milk ladder?
Healthcare professionals decide, along with the parents/child, when the reintroduction of foods should start. In those that have a home supervised challenge it is usually performed using a step-by-step process, commonly using the ‘Milk Ladder’ (MAP) or international Milk Ladder (iMAP)3.
Certain factors should be considered before considering MAP, such as, the age of the child, if they have had a previous anaphylactic reaction, if there is a risk of a severe reaction or shock etc.3.
If it appears safe to start the MAP, the following should be considered:
- Start the MAP when the child is well.
- Avoid starting the MAP during particularly busy periods at work or home when the parent or caregiver may not have the time to focus.
- It’s best to introduce new foods in the morning or at lunchtime rather than in the evening, allowing for careful monitoring throughout the day.
- Start with highly processed milk-containing foods and ensure they are well tolerated before progressing to the next step. The duration at each step varies from child to child, ranging from one day to several days.
- Some children may tolerate more processed foods, such as biscuits and cakes containing milk (earlier steps), but may develop symptoms with yoghurt or cheese (later steps). If this occurs, pause progression and continue offering the tolerated foods. Symptom-triggering foods can be reintroduced at a later stage.
- A small proportion of children may not tolerate baked milk.
Here are some considerations before deciding on the reintroduction of foods (MAP) at home (adapted from Venter et al., 2024)3.
| Factors to consider | For home reintroduction | Against home reintroduction | 
|---|---|---|
| Age | <5 years | >5years | 
| Reaction | No prior anaphylaxis | Prior anaphylaxis | 
| Dose | High previous reaction threshold to baked or non-baked CM | Low previous reaction threshold to baked or no-baked CM, reactions to trace amounts or cross-contamination | 
| Reactivity to baked milk | No | Yes | 
| Asthma | Well controlled | Poorly controlled | 
| Laboratory tests | Small and or decreasing SPT* wheal or serum CM-specific IgE levels | High and or increasing SPT wheal or serum CM-specific IgE levels | 
*SPT, Skin Prick Test; IgE, Immunoglobulin E; CM, Cow’s milk
- World Health Organization (WHO). Complementary Feeding: Report of the Global Consultation, Geneva, 10–13 December 2001. Summary of Guiding Principles. Geneva: World Health Organization; 2002. Available from: http://www.who.int/nutrition/publications/Complementary_Feeding.pdf. Accessed 2025.
- Fewtrell M, Bronsky J, Campoy C, et al. Complementary feeding: a position paper by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) Committee on Nutrition. J Pediatr Gastroenterol Nutr. 2017;64(1):119–132.
- Venter C, Meyer R, Groetch M, et al; DRACMA Panel. World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guidelines update – XVI – Nutritional management of cow's milk allergy. World Allergy Organ J. 2024 Aug 12;17(8):100931.
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Date of publication: 06/06/2025
 
   
  