Allergy and Intolerance

Immunological and Nutritional Etiologies

Allergies, food intolerances, and autoimmune diseases are critical considerations in the differential diagnosis of persistent, unexplained crying and irritability in the infant. These conditions may manifest in infancy with a broad spectrum of systemic and gastrointestinal symptoms, among which is gastroesophageal reflux (GER), where inconsolable crying is frequently a presenting complaint.

It is important to classify these conditions as the body reacts in different ways :

Food Hypersensitivity (Allergy)

The immune system causes different reactions to food proteins.

Type I Hypersensitivity: Characterized by rapid onset (minutes to two hours) and acute symptoms (e.g., itchy, red or skin-colored raised welts, deeper swelling around eyes, lips, face, and genitals, potential anaphylaxis). Common IgE allergens include dairy, egg, peanut, and tree nuts.

Dairy is the single most common food allergy in infants. It involves an allergic reaction to the proteins found in bovine milk. The proteins are casein and whey. Although milk is primarily composed of casein (80%), it is broken down more efficiently than the whey. Whey is found in human milk and is more commonly associated with allergic reactions. (Caffarelli, 2025) There is a cross reactivity with other mammalian milks. (Cox, 2021)

Proteins in soy are a common allergen, especially in infants using soy-based formulas. Soy has a high rate of co-sensitization which leads to necessary clinical avoidance of both foods in many affected infants. This co-sensitization is attributed to an underlying genetic atopic predisposition in the infant, rather than structural protein homology. (Vanderplas, 2007; Candevra, 2015)

Egg is the second most common allergy in infants. The proteins in the egg white are usually the primary culprits. (Urisu, 2015) Cross-reactivity with other eggs is common. (Cox, 2021)

Peanut allergy is typically severe and persistent. Current guidelines often recommend early introduction for high-risk infants to prevent the allergy. (Fewtrell, 2017) There is cross-reactivity with legumes including soy, chickpea, and lentils.(Cox, 2021)

General Food Sensitivities in Breastfed Babies

Symptoms: When a breastfed baby is sensitive to something in the mother’s diet (often dairy, soy, egg, or wheat), the signs often fall into a few categories:

• Gastrointestinal: Fussiness/colic, excessive crying, reflux, spitting up, watery/mucousy/bloody stools, infrequent stools, vomiting, sudden waking with discomfort, or a hard/bloated tummy.
• Skin: Rashes, eczema, hives, or dry skin.
• Respiratory: Nasal congestion.
• Growth: Weight loss or failure to thrive (less common, but serious).

Type 2 sensitivity: These are characterized by delayed, chronic, and gastrointestinal symptoms. Key examples include Cow’s Milk Protein Allergy (CMPA), Food Protein-Induced Enterocolitis Syndrome (FPIES) and Food Protein-Induced Allergic Proctocolitis (FPIAP). Reactions generally occur 2-8 hours after ingestion. This can be acute or chronic with diarrhea, poor weight gain and failure to thrive. The most common causes are rice, oats, dairy and soy. Soy, egg, and wheat are also trigger foods. (Atanaskovic-Markovic, 2014) 

Food Protein-Induced Enterocolitis Syndrome (FPIES), Food Protein-Induced Allergic Proctocolitis (FPIAP) (blood and mucus in the stool of a healthy infant) and Cow’s Milk Protein Allergy (CMPA) are important examples of non-IgE mediated conditions. CMPA is one of the most common foods responsible for these allergic reactions in children. (Dupont, 2018; Lo, 2025) In these conditions there is an aberrant immune reaction to cow’s milk proteins, particularly casein or β-lactoglobulin. (Darma, 2024) Clinical manifestations of CMPA are family history of atopy or allergic disease, respiratory manifestations, skin manifestations, feeding refusal, failure to thrive/poor weight gain, rectal bleeding, blood in stool or mucous. There may be vomiting, bloating, abdominal cramps, flatulence, borborygmi, constipation and diarrhea. (Darma, 2022; Chandra, 2015) These conditions frequently result in feeding refusal, irritability, gastrointestinal inflammation, and occult or gross blood in stool. The skin prick test for cow’s milk proteins usually yields negative results, but it can become positive over time. (Caffarelli, 2025) FPIES to cow’s milk generally resolves within 3 years of age. The tolerance achievement is ascertained by oral food challenge that is usually performed 12–18 months following the last reaction. (Nowak-Wegrzyn, 2017)

Here’s a summary of what the research suggests regarding wheat and breastfed infants:

While the focus isn’t exclusively on wheat/gluten, research on Maternal Diet-Related Food Sensitivities/Intolerances (MSPI) in infants often includes wheat as a common trigger. Allergy to the proteins in wheat occurs as does the cross-reactivity to barley and rye. (Cox, 2021) Conversely children with birch or grass allergy may be sensitized to wheat due to cross-reactivity. (Nilsson, 2018) Wheat allergy is distinct from Celiac Disease which is an autoimmune disorder triggered by gluten.

Food Intolerance: These are reactions not caused the the immune system. These are often due to enzyme deficiencies. While typically less acute, they can still cause significant discomfort, abdominal pain, and distress, contributing to excessive crying in the infant or different symptoms in the child. Lactose intolerance is the most common. While the signs and symptoms may overlap with CMPA, chronic diarrhea, bloating/abdominal distension, flatulence, borborygmi, abdominal pain and cramping, perianal rash are common and some infants will have vomiting. (Toca, 2022; Di Costanzo, 2021) This may also present temporarily following a gastrointestinal infection.

Protein-Induced Constipation:

Non-Allergic Sensitivity: Linked to the properties of the casein protein in cow’s milk. Chronic, painful constipation characterized by hard, pellet-like stools. The pain leads to fecal retention, exacerbating irritability and crying. (Iacono, 1998; Daher, 2001)

In summary, CMPA presents with diverse signs and symptoms. hypersensitity 1 reactions cause a quick onset of hypersensitivity symptoms, whereas hypersensitivity 2 and mixed forms primarily result in gastrointestinal inflammation and other chronic symptoms often influenced by maternal diet and typically resolving within the early years of life. (Carrarelli, 2025)

Eczema /Atopic Dermatitis (AD)

It involves a complicated interaction between a compromised skin barrier, itching, skin inflammation, and immune dysregulation, all influenced by both genetic and environmental factors. (Caffarelli, 2025) It is both a risk factor for CMPA and caused by CMPA even in breastfed infants. Exacerbation of eczema occurs 6-48 hours in the infant after breastfeeding. (Jakobsson & Lindberg, 2008) Removing egg and bovine milk in cases of more severe atopic dermatitis significantly improved the condition while reintroduction worsened the symptoms. (Cant, 1986)

Autoimmune Disease

Celiac disease (CD) is an autoimmune disorder triggered by gluten in genetically susceptible individuals characterized by a variable combination of gluten-dependent symptoms, presence of specific autoantibodies and enteropathy.  The ingestion of gluten, a protein found in wheat, barley, and rye, leads to T-cell mediated damage to the lining of the small intestine (villous atrophy). Environmental factors, some operating already before birth, have been identified, with feeding pattern in the first year of life (breast feeding, amount and time of introduction of gluten) and infections being the most relevant.(Auricchio, 2021) Interventions have been so far limited to modifications of feeding patterns.  Early exposure to gluten during weaning and early childhood increases the risk for provoking celiac disease in those with HLA risk types. (Szajewska, 2024)

Transfer of Gluten Peptides

Gliadin Peptides in Breast Milk: Studies have shown that immunogenic gluten peptides (like Gliadin Immunogenic Peptides or GIP) from the mother’s diet can be transferred into breast milk. The secretion of these peptides is dynamic and varies significantly between individuals and over time, influenced by maternal diet and other factors.

Transfer of allergenic protein from breast milk to infant:

The time it takes for an allergenic protein (casein, whey, egg, wheat, soy) to transfer from the mother’s diet to her breast milk and then to the infant is quite rapid, though the total time it takes for symptoms to show and clear up can vary greatly. (Caffarelli, 2025)

Key Findings on Protein Transfer

• Rapid Appearance: Studies suggest that allergenic proteins, such as those from cow’s milk and peanuts, can be detected in breast milk as quickly as 1-2 hours after the mother consumes the food.
• Peak Concentration: The concentration of the protein in breast milk often peaks around 1-8 hours after ingestion.
• Clearance from Breast Milk: In many cases, detectable levels of these proteins (like cow’s milk protein, peanut, and egg) have been found to clear from the breast milk within 6-8 hours after the mother’s ingestion. However, some studies have occasionally detected very low levels of cow’s milk protein for up to a few days or even a week in some mothers, though these low levels may not be clinically significant enough to cause a reaction.

Time for Infant Symptoms to Show and Clear

It’s important to distinguish between the transfer time to the milk and the time it takes for the baby to show symptoms or for those symptoms to resolve:

• Symptom Onset:
  • Immediate (IgE-mediated reactions): Symptoms like hives, swelling, or vomiting can occur within minutes up to 2 hours after the baby is fed the breast milk containing the allergen.
  • Delayed (Non-IgE-mediated reactions): Symptoms like bloody stool (proctocolitis), severe colic, or eczema can appear hours or even days (24-48 hours, or sometimes 3-4 days) after the exposure.
• Symptom Improvement (Clearance from Baby):
  • Once a mother completely eliminates an allergen from her diet, it can take anywhere from 3 to 7 days for the baby’s symptoms to start improving, and up to 2 to 4 weeks (and sometimes longer) for the baby’s system to fully clear the protein and for chronic inflammation or irritation in the gut to heal.

The diagnosis of CMPA and other suspected allergens in breastfed babies embraces detailed history, allergy tests (skin testing and/or specific IgE antibodies to proteins), and oral food challenge (OFC) that is considered the gold standard for diagnosis. Guidelines suggest continuing breastfeeding and eliminating suspected allergens from the maternal diet when the infant has clinical symptoms. (Caffarelli, 2025) There is evidence as well for maternal low FODMAPS diet to improve infant symptoms. (Iacovou, 2018) Attention to maternal nutrition to avoid utrient deficiency is important. Certain nutrients, like calcium, iron, zinc, copper, and folate, are relatively unaffected by maternal diet. In contrast, nutrients such as thiamine, riboflavin, vitamins B6 and B12, choline, vitamins A and D, selenium, iodine, and key fatty acids like docosahexaenoic acid (DHA) are more directly influenced by what the mother consumes, making it important to monitor and support maternal nutrition during breastfeeding. (Copp, 2018) If the mother continues with an elimination diet, careful attention to adequate protein intake is important, and supplementation with calcium and vitamin D for maternal skeletal health is recommended, while iodine and vitamin B12 supplementation may be considered. (Kvammen, 2018) Fermented dairy products are positive for a healthy gut microbiome which is difficult to replace with a dairy free diet.

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