Study clarifies why most colic isn’t caused by cow’s milk allergy

New evidence shows that colic is usually a benign gut–brain interaction disorder, and only infants with additional allergic symptoms should undergo a structured cow’s-milk elimination and reintroduction trial.

Study: Infantile Colic: When to Suspect Cow’s Milk Allergy. Image Credit: Jirapong Manustrong / Shutterstock

In a recent review published in the journal Nutrients, researchers evaluated existing evidence on whether cow’s milk allergy (CMA) contributes to infant colic and examined when CMA should be suspected in infants with excessive crying.

They concluded that CMA is unlikely to cause colic in otherwise healthy infants without other allergic symptoms. However, when standard colic management fails and allergic signs are present, a short diagnostic elimination diet followed by reintroduction may help confirm CMA, and better-designed trials are urgently needed.

Concerns over Infant Colic

Infantile colic affects 20–30% of infants worldwide and is characterized by periods of excessive, unexplained crying in the first few months of life. Although crying is a normal form of communication, some infants cry more intensely or more frequently, causing distress for caregivers and, in rare instances, increasing the risk of parental frustration.

Cultural and socioeconomic factors influence what caregivers consider “excessive,” and parental anxiety can perpetuate crying through a feedback cycle. Importantly, many studies do not clearly distinguish normal crying from crying caused by underlying medical conditions, which must be ruled out before diagnosing colic.

CMA is relatively common in infancy, though its true prevalence varies depending on diagnostic methods. Previous guidelines have briefly touched on whether colic may serve as a symptom of non-immunoglobulin-E (IgE)-mediated CMA, but the relationship remains debated.

To address this, the authors searched three medical databases through June 2025 for English-language studies on cow’s milk allergy and infant colic, ultimately identifying 135 papers, including 18 clinical trials evaluating cow’s milk elimination diets.

Recommended management in infantile colic.

Features of Colic

Infantile colic is now classified as a disorder of gut–brain interaction, reflecting its complex and multifactorial nature. Historically attributed to intestinal gas, colic is characterized by excessive crying accompanied by behaviors such as leg flexion, back arching, and abdominal distension.

The updated Rome IV criteria define colic as repeated episodes of unexplained crying or irritability in otherwise healthy infants under 5 months old. Earlier duration-based thresholds were removed due to their arbitrary nature, and terms like “paroxysmal” were eliminated because crying patterns do not reliably differ from normal infant crying.

The review further highlights that many infants do not present with isolated colic but instead experience colic as part of broader clusters of symptoms of disorder-of-gut–brain-interaction.

Possible Causes of Colic

Evidence points to a combination of gastrointestinal and non-gastrointestinal factors. Non-gastrointestinal contributors include suboptimal feeding practices, parent–infant interaction issues, neurodevelopmental immaturity, and environmental exposures such as maternal smoking.

Gastrointestinal explanations include motility disturbances, visceral hypersensitivity, gut dysbiosis, and both IgE– and non-IgE-mediated food allergies, especially CMA. Some hormonal differences, such as elevated motilin and ghrelin, suggest that transient neural–gut dysregulation may cause hyperperistalsis.

Microbiota studies consistently show that infants with colic have reduced Bifidobacteria and Lactobacillus and increased Enterobacteriaceae, potentially contributing to gas formation, inflammation, and discomfort. Lactose intolerance has also been proposed, given higher intestinal hydrogen production in some colicky infants, though most term infants produce adequate lactase.

However, the review emphasises that lactase drops and lactose-reduced formulas are not routinely recommended, as the supporting evidence is inconsistent and insufficient for universal use.

Long Term Outcomes

Although colic typically resolves by 4–5 months, it can significantly affect families. Long-term follow-up studies suggest mixed associations with later outcomes. Some cohorts found no increased risk of asthma or wheezing, while others reported higher rates of eczema, allergic rhinitis, and food allergy in children with a history of colic.

Concurrent atopic conditions also appear more common in some populations. Colic severe enough to require hospitalization has been linked to later mental health concerns, though inconsistently.

Relationship Between Colic and CMA

CMAs present across a broad clinical spectrum, making diagnosis challenging. IgE-mediated allergy can be supported by skin prick tests or specific IgE levels, but confirmation still requires an elimination diet followed by an oral food challenge. Non-IgE-mediated CMA lacks reliable laboratory markers, so diagnosis relies on symptom patterns and response to dietary elimination with planned reintroduction.

Because colic and CMA share overlapping symptoms such as abdominal discomfort, regurgitation, and distressed crying, CMA is frequently considered in infants with persistent colic. However, many early studies suggesting a strong link were limited by weak design, lack of controlled challenges, and retrospective reporting.

More recent evidence indicates that colic alone is rarely the only manifestation of CMA. Breastfeeding studies have not consistently supported a link between maternal dairy intake and colic, and large cohort data show similar colic rates across feeding methods.

The authors also caution clinicians to avoid overdiagnosing CMA, noting that relying on single symptoms, including crying, can lead to unnecessary elimination diets.

Conclusions

Infant colic is essentially a benign disorder of gut–brain interaction, and crying patterns depend heavily on caregiver perception and reporting. Most infants improve with general soothing strategies, and routine use of anti-reflux medications, lactase drops, or lactose-restricted formulas is not recommended when crying is the only symptom.

CMA plays an uncertain role in colic but may be considered when persistent crying occurs alongside other allergic features. In such cases, a short, structured elimination diet followed by reintroduction is essential for confirmation.

The review underscores that soy formula is not recommended for colic, as supporting evidence for benefit is lacking.

Additionally, certain probiotics, particularly Limosilactobacillus reuteri DSM 17938 and Bifidobacterium animalis BB-12, have demonstrated benefit in breastfed infants and represent the strains with the strongest supporting evidence.

More rigorous clinical trials are needed to clarify the roles of CMA, lactose, and microbiota in colic.