Colic may be a risk factor for developing food allergies later in childhood, according to new research published in the Journal of Pediatrics.

In a prospective cohort study of over 1200 children followed from birth to adolescence, infants who had colic had a 70% higher risk of developing a food allergy by age 2-3 compared with children who hadn’t suffered from the condition.

“Colic may be a meaningful early signal that an infant is in a somewhat higher-risk group, especially for later peanut and tree nut allergy,” said Jenifer Lightdale, MD, a professor of pediatrics at Harvard Medical School in Boston and senior author of the study. “I think the message is not alarm, but attention: Infant colic may deserve to be considered as part of a broader, developmental, immunologic story.”

The study began in 1999 and followed participants from infancy through adolescence in eastern Massachusetts. The cohort was 50% girls and 70% non-Hispanic White individuals. A quarter of children were reported by parents to have colic, defined as excessive crying with signs of abdominal pain.

Food allergy outcomes were based on parent-reported data collected via questionnaires in early childhood and adolescence. In early childhood, immunoglobulin E (IgE) antibody levels for egg white, cow’s milk, peanut, wheat, soy, and sesame were measured in a subset of 268 children.

At age 2-3 years, researchers found a modest association with colic for milk and egg allergies. Colic was also associated with a 2.5-fold higher risk for peanut IgE sensitization, while no clear or consistent associations were observed for other allergens.

As children aged, the association became more specific to peanut and tree nut allergies. In early adolescence (around 13 years old), peanut allergy was reported in 8% of those with colic vs 4% of those without (OR [odds ratio], 2.1; 95% CI, 1.1-4.1), and tree nut allergy in 8% vs 3% in those without (OR, 2.6; 95% CI, 1.3-5.2).

By late adolescence (age, 17-20 years) the association was strongest for peanut allergy, with an approximately threefold increased risk, while the association with tree nut allergy remained elevated but less certain.

Researchers also looked at children with excessive crying alone and found no association with food allergies.

The heightened risk for peanut and tree allergies did not surprise Rita Kachru, MD, a pediatric and adult allergist-immunologist and chief of clinical immunology and allergy at UCLA Health in Los Angeles, who was not associated with the study. They tend to be the most persistent allergens compared with those like cow’s milk and egg, which most children outgrow, she said.

Peanut and tree nut allergies are often IgE mediated, Lightdale said. The participant’s responses to these particular allergens means colic may signal altered immune function.

Colic affects around 20% of newborns. The findings point to a shift in how clinicians understand it.

“For many years, colic has been viewed as a benign and transient condition,” Lightdale said. “Our findings add to a growing body of work suggesting that colic may, in some infants, be an early manifestation of altered gut-immune signaling.”

Rather than causing food allergy, colic is likely a clinical marker of underlying inflammatory or immune predisposition that can later manifest as allergic disease, Lightdale said.

Affected infants have been shown to have distinct microbiome profiles. Colic is associated with proinflammatory microbial patterns and an increased risk for gut-brain disorders and atopic disease in later life.

If a baby has colic, Kachru advises pediatricians to ask about further risk factors such as atopic dermatitis and family history of allergic disease. But based on the study, she now considers colic alone as significant enough of a risk factor to advise early introduction of food allergens in accordance with current guidelines, once colic symptoms are managed.

Funding was provided by the National Institutes of Health.

Sources cited in this article reported having no disclosures.

Brittany Vargas is a journalist covering medicine, mental health, and wellness.