More than one third of infants with suspected peanut allergies tolerated peanuts during supervised oral food challenges despite having a clinical history of allergic reactions and positive allergy tests, according to new research.

The findings, published in The Journal of Allergy and Clinical Immunology: In Practice, suggest that oral food challenges should be considered more routinely to confirm peanut allergies in infants, the researchers said.

“Oral food challenge should be considered for all babies who present with a history of reaction and positive skin prick or blood test, except in babies whose initial reaction to peanut ingestion was consistent with anaphylaxis,” said Kirsten Perrett, MBBS, PhD, director of the National Allergy Centre of Excellence in Melbourne, Australia, who led the study. “Families should always be counselled on the risk of anaphylaxis with any oral food challenge and the decision to proceed should be a shared decision.”

Given the findings, researchers suggested that some infants may experience transient allergic responses. Correcting an inaccurate allergy diagnosis enables the early introduction of peanuts, reducing the risk for subsequent allergy while sparing families from unnecessary avoidance and a reduced quality of life.

“The worry about the ‘what-ifs’ is an underrecognized component of an allergy diagnosis,” said Abigail Lang, MD, MSCI, the medical director for the Food Allergy Immunotherapy and Advanced Treatments Program at Ann and Robert H. Lurie Children’s Hospital of Chicago. “The fear of what might happen is a huge stress, especially for families with infants and babies who can’t tell you how they’re feeling,” said Lang, who was not associated with the study.

Oral food challenges are considered the gold standard for diagnosing food allergies but are not routinely performed before initiating oral immunotherapy because of safety concerns, limited resources, caregiver concerns, or the belief that they’re unnecessary when a patient has a clinical history and positive sensitization test. The 2020 US peanut allergy diagnostic practice parameter recommends using oral challenges when diagnostic uncertainty remains after reviewing the clinical history and allergy tests.

Researchers retrospectively evaluated data from Australia’s Allergy Development to an Accelerated Path to Tolerance oral immunotherapy program, established in 2024 to standardize peanut allergy treatment across 10 public pediatric hospitals.

Between 2024 and 2025, researchers assessed 1275 infants with suspected peanut allergies. Eligible infants had experienced an allergic reaction to peanuts before age 12 months and showed evidence of sensitization on skin prick testing or peanut-specific immunoglobulin E testing. Of these, 778 underwent oral food challenges before age 18 months; 45.5% were female.

During the challenges, the infants received up to seven escalating doses of peanut protein, ranging from 15 mg to 1300 mg.

Overall, 35% of the infants tolerated peanuts without an allergic reaction. Anaphylaxis occurred in roughly 8% of all challenges, representing 12% of positive challenges, and was safely managed with adrenaline.

Regarding these risks, clinicians should “try to be very honest and acknowledge the fear and how scary it is to see your kid have a reaction,” Lang said. “But the potential benefits may outweigh the risk for a lot of families. It’s really about shared decision making.”

Children who had allergic reactions during the challenges tended to have higher degrees of sensitization in skin prick tests and higher levels of peanut-specific antibodies in their blood. However, neither test reliably predicted the severity of a reaction or the amount of peanut protein needed to trigger one.

Oral food challenges also helped guide immunotherapy dosing. Treatment began at a maximum of one dose level below the amount that triggered a nonanaphylactic reaction during the challenge, or two dose levels below if anaphylaxis occurred. Nearly 98% of the 394 infants who began treatment successfully tolerated their starting dose.

Oral food challenges require approximately half a day of clinical time, specialized staff, and supervision, Perrett said.

Limited resources could make the widespread implementation of oral food challenges difficult, Lang agreed. Owing to the hospital-based settings used in the study, researchers had access to emergency services, which may not be available at smaller facilities. Using biomarkers to identify lower-risk infants could help expand access to challenges in less specialized settings, but greater access to allergists and oral immunotherapy is also needed.

Perrett and Lang reported no relevant conflicts of interest.

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