Estimating the causal effect of early peanut introduction on the risk of food protein enterocolitis syndrome (fpies)

The National Institute of Allergy and Infectious Diseases awarded Northwestern University $250,642 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to estimate the causal effect of early peanut introduction on the risk of peanut-induced food protein enterocolitis syndrome (FPIES).

The research leverages existing electronic health record data and caregiver surveys from the IREACH trial, a randomized controlled trial conducted across 30 pediatric practices that collected data from 18,480 infants. The study has two primary aims: to estimate causal models of peanut FPIES incidence as a function of early peanut introduction using EHR-validated survey data, and to determine the effect of the IREACH intervention on caregiver-reported food-related allergic reactions and FPIES incidence to the top nine allergenic foods. The research addresses a clinical concern that the 2017 Addendum guidelines recommending early peanut introduction around age six months to prevent immunoglobulin E-mediated peanut allergy may have unintended consequences for children susceptible to FPIES, a non-IgE-mediated food allergy affecting 0.51 percent of U.S. children.

Work is performed at Northwestern University in Chicago, Illinois, with a period of performance from September 1, 2026, through August 31, 2028.

Abstract

And abstract background: food protein-induced enterocolitis syndrome (fpies) is a non-immunoglobulin e (IGE) mediated food allergy with clinical presentation of gastrointestinal symptoms including vomiting and diarrhea 1- 4 hours after ingestion of a food trigger. Fpies impacts 0.51% of US children and most present with symptoms before age one. An increase in the number of peanut fpies cases coincided with a major change in clinical guidance around the prevention of IGE- mediated peanut allergy. In 2017, the addendum guidelines for the prevention of peanut allergy (PPA guidelines) encouraged pediatric clinicians to recommend the introduction of peanut containing foods for most children around 6 months of age. While this guidance may help prevent peanut allergy, the early introduction of allergenic solids may have unintended harm for some children. Specific aims and methods: this study aims to assess the impact of early introduction of peanut-containing foods on the risk of developing peanut-induced, fpies. We will do this by leveraging data and exogenous variation stemming from the intervention to reduce early peanut allergy in children (ireach) trial. Ireach is a pediatric practice-based, randomized control trial of a clinician-facing intervention. In total, electronic health record (EHR) data of 18480 infants were collected from 30 pediatric practices. This project will leverage existing EHR data and caregiver surveys in a subset of infants. The study aims are as follows: 1) to estimate causal models of the incidence of peanut fpies as a function of early peanut introduction using EHR-validated survey data, and 2) to determine the effect of the ireach intervention on caregiver-reported food related allergic reactions and fpies incidence to the top nine allergenic foods. Hypotheses and expected results: our primary study hypotheses are based on a conceptual model associating early peanut introduction early with the development of peanut fpies. Specifically, we hypothesize that the early introduction of peanut containing foods will be associated with a higher incidence of peanut fpies. Secondary hypotheses will test spillover effects of ireach on the likelihood of reactions to the other top allergenic solids and corresponding fpies. Significance and effects on other research: the results of this study will address a question of great public health significance currently being examined by the united states preventive services task force. This study will provide the necessary evidence to provide rationale for a large-scale investigation of the factors that make early introduction risky for some children.