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Risk Factors for Severe Anaphylaxis in Children. OBJECTIVE: To identify risk factors associated with severe anaphylaxis in children. STUDY DESIGN: We carried out a multicenter prospective observational study including children less than 18 years old diagnosed with anaphylaxis in 7 Spanish pediatric emergency departments (EDs) between May 2016 and April 2018. Children were considered to have severe anaphylaxis if they met one or more of the following criteria: requirement for 2 or more doses of epinephrine, clinically important biphasic reaction, endotracheal intubation, intensive care unit admission, and/or death. RESULTS: We included 453 episodes of anaphylaxis. Of these, 61 were classified as severe anaphylaxis (13.5%, 95% CI [10.6-16.9]): 53 (11.7%) required more than 1 dose of epinephrine, and there were 14 (3.1%) cases of clinically important biphasic reactions, 2 (0.4%) intubations in the ED, and 6 (1.3%) admissions to the intensive care unit. No patients died. In the multivariable regression, we identified 5 independent risk factors for severe anaphylaxis: history of asthma (P = .002; OR 2.705, 95% CI [1.431-5.113]), onset of the symptoms less than 5 minutes after the allergen exposure (P = .002; OR 2.619, 95% CI [1.410-4.866]), non-well appearance (P = .005; OR 2.973, 95% CI [1.380-6.405]), tachycardia (P = .014; OR 2.339, 95% CI [1.191-4.959]), and hypotension (P = .036; OR 3.725, 95% CI [1.087-12.762]). CONCLUSIONS: Childhood anaphylaxis is usually well controlled in the ED. Children with a history of asthma, rapid onset of the symptoms, who are non-well appearing, or have tachycardia or hypotension upon arrival to the ED are more likely to have severe episodes.