A Double-Blind, Randomized, Crossover Allergy Study of an Extensively Hydrolyzed Casein Formula

Abstract

Background: Extensively hydrolyzed formulas are used for the dietary management of cow's milk allergy. There is a limited repertoire of commercially available formulas for infants with cow's milk allergy. Methods: This was a multi-center, double-blind, randomized, crossover clinical study of 75 children younger than 12 years, 11 months with documented cow's milk allergy. The primary outcome was the incidence of reactivity of a new extensively hydrolyzed casein formula and Nutramigen ® during a Double-Blind Oral Food Challenge. A subset of subjects under the age of three years, 11 months at the time of enrollment received either the new formula or Nutramigen ® for 16 weeks to investigate tolerance, taste preferences, growth and nutritional variables. Results: Sixty-one subjects completed both challenges in the per-protocol groups. The new formula was noninferior to Nutramigen regarding allergic symptoms of reactivity in both per protocol and intent to treat analyses, the latter addressing risk of bias from attrition during DBOFC. Both formulas met the American Academy of Pediatrics criteria for hypoallergenicity and had similar adverse event profiles. The new formula was comparable to Nutramigen ® in supporting growth and tolerance. Conclusion: The new hypoallergenic formula broadens access to formulations for dietary management of children with cow's milk allergy. Intent to treat analyses should be included in DBOFC studies of hypoallergenicity to reduce risk of bias from early discontinuation.

Determination of Casein Allergens in Extensively Hydrolyzed Casein Infant Formula by Liquid Chromatography-Tandem Mass Spectrometry

“…The incurred sample contained 20 µg/g casein (70.8 µg/g NFDM) on a powder basis, which is below the lowest observed adverse effect level (LOAEL) for milk allergens according the U.S. Food and Drug Administration ( 16 ) based on a 100 mL dose for infant formula. We estimated that a level of casein ≤10 ppm is clinically relevant based on LOAELs for whole milk protein in children ( 17 ) and results from a clinical trial confirming the hypoallergenicity of an extensively hydrolyzed casein formula ( 18 ). However, the method has been validated near the LOQ since clinically relevant targets may change as new information becomes available.…”