Continuous cow’s milk protein ingestion during infancy may promote casein-specific IgG4 production

BackgroundEarly supplementation and subsequent discontinuation of cow's milk formula (CMF) may increase the risk of cow's milk allergy in breast-fed infants, but little is known about the relationship between continuous CMF ingestion and cow's milk protein–specific immunoglobulin production.ObjectiveThis study aimed to clarify the aforesaid relationship in cow's milk–sensitized infants.MethodsUsing data from a randomized controlled trial of a Japanese birth cohort, we performed a subgroup analysis of participants who had ingested CMF in the first 3 days of life and exhibited a positive skin prick test response to cow's milk at age 6 months. We compared the differences in median titers of cow's milk–specific IgE, casein-specific IgE, and casein-specific IgG4 levels between participants who continued daily or intermittent CMF ingestion up to age 6 months (the "continuous group") and participants who discontinued CMF ingestion before age 6 months (the "discontinued group").ResultsFrom among 462 trial participants, 49 (10.6%) were included in this study (21 in the continuous group and 29 in the discontinued group). The median titer of cow's milk–specific IgE was 0.17 kUA/L (interquartile range [IQR] = <0.10 to 0.57) in the continuous group and 0.66 kUA/L (IQR = 0.49-1.18) in the discontinued group (P = .0008). The median titer of casein-specific IgE was <0.10 kUA/L (IQR = <0.10 to 0.15) in the continuous group and <0.10 kUA/L (IQR = <0.10 to 0.37) in the discontinued group (P = .51). The median titer of casein-specific IgG4 was 2.58 mgA/L (IQR = 0.77-6.73) in the continuous group and 0.09 mgA/L (IQR = 0.07-0.13) in the discontinued group (P < .0001).ConclusionContinuous CMF ingestion may promote casein-specific IgG4 production in cow's milk–sensitized infants.