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

## TL;DR

Continuous cow's milk formula feeding in early infancy may increase casein-specific IgG4 levels in infants sensitive to cow's milk.

## Contribution

This study identifies a link between continuous cow’s milk formula ingestion and increased casein-specific IgG4 production in sensitized infants.

## Key findings

- Continuous CMF ingestion was associated with significantly higher casein-specific IgG4 levels compared to discontinued ingestion.
- Continuous CMF ingestion was linked to lower cow’s milk–specific IgE levels compared to discontinued ingestion.
- Casein-specific IgE levels were not significantly different between the continuous and discontinued groups.

## Abstract

Early 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.

This study aimed to clarify the aforesaid relationship in cow’s milk–sensitized infants.

Using 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”).

From 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).

Continuous CMF ingestion may promote casein-specific IgG4 production in cow’s milk–sensitized infants.