Association of Cytokines in Breast Milk with Otitis Media Infection and Fever Frequency in Infants: A Case–Control Study

<b><i>Introduction:</i></b> Infants have an immature immune system, making them more susceptible to infectious diseases, including otitis media (OM). Breastfeeding is known to reduce OM risk. Although cytokines in breast milk regulate immune functions, their association with OM incidence is underexplored. This study investigated the breast milk cytokines associated with OM in infancy. <b><i>Methods:</i></b> A case-control study was conducted using mother-child pairs from the Chiba Study of Mother and Child Health (16 cases, 53 controls) with a history of OM. Breast milk samples were collected at three time points (colostrum, 1 month, and 4 months postpartum), and cytokine concentrations were measured. We compared cytokine levels between cases and controls and analyzed differences between primiparous and multiparous mothers, including subgroup analysis for multiparous mothers. <b><i>Results:</i></b> Children in the case group were more likely to have multiparous mothers. Cytokine concentrations were highest in colostrum and decreased over time, except for interleukin-7 (IL-7), which increased at 1 month postpartum. However, among multiparous mothers, IL-7 concentration was higher in the control group at 1 month postpartum (66.3 [45.7, 84.7] versus 14.1 [0.00, 42.5] pg/mL). <b><i>Conclusions:</i></b> IL-7 in mature breast milk significantly prevents OM, potentially in infants born to multiparous mothers. <b><i>Trial Registration:</i></b> This trial was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (trial registration number: UMIN000046221, registration date: 29/11/2021).