||BACKGROUND: Breast-feeding is recommended for the prevention of eczema, asthma, and allergy, particularly in high-risk families, but recent studies have raised concern that this may not protect children and may even increase the risk. However, disease risk, disease manifestation, lifestyle, and the choice to breast-feed are interrelated, and therefore, analyzing true causal effects presents a number of methodologic challenges. OBJECTIVE: First, to assess the effect from duration of exclusive breast-feeding on the development of eczema and wheezy disorders during the first 2 years of life in a high-risk clinical birth cohort. Second, to assess any influence from the fatty acid composition of mother's milk on the risk from breast-feeding. METHODS: We studied disease development during the first two years of life of the 411 infants from the Copenhagen Study on Asthma in Childhood (COPSAC) birth cohort, born to mothers with a history of asthma. We analyzed the effect from duration of breast-feeding before disease onset on the disease risk, avoiding the effect from disease-related modification of exposure (inverse causation). Polyunsaturated fatty acids were measured in breast milk. RESULTS: Breast-feeding significantly increased the risk of eczema adjusted for demographics, filaggrin variants, parents' eczema, and pets at home (N = 306; relative risk, 2.09; 95% CI 1.15-3.80; P = .016) but reduced the risk of wheezy episodes (relative risk, 0.67; 95% CI 0.48-0.96; P = .021) and of severe wheezy exacerbation (relative risk, 0.16; 95% CI 0.03-1.01; P = .051). There was no association between the fatty acid composition of mother's milk and the risk of eczema or wheeze. CONCLUSION: The risk of eczema was increased in infants with increasing duration of breast-feeding. In contrast, the risk of wheezy disorder and severe wheezy exacerbations was reduced. There were no significant effects from the fatty acid composition of the breast milk on risk of eczema or wheezy disorders.