To determine whether different modes of infant feeding are associated with childhood asthma, including differentiating between direct breastfeeding and expressed breast milk.Study designWe studied 3296 children in the Canadian Healthy Infant Longitudinal Development birth cohort. The primary exposure was infant feeding mode at 3 months, reported by mothers and categorized as direct breastfeeding only, breastfeeding with some expressed breast milk, breast milk and formula, or formula only. The primary outcome was asthma at 3 years of age, diagnosed by trained healthcare professionals.ResultsAt 3 months of age, the distribution of feeding modes was 27% direct breastfeeding, 32% breastfeeding with some expressed breast milk, 26% breast milk and formula, and 15% formula only. At 3 years of age, 12% of children were diagnosed with possible or probable asthma. Compared with direct breastfeeding, any other mode of infant feeding was associated with an increased risk of asthma. These associations persisted after adjusting for maternal asthma, ethnicity, method of birth, infant sex, gestational age, and daycare attendance (some expressed breast milk: aOR, 1.64, 95% CI, 1.12-2.39; breast milk and formula, aOR,?1.73, 95% CI, 1.17-2.57; formula only: aOR,?2.14, 95% CI, 1.37-3.35). Results were similar after further adjustment for total breastfeeding duration and respiratory infections.ConclusionsModes of infant feeding are associated with asthma development. Direct breastfeeding is most protective compared with formula feeding; indirect breast milk confers intermediate protection. Policies that facilitate and promote direct breastfeeding could have impact on the primary prevention of asthma.Previous article in issueNext article in issueKeywordsbreastfeedingpumped breast milkasthmaAbbreviationCHILDCanadian Healthy Infant Longitudinal DevelopmentBreast milk is widely known to be the optimal source of infant nutrition. The importance of breastfeeding is well-recognized for infants’ short-term health with respect to growth, immune function, and gastrointestinal health.1 In addition to these immediate clinical benefits, there are potential long-term advantages that are realized after the breastfeeding period. An extensive body of literature suggests that breastfeeding may contribute to protection against autoimmune, malignant, and inflammatory diseases, including allergic diseases and asthma.1-5 However, very few studies distinguish between breastfeeding, where the infant suckles directly at the mother’s breast, and consumption of human milk, which can be expressed and fed from a bottle. This distinction is important because an increasing number of mothers are providing expressed breast milk to their infants.6,7 For example in the United States, where there is no national policy for paid maternity leave and the average mother returns to work after just 10 weeks,8 more than 25% of nursing mothers regularly provide expressed breast milk to their infants.9Although several studies,5,10,11 including our own,12 have found that breastfeeding is protective against asthma or wheezing disorders, a recent meta-analysis found that evidence for this association was inconsistent across studies, with high heterogeneity (I2?=?63% across 29 studies) related to differences in study designs and settings.13 This inconsistency may also be related to differences in infant feeding modes, which are known to vary widely between countries,6 but are generally not documented in epidemiologic studies.To date, only 1 study has examined respiratory health among infants fed direct breast milkversus bottled breast milk14; Soto-Ramirez et al found that any mode of infant feeding that included formula or expressed breast milk conferred an increased risk for coughing and wheezing episodes by 1 year of age, compared with direct breastfeeding. A proposed mechanism for this association is the alteration of breast milk components, such as bioactive proteins and microbiota, during the expression and storage of breast milk.15-17 In addition, during active infection in the nursing infant, direct breastfeeding is thought to trigger an increased immune response in the lactating mother, leading to a transfer of protective factors to her relatively immunocompromised offspring.18 Direct contact through breastfeeding also transmits potentially protective maternal skin microbes,19 and the physical exercise associated with suckling at the breast is thought to improve airflow and increase lung capacity.20 However, the potential impact of expressed breast milk on childhood asthma development remains unknown because no studies have examined this association beyond the first year of life.Using prospective data from the national Canadian Healthy Infant Longitudinal Development (CHILD) population-based birth cohort,21 we undertook a study to determine the association of infant feeding modes in the first 3 months of life with asthma development by 3 years of age. We hypothesized that any mode of feeding that included expressed breast milk or formula would be associated with an increased risk of asthma compared with direct breastfeeding.MethodsThis study included 3296 infants from the CHILD study,21 a general population-based national birth cohort that recruited pregnant women from Toronto, Winnipeg, Edmonton, and Vancouver from 2009 to 2012. The CHILD Study enrolled women at least 18 years of age in their second or third trimester of pregnancy with proficiency in English and residing within reasonable proximity to a recruitment center. Exclusion criteria for the CHILD study were children with major congenital anomalies, born preterm (<356/7 weeks of gestation), of multiple births, or resulting from in vitro fertilization. Written informed consent was obtained by caregivers at enrollment and the study was approved by the Human Research Ethics Boards of the Universities of Alberta, British Columbia, Manitoba, Toronto and McMaster University.Modes of feeding were reported by mothers at 3 months and infants were classified into 4 categories: (1) breast milk only—all direct breastfeeding (no expressed milk or formula from birth to 3 months of age); (2) breast milk only—some expressed breast milk (received some breast milk expressed with a pump before 3 months of age, but no formula); (3) formula and breast milk (formula introduced before 3 months of age, but still receiving some direct or expressed breast milk at 3 months of age); or (4) formula only (not receiving any breast milk at 3 months of age).A semistructured assessment of asthma was performed at 3 years of age. The diagnosis of asthma was made after a focused history and physical examination by a limited number of well-trained healthcare professionals (2 or 3 physicians, nurses, or clinical research associates at each site) and classified for this analysis as possible or probable asthma or no asthma. In a sensitivity analysis, we evaluated the modified Asthma Predictive Index as an alternative outcome, adapted from Guilbert et al22 and defined as a diagnosis of possible or probable asthma plus one of the following: diagnosed atopic dermatitis,21 positive skin prick test to any allergen (wheal diameter ?2?mm greater than the response to the negative control),21 or parental history of diagnosed asthma (self- reported by parents).Infant sex, gestational age, method of birth, maternal age, and number of older siblings (parity) were documented from hospital records. Maternal ethnicity, history of asthma, and tobacco smoking during pregnancy and infancy were self-reported by standardized questionnaire. Maternal education and home ownership were also self-reported during pregnancy, and assessed as measures of socioeconomic status. Daycare attendance at 1 year of age was defined as spending 7 or more hours a week with at least 3 other children at a location away from home. The total duration of any breastfeeding (infant age at breastfeeding cessation) and number of respiratory infections (colds) were documented from maternal questionnaires completed at 3, 6, 12, 18, and 24 months postpartum.Statistical AnalysesLogistic regression was used to investigate associations between modes of infant feeding and asthma. First, potential confounders (listed above) were tabulated against infant feeding mode and asthma. Those found to be significantly associated with both feeding mode and asthma (P?.05 by ?2 test) were subsequently included in logistic regression models. Regression models were also adjusted for 3 established asthma risk factors selected a priori(infant sex, maternal ethnicity, and maternal asthma). Results are presented as crude odds ratios (ORs) and adjusted ORs (aORs) with 95% confidence intervals (CI). Analyses were conducted for the 2534 children with complete data for infant feeding, asthma diagnosis, and essential covariates (Figure?1; available at www.jpeds.com). Children who were lost to follow-up or had incomplete feeding data (n?=?762) were similar to those with complete data (n?=?2534) with respect to infant feeding patterns, maternal asthma, and child asthma (Table?I). Mothers of children with complete data were more likely to be white and have a higher socioeconomic status, and less likely to smoke. To address potential bias from incomplete data and loss to follow-up, a sensitivity analysis was performed in the full cohort after multiple imputation of missing feeding, asthma, and covariate data. Multiple imputation (n?=?20 imputed datasets) was performed with fully conditional specification (chained equations) using all essential covariates plus the following auxiliary variables: maternal age, parity, and postsecondary education; history of prenatal smoke exposure; and study site. We present results from the imputed data as the main findings because they are adjusted (through multiple imputation) for potential bias from missing data. Additional sensitivity analyses were performed to evaluate an alternative outcome definition (modified Asthma Predictive Index, as defined), and to adjust for respiratory infections (among all infants) and breastfeeding duration (excluding infants in the formula-only group). All analyses were performed using SAS version 9.4 (SAS Institute, Cary, North Carolina).