Association of Infant Feeding Methods and Excess Weight from Birth to Age 6.

Objective: To examine the associations between human milk feeding method (at the breast versus bottle) and measures of child adiposity during the first 6 years of life. Study Design: Women 12 months' postpartum who delivered a singleton, liveborn infant at >24 weeks gestation completed a survey assessing infant feeding methods and sociodemographics. Mothers were recontacted when the child was 6 years old for a follow-up study assessing growth (N = 269). Children were categorized as ever or never having excess weight using weight-for-age z-scores (WAZ), weight-for-height z-scores (WHZ), and body mass index-for-age z-scores (BMIZ) from birth to 6 years. Modified Poisson regression estimated associations between the duration of each feeding method (exclusive and combined) with excess weight status. Mixed-effect models estimated associations between feeding methods and trajectories of the outcomes. Results: For all feeding practices, increasing duration (in months) was unassociated with the risk of ever having excess weight by age 6 years. Based on mixed models, longer duration of feeding human milk by any method was associated with lower BMIZ (adj ß for 6-12 months versus 0-3 months = -0.50, 95% CI: -0.99 to -0.01) and also with the shape of the BMIZ trajectory curve. No other associations between feeding methods and excess weight outcomes were observed. Conclusions: Longer duration of feeding human milk was associated with lower average BMIZ in early childhood but feeding at the breast and feeding expressed milk were not clearly associated with the outcomes when considered separately. Larger studies would help clarify the associations between these specific feeding methods and outcomes. IRB17-00876.

Infant Feeding Practices During the First Postnatal Year and Risk of Asthma and Allergic Disease During the First 6 Years of Life.

Background: Breastfeeding may protect against childhood asthma and allergic diseases. Studies have not focused on the mode of feeding human milk and followed children to school age although feeding human milk from a bottle rather than the breast may alter the risk of disease. Materials and Methods: At 12 months' postpartum, women in the Moms2Moms study (Columbus, OH) completed a survey assessing sociodemographic and infant feeding behaviors. At 6 years' postpartum, they completed a survey and pediatric medical records were abstracted to assess asthma and allergic disease diagnoses. Logistic regression models were used to estimate associations between infant feeding behaviors and asthma or allergic disease. Results: Of 285 children, 16% had asthma and 44% ever had ≥1 allergy diagnosis. Longer durations of each infant feeding behavior were not clearly associated with increased odds of asthma or allergic disease by age 6. Results suggested that longer durations of breast milk feeding (regardless of the mode of feeding) may be related to a lower risk of food allergy (e.g., odds ratio [OR]1-month, adjusted = 0.96, 95% confidence interval [CI] = 0.87-1.05; OR12-month, adjusted = 0.57, 95% CI = 0.19-1.74), but that the mode of feeding (regardless of the substance fed) may be more meaningful for environmental allergies (e.g., exclusive direct breast milk feeding OR12-month, adjusted = 0.32, 95% CI = 0.06-1.81). However, effect estimates were imprecise and CIs included the null. Conclusions: Although no clear associations between mode of breast milk feeding (breast versus expressed) and asthma and allergy outcomes were observed, future research with larger samples should further evaluate these associations.

Dual Inhibition of MEK and PI3K/Akt Rescues Cancer Cachexia through both Tumor-Extrinsic and -Intrinsic Activities.

Involuntary weight loss, a part of the cachexia syndrome, is a debilitating comorbidity of cancer and currently has no treatment options. Results from a recent clinical trial at our institution showed that biliary tract cancer patients treated with a MEK inhibitor exhibited poor tumor responses but surprisingly gained weight and increased their skeletal muscle mass. This implied that MEK inhibition might be anticachectic. To test this potential effect of MEK inhibition, we utilized the established Colon-26 model of cancer cachexia and the MEK1/2 inhibitor MEK162. Results showed that MEK inhibition effectively prevented muscle wasting. Importantly, MEK162 retained its ability to spare muscle loss even in mice bearing a Colon-26 clone resistant to the MEK inhibitor, demonstrating that the effects of blocking MEK are at least in part independent of the tumor. Because single-agent MEK inhibitors have been limited as a first-line targeted therapy due to compensatory activation of other oncogenic signaling pathways, we combined MEK162 with the PI3K/Akt inhibitor buparlisib. Results showed that this combinatorial treatment significantly reduced tumor growth due to a direct activity on Colon-26 tumor cells in vitro and in vivo, while also preserving skeletal muscle mass. Together, our results suggest that as a monotherapy, MEK inhibition preserves muscle mass, but when combined with a PI3K/Akt inhibitor exhibits potent antitumor activity. Thus, combinatorial therapy might serve as a new approach for the treatment of cancer cachexia. Mol Cancer Ther; 16(2); 344-56. ©2016 AACRSee related article by Kobayashi et al., p. 357.