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.

To attend, or not to attend: Examining caregiver intentions and study compliance in a pediatric, randomized controlled trial.

BACKGROUND/AIMS: The Intent to Attend is a brief questionnaire recommended by the National Research Council to address dropout concerns and improve prediction of missing data in clinical trials, although implementation has been very limited. As a formative study in pediatric research, the relationship between caregiver intentions and study compliance was investigated in a 180-day trial of dietary supplementation of preterm toddlers. Treatment effect estimation in the context of missing data was also explored. METHODS: Study compliance (i.e. study completion, supplement adherence, and diary completion) was tracked over three study visits. Baseline questionnaires asked caregivers about intentions concerning study completion via the Intent to Attend, screened for mental health symptoms (depression, trait anxiety), and captured family demographics. Simple and multiple logistic regression models were built to examine associations between caregiver intent and compliance outcomes. The Intent to Attend was also employed as an auxiliary variable to account for missing data within mixed models estimating the treatment effect on the primary outcomes. RESULTS: Of the 316 caregiver-child dyads included, 95% of caregivers with low intentions had a child complete the study, but only 87% of caregivers with high intentions had a child complete the study. Low intentions to complete the study were associated with a more than 60% lower odds of study non-completion, but the confidence interval included the null (odds ratio: 0.36; 95% confidence interval: 0.11, 1.20). No effect measure modification by caregiver mental health, child sex, or annual income was detected. Income was the only significant predictor of study non-completion; the lowest income group was almost four times more likely to be study non-completers compared with the highest income group, even after adjustment for child sex and caregiver mental health (adjusted odds ratio = 3.59, 95% confidence interval: 1.38, 9.31). When using Intent to Attend as an auxiliary variable, similar results were obtained when compared with the original treatment effect estimates on the primary outcomes. CONCLUSION: Contrary to prior adult studies, there is no clear relationship between caregiver intentions and study compliance. Findings elucidate the complexities of caregiver-child interactions during pediatric trial participation.

C/EBPß regulates the M2 transcriptome in ß-adrenergic-stimulated macrophages.

At the M2 terminal of the macrophage activation spectrum, expression of genes is regulated by transcription factors that include STAT6, CREB, and C/EBPß. Signaling through ß-adrenergic receptors drives M2 activation of macrophages, but little is known about the transcription factors involved. In the present study, we found that C/EBPß regulates the signaling pathway between ß-adrenergic stimulation and expression of Arg1 and several other specific genes in the greater M2 transcriptome. ß-adrenergic signaling induced Cebpb gene expression relatively early with a peak at 1 h post-stimulation, followed by peak Arg1 gene expression at 8 h. C/EBPß transcription factor activity was elevated at the enhancer region for Arg 1 at both 4 and 8 h after stimulation but not near the more proximal promoter region. Knockdown of Cebpb suppressed the ß-adrenergic-induced peak in Cebpb gene expression as well as subsequent accumulation of C/EBPß protein in the nucleus, which resulted in suppression of ß-adrenergic-induced Arg1 gene expression. Analysis of genome-wide transcriptional profiles identified 20 additional M2 genes that followed the same pattern of regulation by ß-adrenergic- and C/EBPß-signaling. Promoter-based bioinformatic analysis confirmed enrichment of binding motifs for C/EBPß transcription factor across these M2 genes. These findings pinpoint a mechanism that may be targeted to redirect the deleterious influence of ß-adrenergic signaling on macrophage involvement in M2-related diseases such as cancer.