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The prevalence of maternal obesity has increased dramatically with adverse consequences on infant health. Prior studies have reported associations between maternal obesity and childhood wheeze, asthma as well as lower respiratory tract infections (LRTI). However, studies examining the association of obesity with early-life LRTIs in low-income urban minority populations are still lacking. This is a critical gap because both obesity and infant respiratory morbidity are more prevalent and severe in these communities. We examined mother-child dyads from the Boston Birth Cohort (BBC) to define the longitudinal association of maternal pre-pregnancy BMI and LRTI in infancy, defined as the presence of bronchiolitis, bronchitis, or pneumonia during the first year of life (< 12 months of age). A total of 2,790 mother-child dyads were included in our analyses. Infants born to pre-pregnancy obese mothers (n = 688, 25%) had 1.43 increased odds (adjOR = 1.43, 95% CI 1.08-1.88, p = 0.012) of developing LRTI during the first year of life when compared with newborns born to normal-weight mothers after adjusting by relevant LRTI risk factors. Notably, infants born to overweight mothers (n = 808, 29%) followed a similar trend (adjOR = 1.31, 95% CI 1.00-1.72, p = 0.048). Our study demonstrated that maternal pre-pregnancy obesity is an independent risk factor for the development of LRTI during infancy in a low-income urban minority birth cohort.

Human respiratory conditions are largely influenced by the individual's sex resulting in overall higher risk for males. Sex-based respiratory differences are present at birth suggesting a strong genetic component. Our objective was to characterize early life sex-based genomic signatures determined by variable X-chromosome methylation in the airways. We compared male versus female genome-wide DNA methylation in nasal airway samples from newborns and infants aged 1-6 months (N = 12). We analyzed methylation signals across CpG sites mapped to each X-linked gene using an unsupervised classifier (principal components) followed by an internal evaluation and an exhaustive cross-validation. Results were validated in an independent population of children (N = 72) following the same algorithm. X-linked genes with significant sex-based differential methylation in the nasal airway of infants represented only about 50% of the unique protein coding transcripts. X-linked genes without significant sex-based differential methylation included genes with evidence of escaping X-inactivation and female-biased airway expression. These genes showed similar methylation patterns in males and females suggesting unbalanced X-chromosome dosage. In conclusion, we identified that the human airways have already sex-based DNA methylation signatures at birth. These early airway epigenomic marks may determine sex-based respiratory phenotypes and overall predisposition to develop respiratory disorders later in life.