Disrupted prenatal maternal cortisol, maternal obesity, and childhood wheeze: Insights into prenatal programming

Rationale: Exploring prenatal factors influencing childhood wheeze may inform programming mechanisms. Objectives: We examined associations among prenatal maternal cortisol profiles, maternal obesity, and repeated wheeze up to age 2 years (n = 261). Methods: Salivary cortisol was collected five times per day over 3 days at 29.0 ± 4.9 weeks gestation. Mothers were categorized as obese (body mass index ≥ 30 kg/m²) versus nonobese (body mass index < 30 kg/m²). Using logistic regression, we examined the influence of log-transformed cortisol metrics (level at each time point, morning rise, diurnal and afternoon slopes) and obesity on wheeze adjusting for covariates. Linear mixed models were implemented to examine associations between cortisol trajectories and wheezing. Interactions between maternal cortisol and obesity were considered. Measurements and Main Results: Mothers were primarily minority (56.5% Hispanic, 24.1% African American), 61% had less than or equal to 12 years of education, 34% were obese, and 8.4% of children had repeated wheeze. An interquartile range increase in mean log cortisol at bedtime (odds ratio, 2.2; 95% confidence interval, 1.09-4.09) and maternal obesity (odds ratio, 3.43; 95% confidence interval, 1.26-9.35) were independently associated with wheeze. Linear mixed models revealed an association between a flatter afternoon slope (slower decline in log cortisol per hour) and repeated wheezein children of obese mothers (children with [-0.017 change] and without [-0.061 change] wheeze [P = 0.009 for time x wheeze interaction]), but not in children of nonobese mothers (with [-0.050 change] and without [-0.061 change] wheeze [P = 0.51]). Conclusions: Maternal prenatal cortisol disruption and obesity were independently associated with children's wheeze. Obese women with adverse cortisol profiles were most likely to have children with repeated wheeze.