Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex.

ABSTRACT

RATIONALE Impact of ambient pollution upon children's asthma may differ by sex, and exposure dose and timing. Psychosocial stress can also modify pollutant effects. These associations have not been examined for in utero ambient nitrate exposure. OBJECTIVES: We implemented Bayesian-distributed lag interaction models to identify sensitive prenatal windows for the influence of nitrate (NO3-) on child asthma, accounting for effect modification by sex and stress. METHODS: Analyses included 752 mother-child dyads. Daily ambient NO3- exposure during pregnancy was derived using a hybrid chemical transport (Geos-Chem)/land-use regression model and natural log transformed. Prenatal maternal stress was indexed by a negative life events score (high [>2] vs. low [≤2]). The outcome was clinician-diagnosed asthma by age 6 years. MEASUREMENTS AND MAIN RESULTS: Most mothers were Hispanic (54%) or black (29%), had a high school education or less (66%), never smoked (80%), and reported low prenatal stress (58%); 15% of children developed asthma. BDILMs adjusted for maternal age, race, education, prepregnancy obesity, atopy, and smoking status identified two sensitive windows (7-19 and 33-40 wk gestation), during which increased NO3- was associated with greater odds of asthma, specifically among boys born to mothers reporting high prenatal stress. Cumulative effects of NO3- across pregnancy were also significant in this subgroup (odds ratio = 2.64, 95% confidence interval = 1.27-5.39; per interquartile range increase in ln NO3-). CONCLUSIONS: Prenatal NO3- exposure during distinct sensitive windows was associated with incident asthma in boys concurrently exposed to high prenatal stress.