Associations between prenatal metal and metalloid mixtures in teeth and reductions in childhood lung function

Background: Metal(oid)s have been cross-sectionally associated with lung function outcomes in childhood but there is limited data on their combined effects starting in utero. Child sex may further modify these effects. Objective: Examine associations between in utero and early life exposure to metals assessed via novel dentine biomarkers and childhood lung function and explore effect modification by child sex. Methods: Analyses included 291 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a longitudinal birth cohort study in Mexico City. Weekly dentine levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) were measured from 15 weeks pre-birth to 15 weeks post birth in deciduous children's teeth. Lung function was tested at ages 8–14 years and then modeled as age, height and sex adjusted z-scores. Associations were modeled using lagged weighted quantile sum (LWQS) regression to evaluate the potential for a time-varying mixture effect adjusting for maternal age and education at enrollment and exposure to environmental tobacco smoke in pregnancy. Models were also stratified by sex. Results: We identified a window of susceptibility at 12–15 weeks pre-birth in which the metal mixture was associated with lower FVC z-scores in children aged 8–14 years. Cd and Mn were the largest contributors to the mixture effect (70 %). There was also some evidence of effect modification by sex, in which the mean weights and weighted correlations over the identified window was more evident in males when compared to females. In the male stratum, Cd, Mn and additionally Pb also dominated the mixture association. Conclusions: Prenatal metal(oid) exposure was associated with lower lung function in childhood. These findings underscore the need to consider both mixtures and windows of susceptibility to fully elucidate effects of prenatal metal(oid) exposure on childhood lung function.