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Background Polychlorinated biphenyls (PCBs) remain ubiquitous environmental contaminants. Developmental exposures are suspected to impact reproduction. Analysis of mixtures of PCBs may be problematic as components have a complex correlation structure, and along with limited sample sizes, standard regression strategies are problematic. We compared the results of a novel, empirical method to those based on categorization of PCB compounds by (1) hypothesized biological activity previously proposed and widely applied, and (2) degree of ortho- substitution (mono, di, tri), in a study of the relation of maternal serum PCBs and daughter’s time to pregnancy.
Methods We measured PCBs in maternal serum samples collected in the early postpartum in 289 daughters in the Child Health and Development Studies birth cohort. We queried time to pregnancy in these daughters 28–31 years later. We applied a novel weighted quantile sum approach to find the bad-actor compounds in the PCB mixture found in maternal serum. The approach includes empirical estimation of the weights through a bootstrap step which accounts for the variation in the estimated weights.
Results Bootstrap analyses indicated the dominant functionality groups associated with longer TTP were the dioxin-like, anti-estrogenic group (average weight, 22%) and PCBs not previously classified by biological activity (54%). In contrast, the unclassified PCBs were not important in the association with shorter TTP, where the anti-estrogenic groups and the PB-inducers group played a more important role (60% and 23%, respectively). The highly chlorinated PCBs (average weight, 89%) were mostly associated with longer TTP; in contrast, the degree of chlorination was less discriminating for shorter TTP. Finally, PCB 56 was associated with the strongest relationship with TTP with a weight of 47%.
Conclusions Our empirical approach found some associations previously identified by two classification schemes, but also identified other bad actors. This empirical method can generate hypotheses about mixture effects and mechanisms and overcomes some of the limitations of standard regression techniques.
© 2013 Gennings et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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VCU Biostatistics Publications
Histograms for bootstrap distributions of weights for the PCB congeners in the weighted quartile score with a positive slope parameter in a Weibull proportional hazards model adjusted for race (African American vs all other) and whether the daughter was breast fed (yes or no). Figure S2. Histograms for bootstrap distributions of weights for the PCB congeners in the weighted quartile score with a negative slope parameter in a Weibull proportional hazards model adjusted for race (African American vs all other) and whether the daughter was breast fed (yes or no). Table S1. Correlation estimates for the PCB congeners based on maternal serum concentrations (N = 289).