Joan Forns1, Siddhartha Mandal1, Nina Iszatt1, Anuschka Polder2, Cathrine Thomsen3, Jan Ludvig Lyche4, Hein Stigum5, Roel Vermeulen6, Merete Eggesbø7. 1. Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. 2. Department of Food Safety and Infection Biology, Norwegian University of Life Sciences, Ås, Norway. 3. Department of Exposure and Risk Assessment, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway. 4. Department of Food Safety and Infection Biology, Norwegian University of Life Science, Oslo, Norway. 5. Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway. 6. Institute for Risk Assessment Sciences (IRAS), Division Environmental Epidemiology, Utrecht, The Netherlands. 7. Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: Merete.eggesbo@fhi.no.
Abstract
BACKGROUND: The aim of this study was to assess the association between postnatal exposure to multiple persistent organic pollutants (POPs) measured in breast milk samples and early behavioral problems using statistical methods to deal with correlated exposure data. METHODS: We used data from the Norwegian HUMIS study. We measured concentrations of 24 different POPs in human milk from 612 mothers (median collection time: 32 days after delivery), including 13 polychlorinated biphenyls (PCB) congeners, 6 polybrominated diphenyl ethers (PBDE) congeners and five organochlorine compounds. We assessed child behavioral problems at 12 and 24 months using the infant toddler symptom checklist (ITSC). Higher score in ITSC corresponds to more behavioral problems. First we performed principal component analysis (PCA). Then two variable selection methods, elastic net (ENET) and Bayesian model averaging (BMA), were applied to select any toxicants associated with behavioral problems. Finally, the effect size of the selected toxicants was estimated using multivariate linear regression analyses. RESULTS: p,p'-DDT was associated with behavioral problems at 12 months in all the applied models. Specifically, the principal component composed of organochlorine pesticides was significantly associated with behavioral problems and both ENET and BMA identified p,p'-DDT as associated with behavioral problems. Using a multiple linear regression model an interquartile increase in p,p'-DDT was associated with a 0.62 unit increase in ITSC score (95% CI 0.45, 0.79) at 12 months, corresponding to more behavioral problems. The association was modified by maternal education: the effect of p,p'-DDT was strongest in women with lower education (β=0.59; 95%CI: 0.38, 0.81) compared to the mother with higher education (β=0.14; 95%CI: -0.05, 0.34) (p-value for interaction=0.089). At 24 months, neither selection method consistently identified any toxicant associated with behavioral problems. CONCLUSION: Within a mixture of 24 toxicants measured in breast milk, p,p'-DDT was the single toxicant associated with behavioral problems at 12 months using different methods for handling numerous correlated exposures.
BACKGROUND: The aim of this study was to assess the association between postnatal exposure to multiple persistent organic pollutants (POPs) measured in breast milk samples and early behavioral problems using statistical methods to deal with correlated exposure data. METHODS: We used data from the Norwegian HUMIS study. We measured concentrations of 24 different POPs in human milk from 612 mothers (median collection time: 32 days after delivery), including 13 polychlorinated biphenyls (PCB) congeners, 6 polybrominated diphenyl ethers (PBDE) congeners and five organochlorine compounds. We assessed child behavioral problems at 12 and 24 months using the infant toddler symptom checklist (ITSC). Higher score in ITSC corresponds to more behavioral problems. First we performed principal component analysis (PCA). Then two variable selection methods, elastic net (ENET) and Bayesian model averaging (BMA), were applied to select any toxicants associated with behavioral problems. Finally, the effect size of the selected toxicants was estimated using multivariate linear regression analyses. RESULTS:p,p'-DDT was associated with behavioral problems at 12 months in all the applied models. Specifically, the principal component composed of organochlorine pesticides was significantly associated with behavioral problems and both ENET and BMA identified p,p'-DDT as associated with behavioral problems. Using a multiple linear regression model an interquartile increase in p,p'-DDT was associated with a 0.62 unit increase in ITSC score (95% CI 0.45, 0.79) at 12 months, corresponding to more behavioral problems. The association was modified by maternal education: the effect of p,p'-DDT was strongest in women with lower education (β=0.59; 95%CI: 0.38, 0.81) compared to the mother with higher education (β=0.14; 95%CI: -0.05, 0.34) (p-value for interaction=0.089). At 24 months, neither selection method consistently identified any toxicant associated with behavioral problems. CONCLUSION: Within a mixture of 24 toxicants measured in breast milk, p,p'-DDT was the single toxicant associated with behavioral problems at 12 months using different methods for handling numerous correlated exposures.
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