title: Novel application of statistical methods for analysis of multiple toxicants identifies DDT as a risk factor for early child behavioral problems.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Joan
authors.initials: J
authors.lastname: Forns
authors.affiliation: Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mandal
authors.affiliation: Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Iszatt
authors.affiliation: Department of Food Safety and Infection Biology, Norwegian University of Life Sciences, Ås, Norway.
authors.forename: Anuschka
authors.initials: A
authors.lastname: Polder
authors.affiliation: Department of Exposure and Risk Assessment, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Cathrine
authors.initials: C
authors.lastname: Thomsen
authors.affiliation: Department of Food Safety and Infection Biology, Norwegian University of Life Science, Oslo, Norway.
authors.forename: Jan Ludvig
authors.initials: JL
authors.lastname: Lyche
authors.affiliation: Department of Chronic Diseases, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Hein
authors.initials: H
authors.lastname: Stigum
authors.affiliation: Institute for Risk Assessment Sciences (IRAS), Division Environmental Epidemiology, Utrecht, The Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
authors.affiliation: Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. Electronic address: Merete.eggesbo@fhi.no.
authors.forename: Merete
authors.initials: M
authors.lastname: Eggesbø
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D002675:Child, Preschool; D003627:Data Interpretation, Statistical; D004784:Environmental Monitoring / Q000706:statistics & numerical data; D004785:Environmental Pollutants / Q000032:analysis*; D005260:Female; D055768:Halogenated Diphenyl Ethers / Q000032:analysis; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000032:analysis*; D007223:Infant; D016014:Linear Models; D008297:Male; D008895:Milk, Human / Q000737:chemistry*; D009664:Norway / Q000453:epidemiology; D000066553:Problem Behavior; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D004785:Environmental Pollutants; D055768:Halogenated Diphenyl Ethers; D006843:Hydrocarbons, Chlorinated; C086401:pentabromodiphenyl ether
keywords: Child development; Chlordane; Complex mixtures; Dichlorodiphenyl dichloroethylene; Dichlorodiphenyldichloroethane; Hexachlorobenzene; Nervous system; Polybrominated diphenyl ethers; Polychlorinated biphenyls