title: Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic combination of newborn blood concentrations and questionnaire data: a case control study.
abstract: BACKGROUND
  Methylmercury (MeHg), known for well over a century as a neurotoxin in adults, has more recently been studied for potential detrimental effects during early brain development. While several studies have estimated mercury exposure, they usually rely on either a single biomarker or questionnaire data, each of which has limitations. The goal of this paper was to develop a toxicokinetic model that incorporates both biomarker and questionnaire data to estimate the cumulative exposure to MeHg through seafood consumption using data collected from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study.
  
  
  METHODS
  We utilized a previously described discrete-time model that estimates blood MeHg concentration given a piecewise-constant ingestion rate and single-compartment pharmacokinetics. We measured newborn bloodspot Hg concentrations and obtained information pertaining to maternal fish consumption using a questionnaire. Using MeHg concentration estimates from the toxicokinetic model, cumulative MeHg exposure was estimated in children with autism, children with developmental delay, and typically developing children. Median estimated cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis Test. Multinomial logistic regression models were constructed to assess the association between cumulative MeHg concentration and the risk of autism and developmental delay (vs. typical development).
  
  
  RESULTS
  The estimated average MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median cumulative MeHg over gestation was similar across diagnostic groups (p-values raged from 0.91 to 0.98). After adjusting for potential confounding, we found no association between cumulative MeHg exposure and the risk of autism (OR = 0.95, 95% CI: 0.95, 1.12) or developmental delay (OR = 1.00, 95% CI: 0.89, 1.13).
  
  
  CONCLUSIONS
  The toxicokinetic model described in this paper yielded fish MeHg concentration estimates that are consistent with fish species containing lower levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably elevate the risk of autism or developmental delay. Based on the regression standard error for the association between ASD and TD, we would have reported statistical significance for an adjusted odds ratio of 1.09 or larger. This method can easily be extended to other epidemiologic studies in which there is a biomarker measurement and questionnaire data regarding exposure.
authors.affiliation: University of California, Davis, Davis, CA, USA. sjmckean@ucdavis.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McKean
authors.affiliation: Program in Public Health and Department of Statistics, University of California, Irvine, Irvine, CA, USA. sbartell@uci.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bartell
authors.affiliation: Department of Pediatrics, University of California, Davis, Sacramento, CA, USA. robin.hansen@ucdmc.ucdavis.edu.|MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA, USA. robin.hansen@ucdmc.ucdavis.edu.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Hansen
authors.affiliation: Interdisciplinary Center for Plasma Mass Spectrometry, University of California, Davis, Davis, CA, 95616, USA. robin.hansen@ucdmc.ucdavis.edu.
authors.forename: Gry H
authors.initials: GH
authors.lastname: Barfod
authors.affiliation: Department of Civil and Environmental Engineering, University of California, Davis, Davis, CA, USA. pggreen@ucdavis.edu.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Green
authors.affiliation: MIND Institute, School of Medicine, University of California, Davis, Sacramento, CA, USA. ihp@phs.ucdavis.edu.|Department of Public Health Sciences, University of California, Davis, Davis, CA, USA. ihp@phs.ucdavis.edu.
authors.forename: Irva
authors.initials: I
authors.lastname: Hertz-Picciotto
mesh_terms: D000328:Adult; D000818:Animals; D001321:Autistic Disorder / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D002140:California; D016022:Case-Control Studies; D002657:Child Development; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000209:etiology*; D016021:Epidemiologic Studies; D005260:Female; D005506:Food Contamination / Q000032:analysis; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D008628:Mercury / Q000097:blood*; D008767:Methylmercury Compounds / Q000009:adverse effects* / Q000032:analysis*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood*; D017747:Seafood / Q000032:analysis; D012959:Socioeconomic Factors; D011795:Surveys and Questionnaires
chemical_list: D015415:Biomarkers; D008767:Methylmercury Compounds; D008628:Mercury