title: Negative confounding by essential fatty acids in methylmercury neurotoxicity associations.
abstract: BACKGROUND
  Methylmercury, a worldwide contaminant of fish and seafood, can cause adverse effects on the developing nervous system. However, long-chain n-3 polyunsaturated fatty acids in seafood provide beneficial effects on brain development. Negative confounding will likely result in underestimation of both mercury toxicity and nutrient benefits unless mutual adjustment is included in the analysis.
  
  
  METHODS
  We examined these associations in 176 Faroese children, in whom prenatal methylmercury exposure was assessed from mercury concentrations in cord blood and maternal hair. The relative concentrations of fatty acids were determined in cord serum phospholipids. Neuropsychological performance in verbal, motor, attention, spatial, and memory functions was assessed at 7 years of age. Multiple regression and structural equation models (SEMs) were carried out to determine the confounder-adjusted associations with methylmercury exposure.
  
  
  RESULTS
  A short delay recall (in percent change) in the California Verbal Learning Test (CVLT) was associated with a doubling of cord blood methylmercury (-18.9, 95% confidence interval [CI]=-36.3, -1.51). The association became stronger after the inclusion of fatty acid concentrations in the analysis (-22.0, 95% confidence interval [CI]=-39.4, -4.62). In structural equation models, poorer memory function (corresponding to a lower score in the learning trials and short delay recall in CVLT) was associated with a doubling of prenatal exposure to methylmercury after the inclusion of fatty acid concentrations in the analysis (-1.94, 95% CI=-3.39, -0.49).
  
  
  CONCLUSIONS
  Associations between prenatal exposure to methylmercury and neurobehavioral deficits in memory function at school age were strengthened after fatty acid adjustment, thus suggesting that n-3 fatty acids need to be included in analysis of similar studies to avoid underestimation of the associations with methylmercury exposure.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA. Electronic address: achoi@hsph.harvard.edu.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Choi
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulla B
authors.initials: UB
authors.lastname: Mogensen
authors.affiliation: Department of Medical Biochemistry, St. Olavs Hospital, Trondheim University Hospital, N-7021 Trondheim, Norway; Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.
authors.forename: Kristian S
authors.initials: KS
authors.lastname: Bjerve
authors.affiliation: Faroese Hospital System, Torshavn, Faroe Islands.
authors.forename: Frodi
authors.initials: F
authors.lastname: Debes
authors.affiliation: Faroese Hospital System, Torshavn, Faroe Islands.
authors.forename: Pal
authors.initials: P
authors.lastname: Weihe
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA; Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Philippe
authors.initials: P
authors.lastname: Grandjean
authors.affiliation: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Esben
authors.initials: E
authors.lastname: Budtz-Jørgensen
mesh_terms: D001288:Attention / Q000187:drug effects; D002648:Child; D015331:Cohort Studies; D003718:Denmark; D005228:Fatty Acids, Essential / Q000032:analysis / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000032:analysis / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005506:Food Contamination / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D011939:Mental Recall / Q000187:drug effects; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D009483:Neuropsychological Tests; D009498:Neurotoxins / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology* / Q000523:psychology*; D017747:Seafood / Q000032:analysis / Q000633:toxicity
chemical_list: D005228:Fatty Acids, Essential; D015525:Fatty Acids, Omega-3; D008767:Methylmercury Compounds; D009498:Neurotoxins
keywords: Methylmercury compounds; Negative confounding; Neuropsychological measures; Omega-3 fatty acids; Prenatal exposure delayed effects; Structural equation modeling