title: Prenatal exposure to persistent organochlorine pollutants is associated with high insulin levels in 5-year-old girls.
abstract: BACKGROUND
  Several persistent organochlorine pollutants (POPs) possess endocrine disrupting abilities, thereby potentially leading to an increased risk of obesity and metabolic diseases, especially if the exposure occurs during prenatal life. We have previously found associations between prenatal POP exposures and increased BMI, waist circumference and change in BMI from 5 to 7 years of age, though only among girls with overweight mothers.
  
  
  OBJECTIVE
  In the same birth cohort, we investigated whether prenatal POP exposure was associated with serum concentrations of insulin and leptin among 5-year-old children, thus possibly mediating the association with overweight and obesity at 7 years of age.
  
  
  METHODS
  The analyses were based on a prospective Faroese Birth Cohort (n=656), recruited between 1997 and 2000. Major POPs, polychlorinated biphenyls (PCBs), p,p'-dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene (HCB), were measured in maternal pregnancy serum and breast milk. Children were followed-up at the age of 5 years where a non-fasting blood sample was drawn; 520 children (273 boys and 247 girls) had adequate serum amounts available for biomarker analyses by Luminex® technology. Insulin and leptin concentrations were transformed from continuous to binary variables, using the 75th percentile as a cut-off point. Multiple logistic regression was used to investigate associations between prenatal POP exposures and non-fasting serum concentrations of insulin and leptin at age 5 while taking into account confounders.
  
  
  RESULTS
  Girls with highest prenatal POP exposure were more likely to have high non-fasting insulin levels (PCBs 4th quartile: OR=3.71; 95% CI: 1.36, 10.01. DDE 4th quartile: OR=2.75; 95% CI: 1.09, 6.90. HCB 4th quartile: OR=1.98; 95% CI: 1.06, 3.69) compared to girls in the lowest quartile. No significant associations were observed with leptin, or among boys. A mediating effect of insulin or leptin on later obesity was not observed.
  
  
  CONCLUSIONS
  These findings suggest, that for girls, prenatal exposure to POPs may play a role for later development of metabolic diseases by affecting the level of insulin.
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark; The Parker Institute and Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Nordre Fasanvej 57, Hovedvejen, Entrance 5, 1st floor, 2000 Frederiksberg, Denmark. Electronic address: jltp@mac.com.
authors.forename: Jeanett L
authors.initials: JL
authors.lastname: Tang-Péronard
authors.affiliation: The Parker Institute and Institute of Preventive Medicine, Research Unit for Dietary Studies, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Nordre Fasanvej 57, Hovedvejen, Entrance 5, 1st floor, 2000 Frederiksberg, Denmark; The Boden Institute of Obesity, Nutrition, Exercise & Eating Disorders, Sydney Medical School, Sydney, Australia; National Institute of Public Health, University of Southern Denmark, Østerfarimagsgade 5A, 2, 1353 Copenhagen K, Denmark.
authors.forename: Berit L
authors.initials: BL
authors.lastname: Heitmann
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark.
authors.forename: Tina K
authors.initials: TK
authors.lastname: Jensen
authors.affiliation: National Food Institute, Division of Toxicology and Risk Assessment, Technical University of Denmark, Mørkhøj Bygade 19, 2860 Søborg, Denmark.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Vinggaard
authors.affiliation: Department of Endocrinology, Hvidovre University Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Department of Occupational Medicine and Public Health, The Faroese Hospital System, Sigmundargøta 5, 100 Tórshavn, Faroe Islands; Neonatal Screening Laboratories, PO-Box 911009, d-30430 Hannover, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Steuerwald
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark; Harvard School of Public Health, Boston, MA 02215, United States.
authors.forename: Philippe
authors.initials: P
authors.lastname: Grandjean
authors.affiliation: Department of Occupational Medicine and Public Health, The Faroese Hospital System, Sigmundargøta 5, 100 Tórshavn, Faroe Islands.
authors.forename: Pál
authors.initials: P
authors.lastname: Weihe
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Nielsen
authors.affiliation: Department of Environmental Medicine, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 17, 5000 Odense C, Denmark.
authors.forename: Helle R
authors.initials: HR
authors.lastname: Andersen
mesh_terms: D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D052244:Endocrine Disruptors / Q000009:adverse effects / Q000032:analysis*; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis*; D005260:Female; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000009:adverse effects / Q000032:analysis*; D007328:Insulin / Q000097:blood*; D020738:Leptin / Q000097:blood; D016015:Logistic Models; D008297:Male; D009765:Obesity / Q000097:blood / Q000209:etiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000139:chemically induced; D011446:Prospective Studies; D012737:Sex Factors
chemical_list: D052244:Endocrine Disruptors; D006843:Hydrocarbons, Chlorinated; D007328:Insulin; D020738:Leptin
keywords: Insulin; Leptin; Metabolic markers; Persistent organochlorine pollutants; Prenatal exposure