title: Prenatal Phthalate, Perfluoroalkyl Acid, and Organochlorine Exposures and Term Birth Weight in Three Birth Cohorts: Multi-Pollutant Models Based on Elastic Net Regression.
abstract: BACKGROUND
  Some legacy and emerging environmental contaminants are suspected risk factors for intrauterine growth restriction. However, the evidence is equivocal, in part due to difficulties in disentangling the effects of mixtures.
  
  
  OBJECTIVE
  We assessed associations between multiple correlated biomarkers of environmental exposure and birth weight.
  
  
  METHODS
  We evaluated a cohort of 1,250 term (≥ 37 weeks gestation) singleton infants, born to 513 mothers from Greenland, 180 from Poland, and 557 from Ukraine, who were recruited during antenatal care visits in 2002-2004. Secondary metabolites of diethylhexyl and diisononyl phthalates (DEHP, DiNP), eight perfluoroalkyl acids, and organochlorines (PCB-153 and p,p´-DDE) were quantifiable in 72-100% of maternal serum samples. We assessed associations between exposures and term birth weight, adjusting for co-exposures and covariates, including prepregnancy body mass index. To identify independent associations, we applied the elastic net penalty to linear regression models.
  
  
  RESULTS
  Two phthalate metabolites (MEHHP, MOiNP), perfluorooctanoic acid (PFOA), and p,p´-DDE were most consistently predictive of term birth weight based on elastic net penalty regression. In an adjusted, unpenalized regression model of the four exposures, 2-SD increases in natural log-transformed MEHHP, PFOA, and p,p´-DDE were associated with lower birth weight: -87 g (95% CI: -137, -340 per 1.70 ng/mL), -43 g (95% CI: -108, 23 per 1.18 ng/mL), and -135 g (95% CI: -192, -78 per 1.82 ng/g lipid), respectively; and MOiNP was associated with higher birth weight (46 g; 95% CI: -5, 97 per 2.22 ng/mL).
  
  
  CONCLUSIONS
  This study suggests that several of the environmental contaminants, belonging to three chemical classes, may be independently associated with impaired fetal growth. These results warrant follow-up in other cohorts.
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, the Netherlands.
authors.forename: Virissa
authors.initials: V
authors.lastname: Lenters
authors.forename: Lützen
authors.initials: L
authors.lastname: Portengen
authors.forename: Anna
authors.initials: A
authors.lastname: Rignell-Hydbom
authors.forename: Bo A G
authors.initials: BA
authors.lastname: Jönsson
authors.forename: Christian H
authors.initials: CH
authors.lastname: Lindh
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
authors.forename: Gunnar
authors.initials: G
authors.lastname: Toft
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Bonde
authors.forename: Dick
authors.initials: D
authors.lastname: Heederik
authors.forename: Lars
authors.initials: L
authors.lastname: Rylander
authors.forename: Roel
authors.initials: R
authors.lastname: Vermeulen
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001724:Birth Weight / Q000187:drug effects*; D002210:Caprylates / Q000097:blood* / Q000633:toxicity; D015331:Cohort Studies; D003633:Dichlorodiphenyl Dichloroethylene / Q000097:blood / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005060:Europe; D005260:Female; D005466:Fluorocarbons / Q000097:blood* / Q000633:toxicity; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000097:blood / Q000633:toxicity*; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D010795:Phthalic Acids / Q000097:blood* / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000097:blood / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D006843:Hydrocarbons, Chlorinated; D010795:Phthalic Acids; D003633:Dichlorodiphenyl Dichloroethylene; C023036:perfluorooctanoic acid; D011078:Polychlorinated Biphenyls; C014024:2,4,5,2',4',5'-hexachlorobiphenyl