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In Utero Exposure to Compounds with Dioxin-like Activity and Birth Outcomes

Vafeiadi, Marinaa,b,c; Agramunt, Silviaa,b,d; Pedersen, Mariea,b,c,e; Besselink, Harrief; Chatzi, Ledag; Fthenou, Elenig; Fleming, Sarahh; Hardie, Laura J.h; Wright, Johni; Knudsen, Lisbeth E.j; Nielsen, Jeanette K.S.j; Sunyer, Jordia,b,c,k; Carreras, Ramond,l; Brunborg, Gunnarm; Gutzkow, Kristine B.m; Nygaard, Unni C.n; Løvik, Martinuso; Kyrtopoulos, Soterios A.p; Segerbäck, Danq; Merlo, Domenico F.r; Kleinjans, Jos C.s; Vrijheid, Martinea,b,c; Kogevinas, Manolisa,b,c,tThe NewGeneris Consortium

doi: 10.1097/EDE.0000000000000046

Background: Maternal exposure to dioxins and dioxin-like compounds may affect fetal growth and development. We evaluated the association between in utero dioxin-like activity and birth outcomes in a prospective European mother–child study.

Methods: We measured dioxin-like activity in maternal and cord blood plasma samples collected at delivery using the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR CALUX) bioassay in 967 mother–child pairs, in Denmark, Greece, Norway, Spain, and England. Multiple linear regression models were used to investigate the associations with birth weight, gestational age, and head circumference.

Results: Plasma dioxin-like activity was higher in maternal sample than in cord samples. Birth weight was lower with medium (−58 g [95% confidence interval (CI) = −176 to 62]) and high (−82 g [−216 to 53]) tertiles of exposure (cord blood) compared with the lowest tertile. Gestational age was shorter by approximately half a week in the highest compared with the lowest (−0.4 weeks [95% CI = −0.8 to −0.1]). This association was stronger in boys than in girls, although the statistical evidence for interaction was weak (P = 0.22). Analysis based on CALUX-toxic equivalents expressed per milliliter of plasma showed similar trends. We found no association between dioxin-like activity in maternal plasma and birth outcomes.

Conclusions: Results from this international general population study suggest an association between low-level prenatal dioxin-like activity and shorter gestational age, particularly in boys, with weaker associations for birth weight.

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From the aCentre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; bMunicipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain; cCIBER Epidemiología y SaludPública (CIBERESP), Barcelona, Spain; dParc de Salut Mar, Obstetrics and Gynecology Department, Barcelona, Spain; eNational Institute of Health and Medical Research (INSERM), Team of Environmental Epidemiology Applied to Reproduction and Respiratory Health, Institute Albert Bonniot, Grenoble, France; fBiodetection Systems B.V., Amsterdam, The Netherlands; gDepartment of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Greece; hCentre for Epidemiology and Biostatistics, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom; iBradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom; jSection of Environmental Health, Department of Public Health, University of Copenhagen, Copenhagen, Denmark; kFaculty of Health and Life sciences, Pompeu Fabra University, Barcelona, Spain; lDepartment of Pediatrics, Obstetrics and Gynecology and Preventive Medicine, Faculty of Medicine, Autonomous University of Barcelona, Barcelona, Spain; mDepartment of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway; nDepartment of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway; oDepartment of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; pInstitute of Biological Research and Biotechnology, National Hellenic Research Foundation, Athens, Greece; qDepartment of Biosciences and Nutrition, Unit of Molecular Epidemiology, Karolinska Institute, Huddinge, Sweden; rEpidemiology, Biostatistics, and Clinical Trials, IRCCS AOU San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; sDepartment of Toxicogenomics, Maastricht University, Maastricht, The Netherlands; and tNational School of Public Health, Athens, Greece.

The authors report no conflicts of interest.

The NewGeneris (Newborns and Genotoxic exposure risks) study was funded by the European Union (EU contract no. FOOD-CT-2005-016320). The study was also supported by grants obtained locally including: the National Institute for Health Research, United Kingdom (Programme grant RP-PG-0407-10044), the Norwegian Ministry of Health, the Norwegian Ministry of Education and Research, the Norwegian Research Council/FUGE (grant no. 151918/S10), the EUfunded HiWATE (contract no. Food-CT-2006-036224), the US NIH/NIEHS (contract no. NO-ES-75558) and the US NIH/NINDS (grant no. 1 UO1 NS 047537-01). M.P. holds a Juan de la Cierva post-doctoral fellowship awarded from the Spanish Ministry of Science and Innovation (JCI-2011-09479). H.B. is employed by Biodetection Systems B.V., Amsterdam, The Netherlands.

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Correspondence: Manolis Kogevinas, Centre for Research in Environmental Epidemiology (CREAL), 88 Doctor Aiguader Road, Barcelona 08003, Spain. E-mail:

© 2014 by Lippincott Williams & Wilkins, Inc