In Utero Exposure to Dioxins and Dioxin-like Compounds and Anogenital Distance in Newborns and Infants
Marina Vafeiadi,1,2,3,4 Silvia Agramunt,1,2,5 Eleni Papadopoulou,1,2,3,4,6 Harrie Besselink,7 Kleopatra Mathianaki,8 Polyxeni Karakosta,8 Ariana Spanaki,9 Antonis Koutis,8 Leda Chatzi,8 Martine Vrijheid,1,2,3 and Manolis Kogevinas1,2,3,6
1Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; 2Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain; 3CIBER Epidemiología y Salud Pública (CIBERESP), Spain; 4Pompeu Fabra University, Barcelona, Spain; 5Parc de Salut Mar, Obstetrics and Gynecology Department, Barcelona, Spain; 6National School of Public Health, Athens, Greece; 7Biodetection Systems B.V., Amsterdam, the Netherlands; 8Department of Social Medicine, Medical School, University of Crete, Heraklion, Crete, Greece; 9Venizeleio Hospital, Heraklion, Crete, Greece
Background: Anogenital distance in animals is used as a measure of fetal androgen action. Prenatal exposure to dioxins and dioxin-like compounds in rodents causes reproductive changes in male offspring and decreases anogenital distance.
Objective: We assessed whether in utero exposure to dioxins and dioxin-like compounds adversely influences anogenital distance in newborns and young children (median age, 16 months; range, 1–31 months).
Methods: We measured anogenital distance among participants of the “Rhea” mother–child cohort study in Crete and the Hospital del Mar (HMAR) cohort in Barcelona. Anogenital distance (AGD; anus to upper penis), anoscrotal distance (ASD; anus to scrotum), and penis width (PW) were measured in 119 newborn and 239 young boys; anoclitoral (ACD; anus to clitoris) and anofourchetal distance (AFD; anus to fourchette) were measured in 118 newborn and 223 young girls. We estimated plasma dioxin-like activity in maternal blood samples collected at delivery with the Dioxin-Responsive Chemically Activated LUciferase eXpression (DR CALUX®) bioassay.
Results: Anogenital distances were sexually dimorphic, being longer in males than females. Plasma dioxin-like activity was negatively associated with AGD in male newborns. The estimated change in AGD per 10 pg CALUX®–toxic equivalent/g lipid increase was –0.44 mm (95% CI: –0.80, –0.08) after adjusting for confounders. Negative but smaller and nonsignificant associations were observed for AGD in young boys. No associations were found in girls.
Conclusions: Male infants may be susceptible to endocrine-disrupting effects of dioxins. Our findings are consistent with the experimental animal evidence used by the Food and Agriculture Organization/World Health Organization to set recommendations for human dioxin intake.
Key words: anogenital distance, dioxin-like compounds, dioxins, DR CALUX®, persistent organic pollutants.
Environ Health Perspect 121:125–130 (2013). http://dx.doi.org/10.1289/ehp.1205221 [Online 19 November 2012]
Address correspondence to M. Kogevinas, Centre for Research in Environmental Epidemiology (CREAL), 88 Dr. Aiguader St., 08003 Barcelona, Spain. Telephone: 34 93 214 7332. E-mail: firstname.lastname@example.org
Supplemental Material is available online (http://dx.doi.org/10.1289/ehp.1205221).
We thank all study participants for their generous collaboration. We also thank D. Martinez for assisting in the statistical analysis.
This study was partly funded by FP6 and FP7 European Union grants (contract number FOOD-CT-2005-016320 and 241604 respectively).
H.B. is employed by Biodetection Systems B.V., the company that performed the DR CALUX® bioassay. The authors declare they have no actual or potential competing financial interests.
Received 16 March 2012; Accepted 22 October 2012; Online 19 November 2012.
Recent Advance Publications
- Recruitment of Normal Stem Cells to an Oncogenic Phenotype by Noncontiguous Carcinogen-Transformed Epithelia Depends on the Transforming Carcinogen
- Associations between Fine and Coarse Particles and Mortality in Mediterranean Cities: Results from the MED-PARTICLES Project
- Diabetes, Metabolic Syndrome, and Obesity in Relation to Serum Dioxin Concentrations: The Seveso Women’s Health Study
- The Racial/Ethnic Distribution of Heat Risk-Related Land Cover in Relation to Residential Segregation
- Roxarsone, Inorganic Arsenic, and Other Arsenic Species in Chicken: A U.S.-Based Market Basket Sample
- N-6-Adenine-Specific DNA Methyltransferase 1 (N6AMT1) Polymorphisms and Arsenic Methylation in Andean Women
- A Prospective Study of Arsenic Exposure, Arsenic Methylation Capacity, and Risk of Cardiovascular Disease in Bangladesh