Research | Children’s Health Intrauterine Exposure to Environmental Pollutants and Body Mass Index during the First 3 Years of Life Stijn L. Verhulst,1 Vera Nelen,2 Elly Den Hond,3,4 Gudrun Koppen,3,4 Caroline Beunckens,5 Carl Vael,6 Greet Schoeters,3,4 and Kristine Desager1 1Department of Pediatrics, University of Antwerp, Antwerp, Belgium; 2Provincial Institute for Hygiene, Antwerp, Belgium; 3VITO (Flemish Institute of Technological Research), Mol, Belgium; 4Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium; 5Center for Statistics, Hasselt University, Hasselt, Belgium; 6Department of Microbiology, University of Antwerp, Antwerp, Belgium Objectiv : We investigated the association between body mass index (BMI) standard devia- tion score (SDS) and prenatal exposure to hexachlorobenzene, dichlorodiphenyldichloroethylene (DDE), dioxin-like compounds, and polychlorinated biphenyls (PCBs). Meth Ods : In this prospective birth cohort study, we assessed a random sample of mother–infant pairs (n = 138) living in Flanders, Belgium, with follow-up until the children were 3 years of age. We measured body mass index as standard deviation scores (BMI SDS) of children 1–3 years of age as well as pollutants measured in cord blood. Rtluse : DDE correlated with BMI SDS, with effect modification by maternal smoking and the child’s age. At 1 year, children of smoking mothers had higher BMI SDS than did children of nonsmok- ing mothers. At 3 years, this difference was reduced because of the faster rate of decline in BMI SDS in the former group. hTis relationship held except for children with high levels of DDE. DDE had a small effect on BMI SDS at 3 years of age in children of nonsmoking mothers (difference in BMI SDS for DDE concentrations between the 90th and 10th percentiles = 0.13). On the other hand, smok- ing enhanced the relation between DDE and BMI SDS at 3 years (difference in BMI SDS for DDE concentrations between the 90th and 10th percentiles = 0.76). Increasing concentrations of PCBs were associated with higher BMI SDS values at all ages (parameter estimate = 0.003 ± 0.001; p = 0.03). c Onclusi On : In this study we demonstrated that intrauterine exposure to DDE and PCBs is asso- ciated with BMI during early childhood. Future studies are warranted to confirm our findings and to assess possible mechanisms by which these pollutants could alter energy metabolism. Kye w ORsd : body mass index, childhood, dichlorodiphenyldichloroethylene, dioxin-like compounds, hexachlorobenzene, obesity, polychlorinated biphenyls. Environ Health Perspect 117:122–126 (2009). doi:10.1289/ehp.0800003 available via http://dx.doi.org/ [Online 8 October 2008] The prevalence of childhood obesity is reaching epidemic proportions worldwide (Kelishadi 2007). Furthermore, obese chil- dren and adolescents are at risk of becom- ing obese adults (Guo et al. 2002; Whitaker et al. 1997). This increased risk exists even for preschool-age children (Nader et al. 2006; Sachdev et al. 2005). Obese children and ado- lescents can develop serious comorbidities, including type 2 diabetes and metabolic syn- drome (Sinha et al. 2002; Weiss et al. 2004). Although the main accepted cause of obesity is a genetic predisposition coupled with overeat- ing and a lack of physical activity, there is still much uncertainty related to its etiology. For instance, it has been hypothesized that early environmental influences may contribute to the development of obesity. This hypothesis is illustrated by Toschke et al. (2002), whose study associated maternal smoking during pregnancy with childhood obesity. Therefore, it seems possible that chemical toxicants may also contribute to the etiology of childhood obesity. Recent reviews support the hypoth- esis that even brief exposures early in life to environmental endocrine-disrupting chemicals may increase one’s body weight (Newbold et al. 2007, 2008). A number of chemicals could indeed deregulate endocrine set points, influencing growth and development later in 122 life. These chemicals include the pesticides dichlorodiphenyldichloroethylene (DDE) and hexachlorobenzene, dioxin-like compounds, and polychlorinated biphenyls (PCBs). DDE is the main metabolite of the pesticide DDT (dichlorodiphenyltrichloroethane). Although the use of DDT is prohibited in most coun- tries, it is known to accumulate in the air, soil, and water, and it is biomagnified in the food chain [Agency for Toxic Substances and Disease Registry (ATSDR) 2007]. Until the early 1970s, hexachlorobenzene was used as a pesticide and in the production of fire- works, ammunition, and synthetic rubber. Currently, it is a by-product created by several processes. Furthermore, it breaks down very slowly and accumulates in animals, wheat, and vegetables (ATSDR 2007). PCBs and diox- ins are halogenated hydrocarbons and highly persistent environmental pollutants. Dioxins are by-products from incineration processes and pesticide production, are not intention- ally produced, and have no direct commercial value. There are no known natural sources of PCBs, which have been used as coolants and lubricants in electrical equipment. The industrial manufacturing of PCBs has been essentially prohibited since 1977, but, similar to dioxins, they are unintentionally formed as by-products from many chemical and thermal reactions (ATSDR 2007; Lundqvist et al. 2006). DDE, hexachlorobenzene, PCBs, and dioxins are all considered endocrine dis- ruptors, defined as chemical substances that mimic or affect levels of endocrine media- tors (Lundqvist et al. 2006). Indeed, studies have shown that these toxicants may interfere with thyroid hormone (Brucker-Davis 1998; Koppe et al. 2006; Takser et al. 2005), sex hormones (Jurewicz et al. 2006; Kelce and Wilson 1997; Koppe et al. 2006), and glucose metabolism (Lee et al. 2007; Lelli et al. 2007; Vasiliu et al. 2006). To date, few prospective studies have investigated the association between prenatal exposure to chemicals and body mass index (BMI) (Gladen et al. 2000, 2004; Karmaus and Eneli 2004). In this study we investi- gated the association between BMI during the first 3 years of life and prenatal exposure to environmental pollutants hexachlorobenzene, DDE, dioxin-like compounds, and PCBs. We performed the analysis in three steps. First, we analyzed the association between the pollutants and BMI during childhood. Because this was a longitudinal study, we also assessed the interaction with age. Furthermore, we assessed effect modification by sex because of possible sex-specific effects (Gladen et al. 2000) and possible effect modification by maternal smoking (Sagiv et al. 2007). Second, if a pollutant was associated with BMI, we then checked for a possible influence on birth weight or length to assess whether the influ- ence of the pollutant on childhood growth already started from birth. Third, we checked whether the pollutant influenced height and/ or weight between 1 and 3 years of age. Materials and Methods Study design. In Flanders, the northern part of Belgium, we conducted a large-scale human biomonitoring study as part of the Flemish Address correspondence to S. Verhulst, University of Antwerp, Department of Pediatrics, Universiteitsplein 1, 2610 Wilrijk, Belgium. Telephone: 32475391944. Fax: 3238214447. E-mail: stijn.verhulst@ua.ac.be The study was commissioned, financed, and steered by the Ministry of the Flemish Community (Department of Science, Department of Public Health, and Department of Environment), without any responsibility for the scientific content. The authors declare they have no competing financial interests. Received 16 July 2008; accepted 8 October 2008. ovlume 117 | number 1 | January 2009 • Environmental Health Perspectives