Birth Weight and Prenatal Exposure to PCBs and DDE
Birth Weight and Prenatal Exposure to PCBs and DDE
Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight.
Methods: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p'-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions.
Results: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20–484 ng/L) and that of p,p'-DDE was 528 ng/L (range of cohort medians 50–1,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): –250, –50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p'-DDE was associated with a 7-g decrease in birth weight (95% CI: –18, 4 g).
Conclusions: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p'-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.
From the 1930s, polychlorinated biphenyls (PCBs) have been manufactured in large quantities for use in many industrial applications until they were banned in most countries in the 1970s. Dichlorodiphenyltrichloroethane (DDT) is a pesticide that since the 1940s has been used worldwide for malaria vector control, and it is still in use in some areas (Aneck-Hahn et al. 2007; Ayotte et al. 2001). PCBs and the main DDT metabolite dichlorodiphenyldichloroethylene (p,p'-DDE) bioaccumulate in fat tissues, biomagnify through the food chain, are highly persistent in living organisms, and comprise the bulk of organochlorine residues in human tissues (Longnecker et al. 2003). The concentrations of these chemicals in blood, fat, and milk have decreased over the past 30 years but are still detectable in blood of the general population all over the globe (Jonsson et al. 2005). It has been suggested that organochlorines may interfere with fetal growth through interaction with endogenous steroid hormone signaling (Faroon and Olson 2000; Lopez-Espinosa et al. 2009). Birth weight restriction related to PCBs was first described in humans after the 1968 Yusho incident in Japan, where thousands of pregnant women were intoxicated by PCB-contaminated cooking rice oil (Yamashita and Hayashi 1985). During the past 15 years, additional research has addressed human reproductive toxicity of PCBs in studies of fishing communities, fish eaters, and the general population in various regions, as reviewed by Toft et al. (2004) and Longnecker et al. (2003). Findings from these studies on the relation between maternal PCB exposure and birth weight are not consistent—some indicating an inverse association (Fein et al. 1984; Karmaus and Zhu 2004; Murphy et al. 2010; Patandin et al. 1998; Rylander et al. 1995, 1996, 1998; Wojtyniak et al. 2010), an inverse association among male infants only (Sonneborn et al. 2008), a positive association (Dar et al. 1992), or no association at all (Gladen et al. 2003; Grandjean et al. 2001; Longnecker et al. 2005; Mendez et al. 2010; Vartiainen et al. 1998).
A large U.S. study of women giving birth between 1959 and 1966 (when DDT was still being used) found a dose–response relationship between DDE concentration in maternal serum and low birth weight (Longnecker et al. 2001). Children in the high exposure group (> 60 ng/g) weighed 150 g less and were born about 1 week earlier than the children in the low exposure group (< 15 ng/g). Similar results were observed in an Indian study of pregnant women with high DDT exposures (Siddiqui et al. 2003), but serum DDT and/or DDE was not associated with birth weight in two other studies (Gladen et al. 2003; Wojtyniak et al. 2010).
Many factors may contribute to the discrepant findings in earlier observational studies of reproductive effects of PCBs. This includes correlations in some populations between persistent organochlorines (POCs) and such dietary nutrients as n-3 fatty acids that may increase gestational age (Grandjean et al. 2001), limited study size, insufficient exposure levels or contrasts between compared populations (Wojtyniak et al. 2010), exposure to different mixtures of PCB congeners (Murphy et al. 2010), confounding by other organochlorines such as hexachlorobenzene (HCB) (Eggesbo et al. 2009), and different susceptibility of studied populations (Sonneborn et al. 2008). Publication bias could also be a problem, with studies not finding an association being underreported.
A recent review concluded that large-scale studies with a sufficient number of participants in well-defined groups with substantial exposure contrast are needed to further elucidate the possible adverse effects of POCs on human reproductive health (Toft et al. 2004). The ENRIECO (ENvironmental Health RIsks in European birth COhorts) framework of European birth cohorts and the cohorts included in the EU (European Union) OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) project provide the basis for such a study.
The objective of this study was to examine associations between biological markers of exposure to POCs and birth weight in 12 European birth cohorts, including possible modifying effects of sex and tobacco smoking.
Abstract and Introduction
Abstract
Objectives: Exposure to high concentrations of persistent organochlorines may cause fetal toxicity, but the evidence at low exposure levels is limited. Large studies with substantial exposure contrasts and appropriate exposure assessment are warranted. Within the framework of the EU (European Union) ENRIECO (ENvironmental Health RIsks in European Birth Cohorts) and EU OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) projects, we examined the hypothesis that the combination of polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE) adversely affects birth weight.
Methods: We used maternal and cord blood and breast milk samples of 7,990 women enrolled in 15 study populations from 12 European birth cohorts from 1990 through 2008. Using identical variable definitions, we performed for each cohort linear regression of birth weight on estimates of cord serum concentration of PCB-153 and p,p'-DDE adjusted for gestational age and a priori selected covariates. We obtained summary estimates by meta-analysis and performed analyses of interactions.
Results: The median concentration of cord serum PCB-153 was 140 ng/L (range of cohort medians 20–484 ng/L) and that of p,p'-DDE was 528 ng/L (range of cohort medians 50–1,208 ng/L). Birth weight decreased with increasing cord serum concentration of PCB-153 after adjustment for potential confounders in 12 of 15 study populations. The meta-analysis including all cohorts indicated a birth weight decline of 150 g [95% confidence interval (CI): –250, –50 g] per 1-µg/L increase in PCB-153, an exposure contrast that is close to the range of exposures across the cohorts. A 1-µg/L increase in p,p'-DDE was associated with a 7-g decrease in birth weight (95% CI: –18, 4 g).
Conclusions: The findings suggest that low-level exposure to PCB (or correlated exposures) impairs fetal growth, but that exposure to p,p'-DDE does not. The study adds to mounting evidence that low-level exposure to PCBs is inversely associated with fetal growth.
Introduction
From the 1930s, polychlorinated biphenyls (PCBs) have been manufactured in large quantities for use in many industrial applications until they were banned in most countries in the 1970s. Dichlorodiphenyltrichloroethane (DDT) is a pesticide that since the 1940s has been used worldwide for malaria vector control, and it is still in use in some areas (Aneck-Hahn et al. 2007; Ayotte et al. 2001). PCBs and the main DDT metabolite dichlorodiphenyldichloroethylene (p,p'-DDE) bioaccumulate in fat tissues, biomagnify through the food chain, are highly persistent in living organisms, and comprise the bulk of organochlorine residues in human tissues (Longnecker et al. 2003). The concentrations of these chemicals in blood, fat, and milk have decreased over the past 30 years but are still detectable in blood of the general population all over the globe (Jonsson et al. 2005). It has been suggested that organochlorines may interfere with fetal growth through interaction with endogenous steroid hormone signaling (Faroon and Olson 2000; Lopez-Espinosa et al. 2009). Birth weight restriction related to PCBs was first described in humans after the 1968 Yusho incident in Japan, where thousands of pregnant women were intoxicated by PCB-contaminated cooking rice oil (Yamashita and Hayashi 1985). During the past 15 years, additional research has addressed human reproductive toxicity of PCBs in studies of fishing communities, fish eaters, and the general population in various regions, as reviewed by Toft et al. (2004) and Longnecker et al. (2003). Findings from these studies on the relation between maternal PCB exposure and birth weight are not consistent—some indicating an inverse association (Fein et al. 1984; Karmaus and Zhu 2004; Murphy et al. 2010; Patandin et al. 1998; Rylander et al. 1995, 1996, 1998; Wojtyniak et al. 2010), an inverse association among male infants only (Sonneborn et al. 2008), a positive association (Dar et al. 1992), or no association at all (Gladen et al. 2003; Grandjean et al. 2001; Longnecker et al. 2005; Mendez et al. 2010; Vartiainen et al. 1998).
A large U.S. study of women giving birth between 1959 and 1966 (when DDT was still being used) found a dose–response relationship between DDE concentration in maternal serum and low birth weight (Longnecker et al. 2001). Children in the high exposure group (> 60 ng/g) weighed 150 g less and were born about 1 week earlier than the children in the low exposure group (< 15 ng/g). Similar results were observed in an Indian study of pregnant women with high DDT exposures (Siddiqui et al. 2003), but serum DDT and/or DDE was not associated with birth weight in two other studies (Gladen et al. 2003; Wojtyniak et al. 2010).
Many factors may contribute to the discrepant findings in earlier observational studies of reproductive effects of PCBs. This includes correlations in some populations between persistent organochlorines (POCs) and such dietary nutrients as n-3 fatty acids that may increase gestational age (Grandjean et al. 2001), limited study size, insufficient exposure levels or contrasts between compared populations (Wojtyniak et al. 2010), exposure to different mixtures of PCB congeners (Murphy et al. 2010), confounding by other organochlorines such as hexachlorobenzene (HCB) (Eggesbo et al. 2009), and different susceptibility of studied populations (Sonneborn et al. 2008). Publication bias could also be a problem, with studies not finding an association being underreported.
A recent review concluded that large-scale studies with a sufficient number of participants in well-defined groups with substantial exposure contrast are needed to further elucidate the possible adverse effects of POCs on human reproductive health (Toft et al. 2004). The ENRIECO (ENvironmental Health RIsks in European birth COhorts) framework of European birth cohorts and the cohorts included in the EU (European Union) OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life) project provide the basis for such a study.
The objective of this study was to examine associations between biological markers of exposure to POCs and birth weight in 12 European birth cohorts, including possible modifying effects of sex and tobacco smoking.
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