Birth Weight and Prenatal Exposure to Polychlorinated Biphenyls (PCBs) and Dichlorodiphenyldichloroethylene (DDE): A Meta-analysis within 12 European Birth Cohorts (original) (raw)
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Regulatory Toxicology and Pharmacology, 2012
Impact of prenatal PCB exposure on birth weight was investigated in various children cohorts and findings of published studies show inconsistencies. Because a direct comparison of results obtained from different studies remains difficult, the ''biological concentration-birth weight'' relationship is not clearly established. The objective of this research was to perform a systematic analysis of published epidemiological data to reassess relationship between prenatal PCB exposure and low birth weight, using toxicokinetic considerations and a novel standardization procedure of biological concentration data across studies. A systematic analysis of 20 epidemiological studies published up to 2011 on this topic was conducted. This was achieved through a standardization of reported exposure data in terms of total PCBs per kg of lipids in maternal plasma. Systematic analysis of the ''standardized biological concentration-birth weight'' relationship across studies was then conducted through the application of Hill criteria. Combining results of all 20 reviewed studies did not allow to establish an association between prenatal exposure to PCBs at the described levels and abnormal birth weight (<2500 g). Our approach provides a framework for the use of published data to establish ''PCB biological concentration-response'' relationships.
Environmental Health, 2013
Background: Prenatal exposure to persistent organic pollutants, e.g. polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) has been suggested to negatively affect birth weight although epidemiological evidence is still inconclusive. We investigated if prenatal exposure to PCBs and PBDEs is related to birth weight in a Swedish population with background exposure. Methods: Breast milk was sampled during the third week after delivery from first-time mothers in Uppsala county, Sweden 1996-2010 (POPUP cohort) (N = 413). Samples were analysed for di-ortho PCBs 153, 180) and tetra-to hexa-brominated PBDEs 99, 100, 153). Simple and multiple linear regression models were used to investigate associations between lipid-adjusted, ln-transformed PCB and PBDE concentrations, and birth weight. Covariates included in the multivariate regression model were PCB and PBDE exposure, maternal age, prepregnancy BMI, weight gain during pregnancy, education, smoking, gender of the infant and gestational length. The effect of including fish consumption was also investigated. Results: In the multivariate model, prenatal exposure to di-ortho PCBs was significantly associated with increased birth weight (β = 137; p = 0.02). The result did not change when gestational length was added to the model. An inverse association between PBDE(4) (sum of BDE-47, -99, -100 and −153) and birth weight was observed in the multivariate model including gestational length (β = −106; p = 0.04). Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders of the association between di-ortho PCBs and birth weight. The associations were not alleviated after adjustment for fish consumption, a major source of PCB and PBDE exposure. The observed associations were stronger for boys than for girls. Conclusions: Our results indicate that prenatal exposure to di-ortho PCBs and PBDE(4) may influence birth weight in different directions, i.e. PCB exposure was associated with higher birth weight and PBDE exposure with lower birth weight. Maternal pre-pregnancy BMI and weight gain during pregnancy were important confounders that may hide positive association between di-ortho PCB exposure and birth weight if they are not included in the statistical model. We speculate that even small PCB-and PBDE-induced shifts in the distribution of birth weight may influence future public health in populations with background exposure.
BACKGROUND: Recent experimental evidence suggests that prenatal exposure to endocrine-disrupting chemicals (EDCs) may increase postnatal obesity risk and that these effects may be sex or diet dependent. OBJECTIVES: We explored whether prenatal organochlorine compound (OC) concentrations [polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (DDE), and dichlorodiphenyltrichloroethane (DDT)] were associated with overweight at 6.5 years of age and whether child sex or fat intakes modified these associations. METHODS: We studied 344 children from a Spanish birth cohort established in 1997-1998. Overweight at 6.5 years was defined as a body mass index (BMI) z-score ≥ 85th percentile of the World Health Organization reference. Cord blood OC concentrations were measured and treated as categorical variables (tertiles). Children's diet was assessed by food frequency questionnaire. Relative risks (RRs) were estimated using generalized linear models. RESULTS: After multivariable adjustment, we found an increased RR of overweight in the third tertile of PCB exposure [RR = 1.70; 95% confidence interval (CI): 1.09, 2.64] and the second tertile of DDE exposure (RR = 1.67; 95% CI: 1.10, 2.55), but no association with DDT exposure in the population overall. Associations between overweight and PCB and DDE concentrations were strongest in girls (p-interaction between 0.01 and 0.28); DDT was associated with overweight only in boys. For DDT we observed stronger associations in children with fat intakes at or above compared with below the median, but this interaction was not significant (p-interaction > 0.05). CONCLUSIONS: This study suggests that prenatal OC exposures may be associated with overweight in children and that sex and high-fat intake may influence susceptibility.
Fetal Exposure to PCBs and Their Hydroxylated Metabolites in a Dutch Cohort
Environmental Health Perspectives, 2004
Polychlorinated biphenyls (PCBs) are still the most abundant pollutants in wildlife and humans. Hydroxylated PCB metabolites (OH-PCBs) are known to be formed in humans and wildlife. Studies in animals show that these metabolites cause endocrine-related toxicity. The health effects in humans have not yet been evaluated, especially the effect on the fetus and newborn. The aim of this study is to measure the levels of PCBs and OH-PCBs in maternal and cord blood samples in a population with background levels of PCBs. We analyzed 51 maternal and corresponding cord blood samples in the northern part of the Netherlands. The PCB concentrations in maternal plasma ranged from 2 to 293 ng/g lipid, and OH-PCB concentrations from nondetectable (ND) to 0.62 ng/g fresh weight. In cord plasma, PCB concentrations were 1-277 ng/g lipid, and OH-PCB concentrations, ND to 0.47 ng/g fresh weight. The cord versus maternal blood calculated ratio was 1.28 ± 0.56 for PCBs and 2.11 ± 1.33 for OH-PCBs, expressed per gram of lipid. When expressed per gram fresh weight, the ratios are 0.32 ± 0.15 and 0.53 ± 0.23 for PCBs and OH-PCBs, respectively. A significant correlation between the respective maternal and cord levels for both PCBs and OH-PCBs was found. Our results indicate that OH-PCBs and PCBs are transferred across the placenta to the fetus in concentrations resulting in levels of approximately 50 and 30%, respectively, of those in maternal plasma. More research in humans is needed to evaluate potential negative effects of these endocrine disruptors on the fetus.
Environmental Health, 2008
Background: Polychlorinated biphenyls (PCBs) are ubiquitous industrial chemicals that persist in the environment and in human fatty tissue. PCBs are related to a class of compounds known as dioxins, specifically 2,3,7,8-TCDD (tetrachloro-dibenzodioxin), which has been implicated as a cause of altered sex ratio, especially in relation to paternal exposures. Methods: In the 1960's, serum specimens were collected from pregnant women participating in the Child Health and Development Study in the San Francisco Bay Area. The women were interviewed and their serum samples stored at-20°C. For this study, samples were thawed and a total of eleven PCBs were determined in 399 specimens. Secondary sex ratio, or sex ratio at birth, was evaluated as a function of maternal serum concentrations using log-binomial and logistic regression, controlling for hormonally active medications taken during pregnancy. Results: The relative risk of a male birth decreased by 33% comparing women at the 90 th percentile of total PCBs with women at the 10 th percentile (RR = 0.67; 95% CI, 0.48-0.94; p = 0.02), or by approximately 7% for each 1 μg/L increase in total PCB concentration. Although some congener-specific associations with sex ratio were only marginally statistically significant, all nine PCB congeners with < 30% of samples below the LOQ showed the same direction of association, an improbable finding under the null hypothesis. Conclusion: Maternal exposure to PCBs may be detrimental to the success of male sperm or to the survival of male embryos. Findings could be due to contaminants, metabolites or PCBs themselves.
Polychlorinated biphenyls in serum and time to pregnancy
Environmental Research, 2004
Polychlorinated biphenyls (PCBs) may affect the female reproductive system in both animals and humans. In Sweden, a main exposure source to PCBs is consumption of fatty fish from the Baltic Sea. From 165 female consumers of such fish (fishermen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s sisters), information on time to pregnancy (TTP) and miscarriages was collected, blood was drawn, and serum was analyzed for 2,2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;,4,4&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;,5,5&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-hexachlorobiphenyl (CB-153), a biomarker for total PCB exposure. TTP and miscarriage data, as well as plasma CB-153 concentrations, for 121 fishermen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s wives were available from previous studies. Thus, information on 286 women was available for investigation of whether a high exposure to PCB affects fertility negatively by increasing the TTP. The concentrations of CB-153 at the time of conception were estimated and trichotomized into low, medium, and high exposure groups. When we analyzed the joint data set of fishermen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s wives and fishermen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s sisters, a decrease rather than an increase in TTP was indicated for women in the medium (fecundability ratio 1.27 [95% confidence interval 0.89-1.82]) and high (fecundability ratio 1.42 [0.99-2.03]) exposure groups compared to those in the low exposure group. Similar results were found when we stratified on the original data set (fishermen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s wives and fishermen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s sisters) or childhood exposure. Women with miscarriages had lower estimated past CB-153 concentrations than women with live births. Our data provide no evidence of a hazardous effect associated with CB-153 concentration in the exposure range assessed. The exposure levels found in the fishermen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s families, although high compared to that in the general Swedish population, may not be high enough to negatively affect fertility.
Environmental Research, 2005
Fish consumption may be beneficial for a developing human fetus, but fish may also contain contaminants that could be detrimental. Great Lakes sport-caught fish (GLSCF) are contaminated with polychlorinated biphenyls (PCBs) and dichlorodiphenyl dichloroethylene (DDE), but the effects of these contaminants on birth outcome are not clear. To distinguish potential contaminant effects, we examined (1) whether the decrease over time in contaminant levels in GLSCF is paralleled by an increase in birth weight of children of GLSCF-consuming mothers and (2) the relation between maternal serum concentrations of these contaminants and birth weight. Mothers (n=511) were interviewed from 1993 to 1995, and maternal serum was collected from 1994 to 1995 (n=143). Potential confounders considered were child gender, maternal age at delivery, maternal prepregnancy body mass index, maternal cigarette and alcohol use during pregnancy, maternal education level, maternal parity, and maternal breastfeeding. Children born during 1970-1977, 1978-1984, and 1985-1993 to mothers who ate more than 116 meals of GLSCF before pregnancy were, on average, 164 g lighter, 46 g heavier, and 134 g heavier, respectively, than children of mothers who ate no GLSCF before pregnancy (P trend=0.05). GLSCF-consuming mothers had higher serum PCB and DDE concentrations, but only increased DDE was associated with lower birth weight. The data suggest that fetal DDE exposure (as indicated by maternal serum DDE concentration) may decrease birth weight and that decreased birth weight effects associated with GLSCF consumption have decreased over time.
American Journal of Epidemiology, 2005
Polychlorinated biphenyls (PCBs), once used widely in transformers and other applications, and 1,1-dichloro-2,2bis(p-chlorophenyl)ethylene (DDE), the main metabolite of the pesticide 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), are hormonally active agents. Changes in menstrual cycle functioning associated with PCBs and DDE, and increased odds of spontaneous abortion associated with DDE, suggest that these compounds could affect fertility. The authors investigated the association between PCB and DDE exposure and time to pregnancy by using serum levels measured in 390 pregnant women in the Collaborative Perinatal Project enrolled at 12 study centers in the United States from 1959 to 1965. They estimated adjusted fecundability odds ratios by using Cox proportional hazards modeling for discrete time data. Compared with time to pregnancy for women in the lowest exposure category (PCBs <1.24 lg/liter, DDE <14 lg/liter), time to pregnancy increased for women in the highest exposure category in terms of both PCBs (fecundability odds ratio for PCBs 5.00 lg/liter ¼ 0.65, 95% confidence interval: 0.36, 1.18) and DDE (fecundability odds ratio for DDE 60 lg/liter ¼ 0.65, 95% confidence interval: 0.32, 1.31). Overall, time to pregnancy increased with increasing serum PCB levels but was less suggestive of an association with DDE. Both trends were imprecise and attenuated when expressed on a lipid basis. Overall, evidence of an association between PCB or DDE exposure and time to pregnancy was weak and inconclusive.
Environmental Health Perspectives, 1998
Polyhlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyis (PCBs) were analyzed in 167 random human milk samples from urban and rral areas in Finland. Dietary habits and background information on each mother and child were gathered by questionnaire. Body mass indexes (BMI) before pregnancy and delivery in the mral area were 5-10% higher than in the urban area, but fat content of mother's milk was about 10% higher in the urban area. The mean weights of children (t standard deviation) were similar in the rual and urban areas among prinmiparae, 3,500 * 597 g and 3,505 * 454 g,.respectively, although dioxin international toxic equivalents (I-TEQs) were significantly higher in the urban area. The mother's level of education did not affect the weight of the child, but concentrations of PCDDs/PCDFs (l-TEQ 2,3,4,7,8-Cl, dibenzofuran, 1,2,3,7,8-Cl5 dibenzodioxn) and PCBs [sum of PCBs (XPCB), PCB-TEQ, and most PCB congeners] increased with advanced education. This is considered to be due to differences in the mother's consumption of fish. The birth weight, especialy of boys, slighdty decreased with increasing concentrations of I-TEQ, 2,3,4,7,8-Cl5 dibenzofuran, 1,2,3,7,8-Cl, dibenzodioxin, and 2,3,7,8-Cl4 dibenzodioxin; however, when the analysis was restricted to primiparac, there was no statistically significant correlation between birth weight and the concentrtions of PCDDs/PCDFs. No correlation was found between the weight of the child and ZPCBs, PCB-TEQs, or individual PCB congeners in the whole material or among priniparae, or among boys or girls. The concentrations of PCDDs/PCDFs and EPCBs in human milk were modeled for primiparae by weighing fish consumption, age of mother, milk fat content, and BMI before pregnancy. The linear regression resulted in values of R = 0.67 and 0.30 for the modeled dioxin I-TEQs in the urban and rural areas, respectively, and the corresponding values for XPCBs of R = 0.60 and 0.11. The increase of PCDD/PCDF body burden was calculated to be on average 0.58 pg I-TEQ/g milk fat/year in the urban area and 0.39 pg I-TEQ/g milk fatlyear in the rural area.
American Journal of Epidemiology, 1998
The authors examined the hypothesized association between the body burden of polychlorinated biphenyls (PCB) in women and the risk of low birth weight for their infants. In Sweden, a main exposure route for PCBs and other persistent organochlorine compounds is through the consumption of fatty fish from the Baltic Sea (on the Swedish east coast). A previous comparison between a cohort of consumers of large quantities of fish from the Swedish east coast and a reference population, together with a following analysis based on questionnaire data from a case-control study within the east coast cohort, supported the hypothesized association. In 1995, blood samples were collected from the wives and ex-wives of fishermen from the Swedish east coast (n = 192) who had given birth during the period 1973-1991. Cases (n = 57), i.e., infants with low birth weight (1,500-2,750 g), were matched with controls (n = 135; birth weight, 3,250-4,500 g) on gender, parity, and calendar year of birth. The concentration of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) in plasma was analyzed; it has been suggested that CB-153 is a relevant biomarker of exposure to PCBs. The concentration of CB-153 in the plasma of mothers during the year of childbirth was "estimated" using some alternative plausible kinetic models. For two alternative estimated exposure datasets, which were focused on separately, an increase in the risk of a low birth weight was observed at a CB-153 concentration of 300 and 400 ng/g lipid weight, respectively (adjusted odds ratios of 2.1 (95% confidence interval (Cl) 1.0-4.7) and 2.3 (95% Cl 0.9-5.9)). The present results strengthen the findings reported previously for this study population.