The Senior Citizens' Clubs in the Urban Area and the Orientation of Their Activating Policy -Results and Inference from a Questionnaire Survey in Hyogo Prefecture-

Background: Several studies have reported decreases in birth size associated with exposure to organochlorine compounds (OCs), but uncertainties remain regarding the critical windows of prenatal exposure and the effects on fetal body segments. Objective: We examined the relationship between prenatal OC concentrations and fetal anthropometry. Methods: We measured 4,4´-dichlorodiphenyldichloroethylene (4,4´-DDE), hexachlorobenzene (HCB), and polychlorinated biphenyl (PCB) congeners (138, 153, and 180) in 2,369 maternal and 1,140 cord serum samples in four Spanish cohorts (2003–2008). We used linear mixed models to obtain longitudinal growth curves for estimated fetal weight (EFW), abdominal circumference (AC), biparietal diameter (BPD), and femur length (FL) adjusted by parental and fetal characteristics. We calculated standard deviation (SD) scores of growth at 0–12, 12–20, and 20–34 weeks of gestation as well as size at gestational week 34 for the four parameters. We studied the association between OCs and the fetal outcomes by cohort-specific linear models and subsequent meta-analyses. Results: PCBs were associated with a reduction in AC up to mid-pregnancy, and BPD and FL from gestational week 20 onward. An inverse association was also found between HCB and AC growth in early pregnancy. The reduction of these parameters ranged from –4% to –2% for a doubling in the OC concentrations. No association between 4,4´-DDE and fetal growth was observed. Conclusions: To our knowledge, this is the first study to report an association between prenatal exposure to some PCBs and HCB and fetal growth: AC during the first two trimesters of pregnancy, and BPD and FL later in pregnancy

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk

dyab115Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts.We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline.Some associations were observed at higher concentrations of p, p’-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95\.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted \gt;6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted \gt;6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk.Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer.Peer reviewe

Plasma concentrations of persistent organic pollutants and pancreatic cancer risk

Background: Findings and limitations of previous studies on persistent organic pollutants (POPs) and pancreatic cancer risk support conducting further research in prospective cohorts. Methods: We conducted a prospective case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Participants were 513 pancreatic cancer cases and 1020 matched controls. Concentrations of 22 POPs were measured in plasma collected at baseline. Results: Some associations were observed at higher concentrations of p, p'-DDT, trans-nonachlor, β-hexachlorocyclohexane and the sum of six organochlorine pesticides and of 16 POPs. The odds ratio (OR) for the upper quartile of trans-nonachlor was 1.55 (95% confidence interval 1.06-2.26; P for trend = 0.025). Associations were stronger in the groups predefined as most valid (participants having fasted >6 h, with microscopic diagnostic confirmation, normal weight, and never smokers), and as most relevant (follow-up ≥10 years). Among participants having fasted >6 h, the ORs were relevant for 10 of 11 exposures. Higher ORs were also observed among cases with microscopic confirmation than in cases with a clinical diagnosis, and among normal-weight participants than in the rest of participants. Among participants with a follow-up ≥10 years, estimates were higher than in participants with a shorter follow-up (for trans-nonachlor: OR = 2.14, 1.01 to 4.53, P for trend = 0.035). Overall, trans-nonachlor, three PCBs and the two sums of POPs were the exposures most clearly associated with pancreatic cancer risk. Conclusions: Individually or in combination, most of the 22 POPs analysed did not or only moderately increased the risk of pancreatic cancer

Association between exposure to organochlorine compounds and maternal thyroid status: Role of the iodothyronine deiodinase 1 gene

Introduction: Exposure to organochlorine compounds (OCs) may interfere with thyroid hormone (TH) homeostasis. The disruption of the deiodinase (DIO) enzymes has been proposed as a mechanism of action. Aim: To evaluate the association between exposure to OCs and TH status in pregnant women, as well as to explore the role of genetic variations in the DIO1 and DIO2 genes. Methods: The study population (n = 1128) was composed of pregnant women who participated in the INMA Project (Spain, 2003–2006). Hexachlorobenzene (HCB), 1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene (4,4´-DDE), b-hexachlorocyclohexane (b-HCH), polychlorobiphenyl (PCB) congeners 138, 153 and 180, thyroid stimulating hormone (TSH), total triiodothyronine (TT3) and free thyroxine (FT4) were measured in serum samples taken during the first trimester of pregnancy (mean [standard deviation (SD)]: 13.5 [2] weeks of gestation). Polymorphisms in DIO1 (rs2235544) and DIO2 (rs12885300) were genotyped in maternal DNA. Sociodemographic and dietary characteristics were obtained by questionnaire. Results: A 2-fold increase in HCB was associated with lower TT3 (% change = − 1.48; 95%CI: − 2.36, − 0.60). Women in the third tertile for b-HCH had lower TT3 (% change = − 3.19; 95%CI: − 5.64, − 0.67). The interactions between DIO1 rs2235544 and PCB153 and b-HCH were statistically significant. The inverse association between PCB153 and TT3 was the strongest among women with AA genotype. Women with CC genotype presented the strongest inverse association between b-HCH and FT4. Conclusion: Exposure to HCB and b-HCH was associated to a disruption in maternal TT3. The DIO1 rs2235544 SNP modified the association between exposure to some of the OCs (specifically b-HCH and PCB153) and maternal thyroid hormone levels. These results strengthen the hypothesis that DIO enzymes play a role in explaining the disruption of thyroid hormones in relation to exposure to OCs. Abbreviations 4,4′-DDE1,1-dichloro-2,2-bis(4-chlorophenyl)ethylene b-HCHb-hexachlorocyclohexane DIOdeiodinase FT4free thyroxine HCBHexachlorobenzene LODlimit of detection OCsorganochlorine compounds PCBspolychlorobiphenyls TBGthyroxine-binding globulin THthyroid hormones TSHthyroid stimulating hormone TTRtransthyretin TT3total triiodothyronin

Prenatal exposure to endocrine disrupting chemicals and risk of being born small for gestational age: Pooled analysis of seven European birth cohorts

Background and aims: There is evidence that endocrine disrupting chemicals (EDCs) have developmental effects at environmental concentrations. We investigated whether some EDCs are associated with the adverse birth outcome Small for Gestational Age (SGA). Methods: We used PCB 153, p,p’-DDE, HCB, PFOS and PFOA measured in maternal, cord blood or breast milk samples of 5446 mother-child pairs (subset of 693 for the perfluorinated compounds) from seven European birth cohorts (1997–2012). SGA infants were those with birth weight below the 10th percentile for the norms defined by gestational age, country and infant's sex. We modelled the association between measured or estimated cord serum EDC concentrations and SGA using multiple logistic regression analyses. We explored effect modification by child's sex and maternal smoking during pregnancy. Results: Among the 5446 newborns, 570 (10.5%) were SGA. An interquartile range (IQR) increase in PCB 153 was associated with a modestly increased risk of SGA (odds ratio (OR) of 1.05 [95% CI: 1.04–1.07]) that was stronger in girls (OR of 1.09 [95% CI: 1.04–1.14]) than in boys (OR of 1.03 [95% CI: 1.03–1.04]) (p-interaction = 0.025). For HCB, we found a modestly increased odds of SGA in girls (OR of 1.04 [95% CI: 1.01–1.07] per IQR increase), and an inverse association in boys (OR of 0.90 [95% CI: 0.85–0.95]) (p-interaction = 0.0003). Assessment of the HCB-sex-smoking interaction suggested that the increased odds of SGA associated with HCB exposure was only in girls of smoking mothers (OR of 1.18 [95% CI: 1.11–1.25]) (p-interaction = 0.055). Higher concentrations of PFOA were associated with greater risk of SGA (OR of 1.64 [95% CI: 0.97–2.76]). Elevated PFOS levels were associated with increased odds of SGA in newborns of mothers who smoked during pregnancy (OR of 1.63 [95% CI: 1.02–2.59]), while an inverse association was found in those of non-smoking mothers (OR of 0.66 [95% CI: 0.61–0.72]) (p-interaction = 0.0004). No significant associations were found for p,p’-DDE. Conclusions: Prenatal environmental exposure to organochlorine and perfluorinated compounds with endocrine disrupting properties may contribute to the prevalence of SGA. We found indication of effect modification by child's sex and smoking during pregnancy. The direction of the associations differed by chemical and these effect modifiers, suggesting diverse mechanisms of action and biological pathways