Azemira Sabaredzovic

Placental transfer of perfluorinated compounds is selective--a Norwegian Mother and Child sub-cohort study.

Perfluorinated compounds (PFCs) comprise a large group of man-made fluorinated chemicals used in a number of consumer products and industrial applications. PFCs have shown to be persistent, bio-accumulative and widespread in the environment. Animal studies have demonstrated hepatotoxicity, immunotoxicity, developmental toxicity as well as hormonal effects. We investigated prenatal exposure to several PFCs and detected up to seven different PFCs in 123 paired samples of human maternal and cord blood, from a subcohort of the Norwegian Mother and Child Cohort Study (MoBa). The maternal and foetal levels were significantly correlated for all PFCs tested with median PFC concentrations in cord blood ranging between 30 and 79% of the maternal concentrations, demonstrating placental passage. The composition of the different PFCs varied between cord and maternal blood, with a higher proportion of shorter chained PFCs together with a higher amount of the branched isomers of perfluorooctane sulfonate (PFOS) in cord blood. Additionally, the sulfonate group seems to impede transfer efficiency. This indicates a selective placental passage of the different PFCs and hence a specific foetal exposure.

Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women.

BACKGROUND Perfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women. METHODS This study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003 to 2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks of gestation and a dietary questionnaire was completed at 22 weeks of gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaikes information criterion (AIC). RESULTS Parity was the determinant with the largest influence on plasma PFAS concentrations, with r(2) between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p<0.001 except for PFHxS, p<0.01). In all these models, duration of breastfeeding was associated with reduced PFAS levels. PFOA showed the largest reduction from breastfeeding, with a 2-3% reduction per month of breastfeeding in typical cases. Levels of PFOS, PFOA, and PFNA increased with time since most recent pregnancy. While pregnancy-related factors were the most important predictors, diet was a significant factor explaining up to 4% of the variance. One quartile increase in estimated dietary PFAS intake was associated with plasma PFOS, PFOA, PFHxS, and PFNA concentration increases of 7.2%, 3.3%, 5.8% and 9.8%, respectively, resulting in small, although non-trivial absolute changes in PFAS concentrations. CONCLUSION Previous pregnancies and breastfeeding duration were the most important determinants of PFASs in this sample of pregnant women.

Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study

BACKGROUND Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. METHODS This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. RESULTS Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI=2.5, 4.9). CONCLUSION Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal.

Reliability of perfluoroalkyl substances in plasma of 100 women in two consecutive pregnancies

The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently under active investigation. Such investigations typically rely on a single measure of PFAS concentration, yet the longer-term reliability of a single measure has not been well characterized, especially among reproductive-aged women. Our aim was to investigate the association between PFAS plasma concentrations of 100 women in two consecutive pregnancies and explore changes in plasma concentration related to reproductive factors. The women in our study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from 2003 to 2009. About half of them breastfed exclusively for 6 months and the rest of the participants did not breastfeed between the two consecutive pregnancies (median time between pregnancies: 18 months). Maternal blood was collected at mid-pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were restricted to 6 PFASs that were quantifiable in more than 80% of the samples. We estimated the correlation between repeated PFAS measurements, the percentage change between pregnancies and the effect of several reproductive factors in multivariate linear regression models of PFAS concentrations in the second pregnancy. The Pearson correlation coefficient between repeated PFAS measurements was, for perfluorooctane sulfonate (PFOS), 0.80; perfluorooctanoate (PFOA), 0.50; perfluorohexane sulfonate (PFHxS), 0.74; perfluorononanoate (PFNA), 0.39; perfluoroundecanoate (PFUnDA), 0.71; and perfluorodecanoate (PFDA), 0.60. Adjustment for maternal age, delivery year, and time and breastfeeding between pregnancies did not substantially affect the observed correlations. We found 44-47% median reductions in the concentrations of PFOS, PFOA and PFHxS between pregnancies, while the change in concentrations between pregnancies was smaller and more variable for PFNA, PFUnDA and PFDA. The variation in plasma concentrations in the second pregnancy was mainly accounted for by the concentration in the first pregnancy; for PFOS, PFOA, and PFNA, breastfeeding also accounted for a substantial proportion. In conclusion, we found the reliability of PFAS measurements in maternal plasma to be moderate to high, and in these data, several factors, especially breastfeeding, were related to plasma concentrations.

In utero exposure to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia (Min/+) mice

We examined whether perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) had obesogenic effects and if they increased spontaneous intestinal tumorigenesis in the mouse model C57BL/6J-Min/+ (multiple intestinal neoplasia) after in utero exposure. The dams were exposed to PFOA or PFOS (0.01, 0.1 or 3.0mg/kg bw/day) by po gavage on GD1-17. The Min/+ and wild-type offspring were terminated at week 11 for examination of intestinal tumorigenesis or at week 20 for obesogenic effect, respectively. Body weights of the dams and pups were recorded throughout life. Food intake was determined at week 6 and 10. Blood glucose (non-fasted) was measured at week 6 and 11. No obesogenic effect of PFOA or PFOS was observed up to 20 weeks of age. PFOA or PFOS did not increase the incidence or number of tumors in the small intestine or colon of the Min/+ mice or affect their location along the intestines. Feed intake was not affected. There were some indications of toxicity of PFOA, but not of PFOS. There was lower survival of pups after 3.0mg/kg PFOA, lower body weight in pups after 3.0 and possibly 0.1mg/kg PFOA, and increased relative liver weight after 0.01 and possibly 0.1mg/kg PFOA. Plasma glucose was lower after 0.01 and 0.1mg/kg PFOA. In conclusion, exposure to PFOA and PFOS in utero with the doses used did not have obesogenic effect on either Min/+ or wild-type mice, at least not up to 11 or 20 weeks of age, nor increased intestinal tumorigenesis in Min/+ mice.

Analysis of Alcohol and Drugs in Oral Fluid From Truck Drivers in Norway

Objective: To examine alcohol and drug use among truck drivers compared to car or van drivers in Norway by analyzing samples of oral fluid. Methods: Drivers were selected for a voluntary and anonymous study using a stratified multistage cluster sampling procedure. Drivers of trucks were recruited at two control stations for heavy vehicles in southeastern Norway in collaboration with the Norwegian Roads Administration, and drivers of cars and vans were recruited in a roadside survey in collaboration with the mobile police service. Samples of oral fluid were taken by using the Statsure Saliva Sampler (Statsure Diagnostic Systems, Framingham, MA), and the drivers’ gender, age, and nationality were recorded. Samples of oral fluid were analyzed for alcohol or drugs, in total 28 psychoactive substances. Results: About 97 percent of the truck drivers and 94 percent of the car or van drivers agreed to participate in the study. Of the 882 studied truck drivers studied, 1.4 percent were female and 29.1 percent were Norwegian; of the 5305 car or van drivers, 27.6 percent were female and 90.9 percent were Norwegian. Alcohol or drugs were found in 1.9 and 6.6 percent of the samples from truck drivers and car/van drivers, respectively. The adjusted odds ratio (OR) for the detection of a psychoactive substance in a sample from a truck driver compared to car or van driver was 0.29; the 95 percent confidence interval (95% CI) was 0.17 to 0.53. The adjusted OR for the detection of an illegal drug was 0.42 (95% CI: 0.18–0.82), the adjusted OR for the detection of a psychoactive medicinal drug was 0.29 (95% CI: 0.13–0.68), and the adjusted OR for the detection of alcohol was 0.13 (95% CI: 0.02–1.10). Conclusions: The proportion of oral fluid samples containing psychoactive substances was lower for truck drivers than for car or van drivers.

Perfluoroalkyl substances measured in breast milk and child neuropsychological development in a Norwegian birth cohort study

Perfluoroalkyl substances (PFASs) are chemicals with potential neurotoxic effects although the current evidence is still limited. This study investigated the association between perinatal exposure to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and neuropsychological development assessed at 6, 12 and 24 months. We measured PFOS and PFOA in breast milk samples collected one month after delivery by mothers of children participating in the HUMIS study (Norway). Cognitive and psychomotor development was measured at 6 and at 24 months using the Ages and Stages Questionnaire (ASQ-II). Behavioral development was assessed using the infant-toddler symptom checklist (ITSC) at 12 and at 24 months. Weighted logistic regression and weighted negative binomial regression models were applied to analyze the associations between PFASs and ASQ-II and ITSC, respectively. The median concentration of PFOS was 110 ng/L, while the median for PFOA was 40 ng/L. We did not detect an increased risk of having an abnormal score in ASQ-II at 6 months or 24 months. Moreover, no consistent increase in behavioral problems assessed at 12 and 24 months by ITSC questionnaire was detected. We observed no association between perinatal PFOS and PFOA exposure and early neuropsychological development. Further longitudinal studies are needed to confirm the effects of these compounds on neuropsychological development in older children.

Perfluoroalkyl Substances During Pregnancy and Validated Preeclampsia Among Nulliparous Women in the Norwegian Mother and Child Cohort Study

Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003-2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)(2)), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.

Phthalate metabolites in Norwegian mothers and children: Levels, diurnal variation and use of personal care products

Exposure to phthalates has been associated with reproductive and developmental toxicity. Data on levels of these compounds in the Norwegian population is limited. In this study, urine samples were collected from 48 mothers and their children in two counties in Norway. Eleven different phthalate metabolites originating from six commonly used phthalates in consumer products were determined. Concentrations of phthalate metabolites were significantly higher in children compared to mothers except for mono-ethyl phthalate (MEP). The mothers provided several urine samples during 24hours (h) and diurnal variation showed that the concentrations in the morning urine samples (24-8h) were significantly higher than at other time-periods for most of the phthalate metabolites. Intraclass correlation coefficients (ICCs) for 24-hour time-period were in the range of 0.49-0.81. These moderate to high ICCs indicate that one spot urine sample can be used to estimate the exposure to phthalates. Since a significant effect of time of day was observed, it is still advisable to standardize the collection time point to reduce the variation. For the mothers, the use of personal care products (PCPs) were less associated with morning urine samples than early day (8-12h) and evening (16-24h) urine samples. The use of perfume and hair products were positively associated with the urinary concentrations of low molecular weight phthalates. Use of shower soap and shampoo were positively associated with urinary concentration of di(2-ethylhexyl) phthalate (DEHP) metabolites. For children, face cream use was positively associated with phthalate metabolites in the morning samples, and hand soap use was negatively associated with concentration of urinary DEHP metabolites in afternoon/evening samples. Since different PCPs were associated with the urinary phthalate metabolites in different time-periods during a day, more than one spot urine sample might be required to study associations between urinary phthalate metabolites and the use of PCPs.

Examining confounding by diet in the association between perfluoroalkyl acids and serum cholesterol in pregnancy.

BACKGROUND Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have consistently been associated with higher cholesterol levels in cross sectional studies. Concerns have, however, been raised about potential confounding by diet and clinical relevance. OBJECTIVE To examine the association between concentrations of PFOS and PFOA and total cholesterol in serum during pregnancy taking into considerations confounding by diet. METHODS 854 Danish women who gave birth in 1988-89 and provided a blood sample and reported their diet in week 30 of gestation. RESULTS Mean serum PFOS, PFOA and total cholesterol concentrations were 22.3 ng/mL, 4.1 ng/mL and 7.3 mmol/L, respectively. Maternal diet was a significant predictor of serum PFOS and PFOA concentrations. In particular intake of meat and meat products was positively associated while intake of vegetables was inversely associated (P for trend <0.01) with relative difference between the highest and lowest quartile in PFOS and PFOA concentrations ranging between 6% and 25% of mean values. After adjustment for dietary factors both PFOA and PFOS were positively and similarly associated with serum cholesterol (P for trend ≤0.01). For example, the mean increase in serum cholesterol was 0.39 mmol/L (95%CI: 0.09, 0.68) when comparing women in the highest to lowest quintile of PFOA concentrations. In comparison the mean increase in serum cholesterol was 0.61 mmol/L (95%CI: 0.17, 1.05) when comparing women in the highest to lowest quintile of saturated fat intake. CONCLUSION In this study associations between PFOS and PFOA with serum cholesterol appeared unrelated to dietary intake and were similar in magnitude as the associations between saturated fat intake and serum cholesterol.