33 research outputs found

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

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    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

    Determination of phthalate metabolites in human urine using column switching LC-MS/MS

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    The need for sensitive and rapid methods for determination of human exposure to phthalates has increased in the recent years. This is due to ubiquitous use of phthalates and the potential health risks associated with exposure to them. This thesis presents an accurate, sensitive and automated analytical method for measuring 13 phthalate metabolites (free and conjugated) in human urine using on-line solid phase extraction coupled to high performance liquid chromatography – electrospray ionization – tandem mass spectrometry. A small volume of urine sample (300 μL) is required. Glucoronidated phthalate metabolites are deconjugated by incubation with glucoronidase enzyme (Escherihia coli-K 12) and the reaction is stopped by adding formic acid. This is the only sample preparation needed prior to injection into the column switching system. Thus the method involves minimal sample handling and minimizes possible contaminations from the surroundings. The method has been validated by spiking synthetic urine at 11 concentration levels in the range of 0.1-500 ng phthalate metabolites/mL synthetic urine. For 12 out of 13 phthalate metabolites isotopically labelled internal standards were used. The method is sensitive with limits of detection in the low nanogram range (0.01-0.10 ng phthalate metabolite/mL urine), and rapid with total run time of 27 minutes. The accuracy of the method given as recovery relative to the internal standard was 90-120% (in the range of 1-500 ng phthalate metabolite/ mL urine). The repeatability, given as relative standard deviation, was below 20% for most compounds. The accuracy was also evaluated by analyzing two urine samples from the “External Quality Assessment Scheme” and was found satisfactory. The method has been applied on 17 samples of human urine from three Norwegian women. All 13 phthalate metabolites were found to be above the limit of detection and in the same concentration ranges as found in other studies. Most phthalate metabolites were found to be strongly intercorrelated. The high sensitivity, high throughput and minimal manual handling make the method suitable for large-scale human biomonitoring studies

    Pregnancy Exposure to Phenols and Anthropometric Measures in Gestation and at Birth

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    International audienceBackground: Some synthetic phenols alter pathways involved in fetal development. Despite their high within-subject temporal variability, earlier studies relied on spot urine samples to assess pregnancy exposure. In this study, we examined associations between prenatal phenol exposure and fetal growth. Methods: We measured concentrations of two bisphenols, four parabens, benzophenone-3, and triclosan in 478 pregnant women in two weekly pools of 21 samples each, collected at 18 and 34 gestational weeks. We used adjusted linear regressions to study associations between phenol concentrations and growth outcomes assessed twice during pregnancy and at birth. Results: Benzophenone-3 was positively associated with all ultrasound growth parameters in at least one time point, in males but not females. In females, butylparaben was negatively associated with third-trimester abdominal circumference and weight at birth. We observed isolated associations for triclosan (negative) and for methylparaben and bisphenol S (positive) and late pregnancy fetal growth. Conclusions: Our results suggest associations between prenatal exposure to phenols and fetal growth. Benzophenone-3 was the exposure most consistently (positively) associated across all growth parameters

    Pre- and early post-natal exposure to phthalates and DINCH in a new type of mother-child cohort relying on within-subject pools of repeated urine samples

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    International audienceFor non-persistent chemicals such as phthalates, a single spot urine sample only reflects exposure in the past few hours. Collecting repeated urine samples for each participant over windows of sensitivity is expected to improve exposure characterization but has rarely been done. We aimed to rely on within-subject pools of repeated urine samples to assess phthalate exposure during pregnancy and infancy. Women of the French SEPAGES mother-child cohort were asked to collect three urine samples per day over seven consecutive days, twice during their pregnancy (approximatively second (T2) and third (T3) trimesters). For their infants they also collected one sample per day during a week at two (M2) and twelve months (M12). Samples were pooled (within-subject, within-period) prior to phthalate and DINCH metabolite concentrations assessment. Number of pooled samples assayed was 477, 456, 152 and 100 for T2, T3, M2 and M12, respectively. All metabolites were detected in more than 95% of the pooled samples except for the two DINCH metabolites (oh- and oxo-MINCH), MMCHP and oh-MPHP at M2 for which detection frequencies ranged between 64% and 88%. Maternal concentrations of MiBP, MBzP, DEHP metabolites and oxo-MiNP decreased between 2014 and 2017, whereas concentrations of oh-MiNP and the two DINCH metabolites increased (Mann-Kendall p-values < 0.05). While improved compared to studies that relied on spot samples, Intraclass Correlation Coefficients for the pregnancy were below 0.40 for most metabolites. Spearman correlation coefficients between pooled samples collected in infancy were lower than those observed during pregnancy, and were all below 0.30. Exposure to emerging phthalate substitutes such as DINCH and DPHP seems widespread among pregnant women and infants. Collecting repeated urine samples in pregnant women and infants is feasible. The relatively low correlation across trimesters and between maternal and infant samples highlights the need to collect biospecimens in the assumed sensitive time window

    Associations between a mixture of phenols and phthalates and child behaviour in a French mother–child cohort with repeated assessment of exposure

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    International audienceBackground: Synthetic phenols and phthalates can interfere with biological pathways involved in brain development. Despite the high within-subject temporal variability of urinary concentrations observed for their metabolites, studies investigating effects of phenols and phthalates on child behaviour often relied on a limited number of spot biospecimens to assess exposure. Besides, the majority did not consider mixture effects.Objectives: To study the combined effect of prenatal exposure to synthetic phenols and phthalates on child behaviour using repeated exposure measurements.Methods: We assessed concentrations of 12 phenols, 13 phthalate and 2 non-phthalate plasticizer metabolites in within-subject pools of multiple urine samples (median = 21 samples per individual pool) collected at two distinct time points during pregnancy in 416 mother-child pairs from the French SEPAGES cohort. Child behaviour was evaluated at two years using the Child Behaviour Checklist 1.5-5 (CBCL). Associations between a mixture of biomarkers of exposure and externalizing and internalizing behaviour scores were studied using adjusted Weighted Quantile Sum (WQS) regressions with a repeated holdout validation (100 repetitions).Results: The positive WQS indexes were associated with both the externalizing and internalizing behaviour scores in the whole population, indicating greater risk of behavioural problems. Stratification for child sex suggested stronger associations in girls than boys. On average, girls externalizing and internalizing scores increased by 3.67 points (95% CI: 1.24, 6.10) and 2.47 points (95 %CI: 0.60, 4.33) respectively, for an increase of one tertile in the WQS index, compared with 1.70 points (95 %CI: -0.42, 3.81) and 1.17 points (95 %CI: -0.50, 2.84) in boys. Main contributors for the associations observed in girls were bisphenol A (weight of 18%), triclosan (17%) and monoethyl phthalate (MEP, 15%) for the externalizing score and MEP (19%), mono-benzyl phthalate (MBzP, 19%) and mono-n-butyl phthalate (MnBP, 16%) for the internalizing score.Discussion: Our results suggest adverse associations between in utero exposure to a mixture of phenols and phthalates and child behaviour, mainly in girls. Public health consequences may be substantial due to the widespread exposure of the population to these compounds

    Perfluoroalkyl substances (PFASs) in white whales (Delphinapterus leucas) from Svalbard – A comparison of concentrations in plasma sampled 15 years apart

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    The objective of the present study was to investigate recent concentrations of perfluoroalkyl substances (PFASs) in white whales (Delphinapterus leucas) from Svalbard and compare them to concentrations found in white whales sampled from that same area 15 years ago. Plasma collected from live-captured white whales from two time periods (2013–2014, n = 9, and 1996–2001, n = 11) were analysed for 19 different PFASs. The 11 PFASs detected included seven C8–C14 perfluoroalkyl carboxylates (PFCAs) and three C6–C8 perfluoroalkyl sulfonates (PFSAs) as well as perfluorooctane sulfonamide (FOSA). Recent plasma concentrations (2013–2014) of the dominant PFAS in white whales, perfluorooctane sulfonate (PFOS; geometric mean = 22.8 ng/mL), was close to an order of magnitude lower than reported in polar bears (Ursus maritimus) from Svalbard. PFOS concentrations in white whales were about half the concentrations in harbour (Phoca vitulina) and ringed (Pusa hispida) seals, similar to hooded seals (Cystophora cristata) and higher than in walruses (Odobenus rosmarus) from that same area. From 1996 to 2001 to 2013–2014, plasma concentrations of PFOS decreased by 44%, whereas four C9-12 PFCAs and total PFCAs increased by 35–141%. These results follow a similar trend to what has been reported in other studies of Arctic marine mammals from Svalbard. The most dramatic change has been the decline of PFOS concentrations since 2000, corresponding to the production phase-out of PFOS and related compounds in many countries around the year 2000 and a global restriction on these substances in 2009. Still, the continued dominance of PFOS in white whales, and increasing concentration trends for several PFCAs, even though exposure is relatively low, calls for continued monitoring of concentrations of both PFCAs and PFSAs and investigation of biological effects

    Perfluoroalkyl substances (PFASs) in white whales (Delphinapterus leucas) from Svalbard – A comparison of concentrations in plasma sampled 15 years apart

    No full text
    The objective of the present study was to investigate recent concentrations of perfluoroalkyl substances (PFASs) in white whales (Delphinapterus leucas) from Svalbard and compare them to concentrations found in white whales sampled from that same area 15 years ago. Plasma collected from live-captured white whales from two time periods (2013–2014, n = 9, and 1996–2001, n = 11) were analysed for 19 different PFASs. The 11 PFASs detected included seven C8–C14 perfluoroalkyl carboxylates (PFCAs) and three C6–C8 perfluoroalkyl sulfonates (PFSAs) as well as perfluorooctane sulfonamide (FOSA). Recent plasma concentrations (2013–2014) of the dominant PFAS in white whales, perfluorooctane sulfonate (PFOS; geometric mean = 22.8 ng/mL), was close to an order of magnitude lower than reported in polar bears (Ursus maritimus) from Svalbard. PFOS concentrations in white whales were about half the concentrations in harbour (Phoca vitulina) and ringed (Pusa hispida) seals, similar to hooded seals (Cystophora cristata) and higher than in walruses (Odobenus rosmarus) from that same area. From 1996 to 2001 to 2013–2014, plasma concentrations of PFOS decreased by 44%, whereas four C9-12 PFCAs and total PFCAs increased by 35–141%. These results follow a similar trend to what has been reported in other studies of Arctic marine mammals from Svalbard. The most dramatic change has been the decline of PFOS concentrations since 2000, corresponding to the production phase-out of PFOS and related compounds in many countries around the year 2000 and a global restriction on these substances in 2009. Still, the continued dominance of PFOS in white whales, and increasing concentration trends for several PFCAs, even though exposure is relatively low, calls for continued monitoring of concentrations of both PFCAs and PFSAs and investigation of biological effects
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