| 1. |
- Bjorvang, Richelle D., et al.
(författare)
-
Persistent organic pollutants, pre-pregnancy use of combined oral contraceptives, age, and time-to-pregnancy in the SELMA cohort
- 2020
-
Ingår i: Environmental Health. - : BMC. - 1476-069X. ; 19:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background We are exposed to several chemicals such as persistent organic pollutants (POPs) in our everyday lives. Prior evidence has suggested that POPs may have adverse effects on reproductive function by disrupting hormone synthesis and metabolism. While there is age-related decline of fertility, the use of hormonal combined oral contraceptives (COCs) and its association to return of fertility remains controversial. The goal of this study is to investigate the association between exposure to POPs, both individually and as a mixture, and fecundability measured as time-to-pregnancy (TTP) according to pre-pregnancy use of COCs and age. Methods Using the SELMA (Swedish Environmental Longitudinal Mother and Child, Allergy and Asthma) study, we have identified 818 pregnant women aged 18-43 years (mean 29 years) with data on how long they tried to get pregnant and what was their most recently used contraceptive method. These data were collected at enrollment to the study (median week 10 of pregnancy). Concentrations of 22 POPs and cotinine were analyzed in the blood samples collected at the same time as the questions on TTP and pre-pregnancy use of contraceptive. Analyses were done on the association between POPs exposure and TTP measured as continuous (months) and binary (infertile for those with TTP > 12 months). To study the chemicals individually, Cox regression and logistic regression were used to estimate fecundability ratios (FRs) and odds ratios (ORs), respectively. Weighted quantile sum (WQS) regression was used to investigate the chemicals as a mixture where chemicals of concern were identified above the 7.6% threshold of equal weights. To perform the subgroup analysis, we stratified the sample according to use of COCs as the most recent pre-pregnancy contraception method and age (< 29 years, and >= 29 years). The models were adjusted for parity, regularity of menses, maternal body mass index (BMI) and smoking status, and stratified as described above. Results Prior to stratification, none of the POPs were associated with fecundability while increased exposure to HCB, PCB 74 and 118 had higher odds of infertility. Upon stratification, POP exposure was significantly associated with longer TTP in women aged >= 29 years who did not use COC. Specifically, PCBs 156, 180, 183, and 187 were associated with reduced fecundability while PCBs 99, 153, 156, 180, 183, and 187 had higher odds of infertility. As a mixture, we identified the chemicals of concern for a longer TTP include PCBs 118, 156, 183, and 187. Moreover, chemicals of concern identified with increased odds of infertility were PCB 74, 156, 183, 187, and transnonachlor. Conclusion Serum concentrations of selected POPs, both as individual chemicals and as a mixture, were significantly associated with lower fecundability and increased odds of infertility in women aged 29 years and above not using COC as their most recent pre-pregnancy contraceptive. Our findings suggest that pre-pregnancy use of oral contraceptive and age may modify the link between POPs and fecundability. The differences of specific chemicals in the individual analysis and as a mixture support the need to study combination effects of chemicals when evaluating reproductive outcomes.
|
|
| 2. |
- Björvang, Richelle D., et al.
(författare)
-
Mixtures of persistent organic pollutants are found in vital organs of late gestation human fetuses
- 2021
-
Ingår i: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 283
-
Tidskriftsartikel (refereegranskat)abstract
- Persistent organic pollutants (POPs) are industrial chemicals with long half-lives. Early life exposure to POPs has been associated with adverse effects. Fetal exposure is typically estimated based on concentrations in maternal serum or placenta and little is known on the actual fetal exposure. We measured the concentrations of nine organochlorine pesticides (OCPs), ten polychlorinated biphenyl (PCB) congeners, and polybrominated diphenyl ether (PBDE) congeners by gas chromatography – tandem mass spectrometry in maternal serum, placenta, and fetal tissues (adipose tissue, liver, heart, lung and brain) in 20 pregnancies that ended in stillbirth (gestational weeks 36–41). The data were combined with our earlier data on perfluoroalkyl substances (PFASs) in the same cohort (Mamsen et al. 2019). HCB, p,p’-DDE, PCB 138 and PCB 153 were quantified in all samples of maternal serum, placenta and fetal tissues. All 22 POPs were detected in all fetal adipose tissue samples, even in cases where they could not be detected in maternal serum or placenta. Tissue:serum ratios were significantly higher in later gestations, male fetuses, and pregnancies with normal placental function. OCPs showed the highest tissue:serum ratios and PFAS the lowest. The highest chemical burden was found in adipose tissue and lowest in the brain. Overall, all studied human fetuses were intrinsically exposed to mixtures of POPs. Tissue:serum ratios were significantly modified by gestational age, fetal sex and placental function. Importantly, more chemicals were detected in fetal tissues compared to maternal serum and placenta, implying that these proxy samples may provide a misleading picture of actual fetal exposures.
|
|
| 3. |
- Björvang, Richelle D., et al.
(författare)
-
Persistent organic pollutants and the size of ovarian reserve in reproductive-aged women
- 2021
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 155
-
Tidskriftsartikel (refereegranskat)abstract
- Industrial chemicals such as persistent organic pollutants (POPs) have been associated with reduced fertility in women, including longer time-to-pregnancy (TTP), higher odds for infertility, and earlier reproductive senescence. Fertility is highly dependent on the ovarian reserve, which is composed of a prenatally determined stock of non-growing follicles. The quantity and quality of the follicles decline with age, thereby eventually leading to menopause. In the clinical setting, assessing ovarian reserve directly through the histological analysis of follicular density in ovaries is not practical. Therefore, surrogate markers of ovarian reserve, such as serum anti-Müllerian hormone (AMH) are typically used. Here, we studied associations between chemical exposure and ovarian reserve in a cohort of pregnant women undergoing elective caesarean section (n = 145) in Stockholm, Sweden. Full data (histological, clinical, serum) were available for 50 women. We estimated the size of the reserve both directly by determining the density of follicles in ovarian cortical tissue samples, and indirectly by measuring AMH in associated serum samples. Concentrations of 9 organochlorine pesticides (OCPs), 10 polychlorinated biphenyls (PCBs), 3 polybrominated diphenylethers (PBDEs) and 9 perfluoroalkyl substances (PFAS) were determined in serum, and clinical data were retrieved from electronic medical records. Healthy follicle densities (median 0, range 0–193 follicles/mm3) and AMH levels (median 2.33 ng/mL, range 0.1–14.8 ng/mL) varied substantially. AMH correlated with the density of growing follicles. Twenty-three chemicals detected in more than half of the samples were included in the analyses. None of the chemicals, alone or as a mixture, correlated with AMH, growing or atretic follicles. However, HCB, transnonachlor, PCBs 74 and 99 were associated with decreased non-growing follicle densities. HCB and transnonachlor were also negatively associated with healthy follicle density. Further, mixture of lipophilic POPs (PBDE 99, p,p’-DDE, and PCB 187) was associated with lower non-growing follicle densities. In addition, exposure to HCB, p,p’-DDE, and mixture of OCPs were significantly associated with higher odds of infertility. The results suggest that exposure to chemicals may reduce the size of ovarian reserve in humans, and strongly encourage to study mechanisms behind POP-associated infertility in women in more detail.
|
|
| 4. |
- Schillemans, Tessa, et al.
(författare)
-
Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study
- 2021
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1–0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3–2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
|
|
| 5. |
- Svensson, Katherine, et al.
(författare)
-
Prenatal exposures to mixtures of endocrine disrupting chemicals and children's weight trajectory up to age 5.5 in the SELMA study
- 2021
-
Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Exposure to endocrine disrupting chemicals (EDCs) may impact early growth, although information is limited on exposure to combination of multiple EDCs. We aimed to evaluate the effect of prenatal exposure to EDC mixtures on birthweight z-scores and childhood weight trajectories. Twenty-six proven and suspected EDCs, were analyzed in prenatal urine and blood samples from 1118 mothers participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) study. Two growth parameters were estimated from each child's weight trajectory from birth to 5.5 years of age: infant growth spurt rate and age at infant peak growth velocity (PGV). Weighted quantile sum (WQS) regression was used to estimate the mixture effect and identify chemicals of concern. A one-unit increase in the EDC mixture WQS index, was associated with decreased birthweight z-scores of 0.11 (95% CI - 0.16, - 0.06), slower infant growth spurt rate of 0.01 (95% CI - 0.03, - 0.01, on the log(10) scale), and delayed age at infant PGV of 0.15 months (95% CI 0.07, 0.24) after adjusting for potential confounders. Stratified analysis by sex, showed that delayed age at infant PGV was mostly observed in girls with 0.51 months (95% CI 0.26, 0.76). Identified chemicals of concern included perfluorinated alkyl substances (PFAS), Triclosan, phthalates, non-phthalate plasticizers, bisphenols, polycyclic aromatic hydrocarbons, pesticides and PCBs. Prenatal exposure to EDC mixtures was associated with lower birthweight and altered infant weight gain trajectories.
|
|
| 6. |
- Tanner, Eva M, et al.
(författare)
-
Early prenatal exposure to suspected endocrine disruptor mixtures is associated with lower IQ at age seven
- 2020
-
Ingår i: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 134, s. 1-11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Endocrine disrupting chemicals (EDCs) are xenobiotics with the ability to interfere with hormone action, even at low levels. Prior environmental epidemiology studies link numerous suspected EDCs, including phthalates and bisphenol A (BPA), to adverse neurodevelopmental outcomes. However, results for some chemicals were inconsistent and most assessed one chemical at a time.Objectives: To evaluate the overall impact of prenatal exposure to an EDC mixture on neurodevelopment in school-aged children, and identify chemicals of concern while accounting for co-exposures.Methods: Among 718 mother-child pairs from the Swedish Environmental Longitudinal, Mother and child, Asthma and allergy study (SELMA) study, we used Weighted Quantile Sum (WQS) regression to assess the association between 26 EDCs measured in 1st trimester urine or blood, with Wechsler Intelligence Scale for Children (IV) Intelligence Quotient (IQ) scores at age 7 years. Models were adjusted for child sex, gestational age, mother's education, mother's IQ (RAVEN), weight, and smoking status. To evaluate generalizability, we conducted repeated holdout validation, a machine learning technique.ResultsUsing repeated holdout validation, IQ scores were 1.9-points (CI = −3.6, −0.2) lower among boys for an inter-quartile-range (IQR) change in the WQS index. BPF made the largest contribution to the index with a weight of 14%. Other chemicals of concern and their weights included PBA (9%), TCP (9%), MEP (6%), MBzP (4%), PFOA (6%), PFOS (5%), PFHxS (4%), Triclosan (5%), and BPA (4%). While we did observe an inverse association between EDCs and IQ among all children when training and testing the WQS index estimate on the full dataset, these results were not robust to repeated holdout validation.Conclusion: Among boys, early prenatal exposure to EDCs was associated with lower intellectual functioning at age 7. We identified bisphenol F as the primary chemical of concern, suggesting that the BPA replacement compound may not be any safer for children. Future studies are needed to confirm the potential neurotoxicity of replacement analogues.
|
|
