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
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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.
Paracetamol (N-acetyl-p-aminophenol (APAP), otherwise known as acetaminophen) is the active ingredient in more than 600 medications used to relieve mild to moderate pain and reduce fever. APAP is ...widely used by pregnant women as governmental agencies, including the FDA and EMA, have long considered APAP appropriate for use during pregnancy when used as directed. However, increasing experimental and epidemiological research suggests that prenatal exposure to APAP might alter fetal development, which could increase the risks of some neurodevelopmental, reproductive and urogenital disorders. Here we summarize this evidence and call for precautionary action through a focused research effort and by increasing awareness among health professionals and pregnant women. APAP is an important medication and alternatives for treatment of high fever and severe pain are limited. We recommend that pregnant women should be cautioned at the beginning of pregnancy to: forego APAP unless its use is medically indicated; consult with a physician or pharmacist if they are uncertain whether use is indicated and before using on a long-term basis; and minimize exposure by using the lowest effective dose for the shortest possible time. We suggest specific actions to implement these recommendations. This Consensus Statement reflects our concerns and is currently supported by 91 scientists, clinicians and public health professionals from across the globe.
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•Early prenatal exposure to 26 suspected endocrine disruptors was related to lower IQ in children.•The endocrine disruptor mixture disproportionately impacted boys.•Replacement ...analogue bisphenol F (BPF), may not be a safer alternative to BPA.•Preventing short-lived pollutant exposure among pregnant women may mitigate effects.
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.
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.
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.
Using 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.
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.
Many first trimester sporadic miscarriages are unexplained and the role of environmental exposures is unknown. The present aim was to study if levels of Perfluoroalkyl substances (PFASs) in early ...pregnancy are associated with unexplained, sporadic first trimester miscarriage. The study was performed within the Swedish SELMA pregnancy cohort. Seventy-eight women with non-recurrent first trimester miscarriage were included and 1449 women were available as live birth controls. Eight PFASs were measured in first trimester serum. A doubling of perfluorooctanoic acid (PFOA) exposure, corresponding to an inter-quartile increase, was associated with an odds ratio (95%CI) for miscarriage of 1.48 (1.09-2.01) when adjusting for parity, age and smoking. Analyses per quartiles of PFOA exposure indicated a monotonic dose response association with miscarriage. A similar, but not significant, pattern was observed for perfluorononanoic acid (PFNA). For other PFAS, there were no associations with miscarriage. We have previously shown associations between early pregnancy PFAS exposures and preeclampsia, as well as lower birth weight. Now we report an association between PFOA and miscarriage within the same cohort, which may suggest shared but unknown mechanisms. The study can only represent a period of early placentation and clinical pregnancy loss during the second half of the first trimester.
Phthalates are widely used in consumer products. Exposure to phthalates can lead to adverse health effects in humans, with early‐life exposure being of particular concern. Phthalate exposure occurs ...mainly through ingestion, inhalation, and dermal absorption. However, our understanding of the relative importance of different exposure routes is incomplete. This study estimated the intake of five phthalates from the residential indoor environment for 455 Swedish pregnant women in the SELMA study using phthalate mass fraction in indoor dust and compares these to total daily phthalate intakes back‐calculated from phthalate metabolite concentrations in the women's urine. Steady‐state models were used to estimate indoor air phthalate concentrations from dust measurements. Intakes from residential dust and air made meaningful contributions to total daily intakes of more volatile di‐ethyl phthalate (DEP), di‐n‐butyl phthalate (DnBP), and di‐iso‐butyl phthalate (DiBP) (11% of total DEP intake and 28% of total DnBP and DiBP intake combined). Dermal absorption from air was the dominant pathway contributing to the indoor environmental exposure. Residential exposure to less volatile phthalates made minor contributions to total intake. These results suggest that reducing the presence of low molecular weight phthalates in the residential indoor environment can meaningfully reduce phthalate intake among pregnant women.
Early life is suggested to be a critical time in determining subsequent asthma development, but the extent to which the effect of early-life exposure to ambient air pollution on childhood asthma is ...unclear.
We investigated doctor-diagnosed asthma in preschool children due to exposure to ambient air pollution in utero and during the first year of life.
In total 2490 children aged 3–6 years participated in a questionnaire study regarding doctor-diagnosed asthma between September 2011 and January 2012 in China. Children’s exposure to critical air pollutants, sulfur dioxide (SO2) as proxy of industrial air pollution, nitrogen dioxide (NO2) as proxy of traffic pollution, and particulate matter≤10µm in diameter (PM10) as a mixture, was estimated from the concentrations measured at the ambient air quality monitoring stations by using an inverse distance weighted (IDW) method. Logistic regression analysis was employed to determine the relationship between early-life exposure and childhood asthma in terms of odds ratio (OR) and 95% confidence interval (CI).
Association between early-life exposure to air pollutants and childhood asthma was observed. SO2 and NO2 had significant associations with adjusted OR (95% CI) of 1.45 (1.02–2.07) and 1.74 (1.15–2.62) in utero and 1.62 (1.01–2.60) and 1.90 (1.20–3.00) during the first year for per 50µg/m3 and 15µg/m3 increase respectively. Exposure to the combined high level of SO2 and NO2 in China significantly elevated the asthmatic risk with adjusted OR (95% CI) of 1.76 (1.18–2.64) in utero and 1.85 (1.22–2.79) during the first year compared to the low level exposure. The associations were higher for males and the younger children aged 3–4 than females and the older children aged 5–6.
Early-life exposure to ambient air pollution is associated with childhood asthma during which the level and source of air pollution play important roles. The high level and nature of combined industrial and traffic air pollution in China may contribute to the recent rapid increase of childhood asthma.
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•Early life exposure to ambient air pollution is associated with childhood asthma.•Level and source of air pollution act important roles in the development of asthma.•Asthmatic risk of air pollution is higher for the male and the younger.•Combined industrial and traffic air pollution elevates the asthmatic risk.•Asthmatic risk of industrial air pollution in China cannot be overlooked.
Humans are continuously exposed to chemicals with suspected or proven endocrine disrupting chemicals (EDCs). Risk management of EDCs presents a major unmet challenge because the available data for ...adverse health effects are generated by examining one compound at a time, whereas real‐life exposures are to mixtures of chemicals. In this work, we integrate epidemiological and experimental evidence toward a whole mixture strategy for risk assessment. To illustrate, we conduct the following four steps in a case study: (1) identification of single EDCs (“bad actors”)—measured in prenatal blood/urine in the SELMA study—that are associated with a shorter anogenital distance (AGD) in baby boys; (2) definition and construction of a “typical” mixture consisting of the “bad actors” identified in Step 1; (3) experimentally testing this mixture in an in vivo animal model to estimate a dose–response relationship and determine a point of departure (i.e., reference dose RfD) associated with an adverse health outcome; and (4) use a statistical measure of “sufficient similarity” to compare the experimental RfD (from Step 3) to the exposure measured in the human population and generate a “similar mixture risk indicator” (SMRI). The objective of this exercise is to generate a proof of concept for the systematic integration of epidemiological and experimental evidence with mixture risk assessment strategies. Using a whole mixture approach, we could find a higher rate of pregnant women under risk (13%) when comparing with the data from more traditional models of additivity (3%), or a compound‐by‐compound strategy (1.6%).
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Weighted Quantile Sum (WQS) regression is a method commonly used in environmental epidemiology to assess the impact of chemical mixtures in relation to a health outcome of interest. ...Data are partitioned into a single training and test set to reduce sample-specific chemical weights. However, in typical epidemiology sample sizes, this may produce unstable chemical weights and WQS index estimates, and investigators may resort to training and testing on the same data. To solve this problem, we propose repeated holdout validation whereby data are randomly partitioned 100 times, producing a distribution of validated results. Taking the mean as the final estimate, confidence estimates may also be calculated for inference. Further, this method helps characterize the variability in chemical weights, aiding in the identification of chemicals of concern. This is important since it may direct future research into specific chemicals.
Using data from 718 mother-child pairs in the Swedish Environmental Longitudinal, Mother and Child, Asthma and Allergy (SELMA) study, we assessed the association between prenatal exposure to 26 endocrine disrupting chemicals and child Intelligence Quotient (IQ). Results using a single partition were unstable, varying by random seed. The WQS index estimate was significant when all data was used (e.g. no partition) (β = −2.2 CI = −3.43, −0.98), but attenuated and nonsignificant using repeated holdout validation (β = −0.82 CI = −2.11, 0.45). When implementing WQS in epidemiologic studies with limited sample sizes, repeated holdout validation is a viable alternative to using a single, or no partitioning. Repeated holdout can both stabilize results and help characterize the uncertainty in identifying chemicals of concern, while maintaining some of the the rigor of holdout validation.
•Repeated holdout validation improves the stability of WQS estimates in finite study samples•Uncertainty in identifying toxic chemicals of concern is acknowledged and characterized
Phthalates are used as plasticizers in soft polyvinyl chloride (PVC) and in a large number of consumer products. Because of reported health risks, diisononyl phthalate (DiNP) has been introduced as a ...replacement for di(2-ethylhexyl) phthalate (DEHP) in soft PVC. This raises concerns because animal data suggest that DiNP may have antiandrogenic properties similar to those of DEHP. The anogenital distance (AGD)--the distance from the anus to the genitals--has been used to assess reproductive toxicity.
The objective of this study was to examine the associations between prenatal phthalate exposure and AGD in Swedish infants.
AGD was measured in 196 boys at 21 months of age, and first-trimester urine was analyzed for 10 phthalate metabolites of DEP (diethyl phthalate), DBP (dibutyl phthalate), DEHP, BBzP (benzylbutyl phthalate), as well as DiNP and creatinine. Data on covariates were collected by questionnaires.
The most significant associations were found between the shorter of two AGD measures (anoscrotal distance; AGDas) and DiNP metabolites and strongest for oh-MMeOP mono-(4-methyl-7-hydroxyloctyl) phthalate and oxo-MMeOP mono-(2-ethyl-5-oxohexyl) phthalate. However, the AGDas reduction was small (4%) in relation to more than an interquartile range increase in DiNP exposure.
These findings call into question the safety of substituting DiNP for DEHP in soft PVC, particularly because a shorter male AGD has been shown to relate to male genital birth defects in children and impaired reproductive function in adult males and the fact that human levels of DiNP are increasing globally.
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