Per- and polyfluoroalkyl substances (PFAS) are widespread environmental pollutants with documented developmental toxicity. Prior research of prenatal PFAS exposure and offspring neurodevelopment did not consider the possible influence from paternal exposure. Using the INUENDO cohort, we studied 334 father-mother-singleton triads enrolled from antenatal clinics in Greenland, Poland, and Ukraine. We measured five PFAS in parental serum samples collected around the 31 weeks of gestation. We assessed child behavioral difficulties at ages 5-9 years by the parent-rated Strength and Difficulties Questionnaire using country- and sex-specific cut-offs (≥90th percentile). We performed analyses stratified by child's sex, coadjusting for maternal or paternal PFAS and other confounders and estimating PFAS mixture effects using quantile g-computation. In male children, multiple maternal PFAS, modeled as individual chemicals or a mixture, were associated with externalizing difficulties. Maternal perfluorononanoic acid (PFNA) was associated with internalizing difficulties in female children. In contrast, paternal exposure to individual PFAS or PFAS mixture was not associated with behavioral difficulties in children of either sex. In summary, maternal prenatal exposure to PFAS, but not paternal PFAS, was associated with mid-childhood behavioral difficulties in a sex-specific manner. Comparing the parent-specific PFAS associations strengthened evidence against confounding shared in the family.

Chlorinated paraffins (CPs), widely distributed environmental and industrial pollutants, have been linked to impaired neurodevelopment. However, evidence for this potential association between CP exposure and the risk of Attention-Deficit Hyperactivity Disorder (ADHD) and subtypes is lacking. To investigate this possible association between chlorinated paraffins exposure and the risk of ADHD and its subtypes in children and adolescents, a large cross-sectional study was conducted in the Pearl River Delta (PRD) in China involving 122,965 completed questionnaires. Particle matters <2.5 μm (PM2.5) samples and PM2.5-bound short-chain CPs (SCCPs), medium-chain CPs (MCCPs), and long-chain CPs (LCCPs) in the PRD were collected and detected. Generalized linear mixed models (GLMM) and restricted cubic spline (RCS) models were used to estimate the association between CP exposure and ADHD symptoms and subtypes, as well as dose-response relationships. Quantile g-computation models (qgcomp) were performed to explore further the joint effects of a mixture of CPs exposure on ADHD symptoms and subtypes. A total of 7139 participants (5.8 %) were diagnosed with ADHD. GLMM analysis found that an interquartile range (IQR) increase in ∑CP concentrations was associated with the risk of ADHD after adjusting the covariates, and the odds ratio and corresponding 95 % confidence interval was 1.57 (1.54, 1.61). The RCS model showed a monotone-increased dose-response association between CP exposure and ADHD symptoms. Qgcomp model analysis indicated that SCCPs and MCCPs were the major contributors to the risk of ADHD symptoms. Furthermore, girls exhibited a significantly higher risk of developing ADHD and it subtypes compared to boys following exposure to CPs. Above all, our findings suggest that PM2.5-bound CP exposure may increase the risk of ADHD symptoms and subtypes, and provide novel evidence for atmospheric environmental risk factors for ADHD.

Exposure to per- and polyfluoroalkyl substances (PFAS) is ubiquitous and may be associated with neurodevelopmental toxicity. However, epidemiological studies report mixed results on the risks of gestational PFAS exposure for children's neurobehavioral impairment. We aimed to examine the associations between prenatal PFAS exposure and children's neurobehavioral and social problems. We measured plasma concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulphonate (PFHxS) in first-trimester blood from 757 women from the Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study. Children were assessed at 3-4 years with the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2) (n = 756 and 496, respectively). We used multivariable linear regression to examine associations between individual and summed log2-transformed PFAS and scores on these assessments. Effect modification by sex was evaluated through interaction terms and stratified analyses. In the sample combining both sexes, a doubling of maternal PFOA was significantly associated with lower T-scores on the following SRS-2 scales: Social Motivation, DSM-Social Communication, and SRS Total score (B ranging from -1.08 to -0.78), suggesting lesser impairments with higher exposure. In sex-stratified analysis, PFOA was related to significantly lower T-scores in boys for these BASC-2 scales: Behavioral Symptoms Index, Externalizing Problems, Aggression, and Hyperactivity (B ranging from -1.32 to -1.03). In girls, however, PFAS were associated with more problem behaviors, but most associations were small and the CIs included the null, with the exception of PFOA being significantly associated with higher T-scores for the BASC-2Anxiety scale (B = 1.84, 95% CI: 0.36, 3.32). In conclusion, we did not observe strong associations between prenatal exposure to the PFAS evaluated and children's neurobehavioral and social development in this population with low exposure levels. The results show mixed findings, depending on children's sex, neurodevelopmental outcome, and specific PFAS.

Attention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in childhood. There is growing evidence that both preterm birth and maternal education levels substantially affect the likelihood of ADHD in children. However, there are limited systematic reviews and meta-analyses examining these associations.

To systematically review and conduct a meta-analysis on the association of preterm birth and maternal education level on the risk of ADHD in children.

We conducted a comprehensive literature search across MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library, including studies published up to June 17, 2024. Data synthesis was performed using random-effect models, and the quality of studies was assessed using the Newcastle-Ottawa Scale.

This study included twelve studies, which revealed a significant association between premature delivery and an increased risk of ADHD in children [odds ratio (OR) = 2.76, 95% confidence interval (CI): 2.52-3.04, P < 0.001, I² = 1.9%). Conversely, higher maternal education levels were significantly associated with a reduced risk of ADHD in children (OR = 0.59, 95%CI: 0.48-0.73, P < 0.001, I² = 47.1%). Subgroup analysis further indicated that maternal education levels significantly influenced ADHD risk, particularly in studies conducted in China (OR = 0.59, 95%CI: 0.46-0.75, P < 0.001, I² = 81.2%), while no significant association was observed in studies from other regions (OR = 1.25, 95%CI: 0.66-2.40, P = 0.495, I² = 92.3%). The sensitivity analysis confirmed the robustness of our findings, showing no significant publication bias.

This study found that preterm birth significantly increases the risk of ADHD in children, while a higher maternal education level serves as a protective factor against ADHD. To reduce the incidence of ADHD in children, public health policies should focus on early intervention for preterm infants and improving maternal education levels.

Perfluoroalkyl substances (PFASs) have elimination half-lives in years in humans and are persistent in the environment. PFASs can cross the placenta and impact fetal development. Exposure to PFASs may lead to adverse effects through epigenetic mechanisms. This study aimed to investigate whether prenatal exposure to perfluorooctyl sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUA) was associated with global histone methylation level changes among the 130 2-year-old children followed-up in a birth cohort study in Taiwan. PFOS, PFOA, PFNA, and PFUA were measured by UHPLC/MS/MS in cord blood. Global histone methylation levels were measured from the blood leukocytes of 2-year-old children by Western blotting. Multivariable regression analyses were applied to adjust for potential confounding effects. Among the 2-year-old children, an IQR increase in the natural log-transformed PFUA exposure was associated with an increased H3K4me3 level by 2.76-fold (95%CI = (0.79, 4.73), p = 0.007). PFOA and PFNA exposures was associated with a decreased H3K27me3 level by 2.35-fold (95%CI = (-4.29, -0.41), p = 0.01) and 2.01-fold (95%CI = (-4.00, -0.03), p = 0.04), respectively. Our findings suggest that prenatal PFAS exposure affected histone post-translational modifications.

Background/Objectives: Endocrine disruptors are ubiquitous agents in the environment and are present in everyday consumer products. These agents can interfere with the endocrine system, and subsequently the reproductive system, especially in pregnancy. An increasing number of studies have been conducted to discover and describe the health effects of these agents on humans, including pregnant women, their fetuses, and the placenta. This review discusses prenatal exposure to various endocrine disruptors, focusing on bisphenols, phthalates, organophosphates, and perfluoroalkyl substances, and their effects on pregnancy and fetal development. Methods: We reviewed the literature via the PubMed and EBSCO databases and included the most relevant studies. Results: Our findings revealed that several negative health outcomes were linked to endocrine disruptors. However, despite the seriousness of this topic and the abundance of research on these agents, it remains challenging to draw strong conclusions about their effects from the available studies. This does not allow for strong, universal guidelines and might result in poor patient counseling and heterogeneous approaches to regulating endocrine disruptors. Conclusions: The seriousness of this matter calls for urgent efforts, and more studies are needed in this realm, to protect pregnant patients, and ultimately, in the long term, society.

PFAS (per- and polyfluoroalkyl substances) have been extensively used across numerous industries and consumer goods. Due to their high persistence and mobility, they are ubiquitous in the environment. Exposure to PFAS occurs in people via multiple pathways such as dermal contact, water supply, air inhalation, and dietary intake. Even if some PFAS are being phased out because of their persistent presence in the environment and harmful impacts on human health, mixes of replacement and legacy PFAS will continue to pollute the ecosystem. Numerous toxicological investigations have revealed harmful effects of PFAS exposure on female reproductive health, e.g., polycystic ovaries syndrome, premature ovarian failure, endometriosis, reproductive system tumors, pregnancy complications, and adverse pregnancy outcomes. Despite extensive epidemiological studies on the reproductive toxicity of PFAS, research findings remain inconsistent, and the underlying mechanisms are not well understood. In this review, we give an in-depth description of the sources and pathways of PFAS, and then review the reproductive toxicity of PFAS and its possible mechanisms.

Background: Epidemiological research investigating the impact of exposure to plastics, and plastic-associated chemicals, on human health is critical, especially given exponentially increasing plastic production. In parallel with increasing production, academic research has also increased exponentially both in terms of the primary literature and ensuing systematic reviews with meta-analysis. However, there are few overviews that capture a broad range of chemical classes to present a state of play regarding impacts on human health. Methods: We undertook an umbrella review to review the systematic reviews with meta-analyses. Given the complex composition of plastic and the large number of identified plastic-associated chemicals, it was not possible to capture all chemicals that may be present in, and migrate from, plastic materials. We therefore focussed on a defined set of key exposures related to plastics. These were microplastics, due to their ubiquity and potential for human exposure, and the polymers that form the matrix of consumer plastics. We also included plasticisers and flame retardants as the two classes of functional additive with the highest concentration ranges in plastic. In addition, we included bisphenols and per- and polyfluoroalkyl substances (PFAS) as two other major plastic-associated chemicals with significant known exposure through food contact materials. Epistemonikos and PubMed were searched for systematic reviews with meta-analyses, meta-analyses, and pooled analyses evaluating the association of plastic polymers, particles (microplastics) or any of the selected groups of high-volume plastic-associated chemicals above, measured directly in human biospecimens, with human health outcomes. Results: Fifty-two systematic reviews were included, with data contributing 759 meta-analyses. Most meta-analyses (78%) were from reviews of moderate methodological quality. Across all the publications retrieved, only a limited number of plastic-associated chemicals within each of the groups searched had been evaluated in relevant meta-analyses, and there were no meta-analyses evaluating polymers, nor microplastics. Synthesised estimates of the effects of plastic-associated chemical exposure were identified for the following health outcome categories in humans: birth, child and adult reproductive, endocrine, child neurodevelopment, nutritional, circulatory, respiratory, skin-related and cancers. Bisphenol A (BPA) is associated with decreased anoclitoral distance in infants, type 2 diabetes (T2D) in adults, insulin resistance in children and adults, polycystic ovary syndrome, obesity and hypertension in children and adults and cardiovascular disease (CVD); other bisphenols have not been evaluated. Phthalates, the only plasticisers identified, are associated with spontaneous pregnancy loss, decreased anogenital distance in boys, insulin resistance in children and adults, with additional associations between certain phthalates and decreased birth weight, T2D in adults, precocious puberty in girls, reduced sperm quality, endometriosis, adverse cognitive development and intelligence quotient (IQ) loss, adverse fine motor and psychomotor development and elevated blood pressure in children and asthma in children and adults. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) but not other flame retardants, and some PFAS were identified and are all associated with decreased birth weight. In general populations, PCBs are associated with T2D in adults and endometriosis, bronchitis in infants, CVD, non-Hodgkin's lymphoma (NHL) and breast cancer. In PCB-poisoned populations, exposure is associated with overall mortality, mortality from hepatic disease (men), CVD (men and women) and several cancers. PBDEs are adversely associated with children's cognitive development and IQ loss. PBDEs and certain PFAS are associated with changes in thyroid function. PFAS exposure is associated with increased body mass index (BMI) and overweight in children, attention deficit hyperactive disorder (ADHD) in girls and allergic rhinitis. Potential protective associations were found, namely abnormal pubertal timing in boys being less common with higher phthalate exposure, increased high-density lipoprotein (HDL) with exposure to mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and reduced incidence of chronic lymphocytic lymphoma (a subtype of NHL) with PCB exposure. Conclusions: Exposure to plastic-associated chemicals is associated with adverse outcomes across a wide range of human health domains, and every plastic-associated chemical group is associated with at least one adverse health outcome. Large gaps remain for many plastic-associated chemicals. Recommendations: For research, we recommend that efforts are harmonised globally to pool resources and extend beyond the chemicals included in this umbrella review. Priorities for primary research, with ensuing systematic reviews, could include micro- and nanoplastics as well as emerging plastic-associated chemicals of concern such as bisphenol analogues and replacement plasticisers and flame retardants. With respect to chemical regulation, we propose that safety for plastic-associated chemicals in humans cannot be assumed at market entry. We therefore recommend that improved independent, systematic hazard testing for all plastic-associated chemicals is undertaken before market release of products. In addition because of the limitations of laboratory-based testing for predicting harm from plastic in humans, independent and systematic post-market bio-monitoring and epidemiological studies are essential to detect potential unforeseen harms.

Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated.

We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817).

The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence.

High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

Polymers are the main building blocks of plastic, with the annual global production volume of fossil carbon-based polymers reaching over 457 million metric tons in 2019 and this figure is anticipated to triple by 2060. There is potential for environmental harm and adverse human health impacts associated with plastic, its constituent polymers and the chemicals therein, at all stages of the plastic life cycle, from extraction of raw materials, production and manufacturing, consumption, through to ultimate disposal and waste management. While there have been considerable research and policy efforts in identifying and mitigating the impacts associated with problematic plastic products such as single-use plastics and hazardous chemicals in plastics, with national and/or international regulations to phase out their use, plastic polymers are often overlooked. In this review, the polymer dimension of the current knowledge on environmental release, human exposure and health impacts of plastic is discussed across the plastic life cycle, including chemicals used in production and additives commonly used to achieve the properties needed for applications for which the polymers are generally used. This review focuses on polycarbonate, polystyrene, polyvinyl chloride, and polybutadiene, four common plastic polymers made from the hazardous monomers, bisphenol, styrene, vinyl chloride and 1,3-butadiene, respectively. Potential alternative polymers, chemicals, and products are considered. Our findings emphasise the need for a whole system approach to be undertaken for effective regulation of plastics whereby the impacts of plastics are assessed with respect to their constituent polymers, chemicals, and applications and across their entire life cycle.

Studies on the role of the gut microbiota in the associations between per- and polyfluoroalkyl substance (PFAS) exposure and adverse neurodevelopment are limited. Umbilical cord serum and faeces samples were collected from children, and the Strengths and Difficulties Questionnaire (SDQ) was conducted. Generalized linear models, linear mixed-effects models, multivariate analysis by linear models and microbiome regression-based kernel association tests were used to evaluate the associations among PFAS exposure, the gut microbiota, and neurobehavioural development. Perfluorohexane sulfonic acid (PFHxS) exposure was associated with increased scores for conduct problems and externalizing problems, as well as altered gut microbiota alpha and beta diversity. PFHxS concentrations were associated with higher relative abundances of Enterococcus spp. but lower relative abundances of several short-chain fatty acid-producing genera (e.g., Ruminococcus gauvreauii group spp.). PFHxS exposure was also associated with increased oxidative phosphorylation. Alpha and beta diversity were found significantly associated with conduct problems and externalizing problems. Ruminococcus gauvreauii group spp. abundance was positively correlated with prosocial behavior scores. Increased alpha diversity played a mediating role in the associations of PFHxS exposure with conduct problems. Our results suggest that the gut microbiota might play an important role in PFAS neurotoxicity, which may have implications for PFAS control.

Per-and polyfluoroalkyl substances (PFAS) are ubiquitous in the environment and accumulate in humans. Toxicological studies have indicated the potential neurotoxicity of PFAS during the fetal development. However, in epidemiological studies, the association between prenatal exposure to PFAS and executive function in offspring remains unclear.

To investigate the association between prenatal exposure to PFAS and executive function in offspring.

This study included 1765 mother-child pairs in the Shanghai Birth Cohort, a prospective birth cohort enrolled during 2013-2016. The levels of 10 PFAS were measured in maternal plasma samples collected during early gestation. Child executive function was assessed at 4 years of age using the parent-reported Behavior Rating Inventory of Executive Function-Preschool version (BRIEF-P), which provided 4 composite measures: Inhibitory Self-Control Index, Flexibility Index, Emergent Metacognition Index, and Global Executive Composite. We used multivariable linear regression to examine the associations between individual PFAS and BRIEF-P scores. Bayesian kernel machine regression (BKMR) was employed to evaluate the joint effects. We also investigated whether these associations were modified by sex.

We found no significant associations between prenatal PFAS exposure and BRIEF-P scores when the child was 4 years old. BKMR analysis showed no joint effect of the PFAS mixture on child executive function. RCS analysis indicated that the majority of relationships between PFAS and BRIEF-P did not deviate from the linear relationship, even though there was a nonlinear association between PFUA and EMI. Additionally, the associations were not modified by sex.

Overall, our findings showed that there were no associations between prenatal exposure to PFAS and child executive function at 4 years of age.

This study investigates the association between prenatal exposure to per- and polyfluoroalkyl substances (PFASs) and the incidence and frequency of respiratory tract infections (RTIs) in preschool children. We selected 527 mother-infant pairs from Wuhan Healthy Baby Cohort (WHBC), China. Ten PFASs were measured in umbilical cord serum, and we collected data on common RTIs in preschool children aged 4 years through a questionnaire. Associations of single PFASs with the incidence and frequency of RTIs were analyzed via Logistic regression and Poisson regression, while the collective effect was assessed by weighted quantile sum (WQS) regression. Furthermore, stratified and interaction analyses were performed to evaluate if there were sex-specific associations. We found a positive correlation between perfluorododecanoic acid (PFDoDA) and the incidence of tonsillitis, with several PFASs also showing positive associations with its frequency. Moreover, perfluorotridecanoic acid (PFTrDA) showed a positive link with the frequency of common cold. The results of WQS regression revealed that after adjusting for other covariates, PFASs mixture showed a positive association with the incidence of tonsillitis, the frequency of common cold, and episodes. In particular, perfluoroundecanoic acid (PFUnDA), PFDoDA, PFTrDA, perfluorodecanoic acid (PFDA) and 8:2 chlorinated polyfluorinated ether sulfonic acid (8:2 Cl-PFESA) had the most significant impact on this combined effect. The results suggest that both single and mixed exposures to PFASs may cause RTIs in preschool children. However, there was no statistically significant interaction between different PFASs and sex.

Although numerous studies have examined the effect of prenatal per- and polyfluoroalkyl substances (PFAS) exposure on neurodevelopment in children, findings have been inconsistent.

To better understand the effects of PFAS exposure during pregnancy on offspring neurodevelopment, we conducted a systematic review of prenatal exposure to different types of PFAS and neurodevelopment in children.

A comprehensive search was conducted in the PubMed, Web of Science, and EMBASE electronic databases up to March 2023. Only birth cohort studies that report a specific association between PFAS exposure during pregnancy and neurodevelopment were included in this review.

31 birth cohort studies that met the inclusion criteria were qualitatively integrated. Among these, 14 studies investigated the impact of PFAS exposure during pregnancy on cognition, 13 on neurobehavior, and 4 on both cognition and neurobehavior. Additionally, 4 studies explored the influence of PFAS on children's comprehensive development.

Prenatal PFAS exposure was associated with poor neurodevelopment in children, including psychomotor development, externalizing behavior, and comprehensive development. However, conclusive evidence regarding its effects on other neurological outcomes remains limited. In addition, sex-specific effects on social behavior and sleep problems were identified.

The global production and use of plastic materials has increased dramatically since the 1960s and there is increasing evidence of human health impacts related to exposure to plastic-associated chemicals. There is, however, no comprehensive, regulatory, post-market monitoring for human health effects of plastic-associated chemicals or particles and it is unclear how many of these have been investigated for effects in humans, and therefore what the knowledge gaps are.

To create a systematic evidence map of peer-reviewed human studies investigating the potential effects of exposure to plastic-associated particles/chemicals on health to identify research gaps and provide recommendations for future research and regulation policy.

Medline and Embase databases were used to identify peer-reviewed primary human studies published in English from Jan 1960 - Jan 2022 that investigated relationships between exposures to included plastic-associated particles/chemicals measured and detected in bio-samples and human health outcomes. Plastic-associated particles/chemicals included are: micro and nanoplastics, due to their widespread occurrence and potential for human exposure; polymers, the main building blocks of plastic; plasticizers and flame retardants, the two most common types of plastic additives with the highest concentration ranges in plastic materials; and bisphenols and per- or polyfluoroalkyl substances, two chemical classes of known health concern that are common in plastics. We extracted metadata on the population and study characteristics (country, intergenerational, sex, age, general/special exposure risk status, study design), exposure (plastic-associated particle/chemical, multiple exposures), and health outcome measures (biochemical, physiological, and/or clinical), from which we produced the interactive database 'Plastic Health Map' and a narrative summary.

We identified 100,949 unique articles, of which 3,587 met our inclusion criteria and were used to create a systematic evidence map. The Plastic Health Map with extracted metadata from included studies are freely available at https://osf.io/fhw7d/ and summary tables, plots and overall observations are included in this report.

We present the first evidence map compiling human health research on a wide range of plastic-associated chemicals from several different chemical classes, in order to provide stakeholders, including researchers, regulators, and concerned individuals, with an efficient way to access published literature on the matter and determine knowledge gaps. We also provide examples of data clusters to facilitate systematic reviews and research gaps to help direct future research efforts. Extensive gaps are identified in the breadth of populations, exposures and outcomes addressed in studies of potential human health effects of plastic-associated chemicals. No studies of the human health effects of micro and/or nanoplastics were found, and no studies were found for 26/1,202 additives included in our search that are of known hazard concern and confirmed to be in active production. Few studies have addressed recent "substitution" chemicals for restricted additives such as organophosphate flame retardants, phthalate substitutes, and bisphenol analogues. We call for a paradigm shift in chemical regulation whereby new plastic chemicals are rigorously tested for safety before being introduced in consumer products, with ongoing post-introduction biomonitoring of their levels in humans and health effects throughout individuals' life span, including in old age and across generations.

Per- and polyfluoroalkyl substances (PFAS) are chemical substances spread throughout the environment worldwide. Exposure during pregnancy represents a specific window of vulnerability for child health.

Our objective was to assess the impact of prenatal exposure to multiple PFAS on emotional and behavioral functions in 12-y-old children.

In the PELAGIE mother-child cohort (France), prenatal exposure to nine PFAS was measured from concentrations in cord serum samples. Behavior was assessed at age 12 y using the parent-reported Strengths and Difficulties Questionnaire (SDQ) and the self-reported Dominic Interactive for Adolescents (DIA) for 444 children. Associations were estimated using negative binomial models for each PFAS. Bayesian kernel machine regression (BKMR) models were performed to assess the exposure mixture effect on children's behavior.

In our study population, 73% of mothers had spent more than 12 y in education. Higher scores on SDQ externalizing subscale were observed with increasing cord-serum concentration of perfluorooctanoic acid (PFOA) and perfluorononanoic acid (PFNA) [adjusted mean ratio ( aMR ) = 1.18 , 95% confidence interval (CI): 1.03, 1.34, and aMR = 1.14 (95% CI: 1.00, 1.29) for every doubling of concentration, respectively]. Results for the hyperactivity score were similar [aMR = 1.20 (95% CI: 1.04, 1.40) and aMR = 1.18 (95% CI: 1.02, 1.36), respectively]. With regard to major depressive disorder and internalizing subscales, perfluorodecanoic acid (PFDA) was associated with higher self-reported DIA scores [aMR = 1.14 (95% CI: 1.01, 1.27) and aMR = 1.11 (95% CI: 1.02, 1.21), respectively]. In terms of the anxiety subscale, PFDA and PFNA were associated with higher scores [aMR = 1.11 (95% CI: 1.02, 1.21) and aMR = 1.10 (95% CI: 1.01, 1.19), respectively]. Concurrent increases in the PFAS concentrations included in the BKMR models showed no change in the SDQ externalizing and DIA internalizing subscales scores.

Prenatal exposure to PFNA and PFOA were associated with increasing scores for measures of externalizing behaviors, specifically hyperactivity. We also identified associations between PFNA and PFDA prenatal exposure levels and increasing scores related to internalizing behaviors (general anxiety and major depressive disorder), which adds to the as yet sparse literature examining the links between prenatal exposure to PFAS and internalizing disorders. https://doi.org/10.1289/EHP12540.

Although heritability estimates suggest a role for genetic components, environmental risk factors have been described as relevant in the etiology of attention deficit/hyperactivity disorder (ADHD). Several studies have investigated the role of toxicological pollution, i.e., air pollution, heavy metals, POPs, and phthalates. Clear evidence for association of ADHD and environmental factors has not been provided yet. To answer this, we have assessed all available systematic reviews and meta-analyses that focused on the association between pollutant exposure and either ADHD diagnosis or symptoms. More than 1800 studies were screened of which 14 found eligible. We found evidence of a significant role for some pollutants, in particular heavy metals and phthalates, in the increased risk of developing ADHD symptoms. However, at the current stage, data from existing literature also do not allow to weight the role of the different environmental pollutants. We also offer a critical examination of the reviews/meta-analyses and provide indications for future studies in this field. PROSPERO registration: CRD42022341496.

Exposure to endocrine-disrupting chemicals (EDCs) can promote infant neurodevelopmental impairment and maternal postpartum depression (PPD). However, the associations between lactation exposure to EDCs, maternal PPD, and infant neurodevelopment are unclear. Hence, we investigated these relationships in infants aged 36-42 months. We recruited 221 Korean mothers and analyzed 29 EDCs. The Edinburgh Postnatal Depression Scale (EPDS) was used to assess maternal PPD. Bayley scales of infant development; the Swanson, Nolan, and Pelham rating scale (SNAP); and the Child Behavior Checklist (CBCL) were used to assess neurodevelopment in infants exposed to the top 30% of EDC over three years. Multiple regression analyses were adjusted for maternal age, pre-pregnancy body mass index, education, income, employment, residence, and infant age and sex. The rates of infants with clinically abnormal diagnoses on neurologic developmental tests (Balyey, SNAP, and CBCL scales) ranged from 7.7 to 38.5% in this study, with the motor and hyperactivity/impulsivity areas scoring the highest among 65 boys and girls. Mono-2-ethylhexyl phthalate (MEHP) and mono-isononyl phthalate (MiNP) levels in breast milk significantly correlated with infant inattention and hyperactivity. Perfluorononanoic acid (PFNA) and perfluorooctyl sulfonate (PFOS) levels correlated significantly with motor development of BSID-III and total CBCL score which mean infant might have lower developmental status. EDC concentrations in breast milk were not associated with maternal PPD. Overall, lactational exposure to EDCs during the postpartum period can exert a negative effect on maternal PPD and infant neurodevelopment.

Although some studies report that exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy and early life stages of a child could adversely impact neurodevelopment, literature shows mixed evidence.

Using an ecological framework for human development, we assessed the association of risk factors for environmental PFAS exposure and childhood PFAS concentrations with behavioral difficulties among school-age children exposed to PFAS from birth, while also controlling for the important influence of the parenting and familial environment.

The study participants included 331 school-age children (6-13 years) born in a PFAS-contaminated area in the Veneto Region (Italy). We study the associations between environmental risk factors of maternal PFAS exposure (residential time, consumption of tap water, residence in Red zone A or B), and breastfeeding duration with parent assessments of children's behavioral problems (using the Strengths and Difficulties Questionnaire [SDQ]), adjusting for socio-demographic, parenting and familial variables. The direct relationships between serum blood PFAS concentrations and SDQ scores was evaluated in a subset of children (n = 79), both with single PFAS and weighted quantile sum (WQS) regressions.

Poisson regression models reported positive associations between high consumption of tap water and externalizing SDQ scores (Incidence Rate Ratio [IRR]: 1.18; 95% confidence interval [CI]: 1.04-1.32) and total difficulty scores (IRR: 1.14; 95% CI: 1.02-1.26). Childhood perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with higher internalizing SDQ scores (4th vs. 1st quartile, PFOS IRR: 1.54, 95% CI: 1.06-2.25), externalizing scores (4th vs. 1st quartile, PFHxS IRR: 1.59, 95% CI: 1.09-2.32), and total difficulty scores (4th vs. 1st quartile, PFOS IRR: 1.37, 95% CI: 1.05-1.71; PFHxS IRR: 1.54, 95% CI: 1.09-1.90). The WQS regressions confirmed the associations reported by single-PFAS analyses.

We observed cross-sectional associations of tap water consumption and childhood PFOS, and PFHxS concentrations with greater behavioral difficulties.

Per- and polyfluoroalkyl substances (PFAS) are a class of man-made chemicals that are persistent in the environment. They can be transferred across the placenta to fetuses and through human milk to infants. The American Academy of Pediatrics advises that the benefits of breastfeeding infants almost always outweigh the potential risks of harm from environmental chemicals. However, there are few chemical-specific summaries of the potential harms of exposure to PFAS during the neonatal period through breastfeeding. This systematic review explores whether exposure to PFAS through breastfeeding is associated with adverse health outcomes among infants and children using evidence from human and animal studies. Systematic searches identified 4297 unique records from 7 databases. The review included 37 total articles, including 9 animal studies and 1 human study measuring the direct contribution of exposure of the infant or pup through milk for any health outcome. Animal studies provided evidence of associations between exposure to PFOA through breastfeeding and reduced early life body weight gain, mammary gland development, and thyroid hormone levels. They also provided limited evidence of associations between PFOS exposure through breastfeeding with reduced early life body weight gain and cellular changes in the hippocampus. The direct relevance of any of these outcomes to human health is uncertain, and it is possible that many adverse health effects of exposure through breastfeeding have not yet been studied. This review documents the current state of science and highlights the need for future research to guide clinicians making recommendations on infant feeding.

A small subset of per- and polyfluoroalkyl substances (PFAS) are routinely screened in human blood. These compounds generally explain <50 % of the total PFAS in human blood. The percentage of known PFAS in human blood has been decreasing as replacement PFAS and more complex PFAS chemistries are introduced to the market. Most of these novel PFAS have not been previously identified. Non-targeted methods are required to characterize this "dark matter" PFAS. Our objective was to apply non-targeted PFAS analysis to human blood to gain an understanding about the sources, concentrations, and toxicity of these compounds. A high-resolution tandem mass spectrometry (HRMS) and software workflow for PFAS characterization in dried blood spots is reported. Dried blood spots are a less invasive collection technique compared to venous blood draws, allowing collection from vulnerable populations. Biorepositories of archived dried blood spots are available internationally from newborns and present opportunities to study prenatal exposure to PFAS. In this study, dried blood spot cards were analyzed using iterative MS/MS by liquid chromatography HRMS. Data processing was conducted using FluoroMatch Suite including a visualizer tool that presents homologous series, retention time vs m/z plots, MS/MS spectra, feature tables, annotations, and fragments for fragment screening. The researcher performing data-processing and annotation was blinded to the fact that standards were spiked in, and was able to annotate 95 % of standards spiked on dried blood spot samples, signifying a low false negative rate using FluoroMatch Suite. A total of 28 PFAS (20 standards and 4 exogenous compounds) were detected across five homologous series with Schymanski Level 2 confidence. Of these 4, 3 were perfluoroalkyl ether carboxylic acids (PFECA), a chemical class of PFAS which is increasingly being detected in environmental and biological matrices but is not currently screened in most targeted analysese. A further 86 potential PFAS were detected using fragment screening. PFAS are extremely persistent and widespread yet remain largely unregulated. Our findings will contribute to an improved an understanding of exposures. Application of these methods in environmental epidemiology studies have the potential to inform policy with regards to PFAS monitoring, regulation, and individual-level mitigation strategies.

Perfluoroalkyl substances (PFASs) are ubiquitous global contaminants that do not readily biodegrade and are therefore routinely found worldwide in wildlife, humans, and the environment. There is a paucity of global assessments to understand regional and continental differences in exposure to PFASs and the associated health risks, including those for Indigenous Arctic communities who consume high trophic marine diets. We aimed to estimate the long-term exposure of dietary PFASs from consumption of polar bear and ringed seal meat and establish its association with blood serum concentrations of PFASs in Inuit in Ittoqoortoormiit (Scoresby Sound), East Greenland. We also aimed to assess the risk of immune suppression on the basis of European Food Safety Authority (EFSA) thresholds for weekly intake and blood serum concentrations of PFASs. Last, we conducted a worldwide risk assessment based on blood concentrations of PFASs emphasising Arctic exposure in a global context.

In this mixed-methods study, we conducted interviews to compare dietary exposure of PFASs in anonymous, non-pregnant, Inuit adults (aged ≥18 years) from full-time or part-time hunter families in Ittoqoortoormiit, East Greenland with ESFA toxic threshold values for tolerable weekly intake of the four most immunotoxic PFASs (∑4PFAS; perfluorooctanoic acid, perfluorononanoic acid, perfluorohexanesulfonic acid, and perfluorooctane sulfonate). Independent hospital staff from the local hospital randomly selected participants using simple randomisation using a telephone directory. Blood serum concentrations were then compared with EFSA risk categories: low (0·7-9·5 ng/mL), moderate (>9·5-17·5 ng/mL), high (>17·5-31·9 ng/mL), and severe (>31·9 ng/mL). We also reviewed the available scientific literature of ∑4PFAS concentrations in human blood to place the Inuit dataset in a broader global context.

Between Sept 21, and Oct 2, 2015, 22 participants were enrolled in the study, of which 12 were male and ten were female. Sex data were obtained from personal social security numbers and options were male or female. As a result of a subsistence diet high in marine mammal muscle, 322 (92%) of 350 people in the Ittoqoortoormiit cohort exceeded the established immunotoxic thresholds of ∑4PFASs set by EFSA's tolerable weekly intake of 4·4 ng/kg, and 301 (86%) were in the most severe risk category (>31·9 ng/mL) based on blood serum concentrations. This Inuit cohort had the highest non-occupational long-term exposure to PFASs worldwide despite their remote location relative to industrial sources. Using country-wide average values across global studies, we found that blood serum concentrations of PFASs in populations from European countries, North America, the Arctic, and Australia were generally higher than those in South America, Africa, and mainland Asia, with the highest concentrations found in people from USA, Canada, Greenland, Faroe Islands, Denmark, Iceland, Norway, Sweden, the UK, Spain, Poland, and Australia. These high exposure countries all fall within the EFSA moderate-risk and high-risk categories.

PFAS contamination of the environment and human populations occurs worldwide. This pollution not only poses substantial risks for immune system adverse events but also cardiovascular, cancerous, and reproductive endpoints. Data on such PFAS exposure is scarce in numerous countries. Therefore, it is important to also map out the exposure in these countries to enable a thorough global assessment of exposure and risks.

Danish Cooperation for Environment in the Arctic.

Per- and polyfluoroalkyl substances (PFASs) are widespread environmental pollutants. There is increasing evidence that PFASs have various adverse health effects, including renal toxicity, metabolic dysfunction, endocrine disruption, and developmental toxicity. PFASs have been found to accumulate in the placenta, and some PFASs can cross the placental barrier and subsequently accumulate in the fetus via the maternal-fetal circulation. An increasing number of studies have shown that early life exposure to PFASs can affect fetal neurodevelopment. This paper reviews the characteristics of indirect exposure to PFASs in early life, the effects on neurodevelopment in offspring, and the possible mechanisms of toxic effects.

There is evidence that exposure to perfluoroalkyl substances (PFAS) is associated with attention-deficit/hyperactivity disorder (ADHD) symptoms. Previous studies have focused on prenatal exposure to PFAS, and only few studies have examined the associations of early-childhood exposure, especially at low exposure levels. This study explored the association between early-childhood exposure to PFAS and ADHD symptoms later in childhood. In 521 children, we measured the serum levels of six PFAS in peripheral blood at the ages of 2 and 4 years, including perfluorooctanoate (PFOA), perfluornonanoicacid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonate (PFOS). The ADHD Rating Scale IV (ARS) was utilized to measure ADHD traits at 8 years of age. We explored the relationship between PFAS and ARS scores using Poisson regression models after adjusting for potential confounders. Levels of exposure to individual PFAS and the summed value were divided into quartiles to examine possible nonlinear relationships. All six PFAS exhibited inverted U-shaped curves. Children in the 2nd and 3rd quartile levels of each PFAS showed higher ARS scores than those in the1^st quartile level. Below the 3rd quartile of the summed levels of six PFAS (ΣPFAS), a doubling of the ΣPFAS was associated with an 20.0 % (95 % CI: 9.5 %, 31.5 %) increase in ADHD scores. However, at the age of 4 years, none of the evaluated PFAS exhibited linear or nonlinear associations with the ARS scores. Thus, school-aged children may be vulnerable to the neurotoxic effects of exposure to PFAS at age 2 that contribute to ADHD, particularly at low to mid-levels.

Epidemiological evidence regarding the effects of prenatal exposure to perfluoroalkyl substances (PFASs) on neurodevelopment in children is inconclusive. In 449 mother-child pairs from the Shanghai-Minhang Birth Cohort Study, we measured the concentrations of 11 PFASs in maternal plasma samples obtained at 12-16 weeks of gestation. We assessed children's neurodevelopment at 6 years of age by the fourth edition of the Chinese Wechsler Intelligence Scale for Children and Child Behavior Checklist for ages 6-18. We evaluated the association between prenatal exposure to PFASs and children's neurodevelopment and the effect modification of maternal dietary factors during pregnancy and the child's sex. We found that prenatal exposure to multiple PFASs was associated with increased scores for attention problems, and the individual effect of perfluorooctanoic acid (PFOA) was statistically significant. However, no statistically significant association between PFASs and cognitive development was observed. Additionally, we found the effect modification of maternal nut intake and child's sex. In conclusion, this study suggests that prenatal exposure to PFASs was associated with more attention problems, and maternal nut intake during pregnancy may alter the potential effect of PFASs. However, these findings were exploratory because of multiple testing and the relatively small sample size.

Drinking water can be a major source of poly- and perfluoroalkyl substance (PFAS) exposure for humans. The lack of historic data on PFAS drinking-water concentrations and consumption patterns are a limiting factor for developing estimates of past exposure. Here, in contribution to a community-scale PFAS health effects study near fire training facilities that contaminated a local aquifer with PFASs, we present a novel water-infrastructure, mass-balance mixing model coupled to a non-steady state, single-compartment toxicokinetic model that used Monte Carlo simulations to estimate the start of PFAS exposure in drinking water for individuals within three PFAS-impacted communities in El Paso County, Colorado. Our modeling focused on perfluorohexane sulfonic acid (PFHxS) because median serum PFHxS concentrations in a sample of local residents (n = 213) were twelve times the median observed in the U.S. National Health and Nutrition Examination Survey (2015-2016). Modeling results for study participants were grouped according to their community of residence, revealing a median start of exposure for the town of Fountain of 1998 (25-75% interquartile range [IQR], 1992 to 2010), 2006 (IQR 1995 to 2012) for Security, and 2009 (IQR 1996-2012) for Widefield. Based on the towns' locations relative to an identified hydraulically upgradient PFAS source, the modeled exposure sequencing does not completely align with this conceptual flow model, implying the presence of an additional PFAS source for the groundwater between Widefield and Fountain.

Milk formation in the breast during breastfeeding is a complex hormonally regulated process, potentially sensitive to the effects of endocrine-disrupting chemical exposures. The environmental chemicals, per- and polyfluoroalkyl substances (PFAS) are known endocrine disruptors. PFAS exposure have been associated with insufficient mammary gland development in mice and reduced breastfeeding duration in humans. The aim of this review was to gather the epidemiological evidence on the association between PFAS exposure and breastfeeding duration. Using PubMed and Embase, we performed a systematic literature search (on 23 January 2023) to identify epidemiological studies examining the association between maternal PFAS exposure and breastfeeding duration. Animal studies, reviews, and non-English studies were excluded. The risk of bias was assessed using the risk of bias in non-randomized studies of exposures tool. Estimates describing the association between PFAS exposure and the duration of breastfeeding were identified, and the data were synthesized separately for each type of PFAS and for the duration of exclusive and total breastfeeding. Six studies with between 336 and 2374 participants each were identified. PFAS exposure was assessed in serum samples (five studies) or based on residential address (one study). Five out of six studies found shorter total duration of breastfeeding with higher PFAS exposure. The most consistent associations were seen for perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA). The finding of a potential causal association between PFAS exposure and breastfeeding duration is in agreement with findings from experimental studies.

The neurotoxic effects of prenatal exposure to per- and polyfluoroalkyl substances (PFAS) on offspring animals are well-documented. However, epidemiological evidence for legacy PFAS is inconclusive, and for alternative PFAS, it is little known. In this investigation, we selected 718 mother-child pairs from the Chinese Maoming Birth Cohort Study and measured 17 legacy and alternative PFAS in the third-trimester serum. Neuropsychological developments (communication, gross motor function, fine motor function, problem solving ability, and personal-social skills) were assessed at 3, 6, 12, 18, 24, and 36 months using the Ages and Stages Questionnaires 3rd edition. Trajectories of each subscale were classified into persistently low and persistently high groups via group-based trajectory modeling. Logistic regression and grouped weighted quantile sum were fitted to assess the potential effects of individual PFAS and their mixtures, respectively. Higher linear PFHxS levels were associated with elevated odds for the persistently low trajectories of communication (OR = 1.73; 95% CI: 1.12, 2.66) and problem solving ability (OR = 2.11; 95% CI: 1.14, 3.90). Similar findings were observed for linear PFOS, 1m-PFOS, PFDA, PFDoDA, PFUnDA, and legacy PFAS mixture. However, no association was observed for alternative PFAS and their mixture. We provided insights into the longitudinal links between prenatal legacy/alternative PFAS exposure and neuropsychological development trajectories over the first 3 years of life.

The relative contribution of environmental contaminants is an important, and frequently unanswered, question in human or ecological risk assessments. This interpretation of relative importance allows determination of the overall effect of a set of variables relative to other variables on an adverse health outcome. There are no underlying assumptions of independence of variables. The tool developed and used here is specifically designed for studying the effects of mixtures of chemicals on a particular function of the human body.

We apply the approach to estimate the contributions of total exposure to six PFAS (perfluorodecanoic acid, perfluorohexane sulfonic acid, 2-(N-methyl-PFOSA) acetate, perfluorononanoic acid, perfluoroundecanoic acid and perfluoroundecanoic acid) to loss of bone mineral density relative to other factors related to risk of osteoporosis and bone fracture, using data from subjects who participated in the US National Health Examination and Nutrition Surveys (NHANES) of 2013-2014.

PFAS exposures contribute to bone mineral density changes relative to the following variables: age, weight, height, vitamin D2 and D3, gender, race, sex hormone binding globulin, testosterone, and estradiol.

We note significant alterations to bone mineral density among more highly exposed adults and significant differences in effects between men and women.

Epidemiological data on the effects of perfluoroalkyl and polyfluoroalkyl substances (PFAS) on infant neurodevelopment trajectories are far from being sufficiently addressed. In this study, 1285 mother-child pairs were recruited during 2016-2017. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure 16 PFAS levels in cord serum. Ages and Stages Questionnaires were used to examine children's neurodevelopment at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Children with relatively low scores from 2 to 24 months were classified into a low-score group and were used as a risk group in each domain. Multiple linear regression, logistic regression, and quantile-based g-computation were performed to assess associations of single or mixture PFAS exposures with neurodevelopment and trajectories. Perfluorooctane sulphonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and 6:2 chlorinated polyfluorooctane ether sulfonate (6:2Cl-PFESA) were detected in over 90 % samples. PFOA had the highest concentration (median: 4.61 μg/L). Each ln-unit (μg/L) increase of PFAS (e.g., PFOA, PFOS, PFHxS, 6:2Cl-PFESA) was associated with poor scores of communication domain at 6 months, with the effect size ranging from -0.69 to -0.44. PFOS (OR: 1.14, (1.03, 1.26), PFDA (OR:1.08, (1.02, 1.15)), PFHxS (OR:1.31, (1.12, 1.56)), and 6:2Cl-PFESA (OR:1.08, (1.00, 1.16)) were associated with an increased risk of being in the low-score group in the early childhood communication domain's trajectory. Each mixture quartile increment was associated with a 1.60 (-2.76, -0.45) decrease in communication domain scores of 6-month-old infants, and the mixture effect was mainly attributed to PFOS. Each mixture quartile increase was associated with a 1.23-fold (1.03, 1.46) risk of being in the low-score group of the communication domain, and the mixture effect was mainly attributed to PFOS. In conclusion, PFAS and their mixtures might adversely affect childhood neurodevelopment. The gender-specific associations existed in the above associations.

Per-/polyfluoroalkyl substances (PFASs) have been linked to preeclampsia with inconsistent directions for outcomes. However, information regarding the joint effects of PFASs mixtures on preeclampsia as well as their associations with the low birth weight (LBW) and small for gestational age (SGA) is nascent. The present study included 82 women with preeclampsia and 169 healthy participants from Hangzhou, China. Fifteen PFASs were analyzed in maternal serum before delivery. PFOA and 6:2Cl-PFESA were associated with higher incidence of preeclampsia both linearly and by tertile. Each log-unit increase in serum PFOA (OR:5.29, 95% CI: 1.05, 26.7, p = 0.044) and 6:2 Cl-PFESA (OR:1.02, 95%CI: 1.00, 1.48, p = 0.045) concentrations were associated with increased risks of preeclampsia. These effects were more profound among primiparous women carrying female fetuses. Both PFOA and PFUnDA concentrations were significantly associated with higher odds of early-onset preeclampsia, but the associations tended to be null for late-onset. In addition, each logarithmic increment in PFOA concentrations were significantly associated with a 0.262 and 0.224 mmHg increase in systolic (95% CI: 0.147, 0.377) and diastolic (95% CI: 0.133, 0.314) blood pressures. Using Bayesian kernel machine regressions (BKMR), the overall effects of PFASs mixture concentrations on preeclampsia showed an increasing trend, with PFOA being the largest contributor. With regard to birth weight, the Cox proportional hazards model indicated that significantly higher risks of the LBW were associated with preeclampsia than normal pregnancy (OR: 4.56, 95% CI: 2.44, 6.68, p = 0.000). Increased LBW risks were found for the higher PFOA exposure both linearly and by tertile. Besides, serum PFOA and PFUnDA concentrations were significantly associated with higher odds of SGA development. Nevertheless 4:2 FTS and ADONA were inversely associated with LBW and SGA incidences. Further adverse birth outcomes should be explored to elucidate the health implications of PFASs exposure and preeclampsia development.

Climate change may affect mental health. We conducted an umbrella review of meta-analyses examining the association between mental health and climate events related to climate change, pollution and green spaces. We searched major bibliographic databases and included meta-analyses with at least five primary studies. Results were summarized narratively. We included 24 meta-analyses on mental health and climate events (n = 13), pollution (n = 11), and green spaces (n = 2) (two meta-analyses provided data on two categories). The quality was suboptimal. According to AMSTAR-2, the overall confidence in the results was high for none of the studies, for three it was moderate, and for the other studies the confidence was low to critically low. The meta-analyses on climate events suggested an increased prevalence of symptoms of post-traumatic stress, depression, and anxiety associated with the exposure to various types of climate events, although the effect sizes differed considerably across study and not all were significant. The meta-analyses on pollution suggested that there may be a small but significant association between PM2.5, PM10, NO2, SO2, CO and mental health, especially depression and suicide, as well as autism spectrum disorders after exposure during pregnancy, but the resulting effect sizes varied considerably. Serious methodological flaws make it difficult to draw credible conclusions. We found reasonable evidence for an association between climate events and mental health and some evidence for an association between pollution and mental disorders. More high-quality research is needed to verify these associations.

In vivo, in vitro, and epidemiological evidence suggests that perfluoroalkyl substances (PFAS) may alter thyroid function in human health, with negative effects on maternal and fetal development outcomes. However, data on the effects of PFAS on thyroid hormones remain controversial. Here, we conducted a meta-analysis of 13 eligible studies searched from Embase, PubMed, and Web of Science by July 10, 2022, to explore the relationship between maternal exposure to PFAS and thyroid health effects, including thyroid stimulating hormone (TSH), triiodothyronine (TT3), thyroxin (TT4), free T3 (FT3), and free T4 (FT4). The estimated values (β) and the corresponding confidence intervals (95%CI) were extracted for analysis. The tests for heterogeneity, sensitivity and publication bias between studies were performed using Stata 15.0. The combined results showed a positive association between changes in TSH and exposure to perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), with no significant correlation observed between changes in other thyroid hormones and exposure to PFAS. This difference was attributed to sample size, region, sample type, body mass index (BMI), and gestational week. Our data recommend verifying the relationship between PFAS exposure and thyroid health effects in a large sample population cohort in future studies. In addition, health care should be taken into account in early and mid-pregnancy.

Telomere length (TL) at birth predicts later life TL and is related to health. Prenatal exposure to environmental pollutants might affect TL, but the associations between intrauterine per- and polyfluoroalkyl substances (PFASs) exposure and neonatal TL remained inconclusive. This study aimed to explore the single pollutant and mixture associations between legacy and novel PFASs and TL in newborns. In 908 mother-newborn pairs from Wuhan, China, thirteen PFASs were measured in cord serum, and TL was determined in cord leukocytes. Weighted quantile sum (WQS) regression and generalized linear model (GLM) were utilized to analyze the associations between PFASs mixture and single PFASs and TL in newborns. Furthermore, stratified and interaction analyses were performed to evaluate if there were sex-specific associations. The concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA) ranked the highest (geometric mean, 4.12, 1.61, and 0.77 ng/mL, respectively) among the 13 measured PFASs. Each unit increase in WQS index of PFASs mixture was associated with -5.19 % change (95% CI, -9.44, -0.73) of neonatal TL, and 8:2 Cl-PFESA contributed most (32.59 %) to the mixture association. In stratified analyses by neonatal sex, PFOS (-4.73 % change, 95% CI, -8.40, -0.93 for per doubling concentration) and 8:2 Cl-PFESA (-4.52 % change, 95% CI, -8.20, -0.70) were negatively associated with neonatal TL in male newborns, but no significant association appeared in females. In summary, intrauterine exposure to PFASs in mixture was associated with shorter neonatal TL, and the negative associations of 8:2 Cl-PFESA and PFOS with neonatal TL were observed only in boys. Future risk assessments are needed to pay more attention to the health effects of novel PFASs.

Exposure to per- and polyfluoroalkyl substances (PFAS) during pregnancy has been suggested to be associated with neurobehavioral problems in offspring. However, current epidemiological studies on the association between prenatal PFAS exposure and neurobehavioral problems among offspring, especially attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), are inconsistent. Therefore, we aimed to study the relationship between PFAS exposure during pregnancy and ADHD and ASD in offspring based on meta-analyses. Online databases, including PubMed, EMBASE, and Web of Science, were searched comprehensively for eligible studies conducted before July 2021. Eleven studies (up to 8493 participants) were included in this analysis. The pooled results demonstrated that exposure to perfluorooctanoate (PFOA) was positively associated with ADHD in the highest quartile group. Negative associations were observed between perfluorooctane sulfonate (PFOS) and ADHD/ASD, including between perfluorononanoate (PFNA) and ASD. There were no associations found between total PFAS concentration groups and neurobehavioral problems. The trial sequential analyses showed unstable results. Our findings indicated that PFOA and PFOS exposure during pregnancy might be associated with ADHD in offspring and that prenatal PFOS and PFNA exposure might be associated with ASD in offspring. According to the limited evidence obtained for most associations, additional studies are required to validate these findings.

Per- and polyfluoroalkyl substances (PFASs) are a large group of chemicals reported in global environment and are responsible for various adverse impacts on humans and environment. We report a comprehensive study on occurrence of PFASs, including legacy, substitute and emerging ones, from Pakistan. Surface water samples were collected from five ecologically important freshwater reservoirs in Pakistan, namely, Head Panjnad (HP), Head Trimmu (HT), Chashma Barrage (CB), Head Blloki (HB), and Head Qadirabad (HQ). The detection frequencies of PFASs ranged between 37 %-100 %. The highest concentration of ∑₁₅PFASs was detected at HP (114.1 ng L^-1), whereas the lowest at HQ (19.9 ng L^-1). Among the analyzed PFASs, 6:2 fluorotelomer sulfonic acid (6:2 FTS) and perfluorooctanoic acid (PFOA) showed maximum mean concentrations of 9.1 ng L^-1 and 7 ng L^-1 at HP, followed by Perfluorooctane sulfonic acid (PFOS) with level of 0.99 ng L^-1 at HT. The ecological risk assessment for selected species i.e., daphnid, mysid, fish and green algae showed that PFOS, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) exhibited moderate risk i.e., Hazard Quotients (HQs) < 1 to the modeled organisms, whereas perfluorobutane sulfonic acid (PFBS) showed the high risk to green algae (HQs = 8.6) and PFOA presented a high risk to all the organisms (HQs ranged between 1.04 and 7.38). The level of ∑PFASs at HP (114.1 ng L^-1) exceed the EU guideline value of ∑PFASs in water (100 ng L^-1), however the risk quotient (RQ_mix) values of all age groups were < 1 implying that the detected PFASs in water do not pose risk to human health. Source apportionment through Positive Matrix Factorization (PMF) showed that industrial effluent is the main source of PFASs in freshwater reservoirs. Comparable concentrations of legacy and substitute PFASs in this study indicate that legacy PFASs are still in use adjacent to ecologically important water reservoirs.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent endocrine-disrupting chemicals associated with long-term health outcomes. PFAS are transferred from maternal blood to human milk, an important exposure source for infants, and understanding of this transfer is evolving. We characterized concentrations of 10 PFAS in human milk (n = 426) and compared milk-to-plasma concentrations of 9 PFAS among a subset of women with paired samples (n = 294) from the New Hampshire Birth Cohort Study using liquid chromatography-isotope dilution tandem mass spectrometry. We examined the relationship between perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in plasma versus milk and fit linear regression models to assess relationships between milk PFOA and PFOS and participant characteristics. The median plasma PFOA concentration was 0.94 ng/mL (interquartile range, IQR, 0.59-1.34) and that of PFOS was 2.60 ng/mL (IQR 1.80-3.90); the median milk PFOA concentration was 0.017 ng/mL (IQR 0.012-0.027) and that of PFOS was 0.024 ng/mL (IQR 0.016-0.036). PFOA and PFOS plasma and milk concentrations showed correlations of ρ = 0.83 and 0.77, respectively (p < 0.001). Parity, previous lactation, week of milk collection, and body mass index were inversely associated with milk PFAS. We estimate that even among our general population cohort, some infants (∼6.5%) are exposed to amounts of PFAS via milk that may have long-term health impacts.

Per- and polyfluoroalkyl substances (PFAS) are shown to have neurotoxic effects on animals, but epidemiological evidence for associations between childhood PFAS exposure and neurodevelopment is inconclusive. We examined if childhood PFAS concentrations are associated with a diagnosis of autism spectrum disorder (ASD), developmental delay (DD), and other early concerns (OEC) in development.

We included 551 children 2-5 years old from the CHildhood Autism Risks from Genetics and Environment (CHARGE) case-control study. Children were clinically diagnosed and classified as having ASD, DD, OEC, and typical development (TD). Fourteen PFAS were quantified in child serum samples collected when diagnostic assessments were performed. We used multinomial logistic regression models to investigate the cross-sectional associations of individual PFAS concentrations with neurodevelopmental outcomes and weighted quantile sum (WQS) regression models with repeated holdout validation to investigate the associations with PFAS mixtures.

Childhood perfluorooctanoic acid (PFOA) was associated with increased odds of ASD (odds ratio [OR] per ln ng/mL increase: 1.99, 95% confidence interval [CI]: 1.20, 3.29) and DD (OR: 2.16, 95% CI: 1.21, 3.84) versus TD. Perfluoroheptanoic acid (PFHpA) was associated with increased odds of ASD (OR: 1.61, 95% CI: 1.21, 2.13). However, perfluroundecanoic acid (PFUnDA) was associated with decreased odds of ASD (OR: 0.43, 95% CI: 0.26, 0.69). From mixture analyses, the WQS index was associated with increased odds of ASD (average OR: 1.57, 5th and 95th percentile: 1.16, 2.13). Child's sex and homeownership modified associations of perfluorodecanoic acid (PFDA) with DD and ASD, respectively.

In this case-control study, childhood PFOA, PFHpA, and a PFAS mixture was associated with increased odds of ASD, while PFUnDA was associated with decreased odds of ASD. Because we used concurrent measurements of PFAS, our results do not imply causal relationships and thus need to be interpreted with caution.

Despite their large numbers and widespread use, very little is known about the extent to which per- and polyfluoroalkyl substances (PFAS) can cross the placenta and expose the developing fetus.

The aim of our study is to develop a computational approach that can be used to evaluate the of extend to which small molecules, and in particular PFAS, can cross to cross the placenta and partition to cord blood.

We collected experimental values of the concentration ratio between cord and maternal blood (R_CM) for 260 chemical compounds and calculated their physicochemical descriptors using the cheminformatics package Mordred. We used the compiled database to, train and test an artificial neural network (ANN). And then applied the best performing model to predict R_CM for a large dataset of PFAS chemicals (n = 7982). We, finally, examined the calculated physicochemical descriptors of the chemicals to identify which properties correlated significantly with R_CM.

We determined that 7855 compounds were within the applicability domain and 127 compounds are outside the applicability domain of our model. Our predictions of R_CM for PFAS suggested that 3623 compounds had a log R_CM > 0 indicating preferable partitioning to cord blood. Some examples of these compounds were bisphenol AF, 2,2-bis(4-aminophenyl)hexafluoropropane, and nonafluoro-tert-butyl 3-methylbutyrate.

These observations have important public health implications as many PFAS have been shown to interfere with fetal development. In addition, as these compounds are highly persistent and many of them can readily cross the placenta, they are expected to remain in the population for a long time as they are being passed from parent to offspring.

Understanding the behavior of chemicals in the human body during pregnancy is critical in preventing harmful exposures during critical periods of development. Many chemicals can cross the placenta and expose the fetus, however, the mechanism by which this transport occurs is not well understood. In our study, we developed a machine learning model that describes the transplacental transfer of chemicals as a function of their physicochemical properties. The model was then used to make predictions for a set of 7982 per- and polyfluorinated alkyl substances that are listed on EPA's CompTox Chemicals Dashboard. The model can be applied to make predictions for other chemical categories of interest, such as plasticizers and pesticides. Accurate predictions of R_CM can help scientists and regulators to prioritize chemicals that have the potential to cause harm by exposing the fetus.

Perfluorooctanoic acid (PFOA) is widely used throughout different industries, including the food industry, because it is resistant to heat and prevents water or oil from easily permeating into or contaminating materials coated by PFOA. Although many studies have reported an association between PFOA exposure and the risk of developing hepatic diseases, it is still in debate because they have shown conflicting results. Therefore, this study conducted a systematic review and meta-analysis on the relationship between PFOA exposure and hepatic diseases.

This study searched studies related to hepatic diseases due to PFOA exposure until 31 December 2021, using PubMed, EMBASE, and Web of Science. This study performed a systematic review and meta-analysis through research question development, literature screening, data extraction, and risk of bias evaluation. This study found 8280 studies after excluding duplicate literature and selected 5 studies in the final stage. Among them, two studies were included in the meta-analysis.

The results of the meta-analysis showed that the ALT of people exposed to PFOA was 117% higher than the ALT of those not exposed to PFOA, and it was significantly different (OR = 1.167; 95% CI, 1.086-1.254).

However, since the number of studies included in the analysis was not large enough to conclude that PFOA exposure was associated with the development of hepatic diseases, more observational studies are needed to confirm its long-term effects.