Abstract Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States. 

https://www.nature.com/articles/s41467-023-38710-3.pdf

Newborn metabolomic signatures of maternal per- and polyfluoroalkyl substance exposure and reduced length of gestation

The concentrations of per- and polyfluoroalkyl substances (PFAS) were determined in raw influent, final effluent, and treated biosolids at Canadian wastewater treatment plants (WWTPs) to evaluate the fate of PFAS through liquid and solids trains of typical treatment process types used in Canada and to assess time trends of PFAS in wastewater between 2009 and 2021. Data for 42 PFAS in samples collected from 27 WWTP across Canada were used to assess current concentrations and 48 WWTPs were included in the time trends analysis. Although regulated and phased-out of production by industry since the early 2000s and late 2000s/early2010s, respectively, perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other long-chain PFAS continue to be widely detected in Canadian wastewater and biosolids. Short-chain PFAS that are not currently regulated in Canada were also widely detected. In general, elevated concentrations of several PFAS were observed at WWTPs that receive landfill leachate. Except for PFOS, concentrations of long-chain perfluoroalkyl carboxylates (PFCAs) and perfluoroalkane sulfonates (PFSAs) generally decreased over time in influent, effluent, and biosolids, which is attributable to industrial production phase-outs and regulations. Concentrations of PFOS did not decrease over time in wastewater media. This indicates that regulatory action and industrial phase-outs of PFOS are slow to be reflected in wastewater. Concentrations of short-chain PFCAs in wastewater influent and effluent consistently increased between 2009 and 2021, which reflect the use of short-chain PFAS as replacements for phased-out and regulated longer-chained PFAS. Short-chain PFAS were infrequently detected in biosolids. Continued periodic monitoring of PFAS in wastewater matrices in Canada and throughout the world is recommended to track the effectiveness of regulatory actions, particularly activities to address the broad class of PFAS. 

Per- and polyfluoroalkyl substances (PFAS) in Canadian municipal wastewater and biosolids: Recent patterns and time trends 2009 to 2021.

We aimed to assess the association between weight-adjusted waist circumference index (WWI) and gallstone prevalence in US adults.We selected individuals from the National Health and Nutrition Examination Survey (NHANES) database from 2017 to 2020 and used logistic regression analyses, subgroup analyses, and dose-response curves to assess the association between WWI and gallbladder stone prevalence and age, sex, and ethnicity.A total of 7971 participants aged ≥20 years were enrolled in our study; 828 patients had a self-reported history of gallstones. After correcting for confounders, for each unit of WWI after Ln conversion, the prevalence of gallbladder stones increased by 34% (OR=1.34, 95% CI:1.20, 1.50). Dose-response curves showed a positive correlation between WWI and gallbladder stone prevalence.According to the subgroup analysis, the positive association between TyG index and high-frequency HI was more significant in males(OR=1.34, 95% CI:1.07, 1.69), <40 years old(OR=1.42, 95% CI:1.18, 1.71), white people Americans(OR=1.35, 95% CI:1.08, 1.68) and other races(OR= 1.56, 95% CI:1.13, 2.14).Higher WWI was positively associated with the prevalence of gallbladder stones and was associated with gender, age, and ethnicity. This is noteworthy, although a causal relationship could not be established.

Relationship between weight-adjusted waist circumference index and prevalence of gallstones in U.S. adults: a study based on the NHANES 2017-2020

Contact to perfluoroalkyl substances and thyroid health effects: A meta-analysis directing on pregnancy.

Environmental exposure to volatile organic compounds (VOCs) is ubiquitous, and this study explored whether exposure to VOCs is associated with the risk of kidney stones. We performed a nationally representative US cross-sectional study using data from five survey cycles (2011-2020) of the National Health and Nutrition Examination Survey (NHANES) program. Exposure to VOCs was determined by urine creatinine-corrected metabolites of VOCs (mVOCs). In total 5505 participants and 15 urine mVOCs were included for analysis, and the prevalence of kidney stones was 9.57 % (527/5505). Multivariable logistic regression showed that urine AMCC (parent VOCs (pVOCs): N, N-Dimethylformamide), 3,4-MHA (pVOCs: xylene), MA (pVOCs: ethylbenzene; styrene), DHBMA (pVOCs: 1,3-butadiene), HMPMA (pVOCs: crotonaldehyde) and 2HPMA (pVOCs: propylene oxide) were significantly associated with an increased risk of kidney stones in US general population. Sub-analysis revealed that there was a more pronounced association in women and the overweight/obesity group (body mass index ≥ 25). Moreover, the weighted quantile sum (WQS) regression model and the Bayesian kernel machine regression (BKMR) model consistently identified a positive association between co-exposure to VOCs and the risk of kidney stones, in which AMCC played the most important role among the 15 mVOCs. Mediation analysis further identified serum high-density lipoprotein cholesterol (HDL) as a mediator of the association between VOC co-exposure and kidney stones. Our study draws attention to the previously unknown positive associations between non-occupational VOC exposure and the risk of kidney stones in the general population. However, further studies are required to clarify the existence of such causation. 

Serum HDL partially mediates the association between exposure to volatile organic compounds and kidney stones: A nationally representative cross-sectional study from NHANES.

Background A large body of emerging evidence suggests that per- and polyfluoroalkyl substances (PFAS) affect birth outcomes in various pathways, but the evidence is inconsistent. Therefore, this study aimed to systematically review the epidemiological evidence on PFAS exposure and birth outcomes. Methods Three electronic databases were searched for epidemiological studies through February 13, 2021. We used random-effects meta-analysis for eight birth outcome indicators to calculate summary effect estimates for various exposure types. The risk of bias and the overall quality and level of evidence for each exposure-outcome pair were assessed. Results The initial search identified 58 potentially eligible studies, of which 46 were ultimately included. Many PFAS were found to have previously unrecognized statistically significant associations with birth outcomes. Specifically, birth weight (BW) was associated with PFAS, with effect sizes ranging from −181.209 g (95% confidence interval (CI) = −360.620 to −1.798) per 1 ng/ml increase in perfluoroheptanesulfonate (PFHpS) to −24.252 g (95% CI = −38.574 to −9.930) per 1 ln (ng/ml) increase in perfluorodecaoic acid (PFDA). Similar patterns were observed between other PFAS and birth outcomes: perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) with birth length (BL) and ponderal index (PI), PFOS and perfluorododecanoic acid (PFDoDA) with head circumference (HC), PFHpS with gestational age (GA), and perfluorononanoic acid (PFNA) and PFHpS with preterm birth (PTB). Additionally, PFDA showed a statistically significant association with small for gestational age (SGA). The level of the combined evidence for each exposure-outcome pair was considered to be “moderate”. Conclusion This study showed that PFAS exposure was significantly associated with increased risks of various adverse birth outcomes and that different birth outcome indicators had different degrees of sensitivity to PFAS. Further studies are needed to confirm our results by expanding the sample size, clarifying the effects of different types or doses of PFAS and the time of blood collection on birth outcomes, and fully considering the possible confounders.

Association Between Exposure to Per- and Polyfluoroalkyl Substances and Birth Outcomes: A Systematic Review and Meta-Analysis

Objectives We aimed to evaluate the relationship between the proportion of Android to Gynoid ratio and the incidence of kidney stones among US adults. Methods Participants aged 20-59 years from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) database were selected to assess the association between Android to Gynoid ratio and kidney stone prevalence using logistic regression analysis, subgroup analysis and calculation of dose-response curves. Results This study ultimately included 10858 participants, of whom 859 self-reported a history of kidney stones. And after adjusting for all confounders, an increased Android to Gynoid ratio was associated with an increased prevalence of kidney stones (OR=2.75, 95% CI:1.62-4.88). And subgroup analysis showed an increased prevalence of kidney stones in women (OR=3.55, 95% CI: 1.54-8.22), non-diabetic (OR=2.59, 95% CI: 1.45-4.60), 60 > age ≥ 40 years (OR=3.51, 95% CI: 1.83-6.71), Mexican-American (OR=4.35, 95% CI: 1.40- 13.53) and white (OR=3.86, 95% CI: 1.82-8.18) groups, there was a significant positive association between A/G ratio and kidney stones. In contrast, in the hypertensive subgroup, the A/G ratio was associated with kidney stones in all groups. Conclusions Higher Android to Gynoid ratio is associated with a high prevalence of kidney stone disease.

/pdf/association-between-body-fat-distribution-and-kidney-stones-3i8p0tkd.pdf

Association between body fat distribution and kidney stones: Evidence from a US population

Background The main objective of this study is to explore the effects of hepatitis C (HCV) on the prevalence rate of kidney stones in US women. Method Dates for HCV infection and kidney stones were collected from National Health and Nutrition Examination Survey (NHANES) database, a cross-sectional study. The analysis samples included adults aged ≥20 years and women from six consecutive cycles of the NHANES 2007–2018. The association between HCV infection and kidney stones was performed by using logistic regression models. Subgroup analyses were conducted to find sensitive crowds. Results A total of 13,262 participants were enrolled, including 201 infected with HCV. After adjustment for potential confounders, we revealed a positive relationship between HCV and kidney stones (OR = 1.70, 95%CI:1.13–2.56). The crowds' statistically significant difference was characterized by other races (OR = 8.17, 95%CI:1.62–41.22) and BMI within 25–29.9 kg/m2 (OR = 2.45, 95%CI:1.24–4.83). Conclusions HCV infection may affect the prevalence of urolithiasis in US women, even the causal relationship remains unclear, the relation deserves special attention. We considered such a study an ideal way to begin exploring the effects of HCV on kidney stones.

Relationship between hepatitis C and kidney stone in US females: Results from the National Health and Nutrition Examination Survey in 2007–2018

Objective The purpose of this study was to examine whether the METS-IR index is associated with kidney stones in American adults. Method Participants from the National Health and Nutrition Examination Survey (NHANES) database from 2007-2018 were selected for logistic regression analysis, subgroup analyses, and the calculation of dose-response curves to assess the association between the METS-IR index and the incidence of kidney stones. Result This study enrolled 30,612 adults aged >20 years, 2901 of whom self-reported having had kidney stones in the past. And, after controlling for potential confounders, each unit increase in the METS-IR index was linked with a 1.23 percent rise in kidney stone incidence (OR= 1.0123, 95% CI: 1.0092 - 1.0155), with stratified analysis indicating that this was true in all subgroups. Between all groups, an elevated METS-IR index was related to kidney stone formation, and the dose-response curve revealed a positive non-linear connection between METS-IR index and kidney stone risk, with a threshold effect analysis revealing an inflection point value of 50.8314. Conclusion Higher METS-IR index is associated with the occurrence of kidney stones,and while no causative association can be shown, this is cause for concern.

/pdf/is-the-mets-ir-index-a-potential-new-biomarker-for-kidney-1z7rpgwx.pdf

Is the METS-IR Index a Potential New Biomarker for Kidney Stone Development?

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Association Between Exposure to Per- and Polyfluoroalkyl Substances and Birth Outcomes: A Systematic Review and Meta-Analysis

Association between body fat distribution and kidney stones: Evidence from a US population

Relationship between hepatitis C and kidney stone in US females: Results from the National Health and Nutrition Examination Survey in 2007–2018

Is the METS-IR Index a Potential New Biomarker for Kidney Stone Development?