Metabolomics of childhood exposure to perfluoroalkyl substances: a cross-sectional study

Kingsley, Samantha L.; Walker, Douglas I.; Calafat, Antònia M.; Chen, Aimin; Papandonatos, George D.; Xu, Yingying; Jones, Dean P.; Lanphear, Bruce P.; Pennell, Kurt D.; Braun, Joseph M.

doi:10.1007/s11306-019-1560-z

Cited by 60 publications

(36 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…(Wang, X. et al 2017) Two studies in children also showed that PFAS levels in blood were associated with significant alterations in glycophospholipid metabolism and several amino acid pathways such as tyrosine, aspartate and asparagine. (Alderete et al 2019; Kingsley et al 2019)…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach

Jin

McConnell

Catherine

et al. 2020

Environment International

Self Cite

156

View full text Add to dashboard Cite

Background: Toxicant-associated steatohepatitis has been described in adults but less is known regarding the role of toxicants in liver disease of children. Perfluoroalkyl substances (PFAS) cause hepatic steatosis in rodents, but few previous studies have examined PFAS effects on severity of liver injury in children. Objectives: We aimed to examine the relationship of PFAS to histologic severity of nonalcoholic fatty liver disease (NAFLD) in children. Methods: Seventy-four children with physician-diagnosed NAFLD were recruited from Children’s Healthcare of Atlanta between 2007 and 2015. Biopsy-based liver histological features were scored for steatosis, lobular and portal inflammation, ballooning, and fibrosis. Plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonic acid (PFHxS), and untargeted plasma metabolomic profiling, were determined using liquid chromatography with high-resolution mass spectrometry. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with PFAS. A structural integrated analysis was applied to identify latent clusters of children with more severe form of NAFLD based on their PFAS levels and metabolite pattern. Results: Patients were 7-19 years old, mostly boys (71%), Hispanic (51%), and obese (85%). The odds of having nonalcoholic steatohepatitis (NASH), compared to children with steatosis alone, was significantly increased with each interquartile range (IQR) increase of PFOS (OR: 3.32, 95% CI: 1.40-7.87) and PFHxS (OR: 4.18, 95% CI: 1.64-10.7). Each IQR increase of PFHxS was associated with increased odds for liver fibrosis (OR: 4.44, 95% CI: 1.34-14.8), lobular inflammation (OR: 2.87, 95% CI: 1.12-7.31), and higher NAFLD activity score (β coefficient 0.46; 95% CI: 0.03, 0.89). A novel integrative analysis identified a cluster of children with NASH, characterized by increased PFAS levels and altered metabolite patterns including higher plasma levels of phosphoethanolamine, tyrosine, phenylalanine, aspartate and creatine, and decreased plasma levels of betaine. Conclusions: Higher PFAS exposure was associated with more severe disease in children with NAFLD. PFAS may be an important toxicant contributing to NAFLD progression; however larger, longitudinal studies are warranted to confirm these findings.

show abstract

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated reference standardization provides estimates of concentrations consistent with both endogenous and exogenous compounds,(Accardi et al 2016; Go et al 2015a; Walker et al 2019) and high-correlation with PFAS measurements by validated, targeted approaches. (Kingsley et al 2019)…”

Section: Methodsmentioning

confidence: 99%

Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach

Jin

McConnell

Catherine

et al. 2020

Environment International

Self Cite

156

View full text Add to dashboard Cite

show abstract

“…PFASs, on the other hand, are a group of man-made chemicals that have been widely used since the 1950s in both household and industrial products. PFASs also have long biological half-lives, and are readily detected in humans [3][4][5][6][7]. Structurally, several PFAS compounds resemble endogenous fatty acids, with fluorine substitution in place of hydrogen.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of perfluoroalkyl substances and bile acids in human serum using ultra-high-performance liquid chromatography–tandem mass spectrometry

et al. 2019

View full text Add to dashboard Cite

There is evidence of a positive association between per-and polyfluoroalkyl substances (PFASs) and cholesterol levels in human plasma, which may be due to common reabsorption of PFASs and bile acids (BAs) in the gut. Here we report development and validation of a method that allows simultaneous, quantitative determination of PFASs and BAs in plasma, using 150 μL or 20 μL of sample. The method involves protein precipitation using 96-well plates. The instrumental analysis was performed with ultraperformance liquid chromatography-tandem mass spectrometry (UHPLC-MS), using reverse-phase chromatography, with the ion source operated in negative electrospray mode. The mass spectrometry analysis was carried out using multiple reaction monitoring mode. The method proved to be sensitive, robust, and with sufficient linear range to allow reliable determination of both PFASs and BAs. The method detection limits were between 0.01 and 0.06 ng mL −1 for PFASs and between 0.002 and 0.152 ng mL −1 for BAs, with the exception of glycochenodeoxycholic acid (0.56 ng mL −1). The PFAS measured showed excellent agreement with certified plasma PFAS concentrations in NIST SRM 1957 reference serum. The method was tested on serum samples from 20 healthy individuals. In this proof-of-concept study, we identified significant associations between plasma PFAS and BA levels, which suggests that PFAS may alter the synthesis and/or uptake of BAs.

show abstract

“…In addition, we are able to derive sleep measures from the actigraphy data. 55 56 Other biomarkers We measured other biomarkers including leucocyte DNA methylation, 57 high-resolution metabolomics, 58 gonadal hormone concentrations and vitamin D metabolite concentrations. We also conducted a drug screen on children's urine using a clinical drug panel assay.…”

Section: Physical Activity Diet and Sleepmentioning

confidence: 99%

Adolescent follow-up in the Health Outcomes and Measures of the Environment (HOME) Study: cohort profile

et al. 2020

Self Cite

View full text Add to dashboard Cite

PurposeEnvironmental chemical exposures may adversely affect an array of adolescent health outcomes. Thus, we used the Health Outcomes and Measures of the Environment (HOME) study, a prospective cohort that recruited pregnant women and conducted longitudinal follow-up on children over the first 12 years of life, to determine if and when chemical exposures affect adolescent health.ParticipantsWe recruited 468 pregnant women (age range: 18–45 years) from the Cincinnati, Ohio region to participate in a cohort study between March 2003 and January 2006. Follow-up included two clinic and one home visits during pregnancy, a delivery hospital visit, and four home and six clinic visits when children were aged 4 weeks and 1, 2, 3, 4, 5 and 8 years. Of 441 children available for follow-up, 396 (90%) completed at least one follow-up and 256 (58%) completed the most recent follow-up at 12 years of age (range: 11–14).Findings to dateOur new measures include maternal/child report of internalising symptoms, neuroimaging, dual-energy X-ray absorptiometry-derived estimates of lean/adipose tissue and bone mineral density, and cardiometabolic risk biomarkers. We assessed adolescent exposure to perfluoroalkyl substances, phenols, phthalates and flame retardants. Participants completing follow-up at 12 years of age were similar to the original cohort in terms of baseline factors. Most children had typical and expected values for this age on measures of internalising symptoms, body composition, bone density and cardiometabolic risk markers. Notably, 36% and 11% of children had scores indicative of potential anxiety and depressive disorders, respectively. Approximately 35% of children were overweight or obese, with higher prevalence among girls. Thirty-three per cent of children had borderline or high triglyceride concentrations (>90 mg/dL).Future plansWe will examine associations of early life environmental chemical exposures with adolescent health measures while considering potential periods of heightened susceptibility and mixture effects.Trial registration numberNCT00129324.

show abstract

Metabolomics of childhood exposure to perfluoroalkyl substances: a cross-sectional study

Cited by 60 publications

References 67 publications

Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach

Perfluoroalkyl substances and severity of nonalcoholic fatty liver in Children: An untargeted metabolomics approach

Simultaneous determination of perfluoroalkyl substances and bile acids in human serum using ultra-high-performance liquid chromatography–tandem mass spectrometry

Adolescent follow-up in the Health Outcomes and Measures of the Environment (HOME) Study: cohort profile

Contact Info

Product

Resources

About