Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study.

BACKGROUND Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. METHODS This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003-2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. RESULTS Seven PFASs were quantifiable in >50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2mg/dL per inter-quartile shift (95% CI=0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI=2.5, 4.9). CONCLUSION Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal.

[1]  G. Hobbs,et al.  Circulating maternal perfluoroalkyl substances during pregnancy in the C8 Health Study. , 2013, Environmental science & technology.

[2]  Geary W Olsen,et al.  Comparison of human whole blood, plasma, and serum matrices for the determination of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other fluorochemicals. , 2007, Environmental research.

[3]  Harvey J Clewell,et al.  Development of Pbpk Models for Pfoa and Pfos for Human Pregnancy and Lactation Life Stages , 2013, Journal of toxicology and environmental health. Part A.

[4]  D. Consonni,et al.  Thirty Years of Medical Surveillance in Perfluooctanoic Acid Production Workers , 2009, Journal of occupational and environmental medicine.

[5]  Jeffrey H Mandel,et al.  Epidemiologic Assessment of Worker Serum Perfluorooctanesulfonate (PFOS) and Perfluorooctanoate (PFOA) Concentrations and Medical Surveillance Examinations , 2003, Journal of occupational and environmental medicine.

[6]  R. Collins,et al.  Stability of plasma analytes after delayed separation of whole blood: implications for epidemiological studies. , 2003, International journal of epidemiology.

[7]  M. Longnecker,et al.  Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women. , 2013, Environment international.

[8]  J. Giesy,et al.  Peer Reviewed: Perfluorochemical Surfactants in the Environment , 2002 .

[9]  P. Ayotte,et al.  Effects of perfluorooctanesulfonate exposure on plasma lipid levels in the Inuit population of Nunavik (Northern Quebec). , 2010, Environmental research.

[10]  T. Arbuckle,et al.  Do perfluoroalkyl substances affect metabolic function and plasma lipids?--Analysis of the 2007-2009, Canadian Health Measures Survey (CHMS) Cycle 1. , 2013, Environmental research.

[11]  Geary W Olsen,et al.  Distribution of perfluorooctanesulfonate and perfluorooctanoate into human plasma lipoprotein fractions. , 2012, Toxicology letters.

[12]  L. S. Haug,et al.  Characterisation of human exposure pathways to perfluorinated compounds--comparing exposure estimates with biomarkers of exposure. , 2011, Environment International.

[13]  E. Gratacós,et al.  Atherogenic lipoprotein subfraction profile in preeclamptic women with and without high triglycerides: different pathophysiologic subsets in preeclampsia. , 2005, Metabolism: clinical and experimental.

[14]  P. Ridker,et al.  Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. , 2007, JAMA.

[15]  D. Gordon,et al.  A single cholesterol measurement underestimates the risk of coronary heart disease. An empirical example from the Lipid Research Clinics Mortality Follow-up Study. , 1990, JAMA.

[16]  Jan Alexander,et al.  Diet and particularly seafood are major sources of perfluorinated compounds in humans. , 2010, Environment international.

[17]  A. Calafat,et al.  Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999-2008. , 2011, Environmental science & technology.

[18]  T. Woodruff,et al.  Environmental Chemicals in Pregnant Women in the United States: NHANES 2003–2004 , 2011, Environmental health perspectives.

[19]  D. Luthy,et al.  Maternal plasma lipid concentrations in early pregnancy and risk of preeclampsia. , 2004, American journal of hypertension.

[20]  J. Bar-Tana,et al.  Mode of Action of Peroxisome Proliferators as Hypolipidemic Drugs. , 1995, The Journal of Biological Chemistry.

[21]  H. Meltzer,et al.  The biobank of the Norwegian mother and child cohort Study: A resource for the next 100 years , 2006, European Journal of Epidemiology.

[22]  Roger G Perkins,et al.  The Toxicology of Perfluorooctanoate , 2004, Critical reviews in toxicology.

[23]  P. Magnus,et al.  Cohort profile: the Norwegian Mother and Child Cohort Study (MoBa). , 2006, International journal of epidemiology.

[24]  John W. Froehlich,et al.  Half-Life of Serum Elimination of Perfluorooctanesulfonate,Perfluorohexanesulfonate, and Perfluorooctanoate in Retired Fluorochemical Production Workers , 2007, Environmental health perspectives.

[25]  B. Koletzko,et al.  Pre- and postnatal exposure to perfluorinated compounds (PFCs). , 2010, Environmental science & technology.

[26]  John W Green,et al.  Cross-Sectional Study of Lipids and Liver Enzymes Related to a Serum Biomarker of Exposure (ammonium perfluorooctanoate or APFO) as Part of a General Health Survey in a Cohort of Occupationally Exposed Workers , 2007, Journal of occupational and environmental medicine.

[27]  C. Packard,et al.  Lipoprotein subfraction changes in normal pregnancy: threshold effect of plasma triglyceride on appearance of small, dense low density lipoprotein. , 1997, The Journal of clinical endocrinology and metabolism.

[28]  L. S. Haug,et al.  A sensitive method for determination of a broad range of perfluorinated compounds in serum suitable for large-scale human biomonitoring. , 2009, Journal of chromatography. A.

[29]  L. Irgens,et al.  The Medical Birth Registry of Norway. Epidemiological research and surveillance throughout 30 years , 2000, Acta obstetricia et gynecologica Scandinavica.

[30]  Ian T Cousins,et al.  Sources, fate and transport of perfluorocarboxylates. , 2006, Environmental science & technology.

[31]  Tobias Frömel,et al.  Biodegradation of fluorinated alkyl substances. , 2010, Reviews of environmental contamination and toxicology.

[32]  R. Luebke,et al.  Immunotoxicity of Perfluorooctanoic Acid and Perfluorooctane Sulfonate and the Role of Peroxisome Proliferator-Activated Receptor Alpha , 2009, Critical reviews in toxicology.

[33]  A. IJzerman,et al.  Nicotinic acid receptor subtypes and their ligands , 2007, Medicinal research reviews.

[34]  Anders Bignert,et al.  Perfluorinated alkyl acids in blood serum from primiparous women in Sweden: serial sampling during pregnancy and nursing, and temporal trends 1996-2010. , 2012, Environmental science & technology.

[35]  M. A. Mohd,et al.  Perfluorooctanesulfonate and related fluorochemicals in human blood from several countries. , 2004, Environmental science & technology.

[36]  Per Magnus,et al.  Self-selection and bias in a large prospective pregnancy cohort in Norway. , 2009, Paediatric and perinatal epidemiology.

[37]  M. Aurell,et al.  Serum lipids and lipoproteins in human pregnancy. , 1966, Clinica chimica acta; international journal of clinical chemistry.

[38]  C. Lau,et al.  Activation of mouse and human peroxisome proliferator-activated receptor-alpha (PPARα) by perfluoroalkyl acids (PFAAs): further investigation of C4-C12 compounds. , 2012, Reproductive toxicology.

[39]  Jane A Hoppin,et al.  Perfluorinated Compounds and Subfecundity in Pregnant Women , 2012, Epidemiology.

[40]  T. Webster,et al.  Exposure to Polyfluoroalkyl Chemicals and Cholesterol, Body Weight, and Insulin Resistance in the General U.S. Population , 2009, Environmental health perspectives.

[41]  J. Klenk,et al.  Analyses of Case–Control Data for Additional Outcomes , 2007, Epidemiology.

[42]  C. Lau,et al.  Perfluoroalkyl acids: a review of monitoring and toxicological findings. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[43]  C. Packard,et al.  Lipoprotein Subfraction Concentrations in Preeclampsia: Pathogenic Parallels to Atherosclerosis , 1997, Obstetrics and gynecology.

[44]  L. Wallentin,et al.  Plasma Lipoproteins Including High Density Lipoprotein Subfractions During Normal Pregnancy , 1985, Obstetrics and gynecology.

[45]  Jiayin Dai,et al.  Association of perfluorooctanoic acid with HDL cholesterol and circulating miR-26b and miR-199-3p in workers of a fluorochemical plant and nearby residents. , 2012, Environmental science & technology.

[46]  Kyle Steenland,et al.  Association of perfluorooctanoic acid and perfluorooctane sulfonate with serum lipids among adults living near a chemical plant. , 2009, American journal of epidemiology.

[47]  Jørn Olsen,et al.  Perfluorinated Chemicals and Fetal Growth: A Study within the Danish National Birth Cohort , 2007, Environmental health perspectives.

[48]  A. Ciampi,et al.  Effects of exposure measurement error when an exposure variable is constrained by a lower limit. , 2003, American journal of epidemiology.

[49]  D. Savitz,et al.  Perfluorooctanoic Acid Exposure and Pregnancy Outcome in a Highly Exposed Community , 2012, Epidemiology.

[50]  C. Lau,et al.  Perfluorooctanoic acid induced developmental toxicity in the mouse is dependent on expression of peroxisome proliferator activated receptor-alpha. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[51]  W. Piechota,et al.  Reference ranges of lipids and apolipoproteins in pregnancy. , 1992, European journal of obstetrics, gynecology, and reproductive biology.

[52]  S. Haeri,et al.  Maternal serum dyslipidemia occurs early in pregnancy in women with mild but not severe preeclampsia. , 2008, American journal of obstetrics and gynecology.

[53]  A. Calafat,et al.  Effect of temperature and duration of storage on the stability of polyfluoroalkyl chemicals in human serum. , 2013, Chemosphere.

[54]  R. Mensink,et al.  Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. , 2003, The American journal of clinical nutrition.

[55]  Z. Akkuş,et al.  Potential atherogenic roles of lipids, lipoprotein(a) and lipid peroxidation in preeclampsia. , 2005, Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology.

[56]  D. Savitz,et al.  Perfluorooctanoic acid, perfluorooctanesulfonate, and serum lipids in children and adolescents: results from the C8 Health Project. , 2010, Archives of pediatrics & adolescent medicine.

[57]  B. Nordestgaard,et al.  Fasting and Nonfasting Lipid Levels: Influence of Normal Food Intake on Lipids, Lipoproteins, Apolipoproteins, and Cardiovascular Risk Prediction , 2008, Circulation.

[58]  Cathrine Thomsen,et al.  Time trends and the influence of age and gender on serum concentrations of perfluorinated compounds in archived human samples. , 2009, Environmental science & technology.

[59]  Hermann Fromme,et al.  Perfluorinated compounds--exposure assessment for the general population in Western countries. , 2009, International journal of hygiene and environmental health.

[60]  K. Vollebregt,et al.  Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study. , 2012, The Journal of clinical endocrinology and metabolism.

[61]  A. Calafat,et al.  Rate of Decline in Serum PFOA Concentrations after Granular Activated Carbon Filtration at Two Public Water Systems in Ohio and West Virginia , 2009, Environmental health perspectives.

[62]  Jonathan P. Benskin,et al.  Exceptionally high serum concentrations of perfluorohexanesulfonate in a Canadian family are linked to home carpet treatment applications. , 2012, Environmental science & technology.

[63]  C. Lau,et al.  Developmental toxicity of perfluorooctane sulfonate (PFOS) is not dependent on expression of peroxisome proliferator activated receptor-alpha (PPAR alpha) in the mouse. , 2009, Reproductive toxicology.