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Predictors of per- and polyfluoroalkyl substance (PFAS) plasma concentrations in 6-10 year old American children Maria H Harris, Sheryl L Rifas-Shiman, Antonia M. Calafat, Xiaoyun Ye, Ana Maria Mora, Thomas F Webster, Emily Oken, and Sharon K. Sagiv Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.6b05811 • Publication Date (Web): 22 Mar 2017 Downloaded from http://pubs.acs.org on March 24, 2017
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Environmental Science & Technology
Predictors of per- and polyfluoroalkyl substance (PFAS) plasma concentrations in 6-10 year old American children Maria H. Harris*,1,2, Sheryl L. Rifas-Shiman3, Antonia M. Calafat4, Xiaoyun Ye4, Ana Maria Mora5,6, Thomas F. Webster5, Emily Oken3,7 and Sharon K. Sagiv1,2
Affiliations 1
Center for Environmental Research and Children’s Health, University of California, Berkeley
School of Public Health, Berkeley, California, USA 2
Division of Epidemiology, University of California, Berkeley School of Public Health,
Berkeley, California, USA 3
Obesity Prevention Program, Department of Population Medicine, Harvard Medical School and
Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA 4
Division of Laboratory Sciences, National Center for Environmental Health, Centers for
Disease Control and Prevention, Atlanta, Georgia, USA 5
Department of Environmental Health, Boston University School of Public Health, Boston,
Massachusetts, USA 6
Central American Institute for Studies on Toxic Substances, Universidad Nacional, Heredia,
Costa Rica 7
Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
*Corresponding author: Maria H Harris, PhD Center for Environmental Research and Children’s Health University of California, Berkeley School of Public Health 1995 University Ave., Suite 265 Berkeley, CA 94720 USA Telephone: (510) 642-9508 Fax: (510) 642-9083 Email:
[email protected] 1 ACS Paragon Plus Environment
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Supporting Information: Tables presenting (1) results from unadjusted bivariable models; (2) predictors of linear and branched PFOS isomer (n-PFOS and sm-PFOS) concentrations; (3) summary statistics for PFAS concentrations measured in maternal plasma samples from early pregnancy; (4) PFAS plasma geometric means by year of collection in Project Viva compared to geometric means for NHANES participants.
Acknowledgments: We thank the participants and staff of Project Viva. We also thank Kayoko Kato, Ayesha Patel, and Tao Jia for the PFAS measurements. This work was supported by grant funding from the National Institutes of Health: R01 ES021447, R01 HD034568, K24 HD069408, and P30 DK092924. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or any other body. The authors declare they have no competing financial interests.
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ABSTRACT
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Certain per- and polyfluoroalkyl substances (PFASs) are suspected developmental
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toxicants, but data on PFAS concentrations and exposure routes in children are limited. We
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measured plasma PFASs in children aged 6-10 years from the Boston-area Project Viva pre-birth
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cohort, and used multivariable linear regression to estimate associations with sociodemographic,
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behavioral, and health-related factors, and maternal PFASs measured during pregnancy. PFAS
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concentrations in Project Viva children (sampled 2007-2010) were similar to concentrations
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among youth participants (aged 12-19 years) in the 2007-8 and 2009-10 National Health and
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Nutrition Examination Survey (NHANES); mean concentrations of most PFASs declined from
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2007 to 2010 in Project Viva and NHANES. In mutually-adjusted models, predictors of higher
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PFAS concentrations included older child age, lower adiposity, carpeting or a rug in the child’s
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bedroom, higher maternal education, and higher neighborhood income. Concentrations of
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perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate
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(PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH) were 26-
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36% lower in children of black mothers compared to children of white mothers and increased 12-
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21% per interquartile range increase in maternal pregnancy PFASs. Breastfeeding duration did
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not predict childhood PFAS concentrations in adjusted multivariable models. Together, the
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studied predictors explained the observed variability in PFAS concentrations to only a modest
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degree.
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BACKGROUND Per- and polyfluoroalkyl substances (PFASs) are a class of synthetic compounds employed since the 1950s in a range of industrial and consumer products, including stain3 ACS Paragon Plus Environment
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resistant fabric and carpet treatments and oil-resistant coatings for food packaging.1-3 Certain
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PFASs are persistent in the environment, accumulate in the human body, and have been widely
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detected in human biosamples.2, 4, 5 Though evidence on the developmental health effects of
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PFASs is mixed, early-life exposure to PFASs has been linked in some studies to
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neurobehavioral problems,6-9 immune suppression,10, 11 and increased adiposity12-14 in children.
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Exposure to PFASs for the general population can occur through use of PFAS-containing
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products and contact with PFASs in household dust and air.2, 15-17 The use of PFASs in food
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packaging as well as their presence in some foods suggests dietary exposures may also be
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important.2, 4, 15, 16 Young children, who have increased hand-to-mouth activity and exposure to
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dust on household surfaces and greater food consumption relative to body weight, may have
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higher uptake of PFAS than adults.15 Breastfeeding may also be an important exposure pathway
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for infants and toddlers.18-20
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Evidence on factors influencing PFAS concentrations in children is limited. PFASs are
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known to cross the placenta,21 and concentrations of PFASs in maternal peripheral blood
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correlate highly with infant cord blood concentrations,22-24 suggesting that placental transfer
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could represent an exposure route for children. Prior studies have also reported higher
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concentrations of PFASs among children with longer duration of breastfeeding.18, 25, 26 In studies
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that examined PFAS concentrations in mothers and children aged 2-826 and 6-1127 years, mother
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and child levels measured at the same time point were moderately to highly correlated, with
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concentrations higher among children.
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Though some studies have reported higher PFAS concentrations in boys28, 29 and older
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children,18, 28, 30 others have not observed consistent patterns by sex18, 30 or age.25, 26 A small
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study investigating potential predictors of serum PFASs in young children (age 2-8 years, n=68)
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in California identified residential dust PFAS levels and frequency of wearing waterproof clothes
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as significant predictors; dietary predictors varied across measured PFAS analytes, but included
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consumption of canned and fresh fish, French fries, hot dogs, chips, and microwave popcorn.26
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Further research is needed to characterize factors affecting PFAS concentrations in
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children, who appear to have higher PFAS body burdens than adults and may also be particularly
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sensitive to potential developmental toxicity. In a large prospective cohort of mothers and
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children followed from pregnancy onwards, we measured plasma concentrations of PFASs in
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children (aged 6-10 years), and examined associations with potential predictors including
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demographic characteristics, behavioral and health-related factors, and maternal PFAS
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concentrations measured in pregnancy.
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METHODS
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Study population
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Participants were drawn from Project Viva, a prospective pre-birth cohort that enrolled
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pregnant mothers from 1999-2002 at their first prenatal visits at Atrius Harvard Vanguard
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Medical Associates, a multispecialty group practice in urban and suburban Eastern
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Massachusetts.31 Of 2,128 enrolled mothers with live single births, 1,668 contributed blood
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samples during early pregnancy (median 9.7 weeks gestation, range 4.8‒21.4) in 1999-2000. At
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visits in mid-childhood (median age 7.7 years, range 6.6-10.6) in 2007-2010, a subset of children
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(n=702) contributed blood samples. The Human Subjects Committees of participating
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institutions approved all study protocols. All mothers provided written informed consent, and
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children provided verbal assent at the mid-childhood visit. The involvement of the Centers for
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Disease Control and Prevention (CDC) laboratory did not constitute engagement in human
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subjects research. All study forms are available at https://www.hms.harvard.edu/viva/.
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Maternal and child PFAS measurements Maternal and child plasma samples were stored in cryovial (non-PFAS containing) tubes
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in liquid nitrogen freezers. Samples were subsequently thawed, aliquoted, shipped to the
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Division of Laboratory Sciences at the Centers for Disease Control and Prevention (CDC) and
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analyzed for concentrations of 8 PFAS analytes: perfluorooctane sulfonate (PFOS),
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perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), perfluorononanoate (PFNA), 2-
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(N-ethyl-perfluorooctane sulfonamido) acetate (Et-PFOSA-AcOH; also known as EtFOSAA), 2-
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(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH; also known as
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MeFOSAA), perfluorodecanoate (PFDeA; also known as PFDA), and perfluorooctane
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sulfonamide (PFOSA; also known as FOSA). Analyses of maternal plasma were conducted in
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2014 and have been previously described.32 Child plasma samples were analyzed in 2015 using
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on-line solid-phase extraction coupled with isotope dilution high-performance liquid
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chromatography-tandem mass spectrometry. Low-concentration quality control materials (QCs)
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and high-concentration QCs, prepared from a calf serum pool, were analyzed with the study
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samples, analytical standards, and with reagent and serum blanks to ensure the accuracy and
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reliability of the data.33 Analytical methods for the maternal and child samples were the same as
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those used to analyze PFAS concentrations in NHANES samples for the 2011-12 and 2013-14
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NHANES cycles, respectively.34, 35 Child plasma samples were also analyzed for concentrations
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of linear and branched isomers of PFOA [n-perfluorooctanoate (n-PFOA), branched
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perfluorooctanoates (Sb-PFOA)] and PFOS [n-perfluorooctane sulfonate (n-PFOS),
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perfluoromethylheptane sulfonates (Sm-PFOS), perfluorodimethylhexane sulfonates (Sm2-
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PFOS)]. A total of 653 child plasma samples had sufficient volume for PFAS quantification and
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limits of detection (LOD) were 0.1 ng/mL; values below the LOD were estimated as LOD/√2
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(0.0707 ng/mL).
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Predictor data Project Viva study staff collected data on participant demographics and health-related
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behaviors via study questionnaires and interviews. We included data on sociodemographic
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characteristics, health history, and behavioral factors that we hypothesized might serve as
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potential predictors of PFAS plasma concentrations in childhood.
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At the mid-childhood visit, mothers were asked about child participants’ fast food
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consumption and the presence of carpeting or rugs in the rooms where the child “usually sleeps”
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and “spends most awake time.” Mothers also reported on children’s outdoor activities in summer
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and winter [“In the past year, how much do your child’s activities (playing outdoors, playing
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sports, spectator sports, etc.) take him/her outside?”] with possible responses “1. not that often,”
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“2. a moderate amount,” “3. quite a lot,” and “4. virtually all the time.” Based on response
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frequency, we categorized outdoor activity time as low (1 or 2 for summer/1 for winter), medium
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(3 for summer/2 for winter) or high (4 for summer/3 or 4 for winter). .
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Project Viva staff measured children’s height and weight at the mid-childhood visit. We
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calculated body mass index (BMI) as weight in kilograms/(height in meters)2 and calculated BMI
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percentiles for age and sex using 2000 CDC reference data.36 Per CDC guidelines, we
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categorized BMI as underweight/normal weight (
