Positive Association Between Perfluoroalkyl Chemicals and Hyperuricemia in Children

Sarah Dee Geiger ) Jie Xiao Anoop Shankar Hyperuricemia in children is associated with increased risk of high blood pressure, metabolic syndrome, and future cardiovascular disease. Serum perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) levels have been shown to be positively associated with hyperuricemia in adults, but the association in children remains unexplored. We therefore examined the association between serum PFOA and PFOS levels and hyperuricemia in a representative sample of US children. A cross-sectional study was performed on 1,772 participants 18 years of age from the National Health and Nutrition Examination Survey 1999-2000 and 2003-2008. The main outcome of interest was hyperuricemia, defined as serum uric acid levels 6 mg/dL. We found that serum levels of PFOA and PFOS were positively associated with hyperuricemia, independent of age, sex, race/ethnicity, body mass index, annual household income, physical activity, serum total cholesterol, and serum cotinine levels. Compared with subjects in quartile 1 (referent), subjects in quartile 4 had multivariable-adjusted odds ratios for hyperuricemia of 1.62 (95% confidence interval: 1.10, 2.37) for PFOA and 1.65 (95% confidence interval: 1.10, 2.49) for PFOS. Our findings indicate that serum perfluoroalkyl chemical levels are significantly associated with hyperuricemia in children even at the lower background exposure levels of the US general population. hyperuricemia; NHANES; pediatrics; perfluoroalkyl chemicals; perfluorooctane sulfonate; perfluorooctanoic acid; PFC; uric acid Abbreviations: CI, confidence interval; LLOD, lower limit of detection; NHANES, National Health and Nutrition Examination Survey; PFC, perfluoroalkyl chemical; PFOA, perfluorooctanoic acid; PFOS, perfluorooctane sulfonate. - Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are 2 of the most studied types of perfluoroalkyl chemicals (PFCs). These chemicals persist in the environment, bioaccumulate, biomagnify along food chains, and have been shown to cause developmental, endocrine, and other adverse health outcomes in laboratory animals (1, 2). Reports from national biomonitoring surveys suggest that detectable levels of PFCs are present in the blood of more than 98% of the US population (3). Known routes of exposure include inhalation, ingestion, and absorption through the skin (49). Potential exposure sources are surfactants, lubricants, polishes, paper and textile coatings, food packaging, and fire-retarding foams, as well as household dust and vegetables and meat products from supermarkets (2, 3, 10, 11). Children tend to experience higher uptake of PFCs than adults, but the relative contribution of each source is unknown (12). Uric acid is a byproduct of purine metabolism with both oxidant and antioxidant properties (13, 14). Elevated serum uric acid levels have an underlying role in gout (15), and studies have shown that moderate elevations in uric acid are also associated with dyslipidemia (16), increased systemic inflammation (17), insulin resistance (18), diabetes mellitus (19), hypertension (20), chronic kidney disease (21), and cardiovascular disease (22). Similarly, studies focused on children have reported associations between elevations in serum uric acid levels and increased risk of hypertension (23), childhood metabolic syndrome (2428), and several other cardiometabolic risk factors (23). Existing studies in populations that are highly exposed to PFCs have demonstrated a positive relationship between exposure to PFCs and elevated serum uric acid in adults (2932). These studies include occupational cohorts of employees from PFC-handling chemical plants (30, 31) as well as a community-based study of residents from the Ohio River valley who were highly exposed to PFOA in drinking water after contamination of their drinking water source from a nearby chemical plant (32). Recently, in a population-based study, Seals et al. (33) demonstrated that PFOA has a concentration-dependent half-life of 2.9 years at higher serum levels and 8.5 years at lower levels, suggesting that, at lower serum levels, PFCs persist in the body for a longer period of time. Given the fact that PFCs are present in the blood of the majority of Americans at low levels (3), in addition to studying population groups with high PFC exposure, it is also important to study the PFCuric acid association at lower background exposure levels typically seen in US general population samples. Furthermore, an important gap in current literature is the fact that the association between PFCs and serum uric acid has not, to our knowledge, been explored in children. Given the role of high serum uric acid levels in childhood metabolic syndrome and other cardiometabolic risk factors (23, 2529) as well as the emerging consensus that the development of cardiovascular disease in adulthood is preceded by metabolic changes occurring in childhood (28, 34, 35), it is important to identify novel risk factors, including environmental factors, associated with hyperuricemia in children. Another advantage of studying associations in children is that, from an epidemiologic point of view, when compared with adults, children generally may have limited cumulative exposure to lifestyle/behavioral risk factors for chronic diseases such as smoking and alcohol intake, and therefore the potential for confounding by these factors tends to be limited. In this context, we sought to examine the association between PFCs and serum uric acid levels in children using National Health and Nutrition Examination Survey (NHANES) data. MATERIALS AND METHODS Study population This study uses 8 years of merged data from NHANES, 19992000, 20032004, 20052006, and 20072008. PFC data were not available for NHANES 20012002. Data collection methods for NHANES have been published and are available online (36). NHANES included a stratified multistage probability sample representative of the civilian noninstitutionalized population in the United States. Selection was based on counties, census blocks, households, and individuals within households and included the oversampling of non-Hispanic blacks and Mexican Americans in order to provide stable estimates of these groups. Subjects were required to sign a consent form before their participation, and approval was obtained from the Human Subjects Committee in the US Department of Health and Human Services. The survey also included biomonitoring for select environmental chemicals, including perfluoroalkyl chemicals, in a random one-third subsample of participants by the National Center for Environmental Health. The central variables for this analysis are laboratory measurements of PFOA, PFOS, and uric acid. Our study sample consisted of children 18 years of age or younger who took part in both the interview and examination components; because NHANES does not sample PFC levels for children under age 12, the age range for this stu (...truncated)