Faculty Bibliography

BACKGROUND:Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are immunotoxic in laboratory studies. Human studies of immune effects are inconsistent. Using the US National Health and Nutrition Examination Survey (NHANES), we examined PFAS serum concentration and indicators of prevalent immune function among 12-19-y-old children. METHODS:In this cross-sectional study, we examined PFAS serum concentration in relation to measles, mumps, and rubella antibody concentrations in NHANES 1999-2000 and 2003-2004 (n = 1,191) and to allergic conditions and allergic sensitization in NHANES 2005-2006 (n = 640). RESULTS:In adjusted, survey-weighted models, a doubling of perfluorooctane sulfonate (PFOS) concentration among seropositive children was associated with a 13.3% (95% confidence interval (CI): -19.9, -6.2) decrease in rubella antibody concentration and a 5.9% decrease in mumps antibody concentration (95% CI: -9.9, -1.6). We observed no adverse association between exposure and current allergic conditions, including asthma. Children with higher PFOS concentration were less likely to be sensitized to any allergen (odds ratio (OR): 0.74; 95% CI: 0.58, 0.95). CONCLUSION/CONCLUSIONS:Increased exposure to several PFAS was associated with lower levels to mumps and rubella antibody concentrations, especially among seropositive individuals. These lower antibody concentrations may indicate a less robust response to vaccination or greater waning of vaccine-derived immunity over time.

BACKGROUND:Rescue and recovery workers responding to the 2001 collapse of the World Trade Center (WTC) sustained exposures to toxic chemicals and have elevated rates of multiple morbidities. METHODS:Using data from the World Trade Center Health Program and the National Death Index for 2002-2011, we examined standardized mortality ratios (SMR) and proportional cancer mortality ratios (PCMR) with indirect standardization for age, sex, race, and calendar year to the U.S. general population, as well as associations between WTC-related environmental exposures and all-cause mortality. RESULTS:We identified 330 deaths among 28,918 responders (SMR 0.43, 95%CI 0.39-0.48). No cause-specific SMRs were meaningfully elevated. PCMRs were elevated for neoplasms of lymphatic and hematopoietic tissue (PCMR 1.76, 95%CI 1.06-2.75). Mortality hazard ratios showed no linear trend with exposure. CONCLUSIONS:Consistent with a healthy worker effect, all-cause mortality among responders was not elevated. There was no clear association between intensity and duration of exposure and mortality. Surveillance is needed to monitor the proportionally higher cancer mortality attributed to lymphatic/hematopoietic neoplasms.

Perfluorooctanoate (PFOA) is detectable in umbilical cord blood and amniotic fluid. Some toxicological findings suggest that perfluoroalkyl substances may be teratogenic. Using data from the C8 Health Project, a 2005-2006 survey in a Mid-Ohio Valley community exposed to PFOA through contaminated drinking water, we examined the association between estimated prenatal PFOA concentration and maternally reported birth defects (n=325) among 10,262 live singleton or multiple births from 1990 to 2006. Logistic regression models accounted for siblings using generalized estimating equations. There was generally no association between estimated PFOA concentration and birth defects, with the possible exception of brain defects, where the odds ratio adjusted for year of conception was 2.6 (95% confidence interval 1.3-5.1) for an increase in estimated PFOA exposure from the 25th to 75th percentile. This estimate, however, was based on 13 cases and may represent a chance finding. Further investigation of this potential association may be warranted.

BACKGROUND:In toxicology studies, perfluorinated compounds affect fetal growth, development, viability, and postnatal growth. There are limited epidemiologic studies on child development. METHODS:We recruited and evaluated 321 children who participated in the C8 Health Project, a 2005-06 survey in a mid-Ohio Valley community highly exposed to perfluorooctanoate (PFOA) through contaminated drinking water. We examined associations between measured childhood PFOA serum concentration and mother and teacher reports of executive function (Behaviour Rating Inventory of Executive Function), attention deficit hyperactivity disorder (ADHD)-like behaviour (Conner's ADHD Diagnostic and Statistical Manual of Mental Disorders IV Scales), and behavioural problems (Behaviour Assessment System for Children) assessed 3 to 4 years later at ages 6-12 years. RESULTS:Overall, neither reports from mothers nor teachers provided clear associations between exposure and child behaviour. Mother reports, however, did suggest favourable associations between exposure and behaviour among boys and adverse associations among girls. On the composite scale from the Behaviour Rating Inventory of Executive Function (n = 318), PFOA exposure had a favourable association among boys (highest vs. lowest quartile β = -6.39; 95% confidence interval [CI] -11.43, -1.35) and an adverse association among girls (highest vs. lowest quartile β = 4.42; 95% CI -0.03, 8.87; interaction P = 0.01). Teacher reports (n = 189) replicated some, but not all of the sex interactions observed in mothers' reports. CONCLUSIONS:Aggregate results did not suggest adverse effects of PFOA on behaviour, but sex-specific results raise the possibility of differing patterns by sex. Results are not consistent between mothers' and teachers' reports. Effect modification by sex may warrant further investigation.

BACKGROUND:Previous research suggests perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) may be associated with adverse pregnancy outcomes. OBJECTIVE:We conducted a population-based study of PFOA and PFOS and birth outcomes from 2005 through 2010 in a Mid-Ohio Valley community exposed to high levels of PFOA through drinking-water contamination. METHODS:Women provided serum for PFOA and PFOS measurement in 2005-2006 and reported reproductive histories in subsequent follow-up interviews. Reported singleton live births among 1,330 women after 1 January 2005 were linked to birth records (n = 1,630) to identify the outcomes of preterm birth (< 37 weeks gestation), pregnancy-induced hypertension, low birth weight (< 2,500 g), and birth weight (grams) among full-term infants. RESULTS:We observed little or no evidence of association between maternal serum PFOA or PFOS and preterm birth (n = 158) or low birth weight (n = 88). Serum PFOA and PFOS were both positively associated with pregnancy-induced hypertension (n = 106), with adjusted odds ratios (ORs) per log unit increase in PFOA and PFOS of 1.27 (95% CI: 1.05, 1.55) and 1.47 (95% CI: 1.06, 2.04), respectively, but associations did not increase monotonically when categorized by quintiles. Results of subanalyses restricted to pregnancies conceived after blood collection were consistent with the main analyses. There was suggestion of a modest negative association between PFOS and birth weight in full-term infants (-29 g per log unit increase; 95% CI: -66, 7), which became stronger when restricted to births conceived after the blood sample collection (-49 g per log unit increase; 95% CI: -90, -8). CONCLUSION/CONCLUSIONS:Results provide some evidence of positive associations between measured serum perfluorinated compounds and pregnancy-induced hypertension and a negative association between PFOS and birth weight among full-term infants.

BACKGROUND:In animal studies, perfluorinated compounds affect fetal growth, development, viability, and postnatal growth. The limited epidemiologic findings on child neurobehavioral development are mixed. METHODS:We recruited and evaluated 320 children who participated in the C8 Health Project, a 2005-2006 survey in a Mid-Ohio Valley community highly exposed to perfluorooctanoate (PFOA) through contaminated drinking water. We examined associations among estimated in utero PFOA exposure, measured childhood PFOA serum concentration, and subsequent performance on neuropsychological tests 3-4 years later at ages 6-12 years. We assessed Intelligence Quotient (IQ) reading and math skills, language, memory and learning, visual-spatial processing, and attention. All multivariable linear regression models were adjusted for age, sex, home environment, test examiner, and maternal IQ. Models with measured childhood PFOA were additionally adjusted for child body mass index. RESULTS:Children in the highest as compared with lowest quartile of estimated in utero PFOA had increases in Full Scale IQ (β 4.6, 95% confidence interval [CI] = 0.7-8.5) and decreases in characteristics of attention deficit/hyperactivity disorder as measured by the Clinical Confidence Index of Connors' Continuous Performance Test-II (β -8.5, 95% CI = -16.1 to -0.8). There were negligible associations between PFOA and reading or math skills or neuropsychological functioning. CONCLUSION/CONCLUSIONS:These results do not suggest an adverse association between the levels of PFOA exposure experienced by children in this cohort and their performance on neuropsychological tests.

BACKGROUND:Influenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established. METHODS:Seventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses. RESULTS:Only 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination. CONCLUSIONS:Protection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.

The extent to which polyfluoroalkyl compounds (PFCs) are detectable in amniotic fluid is unknown. Using paired samples from 28 women, we compared the concentration of 8 PFCs measured in serum, the standard matrix for assessing human exposure, amniotic fluid from routine amniocentesis, and urine. Perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorooctane sulfonate (PFOS), and perfluorohexane sulfonate (PFHxS) were detected in all maternal serum samples. The number of amniotic fluid samples with detectable concentrations differed by PFC (PFOA n=24; PFNA n=10; PFOS n=9; PFHxS n=4). The correlation coefficient between maternal serum and amniotic PFC levels varied considerably by PFC (PFOA ρ=0.64, p<0.001; PFNA ρ=0.05, p=0.9; PFOS ρ=0.76, p=0.01; PFHxS ρ=0.80, p=0.2). Using linear regression, PFOA appeared to be commonly detected in amniotic fluid if the serum concentration exceeded approximately 1.5 ng/mL whereas PFOS was rarely detected in amniotic fluid until the serum concentration was about 5.5 ng/mL. No PFCs were detected in urine.

BACKGROUND:Perfluorooctanoic acid (PFOA) is a potential cause of adverse pregnancy outcomes, but previous studies have been limited by low exposures and small study size. OBJECTIVES/OBJECTIVE:Using birth certificate information, we examined the relation between estimated PFOA exposure and birth outcomes in an area of West Virginia and Ohio whose drinking water was contaminated by a chemical plant. METHODS:Births in the study area from 1990 through 2004 were examined to generate case groups of stillbirth (n = 106), pregnancy-induced hypertension (n = 224), preterm birth (n = 3,613), term low birth weight (n = 918), term small-for-gestational-age (SGA) (n = 353), and a continuous measure of birth weight among a sample of term births (n = 4,534). A 10% sample of term births ≥ 2,500 g were selected as a source of controls (n = 3,616). Historical estimates of serum PFOA were derived from a previously developed fate and transport model. In a second study, we examined 4,547 area births linked to a survey with residential history data. RESULTS:In the analysis based only on birth records, we found no consistent evidence of an association between estimated PFOA exposure and stillbirth, pregnancy-induced hypertension, preterm birth, or indices of fetal growth. In the analysis of birth records linked to the survey, PFOA was unrelated to pregnancy-induced hypertension or preterm birth but showed some suggestion of an association with early preterm birth. Measures of growth restriction showed weak and inconsistent associations with PFOA. CONCLUSIONS:Based on the analysis using the health survey, these results provide little support for an effect of PFOA exposure on most pregnancy outcomes, except for early preterm birth and possibly fetal growth restriction.

BACKGROUND:There are limited data on the associations between maternal or newborn and child exposure to perfluoroalkyl acids (PFAAs), including perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). This study provides an opportunity to assess the association between PFAA concentrations in mother-child pairs in a population exposed to PFOA via drinking water. OBJECTIVES/OBJECTIVE:We aimed to determine the relationship between mother-child PFAA serum concentrations and to examine how the child:mother ratio varies with child's age, child's sex, drinking-water PFOA concentration, reported bottled water use, and mother's breast-feeding intention. METHODS:We studied 4,943 mother-child pairs (children, 1-19 years of age). The child:mother PFAA ratio was stratified by possible determinants. Results are summarized as geometric mean ratios and correlation coefficients between mother-child pairs, overall and within strata. RESULTS:Child and mother PFOA and PFOS concentrations were correlated (r = 0.82 and 0.26, respectively). Up to about 12 years of age, children had higher serum PFOA concentrations than did their mothers. The highest child:mother PFOA ratio was found among children ≤ 5 years (44% higher than their mothers), which we attribute to in utero exposure and to exposure via breast milk and drinking water. Higher PFOS concentrations in children persisted until at least 19 years of age (42% higher than their mothers). Boys > 5 years of age had significantly higher PFOA and PFOS child:mother ratios than did girls. CONCLUSION/CONCLUSIONS:Concentrations of both PFOA and PFOS tended to be higher in children than in their mothers. This difference persisted until they were about 12 years of age for PFOA and at least 19 years of age for PFOS.