Faculty Bibliography

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.

BACKGROUND:We assessed the association between perfluorooctanoic acid (PFOA) and pregnancy outcome in an area with elevated exposure to PFOA from drinking water contaminated by chemical plant releases. METHODS:Serum PFOA was measured, and reproductive and residential histories were obtained during 2005-2006. We estimated serum PFOA levels at the time of pregnancy for 11,737 pregnancies occurring between 1990 and 2006, based on historical information on PFOA releases, environmental distribution, pharmacokinetic modeling, and residential histories. We assessed the association between PFOA and the odds of miscarriage, stillbirth, preeclampsia, preterm birth, term low birthweight, and birth defects, controlling for calendar time, age, parity, education, and smoking. PFOA exposure was evaluated as a continuous measure (with and without log transformation) and in quintiles, combining the lowest 2 quintiles (< 6.8 ng/mL) as the referent. RESULTS:Measures of association between PFOA and miscarriage, preterm birth, term low birthweight, and birth defects were close to the null. Odds of stillbirth were elevated in the fourth quintile only. For preeclampsia, the odds ratio was 1.13 (95% confidence interval = 1.00-1.28) for an interquartile shift in log-transformed PFOA, and the odds ratios were 1.1-1.2 across the upper 3 quintiles of exposure. CONCLUSIONS:In this large, population-based study in a region with markedly elevated PFOA exposure, we found no associations between estimated serum PFOA levels and adverse pregnancy outcomes other than possibly preeclampsia. Conclusions are tempered by inherent limitations in exposure reconstruction and self-reported pregnancy outcome information.

After the emergence of pandemic influenza viruses in 1957, 1968, and 2009, existing seasonal viruses were observed to be replaced in the human population by the novel pandemic strains. We have previously hypothesized that the replacement of seasonal strains was mediated, in part, by a population-scale boost in antibodies specific for conserved regions of the hemagglutinin stalk and the viral neuraminidase. Numerous recent studies have shown the role of stalk-specific antibodies in neutralization of influenza viruses; the finding that stalk antibodies can effectively neutralize virus alters the existing dogma that influenza virus neutralization is mediated solely by antibodies that react with the globular head of the viral hemagglutinin. The present study explores the possibility that stalk-specific antibodies were boosted by infection with the 2009 H1N1 pandemic virus and that those antibodies could have contributed to the disappearance of existing seasonal H1N1 influenza virus strains. To study stalk-specific antibodies, we have developed chimeric hemagglutinin constructs that enable the measurement of antibodies that bind the hemagglutinin protein and neutralize virus but do not have hemagglutination inhibition activity. Using these chimeric hemagglutinin reagents, we show that infection with the 2009 pandemic H1N1 virus elicited a boost in titer of virus-neutralizing antibodies directed against the hemagglutinin stalk. In addition, we describe assays that can be used to measure influenza virus-neutralizing antibodies that are not detected in the traditional hemagglutination inhibition assay.

Studies on ethnic differences in the risk of pre-eclampsia are limited. We linked birth records for 902,460 singleton births for the period 1995-2003 in New York City with hospital discharge data to evaluate the association between ethnicity and the risk of pre-eclampsia and compare risks between US-born and foreign-born women. Logistic regression models adjusted for maternal age, maternal education, parity, self-reported pre-pregnancy maternal weight, smoking during pregnancy and year of delivery were used to compare each ethnic group with non-Hispanic White women. The prevalence of pre-eclampsia in this study population was 3.2%. Among the major ethnic groups considered in our study, East Asian women had the lowest risk of pre-eclampsia (1.4%) and Mexican women had the highest risk (5.0%). Compared with non-Hispanic White women, there was a slightly decreased risk for East Asian women (adjusted OR = 0.8, [95% CI 0.7, 0.8]), similar risk for North African women (adjusted OR = 1.1, [95% CI 0.9, 1.3]), and increased risk for all other major ethnic groups (adjusted ORs: 1.3, 2.9), with the highest risk for Mexican women (adjusted OR = 2.9, [95% CI 2.7, 3.1]). No difference in risks was observed for US- vs. foreign-born women with the exception that foreign-born South-East Asian and Pacific Islanders had an increased risk of pre-eclampsia (adjusted OR = 1.8, [95% CI 1.0, 3.1]) relative to those born in the US. We concluded that there was ethnic heterogeneity in the development of pre-eclampsia among women in New York City and that Asian subgroups should be examined separately in future studies on ethnicity. Our results should contribute to screening for pre-eclampsia taking ethnic variation into account, and may help to suggest leads for the study of the aetiology of the condition.

BACKGROUND:Perfluorinated compounds (PFCs) are persistent environmental pollutants. Toxicology studies demonstrate the potential for perfluorooctanoic acid (PFOA) and other PFCs to affect human growth and development. Attention deficit/hyperactivity disorder (ADHD) is a developmental disorder with suspected environmental and genetic etiology. OBJECTIVES/OBJECTIVE:We examined the cross-sectional association between serum PFC concentration and parent or self-report of doctor-diagnosed ADHD with and without current ADHD medication. METHODS:We used data from the C8 Health Project, a 2005-2006 survey in a Mid-Ohio Valley community highly exposed to PFOA through contaminated drinking water, to study non-Hispanic white children 5-18 years of age. Logistic regression models were adjusted for age and sex. RESULTS:Of the 10,546 eligible children, 12.4% reported ADHD and 5.1% reported ADHD plus ADHD medication use. We observed an inverted J-shaped association between PFOA and ADHD, with a small increase in prevalence for the second quartile of exposure compared with the lowest, and a decrease for the highest versus lowest quartile. The prevalence of ADHD plus medication increased with perfluorohexane sulfonate (PFHxS) levels, with an adjusted odds ratio of 1.59 (95% confidence interval, 1.21-2.08) comparing the highest quartile of exposure to the lowest. We observed a modest association between perfluorooctane sulfonate and ADHD with medication. CONCLUSIONS:The most notable finding for PFOA and ADHD, a reduction in prevalence at the highest exposure level, is unlikely to be causal, perhaps reflecting a spurious finding related to the geographic determination of PFOA exposure in this population or to unmeasured behavioral or physiologic correlates of exposure and outcome. Possible positive associations between other PFCs and ADHD, particularly PFHxS, warrant continued investigation.

PURPOSE/OBJECTIVE:To compare the sexual behaviors of young people in South Africa (SA) and the United States (US) with the aim to better understand the potential role of sexual behavior in HIV transmission in these two countries that have strikingly different HIV epidemics. METHODS:Nationally representative, population-based surveys of young people aged 18-24 years from SA (n = 7,548) and the US (n = 13,451) were used for the present study. RESULTS:The prevalence of HIV was 10.2% in SA and <1% in the US. Young women and men in the US reported an earlier age of first sex than those in SA (mean age of coital debut for women: US [16.5], SA [17.4]; for men: US [16.4], SA [16.7]). The median number of lifetime partners is higher in the US than in SA: women: US (4), SA (2); men: US (4), SA (3). The use of condom at last sex is reported to be lower in the US than in SA: women: US (36.1%), SA (45.4%); men: US (48%), SA (58%). On average, young women in SA report greater age differences with their sex partners than young women in the US. CONCLUSION/CONCLUSIONS:Young people in the US report riskier sexual behaviors than young people in SA, despite the much higher prevalence of HIV infection in SA. Factors above and beyond sexual behavior likely play a key role in the ongoing transmission of HIV in South African youth, and thus should be urgently uncovered to develop maximally effective prevention strategies.