Beth Elston

Perfluorooctanoic Acid Exposure and Pregnancy Outcome in a Highly Exposed Community

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.

Relationship of perfluorooctanoic acid exposure to pregnancy outcome based on birth records in the mid-Ohio Valley.

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: 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.

Exposure to Perfluoroalkyl Acids and Markers of Kidney Function among Children and Adolescents Living near a Chemical Plant

Background: Serum levels of perfluorooctanoic acid (PFOA) have been associated with decreased renal function in cross-sectional analyses, but the direction of the association is unclear. Objectives: We examined the association of measured and model-predicted serum PFOA concentrations with estimated glomerular filtration rate (eGFR), a marker of kidney function, in a highly exposed population (median serum PFOA, 28.3 ng/mL). Methods: We measured serum creatinine, PFOA, perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) and calculated eGFR in 9,660 children 1 to < 18 years of age at study enrollment. We predicted concurrent and historical serum PFOA concentrations using a validated environmental, exposure, and pharmacokinetic model based on individual residential histories, and used linear regression to estimate the association between eGFR and measured and predicted serum PFOA concentrations. We hypothesized that predicted serum PFOA levels would be less susceptible to reverse causation than measured levels. Results: An interquartile range increase in measured serum PFOA concentrations [IQR ln(PFOA) = 1.63] was associated with a decrease in eGFR of 0.75 mL/min/1.73 m2 (95% CI: –1.41, –0.10; p = 0.02). Measured serum levels of PFOS, PFNA, and PFHxS were also cross-sectionally associated with decreased eGFR. In contrast, predicted serum PFOA concentrations at the time of enrollment were not associated with eGFR (–0.10; 95% CI: –0.80, 0.60; p = 0.78). Additionally, predicted serum PFOA levels at birth and during the first ten years of life were not related to eGFR. Conclusions: Our findings suggest that the cross-sectional association between eGFR and serum PFOA observed in this and prior studies may be a consequence of, rather than a cause of, decreased kidney function.

Ambient Fine Particulate Matter, Nitrogen Dioxide, and Term Birth Weight in New York, New York

Building on a unique exposure assessment project in New York, New York, we examined the relationship of particulate matter with aerodynamic diameter less than 2.5 μm and nitrogen dioxide with birth weight, restricting the population to term births to nonsmokers, along with other restrictions, to isolate the potential impact of air pollution on growth. We included 252,967 births in 2008-2010 identified in vital records, and we assigned exposure at the residential location by using validated models that accounted for spatial and temporal factors. Estimates of association were adjusted for individual and contextual sociodemographic characteristics and season, using linear mixed models to quantify the predicted change in birth weight in grams related to increasing pollution levels. Adjusted estimates for particulate matter with aerodynamic diameter less than 2.5 μm indicated that for each 10-µg/m(3) increase in exposure, birth weights declined by 18.4, 10.5, 29.7, and 48.4 g for exposures in the first, second, and third trimesters and for the total pregnancy, respectively. Adjusted estimates for nitrogen dioxide indicated that for each 10-ppb increase in exposure, birth weights declined by 14.2, 15.9, 18.0, and 18.0 g for exposures in the first, second, and third trimesters and for the total pregnancy, respectively. These results strongly support the association of urban air pollution exposure with reduced fetal growth.

Pregnancy-Induced Hypertension and Diabetes and the Risk of Cardiovascular Disease, Stroke, and Diabetes Hospitalization in the Year Following Delivery

Although pregnancy events predict the long-term risk of chronic disease, little is known about their short-term impact because of the rarity of clinical events. We examined hospital discharge diagnoses linked to birth certificate data in the year following delivery for 849,639 births during 1995-2004 in New York City, New York. Adjusted odds ratios characterized the relationship between pregnancy complications and subsequent hospitalization for cardiovascular disease, stroke, and diabetes. Gestational hypertension was related to heart failure (adjusted odds ratio = 2.6, 95% confidence interval: 1.5, 4.5). Preeclampsia was related to all of the outcomes considered except type 1 diabetes, with adjusted odds ratios ranging from 2.0 to 4.1. Gestational diabetes was strongly related to the risk of subsequent diabetes (for type 1 diabetes, adjusted odds ratio = 40.4, 95% confidence interval: 23.8, 68.5; for type 2 diabetes, adjusted odds ratio = 22.6, 95% confidence interval: 16.9, 30.4) but to no other outcomes. The relationship of pregnancy complications to future chronic disease is apparent as early as the year following delivery. Moreover, elucidating short-term clinical outcomes offers the potential for etiological insights into the relationship between pregnancy events and chronic disease over the life course.

Ambient Fine Particulate Matter, Nitrogen Dioxide, and Preterm Birth in New York City.

Background: Recent studies have suggested associations between air pollution and various birth outcomes, but the evidence for preterm birth is mixed. Objective: We aimed to assess the relationship between air pollution and preterm birth using 2008–2010 New York City (NYC) birth certificates linked to hospital records. Methods: We analyzed 258,294 singleton births with 22–42 completed weeks gestation to nonsmoking mothers. Exposures to ambient fine particles (PM2.5) and nitrogen dioxide (NO2) during the first, second, and cumulative third trimesters within 300 m of maternal address were estimated using data from the NYC Community Air Survey and regulatory monitors. We estimated the odds ratio (OR) of spontaneous preterm (gestation < 37 weeks) births for the first- and second-trimester exposures in a logistic mixed model, and the third-trimester cumulative exposures in a discrete time survival model, adjusting for maternal characteristics and delivery hospital. Spatial and temporal components of estimated exposures were also separately analyzed. Results: PM2.5 was not significantly associated with spontaneous preterm birth. NO2 in the second trimester was negatively associated with spontaneous preterm birth in the adjusted model (OR = 0.90; 95% CI: 0.83, 0.97 per 20 ppb). Neither pollutant was significantly associated with spontaneous preterm birth based on adjusted models of temporal exposures, whereas the spatial exposures showed significantly reduced odds ratios (OR = 0.80; 95% CI: 0.67, 0.96 per 10 μg/m3 PM2.5 and 0.88; 95% CI: 0.79, 0.98 per 20 ppb NO2). Without adjustment for hospital, these negative associations were stronger. Conclusion: Neither PM2.5 nor NO2 was positively associated with spontaneous preterm delivery in NYC. Delivery hospital was an important spatial confounder. Citation: Johnson S, Bobb JF, Ito K, Savitz DA, Elston B, Shmool JL, Dominici F, Ross Z, Clougherty JE, Matte T. 2016. Ambient fine particulate matter, nitrogen dioxide, and preterm birth in New York City. Environ Health Perspect 124:1283–1290; http://dx.doi.org/10.1289/ehp.1510266

African American Race and HIV Virological Suppression: Beyond Disparities in Clinic Attendance

Racial disparities in clinic attendance may contribute to racial disparities in plasma human immunodeficiency virus type 1 : HIV-1) RNA levels among HIV-positive patients in care. Data from 946 African American and 535 Caucasian patients receiving HIV care at the University of North Carolina Center for AIDS Research HIV clinic between January 1, 1999, and August 1, 2012, were used to estimate the association between African American race and HIV virological suppression (i.e., undetectable HIV-1 RNA) when racial disparities in clinic attendance were lessened. Clinic attendance was measured as the proportion of scheduled clinic appointments attended (i.e., visit adherence) or the proportion of six 4-month intervals with at least 1 attended scheduled clinic appointment (i.e., visit constancy). In analyses accounting for patient characteristics, the risk ratio for achieving suppression when comparing African Americans with Caucasians was 0.91 (95% confidence interval: 0.85, 0.98). Lessening disparities in adherence or constancy lowered disparities in virological suppression by up to 44.4% and 11.1%, respectively. Interventions that lessen disparities in adherence may be more effective in eliminating disparities in suppression than interventions that lessen disparities in constancy. Given that gaps in care were limited to be no more than 2 years for both attendance measures, the impact of lessening disparities in adherence may be overstated.

Ambient Fine Particulate Matter, Nitrogen Dioxide, and Hypertensive Disorders of Pregnancy in New York City.

Background: Previous studies suggested a possible association between fine particulate matter air pollution (PM2.5) and nitrogen dioxide (NO2) and the development of hypertensive disorders of pregnancy, but effect sizes have been small and methodologic weaknesses preclude firm conclusions. Methods: We linked birth certificates in New York City in 2008–2010 to hospital discharge diagnoses and estimated air pollution exposure based on maternal address. The New York City Community Air Survey provided refined estimates of PM2.5 and NO2 at the maternal residence. We estimated the association between exposures to PM2.5 and NO2 in the first and second trimester and risk of gestational hypertension, mild preeclampsia, and severe preeclampsia among 268,601 births. Results: In unadjusted analyses, we found evidence of a positive association between both pollutants and gestational hypertension. However, after adjustment for individual covariates, socioeconomic deprivation, and delivery hospital, we did not find evidence of an association between PM2.5 or NO2 in the first or second trimester and any of the outcomes. Conclusions: Our data did not provide clear evidence of an effect of ambient air pollution on hypertensive disorders of pregnancy. Results need to be interpreted with caution considering the quality of the available exposure and health outcome measures and the uncertain impact of adjusting for hospital. Relative to previous studies, which have tended to identify positive associations with PM2.5 and NO2, our large study size, refined air pollution exposure estimates, hospital-based disease ascertainment, and little risk of confounding by socioeconomic deprivation, does not provide evidence for an association.

Area-level socioeconomic deprivation, nitrogen dioxide exposure, and term birth weight in New York City.

Numerous studies have linked air pollution with adverse birth outcomes, but relatively few have examined differential associations across the socioeconomic gradient. To evaluate interaction effects of gestational nitrogen dioxide (NO2) and area-level socioeconomic deprivation on fetal growth, we used: (1) highly spatially-resolved air pollution data from the New York City Community Air Survey (NYCCAS); and (2) spatially-stratified principle component analysis of census variables previously associated with birth outcomes to define area-level deprivation. New York City (NYC) hospital birth records for years 2008-2010 were restricted to full-term, singleton births to non-smoking mothers (n=243,853). We used generalized additive mixed models to examine the potentially non-linear interaction of nitrogen dioxide (NO2) and deprivation categories on birth weight (and estimated linear associations, for comparison), adjusting for individual-level socio-demographic characteristics and sensitivity testing adjustment for co-pollutant exposures. Estimated NO2 exposures were highest, and most varying, among mothers residing in the most-affluent census tracts, and lowest among mothers residing in mid-range deprivation tracts. In non-linear models, we found an inverse association between NO2 and birth weight in the least-deprived and most-deprived areas (p-values<0.001 and 0.05, respectively) but no association in the mid-range of deprivation (p=0.8). Likewise, in linear models, a 10 ppb increase in NO2 was associated with a decrease in birth weight among mothers in the least-deprived and most-deprived areas of -16.2g (95% CI: -21.9 to -10.5) and -11.0 g (95% CI: -22.8 to 0.9), respectively, and a non-significant change in the mid-range areas [β=0.5 g (95% CI: -7.7 to 8.7)]. Linear slopes in the most- and least-deprived quartiles differed from the mid-range (reference group) (p-values<0.001 and 0.09, respectively). The complex patterning in air pollution exposure and deprivation in NYC, however, precludes simple interpretation of interactive effects on birth weight, and highlights the importance of considering differential distributions of air pollution concentrations, and potential differences in susceptibility, across deprivation levels.

The population impact of eliminating homelessness on HIV viral suppression among people who use drugs.

Objective:We sought to estimate the change in viral suppression prevalence if homelessness were eliminated from a population of HIV-infected people who use drugs. Design:Community-recruited prospective cohort of HIV-infected people who use drugs in Vancouver, Canada. Behavioural information was collected at baseline and linked to a province-wide HIV/AIDS treatment database. The primary outcome was viral suppression (<50 copies/ml) measured during subsequent routine clinical care. Methods:We employed an imputation-based marginal modelling approach. First, we used modified Poisson regression to estimate the relationship between homelessness and viral suppression (adjusting for sociodemographics, substance use, addiction treatment, and other confounders). Then, we imputed an outcome probability for each individual while manipulating the exposure (homelessness). Population viral suppression prevalence under realized and ‘housed’ scenarios were obtained by averaging these probabilities across the study population. Bootstrapping was conducted to calculate 95% confidence limits. Results:Of 706 individuals interviewed between January 2005 and December 2013, the majority were men (66.0%), of white race/ethnicity (55.1%), and had a history of injection drug use (93.6%). At first study visit, 223 (31.6%) reported recent homelessness, and 37.8% were subsequently identified as virally suppressed. Adjusted marginal models estimated a 15.1% relative increase [95% confidence interval (CI) 9.0–21.7%) in viral suppression in the entire population – to 43.5% (95% CI 39.4–48.2%) – if all homeless individuals were housed. Among those homeless, eliminating this exposure would increase viral suppression from 22.0 to 40.1% (95% CI 35.1–46.1%), an 82.3% relative increase. Conclusion:Interventions to house homeless, HIV-positive individuals who use drugs could significantly increase population viral suppression. Such interventions should be implemented as a part of renewed HIV/AIDS prevention and treatment efforts.