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 in 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 two 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 4th 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 three 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.

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.

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.

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.