Association of diet with per- and polyfluoroalkyl substances in plasma and human milk in the New Hampshire Birth Cohort Study.

Per- and polyfluoroalkyl substances (PFAS) are related to various adverse health outcomes, and food is a common source of PFAS exposure. Dietary sources of PFAS have not been adequately explored among U.S. pregnant individuals. We examined associations of dietary factors during pregnancy with PFAS concentrations in maternal plasma and human milk in the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate (PFDA), were measured in maternal plasma collected at ∼28 gestational weeks and human milk collected at ∼6 postpartum weeks. Sociodemographic, lifestyle and reproductive factors were collected from prenatal questionnaires and diet from food frequency questionnaires at ∼28 gestational weeks. We used adaptive elastic net (AENET) to identify important dietary variables for PFAS concentrations. We used multivariable linear regression to assess associations of dietary variables selected by AENET models with PFAS concentrations. Models were adjusted for sociodemographic, lifestyle, and reproductive factors, as well as gestational week of blood sample collection (plasma PFAS), postpartum week of milk sample collection (milk PFAS), and enrollment year. A higher intake of fish/seafood, eggs, coffee, or white rice during pregnancy was associated with higher plasma or milk PFAS concentrations. For example, every 1 standard deviation (SD) servings/day increase in egg intake during pregnancy was associated with 4.4 % (95 % CI: 0.6, 8.4), 3.3 % (0.1, 6.7), and 10.3 % (5.6, 15.2) higher plasma PFOS, PFOA, and PFDA concentrations respectively. Similarly, every 1 SD servings/day increase in white rice intake during pregnancy was associated with 7.5 % (95 % CI: -0.2, 15.8) and 12.4 % (4.8, 20.5) greater milk PFOS and PFOA concentrations, respectively. Our study suggests that certain dietary factors during pregnancy may contribute to higher PFAS concentrations in maternal plasma and human milk, which could inform interventions to reduce PFAS exposure for both birthing people and offspring.

Plasma per- and polyfluoroalkyl substance mixtures during pregnancy and duration of breastfeeding in the New Hampshire birth cohort study.

BACKGROUND: Prior studies suggest that prenatal per- and polyfluoroalkyl substances (PFAS) exposures are associated with shorter breastfeeding duration. Studies assessing PFAS mixtures and populations in North America are sparse. METHODS: We quantified PFAS concentrations in maternal plasma collected during pregnancy in the New Hampshire Birth Cohort Study (2010-2017). Participants completed standardized breastfeeding surveys at regular intervals until weaning (n = 813). We estimated associations between mixtures of 5 PFAS and risk of stopping exclusive breastfeeding before 6 months or any breastfeeding before 12 months using probit Bayesian kernel machine regression. For individual PFAS, we calculated the relative risk and hazard ratio (HR) of stopping breastfeeding using modified Poisson regression and accelerated failure time models respectively. RESULTS: PFAS mixtures were associated with stopping exclusive breastfeeding before 6 months, primarily driven by perfluorooctanoate (PFOA). We observed statistically significant trends in the association of perfluorohexane sulfonate (PFHxS), PFOA, and perfluorononanoate (PFNA) (p-trends≤0.02) with stopping exclusive breastfeeding. Participants in the highest PFOA quartile had a 28% higher risk of stopping exclusive breastfeeding before 6 months compared to those in the lowest quartile (95% Confidence Interval: 1.04, 1.56). Similar trends were observed for PFHxS and PFNA with exclusive breastfeeding (p-trends≤0.05). PFAS were not associated with stopping any breastfeeding before 12 months. CONCLUSIONS: In this cohort, we observed that participants with greater overall plasma PFAS concentrations had greater risk of stopping exclusive breastfeeding before 6 months and associations were driven largely by PFOA. These findings further support the growing literature indicating that PFAS may be associated with shorter duration of breastfeeding.

Predictors of Breastfeeding Duration in the New Hampshire Birth Cohort Study.

INTRODUCTION: Breastfeeding has significant health benefits for infants and birthing persons, including reduced risk of chronic disease. The American Academy of Pediatrics recommends exclusively breastfeeding infants for 6 months and recently extended its recommendation for continuing to breastfeed with supplementation of solid foods from one to two years. Studies consistently identify lower breastfeeding rates among US infants, with regional and demographic variability. We examined breastfeeding in birthing person-infant pairs among healthy, term pregnancies enrolled in the New Hampshire Birth Cohort Study between 2010 and 2017 (n = 1176). METHODS: Birthing persons 18-45 years old were enrolled during prenatal care visits at ~ 24-28 weeks gestation and have been followed since enrollment. Breastfeeding status was obtained from postpartum questionnaires. Birthing person and infant health and sociodemographic information was abstracted from medical records and prenatal and postpartum questionnaires. We evaluated the effects of birthing person age, education, relationship status, pre-pregnancy body mass index, gestational weight gain (GWG), smoking and parity, and infant sex, ponderal index, gestational age and delivery mode on breastfeeding initiation and duration using modified Poisson and multivariable linear regression. RESULTS: Among healthy, term pregnancies, 96% of infants were breastfed at least once. Only 29% and 28% were exclusively breastfed at 6-months or received any breastmilk at 12-months, respectively. Higher birthing person age, education, and parity, being married, excessive GWG, and older gestational age at delivery were associated with better breastfeeding outcomes. Smoking, obesity, and cesarean delivery were negatively associated with breastfeeding outcomes. CONCLUSIONS: Given the public health importance of breastfeeding for infants and birthing persons, interventions are needed to support birthing persons to extend their breastfeeding duration.

Per- and Polyfluoroalkyl Substances (PFAS) Mixture during Pregnancy and Postpartum Weight Retention in the New Hampshire Birth Cohort Study (NHBCS).

Per- and polyfluoroalkyl substances (PFAS), widely used in industrial and consumer products, are suspected metabolic disruptors. We examined the association between a PFAS mixture during pregnancy and postpartum weight retention in 482 participants from the New Hampshire Birth Cohort Study. PFAS concentrations, including perfluorohexane sulfonate, perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), and perfluorodecanoate, were quantified in maternal plasma collected at ~28 gestational weeks. Postpartum weight change was calculated as the difference between self-reported weight from a postpartum survey administered in 2020 and pre-pregnancy weight abstracted from medical records. Associations between PFAS and postpartum weight change were examined using Bayesian kernel machine regression and multivariable linear regression, adjusting for demographic, reproductive, dietary, and physical activity factors; gestational week of blood sample collection; and enrollment year. PFOS, PFOA, and PFNA were positively associated with postpartum weight retention, and associations were stronger among participants with a higher pre-pregnancy body mass index. A doubling of PFOS, PFOA, and PFNA concentrations was associated with a 1.76 kg (95%CI: 0.31, 3.22), 1.39 kg (-0.27, 3.04), and 1.04 kg (-0.19, 2.28) greater postpartum weight retention, respectively, among participants who had obesity/overweight prior to pregnancy. Prenatal PFAS exposure may be associated with increased postpartum weight retention.

Gestational per- and polyfluoroalkyl substances exposure and infant body mass index trajectory in the New Hampshire Birth Cohort Study.

Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent, potential metabolic disruptors of concern for infants. Mothers participating in the New Hampshire Birth Cohort Study (NHBCS) provided a plasma sample during pregnancy to measure concentrations of seven PFAS, and infant weight and length were abstracted from well-child visits between birth and 12 months. Sex-specific growth patterns of child body mass index (BMI) were fit using a growth mixture model (GMM) and the relative risk ratios (RRR) and 95% Confidence Intervals (95% CI) for the association of maternal plasma PFAS with BMI growth patterns during infancy were estimated by using multinomial logistic model for the group probabilities in the GMM. Four growth patterns were identified: Group 1) a steep increase in BMI during the first 6 months, then a leveling off; Group 2) a gradual increase in BMI across the year; Group 3) a steep increase in BMI during months 1-3, then stable BMI; and Group 4) a gradual increase in BMI with plateau around 3 months (reference group). For boys, higher maternal pregnancy perfluorooctanoate concentrations were associated with a 60% decreased chance of being in group 3 as compared to group 4, after adjusting for potential confounding variables (RRR = 0.4; 95% CI: 0.1, 0.9). For girls, higher maternal perfluorooctane sulfonate (PFOS) concentrations during pregnancy were associated with a higher likelihood of following the growth pattern of groups 2 (RRR = 2.5; 95% CI: 1.0, 6.1) and 3 (RRR = 2.8; 95% CI: 1.0, 7.6) as compared to group 4, adjusting for potential confounding variables. In this cohort, sex-specific associations of maternal plasma PFAS concentrations during pregnancy with growth patterns during the first year of life were observed, with greater BMI growth observed among infant girls born to mothers with higher pregnancy concentrations of PFOS.

Per- and polyfluoroalkyl substance mixtures and gestational weight gain among mothers in the Health Outcomes and Measures of the Environment study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are environmentally persistent chemicals commonly used in the production of household and consumer goods. While exposure to PFAS has been associated with greater adiposity in children and adults, less is known about associations with gestational weight gain (GWG). METHODS: We quantified using mass spectrometry perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS), perfluorohexanesulfanoate (PFHxS) and perfluorononanoate (PFNA) in maternal serum from 18 ± 5 weeks' gestation (mean ± standard deviation (std)) in a prospective pregnancy and birth cohort (2003-2006, Cincinnati, Ohio) (n = 277). After abstracting weight data from medical records, we calculated GWG from 16 ± 2 weeks' gestation (mean ± std) to the measured weight at the last visit or at delivery, rate of weight gain in the 2nd and 3rd trimesters (GWR), and total weight gain z-scores standardized for gestational age at delivery and pre-pregnancy BMI. We investigated covariate-adjusted associations between individual PFAS using multivariable linear regression; we assessed potential effect measure modification (EMM) by overweight/obese status (pre-pregnancy BMI<25 kg/m2 v. ≥25 kg/m2). Using weighted quantile sum regression, we assessed the combined influence of these four PFAS on GWG and GWR. RESULTS: Each doubling in serum concentrations of PFOA, PFOS, and PFNA was associated with a small increase in GWG (range 0.5-0.8 lbs) and GWR (range 0.03-0.05 lbs/week) among all women. The association of PFNA with GWG was stronger among women with BMI≥25 kg/m2 (ß = 2.6 lbs; 95% CI:-0.8, 6.0) than those with BMI<25 kg/m2 (ß = -1.0 lbs; 95% CI:-3.8, 1.8; p-EMM = 0.10). We observed associations close to the null between PFAS and z-scores and between the PFAS exposure index (a combined summary measure) and the outcomes. CONCLUSION: Although there were consistent small increases in gestational weight gain with increasing PFOA, PFOS, and PFNA serum concentrations in this cohort, the associations were imprecise. Additional investigation of the association of PFAS with GWG in other cohorts would be informative and could consider pre-pregnancy BMI as a potential modifier.

Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island.

BACKGROUND: Organophosphate esters (OPEs)-used as flame retardants and plasticizers-are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study (n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors. METHODS: We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks' gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex. RESULTS: We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (ß = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (ß = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (ß = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (ß = - 0.50 cm, 95%CI = - 0.86, - 0.14) and female weight (ß = - 0.19 kg, 95%CI = - 0.36, - 0.02), but positively associated with weekly growth in iliac skinfold thickness (ß = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (ß = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (ß = 0.14 mm, 95%CI = 0.002, 0.28). CONCLUSIONS: Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

Correction to: Occurrence of mental illness following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

Following publication of the original article [1], the author reported that, because of a programming error, incorrect sentences and incorrect Table 3 has been published. The correct sentences and Table 3 are shown below.

Maternal serum perfluoroalkyl substance mixtures and thyroid hormone concentrations in maternal and cord sera: The HOME Study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous. Previous studies have found associations between PFAS and thyroid hormones in maternal and cord sera, but the results are inconsistent. To further address this research question, we used mixture modeling to assess the associations with individual PFAS, interactions among PFAS chemicals, and the overall mixture. METHODS: We collected data through the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort study that between 2003 and 2006 enrolled 468 pregnant women and their children in the greater Cincinnati, Ohio region. We assessed the associations of maternal serum PFAS concentrations measured during pregnancy with maternal (n = 185) and cord (n = 256) sera thyroid stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3) using two mixture modeling approaches (Bayesian kernel machine regression (BKMR) and quantile g-computation) and multivariable linear regression. Additional models considered thyroid autoantibodies, other non-PFAS chemicals, and iodine deficiency as potential confounders or effect measure modifiers. RESULTS: PFAS, considered individually or as mixtures, were generally not associated with any thyroid hormones. A doubling of perfluorooctanesulfonic acid (PFOS) had a positive association with cord serum TSH in BKMR models but the 95% Credible Interval included the null (ß = 0.09; 95% CrI: -0.08, 0.27). Using BKMR and multivariable models, we found that among children born to mothers with higher thyroid peroxidase antibody (TPOAb), perfluorooctanoic acid (PFOA), PFOS, and perfluorohexanesulfonic acid (PFHxS) were associated with decreased cord FT4 suggesting modification by maternal TPOAb status. CONCLUSIONS: These findings suggest that maternal serum PFAS concentrations measured in the second trimester of pregnancy are not strongly associated with thyroid hormones in maternal and cord sera. Further analyses using robust mixture models in other cohorts are required to corroborate these findings.

Reproductive and developmental health effects of prenatal exposure to tetrachloroethylene-contaminated drinking water.

Tetrachloroethylene (PCE) is a common contaminant in both occupational and community settings. High exposure levels in the workplace have been shown to have adverse impacts on reproduction and development but few epidemiological studies have examined these effects at the lower levels commonly seen in community settings. We were presented with a unique opportunity to examine the reproductive and developmental effects of prenatal exposure to PCE-contaminated drinking water resulting from the installation of vinyl-lined water pipes in Massachusetts and Rhode Island from the late 1960s through 1980. This review describes the methods and findings of two community-based epidemiological studies, places their results in the context of the existing literature, and describes the strengths and challenges of conducting epidemiological research on a historical pollution episode. Our studies found that prenatal exposure to PCE-contaminated drinking water is associated with delayed time-to-pregnancy, and increased risks of placental abruption, stillbirths stemming from placental dysfunction, and certain birth defects. No associations were observed with pregnancy loss, birth weight, and gestational duration. Important strengths of this research included the availability of historical data on the affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little opportunity for recall bias and confounding. Challenges arose mainly from the retrospective nature of the exposure assessments. This research highlights the importance of considering pregnant women and their developing fetuses when monitoring, regulating, and remediating drinking water contaminants.

Maternal urinary cadmium, glucose intolerance and gestational diabetes in the New Hampshire Birth Cohort Study.

BACKGROUND: Exposure to cadmium may contribute to the risk of gestational diabetes mellitus (GDM) and glucose intolerance during pregnancy. METHODS: We examined 917 women enrolled from 2009 to 2017 in the New Hampshire Birth Cohort Study. Lifestyle, diet, demographic factors and pregnancy outcomes were collected by questionnaire and medical record review. Cadmium concentrations were measured in urine samples collected at 24-28 weeks gestation. Women were classified as normal (n = 815), glucose intolerant (n = 86), or GDM (n = 16) based on clinical data (i.e., glucose challenge test, oral glucose challenge test). We calculated odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential confounders, using multinomial logistic regression to examine disease severity (normal, glucose intolerant, GDM) and logistic regression to examine the combined outcome of gestational hyperglycemia. RESULTS: Little to no association was observed for glucose intolerance (OR = 1.11, 95%CI 0.85-1.45) or GDM (OR = 0.86, 95% CI 0.51-1.44) with a doubling of urinary cadmium as compared to normal women. The combined outcome of gestational hyperglycemia yielded similar results (OR = 1.07, 95% CI 0.84-1.35). However, when stratified by pre-pregnancy body mass index (BMI), there was a slight association with the combined outcome in normal weight women (OR = 1.32, 95% CI 0.88-1.98) and no association in the overweight or obese women. This positive association remained in restricted analyses of only women with no exposure to smoking during pregnancy and those who had never smoked. CONCLUSIONS: Cadmium exposure was suggestively associated with increased risk of gestational hyperglycemia among women not already at increased risk of GDM due to being overweight or obese; however, associations of cadmium with gestational hyperglycemia were not statistically significant.

Lifetime exposure to ultraviolet radiation and the risk of multiple sclerosis in the US radiologic technologists cohort study.

BACKGROUND: Low exposure to ultraviolet radiation (UVR) from sunlight may be a risk factor for developing multiple sclerosis (MS). Possible pathways may be related to effects on immune system function or vitamin D insufficiency, as UVR plays a role in the production of the active form of vitamin D in the body. OBJECTIVE: This study examined whether lower levels of residential UVR exposure from sunlight were associated with increased MS risk in a cohort of radiologic technologists. METHODS: Participants in the third and fourth surveys of the US Radiologic Technologists (USRT) Cohort Study eligible (N = 39,801) for analysis provided complete residential histories and reported MS diagnoses. MS-specialized neurologists conducted medical record reviews and confirmed 148 cases. Residential locations throughout life were matched to satellite data from NASA's Total Ozone Mapping Spectrometer (TOMS) project to estimate UVR dose. RESULTS: Findings indicate that MS risk increased as average lifetime levels of UVR exposures in winter decreased. The effects were consistent across age groups <40 years. There was little indication that low exposures during summer or at older ages were related to MS risk. CONCLUSION: Our findings are consistent with the hypothesis that UVR exposure reduces MS risk and may ultimately suggest prevention strategies.

Modeled exposure to tetrachloroethylene-contaminated drinking water and the occurrence of birth defects: a case-control study from Massachusetts and Rhode Island.

BACKGROUND: Residents of Massachusetts and Rhode Island were exposed to tetrachloroethylene-contaminated drinking water from 1968 through the early 1990s when it leached from the vinyl lining of asbestos cement water distribution pipes. While occupational exposure to solvents during pregnancy has consistently been linked to an increased risk of certain birth defects, mixed results have been observed for environmental sources of exposure, including contaminated drinking water. The present case-control study was undertaken to examine further the association between prenatal exposure to tetrachloroethylene-contaminated drinking water and the risk of central nervous system defects, oral clefts and hypospadias. METHODS: Cases were comprised of live- and stillborn infants delivered between 1968 and 1995 to mothers who resided in 28 Massachusetts and Rhode Island cities and towns with some PCE-contaminated water supplies. Infants with central nervous system defects (N = 268), oral clefts (N = 112) and hypospadias (N = 94) were included. Controls were randomly selected live-born, non-malformed infants who were delivered during the same period and geographic area as cases (N = 771). Vital records and self-administered questionnaires were used to gather identifying information, birth defect diagnoses, and other relevant data. PCE exposure during the first trimester was estimated using water distribution system modeling software that incorporated a leaching and transport model. Prenatal PCE exposure was dichotomized as "high" or "low" exposure at the level corresponding to an estimated average concentration of 40 µg/L, the criterion for remediation when PCE contamination was discovered in 1980. RESULTS: Mothers with "high" levels of exposure to PCE-contaminated drinking water during the first trimester (> 40 µg/L) had increased odds of having a child with spina bifida (OR: 2.0, 95% CI: 0.8-5.4), cleft lip with or without cleft palate (OR: 3.8, 95% CI: 1.2-12.3) and hypospadias (OR: 2.1, 95% CI:0.5-8.3). No increases in the odds of other defects were observed in relation to "high" exposure levels. CONCLUSIONS: The results of the present study suggest that mothers with "high" PCE exposure levels during the first trimester have increased odds of having a child with spina bifida, cleft lip with or without cleft palate, and hypospadias. These findings support several prior studies that observed an increased risk of selected birth defects following prenatal exposure to solvents in occupational and environmental settings. Even though PCE contamination from vinyl lined pipes was remediated many years ago, it remains a widespread contaminant across the U.S and so environmental regulations must be guided by a precautionary perspective that safeguards pregnant women and their offspring.

Modeled exposure to tetrachloroethylene-contaminated drinking water and the risk of placenta-related stillbirths: a case-control study from Massachusetts and Rhode Island.

BACKGROUND: Residents of Massachusetts and Rhode Island were exposed to tetrachloroethylene (PCE)-contaminated drinking water from 1968 through the early 1990s when the solvent was used to apply a vinyl liner to drinking water mains to address taste and odor problems. Few studies have examined the risk of fetal death among women exposed to solvent-contaminated drinking water. Two previous investigations found moderate increases in the risk of stillbirth among highly exposed women; however, these results were based on a small number of cases. The present case-control study was undertaken to examine further this association with a large number of stillbirths. METHODS: Cases were comprised of stillborn infants delivered between 1968 and 1995 to mothers who resided in 28 Massachusetts and Rhode Island cities and towns with some affected water mains (N = 296). Cases were included if the cause of death was placental abruption and/or placental insufficiency. Controls were randomly selected live-born infants who were delivered in the same time period and geographic area (N = 783). Data on confounding variables were gathered from vital records and questionnaires. PCE exposure was estimated using a leaching and transport model integrated into water system software. RESULTS: Mothers with any PCE exposure had a 1.7-fold increase in the adjusted odds of placenta-related stillbirth (95% CI: 1.2-2.4). The adjusted odds ratio (OR) increased as a woman's exposure level increased: in comparison to unexposed mothers, ORs were 1.5 (95% CI: 1.0-2.3) for low exposure (> 0-median), 1.7 (95% CI: 1.1-2.5) for moderate exposure (>median-90th percentile) and 1.9 (95% CI: 1.1-3.2) for high exposure (>90th percentile) (p value for trend = 0.02). A similar pattern was observed when PCE exposure was dichotomized at 40 µg/L, the suggested action guideline for remediation (OR = 1.5, 95% CI: 1.1-2.2 and OR = 2.6, 95% CI: 1.4-4.8, respectively, for PCE exposure <=40 µg/L and > 40 µg/L) (p value for trend = .003). CONCLUSIONS: We observed a linear dose-dependent increase in the odds of stillbirth due to placental abruption and placental insufficiency with prenatal exposure to PCE contaminated drinking water. Because PCE remains a common drinking water contaminant, these findings highlight the importance of considering pregnant women when monitoring, regulating and remediating drinking water supplies.

Exploring associations between prenatal solvent exposures and teenage drug and alcohol use: a retrospective cohort study.

BACKGROUND: Investigating the effects of prenatal and childhood exposures on behavioral health outcomes in adolescence is challenging given the lengthy period between the exposure and outcomes. We conducted a retrospective cohort study in Cape Cod, Massachusetts to evaluate the impact of prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water on the occurrence of risk-taking behaviors as a teenager. An increased occurrence of risk-taking behaviors, particularly illicit drug use, was observed in those highly exposed to PCE. We hypothesized that there may be other sources of prenatal solvent exposure such as maternal consumption of alcoholic beverages during pregnancy which might modify the previously observed associations between PCE and risk-taking behaviors and so we conducted an exploratory analysis using available cohort data. The current report presents the results of these analyses and describes the difficulties in conducting research on long-term behavioral effects of early life exposures. METHODS: The exploratory analysis compared a referent group of subjects with no early life exposure to PCE or alcohol (n = 242) to subjects with only alcohol exposure (n = 201), subjects with only PCE exposure (n = 361), and subjects with exposure to both PCE and alcohol (n = 302). Surveys completed by the subject's mother included questions on prenatal alcoholic beverage consumption and available confounding variables such as cigarette smoking and marijuana use. Surveys completed by the subjects included questions on risk-taking behaviors such as alcoholic beverage consumption and illicit drug use as a teenager and available confounding variables. PCE exposure was modeled using a leaching and transport algorithm embedded in water distribution system modeling software that estimated the amount of PCE delivered to a subject's residence during gestation and early childhood. RESULTS: Subjects with early life exposure to both PCE and alcohol had an increased risk of using two or more major drugs as a teen (RR = 1.9 (95% CI 1.2, 3.0)) compared to unexposed subjects. Increased risks for only PCE exposure (RR = 1.6 (95% CI 1.0, 2.4) and only alcohol exposure (RR = 1.3 (95% CI 0.7, 2.1)) were also evident but were smaller than the increased risk associated with both exposures. While available confounding variables were controlled, many relevant social risk factors were not obtained due to limitations in the retrospective study design. CONCLUSIONS: This exploratory analysis found evidence for an additive effect of early life exposure to PCE and alcohol on the risk of use of multiple illicit drugs as a teenager. Because of numerous limitations in this retrospective study, further research is needed to examine longstanding behavioral effects of early life exposures. To be most informative, this research should involve long-term prospective data collection.

No Association Between Unintentional Head Injuries and Early-Life Exposure to Tetrachloroethylene (PCE)-Contaminated Drinking Water.

OBJECTIVE: Because of emerging evidence that early-life exposure to the solvent tetrachloroethylene (PCE) has long-lasting neurological consequences, we examined the risk of unintentional head injuries following prenatal and childhood exposure to PCE-contaminated drinking water. METHODS: Participants provided information on head injuries and other relevant characteristics in a self-administered questionnaire. Exposure to PCE was modeled using a leaching and transport algorithm set in water system modeling software. RESULTS: We did not observe any evidence of an increased risk of any type of head injury among exposed participants. CONCLUSIONS: PCE is a widespread water pollutant. Thus, documenting possible health effects of early-life exposure is vital for ensuring that drinking water regulations adequately protect vulnerable populations.

Long-term Neurotoxic Effects of Early-life Exposure to Tetrachloroethylene-contaminated Drinking Water.

BACKGROUND: Tetrachloroethene (PCE) is a common environmental and occupational contaminant and an acknowledged neurotoxicant. From 1968 through 1983, widespread contamination of public drinking water supplies with PCE occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes. OBJECTIVES: A retrospective cohort study (the Cape Cod Health Study) was undertaken to examine possible health consequences of early-life exposure to PCE-contaminated drinking water. This review describes the study methods and findings regarding the effects of prenatal and childhood exposure on neurologic outcomes during early adulthood, including vision, neuropsychological functioning, brain structure, risky behaviors, and mental illness. The review also describes the strengths and challenges of conducting population-based epidemiologic research in this unique setting. METHODS: Participants were identified by cross-matching birth certificates and water system data. Information on health outcomes and confounding variables was collected from self-administered surveys (n = 1689), neuropsychological tests (n = 63), vision examinations (n = 63), and magnetic resonance imaging (n = 42). Early-life exposure to PCE was estimated using a leaching and transport model. The data analysis compared the occurrence of each health outcome among individuals with prenatal and early childhood PCE exposure to unexposed individuals while considering the effect of confounding variables. FINDINGS: The study found evidence that early-life exposure to PCE-contaminated drinking water has long-term neurotoxic effects. The strongest associations were seen with illicit drug use, bipolar disorder, and post-traumatic stress disorder. Key strengths of the study were availability of historical data on affected water systems, a relatively high exposure prevalence and wide range of exposure levels, and little confounding. Challenges arose mainly from the historical nature of the exposure assessments. CONCLUSIONS: The Cape Cod Health Study demonstrates how scientists can take advantage of unique "natural experiments" to learn about the health effects of environmental pollution. This body of work has improved our understanding of the long-term health effects of early-life exposure to this common environmental contaminant and will help risk assessors and policymakers ensure that drinking water supplies in the United States are safe for vulnerable populations.

Risk of Pancreatic Cancer in Female Textile Workers in Shanghai, China, Exposed to Metals, Solvents, Chemicals, and Endotoxin: Follow-Up to a Nested Case-Cohort Study.

OBJECTIVE: We studied associations between pancreatic cancer and occupational exposures to metals, solvents, chemicals, and endotoxin in a cohort of female textile workers in Shanghai, China. To assess the longer-term influences of these agents on pancreatic cancer we extended follow-up of this previously studied cohort. METHODS: We utilized a job exposure matrix to assess occupational exposures for 481 pancreatic cancer cases and a randomly selected sub-cohort of 3191 non-cases. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards modeling adapted for the case-cohort design. RESULTS: We observed a statistically significant trend of increasing hazard ratios associated with solvent exposure, but no associations with any of the remaining occupational exposures, including endotoxin and metals. CONCLUSIONS: Our findings of increasing risk of pancreatic cancer with solvent exposures are consistent with published literature.

Long-term health effects of early life exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

BACKGROUND: While adult exposure to PCE is known to have toxic effects, there is little information on the long-term impact of prenatal and early childhood exposure. We undertook a retrospective cohort study to examine the effects of their early life exposure to PCE-contaminated drinking water. This retrospective cohort study examined whether prenatal and early childhood exposure to PCE-contaminated drinking water influenced the risk of a variety of chronic conditions among adults who were born between 1969 and 1983 in the Cape Cod area of Massachusetts. METHODS: Eight hundred and thirty-one participants with prenatal and early childhood PCE exposure and 547 unexposed participants were studied. Individuals completed questionnaires to gather information on demographic characteristics, chronic conditions, and other sources of solvent exposure. The location of residences from birth through 1990 were used to estimate PCE exposure with U.S. EPA's water distribution system modeling software (EPANET) modified to incorporate a leaching and transport model. RESULTS: No associations were observed between early life PCE exposure and current occurrence of obesity, diabetes, cardiovascular disease, hypertension, color blindness, near- and far sightedness and dry eyes. In contrast, a 1.8-fold increased risk of cancer (95% CI: 0.8, 4.0) was seen among individuals with any early life exposure. These results were based on 31 participants (23 exposed and 8 unexposed) who reported cancers at a variety of anatomical sites, particularly the cervix. A 1.5-fold increase in the risk of epilepsy (95% CI: 0.6, 3.6, based on 16 exposed and 7 unexposed participants) was also observed among individuals with any early life exposure that was further increased to 1.8 (95% CI: 0.7, 4.6) among those with exposure at or above the sample median. CONCLUSIONS: These results suggest that the risk of epilepsy and certain types of cancer such as cervical cancer may be increased among adults who were exposed to PCE-contaminated drinking water exposure during gestation and early childhood. These findings should be interpreted cautiously because of the study limitations and confirmed in follow-up investigations of similarly exposed populations with medically-confirmed diagnoses. This relatively young study population should also be monitored periodically for subsequent changes in disease risk.

Extended follow-up of lung cancer and non-malignant respiratory disease mortality among California diatomaceous earth workers.

OBJECTIVES: Millions of workers worldwide are employed in occupations involving potentiality hazardous exposure to crystalline silica. The diatomaceous earth industry can have particularly high exposures, but there is a lower likelihood of simultaneously occurring confounding exposures. We extended follow-up for diatomaceous earth industry workers previously studied for mortality. METHODS: The cohort included 2342 white men who were employed for at least 1 year at a diatomaceous earth plant in Lompoc, California beginning in 1942. Workers' vital status was updated using the National Death Index through 2011, an extension of 19 years from earlier studies. Detailed work history and quantitative air monitoring measurements estimated exposure intensity. Cox proportional hazards modelling estimated HRs and 95% CIs. SMRs were calculated. RESULTS: Elevated mortality was observed by quartile of cumulative crystalline silica exposure for lung cancer (HR=2.03, 95% CI 1.07 to 3.85, highest quartile, unlagged) and non-malignant respiratory disease (NMRD) (HR=3.59, 95% CI 1.94 to 6.67, highest quartile, unlagged), although trends were not statistically significant. Associations were attenuated when adjusted for smoking and asbestos exposure. Mortality from NMRD was significantly increased over the entire follow-up compared to the general population (SMR=1.37, 95% CI 1.17 to 1.60). An increase for lung cancer was confined to the earlier follow-up (SMR=1.29, 95% CI 1.01 to 1.61). CONCLUSIONS: The risk of lung cancer and NMRD mortality remained elevated, although generally non-significant, and exposure-response trends with cumulative crystalline silica persisted on extended follow-up of this cohort. The findings support a generally consistently observed aetiological relation between crystalline silica and lung cancer.