Prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water and sleep quality in adulthood: a retrospective cohort study.

BACKGROUND: Communities in Cape Cod, Massachusetts were exposed to tetrachloroethylene (PCE) through contaminated drinking water from 1969 to 1983. PCE exposure during adulthood has well-established neurotoxic effects; however, long-term impacts stemming from early life exposure, especially adverse effects on sleep quality, are not well understood. METHODS: The present analysis was based on data from the Cape Cod Health Study, a retrospective cohort study of the long-term neurotoxic impacts of early-life exposure to PCE-contaminated drinking water. Exposure to PCE-contaminated water was estimated using a validated leaching and transport model. Measures of sleep quality were obtained from self-administered questionnaires. Generalized estimating equations were used to generate risk ratios and 95% confidence intervals to estimate the association between early-life PCE exposure and sleep quality among 604 participants. RESULTS: Compared to unexposed participants, any PCE exposure during early life was associated with 1.57 times the risk of reporting breathing pauses during sleep (95% CI 0.92-2.68). Low-level exposure to PCE was associated with 1.50 times the risk of reporting sleep apnea or other sleep disorders (95% CI 0.78-2.89), while high levels of exposure had comparable risk compared to no exposure (RR = 0.94, 95% CI 0.50-1.79). Weak or no associations were observed for other sleep quality outcomes. In stratified analyses participants with mental illness and/or substance use disorder had increased risk ratios for short sleep duration associated with PCE exposure. CONCLUSION: These findings suggest that early-life exposure to PCE may be associated with a moderate increase in the risk of reporting breathing pauses during sleep in adulthood and that a history of mental illness and/or substance use disorder may exacerbate the risk of short sleep duration.

Fine particulate matter and polycystic ovarian morphology.

BACKGROUND: Polycystic ovary morphology (PCOM) is an ultrasonographic finding that can be present in women with ovulatory disorder and oligomenorrhea due to hypothalamic, pituitary, and ovarian dysfunction. While air pollution has emerged as a possible disrupter of hormone homeostasis, limited research has been conducted on the association between air pollution and PCOM. METHODS: We conducted a longitudinal cohort study using electronic medical records data of 5,492 women with normal ovaries at the first ultrasound that underwent a repeated pelvic ultrasound examination during the study period (2004-2016) at Boston Medical Center. Machine learning text algorithms classified PCOM by ultrasound. We used geocoded home address to determine the ambient annual average PM2.5 exposures and categorized into tertiles of exposure. We used Cox Proportional Hazards models on complete data (n = 3,994), adjusting for covariates, and additionally stratified by race/ethnicity and body mass index (BMI). RESULTS: Cumulative exposure to PM2.5 during the study ranged from 4.9 to 17.5 µg/m3 (mean = 10.0 µg/m3). On average, women were 31 years old and 58% were Black/African American. Hazard ratios and 95% confidence intervals (CI) comparing the second and third PM2.5 exposure tertile vs. the reference tertile were 1.12 (0.88, 1.43) and 0.89 (0.62, 1.28), respectively. No appreciable differences were observed across race/ethnicity. Among women with BMI ≥ 30 kg/m2, we observed weak inverse associations with PCOM for the second (HR: 0.93, 95% CI: 0.66, 1.33) and third tertiles (HR: 0.89, 95% CI: 0.50, 1.57). CONCLUSIONS: In this study of reproductive-aged women, we observed little association between PM2.5 concentrations and PCOM incidence. No dose response relationships were observed nor were estimates appreciably different across race/ethnicity within this clinically sourced cohort.

Prenatal and early childhood exposure to tetrachloroethylene (PCE) and non-medical use of prescription drugs: A retrospective cohort study in Cape Cod, MA.

BACKGROUND: Between 1968 and 1983, public drinking water supplies of Cape Cod, Massachusetts were contaminated with the chlorinated solvent tetrachloroethylene (PCE). We previously found an affinity for risk-taking behaviors, including the use of illicit drugs, following prenatal and early childhood exposure to PCE. Using newly collected data, we investigated the risk of non-medical use of prescription drugs (NMUPD) following prenatal and early childhood PCE exposure. METHODS: Participants were identified from a retrospective cohort study ("Cape Cod Health Study") via cross-matching birth certificates and water system data. The original self-administered questionnaire gathered data on demographics, work and medical history, and alcohol and illicit drug use from 618 individuals (363 exposed and 255 unexposed). The follow-up survey added questions on non-medical use of prescription pain relievers, tranquilizers, stimulants and sedatives. A validated leaching and transport model was used to estimate exposure to PCE exposure in drinking water. RESULTS: There was a wide distribution of cumulative prenatal and early childhood PCE exposure levels (range: 0.04 g-3722.2 g). PCE exposed subjects had a 1.92-fold increase in risk of any non-medical use of prescription drugs [Adjusted RR: 1.92, (95% CI: 1.31, 2.83)]. Furthermore, the association followed a dose-response relationship where the risk of NMUPD was higher for those exposed to PCE levels greater than or equal the median level versus those exposed to levels less than the median [Adjusted RR: 2.05 (95% CI: 1.34, 3.15) vs. 1.83 (95% CI: 1.20, 2.79) (p-value for trend < 0.01)]. Additionally, we found moderate increases in risk by level of non-medical use (any non-medical use, non-medical use of 1 or more categories of prescription drugs, or 2+ categories) as well as by category of drug for pain relivers, stimulants and tranquilizers. CONCLUSION: We found that prenatal and early childhood exposure to PCE was associated with a moderate increase in the risk of NMUPD. Exposed subjects had dose-related increased risks of NMUPD of pain relievers, tranquilizers, and stimulants. This study has a number of limitations and is the first to report this association. Additional longitudinal studies of populations exposed to PCE during early life should be conducted to examine its long-term neurotoxic effects.

Multimodal Recruitment to Study Ovulation and Menstruation Health: Internet-Based Survey Pilot Study.

BACKGROUND: Multimodal recruitment strategies are a novel way to increase diversity in research populations. However, these methods have not been previously applied to understanding the prevalence of menstrual disorders such as polycystic ovary syndrome. OBJECTIVE: The purpose of this study was to test the feasibility of recruiting a diverse cohort to complete a web-based survey on ovulation and menstruation health. METHODS: We conducted the Ovulation and Menstruation Health Pilot Study using a REDCap web-based survey platform. We recruited 200 women from a clinical population, a community fair, and the internet. RESULTS: We recruited 438 women over 29 weeks between September 2017 and March 2018. After consent and eligibility determination, 345 enrolled, 278 started (clinic: n=43; community fair: n=61; internet: n=174), and 247 completed (clinic: n=28; community fair: n=60; internet: n=159) the survey. Among all participants, the median age was 25.0 (SD 6.0) years, mean BMI was 26.1 kg/m2 (SD 6.6), 79.7% (216/271) had a college degree or higher, and 14.6% (37/254) reported a physician diagnosis of polycystic ovary syndrome. Race and ethnicity distributions were 64.7% (176/272) White, 11.8% (32/272) Black/African American, 7.7% (21/272) Latina/Hispanic, and 5.9% (16/272) Asian individuals; 9.9% (27/272) reported more than one race or ethnicity. The highest enrollment of Black/African American individuals was in clinic (17/42, 40.5%) compared to 1.6% (1/61) in the community fair and 8.3% (14/169) using the internet. Survey completion rates were highest among those who were recruited from the internet (159/174, 91.4%) and community fairs (60/61, 98.4%) compared to those recruited in clinic (28/43, 65.1%). CONCLUSIONS: Multimodal recruitment achieved target recruitment in a short time period and established a racially diverse cohort to study ovulation and menstruation health. There were greater enrollment and completion rates among those recruited via the internet and community fair.

Influence of Family and Community Socioeconomic Status on the Risk of Adolescent Drug Use.

Background: Adolescent drug use increases the risk of mental, physical and social problems later in life and so it is important to understand its complex etiology that likely includes socioeconomic status (SES). We undertook the present analysis using data from a population-based retrospective cohort study to examine the influence of family and community SES in relation to adolescent drug use. We hypothesized that lower levels of community and parental SES would increase the risk of use and that there would be stronger associations for the more proximate family-level factors. Methods: We used self-administered questionnaires (N=1,402) to obtain information on use of marijuana, inhalants, heroin, cocaine/crack, psychedelics/hallucinogens, Ritalin without a prescription, and club drugs during adolescence. Family SES was gathered from birth certificate data on maternal educational level and paternal occupation. Community SES characteristics at birth, age 10 and age 18 were obtained from the US Census Bureau. Results: An increased risk of adolescent drug use was associated with lower maternal education, non-white collar occupations among fathers, and lower community median income, and poverty and unemployment levels at age 18. The strongest associations were seen for the use of multiple drugs (Risk Ratio (RR): 1.7, 95% CI: 1.4-2.2), inhalants (RR: 2.5, 95% CI: 1.5-2.2), crack/cocaine (RR: 2.8, 95% CI: 1.7-4.5), psychedelics/hallucinogens (RR: 1.8, 95% CI: 1.4-2.4), and club/designer drugs (RR: 1.8, 95% CI: 1.2-2.7) among adolescents whose mothers had only a high school education. Conclusions: These results suggest that use of certain drugs during adolescence is associated with both family and community SES measures. However, maternal education appears to have the greatest influence on use, suggesting that a multi-level approach that engages mothers is needed to prevent adolescent drug use.

Residential proximity to roadways and placental-associated stillbirth: a case-control study.

We conducted a retrospective case-control study of 1,097 women in Massachusetts and Rhode Island, USA, to examine the association between stillbirth related to placental abruption or placental insufficiency and maternal exposure to traffic-related air pollution. We utilized distance to nearest roadway proximity metrics as a proxy for traffic-related air pollution exposure. No meaningful increase in the overall odds of placental-associated stillbirths was observed (adjusted OR: 1.1, 95% CI: 0.5-2.8). However, mothers living within 50 m of a roadway had a 60% increased odds of experiencing a stillbirth related to placental abruption compared to mothers living greater than 200 m away. This suggestive finding was imprecise due to the small case number in the highest exposure category (95% CI: 0.6-4.0). Future studies of placental abruption with more precise exposure assessments are warranted.

Drug use disorder following early life exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study.

BACKGROUND: Many studies of adults with occupational exposure to solvents such as tetrachloroethylene (PCE) have shown adverse effects on cognition, mood and behavioral problems. Much less is known about neurotoxic effects in early life at lower exposure levels seen in community settings. We recently reported that illicit drug use was more frequent among adults from Cape Cod, Massachusetts who were exposed to PCE-contaminated drinking water during gestation and early childhood than their unexposed counterparts. Using newly collected data from this population-based retrospective cohort study, the current analysis examines whether early life PCE exposure is also associated with drug use disorder over the life course. METHODS: Three-hundred and sixty-three subjects with prenatal and early childhood PCE exposure and 255 unexposed subjects were studied. These individuals (median age: 40-41 years) completed self-administered questionnaires on the eleven established diagnostic criteria for drug use disorder and confounding variables. A validated leaching and transport model was used to estimate exposure to PCE-contaminated water. RESULTS: Overall, 23.3% of subjects reported having at least one criterion for drug use disorder over their lifetime. Early life PCE exposure was associated with a modest increase in the lifetime presence of one or more diagnostic criteria for drug use disorder (adjusted RR: 1.4, 95% CI: 1.0-1.8). Compared to unexposed subjects, PCE-exposed subjects were more likely to report having most diagnostic criteria of drug use disorder, including neglecting major roles due to drug use, physical and psychological problems related to drug use, and giving up activities due to drug use. No dose-response relationships were observed with increasing levels of PCE exposure. CONCLUSIONS: These results suggest that exposure to PCE-contaminated drinking water during early life modestly increases the risk of developing diagnostic criteria for drug use disorder later in life. Because this study has several limitations, these findings should be confirmed in follow-up investigations of other exposed populations with more diverse racial and socioeconomic characteristics.

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.

Prospective study of cigarette smoking and fecundability.

STUDY QUESTION: To what extent is cigarette smoking associated with reduced fecundability? SUMMARY ANSWER: Current female smokers, particularly those who had smoked ≥10 cigarettes/day for ≥10 years, had lower fecundability than never smokers, but current male smoking and passive smoking in either partner showed little association with reduced fecundability. WHAT IS KNOWN ALREADY: Female smoking has been identified as a cause of infertility, yet there has been limited characterization of the dose and duration at which an effect is observed. Results for male active smoking and passive smoking in both partners are less consistent. STUDY DESIGN, SIZE, DURATION: We analyzed data from a North American internet-based preconception cohort study of 5473 female and 1411 male pregnancy planners, enrolled from 2013 to 2018. Participants had been attempting conception for ≤6 menstrual cycles at study entry. PARTICIPANTS/MATERIALS, SETTING, METHODS: We collected information on active and passive smoking history on baseline questionnaires. Pregnancy was reported on female bi-monthly follow-up questionnaires. We calculated fecundability ratios (FR) and 95% CI using proportional probabilities regression models, adjusted for demographic, behavioral, medical, reproductive and dietary variables. MAIN RESULTS AND THE ROLE OF CHANCE: Female current regular smoking (FR = 0.90, 95% CI: 0.77, 1.07), current occasional smoking (FR = 0.88, 95% CI: 0.73, 1.06), and former smoking (FR = 0.89, 95% CI: 0.81, 0.98) were associated with small reductions in fecundability. Results were stronger among women who smoked ≥10 cigarettes/day for ≥10 years (FR = 0.77, 95% CI: 0.53, 1.10). Male current regular and former smoking, and current passive smoking in either partner were not meaningfully associated with reduced fecundability. In utero exposure to ≥10 cigarettes/day among females was associated with reduced fecundability (FR = 0.75, 95% CI: 0.52, 1.06). LIMITATIONS, REASONS FOR CAUTION: Numbers of cigarette smokers, particularly within categories of intensity and duration, were small. Under-reporting of smoking may have resulted in non-differential misclassification, and smokers were more likely to be lost to follow-up. WIDER IMPLICATIONS OF THE FINDINGS: Given the consistency of our findings with results from previous studies and our observation of a dose-response relation in intensity of smoking, this study supports an association between female cigarette smoking and lower fecundability. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Institute of Child Health and Human Development (R01-HD086742, R21-HD072326, R03-HD090315 and T32-HD052458). The authors declare no competing interests.

Perceived Stress and Fecundability: A Preconception Cohort Study of North American Couples.

While some epidemiologic studies support the hypothesis that stress can adversely affect fertility, few prospective studies have assessed the association in couples from the general population. We used data from Pregnancy Study Online, a web-based preconception cohort study of pregnancy planners from the United States and Canada (2013-2018), to examine the association between women's and men's perceived stress levels prior to conception and fecundability. Women (aged 21-45 years) and their male partners (aged ≥21 years) who were attempting conception without fertility treatment were eligible. We measured perceived stress using the 10-item Perceived Stress Scale (PSS). We ascertained pregnancy information using bimonthly follow-up questionnaires of female participants. We followed 4,769 couples until self-reported pregnancy, initiation of fertility treatment, loss to follow-up, or 12 menstrual cycles of attempt time, whichever came first. We used proportional probabilities regression models to estimate fecundability ratios and 95% confidence intervals, adjusting for potential confounders. Higher PSS scores among the women were associated with slight reductions in fecundability (comparing PSS scores of ≥25 vs. <10, fecundability ratio = 0.87, 95% confidence interval: 0.74, 1.02). PSS scores among the men were not substantially associated with fecundability.

Exposure to tetrachloroethylene-contaminated drinking water and time to pregnancy.

BACKGROUND: The synthetic solvent tetrachloroethylene (PCE), commonly used in dry cleaning operations, is a human neurotoxicant and carcinogen. However, its effect on reproduction is poorly understood, as prior studies have been limited to small occupational cohorts. We examined the association between PCE exposure from contamination of the public drinking water supply and time-to-pregnancy (TTP) in a cohort of mothers from Cape Cod, Massachusetts. METHODS: The Cape Cod Family Health Study is a retrospective cohort study designed to examine the reproductive and developmental health effects of exposure to PCE-contaminated drinking water. Our analysis included 1565 women who reported 3826 planned pregnancies from 1949 to 1990. Women completed self-administered questionnaires that ascertained TTP for each of her pregnancies, regardless of the outcome, as well as residential history and demographic information. We utilized EPANET water distribution system modeling software and a leaching and transport model to assess PCE exposure for each pregnancy. We used log-binomial regression models to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for potential confounders. We performed a probabilistic bias analysis to examine the effect of outcome misclassification on our results. RESULTS: Any cumulative PCE exposure before pregnancy was associated with a 15% reduction in risk of TTP > 12 months (RR = 0.85, 95% CI: 0.70, 1.03). However, women with the highest average monthly PCE exposure around the time of the pregnancy attempt (≥ 2.5 g) had increased risk of TTP > 12 months (RR = 1.36, 95% CI: 1.06, 1.76). CONCLUSIONS: We found little evidence for long-term, cumulative adverse effects of PCE exposure on TTP, but high levels of PCE exposure around the time of the pregnancy attempt were associated with longer TTP. These associations may be underestimated due to the exclusion of unsuccessful pregnancy attempts from our study population, and may be biased by outcome and exposure misclassification given the long-term recall of TTP and use of a leaching and transport model to estimate PCE exposure.

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.

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.

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.

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.

Associations between residence at birth and mental health disorders: a spatial analysis of retrospective cohort data.

BACKGROUND: Mental health disorders impact approximately one in four US adults. While their causes are likely multifactorial, prior research has linked the risk of certain mental health disorders to prenatal and early childhood environmental exposures, motivating a spatial analysis to determine whether risk varies by birth location. METHODS: We investigated the spatial associations between residence at birth and odds of depression, bipolar disorder, and post-traumatic stress disorder (PTSD) in a retrospective cohort (Cape Cod, Massachusetts, 1969-1983) using generalized additive models to simultaneously smooth location and adjust for confounders. Birth location served as a surrogate for prenatal exposure to the combination of social and environmental factors related to the development of mental illness. We predicted crude and adjusted odds ratios (aOR) for each outcome across the study area. The results were mapped to identify areas of increased risk. RESULTS: We observed spatial variation in the crude odds ratios of depression that was still present even after accounting for spatial confounding due to geographic differences in the distribution of known risk factors (aOR range: 0.61-3.07, P = 0.03). Similar geographic patterns were seen for the crude odds of PTSD; however, these patterns were no longer present in the adjusted analysis (aOR range: 0.49-1.36, P = 0.79), with family history of mental illness most notably influencing the geographic patterns. Analyses of the odds of bipolar disorder did not show any meaningful spatial variation (aOR range: 0.58-1.17, P = 0.82). CONCLUSION: Spatial associations exist between residence at birth and odds of PTSD and depression, but much of this variation can be explained by the geographic distributions of available risk factors. However, these risk factors did not account for all the variation observed with depression, suggesting that other social and environmental factors within our study area need further investigation.

Air pollution and risk of uterine leiomyomata.

BACKGROUND: Air pollution, particularly from vehicle exhaust, has been shown to influence hormonal activity. However, it is unknown whether air pollution exposure is associated with the occurrence of uterine leiomyomata, a hormonally sensitive tumor of the uterus. METHODS: For 85,251 women 25-42 years of age at enrollment in the Nurses' Health Study II, we examined proximity to major roadways and outdoor levels of particulate matter less than 10 microns (PM10) or 2.5 microns (PM2.5) or between 10 and 2.5 microns (PM10-2.5) in diameter for all residential addresses from September 1989 to May 2007. To be eligible for this analysis, a woman had to be alive and respond to questionnaires, premenopausal with an intact uterus, and without diagnoses of cancer or prevalent uterine leiomyomata. Incidence of ultrasound- or hysterectomy-confirmed uterine leiomyomata and covariates were reported on biennial questionnaires sent through May 2007. Multivariable time-varying Cox proportional hazard models were used to estimate the relationship between distance to road or PM exposures and uterine leiomyomata risk. RESULTS: During 837,573 person-years of follow-up, there were 7760 incident cases of uterine leiomyomata. Living close to a major road and exposures to PM10 or PM10-2.5 were not associated with an increased risk of uterine leiomyomata. However, each 10 µg/m increase in 2-year average, 4-year average, or cumulative average PM2.5 was associated with an adjusted hazard ratio of 1.08 (95% confidence interval = 1.00-1.17), 1.09 (0.99-1.19), and 1.11 (1.03-1.19), respectively. CONCLUSIONS: Chronic exposure to PM2.5 may be associated with a modest increased risk of uterine leiomyomata.

Prenatal drinking-water exposure to tetrachloroethylene and ischemic placental disease: a retrospective cohort study.

BACKGROUND: Prenatal drinking water exposure to tetrachloroethylene (PCE) has been previously related to intrauterine growth restriction and stillbirth. Pathophysiologic and epidemiologic evidence linking these outcomes to certain other pregnancy complications, including placental abruption, preeclampsia, and small-for-gestational-age (SGA) (i.e., ischemic placental diseases), suggests that PCE exposure may also be associated with these events. We examined whether prenatal exposure to PCE-contaminated drinking water was associated with overall or individual ischemic placental diseases. METHODS: Using a retrospective cohort design, we compared 1,091 PCE-exposed and 1,019 unexposed pregnancies from 1,766 Cape Cod, Massachusetts women. Exposure between 1969 and 1990 was estimated using water distribution system modeling software. Data on birth weight and gestational age were obtained from birth certificates; mothers self-reported pregnancy complications. RESULTS: Of 2,110 eligible pregnancies, 9% (N = 196) were complicated by ≥1 ischemic placental disease. PCE exposure was not associated with overall ischemic placental disease (for PCE ≥ sample median vs. no exposure, risk ratio (RR): 0.90; 95% confidence interval (CI): 0.65, 1.24), preeclampsia (RR: 0.36; 95% CI: 0.12-1.07), or SGA (RR: 0.98; 95% CI: 0.66-1.45). However, pregnancies with PCE exposure ≥ the sample median had 2.38-times the risk of stillbirth ≥27 weeks gestation (95% CI: 1.01, 5.59), and 1.35-times of the risk of placental abruption (95% CI: 0.68, 2.67) relative to unexposed pregnancies. CONCLUSIONS: Prenatal PCE exposure was not associated with overall ischemic placental disease, but may increase risk of stillbirth.

Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens.

OBJECTIVE: To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth. DESIGN: Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020. METHODS: We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation. RESULTS: We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens. CONCLUSION: Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.

Association between resilience promotion factors during childhood and risk of drug use disorder during adulthood.

Few studies have been conducted on the relationship between "outside-residing" resilience characteristics and the risk of developing drug use disorder later in life. These characteristics include responsive and caring parenting, household routines involving regular family meals and bedtime routines, social support from peers, participation in organized activities, and religious service attendance. We quantified the association between these resilience promotion factors during childhood and the risk of developing criteria for drug use disorder during adulthood using data from a retrospective cohort study of 618 adults born in Massachusetts during 1969-1983, including those with adverse childhood experiences (ACEs). Self-administered questionnaires gathered information on criteria for drug use disorder, ACEs, and family and community resilience promotion factors. Compared to individuals with "low" numbers of resilience promotion factors, 30% (95% CI: 0.5-0.9) and 50% reductions (95% CI: 0.4-0.8) in the risk of developing one or more criteria for drug use disorder were observed among those with "moderate" and "high" numbers of resilience factors, respectively (p value for trend=0.003). Overall, family factors were associated with greater risk reductions than comparable numbers of community factors. Among individuals with ACEs, a "high" number of family factors but not community factors were associated with a reduction in risk (RR:0.6, 95% CI:0.4-1.0 for family factors, RR:1.0, 95% CI:0.5-1.8 for community factors). These results suggest that the risk of developing criteria for drug use disorder decreases in a dose-response fashion according to the number of "outside-residing" resilience promotion factors during childhood, and that family factors are associated with greater risk reductions than community factors, particularly among individuals with ACEs. Coordinated prevention efforts at the family and community level are recommended to reduce the risk of this important societal problem.