Patricia A. Janulewicz

Prenatal exposure to tetrachloroethylene-contaminated drinking water and the risk of congenital anomalies: a retrospective cohort study

BackgroundPrior animal and human studies of prenatal exposure to solvents including tetrachloroethylene (PCE) have shown increases in the risk of certain congenital anomalies among exposed offspring.ObjectivesThis retrospective cohort study examined whether PCE contamination of public drinking water supplies in Massachusetts influenced the occurrence of congenital anomalies among children whose mothers were exposed around the time of conception.MethodsThe study included 1,658 children whose mothers were exposed to PCE-contaminated drinking water and a comparable group of 2,999 children of unexposed mothers. Mothers completed a self-administered questionnaire to gather information on all of their prior births, including the presence of anomalies, residential histories and confounding variables. PCE exposure was estimated using EPANET water distribution system modeling software that incorporated a fate and transport model.ResultsChildren whose mothers had high exposure levels around the time of conception had an increased risk of congenital anomalies. The adjusted odds ratio of all anomalies combined among children with prenatal exposure in the uppermost quartile was 1.5 (95% CI: 0.9, 2.5). No meaningful increases in the risk were seen for lower exposure levels. Increases were also observed in the risk of neural tube defects (OR: 3.5, 95% CI: 0.8, 14.0) and oral clefts (OR 3.2, 95% CI: 0.7, 15.0) among offspring with any prenatal exposure.ConclusionThe results of this study suggest that the risk of certain congenital anomalies is increased among the offspring of women who were exposed to PCE-contaminated drinking water around the time of conception. Because these results are limited by the small number of children with congenital anomalies that were based on maternal reports, a follow-up investigation should be conducted with a larger number of affected children who are identified by independent records.

Assessment of neuropsychological trajectories in longitudinal population-based studies of children

This paper provides a strategy for the assessment of brain function in longitudinal cohort studies of children. The proposed strategy invokes both domain-specific and omnibus intelligence test approaches. In order to minimise testing burden and practice effects, the cohort is divided into four groups with one-quarter tested at 6-monthly intervals in the 0–2-year age range (at ages 6 months, 1.0, 1.5 and 2.0 years) and at annual intervals from ages 3–20 (one-quarter of the children at age 3, another at age 4, etc). This strategy allows investigation of cognitive development and of the relationship between environmental influences and development at each age. It also allows introduction of new domains of function when age-appropriate. As far as possible, tests are used that will provide a rich source of both longitudinal and cross-sectional data. The testing strategy allows the introduction of novel tests and new domains as well as piloting of tests when the test burden is relatively light. In addition to the recommended tests for each age and domain, alternative tests are described. Assessment methodology and knowledge about child cognitive development will change over the next 20 years, and strategies are suggested for altering the proposed test schedule as appropriate.

Affinity for risky behaviors following prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water: a retrospective cohort study

BackgroundMany studies of adults with acute and chronic solvent exposure have shown adverse effects on cognition, behavior and mood. No prior study has investigated the long-term impact of prenatal and early childhood exposure to the solvent tetrachloroethylene (PCE) on the affinity for risky behaviors, defined as smoking, drinking or drug use as a teen or adult.ObjectivesThis retrospective cohort study examined whether early life exposure to PCE-contaminated drinking water influenced the occurrence of cigarette smoking, alcohol consumption, and drug use among adults from Cape Cod, Massachusetts.MethodsEight hundred and thirty-one subjects with prenatal and early childhood PCE exposure and 547 unexposed subjects were studied. Participants completed questionnaires to gather information on risky behaviors as a teenager and young adult, demographic characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure was estimated using the U.S. EPAs water distribution system modeling software (EPANET) that was modified to incorporate a leaching and transport model to estimate PCE exposures from pipe linings.ResultsIndividuals who were highly exposed to PCE-contaminated drinking water during gestation and early childhood experienced 50-60% increases in the risk of using two or more major illicit drugs as a teenager or as an adult (Relative Risk (RR) for teen use = 1.6, 95% CI: 1.2-2.2; and RR for adult use = 1.5, 95% CI: 1.2-1.9). Specific drugs for which increased risks were observed included crack/cocaine, psychedelics/hallucinogens, club/designer drugs, Ritalin without a prescription, and heroin (RRs:1.4-2.1). Thirty to 60% increases in the risk of certain smoking and drinking behaviors were also seen among highly exposed subjects.ConclusionsThe results of this study suggest that risky behaviors, particularly drug use, are more frequent among adults with high PCE exposure levels during gestation and early childhood. These findings should be confirmed in follow-up investigations of other exposed populations.

Risk of Learning and Behavioral Disorders Following Prenatal and Early Postnatal Exposure to Tetrachloroethylene (PCE)-contaminated Drinking Water

This population-based retrospective cohort study examined the association between developmental disorders of learning, attention and behavior and prenatal and early postnatal drinking water exposure to tetrachloroethylene (PCE) on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Mothers completed a questionnaire on disorders of attention, learning and behavior in their children and on potential confounding variables. The final cohort consisted of 2086 children. Results of crude and multivariate analyses showed no association between prenatal exposure and receiving tutoring for reading or math, being placed on an Individual Education Plan, or repeating a school grade (adjusted Odds Ratios (OR)=1.0-1.2). There was also no consistent pattern of increased risk for receiving a diagnosis of Attention Deficit Disorder (ADD) or Hyperactive Disorder (HD), special class placement for academic or behavioral problems, or lower educational attainment. Modest associations were observed for the latter outcomes only in the low exposure group (e.g., adjusted ORs for ADD were 1.4 and 1.0 for low and high exposure, respectively). (All ORs are based on an unexposed referent group.) Results for postnatal exposure through age five years were similar to those for prenatal exposure. We conclude that prenatal and early postnatal PCE exposure is not associated with disorders of attention, learning and behavior identified on the basis of questionnaire responses and at the exposure levels experienced by this population.

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

BackgroundWhile many studies of adults with solvent exposure have shown increased risks of anxiety and depressive disorders, there is little information on the impact of prenatal and early childhood exposure on the subsequent risk of mental illness. This retrospective cohort study examined whether early life exposure to tetrachloroethylene (PCE)-contaminated drinking water influenced the occurrence of depression, bipolar disorder, post-traumatic stress disorder, and schizophrenia among adults from Cape Cod, Massachusetts.MethodsA total of 1,512 subjects born between 1969 and 1983 were studied, including 831 subjects with both prenatal and early childhood PCE exposure and 547 unexposed subjects. Participants completed questionnaires to gather information on mental illnesses, demographic and medical characteristics, other sources of solvent exposure, and residences from birth through 1990. PCE exposure originating from the vinyl-liner of water distribution pipes was assessed using water distribution system modeling software that incorporated a leaching and transport algorithm.ResultsNo meaningful increases in risk ratios (RR) for depression were observed among subjects with prenatal and early childhood exposure (RR: 1.1, 95% CI: 0.9-1.4). However, subjects with prenatal and early childhood exposure had a 1.8-fold increased risk of bipolar disorder (N = 36 exposed cases, 95% CI: 0.9-1.4), a 1.5-fold increased risk post-traumatic stress disorder (N = 47 exposed cases, 95% CI: 0.9-2.5), and a 2.1-fold increased risk of schizophrenia (N = 3 exposed cases, 95% CI: 0.2-20.0). Further increases in the risk ratio were observed for bipolar disorder (N = 18 exposed cases, RR; 2.7, 95% CI: 1.3-5.6) and post-traumatic stress disorder (N = 18 exposed cases, RR: 1.7, 95% CI: 0.9-3.2) among subjects with the highest exposure levels.ConclusionsThe results of this study provide evidence against an impact of early life exposure to PCE on the risk of depression. In contrast, the results provide support for an impact of early life exposure on the risk of bipolar disorder and post-traumatic stress disorder. The number of schizophrenia cases was too small to draw reliable conclusions. These findings should be confirmed in investigations of other similarly exposed populations.

Prenatal and Early Childhood Exposure to Tetrachloroethylene and Adult Vision

Background: Tetrachloroethylene (PCE; or perchloroethylene) has been implicated in visual impairments among adults with occupational and environmental exposures as well as children born to women with occupational exposure during pregnancy. Objectives: Using a population-based retrospective cohort study, we examined the association between prenatal and early childhood exposure to PCE-contaminated drinking water on Cape Cod, Massachusetts, and deficits in adult color vision and contrast sensitivity. Methods: We estimated the amount of PCE that was delivered to the family residence from participants’ gestation through 5 years of age. We administered to this now adult study population vision tests to assess acuity, contrast sensitivity, and color discrimination. Results: Participants exposed to higher PCE levels exhibited lower contrast sensitivity at intermediate and high spatial frequencies compared with unexposed participants, although the differences were generally not statistically significant. Exposed participants also exhibited poorer color discrimination than unexposed participants. The difference in mean color confusion indices (CCI) was statistically significant for the Farnsworth test but not Lanthony’s D-15d test [Farnsworth CCI mean difference = 0.05, 95% confidence interval (CI): 0.003, 0.10; Lanthony CCI mean difference = 0.07, 95% CI: –0.02, 0.15]. Conclusions: Prenatal and early childhood exposure to PCE-contaminated drinking water may be associated with long-term subclinical visual dysfunction in adulthood, particularly with respect to color discrimination. Further investigation of this association in similarly exposed populations is necessary.

Adult neuropsychological performance following prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water

This population-based retrospective cohort study examined adult performance on a battery of neuropsychological tests in relation to prenatal and early postnatal exposure to tetrachloroethylene (PCE)-contaminated drinking water on Cape Cod, Massachusetts. Subjects were identified through birth records from 1969 through 1983. Exposure was modeled using pipe network information from town water departments, a PCE leaching and transport algorithm, EPANet water flow modeling software, and a Geographic Information System (GIS). Results of crude and multivariate analyses among 35 exposed and 28 unexposed subjects showed no association between prenatal and early postnatal exposure and decrements on tests that assess abilities in the domains of omnibus intelligence, academic achievement or language. The results were suggestive of an association between prenatal and early postnatal PCE exposure and diminished performance on tests that assessed abilities in the domains of visuospatial functioning, learning and memory, motor, attention and mood. Because the sample size was small, most findings were not statistically significant. Future studies with larger sample sizes should be conducted to further define the neuropsychological consequences of early developmental PCE exposure.

Spatial analysis of learning and developmental disorders in upper Cape Cod, Massachusetts using generalized additive models

The spatial variability of three indicators of learning and developmental disability (LDD) was assessed for Cape Cod, Massachusetts. Maternal reports of receiving special education services, attention deficit hyperactivity disorder, and educational attainment were available for a birth cohort from 1969-1983. Using generalized additive models and residential history, maps of the odds of LDD were produced that also controlled for known risk factors. While results were not statistically significant, they suggest that children living in certain parts of Cape Cod were more likely to have a LDD. The spatial variation may be due to variation in the physical and social environment.

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

BackgroundWhile 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.MethodsEight 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.ResultsNo 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.ConclusionsThese 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.

Neuropsychological characteristics of Gulf War illness: A meta-analysis

Objective Gulf War illness (GWI) is a disorder related to military service in the 1991 GW. Prominent symptoms include fatigue, pain and cognitive problems. These symptoms were reported by GW Veterans (GWV) immediately after the war and were eventually incorporated into case definitions of GWI. Neuropsychological function in GW veterans has been studied both among deployed GWV and in GWV diagnosed with GWI. Results have been inconsistent between and across GW populations. The purpose of the present investigation was to better characterize neuropsychological function in this veteran population. Methods Meta-analysis techniques were applied to published studies on neuropsychological performance in GWV to identify domains of dysfunction in deployed vs. non-deployed GW-era veterans and symptomatic vs. non-symptomatic GWVs. Results Significantly decreased performance was found in three functional domains: attention and executive function, visuospatial skills and learning/memory. Conclusions These findings document the cognitive decrements associated with GW service, validate current GWI case definitions using cognitive criteria, and identify test measures for use in GWI research assessing GWI treatment trial efficacy.