Elizabeth A. Whelan

Lead Exposures in U.S. Children, 2008: Implications for Prevention

Objective We reviewed the sources of lead in the environments of U.S. children, contributions to children’s blood lead levels, source elimination and control efforts, and existing federal authorities. Our context is the U.S. public health goal to eliminate pediatric elevated blood lead levels (EBLs) by 2010. Data sources National, state, and local exposure assessments over the past half century have identified risk factors for EBLs among U.S. children, including age, race, income, age and location of housing, parental occupation, and season. Data extraction and synthesis Recent national policies have greatly reduced lead exposure among U.S. children, but even very low exposure levels compromise children’s later intellectual development and lifetime achievement. No threshold for these effects has been demonstrated. Although lead paint and dust may still account for up to 70% of EBLs in U.S. children, the U.S. Centers for Disease Control and Prevention estimates that ≥30% of current EBLs do not have an immediate lead paint source, and numerous studies indicate that lead exposures result from multiple sources. EBLs and even deaths have been associated with inadequately controlled sources including ethnic remedies and goods, consumer products, and food-related items such as ceramics. Lead in public drinking water and in older urban centers remain exposure sources in many areas. Conclusions Achieving the 2010 goal requires maintaining current efforts, especially programs addressing lead paint, while developing interventions that prevent exposure before children are poisoned. It also requires active collaboration across all levels of government to identify and control all potential sources of lead exposure, as well as primary prevention.

Menstrual and reproductive risk factors for ischemic heart disease

The role of hormones in ischemic heart disease is of considerable interest, but limited data are available pertaining to risk factors associated with endogenous hormones. We examined the association between menstrual and reproductive factors and ischemic heart disease in a cohort of 867 white, college-educated women who prospectively recorded menstrual cycle data for at least 5 years from their early 20s through their menopause. Ischemic heart disease history was obtained from a self-administered (N = 714) or proxy-administered (N = 153) questionnaire completed at a mean age of 73 years. The analysis included 44,899 person-years of follow-up and 45 cases of myocardial infarction, angioplasty, heart bypass surgery, or ischemic heart disease-related mortality. Ischemic heart disease risk decreased with increasing age at menarche (age-adjusted RR 0.76 per year, 95% CI = 0.60-0.95). Considering menstrual cycle characteristics ages 28-32, there was little overall association with length, variability, or bleeding duration. Ischemic heart disease risk increased with later age at first birth (age-adjusted RR 2.90 for ages 33-43 compared with 25-29) and later age at last birth (age-adjusted RR 3.79 for ages > or =40 compared with 35-39), but there was little association with high parity.

Polychlorinated Biphenyls and Neurodegenerative Disease Mortality in an Occupational Cohort

Background: Production of polychlorinated biphenyls (PCBs) ended in the United States in the 1970s, but PCBs persist in the environment and are detectable in the blood of approximately 80% of Americans over age 50. PCBs decrease dopamine levels in rats and monkeys. Loss of dopamine is the hallmark of Parkinson disease, a neurodegenerative disease. There are no epidemiologic studies of PCBs and neurodegenerative disease. Methods: We conducted a retrospective mortality study of 17,321 PCB-exposed workers to determine whether mortality from Parkinson disease, dementia, and amyotrophic lateral sclerosis was elevated compared with the U.S. population. All workers had a least 90 days employment in 1 of 3 electrical capacitor plants using PCBs from the 1940s to the 1970s. PCB serum levels from a sample of these workers in the 1970s were approximately 10 times the level of community controls. Results: We found no overall excess of Parkinson disease, amyotrophic lateral sclerosis, or dementia in the PCB-exposed cohort (standardized mortality ratios [SMRs]-1.40, 1.11, and 1.26, respectively, and number of deaths-14, 10, and 28 respectively). However, sex-specific analyses revealed that women had an excess of amyotrophic lateral sclerosis (SMR-2.26; 95% confidence interval [CI] = 1.08–4.15; 10 deaths). Furthermore, among highly exposed women (defined by a job-exposure matrix), we found an excess of Parkinson disease (SMR-2.95; 95% CI = 1.08–6.42; 6 deaths) and dementia (SMR-2.04; 95% CI = 1.12–3.43; 14 deaths). Conclusions: Our data are limited due to small numbers and reliance on mortality rather than incidence data, but are suggestive of an effect of PCBs on neurodegenerative disease for women. The literature does not offer an explanation for why women would be more affected than men by PCB exposure for these outcomes.

Mortality and Exposure Response among 14,458 Electrical Capacitor Manufacturing Workers Exposed to Polychlorinated Biphenyls (PCBs)

Background We expanded an existing cohort of workers (n = 2,588) considered highly exposed to polychlorinated biphenyls (PCBs) at two capacitor manufacturing plants to include all workers with at least 90 days of potential PCB exposure during 1939–1977 (n = 14,458). Causes of death of a priori interest included liver and rectal cancers, previously reported for the original cohort, and non-Hodgkin lymphoma (NHL), melanoma, and breast, brain, intestine, stomach, and prostate cancers, based on other studies. Methods We ascertained vital status of the workers through 1998, and cumulative PCB exposure was estimated using a new job exposure matrix. Analyses employed standardized mortality ratios (SMRs; U.S., state, and county referents) and Poisson regression modeling. Results Mortality from NHL, melanoma, and rectal, breast, and brain cancers were neither in excess nor associated with cumulative exposure. Mortality was not elevated for liver cancer [21 deaths; SMR 0.89; 95% confidence interval (CI), 0.55–1.36], but increased with cumulative exposure (trend p-value = 0.071). Among men, stomach cancer mortality was elevated (24 deaths; SMR 1.53; 95% CI, 0.98–2.28) and increased with cumulative exposure (trend p-value = 0.039). Among women, intestinal cancer mortality was elevated (67 deaths; SMR 1.31; 95% CI, 1.02–1.66), especially in higher cumulative exposure categories, but without a clear trend. Prostate cancer mortality, which was not elevated (34 deaths; SMR 1.04; 95% CI, 0.72–1.45), increased with cumulative exposure (trend p-value = 0.0001). Conclusions This study corroborates previous studies showing increased liver cancer mortality, but we cannot clearly associate rectal, stomach, and intestinal cancers with PCB exposure. This is the first PCB cohort showing a strong exposure–response relationship for prostate cancer mortality.

Association of physical and behavioral characteristics with menstrual cycle patterns in women age 29-31 years.

&NA; We examined the association between menstrual cycle characteristics (cycle length, variability, and bleeding length) and physical and behavioral attributes in 766 women age 29‐31 years. Menstrual cycle data were prospectively recorded as part of the Menstruation and Reproductive History Study of college women in Minnesota, begun by Alan Treloar in 1934. Data on lifetime height, weight, physical activity, alcohol and caffeine consumption, and smoking history were collected in 1990 using a self‐administered questionnaire. Cycle variability, as measured by the standard deviation of the cycle length, was increased, and menstrual cycles ≥42 days in length were more common among women in the lowest quartile of Quetelet index [odds ratio (OR) for long cycle = 1.6; 95% confidence interval (CI) = 0.82‐3.0] and among the most physically active (OR = 1.7; 95% CI = 0.93‐3.1). Long menstrual cycles were less common (OR = 0.40; 95% CI = 0.22‐0.73) among women who drank alcohol than among nondrinkers. Variable or long menstrual cycles may reflect anovulation and relatively low levels of estrogen exposure. We would expect, based on our data, reduced estrogen exposure among lean women, physically active women, and those who do not consume alcohol. These findings suggest an explanation for the reported associations between these factors and breast cancer risk.

Work schedule during pregnancy and spontaneous abortion.

Background: There is inconsistent evidence as to whether work schedule (including rotating shifts and night work) can affect reproductive outcomes. Methods: We investigated the association between work schedule and risk of spontaneous abortion in U.S. nurses. The Nurses’ Health Study II is a prospective cohort study established in 1989. In 2001, information about occupational activities and exposures during pregnancy was collected from female nurses for the most recent pregnancy since 1993. Of 11,178 eligible respondents, 9547 (85%) indicated willingness to participate in the occupational study, and 8461 of those (89%) returned the questionnaire, for an overall participation rate of 76%. Of these, 7688 women had pregnancies that were eligible for analysis. Results: Participants reported 6902 live births and 786 (10%) spontaneous abortions. Compared with women who reported usually working “days only” during their first trimester, women who reported usually working “nights only” had a 60% increased risk of spontaneous abortion (RR = 1.6; 95% confidence interval [CI] = 1.3–1.9). A rotating schedule, with or without night shifts, was not associated with an increase in risk (RR = 1.2 [CI = 0.9–1.5] and 1.0 [CI = 0.8–1.2], respectively). Women who reported working more than 40 hours per week during the first trimester were also at increased risk of spontaneous abortion (1.5; 1.3–1.7) compared with women working 21–40 hours, even after adjustment for work schedule. Conclusions: Nightwork and long work hours may be associated with an increased risk of spontaneous abortion. Further studies are needed to determine whether hormonal disturbances attributed to night work affect pregnancy outcome.

Ethylene oxide and breast cancer incidence in a cohort study of 7576 women (United States)

Background: Ethylene oxide (ETO) is a sterilant gas considered to be a human carcinogen, due primarily to excess hematopoietic cancer in exposed cohorts. ETO causes mammary tumors in mice, and has been associated with breast cancer incidence in one small epidemiologic study. Methods: We have studied breast cancer incidence in a cohort of 7576 women employed for at least one year and exposed for an average 10.7 years while working in commercial sterilization facilities. Breast cancer incidence (n = 319) was ascertained via interview, death certificates, cancer registries, and medical records. Interviews were obtained for 68% of the cohort. Results: The standardized incidence ratio (SIR) for incident breast cancer in the whole cohort using external referent rates (SEER) was 0.87 (0.77–0.97). The SIR for those in the top quintile of cumulative exposure, with a 15 year lag, was 1.27 (0.94–1.69), with a positive trend of increasing SIR with increasing exposure (p = 0.002). SIRs are under-estimated because breast cancer incidence in the whole cohort was under-ascertained, due to incomplete response and lack of complete coverage by state cancer registries. In internal nested case–control analyses of those with interviews (complete cancer ascertainment), controlling for reproductive risk factors, a positive exposure–response was found with the log of cumulative exposure with a 15-year lag (p = 0.0005). The odds ratio by quintile of cumulative exposure were 1.00 (0 exposure due to 15 year lag), 1.06, 0.99, 1.24, 1.42, and 1.87. Conclusions: Our data suggest that ETO is associated with breast cancer, but a causal interpretation is weakened due to some inconsistencies in exposure–response trends and possible biases due to non-response and incomplete cancer ascertainment.

Increased frequency of chromosome translocations in airline pilots with long-term flying experience

Background: Chromosome translocations are an established biomarker of cumulative exposure to external ionising radiation. Airline pilots are exposed to cosmic ionising radiation, but few flight crew studies have examined translocations in relation to flight experience. Methods: We determined the frequency of translocations in the peripheral blood lymphocytes of 83 airline pilots and 50 comparison subjects (mean age 47 and 46 years, respectively). Translocations were scored in an average of 1039 cell equivalents (CE) per subject using fluorescence in situ hybridisation (FISH) whole chromosome painting and expressed per 100 CE. Negative binomial regression models were used to assess the relationship between translocation frequency and exposure status and flight years, adjusting for age, diagnostic x ray procedures, and military flying. Results: There was no significant difference in the adjusted mean translocation frequency of pilots and comparison subjects (0.37 (SE 0.04) vs 0.38 (SE 0.06) translocations/100 CE, respectively). However, among pilots, the adjusted translocation frequency was significantly associated with flight years (p = 0.01) with rate ratios of 1.06 (95% CI 1.01 to 1.11) and 1.81 (95% CI 1.16 to 2.82) for a 1- and 10-year incremental increase in flight years, respectively. The adjusted rate ratio for pilots in the highest compared to the lowest quartile of flight years was 2.59 (95% CI 1.26 to 5.33). Conclusions: Our data suggests that pilots with long-term flying experience may be exposed to biologically significant doses of ionising radiation. Epidemiological studies with longer follow-up of larger cohorts of pilots with a wide range of radiation exposure levels are needed to clarify the relationship between cosmic radiation exposure and cancer risk.

Occupational Exposure to Polychlorinated Biphenyls and Risk of Breast Cancer

Background Despite the endocrine system activity exhibited by polychlorinated biphenyls (PCBs), recent studies have shown little association between PCB exposure and breast cancer mortality. Objectives To further evaluate the relation between PCB exposure and breast cancer risk, we studied incidence, a more sensitive end point than mortality, in an occupational cohort. Methods We followed 5,752 women employed for at least 1 year in one of three capacitor manufacturing facilities, identifying cases from questionnaires, cancer registries, and death certificates through 1998. We collected lifestyle and reproductive information via questionnaire from participants or next of kin and used semiquantitative job-exposure matrices for inhalation and dermal exposures combined. We generated standardized incidence ratios (SIRs) and standardized rate ratios and used Cox proportional hazards regression models to evaluate potential confounders and effect modifiers. Results Overall, the breast cancer SIR was 0.81 (95% confidence interval, 0.72–0.92; n = 257), and regression modeling showed little effect of employment duration or cumulative exposure. However, for the 362 women of questionnaire-identified races other than white, we observed positive, statistically significant associations with employment duration and cumulative exposure; only smoking, birth cohort, and self- or proxy questionnaire completion had statistically significant explanatory power when added to models with exposure metrics. Conclusions We found no overall elevation in breast cancer risk after occupational exposure to PCBs. However, the exposure-related risk elevations seen among nonwhite workers, although of limited interpretability given the small number of cases, warrant further investigation, because the usual reproductive risk factors accounted for little of the increased risk.

Job Stress Among Female Flight Attendants

We evaluated the presence of chronic job stressors among flight attendants (FAs) to examine the relationships between these job stressors and psychological distress and job dissatisfaction. Seventy-three female FAs (90% participation) employed at two commercial airlines completed a detailed questionnaire. Standard questions and scale measures were used to assess job stressors, psychological distress, and job dissatisfaction. The association between job stressors and these outcomes was evaluated using multiple regression analysis. Except for fatigue, distress and job dissatisfaction were moderate to low. Job stressors were found to have a substantive effect on these outcomes, following adjustment for individual factors. Despite moderate-to-low levels of distress and dissatisfaction, targeted efforts to reduce selected job stressors and to enhance social support may be important steps toward improving the well-being and satisfaction of FAs.