Lorraine L. Cameron

Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl.

Accidental contamination of the Michigan food chain with polybrominated biphenyls (PBBs) led to the exposure of more than 4,000 individuals in 1973. Because PBB exposure is suspected to disrupt endocrine function, we assessed pubertal development in females 5–24 years of age (N = 327) who were exposed to PBB in utero and, in many cases, through breastfeeding. We estimated in utero PBB exposure using maternal serum PBB measurements taken after exposure (1976–1979) and extrapolated to time of pregnancy using a model of PBB decay. We found that breastfed girls exposed to high levels of PBB in utero (≥7 parts per billion) had an earlier age at menarche (mean age = 11.6 years) than breastfed girls exposed to lower levels of PBB in utero (mean age = 12.2–12.6 years) or girls who were not breastfed (mean age = 12.7 years). This association persisted after adjustment for potential confounders (menarche ratio = 3.4, 95% confidence interval = 1.3–9.0). Perinatal PBB exposure was associated with earlier pubic hair stage in breastfed girls, but little association was found with breast development. The associations observed here lend support to the hypothesis that pubertal events may be affected by pre- and postnatal exposure to organohalogens.

Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: a standardized mortality ratio analysis

BackgroundExposure to arsenic concentrations in drinking water in excess of 300 μg/L is associated with diseases of the circulatory and respiratory system, several types of cancer, and diabetes; however, little is known about the health consequences of exposure to low-to-moderate levels of arsenic (10–100 μg/L).MethodsA standardized mortality ratio (SMR) analysis was conducted in a contiguous six county study area of southeastern Michigan to investigate the relationship between moderate arsenic levels and twenty-three selected disease outcomes. Disease outcomes included several types of cancer, diseases of the circulatory and respiratory system, diabetes mellitus, and kidney and liver diseases. Arsenic data were compiled from 9251 well water samples tested by the Michigan Department of Environmental Quality from 1983 through 2002. Michigan Resident Death Files data were amassed for 1979 through 1997 and sex-specific SMR analyses were conducted with indirect adjustment for age and race; 99% confidence intervals (CI) were reported.ResultsThe six county study area had a population-weighted mean arsenic concentration of 11.00 μg/L and a population-weighted median of 7.58 μg/L. SMR analyses were conducted for the entire six county study area, for only Genesee County (the most populous and urban county), and for the five counties besides Genesee. Concordance of results across analyses is used to interpret the findings. Elevated mortality rates were observed for both males (M) and females (F) for all diseases of the circulatory system (M SMR, 1.11; CI, 1.09–1.13; F SMR, 1.15; CI, 1.13,-1.17), cerebrovascular diseases (M SMR, 1.19; CI, 1.14–1.25; F SMR, 1.19; CI, 1.15–1.23), diabetes mellitus (M SMR, 1.28; CI, 1.18–1.37; F SMR, 1.27; CI, 1.19–1.35), and kidney diseases (M SMR, 1.28; CI, 1.15–1.42; F SMR, 1.38; CI, 1.25–1.52).ConclusionThis is some of the first evidence to suggest that exposure to low-to-moderate levels of arsenic in drinking water may be associated with several of the leading causes of mortality, although further epidemiologic studies are required to confirm the results suggested by this ecologic SMR analysis.

Polybrominated biphenyls, polychlorinated biphenyls, body weight, and incidence of adult-onset diabetes mellitus.

Background: Prior studies have reported an increased risk of diabetes related to polychlorinated biphenyl (PCB) exposure. No study has yet investigated whether polybrominated biphenyls (PBBs), which are similar in chemical structure, increase the incidence of diabetes. Methods: The Michigan PBB cohort was established in 1976 and surveyed again in 1991–1993 and in 2001. PBB and PCB serum levels were measured from blood collected at enrollment. To determine the incidence of adult-onset diabetes, we analyzed cohort members without diabetes at enrollment, ages 20 years and older, with known PBB and PCB levels, who participated in at least 1 follow-up survey (n = 1384). Using Poisson regression, we determined the incidence density ratio (IDR) of diabetes for different serum levels of PBB and PCB, controlling for age, body mass index, smoking, and alcohol consumption at enrollment. Results: Analyzing 25 years of follow-up data, we did not find that higher PBB serum levels were a risk factor for the incidence of diabetes mellitus. However, in women, but not in men, higher PCB serum levels were associated with increased incidence of diabetes (IDR = 2.33; 95% confidence interval = 1.25–4.34 in the highest PCB group compared with the lowest). In both men and women, overweight and obesity increased the diabetes incidence. Conclusions: We found no association between PBB serum levels and diabetes incidence. In women, there was a positive linear association of diabetes incidence with PCB serum levels at enrollment. This finding is in agreement with 2 prior studies indicating a higher relative risk of diabetes in PCB-exposed women.

Maternal exposure to a brominated flame retardant and genitourinary conditions in male offspring.

Background The upward trend in industrial nations in the incidence of male genitourinary (GU) conditions may be attributed to increased exposure to endocrine disruptors. Polybrominated biphenyl (PBB), a brominated flame retardant, is one such suspected endocrine disruptor. Objective We investigated the relationship between maternal serum levels of PBBs and GU conditions among male offspring exposed in utero. Methods In this cohort study of sons born to women accidentally exposed to PBBs during 1973–1974, we examined self-reported data on GU conditions among male offspring in relation to maternal serum PBB levels. We used generalized estimating equations to calculate odds ratios (ORs), controlling for gestational age at birth. Results Of 464 sons, 33 reported any GU condition (13 hernias, 10 hydroceles, 9 cryptorchidism, 5 hypospadias, and 1 varicocele). Four reported both hernia and hydrocele, and one both hernia and cryptorchidism. After adjustment for gestational age at birth, sons of highly exposed women (> 5 ppb) were twice as likely to report any GU condition compared with sons of the least exposed women [≤1 ppb; OR = 2.0; 95% confidence interval (CI), 0.8–5.1]. This risk was increased when we excluded sons born after the exposure but before the mother’s serum PBB measurement (OR = 3.1; 95% CI, 1.0–9.1). We found evidence of a 3-fold increase in reported hernia or hydrocele among sons with higher PBB exposure (test of trend p-value = 0.04). Neither hypospadias nor cryptorchidism was individually associated with PBB exposure. Conclusions Although cryptorchidism and hypospadias were not associated with in utero PBB exposure, this study suggests that other GU conditions may be associated with exposure to endocrine-disrupting chemicals during development.

A decay model for assessing polybrominated biphenyl exposure among women in the Michigan Long-Term PBB Study

The Michigan Long-Term PBB Study was established following exposure to polybrominated biphenyls (PBBs) in the early 1970s. Serum samples from cohort members were analyzed for PBB during 1976–1993. More than 20 years following this industrial incident, some participants still had measurable serum PBB concentration levels. Thus, there is continuing interest in understanding the elimination of PBB from the body. In the present study, we estimated serum PBB decay and investigated the effects of covariates on serum PBB decay rates among 406 female cohort members. We developed a decay model using a general linear mixed model, which attributes unique intercept and slope estimates for each individual while borrowing information across individuals for predicting these quantities. Age at exposure and body mass index (BMI) at the initial measurement were time-independent covariates. Time since exposure, smoking history, pregnancy status, and breast-feeding status were time-dependent covariates. Higher BMI was associated with a slower decay rate; smokers had a faster decay rate than nonsmokers; and increasing age at exposure was marginally associated with a slower decay rate. Our results suggest a faster serum PBB decay rate for women who breast-fed during the interval between serum PBB measurements. To evaluate the predictive performance of our modeling approach, we compared the results from this model with those from a previously developed ordinary least squares (OLS) two-stage decay model. The mixed-effects decay model predicted the observed serum PBB concentration levels significantly better than the OLS two-stage decay model (mixed-effects model, r=0.93; OLS two-stage model, r=0.86; P<0.0001).

Menstrual function among women exposed to polybrominated biphenyls: A follow-up prevalence study

BackgroundAlteration in menstrual cycle function is suggested among rhesus monkeys and humans exposed to polybrominated biphenyls (PBBs) and structurally similar polychlorinated biphenyls (PCBs). The feedback system for menstrual cycle function potentially allows multiple pathways for disruption directly through the hypothalamic-pituitary-ovarian axis and indirectly through alternative neuroendocrine axes.MethodsThe Michigan Female Health Study was conducted during 1997–1998 among women in a cohort exposed to PBBs in 1973. This study included 337 women with self-reported menstrual cycles of 20–35 days (age range: 24–56 years). Current PBB levels were estimated by exponential decay modeling of serum PBB levels collected from 1976–1987 during enrollment in the Michigan PBB cohort. Linear regression models for menstrual cycle length and the logarithm of bleed length used estimated current PBB exposure or enrollment PBB exposure categorized in tertiles, and for the upper decile. All models were adjusted for serum PCB levels, age, body mass index, history of at least 10% weight loss in the past year, physical activity, smoking, education, and household income.ResultsHigher levels of physical activity were associated with shorter bleed length, and increasing age was associated with shorter cycle length. Although no overall association was found between PBB exposure and menstrual cycle characteristics, a significant interaction between PBB exposures with past year weight loss was found. Longer bleed length and shorter cycle length were associated with higher PBB exposure among women with past year weight loss.ConclusionThis study suggests that PBB exposure may impact ovarian function as indicated by menstrual cycle length and bleed length. However, these associations were found among the small number of women with recent weight loss suggesting either a chance finding or that mobilization of PBBs from lipid stores may be important. These results should be replicated with larger numbers of women exposed to similar lipophilic compounds.

Neonatal Withdrawal Syndrome, Michigan, 2000–2009

BACKGROUND Neonatal withdrawal syndrome, which is associated most frequently with opioid use in pregnancy, is an emerging public health concern, with recent studies documenting an increase in the rate of U.S. infants diagnosed. PURPOSE This study examined neonatal withdrawal syndrome diagnosis among Michigan infants from 2000 to 2009 and hospital length of stay (LOS) between infants with and without the syndrome for a subset of years (2006-2009). METHODS Michigan live birth records from 2000 to 2009 were linked with hospital discharge data to identify infants with neonatal withdrawal syndrome. Linked data were restricted to infants born between 2006 and 2009 to examine the difference in hospital LOS between infants with and without the syndrome. Multivariable regression models were constructed to examine the adjusted impact of syndrome diagnosis on infant LOS and fit using negative binomial distribution. Data were analyzed from July 2011 to February 2012. RESULTS From 2000 to 2009, the overall birth rate of infants with neonatal withdrawal syndrome increased from 41.2 to 289.0 per 100,000 live births (p<0.0001). Among infants born from 2006 to 2009, the average hospital LOS for those with the syndrome was between 1.36 (95% CI=1.24, 1.49) and 5.75 (95% CI=5.41, 6.10) times longer than for infants without it. CONCLUSIONS Diagnosis of neonatal withdrawal syndrome increased significantly in Michigan with infants who had the syndrome requiring a significantly longer LOS compared to those without it.

Breast cancer among women in Michigan following exposure to brominated flame retardants

In this updated follow-up, we investigated the breast cancer experience among women in Michigan exposed to brominated flame retardants, some 30 years following exposure. Michigan residents were enrolled in a study cohort after exposure to polybrominated biphenyls (PBBs) through the consumption of contaminated food products. PBB concentrations were measured in serum at the time of enrolment. Cancer experience was determined by linkage to the Michigan Cancer Registry. We conducted a nested case–control study that included 51 women diagnosed with breast cancer during 1974–2004 and 202 age-matched controls. While the data suggest an increase in breast cancer risk with higher PBB exposure, this did not reach statistical significance. The OR of having breast cancer among women with PBB concentrations ≥10 ng/mL compared to women with PBB concentrations at or below the limit of detection of 1 ng/mL was 2.60, 95% CI 0.93 to 7.27, (p=0.07), when adjusted for age and family history of cancer in a first-degree female relative. It remains important to examine exposure to brominated chemicals and possible health effects, and to continue following the cancer experience of participants in this study.

Dietary Exposure to Brominated Flame Retardants and Abnormal Pap Test Results

OBJECTIVE This study examined a possible association of dietary exposure to polybrominated biphenyls (PBBs), a brominated flame retardant, and self-reported abnormal Pap test results and cervical dysplasia as a precursor to cervical cancer. METHODS Women in Michigan who ingested contaminated poultry, beef, and dairy products in the early 1970s were enrolled in a population-based cohort study in Michigan. Serum PBB and serum polychlorinated biphenyl (PCB) concentrations were measured. Reproductive history and health information, including Pap test results, were self-reported by participants. RESULTS Of the women, 23% (223 of 956) reported an abnormal Pap test. In unadjusted analyses, self-reporting an abnormal Pap test was associated with younger age, current smoking (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.19-2.17), and longer duration of lifetime use of oral contraceptives (≥10 years; HR 1.92, 95% CI 1.21-3.06). When adjusting for PCB exposure, age at the interview, and smoking history, there was a slightly elevated risk of self-reporting an abnormal Pap test among the highly exposed women compared to women with nondetectable PBB concentrations (PBB≥13 μg/L, HR 1.23, 95% CI 0.74-2.06); however, the CI was imprecise. When breastfeeding duration after the initial PBB measurement was taken into account, there was a reduced risk of self-reporting an abnormal Pap test among the highly exposed women who breastfed for ≥12 months (HR 0.41, 95% CI 0.06-3.03; referent group: women with nondetectable PBB concentrations who did not breastfeed). CONCLUSIONS It remains important to evaluate the potential reproductive health consequences of this class of chemicals as well as other potential predictors of abnormal Pap tests.

Climate change and temperature extremes: A review of heat- and cold-related morbidity and mortality concerns of municipalities

Cold and hot weather are associated with mortality and morbidity. Although the burden of temperature-associated mortality may shift towards high temperatures in the future, cold temperatures may represent a greater current-day problem in temperate cities. Hot and cold temperature vulnerabilities may coincide across several personal and neighborhood characteristics, suggesting opportunities for increasing present and future resilience to extreme temperatures. We present a narrative literature review encompassing the epidemiology of cold- and heat-related mortality and morbidity, related physiologic and environmental mechanisms, and municipal responses to hot and cold weather, illustrated by Detroit, Michigan, USA, a financially burdened city in an economically diverse metropolitan area. The Detroit area experiences sharp increases in mortality and hospitalizations with extreme heat, while cold temperatures are associated with more gradual increases in mortality, with no clear threshold. Interventions such as heating and cooling centers may reduce but not eliminate temperature-associated health problems. Furthermore, direct hemodynamic responses to cold, sudden exertion, poor indoor air quality and respiratory epidemics likely contribute to cold-related mortality. Short- and long-term interventions to enhance energy and housing security and housing quality may reduce temperature-related health problems. Extreme temperatures can increase morbidity and mortality in municipalities like Detroit that experience both extreme heat and prolonged cold seasons amidst large socioeconomic disparities. The similarities in physiologic and built-environment vulnerabilities to both hot and cold weather suggest prioritization of strategies that address both present-day cold and near-future heat concerns.