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.

Maternal exposure to brominated flame retardants and infant Apgar scores.

Brominated flame retardants (BFRs) and other persistent organic pollutants have been associated with adverse health outcomes in humans and may be particularly toxic to the developing fetus. We investigated the association between in utero polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB) exposures and infant Apgar scores in a cohort of Michigan residents exposed to PBB through contaminated food after an industrial accident. PBB and PCB concentrations were measured in serum at the time the women were enrolled in the cohort. PBB concentrations were also estimated at the time of conception for each pregnancy using a validated elimination model. Apgar scores, a universal measure of infant health at birth, measured at 1 and 5min, were taken from birth certificates for 613 offspring born to 330 women. Maternal PCB concentrations at enrollment were not associated with below-median Apgar scores in this cohort. However, maternal PBB exposure was associated with a dose-related increase in the odds of a below-median Apgar score at 1min and 5min. Among infants whose mothers had an estimated PBB at conception above the limit of detection of 1 part per billion (ppb) to <2.5ppb, the odds ratio=2.32 (95% CI: 1.22-4.40); for those with PBB⩾2.5ppb the OR=2.62 (95% CI: 1.38-4.96; test for trend p<0.01). Likewise, the odds of a below-median 5min Apgar score increased with higher maternal PBB at conception. It remains critical that future studies examine possible relationships between in utero exposures to brominated compounds and adverse health outcomes.

The role of drinking water sources, consumption of vegetables and seafood in relation to blood arsenic concentrations of Jamaican children with and without Autism Spectrum Disorders.

Arsenic is a toxic metal with harmful effects on human health, particularly on cognitive function. Autism Spectrum Disorders (ASDs) are lifelong neurodevelopmental and behavioral disorders manifesting in infancy or early childhood. We used data from 130 children between 2 and 8 years (65 pairs of ASD cases with age- and sex-matched control), to compare the mean total blood arsenic concentrations in children with and without ASDs in Kingston, Jamaica. Based on univariable analysis, we observed a significant difference between ASD cases and controls (4.03 µg/L for cases vs. 4.48 µg/L for controls, P<0.01). In the final multivariable General Linear Model (GLM), after controlling for car ownership, maternal age, parental education levels, source of drinking water, consumption of "yam, sweet potato, or dasheen", "carrot or pumpkin", "callaloo, broccoli, or pak choi", cabbage, avocado, and the frequency of seafood consumption per week, we did not find a significant association between blood arsenic concentrations and ASD status (4.36 µg/L for cases vs. 4.65 µg/L for controls, P=0.23). Likewise, in a separate final multivariable GLM, we found that source of drinking water, eating avocado, and eating "callaloo, broccoli, or pak choi" was significantly associated with higher blood arsenic concentrations (all three P<0.05). Based on our findings, we recommend assessment of arsenic levels in water, fruits, and vegetables, as well as increased awareness among the Jamaican population regarding potential risks for various exposures to arsenic.

Association of daily asthma emergency department visits and hospital admissions with ambient air pollutants among the pediatric Medicaid population in Detroit: time-series and time-stratified case-crossover analyses with threshold effects.

BACKGROUND: Asthma morbidity has been associated with ambient air pollutants in time-series and case-crossover studies. In such study designs, threshold effects of air pollutants on asthma outcomes have been relatively unexplored, which are of potential interest for exploring concentration-response relationships. METHODS: This study analyzes daily data on the asthma morbidity experienced by the pediatric Medicaid population (ages 2-18 years) of Detroit, Michigan and concentrations of pollutants fine particles (PM2.5), CO, NO2 and SO2 for the 2004-2006 period, using both time-series and case-crossover designs. We use a simple, testable and readily implementable profile likelihood-based approach to estimate threshold parameters in both designs. RESULTS: Evidence of significant increases in daily acute asthma events was found for SO2 and PM2.5, and a significant threshold effect was estimated for PM2.5 at 13 and 11 µg m(-3) using generalized additive models and conditional logistic regression models, respectively. Stronger effect sizes above the threshold were typically noted compared to standard linear relationship, e.g., in the time series analysis, an interquartile range increase (9.2 µg m(-3)) in PM2.5 (5-day-moving average) had a risk ratio of 1.030 (95% CI: 1.001, 1.061) in the generalized additive models, and 1.066 (95% CI: 1.031, 1.102) in the threshold generalized additive models. The corresponding estimates for the case-crossover design were 1.039 (95% CI: 1.013, 1.066) in the conditional logistic regression, and 1.054 (95% CI: 1.023, 1.086) in the threshold conditional logistic regression. CONCLUSION: This study indicates that the associations of SO2 and PM2.5 concentrations with asthma emergency department visits and hospitalizations, as well as the estimated PM2.5 threshold were fairly consistent across time-series and case-crossover analyses, and suggests that effect estimates based on linear models (without thresholds) may underestimate the true risk.

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 [< or =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 cohort study of the association between secondary sex ratio and parental exposure to polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB).

BACKGROUND: Polybrominated biphenyl (PBB), a brominated flame retardant, was accidently mixed into animal feed in Michigan (1973-1974) resulting in human exposure through consumption of contaminated meat, milk and eggs. Beginning in 1976 individuals who consumed contaminated products were enrolled in the Michigan Long-Term PBB Study. This cohort presents a unique opportunity to study the association between parental exposures to PBB and offspring sex ratio. METHODS: We identified offspring of female PBB cohort participants (born 1975-1988) and obtained electronic birth records for those born in the state of Michigan. We linked this information to parental serum PBB and PCB concentrations collected at enrollment into the cohort. We modeled the odds of a male birth with generalized estimating equations accounting for the non-independence of siblings born to the same parents. We explored potential confounders: parental age and education at offspring's birth, parental body mass index at cohort enrollment, birth order, gestational age and year of offspring's birth. RESULTS: The overall proportion of male offspring among 865 live births to cohort mothers was 0.542. This was higher than the national male proportion of 0.514 (binomial test: p = 0.10). When both parents were in the cohort (n = 300), we found increased odds of a male birth with combined parents' enrollment PBB exposure > or = the median concentrations (3 microg/L for mothers; 6 microg/L for fathers) compared to combined parents' PBB exposure < the median concentrations (AOR = 1.43, 95% CI: 0.89-2.29), although this did not reach statistical significance. In addition, there was a suggestion of increased odds of a male birth for combined parents' enrollment PCB exposure > or = the median concentrations (6 microg/L for mothers; 8 microg/L for fathers) compared to combined parents' enrollment PCB exposure < the median concentrations (AOR = 1.53, 95% CI: 0.93-2.52). CONCLUSION: This study adds to the body of literature on secondary sex ratio and exposure to environmental contaminants. In this population, combined parental exposure to PBBs or PCBs increased the odds of a male birth. Further research is needed to corroborate these findings and shed light on the biological mechanisms by which these types of chemicals may influence the secondary sex ratio.

In utero exposure to a brominated flame retardant and male growth and development.

Whether environmental exposures alter the timing of puberty is the subject of increasing interest as pubertal age may have consequences for long term health. This study examines the association between exposure to a brominated flame retardant, polybrominated biphenyl (PBB), and puberty and growth. The population consists of sons born to women accidentally exposed to PBBs during 1973-74. Sons 5 to 17 years reported Tanner Stages and answered questions regarding current growth in a mailed questionnaire. Sons 18 to 30 years of age participated in a telephone interview in which they reported retrospective measures of development. Among sons 5-17 years, those with highest exposure (>3 ppb) were less likely to report advanced Tanner stage genital development (OR=0.4, 95% CI: 0.2-0.9) and were less likely to report advanced pubic hair development (OR=0.5; 95% CI: 0.2-1.0), after adjusting for current age, compared to those with lowest exposure (<= 1 ppb). No differences were seen in growth among sons 5-17. However, among sons 18-30 years, those with higher exposure were more likely to weigh less and have lower BMI as adults (test of trend p=0.01 and 0.04, respectively). They were less likely to recall being tall (OR=0.5; 95% CI 0.2-0.9) or heavy (OR=0.6; 95% CI 0.3-1.1) compared to their peers at age 11 years. These results suggest that sons exposed to PBBs in utero may be more likely to have delayed puberty. Further research is needed to corroborate these findings among structurally related compounds and shed light on the biological mechanisms that may be disrupted during puberty and 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).

Multicenter U.S. bilateral MED-EL cochlear implantation study: speech perception over the first year of use.

OBJECTIVE: Binaural hearing has been shown to support better speech perception in normal-hearing listeners than can be achieved with monaural stimulus presentation, particularly under noisy listening conditions. The purpose of this study was to evaluate whether bilateral electrical stimulation could confer similar benefits for cochlear implant listeners. DESIGN: A total of 26 postlingually deafened adult patients with short duration of deafness were implanted at five centers and followed up for 1 yr. Subjects received MED-EL COMBI 40+ devices bilaterally; in all but one case, implantation was performed in a single-stage surgery. Speech perception testing included CNC words in quiet and CUNY sentences in noise. Target speech was presented at the midline (0 degrees), and masking noise, when present, was presented at one of three simulated source locations along the azimuth (-90, 0, and +90 degrees). RESULTS: Benefits of bilateral electrical stimulation were observed under conditions in which the speech and masker were spatially coincident and conditions in which they were spatially separated. Both the "head shadow" and "summation" effects were evident from the outset. Benefits consistent with "binaural squelch" were not reliably observed until 1 yr after implantation. CONCLUSIONS: These results support a growing consensus that bilateral implantation provides functional benefits beyond those of unilateral implantation. Longitudinal data suggest that some aspects of binaural processing continue to develop up to 1 yr after implantation. The squelch effect, often reported as absent or rare in previous studies of bilateral cochlear implantation, was present for most subjects at the 1 yr measurement interval.

PCBs enhance collagen I expression from human peritoneal fibroblasts.

OBJECTIVE: To test the effect of four polychlorinated biphenyl congeners (PCB-77, PCB-105, PCB 153, and PCB 180) on expression of three adhesion markers (transforming growth factor [TGF] beta1, vascular endothelial growth factor [VEGF], and type I collagen) in normal human peritoneal and adhesion fibroblasts. DESIGN: Cell culture study. SETTINGS: University research laboratory. PATIENT(S): Primary cultures of normal peritoneal and adhesion fibroblasts were established from three patients. INTERVENTION(S): Fibroblasts were treated with PCB-77, PCB-105, PCB-153, or PCB-180 at 20 ppm for 24 hours. Total RNA was extracted from each treatment and subjected to real-time reverse transcriptase polymerase chain reaction (RT-PCR). MAIN OUTCOME AND MEASURE(S): The mRNA levels of type I collagen, VEGF, and TGF-beta1. RESULT(S): Normal human peritoneal fibroblasts expressed type I collagen, VEGF, and TGF-beta1. Exposure of normal human fibroblasts to PCB-77, PCB-105, PCB-153, or PCB-180 did not affect mRNA levels of beta-actin, the housekeeping gene used to normalized RNA levels for the real-time RT-PCR, nor did it affect cell viability as assessed by trypan blue exclusion. The PCB treatments, compared with control, resulted in no significant change for TGF-beta1 or VEGF mRNA levels in normal peritoneal and adhesion fibroblasts. In marked contrast, type I collagen mRNA levels were markedly increased in response to the brief 24 hours' exposure to each PCB treatment in both cell types. CONCLUSION(S): The finding that PCB-77, PCB-105, PCB-153, and PCB-180 increased the expression of type I collagen in human normal peritoneal and adhesion fibroblasts is the first demonstration of involvement of organochlorines in the pathogenesis of tissue fibrosis. This may implicate organochlorine exposure as an etiologic factor in a wide variety of previously unlinked human ailments characterized by fibrosis.