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In 1973, accidental contamination of Michigan livestock with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals that have been followed for > 40 years. Besides being exposed to PBBs, this cohort has also been exposed to polychlorinated biphenyls (PCBs), a structurally similar class of environmental pollutants, at levels similar to average US exposure. In this study, we examined the association between current serum PCB and PBB levels and various female reproductive health outcomes to build upon previous work and inconsistencies. Participation in this cross-sectional study required a blood draw and completion of a detailed health questionnaire. Analysis included only female participants who had participated between 2012 and 2015 (N = 254). Multivariate linear and logistic regression models were used to identify associations between serum PCB and PBB levels with each gynecological and infertility outcome. Additionally, a generalized estimating equation (GEE) model was used to evaluate each pregnancy and birth outcome in order to account for multiple pregnancies per woman. We controlled for age, body mass index, and total lipid levels in all analyses. A p-value of β = −0.11, 95% CI = −0.21 to −0.005, p = 0.04). There were no correlations between serum PCB levels and the self-reported gynecological outcomes (pelvic inflammatory disease, endometriosis, polycystic ovarian syndrome, or uterine fibroids). No associations were identified between serum PCB levels and the prevalence of female infertility in women reporting ever having sexual intercourse with a male partner. There were no associations identified between serum PCB levels and pregnancy outcomes (singleton live births or miscarriages) or birth outcomes (preterm birth, birth weight, birth defects, hypertensive disorders of pregnancy, or gestational diabetes). PBB was not associated with any outcome. Further research is needed to determine if and how PCB may reduce pregnancy number.

BACKGROUND: Brominated flame retardants, including polybrominated biphenyls (PBB), are persistent compounds reported to affect sex hormones in animals; less is known about potential effects in humans. An industrial accident in 1973–1974 exposed Michigan residents to PBB through contaminated food. We examined whether this exposure to PBB had long-term effects on menstrual cycle function. METHODS: In 2004–06, we recruited reproductive-aged women in the Michigan PBB Registry who were not pregnant, lactating, or taking hormonal medications. Participants kept daily diaries and provided daily urine for up to 6 months. We assayed urine samples for estrone 3-glucuronide (E(1)3G), pregnanediol 3-glucuronide (Pd3G), and follicle stimulating hormone (FSH). We fit linear mixed models among women aged 35–42 years to describe the relation between serum PBB levels and log-transformed, creatinine-adjusted daily endocrine levels among women who were premenarchal during the exposure incident in 1973–74 (n=70). RESULTS: We observed that high (>3.0 parts per billion (ppb)) and medium (>1.0–3.0 ppb) PBB exposure were associated with lower E(1)3G levels across the menstrual cycle and lower FSH levels during the follicular phase, compared with low PBB exposure (≤1.0 ppb). High PBB exposure was also associated with lower Pd3G levels across the cycle compared with low PBB exposure, whereas Pd3G levels were similar in women with medium and low PBB exposure. CONCLUSIONS: Our results are consistent with a hypothesized effect of exposure to an exogenous estrogen agonist but the modest sample size of the study requires cautious interpretation.

Advanced age increases risk for cancer, cardiovascular disease, and all-cause mortality. However, people do not age at the same rate, and biological age (frequently measured through DNA methylation) can be older than chronological age. Environmental factors have been associated with the rate of biological aging, but it is not known whether persistent endocrine-disrupting compounds (EDCs) like polybrominated biphenyl (PBB) would associate with age acceleration. Three different epigenetic age acceleration measures (intrinsic, extrinsic, and phenotypic) were calculated from existing epigenetic data in whole blood from a population highly exposed to PBB (N=658). Association between serum PBB concentration and these measures was tested, controlling for sex, lipid levels, and estimated cell type proportions. Higher PBB levels associated with increased age acceleration (intrinsic: β=0.24, 95%CI=0.01-0.46, p = 0.03; extrinsic: β=0.39, 95%CI=0.12-0.65, p = 0.004; and phenotypic: β=0.30, 95%CI=0.05-0.54, p = 0.01). Neither age when exposed to PBB nor sex statistically interacted with PBB to predict age acceleration, but, in stratified analyses, the association between PBB and age acceleration was only in people exposed before finishing puberty and in men. This suggests that EDCs can associate with the biological aging process, and further studies are warranted to investigate other environmental pollutants’ effect on aging.

Background Michigan residents were directly exposed to endocrine-disrupting compounds, polybrominated biphenyl (PBB) and polychlorinated biphenyl (PCB). A growing body of evidence suggests that exposure to certain endocrine-disrupting compounds may affect thyroid function, especially in people exposed as children, but there are conflicting observations. In this study, we extend previous work by examining age of exposure’s effect on the relationship between PBB exposure and thyroid function in a large group of individuals exposed to PBB. Methods Linear regression models were used to test the association between serum measures of thyroid function (total thyroxine (T4), total triiodothyronine (T3), free T4, free T3, thyroid stimulating hormone (TSH), and free T3: free T4 ratio) and serum PBB and PCB levels in a cross-sectional analysis of 715 participants in the Michigan PBB Registry. Results Higher PBB levels were associated with many thyroid hormones measures, including higher free T3 (p = 0.002), lower free T4 (p = 0.01), and higher free T3: free T4 ratio (p = 0.0001). Higher PCB levels were associated with higher free T4 (p = 0.0002), and higher free T3: free T4 ratio (p = 0.002). Importantly, the association between PBB and thyroid hormones was dependent on age at exposure. Among people exposed before age 16 (N = 446), higher PBB exposure was associated with higher total T3 (p = 0.01) and free T3 (p = 0.0003), lower free T4 (p = 0.04), and higher free T3: free T4 ratio (p = 0.0001). No significant associations were found among participants who were exposed after age 16. No significant associations were found between TSH and PBB or PCB in any of the analyses conducted. Conclusions This suggests that both PBB and PCB are associated with thyroid function, particularly among those who were exposed as children or prenatally. Electronic supplementary material The online version of this article (10.1186/s12940-019-0509-z) contains supplementary material, which is available to authorized users.

This paper provides highlights from an expert meeting to explore opportunities to reduce cancer risk and promote health at older ages. Factors that increase cancer risk among older adults include exposure to carcinogens from multiple sources, chronic conditions such as obesity and diabetes, and unhealthy behaviors. Emerging research points to chronic social stressors – social isolation, loneliness, and financial hardship – as being linked to accelerated biological aging and increased cancer risk later in life. Older adults may disproportionately encounter these stressors as well as barriers to preventive health care services, accurate health information, and environments that promote health. Researchers can use existing cohort studies of older adults to deepen our understanding of the relative benefit of modifying specific behaviors and circumstances. The evidence points to the value of comprehensive, transdisciplinary approaches to promote health and reduce cancer risk across the entire lifespan, extending through older adulthood. Clinical encounters with older adults provide opportunities for psychosocial and behavioral screening and counseling. In the presence of multiple morbidities, preventive health services may offer greater health benefits than cancer-screening tests. Strategies that involve families and caregivers, promote positive attitudes about aging, and engage many different community sectors have the potential to prevent or delay the development of cancer at older ages.

Although polychlorinated biphenyls and polybrominated biphenyls are no longer manufactured the United States, biomonitoring in human populations show that exposure to these pollutants persist in human tissues. The objective of this study was to identify metabolic variations associated with exposure to 2,2’4,4’,5,5’-hexabromobiphenyl (PBB-153) and 2,2’4,4’,5,5’-hexachlorobiphenyl (PCB-153) in two generations of participants enrolled in the Michigan PBB Registry (http://pbbregistry.emory.edu/). Untargeted, high-resolution metabolomic profiling of plasma collected from 156 individuals was completed using liquid chromatography with high-resolution mass spectrometry. PBB-153 and PCB-153 levels were measured in the same individuals using targeted gas chromatography-tandem mass spectrometry and tested for dose-dependent correlation with the metabolome. Biological response to these exposures were evaluated using identified endogenous metabolites and pathway enrichment. When compared to lipid-adjusted concentrations for adults in the National Health and Nutrition Examination Survey (NHANES) for years 2003–2004, PCB-153 levels were consistent with similarly aged individuals, whereas PBB-153 concentrations were elevated (p

Background Many studies investigating pubertal development use Tanner staging to assess maturation. Endocrine markers in urine and saliva may provide an objective, sensitive, and non-invasive method for assessing development. Objective Our objective was to examine whether changes in endocrine levels can indicate the onset of pubertal development prior to changes in self-rated Tanner stage. Methods Thirty-five girls and 42 boys aged 7 to 15 years were enrolled in the Growth and Puberty (GAP) study, a longitudinal pilot study conducted from 2007–2009 involving children of women enrolled in the Agricultural Health Study (AHS) in Iowa. We collected saliva and urine samples and assessed pubertal development by self-rated Tanner staging (pubic hair, breast development (girls), genital development (boys)) at three visits over six months. We measured dehydroepiandrosterone (DHEA) in saliva and creatinine-adjusted luteinizing hormone (LH), testosterone, follicle stimulating hormone (FSH), estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) concentrations in first morning urine. We evaluated the relationships over time between Tanner stage and each biomarker using repeated measures analysis. Results Among girls still reporting Tanner breast stage 1 at the final visit, FSH levels increased over the 6-month follow-up period and were no longer lower than higher stage girls at the end of follow-up. We observed a similar pattern for testosterone in boys. By visit 3, boys still reporting Tanner genital stage 1 or pubic hair stage 1 had attained DHEA levels that were comparable to those among boys reporting Tanner stages 2 or 3. Conclusions Increasing concentrations of FSH in girls and DHEA and testosterone in boys over a 6-month period revealed the start of the pubertal process prior to changes in self-rated Tanner stage. Repeated, non-invasive endocrine measures may complement the more subjective assessment of physical markers in studies determining pubertal onset.

Exposure to endocrine disrupting chemicals (EDCs) is ubiquitous. EDC exposure, especially during critical periods of development like the prenatal window, may interfere with the body’s endocrine system, which can affect growth and developmental outcomes such as puberty. Most studies have examined one EDC at a time in relation to disease; however, humans are exposed to many EDCs. By studying mixtures, the human experience can be more closely replicated. We investigated the association of prenatal exposure to persistent EDCs (poly- and perfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with early menarche among female offspring in a nested case-control study within the Avon Longitudinal Study of Parents and Children (ALSPAC) recruited in the United Kingdom in 1991–1992. Concentrations of 52 EDCs were quantified in maternal serum samples collected during pregnancy. Daughter’s age at menarche was ascertained through mailed questionnaires sent annually. We used repeated holdout weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) to examine the association between prenatal exposure to multiple EDCs and early menarche (

Context Menstrual cycle function is determined by a complex endocrine axis that controls the ovaries and endometrium. While the late luteal phase is characterized by declining progesterone and estrogen, how these hormonal profiles relate to menstrual bleeding patterns is not well understood. Objective Characterize associations between luteal phase hormonal profiles and subsequent menstrual bleeding patterns, specifically spotting before bleeding. Design, Setting, and Participants We examined creatinine-adjusted urinary estrone 3-glucuronide (E13G) and pregnanediol 3-glucuronide (Pd3G) levels in relation to spotting in 116 premenopausal women (ages 20–47) who kept daily menstrual diaries and collected first morning urine samples for ≥ 2 consecutive cycles or 1 luteal-follicular transition (n = 283 transitions). We used linear mixed models to estimate associations between luteal phase hormone levels and spotting before bleeding. Main Outcome Measure(s) and Results Transitions with ≥ 1 days of spotting before menstrual bleeding (n = 118) had greater luteal phase Pd3G levels vs nonspotting transitions (n = 165). Differences in Pd3G between spotting and nonspotting transitions were largest at menses onset (34.8%, 95% confidence interval, 18.9%, 52.7%). Pd3G levels for spotting transitions dropped to similar levels as nonspotting transitions an average of 1 day later, which aligned with the first day of bleeding for transitions with contiguous spotting. Spotting transitions were preceded by slower rates of Pd3G decline than nonspotting transitions, whereas E13G declines were similar. Conclusions Self-reported bleeding patterns may provide insight into luteal phase Pd3G levels. First bleed appears to be the best choice for defining the end of the luteal phase and achieving hormonal consistency across transitions.

PURPOSE: Endocrine disrupting compounds (EDCs) have been shown to affect multiple biologic processes especially steroid-hormone processes. We sought to determine differences in DNA methylation exists between women with and without endometriosis following exposure to polybrominated biphenyl (PBB). METHODS: Cross-sectional study of 305 females in the Michigan PBB Registry. DNA was extracted, and DNA methylation was interrogated using the MethylationEPIC BeadChip (Illumina, San Diego, California). Demographic data was analyzed using Chi-squared and T tests. Linear regressions were performed for each cytosine-guanine dinucleotide (CpG) site, modeling the logit transformation of the β value as a linear function of the presence of endometriosis. Sensitivity analyses were conducted controlling for estradiol levels and menopausal status. Replication study performed evaluating for any association between CpGs reported in the literature and our findings. RESULTS: In total, 39,877 CpGs nominally associated with endometriosis (p

Widespread polybrominated biphenyls (PBBs) contamination occurred in Michigan from 1973 to 1974, when PBBs were accidentally substituted for a nutritional supplement in livestock feed. People who lived in the state were exposed to PBBs via several routes including ingestion, inhalation and skin absorption. PBBs sequestered in lipid-rich matrices such as adipose tissue, are slowly eliminated after entering the human body, and can also be transferred from a mother to her offspring through the placenta and breastfeeding. Due to the long biological half-lives of PBBs, as well as concerns from the exposed community, biomonitoring measurements were conducted from 2012 to 2015. Because of their similar structures, serum PBBs, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were all measured 40 years after the PBB contamination incident (N = 862). The serum PBB-153 levels among the original highly-exposed groups (i.e., chemical workers, the family of chemical workers, and individuals who lived on or received food from the contaminated farms) remains significantly higher than other Michigan residents. Several predictors such as sampling age, sex, and smoking status were significantly associated with the serum levels of some persistent organic pollutants (POPs). Higher average values and also wider ranges of serum POP levels were found in this study compared to the National Health and Nutrition Examination Survey (NHANES), with the most substantial difference in serum PBB-153. This was true for all groups of Michigan residents including those who were not part of the above-described highly-exposed groups. Moreover, the people born after the contamination incident began also have higher serum PBB-153 levels when compared with more recent NHANES data (2010–2014), which suggests potential intergenerational exposure and/or continued environmental exposure following the contamination period. Keywords: Polybrominated biphenyls (PBBs), Polychlorinated biphenyls (PCBs), Polybrominated diphenyl ethers (PBDEs), Persistent organic pollutants (POPs), Michigan PBB Registry, Biomonitoring

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.

BACKGROUND: Previous studies have reported that hyperthyroid and hypothyroid women experience menstrual irregularities more often compared with euthyroid women, but reasons for this are not well understood and studies on thyroid hormones among euthyroid women are lacking. In a prospective cohort study of euthyroid women, this study characterized the relationship between thyroid hormone concentrations and prospectively-collected menstrual function outcomes. METHODS: Between 2004–2014, 86 euthyroid premenopausal women not lactating or taking hormonal medications participated in a study measuring menstrual function. Serum thyroid hormones were measured before the menstrual function study began. Women then collected first morning urine voids and completed daily bleeding diaries every day for three cycles. Urinary estrogen and progesterone metabolites (estrone 3-glucuronide (E(1)3G) and pregnanediol 3-glucuronide (Pd3G)) and follicle-stimulating hormone were measured and adjusted for creatinine (Cr). RESULTS: Total thyroxine (T(4)) concentrations were positively associated with Pd3G and E(1)3G. Women with higher (vs. lower) T(4) had greater luteal phase maximum Pd3G (Pd3G=11.7 μg/mg Cr for women with high T(4) vs. Pd3G=9.5 and 8.1 μg/mg Cr for women with medium and low T(4), respectively) and greater follicular phase maximum E(1)3G (E(1)3G=41.7 ng/mg Cr for women with high T(4) vs. E(1)3G=34.3 and 33.7 ng/mg Cr for women with medium and low T(4), respectively). CONCLUSIONS: Circulating thyroid hormone concentrations were associated with subtle differences in menstrual cycle function outcomes, particularly sex steroid hormone levels in healthy women. Results contribute to the understanding of the relationship between thyroid function and the menstrual cycle, and may have implications for fertility and chronic disease.

Background: The American Heart Association (AHA) has developed the Life’s Simple 7 metric (no smoking, high levels of physical activity, normal body mass index, no hypertension, no diabetes, no hyperlipidemia, healthy diet) to track behaviors and risk factors associated with cardiovascular health (CVH). Given the potential role that CVH has in cognition and psychological well-being, we aimed to study the association of the Life’s Simple 7 with cognitive function, anxiety, and depressive symptoms in the Emory Health Aging Study (EHAS). Methods: EHAS is an ongoing cohort study with the overall goal of understanding determinants of healthy aging in the general population. Participants 18 years of age or older are recruited at primary care clinics, community events, and through social media, primarily from the Atlanta (GA) area. Information on sociodemographic variables (age, sex, race, education, income), anthropometrics (weight, height), lifestyles (smoking, physical activity), and clinical variables (history of hypertension, diabetes, hypercholesterolemia, cardiovascular disease [CVD]) was collected through online questionnaires. Life’s Simple 7 score (excluding diet; information not available) was defined based on self-reported data, giving 1 point per achieved metric [range 0 (lowest)-6(highest CVH)]. Neurobehavioral variables were measured using validated scales (Cognitive Function Instrument (CFI), range 0-14, for cognition; Patient Health Questionnaire (PHQ)-8, range 0-24, for depressive symptoms; Generalized Anxiety Disorder (GAD) questionnaire, range 0-21, for anxiety; higher scores represent worse function/symptoms). Cross-sectional associations between Life’s Simple 7 score and these scales were assessed using multivariable linear regression adjusting for sociodemographic variables. Results: We included 3,774 participants [mean age (standard deviation, SD) 58 (13), 79% women, 84% white, 9% African American, 7% other) free of self-reported CVD, recruited between October 2015 and October 2016. Levels of CVH in the cohort were relatively high, with 62% participants meeting at least 4 health criteria [mean (SD) score 3.9 (1.3)]. The mean (SD) of CFI, PHQ-8, and GAD were 1.9 (2.1), 3.2 (3.8), 2.4 (3.4), respectively. In analyses adjusted for age, sex, race, education, and income, higher values of Life’s Simple 7 score were related to better cognitive function and lower levels of depressive symptoms and anxiety: estimates (95% confidence interval) per 1-point in Life’s Simple 7 score were -0.16 (-0.22, -0.11) for CFI, -0.5 (-0.6, -0.4) for PHQ-8, and -0.3 (-0.4, -0.2) for GAD. Conclusion: Higher levels of CVH, as assessed with the AHA Life’s Simple 7, were cross-sectionally associated with a beneficial neurobehavioral profile. Prospective studies should evaluate the impact of improving CVH on cognitive and emotional health.

Objective: To better characterize associations between physical risk factors and upper-extremity musculoskeletal symptoms and disorders, a prospective epidemiologic study of 386 manufacturing workers was performed. Background: Methodological limitations of previous studies have resulted in inconsistent associations. Method: An individual, task-based exposure assessment strategy was used to assess upper-extremity exertion intensity, repetition, and time-in-posture categories. Participants recorded time spent performing daily work tasks on a preprinted log, which was then used to calculate time-weighted-average exposures across each week of follow-up. In addition, a weekly Strain Index (SI) risk category was assigned to each participant. Incident musculoskeletal symptoms and disorders were assessed weekly. Proportional hazards analyses were used to examine associations between exposure measures and incident hand/arm and neck/shoulder symptoms and disorders. Results: Incident symptoms and disorders were common (incident hand/arm symptoms = 58/100 person-years (PY), incident hand/arm disorders = 19/100 PY, incident neck/shoulder symptoms = 54/100 PY, incident neck/shoulder disorders = 14/100 PY). Few associations between separate estimates of physical exposure and hand/arm and neck/shoulder outcomes were observed. However, associations were observed between dichotomized SI risk category and incident hand/arm symptoms (hazard ratio [HR] = 1.73, 95% confidence interval [CI] = [0.99, 3.04]) and disorders (HR = 1.93, 95% CI = [0.85, 4.40]). Conclusion: Evidence of associations between physical risk factors and musculoskeletal outcome was strongest when exposure was estimated with the SI, in comparison to other metrics of exposure. Application: The results of this study provide evidence that physical exposures in the workplace contribute to musculoskeletal disorder incidence. Musculoskeletal disorder prevention efforts should include mitigation of these occupational risk factors.

Objective: The aim of this study was to characterize associations between psychosocial and work organizational risk factors and upper-extremity musculoskeletal symptoms and disorders. Background: Methodological limitations of previous studies of psychosocial and work organizational risk factors and musculoskeletal outcomes have produced inconsistent associations. Method: In this prospective epidemiologic study of 386 workers, questionnaires to assess decision latitude (“control”) and psychological job demands (“demand”) were administered to study participants and were used to classify them into job strain “quadrants.” Measures of job stress and job change were collected during each week of follow-up. Incident hand/arm and neck/shoulder symptoms and disorders were ascertained weekly. Associations between exposure measures and musculoskeletal outcomes were estimated with proportional hazard methods. Results: When compared to the low-demand/high-control job strain referent category, large increases in risk of hand/arm disorders were observed for both high-demand/high- control (hazard ratio [HR] = 4.49, 95% confidence interval [CI] = [1.23, 16.4]) and high-demand/low-control job strain categories (HR = 5.18, 95% CI = [1.39, 19.4]). Similar associations were observed for hand/arm symptoms. A strong association was also observed between the low-demand/low-control job strain category and neck/shoulder disorders (HR = 6.46, 95% CI = [1.46, 28.6]). Statistically significant associations were also observed between weekly stress level and weekly job change and several musculoskeletal outcomes. Conclusion: Associations between psychosocial risk factors and work organizational factors and musculoskeletal outcomes were large and in the hypothesized direction. Application: Prevention of occupational musculoskeletal disorders may require attention to psychosocial and work organizational factors in addition to physical factors. Methods to control adverse effects of psychosocial and work organizational risk factors should be explored.

Background: In 1973–1974, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. Residents were enrolled in a registry assembled after the incident, and they and their children participated in follow-up studies to assess subsequent health outcomes. Objectives: We evaluated associations between serum PBBs and polychlorinated biphenyls (PCBs) and markers of thyroid function among Michigan adults. Methods: Serum concentrations of four PBB and four PCB congeners were measured at least once in 753 adults, including 79 women who participated in a 2004–2006 study and 683 women and men with follow-up during 2012–2015. Participants completed questionnaires on health conditions (including physician-diagnosed thyroid disease), behaviors, and demographics. Thyroid hormones were measured in a subset without thyroid disease (n=551). In multivariable linear regression models, PBB and PCB congener concentrations, on both the volume (nanogram/milliliter) and lipid (nanogram/gram lipid) basis, were assessed in relation to thyroid hormones. Logistic regression models were used to estimate associations between serum PBBs and PCBs and thyroid disease. Results: Thyroid disease was common (18% overall; 25% among women). Among women, all odds ratios (ORs) for PBB-153 and thyroid disease were positive for quintiles above the reference level, but estimates were imprecise and were without a monotonic increase. For an interquartile range (IQR) increase in PBB-153 (0.43 ng/mL), the OR (any thyroid disease)=1.12; (95% CI: 0.83, 1.52) (n=105 cases); for hypothyroidism, OR=1.35 (95% CI: 0.86, 2.13) (n=49 cases). There were 21 cases of thyroid disease in men [OR=0.69 (95% CI: 0.33); 1.44 for an IQR increase (0.75 ng/mL) in serum PBB-153]. PCB congeners were statistically significantly associated with greater total and free thyroxine and total triiodothyronine among women and with total and free triiodothyronine among men in lipid-standardized models. Conclusions: We found some evidence to support associations of PBBs and PCBs with thyroid disease and thyroid hormone levels. https://doi.org/10.1289/EHP1302

Introduction: In 1973-74, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. This cohort of exposed individuals and their chi...

Background Phytoestrogens are estrogenic compounds that occur naturally in plants. Phytoestrogens can cross the placenta, and animal studies have found associations between in utero exposure to phy...

The ratio between the second and fourth digits is a sexually dimorphic measure, established in utero and linked to prenatal sex steroid levels. An association was found between prenatal levels of Polybrominated Biphenyls, a synthetic chemical suspected to disrupt the endocrine system function, and the digit ratio in adult women.

This study examines the timing of menarche in relation to infant-feeding methods, specifically addressing the potential effects of soy isoflavone exposure through soy-based infant feeding. Subjects were participants in the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers were enrolled during pregnancy and their children have been followed prospectively. Early-life feeding regimes, categorised as primarily breast, early formula, early soy and late soy, were defined using infant-feeding questionnaires administered during infancy. For this analysis, age at menarche was assessed using questionnaires administered approximately annually between ages 8 and 14.5. Eligible subjects were limited to term, singleton, White females. We used Kaplan-Meier survival curves and Cox proportional hazards models to assess age at menarche and risk of menarche over the study period. The present analysis included 2920 girls. Approximately 2% of mothers reported that soy products were introduced into the infant diet at or before 4 months of age (early soy). The median age at menarche [interquartile range (IQR)] in the study sample was 153 months [144-163], approximately 12.8 years. The median age at menarche among early soy-fed girls was 149 months (12.4 years) [IQR, 140-159]. Compared with girls fed non-soy-based infant formula or milk (early formula), early soy-fed girls were at 25% higher risk of menarche throughout the course of follow-up (hazard ratio 1.25 [95% confidence interval 0.92, 1.71]). Our results also suggest that girls fed soy products in early infancy may have an increased risk of menarche specifically in early adolescence. These findings may be the observable manifestation of mild endocrine-disrupting effects of soy isoflavone exposure. However, our study is limited by few soy-exposed subjects and is not designed to assess biological mechanisms. Because soy formula use is common in some populations, this subtle association with menarche warrants more in-depth evaluation in future studies.

Thyroid hormones, which influence body metabolism and development, could be affected by persistent organic pollutants. We sought to examine the relationship between polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) and thyroid disease. We employed incidence density sampling to perform a nested case control analysis of the Michigan Long-Term PBB Cohort. Cohort members (n=3333) were exposed to PBBs through contaminated cattle feed in 1973-1974 and to PCBs through daily life. Those with detectable serum PBB and PCB concentrations at enrollment were categorized into tertiles of PBB and PCB exposure. Case-patients were cohort members answering "Yes" to "Has a healthcare provider ever told you that you had a thyroid problem?" during follow-up interviews; control-patients were cohort members answering "No". We used odds ratios (OR) with 95% confidence intervals (CI) to compare odds of thyroid disease by PBB and PCB exposure and by various risk factors. Total cumulative thyroid disease incidence after 33 years was 13.9% among women and 2.6% among men. After adjusting for body mass index, we found no statistically significant differences in odds of any type of thyroid disease among women or men with elevated PBB or PCB exposure. Compared to control-patients, women with thyroid disease had increased odds of being overweight/obese (OR=2.82, 95% CI: 1.94-4.11) and developing infertility (OR=1.71, 95% CI: 1.08-2.69), diabetes (OR=1.61, 95% CI: 1.04-2.51), or arthritis (OR=1.71, 95% CI: 1.18-2.50) during follow-up. Additional research should explore potential associations between PBBs/PCBs and thyroid disease among children exposed in utero.

Introduction: Polyfluoroalkyl chemicals (PFCs) are commercially synthesized chemicals used in consumer products. Exposure to certain PFCs is widespread, and some PFCs may act as endocrine disruptors. We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) in the United Kingdom to conduct a nested case-control study examining the association between age at menarche, and exposure to PFCs during pregnancy. Methods: Cases were selected from female offspring in the ALSPAC who reported menarche before the age of 11.5 years (n=218), and controls were a random sample of remaining girls (n=230). Serum samples taken from the girls' mothers during pregnancy (1991–1992) were analyzed using on-line solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry for 8 PFCs. Logistic regression was used to determine association between maternal serum PFC concentrations, and odds of earlier age at menarche. Results: PFOS and PFOA were the predominant PFCs (median serum concentrations of 19.8 ng/mL and 3.7 ng/mL). All but one PFC were detectable in most samples. Total PFC concentration varied by number of births (inverse association with birth order; p-value

This study describes the timing of puberty in 8- to 14-year-old boys enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC) and identifies factors associated with earlier achievement of advanced pubic hair stages. Women were enrolled during pregnancy and their offspring were followed prospectively. We analysed self-reported pubic hair Tanner staging collected annually. We used survival models to estimate median age of attainment of pubic hair stage >1, stage >2 and stage >3 of pubic hair development. We also constructed multivariable logistic regression models to identify factors associated with earlier achievement of pubic hair stages. Approximately 5% of the boys reported Tanner pubic hair stage >1 at age 8; 99% of boys were at stage >1 by age 14. The estimated median ages of entry into stages of pubic hair development were 11.4 years [95% confidence interval (CI) 11.3, 11.4] for stage >1, 12.7 years [95% CI 12.7, 12.8] for stage >2 and 13.5 years [95% CI 13.5, 13.6] for stage >3. Predictors of younger age at Tanner stage >1 included low birthweight, younger maternal age at delivery and being taller at age 8. Associations were found between younger age at attainment of stage >2 and gestational diabetes and taller or heavier body size at age 8. Being taller or heavier at age 8 also predicted younger age at Tanner stage >3. The results give added support to the strong influence of pre-adolescent body size on male pubertal development; the tallest and heaviest boys at 8 years achieved each stage earlier and the shortest boys later. Age at attainment of pubic hair Tanner stages in the ALSPAC cohort are similar to ages reported in other European studies that were conducted during overlapping time periods. This cohort will continue to be followed for maturational information until age 17.

OBJECTIVES: The objective of this study was to explore the influence of maternal prenatal characteristics and behaviors and of weight and BMI gain during early childhood on the timing of various puberty outcomes in girls who were enrolled in the Avon Longitudinal Study of Parents and Children. METHODS: Repeated self-assessments of pubertal development were obtained from ∼4000 girls between the ages of 8 and 14. Data on prenatal characteristics and weight at birth and 2, 9, and 20 months of age were obtained from questionnaires, birth records, and clinic visits. Infants' weights were converted to weight-for-age and BMI SD scores (SDSs; z scores), and change values were obtained for the 0- to 20-month and other intervals within that age range. We used parametric survival models to estimate associations with age of entry into Tanner stages of breast and pubic hair and menarche. RESULTS: Maternal initiation of menarche at age CONCLUSIONS: Many of the maternal prenatal characteristics and weight and BMI gain during infancy seemed to have similar influences across different puberty outcomes. Either such early factors have comparable influences on each of the hormonal processes involved in puberty, or processes are linked and awakening of 1 aspect triggers the others.

There is evidence that sex differences in hip structure are increased during puberty, possibly as a consequence of associated changes in body composition.The objective of the study was to explore relationships between sex, puberty, hip structure, and body composition.The design was a longitudinal birth cohort study: The Avon Longitudinal Study of Parents and Children.Participants included 3914 boys and girls (mean age 13.8 yr).Measures included dual-energy x-ray absorptiometry-derived femoral neck width (FNW), cortical thickness (CT), bending strength [cross-sectional moment of inertia (CSMI)], section modulus, buckling ratio (BR), and femoral neck and total hip bone mineral density.FNW, CT, and CSMI were higher in boys, whereas BR was lower in girls (P0.001). Differences in hip structure were studied according to puberty (self-completion Tanner stage questionnaires). FNW, CT, and CSMI were higher in Tanner stage IV/V vs. I/II, particularly in boys (P0.001, puberty-sex interaction). BR was lower in Tanner stage IV/V, particularly in girls (P=0.008, puberty-sex interaction). Adjusting for height, fat mass, and lean mass resulted in differential attenuation in the sexes, such that CT attenuated by about 80% and about 40% in boys and girls, respectively (P=0.004, puberty-sex interaction for adjusted CT, Tanner stages I/II vs. IV/V). The difference in BR showed little attenuation after adjustment.During puberty, hip-bending strength increases, particularly in boys, due to their greater FNW, reflecting changes in height, fat mass, and lean mass. In contrast, BR falls during puberty, particularly in girls, reflecting their smaller FNW relative to CT, involving mechanisms partly independent of height and body composition.

Purpose The timing of breast and pubic hair development in girls are related, but the degree of correlation has not been well characterized. Periodic observations also are complicated by interval censoring. Methods Data used were from the Avon Longitudinal Study of Parents and Children. Mean age at entry into breast and pubic hair development was determined by the use of parametric survival analysis. The bivariate normal cumulative distribution function was evaluated over the region containing the paired event times; the likelihood was maximized with respect to the correlation coefficient ρ. Results Among 3938 participants, estimated mean ages at entry into Tanner stage 2 for breast and pubic hair development were 10.19 and 10.95, respectively. The likelihood was maximized at ρ = 0.503 to 0.506. This value remained relatively constant among subgroups, although some heterogeneity was observed by maternal and child body mass index and birth order. Conclusions The timing of breast and of pubic hair development is moderately correlated and remain so when it is stratified by characteristics associated with puberty.

The Michigan Female Health Study (MFHS) conducted research focusing on reproductive health outcomes among women exposed to polybrominated biphenyls (PBBs). In the work presented here, the available longitudinal serum PBB exposure measurements are used to obtain predictions of PBB exposure for specific time points of interest via random effects models. In a two-stage approach, a prediction of the PBB exposure is obtained and then used in a second-stage health outcome model. This paper illustrates how a unified approach, which links the exposure and outcome in a joint model, provides an efficient adjustment for covariate measurement error. We compare the use of empirical Bayes predictions in the two-stage approach with results from a joint modeling approach, with and without an adjustment for left- and interval-censored data. The unified approach with the adjustment for left- and interval-censored data resulted in little bias and near-nominal confidence interval coverage in both the logistic and linear model setting.

A strength of time-series analyses is the inherent control of individual-level risk factors that do not vary temporally. However, in studies of adverse pregnancy outcomes, risk factors considered time-invariant at the individual level may vary seasonally when aggregated into a pregnancy risk set. To illustrate, we describe the seasonal patterns of birth in Atlanta and demonstrate how these patterns could lead to confounding in time-series studies of seasonally-varying exposures and preterm birth.The study cohort included all births in 20-county metropolitan Atlanta delivered during the period 1994-2004 (n = 715,875). We assessed the seasonal patterns of estimated conception and birth for the full cohort and for subgroups stratified by sociodemographic factors. Based on the observed patterns, we quantified the degree of potential confounding created by (1) differences in the gestational age distribution in the risk set across calendar months and (2) differences in the sociodemographic composition of the risk set across calendar months.The overall seasonal pattern of birth was characterized by a peak in August-September and troughs in April-May and November-January. Seasonal patterns differed among racial and ethnic groups, maternal education levels, and marital status. As a consequence of these seasonal patterns, systematic seasonal differences in the gestational age distribution and the sociodemographic composition of the risk set led to differences in expected rates of preterm birth across calendar months.Time-series investigations of seasonally-varying exposures and adverse pregnancy outcomes should consider the potential for bias due to seasonal heterogeneity in the risk set.

Preterm birth (before 37 weeks of gestation) is a leading cause of infant morbidity and mortality, affecting 13% of births in the United States in 2005.1 An emerging body of evidence suggests that ambient levels of air pollution may play a role in the incidence of preterm birth.2–4 However, the gestational window of susceptibility has not been consistent across studies, with associations most commonly reported for exposures during early pregnancy (the first month or first trimester)5–9 or in late pregnancy (the third trimester, the last 6 weeks, the last month, the last week).5,7,8,10–14 Previous studies have also been inconsistent regarding the specific pollutants associated with preterm birth, although most studies suggest associations with ambient measures of particulate matter (PM).5–8,11–14 Sulfur dioxide (SO2), as well as traffic related pollutants such as nitrogen dioxide (NO2) and carbon monoxide (CO), have also been associated with preterm birth in several studies.5,8–16 Although the pathophysiology of preterm birth remains poorly understood, evidence suggests a role for inflammatory pathways as well as implantation errors in early pregnancy.17 Both of these pathways offer plausible mechanisms by which air pollution could increase the risk of preterm birth. Air pollution levels in the weeks following conception could disrupt implantation and placentation and increase the risk of preterm birth through suboptimal placental function. In late pregnancy, high levels of air pollution could activate either an acute or sustained inflammatory response leading to the initiation of early labor. To investigate the relationship between ambient air pollution during gestation and the incidence of preterm birth, we conducted a time-series analysis in the central five counties of metropolitan Atlanta during 1994–2004. In addition to the US Environmental Protection Agency (EPA) criteria pollutants (ozone [O3], SO2, NO2, CO, PM10, PM2.5), we investigated speciated particle measurements that are rarely available on a daily basis and have not been previously assessed in relation to preterm birth. We focused on three gestational windows of exposure based on findings from previous air pollution studies, as well as current hypotheses about biological mechanisms leading to preterm birth: the first month of gestation, the final week of gestation and the final six weeks of gestation.

Associations between ambient air pollution levels during weeks 3-7 of pregnancy and risks of cardiovascular malformations were investigated among the cohort of pregnancies reaching at least 20 weeks' gestation that were conceived during January 1, 1986-March 12, 2003, in Atlanta, Georgia. Surveillance records obtained from the Metropolitan Atlanta Congenital Defects Program, which conducts active, population-based surveillance on this cohort, were reviewed to classify cardiovascular malformations. Ambient 8-hour maximum ozone and 24-hour average carbon monoxide, nitrogen dioxide, particulate matter with an average aerodynamic diameter of

Relationships between ambient air pollution levels during pregnancy and adverse pregnancy outcomes have been investigated using one of three analytic approaches: ambient pollution levels have been contrasted over space, time or both space and time. Although the three approaches share a common goal, to estimate the causal effects of pollution on pregnancy outcomes, they face different challenges with respect to confounding.A framework based on counterfactual effect definitions to examine issues related to confounding in spatial, temporal, and spatial-temporal analyses of air pollution and pregnancy outcomes is presented, and their implications for inference are discussed.In spatial analyses, risk factors that are spatially correlated with pollution levels are confounders; the primary challenges relate to the availability and validity of risk factor measurements. In temporal analyses, where smooth functions of time are commonly used to control for confounding, concerns relate to the adequacy of control and the possibility that abrupt changes in risk might be systematically related to pollution levels. Spatial-temporal approaches are subject to challenges faced in both spatial and temporal analyses.Each approach faces different challenges with respect to the likely sources of confounding and the ability to control for that confounding because of differences in the type, availability, and quality of information required. Thoughtful consideration of these differences should help investigators select the analytic approach that best promotes the validity of their research.

Endometriosis among women of reproductive age can result in pain and infertility. The objectives of this study were to test if there is a relation between endometriosis and serum dioxin concentrations as expressed by total toxic equivalence and serum total polychlorinated biphenyl concentrations among women patients at one Atlanta reproductive medicine clinic during 1998-1999; a secondary objective was to provide exposure data for individual congeners of these chemicals and 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane (p,p'-DDE) in women in Atlanta. Laparoscopy including biopsy and visualization of the peritoneal cavity, ovaries, outside of the fallopian tubes and uterus confirmed all endometriosis cases (n=60) and confirmed 30 controls without endometriosis. Other controls had an infertile partner (n=27) or ovulation problems (n=7) with no signs or symptoms of endometriosis. All serum samples were analyzed at the U.S. Centers for Disease Control and Prevention in 2003. Statistical analyses included Fisher's exact chi-square tests and logistic regression. Models were presented for the full study sample and for the subset that included all cases (n=60) and only controls (n=30) with surgical confirmation of disease-free status. Serum concentrations (lipid-adjusted and non lipid-adjusted) of analyzed exposure measures were low and similar for cases and controls and did not explain endometriosis in the study population.

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.

To the Editor: We would like to comment on the article entitled “The influence of age at exposure to PBBs on birth outcomes” (Sweeney and Symanski, 2007, doi:10.1016/j.envres.2007.03.006). We have analyzed a mostly overlapping dataset described in our recently published article, “Maternal exposure to polybrominated and polychlorinated biphenyls: Infant birth weight and gestational age” (Givens et al., 2007). In brief, our sample included 899 infant birth records from 1975–1997 from women in the Michigan Long–Term Polybrominated Biphenyl (PBB) Study who also participated in the 1997–1998 Michigan Female Health Study telephone interview. The study population in Sweeney and Symanski (2007) included a total of 1,111 infant birth records from 1975–1994 from the Michigan Long–Term PBB Study cohort and a smaller cohort, the PCB Silo Cohort. Birth weight and gestational age were analyzed as separate outcomes in mixed–effects models in both articles; however, we found results that differed from Sweeney and Symanski (2007). Our birth weight model (Givens et al., Table 2, 2007) included similar covariates to Sweeney and Symanski’s (2007) model presented in Table 4 (gestational age, maternal age at infant’s birth, PBB, PCB, parity, and infant gender) and a few additional covariates (maternal smoking status and decade of infant’s birth). In comparison to Sweeney and Symanski’s (2007) model, we did not include maternal age at enrollment, interval between blood test (taken at enrollment) and date of infant’s birth, maternal BMI at enrollment, prenatal care and paternal education. Table 2 Collinearity Diagnostics - Principal Components Analysis^ Because our published results were contrary to Sweeney and Symanski’s (2007) results, we have attempted to replicate Sweeney and Symanski’s (2007) findings by including the additional variables of interval and maternal age at enrollment. Although our sample and methodological approaches are somewhat different, we were successfully able to reproduce similar parameter estimates as those presented in Sweeney and Symanski’s (2007) Table 4 (Table 1). Specifically, we were able to reproduce the association of maternal age at enrollment ≤ 10 years with approximately a 200 g heavier birth weight. However, we would like to raise several concerns with the interpretation of this result. The overall conclusion of a “maternal age at exposure” effect does not appear to be substantiated from the data for the following reasons: 1) “maternal age at enrollment” was used as a proxy for “maternal age at exposure,” without considering the potential error introduced by this proxy, 2) a substantial proportion of the population did not have detectable serum PBB in the blood, but Sweeney and Symanski’s (2007) models did not account for this, and 3) there are methodological issues that appear to be the source of the “maternal age at exposure” effect. Table 1 Mixed Models for Infant Birth Weight

Background The prevalence of diabetes is higher among Mexican Americans than among non-Hispanic whites. Higher serum levels of organochlorine pesticides in Mexican Americans have been reported. Few studies have explored the association between pesticide exposure and diabetes. Objectives We set out to examine the association between self-reported diabetes and serum concentrations of organochlorine pesticides among Mexican Americans residing in the southwestern United States from 1982 to 1984. Methods This study was conducted among a sample of 1,303 Mexican Americans 20–74 years of age from the Hispanic Health and Nutrition Examination Survey. Serum concentrations were available for seven pesticides or pesticide metabolites at quantifiable levels in at least 1% of the study population: p,p′-DDT (dichlorodiphenyltrichloroethane), p,p′-DDE (dichlorodiphenyldichloro-ethylene), dieldrin, oxychlordane, β-hexachlorocyclohexane, hexachlorobenzene, and trans-nonachlor. We used logistic regression to evaluate the association of self-reported diabetes with exposure to organochlorine pesticides, with and without adjustment for total serum lipids. Nonfasting serum glucose values were compared among exposure groups. Results Self-reported diabetes was significantly associated with serum levels above the detectable limit for trans-nonachlor, oxychlordane, and β-hexachlorocyclohexane and among those with the highest level of exposure to p,p′-DDT and p,p′-DDE. On adjustment for total serum lipids, the association with p,p′-DDT remained significant. Serum glucose levels were elevated among those exposed to trans-nonachlor and β-hexachlorocyclohexane. Conclusion This study suggests that higher serum levels of certain organochlorine pesticides may be associated with increased prevalence of diabetes. Additional studies with more extensive clinical assessment are needed to confirm this association.

Accidental contamination of livestock in Michigan in 1973 with polybrominated biphenyls (PBBs) led to the establishment of a registry of exposed individuals in 1976. At the time of enrollment, serum was collected and analyzed for PBBs and polychlorinated biphenyls, PCBs. In 1997, women aged 18 years or older and active in the registry were invited to participate in a telephone interview about their health. Using generalized estimating equations to account for correlated outcomes within the same woman, we assessed the risk of spontaneous abortion among 529 women with 1344 potentially exposed pregnancies. PBB and PCB exposure were not associated with risk of spontaneous abortion after adjusting for maternal age at conception, age at menarche, and prior infertility. Compared to pregnancies with PBB exposure below the limit of detection, those with levels above 2.9 ppb had a non-significant reduced odds of spontaneous abortion (adjusted OR=0.73; 95% CI= 0.47-1.13). Compared to pregnancies with PCB exposure below the limit of detection, those with levels above 6.5 ppb had little difference in risk (adjusted OR=0.91; 95% CI= 0.59-1.41). Maternal age at conception above 34 years was significantly associated with elevated risk of spontaneous abortion (OR=2.46; 95% CI= 1.10-5.49). The effect of prior infertility was of borderline significance (OR=1.52; 95% CI= 0.98-2.38). Older age at menarche was associated with decreased risk of spontaneous abortion (adjusted OR=0.58; 95% CI: 0.38-0.89, comparing menarche at 12-13 with menarche

Understanding the influence of maternal exposures on gestational age and birth weight is essential given that pre-term and/or low birth weight infants are at risk for increased mortality and morbidity. We performed a retrospective analysis of a cohort exposed to polybrominated biphenyls (PBB) through accidental contamination of cattle feed and polychlorinated biphenyls (PCB) through residual contamination in the geographic region. Our study population consisted of 444 mothers and their 899 infants born between 1975 and 1997. Using restricted maximum likelihood estimation, no significant association was found between estimated maternal serum PBB at conception or enrollment PCB levels and gestational age or infant birth weight in unadjusted models or in models that adjusted for maternal age, smoking, parity, infant gender, and decade of birth. For enrollment maternal serum PBB, no association was observed for gestational age. However, a negative association with high levels of enrollment maternal serum PBB and birth weight was suggested. We also examined the birth weight and gestational age among offspring of women with the highest (10%) PBB or PCB exposure, and observed no significant association. Because brominated compounds are currently used in consumer products and therefore, are increasingly prevalent in the environment, additional research is needed to better understand the potential relationship between in utero exposure to brominated compounds and adverse health outcomes.

Background: In this review, the epidemiological evidence examining associations between upper extremity musculoskeletal symptoms and disorders and keyboard use intensity (hours of computer use-per day or per-week) and computer user posture was explored. Methods: An OVID Medline® literature search was conducted to identify papers published in the peer-reviewed medical literature between 1966 and November, 2005. A total of 558 citations were found and reviewed. Those papers in which associations between musculoskeletal outcomes and (1) posture (ascertained by a study investigator) or (2) computer use, in units of hours-per-day, hours-per-week, or as a percent of work-time, were included in the review. Results: Thirty-nine epidemiological studies examining associations between computer use and MSD outcomes were identified. While the observational epidemiological literature was heterogeneous, some trends did emerge. It appears that the most consistent finding was the association observed between hours keying and hand/arm outcomes. Associations between some postural effects and musculoskeletal outcomes may also be inferred from the literature. In particular, placing the keyboard below the elbow, limiting head rotation, and resting the arms appears to result in reduced risk of neck/shoulder outcomes. Minimizing ulnar deviation and keyboard thickness appears to result in reduced risk of hand/arm outcomes. Conclusions: Several methodological limitations, including non-representative samples, imprecise or biased measures of exposure and health outcome, incomplete control of confounding, and reversal of cause and effect, may contribute to the heterogeneity of observed results. Suggestions are made for improving the validity of future investigations.

Epidemiologists often use menstrual cycle patterns as indicators of endocrine function in environmental and occupational studies, yet few studies have considered whether menstrual cycle characteristics are associated with fertility or pregnancy outcome.We prospectively studied 470 women to determine whether cycle length or bleed length were associated with fertility or spontaneous abortion. Women completed daily diaries with information on menstrual bleeding, intercourse, birth control use, and covariates. For each menstrual cycle, women collected at least 2 urine samples, which were assayed for human chorionic gonadotropin to define early pregnancies. Women were followed for 1 year or until the end of a clinical pregnancy.Cycles with lengths of 30 to 31 days preceded cycles with the highest fecundity. Shorter cycles were less likely to be followed by conception (fecundity ratio [FR] = 0.6; 95% confidence interval [CI] = 0.4-1.0). Compared with 30- to 31-day cycles, conceptions after shorter and longer cycles were more likely to be spontaneously aborted (for shorter cycles, odds ratio [OR] = 3.0 [95% CI = 0.9-9.6] and for longer cycles, OR = 3.0 [0.9-10.6]). Cycles with 5 days of menstrual bleeding had the highest fecundity. Cycles with up to 4 days of bleeding had lower fecundity (for bleed lengths of 4 days, FR = 0.5 [0.3-0.8] and for bleed lengths less than 4 days, FR = 0.6 [0.3-0.9]). Spontaneous abortion was less likely after bleeds greater than 5 days (OR = 0.4 [0.1-1.1]) when compared with 5-day bleeds.Menstrual cycle characteristics appear to be associated with fertility and spontaneous abortion.

Aims: To examine the effect of two workstation and postural interventions on the incidence of musculoskeletal symptoms among computer users. Methods: Randomised controlled trial of two distinct workstation and postural interventions (an alternate intervention and a conventional intervention) among 376 persons using computer keyboards for more than 15 hours per week. The incidence of neck/shoulder symptoms and hand/arm symptoms during six months of follow up among individuals in the intervention groups was compared to the incidence in computer users who did not receive an intervention (comparison group). For individuals in the intervention groups, study staff adjusted workstations, where possible, and trained individuals to assume the intervention postures. Individuals reported musculoskeletal symptoms in a weekly diary. Participants who reported discomfort intensity of 6 or greater on a 0–10 visual analogue scale or who reported musculoskeletal symptoms requiring use of analgesic medication were considered symptomatic. Results: There were no significant differences in the incidence of musculoskeletal symptoms among the three intervention groups. Twenty two (18.5%) participants in the alternate intervention group, 25 (20.2%) in the conventional intervention group, and 25 (21.7%) in the comparison group developed incident arm or hand symptoms. Thirty eight (33.3%) participants in the alternate intervention group, 36 (31.0%) in the conventional intervention group, and 33 (30.3%) in the comparison group developed incident neck or shoulder symptoms. Compliance with all components of the intervention was attained for only 25–38% of individuals, due mainly to the inflexibility of workstation configurations. Conclusions: This study provides evidence that two specific workplace postural interventions are unlikely to reduce the risk of upper extremity musculoskeletal symptoms among computer users.

Objectives:Because halogenated biphenyl exposure is suspected to disrupt endocrine function, we assessed time to menopause in women aged 24 years and older who were exposed orally to polybrominated biphenyls (PBBs) and polychlorinated biphenyls (PCBs) (n = 874). We also examined smoking in relation to menopause. Methods: To define menopausal status, women were interviewed in 1997 and asked whether they had had any menstrual periods in the previous year, why their menstrual periods had stopped (e.g. surgery), and age at their last menstrual period. Serum PBB and PCB taken at enrollment (1976–1978) into the Michigan PBB registry was used as the measure of halogenated biphenyl exposure. Women whose menopause occurred before their PBB exposure were excluded. Proportional hazard modeling was used to analyze the “risk” for menopause in relation to exposure. Premenopausal women contributed person-time until their interview date, at which time they were censored. Results: We did not find an association between either PBB or PCB exposure and time to menopause. Women who were current smokers had a shorter time to menopause than never smokers (menopause ratio 2.02, 95% C.I. 1.21–3.37). Time to menopause was shortest among women who reported started smoking when they were

Reports in the scientific literature and lay press have suggested that computer users are at increased risk of upper extremity musculoskeletal disorders (MSDs). Early studies often found elevated rates of MSD outcomes among keyboard users when compared to non-users. Attention soon focused on specific aspects of keyboard work that might be responsible for the observed rate increase. In this review, the epidemiological evidence examining associations between MSD outcomes and computer user posture and keyboard use intensity (hours of computer use per day or per week) are examined. Results of epidemiological studies of posture and MSD outcomes have not been entirely consistent. Reasons for the inconsistency in results include cross-sectional study design (with possible failure to assure that measured exposure preceded health effect), imprecision of posture measures used, and difficulties involved in analyzing multiple related variables. Despite the inconsistencies, it appears from the literature that posture is an independent risk factor of modest magnitude for MSDs among computer users. It appears that lowering the height of the keyboard to or below the height of the elbow and resting the arms on the desk surface or chair armrests is associated with reduced risk of neck and shoulder MSDs. Results of epidemiological studies examining computer use (hours keying per day or per week) are more consistent than those examining posture, although some inconsistency is observed. Reasons for the inconsistency include possible selective survival bias resulting from cross-sectional study design, differences in exposure categorization, and possible interaction with other exposure variables. Overall, the literature shows that daily or weekly hours of computer use is more consistently associated with hand and arm MSDs than with neck and shoulder MSDs.

PURPOSE: We examined the relation between serum polybrominated biphenyl (PBB) levels and the risk of benign breast disease in a cohort of Michigan women unintentionally exposed to PBBs in 1973 and interviewed in 1997. METHODS: We used extended Cox models to generate adjusted hazard ratios; models included polychlorinated biphenyls (PCBs) and risk factors for benign breast disease reported in the literature. RESULTS: Two hundred fourteen (23%) of 951 women reported benign breast disease diagnosed by a physician. Compared with women with low PBB exposure, benign breast disease was not reported more frequently among those with moderate (>1–12 parts per billion [ppb]), (odds ratio [OR] 1.08, 95% confidence interval [CI] = 0.80–1.45), or high (>12 ppb), (OR 0.79, 95% CI = 0.46–1.38) PBB exposure. PCB exposure was also not associated with self-reported physician-diagnosed benign breast disease. Age, smoking, and annual number of health-care provider visits were significantly associated with benign breast disease. CONCLUSIONS: Our analysis did not demonstrate an association between serum PBB level and self- reported physician-diagnosed benign breast disease. We did observe an increased risk of benign breast disease for women who smoked, an association that has not been consistently found in previous studies.

Purpose: To describe current stature and pubertal development in North American boys, and to compare these measures with measures observed approximately 30 years ago. Methods: We analyzed data (i.e., height, weight, and Tanner Stage) from the Third National Health and Nutrition Examination Survey (NHANES III), conducted between 1988–1994, and compared it to the National Health Examination Survey, Cycles II and III (HES II/III), conducted from 1963–1965 and 1966–1970. The surveys included physical examination and questionnaire components, employed cross-sectional designs, and are nationally representative. We used logistic regression to calculate median age at onset of pubertal stages. Results: NHANES III included 2481 boys aged 8 to 18 years. HES II comprised 3010 boys aged 8–11 years and HES III comprised 3514 boys aged 12–17 years. The mean heights of the oldest boys in both surveys did not differ significantly; however, at younger ages, boys in the more recent survey were taller (average height difference among those aged 8–14 years was 2.0 cm). Boys in NHANES III were also heavier and had higher body mass index than those in HES II/III. The median estimated ages of onset of pubertal stages in NHANES III were 9.9, 12.2, 13.6, and 15.8 years for genital stages 2–5, respectively, and 11.9, 12.6, 13.6, and 15.7 years for pubic hair stages 2–5, respectively. For some stages, the median estimated age of onset of puberty was earlier among boys in NHANES III than among those in HES III. Conclusions: Differences in mean height at young ages, but not at older ages, suggest that the rate of growth among boys in NHANES III was faster than that of boys in the earlier surveys. This finding, coupled with the finding of earlier ages of onset of some pubertal stages, suggests that boys of this generation may be maturing more rapidly than did boys in the past.