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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.

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

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

In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. Highly exposed individuals and their children have experienced endocrine-related health problems, though the underlying mechanism behind these remains unknown. We investigated whether PBB exposure is associated with variation in DNA methylation in peripheral blood samples from 658 participants of the Michigan PBB registry using the MethylationEPIC BeadChip, as well as investigated what the potential function of the affected regions are and whether these epigenetic marks are known to associate with endocrine system pathways. After multiple test correction (FDR

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: In some cross-sectional epidemiologic studies the shape of the association between serum concentrations of perfluoroalkyl acids (PFAAs) and lipids suggests departures from linearity. Objectives: We used statistical approaches allowing for non-linearity to determine associations of prenatal exposures of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) with lipid concentrations. Methods: PFAAs were measured in serum from pregnant women collected in 1991–1992 at enrollment in the Avon Longitudinal Study of Parents and Children and lipids in serum from their daughters at ages 7 (n = 111) and 15 (n = 88). The associations of PFAAs with lipids were first explored by cubic splines, followed by piecewise linear regressions by tertiles to obtain regression coefficients (β) and their 95% confidence limits (95% CL) (in mg/dL per 1 ng/mL). Results: At age 7, total cholesterol was positively associated with prenatal PFOA concentrations in the lower tertile (β = 15.01; 95% CL = 2.34, 27.69) but not with PFOA concentrations in the middle (β = −3.63; 95% CL = −17.43, 10.16) and upper (β = −1.58; 95% CL = −4.58, 1.42) tertiles. At age 15, a similar pattern was noted as well. Positive associations between LDL-C and prenatal PFOA concentration in the lower tertile were observed in daughters at ages 7 (β = 14.91; 95% CL = 3.53, 28.12) and 15 (β = 13.93; 95% CL = 0.60, 27.26). LDL-C was not associated with PFOA concentrations in the middle or upper tertile at any age. Neither HDL-C nor triglycerides was associated with prenatal PFOA exposure. Non-linear patterns of association of total cholesterol and LDL-C with prenatal PFOS were less consistently noted. Conclusion: Exposure to low levels of PFOA during prenatal development may alter lipid metabolism later in life. Given the small sample size further replication of the association in large independent cohorts is important. Keywords: Lipid metabolism, Endocrine disruption, PFOA, PFOS, Perfluoroalkyl acids, ALSPAC, Fetal origins of adult disease

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.

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.

Thyroid hormones are essential for proper neurodevelopment in early life. There is evidence that exposure to polybrominated diphenyl ethers (PBDEs) affects thyroid function, but previous studies have been inconsistent, and no studies among children have been conducted in the United States where PBDE levels are particularly high. Serum levels of seven PBDE congeners and thyroid hormones and other thyroid parameters were measured in 80 children aged 1-5 years from the southeastern United States between 2011 and 2012. Parents of the children completed questionnaires with details on demographics and behaviors. Multivariate linear regression models were used to estimate the associations between serum PBDE levels, expressed as quartiles and as log-transformed continuous variables, and markers of thyroid function. BDE-47, 99, 100 and 153 were detected in >60% of samples, and were summed (∑PBDE). PBDE congeners and ∑PBDE were positively associated with thyroid-stimulating hormone (TSH). A log-unit increase in ∑PBDE was associated with a 22.1% increase in TSH (95% CI: 2.0%, 47.7%). Compared with children in the lowest quartile of ∑PBDE exposure, children in higher quartiles had greater TSH concentrations as modeled on the log-scale (second quartile: β=0.32, 95% confidence interval (CI): -0.09, 0.74; third quartile: β=0.44, 95% CI: 0.04, 0.85; and fourth quartile: β=0.49, 95% CI: 0.09, 0.89). There was also a tendency toward lower total T4 and higher free T3 with increasing PBDE exposure. Results suggest that exposure to PBDEs during childhood subclinically disrupts thyroid hormone function, with impacts in the direction of hypothyroidism.

Background: Prenatal exposures to polyfluoroalkyl compounds (PFCs) may be associated with adverse changes in fetal and postnatal growth. Objective: We explored associations of prenatal serum concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexane sulfonate (PFHxS) with fetal and postnatal growth in girls. Methods: We studied a sample of 447 singleton girls and their mothers participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Data on weight and length were obtained at birth and at 2, 9, and 20 months. Serum samples were obtained in 1991–1992, from mothers during pregnancy. We explored associations between prenatal PFC concentrations and weight at birth as well as longitudinal changes in weight-for-age SD scores between birth and 20 months. Results: PFOS (median, 19.6 ng/mL), PFOA (median, 3.7 ng/mL), and PFHxS (median, 1.6 ng/mL) were detected in 100% of samples. On average, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 140 g less [95% confidence interval (CI): –238, –42] at birth than girls born to mothers with concentrations in the lower tertile in adjusted models. Similar patterns were seen for PFOA (–133 g; 95% CI: –237, –30) and PFHxS (–108 g; 95% CI: –206, –10). At 20 months, however, girls born to mothers with prenatal concentrations of PFOS in the upper tertile weighed 580 g more (95% CI: 301, 858) when compared with those in the lower tertile. No differences in weight were found for PFOA and PFHxS. Conclusions: Girls with higher prenatal exposure to each of the PFCs examined were smaller at birth than those with lower exposure. In addition, those with higher exposure to PFOS were larger at 20 months.

BackgroundIt is unclear whether pubertal status or timing of puberty explains the increase in depressive symptoms in girls during adolescence.MethodThis is a longitudinal study based on 2506 girls from the Avon Longitudinal Study of Parents and Children (ALSPAC). Self-reported depressive symptoms at 10.5, 13 and 14 years were assessed using the Short Mood and Feelings Questionnaire (SMFQ). Pubertal status (Tanner breast and pubic hair stage) and timing of menarche were derived from questionnaires administered from age 8 to 14 years. We used multivariable regression models to examine the relative contributions of pubertal status and timing in accounting for increases in level of depressive symptoms at 14 years.ResultsWith increasing age, the association between breast development and depressive symptoms strengthened. Pubertal status (breast stage), rather than timing of menarche, was independently associated with depressive symptoms at 14 years. There was strong evidence for a linear relationship between breast stage and depressive symptoms at 14 years [increase in 0.17 s.d. (range 0.10–0.24) of depressive symptoms for advancement of each breast stage].ConclusionsDepressive symptoms in mid-adolescence were more strongly influenced by breast stage than timing of menarche. This could imply that the female rise in depression during adolescence is due to increasing estrogen levels, and might explain why the gender difference in rates of depression emerges at this stage. Future research should be aimed at identifying the mechanism of action of pubertal change, including direct effects of pubertal hormones and indirect effects mediated by psychosocial factors.

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.

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.

Purpose Patterns of pubertal development reflect underlying endocrine function and exposures, and could affect future health outcomes. We used data from a longitudinal cohort to describe factors associated with breast and pubic hair stage and estimate average duration of puberty. Methods Data from the Avon Longitudinal Study of Parents and Children were used to describe timing and duration of pubertal development in girls. Self-reported Tanner stage of breast and pubic hair and menarche status were collected from ages 8–14 through mailed questionnaires. Factors associated with breast and pubic hair stage were identified using ordinal probit models. Age at entry into breast and pubic hair stages, and duration of puberty were estimated using interval-censored parametric survival analysis. Results Among the 3,938 participants, being overweight or obese, of non-white race, being the firstborn, and younger maternal age at menarche were associated with more advanced breast and pubic hair stages. Having an overweight or obese mother was associated with more advanced breast stages. Time spent in breast stages 2 and 3 was longer (1.5 years) than time spent in pubic hair stages 2 and 3 (1 year). The average age at menarche was 12.9 (95% CI, 12.8–12.9) years, and average duration of puberty (time from initiation of puberty to menarche) was 2.7 years. Conclusions Girls in Avon Longitudinal Study of Parents and Children had a slightly longer duration of puberty compared to an earlier British cohort study. Various maternal and child characteristics were associated with breast and pubic hair stage, including both child and maternal body mass.

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.

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

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.

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.

BACKGROUND: CYP17, which encodes cytochrome P450c17α, mediates both steroid 17a-hydroxylase and 17,20-lyase activities, and is essential for the production of glucocorticoids and sex steroids. There is evidence that a common polymorphism in CYPI7 (T27C) is associated with estrogen levels, making it a potential marker of disease risk. METHODS: This is the first study to examine the relationship between CYP17 and estradiol (E 2 ) using serum sampled exclusively from the early follicular phase of the menstrual cycle. We assessed the relationship between CYP17 and serum hormone levels, menstrual cycle length, bleed length, and age at menarche in 164 pre-menopausal women. RESULTS: Among women with body mass index (BMI) ≤25 kg/m 2 , those with the TC and CC genotypes had 19 and 42% higher E 2 (P for trend 0.007) and 14 and 30% higher dehydroepiandrosterone sulphate respectively (P for trend 0.10) than women with the TT genotype. Androstenedione levels did not differ between genotypes. Among women with BMI >25 kg/m 2 , hormone levels did not differ by genotype. Women with the C allele were also more likely to have menstrual cycle lengths

BACKGROUND: Women who carry the FMR1 premutation allele have a significantly increased risk for ovarian dysfunction. We hypothesize that molecular characteristics of the FMR1 gene may explain this increased risk. METHODS: Thus, we examined the effect of FMR1 CGG repeat size and related factors on measures of ovarian dysfunction using data from 507 women with a wide range of repeat sizes. RESULTS AND CONCLUSIONS: We found a significant positive association of repeat size with ovarian dysfunction, but have preliminary evidence that this relationship is non-linear. We suggest that FMR1 repeat size in the lower range (

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.

Background: Variations in testosterone production in females are associated with the occurrence of metabolic and reproductive disorders. Exposure to perfluorooctane sulfonic acid (PFOS) or to perfl...

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 5 minutes, 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 1 minute and 5 minutes. Among infants whose mothers had an estimated PBB at conception above the limit of detection of 1 part per billion, the odds ratio was 2.32 (95 % CI: 1.22– 4.40); for those with PBB ≥ 2.5 ppb the OR=2.62 (95% CI: 1.38-4.96; test for trend p< 0.01). Likewise, the odds of a below–median 5–minute Apgar 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.

In the early 1970s, the largest industrial accident in the United States resulted in widespread contamination of the food supply in Michigan with polybrominated biphenyls (PBBs). The chemical similarity of PBBs to compounds implicated as endocrine disruptors has raised the question of whether PBBs could affect the reproductive system. In the present analysis we examine the relation between serum measurements of PBBs and the frequency and duration of lactation. Persons who lived on or received food from farms exposed to PBBs were enrolled in a registry by the Michigan Department of Public Health. Female members of the cohort were invited to participate in a telephone survey of reproductive outcomes. The three outcomes of interest in the present analysis were a) the decision to breast-feed (yes/no); b) the duration, in months, of breast-feeding as the main source of nutrition; and c) the total duration, in months, of breast-feeding. None of the three outcomes was significantly associated with serum PBB levels, even after controlling for maternal age, previous history of breast-feeding, body mass index, maternal education, household income, history of smoking in the year before pregnancy, consumption of alcohol during the first trimester of pregnancy, history of thyroid disorder, gestational age of the infant in weeks, time to pregnancy, and year of birth.

Jewish women have been reported to have a higher risk for familial breast cancer than non-Jewish women and to be more likely to carry mutations in breast cancer genes such as BRCA1. Because BRCA1 mutations also increase women's risk for ovarian cancer, we asked whether Jewish women are at higher risk for familial ovarian cancer than non-Jewish women. To determine the effects of 1) Jewish religion and 2) ovarian cancer in a first-degree relative on women's risk for epithelial ovarian cancer, we used data from a population-based, case-control study conducted in 8 geographic regions in the United States from 1980 through 1982. The study group included 471 cases and 4,025 controls. Jewish women were more likely to have familial ovarian cancer than non-Jewish women [odds ratio (OR) = 8.4, 95% confidence interval (CI) = 2.6-28]. The risk of having ovarian cancer appeared to be greater in Jewish women having a first-degree relative with ovarian cancer (OR = 8.81, 95% CI = 2.02-38.23) than in non-Jewish women having a first-degree relative with ovarian cancer (OR = 3.01, 95% CI = 1.61-5.64), but differences between Jewish and non-Jewish women were not statistically significant. Jewish women with no first-degree relative with ovarian cancer had no increased risk for ovarian cancer (OR = 1.27, 95% CI = 0.74-2.91) compared to non-Jewish women. These results suggest that Jewish women may have a higher rate of familial ovarian cancer than non-Jewish women, but because the results are based on a small number of Jewish women with familial ovarian cancer, the results need to be confirmed in larger studies.

Hand and arm posture while keying is frequently mentioned as a risk factor for upper extremity musculoskeletal disorders (UEMSDs) among video display terminal (VDT) operators. However, many epidemiologic studies have not included measures of posture of VDT operators, in part, because of the difficulty of assessing posture rapidly and reliably among large numbers of subjects. For a single measure of posture to be useful for estimating dose-response relationships between posture and risk of UEMSDs, the within-subject variability of the postural measure must be smaller than the between-subject variability of the postural measure. In addition, the measure must be stable over time. We estimate the ratio of between- to within-subject variability for manual goniometry by measuring six postural angles on six occasions among 19 subjects using VDTs. For each postural angle, between-subject variability was substantially and statistically significantly larger than within-subject variability. Stability of postural measures over time was sufficient to justify a single postural measurement in epidemiologic studies. We conclude that manual goniometry can provide useful information about upper extremity posture among VDT users for use in epidemiologic studies of UEMSDs.

Members of the workgroup on female reproductive disorders discussed methods to evaluate five principal functions: menstrual dysfunction, infertility, pregnancy loss, lactation disorders, and pregnancy complications. To test each function, a nested strategy was considered, based on progressive levels of effort available to conduct field investigations. This strategy was analogous to the three-tier classification of biomarkers used by other workshops. The lowest level of effort, corresponding to Tier 1, consists only of questionnaires, diaries, and reviews of maternal and infant medical records. The medium level of effort (Tier 2) collects data from questionnaires and diaries, and some biologic specimens. Suggested laboratory analyses included measurement of progesterone in saliva and several glycoprotein hormones in urine that evaluate menstrual dysfunction, infertility, and pregnancy loss. The highest level of effort (Tier 3) involves prospective collection of diary information and simultaneous collection of biological specimens.

Background. Lead is a persistent, toxic substance and its exposure has been associated with later puberty onset and maturity. Current literature on the role of lead on puberty timing of girls is li...

Objective To determine whether postplacental intrauterine device (IUD) insertion can be safely and effectively performed within a teaching program. Study Design This was a prospective cohort of 177 subjects planning vaginal delivery enrolled antenatally who desired postplacental IUD insertion of either the copper T380A IUD or levonorgestrel IUS. Insertions were performed primarily by resident physicians following a training session. Follow-up included a 4- to 8-week visit and telephone calls at 3 and 6 months. Results Ninety-nine subjects underwent successful postplacental IUD insertion of 100 attempts. Seventeen expulsions (17%) were noted: 10 complete and 7 partial. The study identified no differences in outcome by training level; however, the study lacked statistical power to evaluate anything other than large differences. Conclusion Postplacental IUD insertions can be safely and effectively performed within a training program. Implications A training protocol may safely and feasibly be initiated among physicians, advanced practice clinicians or trainees with no prior experience with postplacental IUD insertion. By initiating this practice, access to highly effective contraception may increase for patients who have difficulty returning for a visit or otherwise receiving effective methods.

Upper extremity musculoskeletal disorders may occur as a result of work with keyboard-equipped video display terminals. Many studies of the associations between keyboard use and upper extremity disorders have appeared in both the human factors and occupational epidemiologic literature. Methodological limitations and inconsistent results have limited conclusions that can be made from these studies, however. Although exposure conditions can be carefully controlled, human factors studies are limited by relatively small sample sizes, short exposure durations, and reliance on outcome measures with unknown relevance to chronic adverse health effects. Epidemiologic studies have been limited by poor ascertainment of both exposure and health outcome. Many have failed to control for any potential confounding. An almost exclusive reliance on cross-sectional study designs has resulted in possible bias from selective survival, exposure-effect reversal, and poor estimates of exposures occurring prior to development of the disorder. Given the inconsistency in the literature and the growing controversy surrounding this issue, prospective study of this question using objective methods for assessment of exposure and health outcome is recommended. This design allows identification of incident cases and minimizes bias from selective survival. In addition, ergonomic and psychosocial variables prior to onset of symptoms can be ascertained periodically. Given estimates for up to 100 million video display terminals to be in use in the United States by the year 2000, clarification of the health effects of their use is critical. © 1996 Wiley-Liss, Inc.

Purpose To examine the association between periconceptional self-reported stress levels and fecundability in women. Methods Daily stress was reported on a scale from 1 to 4 (lowest to highest) among 400 women who completed daily diaries including data on lifestyle and behavioral factors, menstrual characteristics, contraceptive use, and intercourse for up to 20 cycles or until pregnancy. Discrete survival analysis was used to estimate the associations between self-reported stress during specific windows of the menstrual cycle and fecundability (cycles at risk until pregnancy), adjusting for potential confounders. Results One hundred thirty-nine women became pregnant. During the follicular phase, there was a 46% reduction in fecundability for a 1-unit increase in self-reported stress during the estimated ovulatory window (fecundability odds ratio [FOR] = 0.54; 95% confidence interval [CI] 0.35–0.84) and an attenuated trend for the preovulatory window (FOR = 0.73; 95% CI 0.48–1.10). During the luteal phase, higher stress was associated with increased probability of conception (FOR = 1.63, 95% CI 1.07–2.50), possibly due to reverse causality. Conclusions Higher stress during the ovulatory window may reduce probability of conception; however, once conception occurs, changes in the hormonal milieu and/or knowledge of the pregnancy may result in increased stress. These findings reinforce the need for encouraging stress management techniques in the aspiring and expecting mother.

To assess whether treatment with metronidazole during pregnancy is associated with preterm birth, low birth weight, or major congenital anomalies, we conducted chart reviews and an analysis of electronic data from a cohort of women delivering at an urban New York State hospital. Of 2,829 singleton/mother pairs, 922 (32.6%) mothers were treated with metronidazole for clinical indications, 348 (12.3%) during the first trimester of pregnancy and 553 (19.5%) in the second or third trimester. There were 333 (11.8%) preterm births, 262 (9.3%) infants of low birth weight, and 52 infants (1.8%) with congenital anomalies. In multivariable analysis, no association was found between metronidazole treatment and preterm birth (odds ratio [OR], 1.02 [95% confidence interval [CI], 0.80 to 1.32]), low birth weight (OR, 1.05 [95% CI, 0.77 to 1.43]), or treatment in the first trimester and congenital anomalies (OR, 0.86 [0.30 to 2.45]). We found no association between metronidazole treatment during the first or later trimesters of pregnancy and preterm birth, low birth weight, or congenital anomalies.

Despite consensus recommendations the usse of screening mammography remins low. We examined physician and patient related variables associated with requests to undergo screening mammography in a primary care setting, in order to assess current barriers to screening mammography at the level of the physician-patient interaction. A sample of 261 women over the age of 50, whose primary care was provided by resident physician in a large, urban, academic medical center were examined. Data concerning patients and physicians demographic and clinical chracteristics were abstracted. The data were analyzed by Chi-square and stepwise logistic regression. Forty-five percent of the patients were offered screening mammography within the study year and 53% were offered mammography over the preceding two years. Variables significantly associated with a request for screening included a previous history of breast disease (p