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Background Cardiovascular health (CVH) declines in young adulthood, and mood disorders commonly emerge during this life stage. This study examined the association between depression, anxiety, and CVH metrics among young adults. Methods and Results We conducted a cross‐sectional analysis of participants aged 18 to 34 years who completed the Emory Healthy Aging Study Health History Questionnaire (n=875). We classified participants as having poor, intermediate, or ideal levels of the 8 CVH metrics using definitions set forth by the American Heart Association with adaptions when necessary. We defined depression and anxiety as absent, mild, or moderate to severe using standard cutoffs for Patient Health Questionnaire and General Anxiety Disorder scales. We used multivariable regression to examine the association between depression and anxiety and CVH, adjusting for age, sex, race and ethnicity, income, and education. The mean participant age was 28.3 years, and the majority identified as women (724; 82.7%); 129 (14.7%) participants had moderate to severe anxiety, and 128 (14.6%) participants had moderate to severe depression. Compared with those without anxiety, participants with moderate to severe anxiety were less likely to meet ideal levels of physical activity (adjusted prevalence ratio [aPR], 0.60 [95% CI, 0.44–0.82]), smoking (aPR, 0.90 [95% CI, 0.82–0.99]), and body mass index (aPR, 0.79 [95% CI, 0.66–0.95]). Participants with moderate to severe depression were less likely than those without depression to meet ideal levels of physical activity (aPR, 0.48 [95% CI, 0.34–0.69]), body mass index (aPR, 0.75 [95% CI, 0.61–0.91]), sleep (aPR, 0.79 [95% CI, 0.66–0.94]), and blood pressure (aPR, 0.92 [95% CI, 0.86–0.99]). Conclusions Anxiety and depression are associated with less ideal CVH in young adults. Interventions targeting CVH behaviors such as physical activity, diet, and sleep may improve both mood and CVH.

Exposure to polychlorinated biphenyls (PCBs), an endocrine-disrupting compound, is ubiquitous despite decades-old bans on the manufacture and use of PCBs. Increased exposure to PCBs is associated with adverse health consequences throughout life, including type 2 diabetes and cancer. PCB exposure is also associated with alterations in epigenetic marks and gene transcription, which could lead to adverse health outcomes, but many of these are population-specific. To further investigate the association between PCB and epigenetic marks, DNA methylation was measured at 787,684 CpG sites in 641 peripheral blood samples from the Michigan Polybrominated Biphenyl (PBB) Registry. 1345 CpGs were associated with increased total PCB level after controlling for age, sex, and 24 surrogate variables (FDR < 0.05). These CpGs were enriched in active promoter and transcription associated regions (p

Aim: Michigan residents were exposed to polybrominated biphenyls (PBBs) when it was accidentally added to the food supply. Highly exposed individuals report sex-specific health problems, but the underlying biological mechanism behind these different health risks is not known. Materials and methods: DNA methylation in blood from 381 women and 277 men with PBB exposure was analyzed with the MethylationEPIC BeadChip. Results: 675 CpGs were associated with PBBs levels in males, while only 17 CpGs were associated in females (false discovery rate

In 1973-74, a polybrominated biphenyl (PBB) flame retardant mixture was shipped to Michigan livestock feed mills in place of a nutritional supplement and contaminated the food supply. Following the accident, the Michigan PBB Registry was established to study the long-term health effects of halogenated compounds and is now led by a community-academic partnership. PBB exposure is associated with altered DNA methylation in sperm, which may lead to adverse birth outcomes in children whose fathers have increased levels of serum PBB or polychlorinated biphenyl (PCB). Paternal PBB and PCB levels of men enrolled in the Michigan PBB Registry (n = 155) were analyzed against matched offspring birthweight and gestational age (n = 336). Birthweight and gestational age were dichotomized at the 25th percentile and 37 weeks, respectively, and paternal PBB and PCB levels were examined as continuous measures and divided into tertiles. Associations of offspring birthweight and gestational age with paternal PBB and PCB serum concentrations were modeled using multivariable linear spline and log-risk regression, adjusting for family clustering, paternal health and lifestyle factors, maternal PBB, and PCB serum concentrations, sex, and offspring gestational age (for birthweight). Fathers in the middle and upper PBB and PCB tertiles had increased risks for lowest quartile birthweight compared to the first tertile, with adjusted risk ratios (aRR) = 1.67 (95% CI: 0.93, 2.99) and aRR = 2.06 (95% CI: 1.12, 3.79) for PBB, and aRR = 1.47 (95% CI: 0.79, 2.75) and aRR = 1.34 (95% CI: 0.70, 2.54) for PCB, respectively. Elevated paternal PBB levels were not associated with an increased risk for preterm birth, while PCB levels were associated with a small, but not significant, decrease in gestational age, β = -0.37 (95% CI: -0.76, 0.03) weeks per log unit increase PCB. The findings suggest that increased paternal PBB and PCB levels negatively impact offspring birthweight, and paternal PCB levels may negatively impact gestational age.

BackgroundAir pollution and neighborhood socioeconomic status (nSES) have been shown to affect cognitive decline in older adults. In previous studies, nSES acts as both a confounder and an effect modifier between air pollution and cognitive decline.ObjectivesThis study aims to examine the individual and joint effects of air pollution and nSES on cognitive decline on adults 50 years and older in Metro Atlanta, USA.MethodsPerceived memory and cognitive decline was assessed in 11,897 participants aged 50+ years from the Emory Healthy Aging Study (EHAS) using the cognitive function instrument (CFI). Three-year average air pollution concentrations for 12 pollutants and 16 nSES characteristics were matched to participants using census tracts. Individual exposure linear regression and LASSO models explore individual exposure effects. Environmental mixture modeling methods including, self-organizing maps (SOM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation explore joint effects, and effect modification between air pollutants and nSES characteristics on cognitive decline.ResultsParticipants living in areas with higher air pollution concentrations and lower nSES experienced higher CFI scores (beta: 0.121; 95% CI: 0.076, 0.167) compared to participants living in areas with low air pollution and high nSES. Additionally, the BKMR model showed a significant overall mixture effect on cognitive decline, indicating synergy between air pollution and nSES. These joint effects explain protective effects observed in single-pollutant linear regression models, even after adjustment for confounding by nSES (e.g., an IQR increase in CO was associated with a 0.038-point decrease (95% CI: -0.06, -0.01) in CFI score).DiscussionObserved protective effects of single air pollutants on cognitive decline can be explained by joint effects and effect modification of air pollutants and nSES. Researchers must consider nSES as an effect modifier if not a co-exposure to better understand the complex relationships between air pollution and nSES in urban settings.

BackgroundAir pollution has been associated with cognitive decline among the elderly. Previous studies have not evaluated the simultaneous effect of neighborhood-level socioeconomic status (N-SES), which can be an essential source of bias.ObjectivesWe explored N-SES as a confounder and effect modifier in a cross-sectional study of air pollution and cognitive function among the elderly.MethodsWe included 12,058 participants age 50+ years from the Emory Healthy Aging Study in Metro Atlanta using the Cognitive Function Instrument (CFI) score as our outcome, with higher scores representing worse cognition. We estimated 9-year average ambient carbon monoxide (CO), nitrogen oxides (NOx), and fine particulate matter (PM2.5) concentrations at residential addresses using a fusion of dispersion and chemical transport models. We collected census-tract level N-SES indicators and created two composite measures using principal component analysis and k-means clustering. Associations between pollutants and CFI and effect modification by N-SES were estimated via linear regression models adjusted for age, education, race and N-SES.ResultsN-SES confounded the association between air pollution and CFI, independent of individual characteristics. We found significant interactions between all air pollutants and N-SES for CFI (p-valuesx, and PM2.5 were associated with 5.4% (95%-confidence interval, -0.2,11.4), 4.9% (-0.4,10.4), and 9.8% (2.2,18.0) increases in CFI, respectively. In lowest N-SES suburban areas, IQR increases in CO, NOx, and PM2.5 were associated with higher increases in CFI, namely 13.4% (1.3,26.9), 13.4% (0.3,28.2), and 17.6% (2.8,34.5), respectively.DiscussionN-SES is an important confounder and effect modifier in our study. This finding could have implications for studying health effects of air pollution in the context of environmental injustice.

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.

Endocrine-disrupting compounds are associated with altered epigenetic regulation and adverse health outcomes, although inconsistent results suggest that people have varied responses to the same exposure. Interpersonal variation in response to environmental exposures is not identified using standard, population-based methods. However, methods that capture an individual’s response, such as analyzing stochastic epigenetic mutations (SEMs), may capture currently missed effects of environmental exposure. To test whether polybrominated biphenyl (PBB) was associated with SEMs, DNA methylation was measured using Illumina’s MethylationEPIC array in PBB-exposed individuals, and SEMs were identified. Association was tested using a linear regression with robust sandwich variance estimators, controlling for age, sex, lipids, and cell types. The number of SEMs was variable (range: 119–18,309), and positively associated with age (p = 1.23e-17), but not with sex (p = 0.97). PBBs and SEMs were only positively associated in people who were older when they were exposed (p = 0.02 vs. p = 0.91). Many subjects had SEMs enriched in biological pathways, particularly in pathways involved with xenobiotic metabolism and endocrine function. Higher number of SEMs was also associated with higher age acceleration (intrinsic: p = 1.70e-3; extrinsic: p = 3.59e-11), indicating that SEMs may be associated with age-related health problems. Finding an association between environmental contaminants and higher SEMs may provide insight into individual differences in response to environmental contaminants, as well as into the biological mechanism behind SEM formation. Furthermore, these results suggest that people may be particularly vulnerable to epigenetic dysregulation from environmental exposures as they age.

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

Objective To evaluate the associations between frequency of business travel and health behaviors and adiposity. Methods Retrospective cross-sectional analysis of de-identified electronic medical records from 795 corporate physical exams. Results Business travel frequency demonstrates a curvilinear relationship with body mass index and body composition in men and women, with domestic and international travel. Linear and quadratic term beta coefficients indicate stronger associations between the sum of domestic and international travel and BMI, body fat percentage, and visceral adipose tissue in women than men, after accounting for age, exercise, and sleep. Based on our male sample population, international travel frequency has a greater influence on adiposity than summed (mostly domestic) travel. Conclusions Frequent business travel adversely affects body composition, with differences by gender and type of travel.

Air pollution has been associated with cognitive function in the elderly. Previous studies have not evaluated the simultaneous effect of neighborhood-level socioeconomic status (N-SES), which can be an essential source of bias.We explored N-SES as a confounder and effect modifier in a cross-sectional study of air pollution and subjective cognitive function.We included 12,058 participants age 50+ years from the Emory Healthy Aging Study in Metro Atlanta using the Cognitive Function Instrument (CFI) score as our outcome, with higher scores representing worse subjective cognitive function. We estimated 9-year average ambient carbon monoxide (CO), nitrogen oxides (NON-SES confounded the association between air pollution and CFI, independent of individual characteristics. We found significant effect modifications by N-SES for the association between air pollution and CFI (p-values0.001) suggesting that effects of air pollution differ depending on N-SES. Participants living in areas with low N-SES were most vulnerable to air pollution. In the lowest N-SES urban areas, interquartile range (IQR) increases in CO, NON-SES is an important confounder and effect modifier in our study. This finding could have implications for studying health effects of air pollution and identifying susceptible populations.

Air pollution and neighborhood socioeconomic status (nSES) have been shown to affect cognitive decline in older adults. In previous studies, nSES acts as both a confounder and an effect modifier between air pollution and cognitive decline.This study aims to examine the individual and joint effects of air pollution and nSES on cognitive decline on adults 50 years and older in Metro Atlanta, USA.Perceived memory and cognitive decline was assessed in 11,897 participants aged 50+ years from the Emory Healthy Aging Study (EHAS) using the cognitive function instrument (CFI). Three-year average air pollution concentrations for 12 pollutants and 16 nSES characteristics were matched to participants using census tracts. Individual exposure linear regression and LASSO models explore individual exposure effects. Environmental mixture modeling methods including, self-organizing maps (SOM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation explore joint effects, and effect modification between air pollutants and nSES characteristics on cognitive decline.Participants living in areas with higher air pollution concentrations and lower nSES experienced higher CFI scores (beta: 0.121; 95 % CI: 0.076, 0.167) compared to participants living in areas with low air pollution and high nSES. Additionally, the BKMR model showed a significant overall mixture effect on cognitive decline, suggesting synergy between air pollution and nSES. These joint effects explain protective effects observed in single-pollutant linear regression models, even after adjustment for confounding by nSES (e.g., an IQR increase in CO was associated with a 0.038-point lower (95 % CI: -0.06, -0.01) CFI score).Observed protective effects of single air pollutants on cognitive decline can be explained by joint effects and effect modification of air pollutants and nSES. Researchers must consider nSES as an effect modifier if not a co-exposure to better understand the complex relationships between air pollution and nSES in urban settings.

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 (

In 1973, the Velsicol Chemical Company, which manufactured FireMaster, a brominated flame retardant, and NutriMaster, a nutritional supplement, mistakenly shipped hundreds of pounds of FireMaster to grain mills around Michigan where it was incorporated into animal feed and then into the food chain across the state. An estimated 6.5 million Michigan residents consumed polybrominated biphenyl (PBB)-laced animal products leading to one of the largest agricultural accidents in U.S. history. To date, there have been no studies investigating the effects of PBB on epigenetic regulation in sperm, which could explain some of the endocrine-related health effects observed among children of PBB-exposed parents. Fusing epidemiological approaches with a novel in vitro model of human spermatogenesis, we demonstrate that exposure to PBB153, the primary component of FireMaster, alters the epigenome in human spermatogenic cells. Using our novel stem cell-based spermatogenesis model, we show that PBB153 exposure decreases DNA methylation at regulatory elements controlling imprinted genes. Furthermore, PBB153 affects DNA methylation by reducing de novo DNA methyltransferase activity at increasing PBB153 concentrations as well as reducing maintenance DNA methyltransferase activity at the lowest tested PBB153 concentration. Additionally, PBB153 exposure alters the expression of genes critical to proper human development. Taken together, these results suggest that PBB153 exposure alters the epigenome by disrupting methyltransferase activity leading to defects in imprint establishment causing altered gene expression, which could contribute to health concerns in the children of men exposed to PBB153. While this chemical is toxic to those directly exposed, the results from this study indicate that the epigenetic repercussions may be detrimental to future generations. Above all, this model may be expanded to model a multitude of environmental exposures to elucidate the effect of various chemicals on germline epigenetics and how paternal exposure may impact the health of future generations.

Endocrine-disrupting compounds (EDCs) are a broad class of chemicals present in many residential products that can disrupt hormone signaling and cause health problems in humans. Multigenerational cohorts, like the Michigan polybrominated biphenyl registry, are ideal for studying the effects of intergenerational exposure. Registry participants report hormone-related health problems, particularly in those exposed before puberty or those in the second generation exposed through placental transfer or breastfeeding. However, more research is needed to determine how EDCs cause health problems and the mechanisms underlying intergenerational exposure. Utilizing existing data in this registry, along with genetic and epigenetic approaches, could provide insight to how EDCs cause human disease and help to determine the risk to exposed populations and future generations.

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 1973, approximately 6.5 million Michigan residents were exposed to an industrial mixture of polybrominated biphenyl (PBB), an endocrine-disrupting compound, when it was added to farm animal feed during a factory accident. Highly exposed individuals and their children have numerous endocrine-related health problems, including genitourinary conditions, spontaneous abortions, and early puberty, though the underlying mechanism behind these health problems remains unknown. Other endocrine-disrupting compounds have been linked to epigenetic differences, but no epigenetic studies have been done for PBB. In this study, DNA from the blood of individuals with PBB exposure was interrogated with the MethylationEPIC BeadChip (N = 658). Associations between each of the ~850,000 CpG sites and current, serum PBB levels were tested with a linear regression that controlled for age, sex, lipid levels, and cell type proportions. After multiple test correction (FDR

In many biomedical studies that involve correlated data, an outcome is often repeatedly measured for each individual subject along with the number of these measurements, which is also treated as an observed outcome. This type of data has been referred as multivariate random length data by Barnhart and Sampson (1995). A common approach to handling such type of data is to jointly model the multiple measurements and the random length. In previous literature, a key assumption is the multivariate normality for the multiple measurements. Motivated by a reproductive study, we propose a new copula-based joint model which relaxes the normality assumption. Specifically, we adopt the Clayton-Oakes model for multiple measurements with flexible marginal distributions specified as semi-parametric transformation models. The random length is modeled via a generalized linear model. We develop an approximate EM algorithm to derive parameter estimators and standard errors of the estimators are obtained through bootstrapping procedures and the finite-sample performance of the proposed method is investigated using simulation studies. We apply our method to the Mount Sinai Study of Women Office Workers (MSSWOW), where women were prospectively followed for 1 year for studying fertility.

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.

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

Background Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight. Objectives We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS–birth weight association observed in epidemiologic studies might be attributable to GFR. Methods We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data. Results The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72 g (95% CI: –3.40, –2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: –8.46, –5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR–birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: –21.66, –7.78) and 14.72 g (95% CI: –8.92, –1.09) reductions in birth weight, respectively. Conclusion Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy. Citation Verner MA, Loccisano AE, Morken NH, Yoon M, Wu H, McDougall R, Maisonet M, Marcus M, Kishi R, Miyashita C, Chen MH, Hsieh WS, Andersen ME, Clewell HJ III, Longnecker MP. 2015. Associations of perfluoroalkyl substances (PFAS) with lower birth weight: an evaluation of potential confounding by glomerular filtration rate using a physiologically based pharmacokinetic model (PBPK). Environ Health Perspect 123:1317–1324; http://dx.doi.org/10.1289/ehp.1408837

In many observational longitudinal studies, the outcome of interest presents a skewed distribution, is subject to censoring due to detection limit or other reasons, and is observed at irregular times that may follow a outcome-dependent pattern. In this work, we consider quantile regression modeling of such longitudinal data, because quantile regression is generally robust in handling skewed and censored outcomes and is flexible to accommodate dynamic covariate-outcome relationships. Specifically, we study a longitudinal quantile regression model that specifies covariate effects on the marginal quantiles of the longitudinal outcome. Such a model is easy to interpret and can accommodate dynamic outcome profile changes over time. We propose estimation and inference procedures that can appropriately account for censoring and irregular outcome-dependent follow-up. Our proposals can be readily implemented based on existing software for quantile regression. We establish the asymptotic properties of the proposed estimator, including uniform consistency and weak convergence. Extensive simulations suggest good finite-sample performance of the new method. We also present an analysis of data from a long-term study of a population exposed to polybrominated biphenyls (PBB), which uncovers an inhomogeneous PBB elimination pattern that would not be detected by traditional longitudinal data analysis.

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.

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: Family history of cardiovascular disease (CVD) is a readily available risk indicator of future CVD, combining the influence of shared genetic, environmental and behavioral risk factors. Though CVD risk factors have been associated with an increased risk of cognitive impairment and decline, less is known about the association between family history of CVD and cognitive function. Evaluating this association may further elucidate the role of cardiovascular health in cognitive health. Methods: The Emory Healthy Aging Study isan ongoing prospective cohort study aimed at identifying predictors of healthy aging and age-related diseases. Participants are primarily residents of the Atlanta area, at least 18 years old, who completed an online baseline health survey. Multiple recruitment forums were used, including clinic waiting rooms, informational letters and emails, community events and online recruitment. Baseline information about demographic (age, race, gender), socioeconomic (education, household income), and health behavior factors (physical activity, smoking) as well as personal health (diabetes, hyperlipidemia, and hypertension) and family health history were collected by online survey. Family history of CVD was defined as self-reported history for any parent or sibling of coronary artery disease, myocardial infarction, or stroke. Cognitive function was measured using the validated Cognitive Function Instrument (CFI) with scores ranging between 0-14 (lower is better). The association between family history of CVD and CFI score was assessed using multivariable linear regression, adjusting for demographic, socioeconomic, lifestyle and CVD risk factors, as well as family history of mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Results: We studied 3801 participants (75% female, 85% white, 10% black, and 5% other), recruited between October 2015 and October 2016. Mean age was 59±13 years and 61% reported a family history of CVD. Adjusting for age, gender, race, education, household income, exercise habits, smoking status and family history of MCI or AD, family history of CVD was associated with poorer cognitive performance (β=0.26; 95% CI (0.12, 0.41)). Additional adjustment for hypertension, hyperlipidemia, diabetes and BMI only slightly attenuated estimates (β=0.22; 95% CI (0.08, 0.41)). In the same model, the estimated β for family history of cognitive impairment was similar: 0.22 (0.07, 0.37). Conclusion: In this cross-sectional study of people from the community, family history of CVD was associated with poorer cognitive function, and this association was of the same magnitude as having a first-degree family member with a history of cognitive impairment. Although longitudinal data are needed, these results underscore the link between cardiovascular and neurocognitive health and potential role of shared genetic and behavioral factors.

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.

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...

We have developed a highly sensitive and selective analytical method capable of quantifying a total of 15 polybrominated and polychlorinated biphenyls (11 PBBs and 4 PCBs) in human serum. Samples were subjected to liquid-liquid extraction followed by solid-phase extraction prior to measurement using gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode. Quantification was performed using isotope-dilution calibration covering a concentration range of 0.005-12.5 ng/mL. Limits of detection for all target compounds were in the low range (0.7-6.5 pg/mL). The method was validated using in-house pooled human serum fortified at two concentrations (0.5 ng/mL and 1.0 ng/mL), whole semen fortified at one concentration (0.25 ng/mL), and NIST Standard Reference Material (SRM) 1958, which includes five of the target compounds. Method accuracies for all target compounds ranged from 84 to 119% with relative standard deviations (RSDs) of

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.