There is growing evidence of pubertal maturation occurring at earlier ages, with many studies based on cross-sectional observations. This study examined age at onset of breast development ...(thelarche), and the impact of BMI and race/ethnicity, in the 3 puberty study sites of the Breast Cancer and the Environment Research Program, a prospective cohort of >1200 girls.
Girls, 6 to 8 years at enrollment, were followed longitudinally at regular intervals from 2004 to 2011 in 3 geographic areas: the San Francisco Bay Area, Greater Cincinnati, and New York City. Sexual maturity assessment using Tanner staging was conducted by using standardized observation and palpation methods by trained and certified staff. Kaplan-Meier analyses were used to describe age at onset of breast maturation by covariates.
The age at onset of breast stage 2 varied by race/ethnicity, BMI at baseline, and site. Median age at onset of breast stage 2 was 8.8, 9.3, 9.7, and 9.7 years for African American, Hispanic, white non-Hispanic, and Asian participants, respectively. Girls with greater BMI reached breast stage 2 at younger ages. Age-specific and standardized prevalence of breast maturation was contrasted to observations in 2 large cross-sectional studies conducted 10 to 20 years earlier (Pediatric Research in Office Settings and National Health and Nutrition Examination Survey III) and found to have occurred earlier among white, non-Hispanic, but not African American girls.
We observed the onset of thelarche at younger ages than previously documented, with important differences associated with race/ethnicity and BMI, confirming and extending patterns seen previously. These findings are consistent with temporal changes in BMI.
Neonicotinoids are the most used pesticides in the world and, despite being harmful to honeybees, they are considered safe for mammals. However, they have been associated with decreasing testosterone ...levels in several experimental animal models. In the present study, we aimed to determine the association of urinary neonicotinoids with serum testosterone in humans. We analyzed data on 2014 male and female participants to the National Health and Nutrition Examination Survey conducted between 2015 and 2016 aged 6 or older. In linear regression adjusted for age and potential confounders, serum total testosterone was 37.78% lower with 10‐fold increase in urinary total neonicotinoids (95% CI: −58.82, −6.00), 20.81% lower with 10‐fold increase in urinary 5‐hydroxy‐imidacloprid (95% CI: −34.94, −3.62) and 25.01% lower with 10‐fold increase in urinary n‐desmethyl‐acetamiprid (95% CI: −39.80, −6.58) among males. Serum free androgen index (FAI) was also decreased with higher urinary n‐desmethyl‐acetamiprid. In females, serum total testosterone was 32.91% lower with 10‐fold increase in urinary total neonicotinoids (95% CI: −54.93, −0.13), 21.32% lower with 10‐fold increase in urinary 5‐hydroxy‐imidacloprid (95% CI: −29.31, −12.42) and 15.42% lower with urinary detection of 5‐hydroxy‐imidacloprid (95% CI: −22.80, −7.34). FAI was likewise reduced with higher urinary levels of 5‐hydroxy‐imidacloprid and N‐desmethyl‐acetamiprid. In conclusion, this study using a sample representative of the US population is the first to report that exposure to neonicotinoids is associated with decreased serum testosterone levels in humans. However, future prospective studies are warranted to confirm these findings.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Perfluorooctanoate (PFOA) has been used extensively in the manufacture of both commercial and household products. PFOA serum concentrations have been associated with adverse health effects, including ...lower body mass in children and infants.
To determine if there is an association between serum PFOA concentration and body mass, serum insulin and lipid profile in exposed young girls.
We conducted a cross-sectional study of PFAS environmental biomarkers and insulin resistance in 6 to 8 year-old girls from Greater Cincinnati (n=353). In 2004–2006, blood samples were obtained to measure polyfluoroalkyl substances (PFAS), fasting insulin, glucose and lipids. Clinical exams included anthropometric measurements and pubertal maturation staging. Linear regression and mediation analyses, specifically structural equation modeling (SEM), were used to determine the strength and direction of the relationships between PFAS, pubertal maturation status, body mass index (BMI), cholesterol and insulin resistance.
The median PFOA (7.7ng/ml) was twice the National Health and Nutrition Examination Survey (2005–2006). Only PFOA, a PFAS sub-species, showed statistically significant relationships with the outcomes. In regression models, PFOA was associated with decreased BMI and waist-to-height ratio (p=0.0008; p=0.0343), HDL-cholesterol (p=0.0046) and had a borderline inverse association with the HOMA Index of insulin resistance (p=0.0864). In SEM, PFOA retained an inverse relationship with BMI (p<0.0001) but the relationships with HOMA and HDL-cholesterol were no longer statistically significant. Pubertal initiation (Tanner breast or pubic stage 2 or greater) and BMI were associated with increased HOMA Index (p<0.0001).
These findings suggest PFOA exposure in young girls affects both BMI and ultimately insulin resistance. In mediation analysis with puberty in the model, the direct effects of PFOA on insulin resistance and were reduced.
•PFAS chemicals are commonly used in manufacturing and are widely detected in humans due to a half-life of 3-4 years.•Studies have shown PFAS exposure during developmental windows results in decreased weight and changes in the lipid profile.•Median serum levels of PFOA in a population of girls, exposed through drinking water, were almost twice the NHANES level.•A strong linear relationship was found between PFOA and BMI, PFOA and HDL cholesterol.•Structural equation modeling revealed that the PFOA exposure effect of decreasing BMI consequently decreased insulin resistance.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Earlier timing and faster tempo of puberty have been linked to adolescents' poor mental health. Previous research rarely adjusted for childhood mental health, did not use physical examination to ...assess puberty, and excluded Latinas and Asian Americans. This study addressed these limitations.
We followed 822 girls, recruited at ages 6-8, for 8 years. Breast and pubic hair development and anxiety and depressive symptoms were assessed prospectively and repeatedly. Structural equation models tested whether pubertal timing and tempo were associated with adolescent mental health symptoms and whether associations varied by ethnicity. Models were adjusted for childhood mental health symptoms, body mass index, and family income.
Earlier breast development was associated with higher depressive symptoms among whites (β = −.19; p < .01) and higher anxiety symptoms among Latinas (β = −.26; p < .05), but lower depressive symptoms among Asians (β = .24, p < .05). Later pubic hair development (b = .24; p < .05) and faster pubic hair tempo (β = .26; p < .01) were associated with higher anxiety symptoms among Latinas. Faster pubic hair tempo was associated with lower depressive symptoms among Asians (β = −.34; p < .05). Tempo of breast development showed no associations.
Findings confirmed that earlier breast development was associated with higher mental health symptoms for Latina and white girls but was protective among Asians. Results for pubic hair and pubertal tempo were inconsistent, requiring future examination. While targeted interventions to prevent mental health problems among early-maturing girls are critical, there is variability among who might benefit most.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The objective of this study was to describe the assessment methods and maturation status for a multisite cohort of girls at baseline recruitment and at ages 7 and 8 years.
The method for pubertal ...maturation staging was developed collaboratively across 3 sites. Girls at ages 6 to 8 years were recruited at 3 sites: East Harlem, New York; greater Cincinnati metropolitan area; and San Francisco Bay area, California. Baseline characteristics were obtained through interviews with caregivers and anthropometric measurements by trained examiners; breast stage 2 was defined as onset of pubertal maturation. The kappa statistic was used to evaluate agreement between master trainers and examiners. Logistic regression models were used to identify factors that are associated with pubertal maturation and linear regression models to examine factors that are associated with height velocity.
The baseline cohort included 1239 girls. The proportion of girls who had attained breast stage 2 varied by age, race/ethnicity, BMI percentile, and site. At 7 years, 10.4% of white, 23.4% of black non-Hispanic, and 14.9% of Hispanic girls had attained breast stage>or=2; at 8 years, 18.3%, 42.9%, and 30.9%, respectively, had attained breast stage>or=2. The prime determinant of height velocity was pubertal status.
In this multisite study, there was substantial agreement regarding pubertal staging between examiners across sites. The proportion of girls who had breast development at ages 7 and 8 years, particularly among white girls, is greater than that reported from studies of girls who were born 10 to 30 years earlier.
Background: Hormonally active environmental agents may alter the course of pubertal development in girls, which is controlled by steroids and gonadotropins. Objectives: We investigated associations ...of concurrent exposures from three chemical classes (phenols, phthalates, and phytoestrogens) with pubertal stages in a multiehnic longitudinal study of 1,151 girls from New York City, New York, greater Cincinnati, Ohio, and northern California who were 6–8 years of age at enrollment (2004–2007). Methods: We measured urinary exposure biomarkers at visit 1 and examined associations with breast and public hair development (present or absent, assessed 1 year later) using multivariate adjusted prevalence ratios (PR) and 95% confidence intervals (CIs). Modification of biomarker associations by age-specific body mass index percentile (BMI%) was investigated, because adipose tissue is a source of peripubertal hormones. Results: Breast development was present in 30% of girls, and 22% had pubic hair. High-molecular-weight phthalate (high MWP) metabolites were weakly associated with public hair development adjusted PR, 0.94 (95% CI, 0.88–1.00), fifth vs. first quintile. Small inverse associations were seen for daidzein with breast stage and for triclosan and high MWP with pubic hair stage; a positive trend was observed low-molecular-weight phthalate biomarkers with breast and pubic hair development. Enterolactone attenuated BMI associations with breast development. In the first enterolactone quintile, for the association of high BMI with any development, the PR was 1.34 (95% CI, 1.23–1.45 vs. low BMI). There was no BMI association in the fifth, highest quintile of enterolactone. Conclusions: Weak hormonally active xenobiotic agents investigated in this study had small associations with pubertal development, mainly among those agents detected at highest concentrations.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Perfluoroalkyl substances (PFAS) are a diverse class of manufactured compounds used in a wide range of industrial processes and consumer products and have been detected in human serum worldwide. ...Previous cross-sectional and cohort studies in humans have suggested exposure to PFAS is associated with a wide array of chronic diseases, including endocrine disruption, developmental health effects, cancer and metabolic changes. We examined the associations between a panel of eight PFAS and indicators of thyroid disruption, kidney function, and body mass index (BMI), all of which were measured at repeated time points (1990–2008) over the course of the study. Participants (N = 210) were selected from the Fernald Community Cohort based on household water supply from a PFAS-contaminated aquifer. In adjusted repeated measures models, we observed several notable associations between serum PFAS and thyroid hormones as well as kidney function as measured by estimated glomerular filtration rate (eGFR). An interquartile (IQR) increase in serum PFOS was associated with a 9.75% (95% CI = 1.72, 18.4) increase in thyroid stimulating hormone. An IQR increase in serum PFNA, PFHxS, and PFDeA was associated with a −1.61% (95% CI = −3.53, −0.59), −2.06% (95% CI = −3.53, −0.59), and −2.20% (95% CI = −4.25, −0.14) change in eGFR, respectively. On the other hand, an IQR increase in serum Me-PFOSA was associated with a 1.53% (95% CI = 0.34, 2.73) increase in eGFR. No significant associations with BMI and serum PFAS were noted. Our findings are in agreement with previous reports that serum PFAS are associated with altered kidney and thyroid function.
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•Repeated measures of serum PFOS are associated with increased thyroid stimulating hormone.•Repeated measures of serum PFNA was positively associated with Total T4 in women.•Repeated measures of serum PFNA, PFHxS, and PFDeA are associated with decreased kidney function.•PFHxS retained high stability between serum measurements over a period greater than 10 years.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Perfluoroalkyl chemicals (PFCs) are a family of commonly used industrial chemicals whose persistence and ubiquity in human blood samples has led to concern about possible toxicity. Several animal ...studies and one recent human study have suggested a link between exposure to PFCs and asthma, although few epidemiologic studies have been conducted.
We investigated children's PFC serum concentrations and their associations with asthma-related outcomes.
We evaluated the association between serum concentrations of eight PFCs, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), with self-reported lifetime asthma, recent wheezing, and current asthma using data from participants 12-19 years of age from the 1999-2000 and 2003-2008 National Health and Nutrition Examination Surveys.
In multivariable-adjusted models, PFOA was associated with higher odds of ever having received a diagnosis of asthma odds ratio (OR) = 1.18; 95% CI: 1.01, 1.39 for a doubling in PFOA, whereas for PFOS there were inverse relationships with both asthma and wheezing (OR = 0.88; 95% CI: 0.74, 1.04, and OR = 0.83; 95% CI: 0.67, 1.02, respectively). The associations were attenuated after accounting for sampling weights. No associations were seen between the other PFCs and any outcome.
This cross-sectional study provides some evidence for associations between exposure to PFCs and asthma-related outcomes in children. The evidence is inconsistent, however, and prospective studies are needed.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Phenolic compounds represent a class of environmental chemicals with potentially endocrine-disrupting capabilities. We investigated longitudinal associations between childhood exposure to phenols, ...from both manmade and natural sources, and subsequent measures of adiposity among girls enrolled in the Breast Cancer and the Environment Research Program between 2004 and 2007. Baseline (ages 6-8 years) urinary concentrations were obtained for creatinine and phenol metabolites: enterolactone, genistein, daidzein, benzophenone-3, bisphenol A, the sum of parabens (methyl, ethyl, and propyl parabens), 2,5-dichlorophenol, and triclosan. Body mass index (weight (kg)/height (m)2), waist circumference, and percent body fat were measured at annual or semiannual examinations through 2015 (n = 1,017). Linear mixed-effects regression was used to estimate how baseline concentrations of phenols (tertile groups) were related to changes in girls' adiposity measurements from ages 7 through 15 years. Enterolactone was inversely associated with body mass index, waist circumference, and percent body fat, while 2,5-dichlorophenol was positively associated with these measurements. A nonmonotonic association was observed for triclosan and girls' adiposity; however, it was due to effect modification by baseline overweight status. Triclosan was positively associated with adiposity only among overweight girls. These results suggest that exposure to specific phenols during childhood may influence adiposity through adolescence.
Exposure to hormonally active chemicals could plausibly affect pubertal timing, so we are investigating this in the Breast Cancer and the Environment Research Program.
Our goal was to examine ...persistent organic pollutants (POPs) in relation to pubertal onset.
Ethnically diverse cohorts of 6- to 8-year-old girls (n = 645) provided serum for measure of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), and lipids. Tanner stages breast (B) and pubic hair (PH), and body mass index (BMI) were measured at up to seven annual clinic visits. Using accelerated failure time models, we calculated time ratios (TRs) for age at Tanner stages 2 or higher (2+) and POPs quartiles (Q1-4), adjusting for confounders (race/ethnicity, site, caregiver education, and income). We also calculated prevalence ratios (PRs) of Tanner stages 2+ at time of blood sampling.
Cross-sectionally, the prevalence of B2+ and PH2+ was inversely related to chemical serum concentrations; but after adjustment for confounders, only the associations with B2+, not PH2+, were statistically significant. Longitudinally, the age at pubertal transition was consistently older with greater chemical concentrations; for example: adjusted TR for B2+ and Q4 for ΣPBDE = 1.05; 95% CI: 1.02, 1.08, for ΣPCB = 1.05; 95% CI: 1.01, 1.08, and for ΣOCP = 1.10; 95% CI: 1.06, 1.14, indicating median ages of about 6 and 11 months older than least exposed, and with similar effect estimates for PH2+. Adjusting for BMI attenuated associations for PCBs and OCPs but not for PBDEs.
This first longitudinal study of puberty in girls with serum POPs measurements (to our knowledge) reveals a delay in onset with higher concentrations.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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