Elevated exposure to multiple trace metals can be neurotoxic even at relatively low levels. These findings are primarily evident from adult occupational studies as well as in children exposed prenatally or in early childhood. Less research has focused on the neurodevelopmental impacts of exposure to metals among school-aged children. We examined associations between exposure to a mixture of four metals (arsenic, cadmium, manganese, lead) measured in hair and markers of cognition, attention, and behavior among 222 6-12 year old children who participated in a 2009-2010 neurodevelopmental follow-up to the C8 Health Project. Using quantile-based g-computation we estimated the adjusted overall metal mixture effect ψ (95 % CI) as the change in outcome per decile increase in all metals in the mixture. Hair metal levels varied by metal, with cadmium being lowest (median 0.007, interquartile range (IQR) 0.013 μg/g) and lead the highest concentration (median 0.152, IQR 0.252 μg/g). Childrens cognitive skills and development, attention/impulsivity, and behavior were all close to standardized population means. Each decile increase in all metals was associated with a Full Scale IQ reduction of 1.01 points (95 % confidence interval (CI) -1.88, -0.15) and Verbal IQ reduction of 1.11 points (95 % CI -1.97, -0.25), adjusted for child age, sex, secondhand smoke exposure, HOME score, maternal education, maternal IQ, and examiner. Maternal report of ADHD-like behaviors and executive functioning also showed adverse associations with the metal mixture. Our findings suggest that similar to exposure during prenatal and early childhood periods, recent exposure to metals during middle childhood is associated with adverse neurodevelopmental consequences. Middle childhood may also be a developmental window of susceptibility to the negative consequences of exposure to environmental neurotoxicants.

Objective

To describe availability and frequency of use of local snack-food outlets and determine whether reported use of these outlets was associated with dietary intakes.

Design

Data were cross-sectional. Availability and frequency of use of three types of local snack-food outlets were reported. Daily dietary intakes were based on the average of up to four 24 h dietary recalls. Multivariable linear regression models estimated average daily intakes of energy, sugar-sweetened beverages (SSB) and snack foods/sweets associated with use of outlets.

Setting

Multi-site, observational cohort study in the USA, 2004-2006.

Subjects

Girls aged 6-8 years (n 1010).

Results

Weekly frequency of use of local snack-food outlets increased with number of available types of outlets. Girls with access to only one type of outlet reported consuming food/beverage items less frequently than girls with access to two or three types of outlets (P <0·001). Girls' daily energy, SSB and snack foods/sweets intakes increased with greater use of outlets. Girls who reported using outlets>1 to 3 times/week consumed 0·27 (95 % CI 0·13, 0·40) servings of SSB more daily than girls who reported no use. Girls who reported using outlets>3 times/week consumed 449·61 (95 % CI 134·93, 764·29) kJ, 0·43 (95 % CI 0·29, 0·58) servings of SSB and 0·38 (95 % CI 0·12, 0·65) servings of snack foods/sweets more daily than those who reported no use.

Conclusions

Girls' frequency of use of local snack-food outlets increases with the number of available types of outlets and is associated with greater daily intakes of energy and servings of SSB and snack foods/sweets.

Dietary acid load (DAL) may be associated with all-cause mortality (ACM) and breast cancer-specific mortality (BCM), and these associations may be modified by serum polychlorinated biphenyl (PCB) levels. Participants included 519 women diagnosed with first primary in situ or invasive breast cancer in 1996/1997 with available lipid-corrected PCB data. After a median of 17 years, there were 217 deaths (73 BCM). Potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores calculated from a baseline food frequency questionnaire estimated DAL. Cox regression estimated covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between PRAL and NEAP with mortality. We evaluated effect measure modification by total serum PCB levels (>median vs. ≤median). PRAL quartile 4 versus quartile 1 was associated with an ACM HR of 1.31 (95%CI = 0.90-1.92). In the upper median of PCBs, ACM HRs were 1.43 (95%CI = 0.96-2.11) and 1.40 (95%CI = 0.94-2.07) for PRAL and NEAP upper medians, respectively. In the lower median of PCBs, the upper median of NEAP was inversely associated with BCM (HR = 0.40, 95%CI = 0.19-0.85). DAL may be associated with increased risk of all-cause mortality following breast cancer among women with high total serum PCB levels, but inversely associated with breast cancer mortality among women with low PCB levels.

Background: Higher socioeconomic position (SEP) has been associated with increased risk of breast cancer. Its relationship with earlier age of pubertal onset, a risk factor for breast cancer, is less clear.Methods: We studied the relationship of SEP to pubertal onset in a multiethnic cohort of 1,237 girls ages 6 to 8 years at baseline. Girls in three U.S. cities were followed for 5 to 8 years with annual clinical examinations from 2004 to 2012. SEP measures were examined for associations with pubertal onset, assessed by breast budding (thelarche) and pubic hair development (adrenarche). Analyses were conducted with accelerated failure time models using a Weibull distribution, with left, right, and interval censoring.Results: Higher body mass index percentage at entry to the study and black or Hispanic race/ethnicity were the strongest predictors of age at pubertal onset. An SEP index comprising household family income, mother's education, and home ownership was an independent predictor of thelarche in adjusted models for all girls together and for white and Latina, separately, but not black girls, and the relationship varied by study site. The SEP index was not related to adrenarche in adjusted models. Overall, girls from the lowest quintile of SEP entered puberty on average 6% earlier than girls from the highest quintile (time ratio = 0.94; 95% confidence interval 0.91-0.97) in adjusted models.Conclusions: Our results suggest that early-life SEP may influence the timing of pubertal development.Impact: Factors related to lower SEP in childhood can adversely affect early development in ways that may increase the risk of breast cancer. Cancer Epidemiol Biomarkers Prev; 26(12); 1714-21. ©2017 AACR.

Background

Tobacco smoke contains known hormonally active chemicals and reproductive toxicants. Several studies have examined prenatal maternal smoking and offspring age at menarche, but few examined earlier pubertal markers, nor accounted for exposure during childhood. Our objective was to examine pre- and postnatal smoke exposure in relation to timing of early pubertal events.

Methods

An ethnically diverse cohort of 1239 girls was enrolled at age 6-8 years old for a longitudinal study of puberty at three US sites. Girls participated in annual or semi-annual exams to measure anthropometry and Tanner breast and pubic hair stages. Prenatal and current tobacco smoke exposures, as well as covariates, were obtained from parent questionnaire. Cotinine was measured in urine collected at enrollment. Using accelerated failure time models, we calculated adjusted time ratios for age at pubertal onset (maturation stages 2 or higher) and smoke exposure.

Results

Girls with higher prenatal (≥5 cigarettes per day) or secondhand smoke exposure had earlier pubic hair development than unexposed (adjusted time ratio: 0.92 [95% CI = 0.87, 0.97] and 0.94 [95% CI = 0.90, 0.97], respectively). Including both exposures in the same model yielded similar associations. Higher urinary cotinine quartiles were associated with younger age at breast and pubic hair onset in unadjusted models, but not after adjustment.

Conclusions

Greater prenatal and childhood secondhand smoke exposure were associated with earlier onset of pubic hair, but not breast, development. These exposures represent modifiable risk factors for early pubertal development that should be considered for addition to the extensive list of adverse effects from tobacco smoke.

To examine the association of breastfeeding or its duration with timing of girls' pubertal onset, and the role of BMI as a mediator in these associations. A population of 1,237 socio-economically and ethnically diverse girls, ages 6-8 years, was recruited across three geographic locations (New York City, Cincinnati, and the San Francisco Bay Area) in a prospective study of predictors of pubertal maturation. Breastfeeding practices were assessed using self-administered questionnaire/interview with the primary caregiver. Girls were seen on at least annual basis to assess breast and pubic hair development. The association of breastfeeding with pubertal timing was estimated using parametric survival analysis while adjusting for body mass index, ethnicity, birth-weight, mother's education, mother's menarcheal age, and family income. Compared to formula fed girls, those who were mixed-fed or predominantly breastfed showed later onset of breast development [hazard ratios 0.90 (95 % CI 0.75, 1.09) and 0.74 (95 % CI 0.59, 0.94), respectively]. Duration of breastfeeding was also directly associated with age at onset of breast development (p trend = 0.008). Associations between breastfeeding and pubic hair onset were not significant. In stratified analysis, the association of breastfeeding and later breast onset was seen in Cincinnati girls only. The association between breast feeding and pubertal onset varied by study site. More research is needed about the environments within which breastfeeding takes place in order to better understand whether infant feeding practices are a potentially modifiable risk factor that may influence age at onset of breast development and subsequent risk for disease in adulthood.

Background and objectives

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.

Methods

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.

Results

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.

Conclusions

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.

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 multiethnic 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 pubic 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 pubic 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 for 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.

Purpose

The relationship between socioeconomic status (SES) and menarche has implications for understanding social level influences on early life development and adult disease, including breast cancer, but remains ill defined. We report here results from the Breast Cancer and the Environment Research Program, which permitted a longitudinal study of age at menarche in relationship to childhood SES in a diverse cohort of 1,069 girls across three urban areas of the United States.

Methods

We assessed the association of SES index quintiles with age at pubertal onset with breast budding and subsequent tempo to the age at menarche between 2004 and 2015 using multiple-event Cox regression models to estimate hazard ratios and 95% confidence intervals.

Results

In an unadjusted model, lower SES was predictive of both earlier pubertal onset and tempo and thus earlier age at menarche in trends across quintiles. After adjusting for the potentially mediating effects of body mass index, SES trends remained significant for both outcomes. After adjusting for both body mass index and race/ethnicity, the association with SES remained substantial for pubertal onset but was much diminished and nonsignificant for tempo and thus age at menarche.

Conclusions

These results suggest that a lower SES environment and social adversity affect the age at menarche primarily by hastening pubertal onset rather than by shortening tempo.

Background and objectives

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.

Methods

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.

Results

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.

Conclusions

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.