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BACKGROUND: College students tend to pour single servings of beer and liquor that are larger than commonly used standards. The reasons for this are unknown. Students might overpour because they lack knowledge of standard serving sizes. Alternatively, they might know how much alcohol to pour but simply have difficulty pouring the correct amounts. Misperceptions of standard serving sizes could lead to inaccuracies in self-reported consumption. If this is the case, then the validity of students' responses on alcohol surveys and the definitions of risky drinking that are based on them would be called into question. This study examined how college students define standard drinks, whether their definitions are similar to the definitions commonly used by alcohol researchers and government agencies, and whether their definitions of standard drinks are related to the sizes of the drinks that they pour. The study also examined whether feedback regarding the accuracy of their definitions of standard drinks leads students to alter their self-reported levels of consumption. METHODS: Students (N = 133) completed an alcohol survey and performed tasks that required them to free-pour a single beer, glass of wine, shot of liquor, or the amount of liquor in a mixed drink. Roughly half of the students received feedback regarding their definitions of standard drinks. All students then were resurveyed about their recent levels of consumption. RESULTS: With the exception of beer, students incorrectly defined the volumes of standard servings of alcohol, overestimating the appropriate volumes. They also overestimated appropriate volumes when asked to free-pour drinks. Positive relationships existed between students' definitions of standard drinks and the sizes of the drinks that they free-poured. Feedback regarding misperceptions of standard drink volumes led to an increase in levels of self-reported consumption, suggesting that students' original estimates of their alcohol consumption were too low. CONCLUSIONS: Despite the recent focus on alcohol education and prevention at the college level, college students have not been taught how to define standard drinks accurately. They tend to overstate the appropriate volumes, leading them to overpour drinks and underreport levels of consumption. Self-reported consumption levels are altered by feedback regarding the accuracy of students' definitions of standard drinks. The findings raise important questions about the validity of students' responses on alcohol surveys and the definitions of risky drinking that are based them. [ABSTRACT FROM AUTHOR]

A comprehensive definition of health includes the assessment of patient experiences of a disease and its treatment. These patient experiences are best captured by standardized patient-reported outcome (PRO) instruments. A PRO is reported directly by the patient (or caregiver) and provides the patient's perspective into how a disease and its treatment impact their lives. PRO instruments are typically standardized, validated questionnaires with items that are scaled and can be combined to represent an underlying health-related construct such as physical, social, and role functioning, psychological well-being, symptoms, pain, and quality of life. Over the past few decades, PROs have become increasingly used in clinical trials as endpoints to better understand treatment benefits from the patient's perspective and in clinical practice to identify unmet needs of patients, health risk surveillance, and monitor outcomes of care. In this paper, we describe the process for developing standardized PRO instruments, from conceptual model development through instrument validation., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

Background: Climate change poses significant health risks, with children being particularly vulnerable to its adverse health effects. Children with asthma are expected to have worsening disease due to increased exposure to heat, air pollution, mold from flooding, and pollen. Understanding caregiver perspectives on these health harms is crucial for informing public health policy and education. Therefore, we aimed to explore caregiver perceptions of climate change-related health risks to children with asthma., Methods: In this cross-sectional study, a survey instrument was created and distributed to caregivers of children with asthma during their visits to pulmonology clinics located in an urban northeastern US setting and via email., Results: Among 198 completed surveys, 78% of participants reported high levels of concern about climate change, with most respondents agreeing that climate change has already impacted their child's health. Examples provided by respondents included worsening asthma control due to air pollution, wildfire events, pollen exposure, and rapid changes in weather. Respondents who self-identified as female had greater concern. Most respondents agreed that these topics should be further discussed with their child's doctor. Although, barriers to such discussions were noted by the respondents., Conclusion: Caregivers of children with asthma have high levels of concern regarding climate change and report adverse impacts on their child's asthma. Clinicians caring for children with asthma should consider discussing the respiratory health impacts of climate change with caregivers. However, barriers to these discussions need further examination., (© 2024 Wiley Periodicals LLC.)

Background: Studies evaluating effects of prenatal polyunsaturated fatty acid (PUFA) intake on childhood asthma reveal mixed results. Inconsistencies may result from not accounting for important modifying factors such as maternal asthma or child sex., Objective: To evaluate whether associations between prenatal PUFA intake and childhood asthma are modified by prenatal active maternal asthma or child sex in 412 mother-child dyads., Methods: Energy-adjusted prenatal dietary and supplement intakes of omega-3 (n-3) and omega-6 (n-6) PUFAs were estimated using the Block98 Food Frequency Questionnaire, administered during pregnancy. Mothers reported asthma in children followed prospectively to 4.0 plus or minus 1.7 years. Generalized additive models with smooth terms for PUFA (n-3, n-6, n-6/n-3 ratio) effects were used to investigate associations between PUFAs and child asthma, without prespecifying the form of these relationships, including effect modification by active maternal asthma or child sex., Results: Among mothers (40% Black, 31% Hispanic), 22% had active asthma in pregnancy; 17.5% of children developed asthma. Lower maternal n-3 PUFA intake was significantly associated with risk of childhood asthma (P = .03), in particular among children of mothers with active asthma and low n-3 PUFA intake (P = .01). This inverse association was more apparent in girls (P = .01) compared with boys (P = .30), regardless of maternal asthma status. For n-6 PUFA and the n-6/n-3 ratio, there was a lower risk of childhood asthma in the midrange of intake and increased risk at higher intake (n-6 PUFA P = .10, n-6/n-3 ratio P = .13)., Conclusion: Consideration of factors that modify effects of prenatal PUFA intake on childhood asthma has implications for designing intervention strategies tailored to impact those at greatest risk., (Copyright © 2021 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Mammographic breast density (MBD) and benign breast disease (BBD) are two of the strongest risk factors for breast cancer. Understanding trends in MBD by age and parity in women with BBD is essential to the clinical management and prevention of breast cancer., Methods: Using data from the Early Determinants of Mammographic Density (EDMD) study, a prospective follow-up study of women born in 1959-1967, we evaluated MBD in 676 women. We used linear regression with generalized estimating equations to examine associations between self-reported BBD and MBD (percent density, dense area, and non-dense area), assessed through a computer-assisted method., Results: A prior BBD diagnosis (median age at diagnosis 32 years) was reported by 18% of our cohort. The median time from BBD diagnosis to first available study mammogram was 9.4 years (range 1.1-27.6 years). Women with BBD had a 3.44% higher percent MBD (standard error (SE) = 1.56, p-value = 0.03) on their first available mammogram than women without BBD. Compared with parous women without BBD, nulliparous women with BBD and women with a BBD diagnosis prior to first birth had 7-8% higher percent MBD (β = 7.25, SE = 2.43, p-value< 0.01 and β = 7.84, SE = 2.98, p-value = 0.01, respectively), while there was no difference in MBD in women with a BBD diagnosis after the first birth (β = -0.22, SE = 2.40, p-value = 0.93)., Conclusion: Women with self-reported BBD had higher mammographic breast density than women without BBD; the association was limited to women with BBD diagnosed before their first birth.

Changes to the maternal inflammatory milieu may be a mechanism through which maternal psychosocial stress is transmitted to the fetus. Research investigating a limited number of immune markers may miss important signals. We take a proteomics approach to investigate maternal lifetime stress and 92 biomarkers of immune system status. Participants were enrolled in an urban, dual-site (Boston, n  = 301 and New York City, n  = 110) pregnancy cohort. We measured maternal lifetime history of stress and trauma using the validated Life Stressor Checklist-Revised (LSC-R). We measured a panel of 92 immune-related proteins in mid-pregnancy serum using proximity extension assay technology. We leveraged the dual-site study design to perform variable selection and inference within the cohort. First, we used LASSO to select immune markers related to maternal stress among Boston mothers. Then, we performed OLS regression to examine associations between maternal stress and LASSO-selected proteins among New York City mothers. LASSO regression selected 19 immune proteins with non-null coefficients (CCL11, CCL23, CD244, CST5, CXCL1, CXCL5, CXCL10, CX3CL1, FGF-23, IL-5, IL-7, IL-10, IL-17C, MCP-2, MMP-1, SLAMF1, ST1A1, TNF-β, and TWEAK). Of these, only the chemotactic cytokine CX3CL1 (i.e. fractalkine) was significantly associated with maternal stress among the validation sample (percent change in LSC-R score per 1% increase in relative fractalkine expression: 0.74, 95% confidence interval: 0.19, 1.28). Expanding research suggests fractalkine plays an important role in many aspects of pregnancy and fetal development and is stress-sensitive. We found that maternal lifetime history of stress and trauma was significantly associated with elevated serum fractalkine levels during pregnancy.

Intrauterine and early-life exposures, including intrauterine smoke exposures and infant growth are associated with mammographic breast density (MBD), a strong breast cancer risk factor. We investigated whether placental morphometry, which is affected by intrauterine smoke exposure and also influences infant growth, predicts %MBD at ages 37-47. In 247 daughters in the Child Health and Development Studies, we found that larger placental surface area and placental thickness were associated with lower %MBD (-0.32 per cm 2 , 95% CI -0.6, -0.05; -37.8 per 0.5 cm, 95% CI= -73.3, -2.3 respectively) independent of mothers' smoking, age, weight, parity and daughters' birthweight and age at mammogram. We also observed a positive interaction between placental surface area and thickness (p < 0.05) such that the highest breast dense area was observed for offspring with the thickest and largest placentas. Factors that impact placental morphometry, in addition to in utero smoke exposure, may influence adult breast architecture and breast cancer risk., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2019. Published by Elsevier Inc.)

Prior studies in the Child Health and Development Studies (CHDS) found in utero exposure to the pesticide, dichlorodiphenyltrichloroethane (DDT), increased breast cancer risk by age 52. Mammographic density is considered a primary risk factor for breast cancer. We conducted a study of 309 daughters from the CHDS to examine in utero DDT exposure and mammographic density in midlife. Among daughters with high (>75th percentile) exposure to p,p'-Dichlorodiphenyldichloroethylene (DDE), p,p'-DDT was significantly correlated with increased dense area and percent density regardless of her body mass in midlife. In the subset of women with lower (<75th percentile) p,p-DDE, p,p'-DDT was associated with increased non-dense breast area. This was explained by adjustment for midlife BMI suggesting that p,p'-DDT may be obesogenic. In aggregate our findings indicate that early life p,p'-DDT exposure impacts breast density in a complex way that depends on the hosts biological ability to sequester and process DDT and levels of exposure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Using prospective data from the Early Determinants of Mammographic Density study (United States, 1959-2008, n = 1121), we examined the associations between maternal body size, birth size, and infant and early childhood growth during 3 time periods (0-4 months, 4-12 months, and 1-4 years) and benign breast disease (BBD) using multivariable logistic regression with generalized estimating equations. A total of 197 women (17.6%) reported receiving a diagnosis of BBD by a physician. Higher body mass index at age 7 years was inversely associated with BBD risk. Rapid weight gain from age 1 year to 4 years, defined as an increase of least 2 major percentiles (e.g., 5th, 10th, 25th, 50th, 75th, and 95th) relative to stable growth, defined as remaining within 2 percentiles, was also inversely associated with BBD (odds ratio (OR) = 0.51, 95% confidence interval (CI): 0.23, 1.15). In contrast, rapid weight gain in infancy was positively associated with BBD relative to stable growth (from 0 to 4 months, OR = 1.65, 95% CI: 1.04, 2.62; from 4 to 12 months, 1.85, 95% CI: 0.89, 3.85), independent of birth weight, which was not associated with BBD. Our results suggest that patterns of early-life weight gain are important to BBD risk. Thus, susceptibility to BBD, like susceptibility to breast cancer, might start in early life., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) is one of the most common food allergies in infants and young children. CMA can result in anaphylactic reactions, and has long term implications on growth and nutrition. There are several studies in diverse populations assessing the epidemiology of CMA. However, assessment is complicated by the presence of other immune-mediated reactions to cow's milk. These include non-IgE and mixed (IgE and non-IgE) reactions and common non-immune mediated reactions, such as lactose intolerance. Estimates of prevalence and population-level patterns are further complicated by the natural history of CMA (given its relatively high rate of resolution) and variation in phenotype (with a large proportion of patients able to tolerate baked cow's milk). Prevalence, natural history, demographic patterns, and long-term outcomes of CMA have been explored in several disparate populations over the past 30 to 40 years, with differences seen based on the method of outcome assessment, study population, time period, and geographic region. The primary aim of this review is to describe the epidemiology of CMA. The review also briefly discusses topics related to prevalence studies and specific implications of CMA, including severity, natural course, nutritional impact, and risk factors.

High birth weight is associated with increased breast cancer risk and, less consistently, with higher mammographic density. In contrast, adolescent body size has been consistently, negatively associated with both MD and breast cancer risk. It is unclear when the direction of these associations changes and whether weight gain in infancy is associated with MD. We evaluated the associations of birth weight and postnatal weight (measured at 4 months, 1 year, and 4 years) by absolute and velocity measures (relative within-cohort percentile changes) with adult mammographic density, assessed using a computer-assisted thresholding program (Cumulus), using linear regression models with generalized estimating equations to account for correlation between siblings in the Early Determinants of Mammographic Density study (1959-2008; n = 700 women with 116 sibling sets; mean age = 44.1 years). Birth weight was positively associated with dense area (per 1-kg increase, β = 3.36, 95% confidence interval (CI): 0.06, 6.66). Weight gains from 0 months to 4 months and 1 year to 4 years were negatively associated with dense area (for 10-unit increase in weight percentile, β = -0.65, 95% CI: -1.23, -0.07, and β = -1.07, 95% CI: -1.98, -0.16, respectively). Findings were similar in the sibling subset. These results support the hypothesis that high birth weight is positively associated with increased breast density and suggest that growth spurts starting in early infancy reduce mammographic dense area in adulthood.

Objectives: To evaluate associations between maternal lifetime traumatic stress and offspring birthweight and examine modifying effects of third trimester cortisol and fetal sex., Study Design: Analyses included 314 mother-infant dyads from an ethnically mixed pregnancy cohort. Maternal lifetime trauma was reported via the Life Stressor Checklist-Revised. Fenton birthweight for gestational age z-scores (BWGA-z) were calculated. A 3-cm scalp-nearest maternal hair segment collected at birth was assayed to reflect cumulative third trimester cortisol secretion. Multivariable regression was used to investigate associations between maternal lifetime trauma and BWGA-z and examine 2- and 3-way interactions with cortisol and fetal sex. Because subjects with low or high cortisol levels could represent susceptible populations, varying coefficient models that relax the linearity assumption on cortisol level were used to assess the modification of maternal lifetime trauma associations with BWGA-z as a function of cortisol., Results: Women were primarily minorities (41% Hispanic, 26% black) with ≤12 years education (63%); 63% reported ≥1 traumatic event. Prenatal cortisol modified the association between maternal lifetime trauma and birthweight. Women with higher lifetime trauma and increased cortisol had significantly lower birthweight infants in males; among males exposed to the 90th percentile of cortisol, a 1-unit increase in trauma score was associated with a 0.19-unit decrease in BWGA-z (95% CI, -0.34 to -0.04). Associations among females were nonsignificant, regardless of cortisol level., Conclusions: These findings underscore the need to consider complex interactions among maternal trauma, disrupted in utero cortisol production, and fetal sex to fully elucidate intergenerational effects of maternal lifetime trauma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Postpartum depression is an important cause of morbidity in mothers and children. The Edinburgh Postpartum Depression Scale (EPDS), the most widely used self-reported measure of postpartum depression, was conceived as a one-dimensional measure. However, evidence that depressive symptoms may be experienced differentially across cultural and racial groups highlights the need to examine structural equivalence using factor analysis across populations. Variation in factor structure for the EPDS remains understudied in middle/low income countries., Methods: We examined the factor structure of the EPDS assessed 6 months postpartum in 628 Mexican women in a longitudinal Mexico City birth cohort. We performed exploratory factor analysis (EFA) to determine the optimal fit in our sample and confirmatory factor analysis (CFA) to examine the fit of two- and three-factor models previously reported in Hispanic populations., Results: The majority of participants had no more than high school education (77%), maternal age was 28 ± 5.4 years and the mean total EPDS score was 6.72 ± 5.8. Using EFA, we identified that the three-factor model provided the optimal fit, with subscales for depression, anxiety, and anhedonia. CFA confirmed that the three-factor model provided the best fit., Limitations: The study population was lower SES, potentially limiting generalizability. The single administration of the EPDS measure in the postpartum period limited our ability to assess stability over time., Conclusions: Better delineation of the multi-factorial structure of the EPDS will allow a more comprehensive understanding of psychological functioning in postpartum women and better inform diagnosis, management and policy., (Copyright © 2018. Published by Elsevier B.V.)

Little research has examined determinants of newborn telomere length, a potential biomarker of lifetime disease risk impacted by prenatal exposures. No study has examined whether maternal exposures in childhood influence newborn telomere length or whether there are sex differences in the maternal factors that influence newborn telomere length. We tested whether a range of maternal risk and protective factors in childhood and pregnancy were associated with newborn telomere length among 151 sociodemographically diverse mother-infant dyads. We further examined whether the pattern of associations differed by infant sex. Newborn telomere length was assessed from cord blood collected at birth. Risk/protective factors included maternal health (smoking, body mass index), socioeconomic status (education, income), stress exposures, and mental health (depressive and posttraumatic stress disorder symptoms) in pregnancy as well as maternal experiences of abuse (physical, emotional, sexual) and familial emotional support in childhood. When examined within the whole sample, only maternal smoking in pregnancy and familial emotional support in childhood emerged as significant predictors of newborn telomere length. Male and female newborns differed in their pattern of associations between the predictors and telomere length. Among males, maternal smoking, higher body mass index, and elevated depressive symptoms in pregnancy and maternal sexual abuse in childhood were associated with shorter newborn telomere length; higher maternal educational attainment and household income in pregnancy and greater maternal familial emotional support in childhood were associated with longer newborn telomere length. Together, these factors accounted for 34% of the variance in male newborn telomere length. None of the risk/protective factors were associated with female newborn telomere length. The results suggest that male fetuses are particularly susceptible to maternal exposure effects on newborn telomere length. These findings have implications for elucidating mechanisms contributing to sex disparities in health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Select hair products contain endocrine disrupting chemicals (EDCs) that may affect breast cancer risk. We hypothesize that, if EDCs are related to breast cancer risk, then they may also affect two important breast cancer risk factors: age at menarche and mammographic breast density., Methods: In two urban female cohorts (N = 248): 1) the New York site of the National Collaborative Perinatal Project and 2) the New York City Multiethnic Breast Cancer Project, we measured childhood and adult use of hair oils, lotions, leave-in conditioners, root stimulators, perms/relaxers, and hair dyes using the same validated questionnaire. We used multivariable relative risk regression models to examine the association between childhood hair product use and early age at menarche (defined as <11 years of age) and multivariable linear regression models to examine the association between childhood and adult hair product use and adult mammographic breast density., Results: Early menarche was associated with ever use of childhood hair products (RR 2.3, 95% CI 1.1, 4.8) and hair oil use (RR 2.5, 95% CI 1.2, 5.2); however, additional adjustment for race/ethnicity, attenuated associations (hair products RR 1.8, 95% CI 0.8, 4.1; hair oil use RR 2.3, 95% CI 1.0, 5.5). Breast density was not associated with adult or childhood hair product or hair oil use., Conclusions: If confirmed in larger prospective studies, these data suggest that exposure to EDCs through hair products in early life may affect breast cancer risk by altering timing of menarche, and may operate through a mechanism distinct from breast density.

Maternal smoking in pregnancy (MSP) has been associated with DNA methylation in specific CpG sites (CpGs) in infants and children. We investigated whether MSP, independent of own personal active smoking, was associated with midlife DNA methylation in CpGs that were previously identified in studies of MSP-DNA methylation in children. We used data on MSP collected from pregnant mothers of 89 adult women born in 1959-1964 and measured DNA methylation in blood (granulocytes) collected in 2001-2007 (mean age: 43 years). Seventeen CpGs were differentially methylated by MSP, with multiple CpGs mapping to CYP1A1, MYO1G, AHRR, and GFI1. These associations were consistent in direction with prior studies (e.g., MSP associated with more and less methylation in AHRR and CYP1A1, respectively) and, with the exception of AHRR CpGs, were not substantially altered by adjustment for active smoking. These preliminary results confirm prior prospective reports that MSP influences the offspring DNA methylation, and extends the timeframe to midlife, and suggest that these effects may persist into adulthood, independently of active smoking.

Purpose: The purpose of the article was to examine the association of early life growth with age at menarche., Methods: Using data from a prospective birth cohort (n = 1134 women, 290 sibling sets), we assessed the association between postnatal growth at 4 months, 1 year, and 4 years and age at menarche, using generalized estimating equations and generalized linear random effects models., Results: Overall, 18% of the cohort experienced early menarche (<12 years). After accounting for postnatal growth in length, faster postnatal change in weight (per 10-percentile increase) in all three periods was associated with an increase (range 9%-20%) in the likelihood of having an early menarche. In adjusted linear models, faster weight gains in infancy and childhood were associated with an average age at menarche that was 1.1-1.3 months earlier compared with stable growth. The overall results were consistent for percentile and conditional growth models. Girls who experienced rapid growth (defined as increasing across two major Centers for Disease Control and Prevention growth percentiles) in early infancy had an average age at menarche that was 4.6 months earlier than girls whose growth was stable., Conclusions: Faster postnatal weight gains in infancy and early childhood before the age of 4 years are associated with earlier age at menarche., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Early life social environment may influence breast cancer through shaping risk factors operating in early life, adolescence and adulthood, or may be associated with breast cancer risk independent of known risk factors. We investigated the associations between early life socioeconomic status (SES) and mammographic density, a strong risk factor for breast cancer, and the extent to which these associations were independent of risk factors across the lifecourse., Methods: We used data from an adult follow-up study of two U.S. birth cohorts of women (average age = 43 years) with prospectively collected data starting during the pregnancy of the mother and continuing through early childhood of the offspring. We collected data on factors in later life periods through computer-assisted interviews with the offspring as adults, and obtained routine clinical mammograms for measurement of percent density and dense and nondense breast areas using a computer assisted method. We used generalized estimating equation models for multivariable analysis to account for correlated data for sibling sets within the study sample (n = 700 composed of 441 individuals and 127 sibling sets)., Results: Highest vs. lowest family income level around the time of birth was associated with smaller dense breast area after adjustment for early life factors (e.g., birthweight, maternal smoking during pregnancy) and risk factors in later life periods, including adult body mass index (BMI) and adult SES (β = -8.2 cm 2 , 95% confidence interval [CI]: -13.3, -3.2). Highest vs. lowest parental educational attainment was associated with higher percent density in models that adjusted for age at mammogram and adult BMI (e.g., β = 4.8, 95% CI = 0.6, 9.1 for maternal education of college or higher degree vs. less than high school), but the association was attenuated and no longer statistically significant after further adjustment for early life factors. There were no associations between early life SES indicators and non-dense area after adjustment for adult BMI. Neither adult education nor adult income was statistically significantly associated with any measure of mammographic density after adjusting for age and adult BMI., Conclusions: We did not observe consistent associations between different measures of early life SES and mammographic density in adulthood.

Objective: We examined the relation between maternal anthropometry and mammographic density in the adult daughter using prospectively collected data., Methods: Our study included a total of 700 mother-daughter dyads participating in an adult follow-up of women born in 2 US birth cohorts: the Child Health and Development Study and the Boston, Massachusetts, and Providence, Rhode Island sites of the National Collaborative Perinatal Project., Results: We observed an increased percent breast density at a mean age of 43.1 years in the daughters of mothers who gained 5 kg or less during pregnancy compared with mother-daughter pairs in which the mother gained 5 to 10 kg (β = 4.8, 95% confidence interval: 1.0 to 8.6). The daughters of mothers who were overweight at the time of conception (prepregnancy BMI ≥25) and who gained >5 kg during pregnancy had a lower percent density (β = -3.2, 95% confidence interval: -6.2 to -0.2) compared with mothers with a BMI <25 at conception who gained >5 kg., Conclusions: We did not find any strong and consistent patterns between maternal anthropometry and the daughter's breast density, a strong predictor of breast cancer risk. A modest association between low gestational weight gain and increased breast density 40 years later in the daughter was observed, even after accounting for adult body size, and if confirmed, possible mechanisms need to be further elucidated., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2016 by the American Academy of Pediatrics.)

Purpose: Rapid infant and childhood growth has been associated with chronic disease later in life, including breast cancer. Early life socioeconomic status (SES) influences childhood growth, but few studies have prospective measures from birth to consider the effects of early life growth and SES on breast cancer risk., Methods: We used prospectively measured early life SES and growth (percentile weight change in height and weight between each pair of consecutive time points at birth, 4 months, 1 and 7 years). We performed linear regression models to obtain standardized estimates of the association between 1 standard deviation increase in early life SES and growth and adult mammographic density (MD), a strong risk factor for breast cancer, in a diverse birth cohort (n = 151; 37% white, 38% black, 25% Puerto Rican; average age at mammogram = 42.4)., Results: In models adjusted for race/ethnicity, prenatal factors, birthweight, infant and childhood growth, and adult body mass index, percentile weight change from 1 year to 7 years was inversely associated with percent MD (standardized coefficient (Stdβ) = -0.28, 95% CI: -0.55 to -0.01), and higher early life SES was positively associated with percent MD (Stdβ = 0.24, 95% CI: 0.04-0.43). Similar associations were observed for dense area, but those estimates were not statistically significant., Conclusions: These results suggest opposite and independent effects of early life SES and growth on MD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Moderate alcohol consumption (15 g/day) has been consistently associated with increased breast cancer risk; however, the association between alcohol and mammographic density, a strong marker of breast cancer risk, has been less consistent. Less is known about the effect of patterns of alcohol intake across the lifecourse., Methods: Using the Early Determinants of Mammographic Density study, an adult follow-up of women born in two US birth cohorts (n = 697; Collaborative Perinatal Project in Boston and Providence sites and the Childhood Health and Development Studies in California), we examined the association between alcohol intake in early adulthood (ages 20-29 years) and at time of interview and mammographic density (percent density and total dense area). We report the difference between nondrinkers and three levels of alcohol intake. We considered confounding by age at mammogram, body mass index, geographic site, race/ethnicity, and reproductive characteristics., Results: Seventy-nine percent of women reported ever consuming alcohol. Compared to nondrinkers in early adulthood, we observed an inverse association between >7 servings/week and percent density in fully adjusted models (β = -5.1, 95% CI -8.7, -1.5; p for trend = <0.01). Associations with dense area were inverse for the highest category of drinking in early adulthood but not statistically significant (p for trend = 0.15). Compared to noncurrent drinkers, the association for current intake of >7 servings/week and percent density was also inverse (β = -3.1, 95% CI -7.0, 0.8; p for trend = 0.01). In contrast, moderate alcohol intake (>0-≤7 servings/week) in either time period was positively associated with dense area; but associations were not statistically significant in fully adjusted models., Conclusions: Our study does not lend support to the hypothesis that the positive association between alcohol intake and breast cancer risk is through increasing mammographic density.

Objective: Early age at menopause is associated with increased risk of cardiovascular disease, stroke, osteoporosis, and all-cause mortality. Cigarette smoke exposure in adulthood is an established risk factor for earlier age at natural menopause and may be related to age at the menopausal transition. Using data from two US birth cohorts, we examined the association between smoke exposure at various stages of the life course (prenatal exposure, childhood exposure to parental smoking, and adult smoke exposure) and menopause status in 1,001 women aged 39 to 49 years at follow-up., Methods: We used logistic regression analysis (adjusting for age at follow-up) to estimate odds ratios (ORs) and 95% confidence intervals (CI) relating smoke exposure to natural menopause and the menopausal transition., Results: The magnitudes of the associations for natural menopause were similar but not statistically significant after adjustment for confounders among (i) women with prenatal smoke exposure who did not smoke on adult follow-up (OR, 2.7; 95% CI, 0.8-9.4) and (ii) current adult smokers who were not exposed prenatally (OR, 2.8; 95% CI, 0.9-9.0). Women who had been exposed to prenatal smoke and were current smokers had three times the risk of experiencing earlier natural menopause (adjusted OR, 3.4; 95% CI, 1.1-10.3) compared with women without smoke exposure in either period. Only current smoking of long duration (>26 y) was associated with the timing of the menopausal transition., Conclusions: Our data suggest that exposure to smoke both prenatally and around the time of menopause accelerates ovarian aging.

Objective: To determine whether an association exists between body mass index (BMI) and embryo ploidy in patients undergoing in vitro fertilization (IVF) with trophectoderm biopsy and 24-chromosome preimplantation genetic screening (PGS)., Design: Retrospective cohort study., Setting: University-based fertility center., Patient(s): 279 women aged 20-45 years with documented height and weight from the day of oocyte retrieval who underwent 24-chromosome PGS between 2010 and 2013., Intervention(s): None., Primary Outcomes: number and percentage of euploid embryos., Result(s): Patients were grouped by World Health Organization (WHO) BMI class: underweight (<18.5, n = 11), normal weight (18.5-24.9, n = 196), overweight (25-29.9, n = 50), and obese (≥30, n = 22). Groups were similar by age (mean ± standard error of the mean: 37.5 ± 1.2 to 39.2 ± 0.9), ovarian reserve, and IVF cycle parameters. There was no difference in the number or percentage of euploid embryos by BMI category (<18.5: 27.6% ± 8.5; 18.5-24.9: 34.5% ± 2.2; 25-29.9: 32.1% ± 4.3; ≥30: 30.9% ± 7.3). Age was inversely related to euploidy, but adjusted multivariate regression models failed to demonstrate a statistically significant relationship between BMI and euploidy in underweight (adjusted odds ratio [AOR] 0.44; 95% confidence interval [CI], 0.09-2.10), overweight (AOR 0.90; 95% CI, 0.43-2.00), or obese (AOR 0.74; 95% CI, 0.25-2.20) patients compared with the normal-weight reference group., Conclusion(s): No statistically significant relationship was identified between BMI and euploidy in an otherwise homogenous cohort of patients undergoing IVF with PGS, suggesting that the negative impact of overweight and obesity on IVF and reproductive outcomes may not be related to aneuploidy., (Copyright © 2015. Published by Elsevier Inc.)

Background: Alcohol consumption is associated with higher breast cancer risk. While studies suggest a modest association between alcohol intake and mammographic density, few studies have examined the association in racial/ethnic minority populations., Methods: We assessed dense breast area and total breast area from digitized film mammograms in an urban cohort of African American (42%), African Caribbean (22%), white (22%), and Hispanic Caribbean (9%) women (n = 189, ages 40-61). We examined the association between alcohol intake and mammographic density (percent density and dense area). We used linear regression to examine mean differences in mammographic density across alcohol intake categories. We considered confounding by age, body mass index (BMI), hormone contraceptive use, family history of breast cancer, menopausal status, smoking status, nativity, race/ethnicity, age at first birth, and parity., Results: Fifty percent currently consumed alcohol. Women who consumed >7 servings/week of alcohol, but not those consuming ≤7 servings/week, had higher percent density compared to nondrinkers after full adjustments (servings/week >7 β = 8.2, 95% Confidence Interval (CI) 1.8, 14.6; ≤7 β = -0.5, 95% CI -3.7, 2.8). There was a positive association between high alcohol intake and dense area after full adjustments (servings/week >7 β = 5.8, 95% CI -2.7, 14.2; ≤7 β = -0.1, 95% CI -4.4, 4.2). We did not observe race/ethnicity modification of the association between alcohol intake and percent density. In women with a BMI of <25 kg/m(2), drinkers consuming >7 servings/week of alcohol had a = 17% increase in percent density compared to nondrinkers (95% CI 5.4, 29.0) and there was no association in women with a BMI ≥ 25 kg/m(2) (BMI ≥ 25-30 kg/m(2) > 7 β = 5.1, 95% CI -8.5, 18.7 and BMI > 30 kg/m(2) > 7 β = 0.5, 95% CI -6.5, 7.5) after adjusting for age and BMI (continuous)., Conclusion: In a racially/ethnically diverse cohort, women who consumed >7 servings/week of alcohol, especially those with a BMI < 25 kg/m(2), had higher percent density.

Purpose: We examined whether obesity and a history of diabetes, hypertension, and elevated cholesterol, individually and in combination, are associated with breast density, a strong risk factor for breast cancer., Methods: We measured percent density and dense area using a computer-assisted method (n = 191; age range = 40-61 years). We used linear regression models to examine the associations of each metabolic condition and the number of metabolic conditions (zero, one, two, and three or four conditions) with breast density., Results: Among individual metabolic conditions, only high blood cholesterol was inversely associated with percent density (β = -5.4, 95% confidence interval [CI]: -8.5, -2.2) and dense area (β = -6.7, 95% CI = -11.1, -2.4). Having multiple metabolic conditions was also associated with lower breast density, with two conditions and three or four conditions versus zero conditions associated with 6.4% (95% CI: -11.2, -1.6) and 7.4% (95% CI: -12.9, -1.9) reduction in percent density and with 6.5 cm(2) (95% CI: -13.1, -0.1) and 9.5 cm(2) (95% CI: -17.1, -1.9) decrease in dense area., Conclusions: A history of high blood cholesterol and multiple metabolic conditions were associated with lower relative and absolute measures of breast density. The positive association between metabolic abnormalities and breast cancer risk may be driven by pathways unrelated to mammographic breast density., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Vitamin D, which influences cellular proliferation and breast tissue characteristics, has been inversely correlated with breast cancer risk. Dietary vitamin D intake has been associated with lower mammographic density (MD), a strong intermediate marker of breast cancer risk., Findings: We examined the relationship between MD and serum 25-hydroxyvitamin D [25(OH)D], an integrated measure of vitamin D status from dietary sources and sunlight exposure, in a multi-ethnic cohort of women undergoing screening mammography. We recruited women age 40-60 years without a history of breast cancer at the time of their routine screening mammogram, and conducted in-person interviews and collected blood specimens. We enrolled 195 women from 2007-2008, 120 gave blood, and 114 were evaluable, including 25% white, 41% African American, 18% African Caribbean, and 16% Hispanic. We digitized mammograms and calculated percent density, dense area, and non-dense area on cranial-caudal images. We measured serum 25(OH)D in batched, archived specimens. Median serum 25(OH)D was 22 ng/ml (range, 8-66 ng/ml). In univariable analysis, higher serum 25(OH)D was associated with white race, higher educational level, ever breast feeding, and blood draw during the summer. After adjusting for body mass index and other confounders, we found no association between serum 25(OH)D and different measures of MD. However, when stratified by season, 25(OH)D was inversely associated with dense area during July-December (p = 0.034)., Conclusions: Overall, our findings suggest that circulating vitamin D, a potentially modifiable breast cancer risk factor, is not associated with MD; the seasonal effects we observed need to be replicated in larger cohorts.

Background: Elevated levels of the pesticide DDT (dichlorodiphenyltrichloroethane) have been positively associated with blood pressure and hypertension in studies among adults. Accumulating epidemiologic and toxicologic evidence suggests that hypertension during adulthood may also be affected by earlier life and possibly the prenatal environment., Objectives: We assessed whether prenatal exposure to the pesticide DDT increases risk of adult hypertension., Methods: We examined concentrations of DDT (p,p´- and o,p´-) and its metabolite p,p´-DDE (dichlorodiphenyldichloroethylene) in prenatal serum samples from a subset of women (n = 527) who had participated in the prospective Child Health and Development Studies birth cohort in the San Francisco Bay area while they were pregnant between 1959 and 1967. We surveyed daughters 39-47 years of age by telephone interview from 2005 to 2008 to obtain information on self-reported physician-diagnosed hypertension and use of hypertensive medication. We used multivariable regression analysis of time to hypertension based on the Cox proportional hazards model to estimate relative rates for the association between prenatal DDT exposures and hypertension treated with medication in adulthood, with adjustment for potential confounding by maternal, early-life, and adult exposures., Results: Prenatal p,p´-DDT exposure was associated with hypertension [adjusted hazard ratio (aHR) = 3.6; 95% CI: 1.8, 7.2 and aHR = 2.5; 95% CI: 1.2, 5.3 for middle and high tertiles of p,p´-DDT relative to the lowest tertile, respectively]. These associations between p,p´-DDT and hypertension were robust to adjustment for independent hypertension risk factors as well as sensitivity analyses., Conclusions: These findings suggest that the association between DDT exposure and hypertension may have its origins early in development.

Epigenetic modifications may be one mechanism linking early life factors, including parental socioeconomic status (SES), to adult onset disease risk. However, SES influences on DNA methylation patterns remain largely unknown. In a US birth cohort of women, we examined whether indicators of early life and adult SES were associated with white blood cell methylation of repetitive elements (Sat2, Alu and LINE-1) in adulthood. Low family income at birth was associated with higher Sat2 methylation (β = 19.7, 95% CI: 0.4, 39.0 for lowest vs. highest income quartile) and single parent family was associated with higher Alu methylation (β = 23.5, 95% CI: 2.6, 44.4), after adjusting for other early life factors. Lower adult education was associated with lower Sat2 methylation (β = -16.7, 95% CI: -29.0, -4.5). There were no associations between early life SES and LINE-1 methylation. Overall, our preliminary results suggest possible influences of SES across the life-course on genomic DNA methylation in adult women. However, these preliminary associations need to be replicated in larger prospective studies.

Global decreases in DNA methylation, particularly in repetitive elements, have been associated with genomic instability and human cancer. Emerging, though limited, data suggest that in white blood cell (WBC) DNA levels of methylation, overall or in repetitive elements, may be associated with cancer risk. We measured methylation levels of three repetitive elements [Satellite 2 (Sat2)], long interspersed nuclear element-1 (LINE-1) and Alu) by MethyLight, and LINE-1 by pyrosequencing in a total of 282 breast cancer cases and 347 unaffected sisters from the New York site of the Breast Cancer Family Registry (BCFR) using DNA from both granulocytes and total WBC. We found that methylation levels in all markers were correlated between sisters (Spearman correlation coefficients ranged from 0.17 to 0.55). Sat2 methylation was statistically significantly associated with increased breast cancer risk [odds ratio (OR) = 2.09, 95% confidence interval (CI) = 1.09-4.03; for each unit decrease in the natural log of the methylation level, OR = 2.12, 95% CI = 0.88-5.11 for the lowest quartile compared with the highest quartile]. These associations were only observed in total WBC but not granulocyte DNA. There was no association between breast cancer and LINE-1 and Alu methylation. If replicated in larger prospective studies, these findings support that selected markers of epigenetic changes measured in WBC, such as Sat2, may be potential biomarkers of breast cancer risk.

Lower global DNA methylation is associated with genomic instability and it is one of the epigenetic mechanisms relevant to carcinogenesis. Emerging evidence for several cancers suggests that lower overall levels of global DNA methylation in blood are associated with different cancer types, although less is known about breast cancer. We examined global DNA methylation levels using a sibling design in 273 sisters affected with breast cancer and 335 unaffected sisters from the New York site of the Breast Cancer Family Registry. We measured global DNA methylation in total white blood cell (WBC) and granulocyte DNA by two different methods, the [ ( 3) H]-methyl acceptance assay and the luminometric methylation assay (LUMA). Global methylation levels were only modestly correlated between sisters discordant for breast cancer (Spearman correlation coefficients ranged from -0.08 to 0.24 depending on assay and DNA source). Using conditional logistic regression models, women in the quartile with the lowest DNA methylation levels (as measured by the [ ( 3) H]-methyl acceptance assay) had a 1.8-fold (95% CI = 1.0-3.3) higher relative association with breast cancer than women in the quartile with the highest DNA methylation levels. When we examined the association on a continuous scale, we also observed a positive association (odds ratio, OR = 1.3, 95% CI = 1.0-1.7, for a one unit change in the natural logarithm of the DPM/μg of DNA). We observed no association between measures by the LUMA assay and breast cancer risk. If replicated in prospective studies, this study suggests that global DNA methylation levels measured in WBC may be a potential biomarker of breast cancer risk even within families at higher risk of cancer.

Background: Exposure to prenatal tobacco smoke (PTS) has been associated with a number of health outcomes in the offspring, including some childhood cancers. Lower levels of genomic DNA methylation have also been associated with several types of cancers. We investigated whether PTS was associated with global DNA methylation levels in the offspring., Methods: Our sample was drawn from a birth cohort of women born between 1959 and 1963 in New York City (n = 90). We measured methylation of repetitive elements (Sat2, Alu, LINE-1) from peripheral blood granulocytes. We combined prospectively collected data on PTS with adult epidemiologic data and blood samples collected in 2001 to 2007 (mean age, 43 years). We used linear regression to assess the association between PTS and repetitive element methylation., Results: Thirty-six percent of mothers smoked during pregnancy. We observed an inverse association between PTS and Sat2 methylation. This inverse association remained even after adjustment for potential mediators including child environmental tobacco smoke exposure, birth size, postnatal weight and height changes, and adult smoking status and alcohol intake (β = -0.22, 95% confidence interval = -0.40 to -0.03 for ever exposed to PTS vs. never exposed using models of log-transformed methylation levels). PTS exposure was not statistically significantly associated with LINE-1 or Alu methylation., Conclusions: PTS exposure, measured at the time of pregnancy and not retrospectively reported, was associated with a decrease in Sat2 methylation but not LINE-1 or Alu methylation., Impact: If replicated in larger studies, this study supports a persistent effect of PTS on DNA methylation levels, as measured by Sat2, in adulthood.

Tobacco smoke has both carcinogenic effects and anti-estrogenic properties and its inconsistent association with breast cancer risk in observational studies may be because of these competing effects across the lifecourse. We conducted a prospective study of prenatal smoke exposure, childhood household smoke exposure, and adult active smoke exposure and mammographic density, a strong intermediate marker of breast cancer risk, in an adult follow-up of existing US birth cohorts. Specifically, we followed up women who were born between 1959 and 1967 and whose mothers participated in either the Collaborative Perinatal Project (Boston and Providence sites) or the Childhood Health and Development Study in California. Of the 1134 women interviewed in adulthood (ranging in age from 39 to 49 years at interview), 79% had a screening mammogram. Cigarette smoking was reported by mothers at the time of their pregnancy; 40% of mothers smoked while pregnant. Women whose mothers smoked during pregnancy had a 3.1% (95% confidence interval (CI) = -6.0%, -0.2%) lower mammographic density than women whose mothers did not smoke during pregnancy. When we further accounted for adult body mass index and adult smoking status, the association remained (β = -2.7, 95% CI = -5.0, -0.3). When we examined patterns of smoking, prenatal smoke exposure without adult smoke exposure was associated with a 5.6% decrease in mammographic density (β = -5.6, 95% CI = -9.6, -1.6). Given the strength of mammographic density as an intermediate marker for breast cancer, the inverse associations between mammographic density and smoking patterns across the lifecourse may help explain the complex association between cigarette smoking and breast cancer risk.

DNA methylation measured in white blood cell DNA is increasingly being used as in studies of cancer susceptibility. However, little is known about the correlation between different assays to measure global methylation and whether the source of DNA matters when examining methylation profiles in different blood cell types. Using information from 620 women, 217 and 403 women with DNA available from granulocytes (Gran), and total white blood cells (WBC), respectively, and 48 women with DNA available from four different sources (WBC, Gran, mononuclear (MN), and lymphoblastoid cell lines (LCL)), we compared DNA methylation for three repetitive elements (LINE1, Sat2, Alu) by MethyLight, luminometric methylation assay (LUMA), and [(3)H]-methyl acceptance assay. For four of the five assays, DNA methylation levels measured in Gran were not correlated with methylation in LBC, MN, or WBC; the exception was Sat2. DNA methylation in LCL was correlated with methylation in MN and WBC for the [(3)H]-methyl acceptance, LINE1, and Alu assays. Methylation in MN was correlated with methylation in WBC for the [(3)H]-methyl acceptance and LUMA assays. When we compared the five assays to each other by source of DNA, we observed statistically significant positive correlations ranging from 0.3-0.7 for each cell type with one exception (Sat2 and Alu in MN). Among the 620 women stratified by DNA source, correlations among assays were highest for the three repetitive elements (range 0.39-0.64). Results from the LUMA assay were modestly correlated with LINE1 (0.18-0.20). These results suggest that both assay and source of DNA are critical components in the interpretation of global DNA methylation patterns from WBC.

Previous studies have reported mixed results regarding the association between age at menarche and environmental tobacco smoke exposure, both prenatally and during early childhood; however, few studies have had data available during both time periods. The present study examined whether exposure to prenatal tobacco smoke (PTS) via maternal smoking during pregnancy or childhood environmental tobacco smoke (ETS) was associated with age at menarche in a multi-ethnic birth cohort. With the uniquely available prospectively collected data on body size and growth at birth and in early life, we further examined whether the association between PTS and ETS exposure and age at menarche was mediated by these variables. From 2001 to 2006, we recruited 262 women born between 1959 and 1963 who were enrolled previously in a New York City site of the National Collaborative Perinatal Project. Mothers who smoked during pregnancy vs. those who did not were more likely to be White, younger, have more education and have lower birthweight babies. Daughters with heavy PTS exposure (≥ 20 cigarettes per day) had a later age at menarche (>12 years vs. ≤ 12 years), odds ratio (OR) =2.1 [95% confidence interval (CI) 0.9, 5.0] compared with daughters with no PTS. Daughters exposed to only childhood ETS had a later age at menarche, OR=2.1 [95% CI 1.0, 4.3], and those exposed to PTS and ETS combined had a statistically significant later age at menarche, OR=2.2 [95% CI 1.1, 4.6] compared with daughters with no PTS and no ETS. These results did not change after further adjustment for birthweight and postnatal growth suggesting that exposure to PTS and ETS is associated with later age at menarche even after considering possible relationships with growth., (© 2010 Blackwell Publishing Ltd.)

Alcohol intake is one of the few modifiable risk factors for breast cancer. Current alcohol intake has been associated with mammographic density, a strong intermediate marker of breast cancer risk, though few studies have examined the effect of both current and average lifetime alcohol intake. We interviewed 262 participants from a New York birth cohort (born 1959-1963) and obtained mammograms from 163 (71.5% of participants with a mammogram). We collected information on alcohol intake by beverage type separately for each decade of life. We used multivariable linear models to assess the associations between current and average lifetime alcohol intake and mammographic density using a quantitative measure of density from digitized images. Overall, current alcohol intake was more strongly associated with mammographic density than average lifetime alcohol intake; compared with nondrinkers, those with current intake of seven or more servings per week had on average 12.3% (95% CI: 4.3, 20.4) higher density, adjusted for average lifetime alcohol intake, age, and body mass index. We observed a consistent inverse association for red wine intake and mammographic density, suggesting that the positive association between mammographic density and overall alcohol intake was driven by other types of alcoholic beverages. Our findings support an association between current alcohol intake and increased mammographic density independent of the effect of average lifetime alcohol intake. If replicated, our study suggests that reducing current alcohol consumption, particularly beer and white wine intake, may be a means of reducing mammographic density regardless of intake earlier in life.

Life-course epidemiologic studies frequently obtain data on perinatal and childhood factors through adult self-report. Data from a prospective US birth cohort of 262 women, born between 1959 and 1963 (average age at adult follow-up, 41.8 years), were used to assess the validity of self-reported birth weight category by sociodemographic characteristics. The effect of reporting error on the associations of birth weight with childhood and adult body mass index was evaluated by comparing the estimates of associations from linear regression analyses. The level of agreement between the birth weight category reported by 85% of the participants and the birth weight recorded at the time of birth was moderate to good (sensitivity = 73%, weighted kappa = 0.67). The validity varied by birth weight category (sensitivity range = 58%-81% for the lowest and highest birth weight category, respectively) and was highest for participants who were white, of lower childhood family income, and born to older mothers. Despite this moderate to good validity, the associations of birth weight with childhood and adult body mass index were attenuated and no longer statistically significant when self-reported birth weight was used. In conclusion, birth weight reported in middle adult life is measured with error, limiting its utility for detecting modest associations with health in later life periods.

Larger body size in childhood is correlated with earlier age at menarche; whether birth and infant body size changes are also associated with age at menarche is less clear. The authors contacted female participants enrolled in the New York site of the US National Collaborative Perinatal Project born between 1959 and 1963 (n = 262). This racially and ethnically diverse cohort (38% white, 40% African American, and 22% Puerto Rican) was used to investigate whether maternal (body size, pregnancy weight gain, age at menarche, smoking) and birth (birth weight, birth length, placental weight) variables and early infant body size changes were associated with age at menarche even after considering later childhood body size. Higher percentile change in weight from ages 4 months to 1 year was associated with earlier age at menarche even after adjustment for later childhood growth (beta = -0.15, 95% confidence interval: -0.27, -0.02 years per 10-percentile change in weight from ages 4 months to 1 year). The association was in the same direction for all 3 racial/ethnic groups but was largest for the white group. These New York Women's Birth Cohort Adult Follow-up data (2001-2006) suggest that infant weight gain, in addition to childhood weight gain, may be associated with earlier age at menarche.

One plausible mechanism for the environment to alter cancer susceptibility is through DNA methylation. Alterations in DNA methylation can lead to genomic instability and altered gene transcription. Genomic DNA methylation levels have been inversely associated with age, suggesting that factors throughout life may be associated with declines in DNA methylation. Using information from a multiethnic New York City birth cohort (born between 1959 and 1963), we examined whether genomic DNA methylation, measured in peripheral blood mononuclear cells, was associated with smoking exposure and other epidemiologic risk factors across the life course. Information on prenatal and childhood exposures was collected prospectively through 1971, and information on adult exposures and blood specimens were collected in adulthood from 2001 to 2007. Methylation levels of leukocyte DNA were determined using a [(3)H]-methyl acceptance assay where higher values of disintegrations per minute per microgram DNA indicate less DNA methylation. Genomic methylation of leukocyte DNA differed by ethnicity (66% of Blacks, 48% of Whites, and 29% of Hispanics were above the median level of disintegrations per minute per microgram DNA; P = 0.03). In multivariable modeling, DNA methylation was statistically significantly associated with maternal smoking during pregnancy, longer birth length, later age at menarche, nulliparity, and later age at first birth. These data, if replicated in larger samples, suggest that risk factors across the life course may be associated with DNA methylation in adulthood. Larger studies and studies that measure within-individual changes in DNA methylation over time are a necessary next step.