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Background: African Americans (AA) are disproportionally affected by cardiovascular disease as compared to other racial-ethnic groups. Exposure to adverse socioeconomic conditions may partially explain disparities in risk factors and prevalence and cardiovascular diseases for AA. We aim to study the impact of poverty status on metabolic syndrome (MetS) and its components among African Americans. Methods: We used data from the National Health and Nutritional Examination Survey (NHANES) cycles 2001-2006. We defined MetS using the Joint Scientific Definition as the presence of any 3/5 components: elevated blood pressure (BP), elevated triglycerides (TGL), lower high-density lipoprotein cholesterol (LDL), elevated fasting plasma glucose (FPG), and elevated waist circumference (WC). Poverty to income ratio (PIR) was categorized as below poverty ( 3) groups. We used multivariable survey-weighted logistic regression models to study the impact of poverty status of prevalence of MetS and its components among AA men and women. Results: Overall, the average aggregate prevalence of MetS among AA sample was 22% in our study with prevalence being 25% for women and 18% among men (p 3) (OR = 1.57, 95%CI = 1.00 - 2.46, p = 0.05) with no association observed among men (OR (PIR = 1) = 0.70, 95%CI = 0.43 - 1.19, p = 0.13). Further, similar associations were observed for individual components among women including: elevated waist circumference (OR = 2.04, 95%CI = 1.37, 3.01, p 3). No association of poverty status with MetS and its components were observed among AA men. Clustering of factors identified key groups that define MetS among women included WC. Conclusion: African American women living below poverty have a higher likelihood of having MetS and 4 of 5 individual components. Clustering of these factors differ across men and women and should be further explored as tools for clinical management. Main Points: 1) Metabolic syndrome remains an important public health burden among African Americans and shows disparities by socioeconomic status; 2) Women living below poverty were more likely to have MetS and associated components as compared to women living above poverty; 3) Clustering of components gave us snapshot of factors that should be considered to develop gender specific targeted health interventions for MetS among African Americans.

Background Unfair treatment such as discrimination and racism contribute to depression and perceived stress in African Americans. Although studies have examined how responding to such treatment is associated with ameliorating depressive symptoms and levels of perceived stress, most do not focus on African Americans. The purpose of this study is to assess how talking to others in response to unfair treatment is associated with self-reported depressive symptoms and perceived stress levels in African Americans. Methods A sample from the 2010–2013 Minority Health Genomics and Translational Research Bio-Repository Database was used and consisted of 376 African American adults aged 30–55 years old residing in the southern region of the United States. Linear regression models were used to assess the association between talking to others following unfair treatment, compared to keeping it to oneself, on self-reported depressive symptoms and perceived stress. The predictor variable was based on the question “If you have been treated unfairly, do you usually talk to people about it or keep it to yourself?”. Results Talking to someone after being treated unfairly was inversely associated with perceived stress ($$\beta$$ β : -3.62, SE: 1.14, p ≤ 0.05) and depressive symptoms ($$\beta$$ β : -3.62, SE: 1.14, p ≤ 0.05). Conclusions African Americans who talked to others in response to unfair treatment had lower depressive symptoms and perceived stress than those who kept it to themselves. More outreach to African Americans regarding the importance of talk in response to exposure to unfair treatment is needed as a potential coping mechanism.

Introduction With increasing cesarean section rates, adverse pregnancy outcomes such as preterm delivery and small-for-gestational-age continue to be public health challenges. Besides having high co-occurrence and interrelation, it is suggested that these outcomes, along with preeclampsia, are associated with reduced subsequent fertility. On the other hand, the loss of a child during the perinatal period is associated with increased reproduction. Failure to consider this factor when estimating the effects of pregnancy outcomes on future reproduction may lead to erroneous conclusions. However, few studies have explored to what degree a perinatal loss contributes to having a next pregnancy in various adverse pregnancy outcomes. Material and methods This was a population-based study of mothers giving birth to their first singleton infant (≥22 gestational weeks) during 1967-2007 who were followed for the occurrence of a second birth in the Medical Birth Registry of Norway until 2014. Relative risks with 95% confidence intervals for having one lifetime pregnancy by preterm delivery, small-for-gestational-age, preeclampsia and cesarean section were obtained by generalized linear models for the binary family and adjusted for maternal age at first birth, education and year of first childbirth. Main outcome measure was having one lifetime pregnancy. Results Nearly 900 000 women gave birth to their first singleton infant in 1967-2007, of which 16% had only one lifetime pregnancy. These women were older at first delivery, had less education and there was a higher proportion of unmarried women than women with two or more births. In women with pregnancy complications where the infant survived the perinatal period, there were the following relative risks for one lifetime pregnancy: increased preterm delivery: 1.21 (1.19-1.22)], small-for-gestational-age: 1.13 (1.12-1.15), preeclampsia: 1.09 (1.07-1.11), cesarean section: 1.24 (1.23-1.25). The risk was significantly reduced if the child was lost (preterm delivery: 0.63 [0.59-0.68], small-for-gestational-age: 0.57 [0.51-0.63], preeclampsia: 0.69 [0.59-0.80], cesarean section: 0.67 [0.56-0.79]), compared with women with no perinatal loss and no adverse outcome. Conclusions The associations between adverse outcomes of pregnancy and the risk of having one lifetime pregnancy were strongly modified by child survival in the perinatal period.

Although annual breast magnetic resonance imaging (MRI) is recommended for women at high risk for breast cancer as an adjunct to screening mammography, breast MRI use remains low. We examined factors associated with breast MRI use in a cohort of women with a family history of breast cancer but no personal cancer history. Study participants came from the Sister Study cohort, a nationwide, prospective study of women with at least 1 sister who had been diagnosed with breast cancer but who themselves had not ever had breast cancer (n = 17 894). Participants were surveyed on breast cancer beliefs, cancer worry, breast MRI use, provider communication, and genetic counseling and testing. Logistic regression was used to assess factors associated with having a breast MRI overall and for those at high risk. Breast MRI was reported by 16.1% and was more common among younger women and those with higher incomes. After adjustment for demographics, ever use of breast MRI was associated with actual and perceived risk. Odds ratios (OR) were 12.29 (95% CI, 8.85-17.06), 2.48 (95% CI, 2.27-2.71), and 2.50 (95% CI, 2.09-2.99) for positive BRCA1/2 test, lifetime breast cancer risk ≥ 20%, and being told by a health care provider of higher risk, respectively. Women who believed they had much higher risk than others or had higher level of worry were twice as likely to have had breast MRI; OR = 2.23 (95% CI, 1.82-2.75) and OR = 1.76 (95% CI, 1.52-2.04). Patterns were similar among women at high risk. Breast cancer risk, provider communication, and personal beliefs were determinants of breast MRI use. To support shared decisions about the use of breast MRI, women could benefit from improved understanding of the chances of getting breast cancer and increased quality of provider communications.

An association between smoking and breast cancer is unresolved, although a higher risk from exposure during windows of susceptibility has been proposed. The objective of this prospective study was to evaluate the association between tobacco smoke and breast cancer with a focus on timing of exposure, especially during early life.Sister study participants (n = 50,884) aged 35-74 were enrolled from 2003 to 2009. Women in the United States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast cancer. Participants completed questionnaires on smoking and environmental tobacco smoke (ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for breast cancer risk.During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was associated with breast cancer risk. However, never smoking women exposed to ETS throughout their childhood had a 17% higher risk of breast cancer (95% CI 1.00-1.36) relative to those with no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI 1.01-1.32) and the HR was most elevated for women born in earlier birth cohorts (1940, HR = 1.44, 95% CI 1.02-2.02; 1940-1949, HR = 1.28, 95% CI 1.01-1.62).In utero ETS and ETS exposure during childhood and adolescence were associated with increased risk of breast cancer and associations varied by birth cohort.

Objective Low parity women are at increased risk of cardiovascular mortality. Unfavourable lipid profiles have been found in one-child mothers years before they conceive. However, it remains unclear whether unfavourable lipid profiles are evident in these women also after their first birth. The aim was to estimate post-pregnancy lipid levels in one-child mothers compared to mothers with two or more children and to assess these lipid’s associations with number of children. Methods We used data on 32 618 parous women (4 490 one-child mothers and 28 128 women with ≥2 children) examined after first childbirth as part of Cohort of Norway (1994–2003) with linked data on reproduction and number of children from the Medical Birth Registry of Norway (1967–2008). Odds ratios (ORs) with 95% confidence intervals (CIs) for one lifetime pregnancy (vs. ≥2 pregnancies) by lipid quintiles were obtained by logistic regression and adjusted for age at examination, year of first birth, body mass index, oral contraceptive use, smoking and educational level. Results Compared to women with the lowest quintiles, ORs for one lifetime pregnancy for the highest quintiles of LDL and total cholesterol were 1.30 (95%CI: 1.14–1.45) and 1.43 (95%CI: 1.27–1.61), respectively. Sensitivity analysis (women

Objective To study prepregnancy serum lipid levels and the association with the number of children. Design Prospective, population-based cohort. Setting Linked data from the Cohort of Norway and the Medical Birth Registry of Norway. Participants 2645 women giving birth to their first child during 1994–2003 (488 one-child mothers and 2157 women with ≥2 births) and 1677 nulliparous women. Main outcome measures ORs for no and one lifetime pregnancy (relative to ≥2 pregnancies) obtained by multinomial logistic regression, adjusted for age at examination, education, body mass index (BMI), smoking, time since last meal and oral contraceptive use. Results Assessed in quintiles, higher prepregnant triglyceride (TG) and TG to high-density lipoprotein (TG:HDL-c) ratio levels were associated with increased risk of one lifetime pregnancy compared with having ≥2 children. Compared with the highest quintile, women in the lowest quintile of HDL cholesterol levels had an increased risk of one lifetime pregnancy (OR 1.7, 95% CI 1.2 to 2.4), as were women with the highest low-density lipoprotein (LDL) cholesterol, TG and TG:HDL-c ratio quintiles (compared with the lowest) (OR 1.2, 95% CI 0.8 to 1.7; OR 2.2, 95% CI 1.5 to 3.2; and OR 2.2, 95% CI 1.5 to 3.2, respectively). Similar effects were found in women with BMI≥25 and the highest LDL and total cholesterol levels in risk of lifetime nulliparity. Conclusion Women with unfavourable prepregnant lipid profile had higher risk of having no or only one child. These findings substantiate an association between prepregnant serum lipid levels and number of children. Previously observed associations between low parity and increased cardiovascular mortality may in part be due to pre-existing cardiovascular disease lipid risk factors.

Introduction: Women facing complex and uncertain situations such as cancer in their families may seek information from a variety of sources to gain knowledge about cancer risk and reduce uncertainty. We describe and assess the relative importance of information sources about familial breast cancer at the individual, family, and healthcare provider levels influencing women's reporting they had enough information to speak with daughters about breast cancer. This outcome we refer to as being informed about breast cancer. Materials and Methods: Sister Study participants, a cohort of women with a family history of breast cancer, were surveyed on family cancer history, family communication, social support, and interactions with healthcare providers (n = 11,766). Adjusted percentages and 95% confidence intervals for being informed about breast cancer versus not being informed were computed for individual-, family-, and provider-level characteristics in three steps using multivariate logistic regression models. Results: We found 65% of women reported being informed about breast cancer while 35% did not. Having a trusted person with whom to discuss cancer concerns, having a lower versus higher perceived risk of breast cancer, having undergone genetic counseling, and being satisfied with physician discussions about breast cancer in their families were predictors of being informed about breast cancer. Conclusions: Although acquiring objective risk information, such as through genetic counseling, may contribute to a basic level of understanding, communication with providers and within other trusted relationships appears to be an essential component in women's reporting they had all the information they need to talk with their daughters about breast cancer.

Young-onset breast cancers tend to be more aggressive than later-onset tumors and may have different risk factor profiles. Among young-onset cases, there may also be etiologic differences between ductal carcinomas in situ (DCIS) and invasive breast cancer, particularly if some factors promote malignant transformation. We evaluated the association between several potential risk factors and young-onset breast cancer in the Two Sister Study (2008–2010), a sister-matched case–control study involving 1,406 women diagnosed with breast cancer before age 50 (1,185 invasive, 221 DCIS) and 1,648 controls. Older age at menarche, younger age at menopause, premenopausal hysterectomy, early age at first-term pregnancy, obesity, and consumption of alcohol were associated with reduced risk of young-onset breast cancer. These patterns remained when we limited analysis to invasive breast cancers. In general, effect estimates were similar for young-onset invasive breast cancer and DCIS, although the number of DCIS cases was small. In this sister-matched case–control study of young-onset breast cancer, many of the studied risk factors were associated with young-onset invasive breast cancer. There were few discernable differences in risk factors for young-onset DCIS versus young-onset invasive breast cancer.

Background: Preterm birth is a common, costly and dangerous pregnancy complication. Seasonality of risk would suggest modifiable causes. Methods: We examine seasonal effects on preterm birth, using data from the Medical Birth Registry of Norway (2 321 652 births), and show that results based on births are misleading and a fetuses-at-risk approach is essential. In our harmonic-regression Cox proportional hazards model we consider fetal risk of birth between 22 and 37 completed weeks of gestation. We examine effects of both day of year of conception (for early effects) and day of ongoing gestation (for seasonal effects on labour onset) as modifiers of gestational-age-based risk. Results: Naive analysis of preterm rates across days of birth shows compelling evidence for seasonality (P

Estrogen plus progestin hormone therapy (HT) is associated with an increased risk of postmenopausal breast cancer, but few studies have examined the impact of HT use on the risk of breast cancer in younger women. We assessed the association between estrogen plus progestin HT or unopposed estrogen HT and young-onset breast cancer using data from the Two Sister Study (2008–2010), a sister-matched study of 1,419 cases diagnosed with breast cancer before the age of 50 years and 1,665 controls. We assessed exposures up to a family-specific index age to ensure comparable opportunities for exposures and used propensity scores to control for birth cohort effects on HT use. Ever HT use was uncommon (7% and 11% in cases and controls, respectively). Use of estrogen plus progestin was not associated with an increased risk of young-onset breast cancer (odds ratio = 0.80, 95% confidence interval: 0.41, 1.59). Unopposed estrogen use was inversely associated with the risk of young-onset breast cancer (odds ratio = 0.58, 95% confidence interval: 0.34, 0.99). Duration of use, age at first use, and recency of use did not modify these associations.

Background: The Sister Study was designed to address gaps in the study of environment and breast cancer by taking advantage of more frequent breast cancer diagnoses among women with a sister history of breast cancer and the presumed enrichment of shared environmental and genetic exposures. Objective: The Sister Study sought a large cohort of women never diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer. Methods: A multifaceted national effort employed novel strategies to recruit a diverse cohort, and collected biological and environmental samples and extensive data on potential breast cancer risk factors. Results: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35–74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and economically well off, substantial numbers of harder-to-recruit women also enrolled (race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income

Background: Preeclampsia (PE) is a dangerous and unpredictable pregnancy complication. A seasonal pattern of risk would suggest that there are potentially preventable environmental contributors, but prior analyses have not adjusted for confounding by PE risk factors that are associated with season of conception. Methods: Seasonal effects were modeled and tested by representing each day of the year as an angle on a unit circle and using trigonometric functions of those angles in predictive models, using “harmonic analysis.” We applied harmonic Cox regression to model confounder-adjusted effects of the estimated day of the year of conception on risk of PE for births from the Medical Birth Registry of Norway for deliveries between 1999 and 2009. We also examined effect measure modification by parity, latitude (region), fetal sex, and smoking. Results: In adjusted models, PE risk was related to season, with higher risk in spring conceptions and lower risk in autumn conceptions, with a risk amplitude (maximum compared with minimum) of about 20%. The pattern replicated across subpopulations defined by parity, latitude (region), fetal sex, and smoking. Conclusions: These results suggest that there is a seasonal driver for PE, with effects that are not modified by parity, latitude, fetal sex, or smoking. https://doi.org/10.1289/EHP963

The prevalence of binge drinking in the United States is rising. While alcohol is a risk factor for breast cancer, less is known about the impact of episodic heavy drinking. In 2003-2009, women aged 35-74 years who were free of breast cancer were enrolled in the Sister Study (n = 50,884). Residents of the United States or Puerto Rico who had a sister with breast cancer were eligible. Multivariable Cox regression was used to estimate adjusted hazard ratios and 95% confidence intervals for breast cancer. During follow-up (mean = 6.4 years), 1,843 invasive breast cancers were diagnosed. Increased breast cancer risk was observed for higher lifetime alcohol intake (for ≥230 drinks/year vs.

Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999-2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.

Background: Local inflammation after tubal ligation may affect ovarian function and breast cancer risk. Methods: We analysed tubal ligation, menopausal characteristics, and breast cancer risk in the Sister Study cohort (N=50 884 women). Results: Tubal ligation was associated with hot flashes (hazard ratio (HR) 1.09; 95% confidence interval (CI): 1.06–1.12) but not menopausal age (HR 0.99; 95% CI: 0.96–1.02). Tubal ligation did not have an impact on breast cancer overall (HR 0.95; 95% CI: 0.85–1.06), but had a suggested inverse relation with oestrogen receptor+/progesterone receptor+ invasive tumours (HR 0.84; 95% CI: 0.70–1.01), possibly because of subsequent hysterectomy/bilateral oophorectomy. Conclusion: Tubal ligation does not influence overall breast cancer risk.

Breast cancer is the most common cancer in women and the leading cause of cancer mortality for women worldwide (1). According to estimates for 2011, there are an estimated 230480 incident cases and 40000 deaths from the disease each year in the United States (2). The Gail model, based on known risk factors including age and reproductive, medical, and family history, is the best breast cancer risk prediction method currently available for populations, but its predictive accuracy for individuals is only about 58.0% to 59.0% (3,4). Rare inherited mutations of the breast cancer susceptibility genes BRCA1 and BRCA2 are strongly associated with familial breast cancer, but together only account for 5% to 10% of breast cancers in the United States (5). Recent genome-wide association studies (GWASs) have identified common polymorphisms associated with breast cancer risk. A panel of 10 such SNPs have a predictive accuracy of 59.7% (4). Thus the known environmental and common genetic risk factors for breast cancer have limited use in predicting a woman’s risk of disease (4–6). Epigenetic modifications, including DNA methylation, are increasingly recognized as important determinants of gene transcriptional regulation that have both heritable and acquired characteristics (7). Aberrant DNA methylation patterns are among the earliest and most common events in carcinogenesis (8), and genome-wide methylation profiling has recently been extended to retrospectively collected blood samples in case–control studies of ovarian, bladder, and head and neck cancers (9–11). But unlike genotype, which remains constant, epigenetic modifications may differ from cell to cell, over time, and with exposure, making the results of case–control studies subject to a number of potential biases (12). In this study we used genomic arrays of 27578 CpGs and prospectively collected blood samples from women in the Sister Study cohort to compare women who subsequently developed breast cancer to those who remained cancer-free. We use these data to address two questions: Does the epigenetic profile differ between women who subsequently develop cancer vs those who do not? Within the case subject group, is there an effect of time to diagnosis—the interval between blood draw and clinical diagnosis of disease? In addition, we examined the predictive power of blood methylation compared with the Gail model and GWAS single nucleotide polymorphisms (SNPs).

Early menarche is related to increased risk of breast cancer. The number of established factors that contribute to early menarche is limited. We studied prenatal and infant exposures in relation to age at menarche in a nationwide cohort of women who have a family history of breast cancer.The study comprised 33,501 women in the Sister Study who were 35-59 years of age at baseline (2003-2009). We used polytomous logistic regression to estimate separate relative risk ratios (rRRs) and 95% confidence intervals (CIs) for associations of self-reported exposures with menarche at ≤10, 11, 14, and ≥15 years relative to menarche at 12-13 years.Early menarche (≤10 or 11 years) was associated with having low birth weight, having had a teenage mother, being firstborn, and specific prenatal exposures: mother's smoking, diethylstilbestrol (DES), prepregnancy diabetes, and pregnancy-related hypertensive disorder. Prenatal exposures most strongly associated with very early menarche (≤10 years) were DES (rRR = 1.56 [95% CI = 1.24-1.96]), maternal prepregnancy diabetes (2.24 [1.37-3.68]), and pregnancy-related hypertensive disorder (1.45 [1.18-1.79]). Soy formula was associated with both very early menarche (1.21 [0.94-1.54]) and late menarche (14 years: 1.17 [0.98-1.40] or ≥15 years: 1.28 [1.06-1.56]).Although menarche is only one marker of pubertal development, it is a commonly used surrogate. The observed associations of prenatal DES and soy formula exposure with age at menarche are consistent with animal data on exogenous estrogens and pubertal timing. Early-life exposures may confound associations between age at menarche and hormonally dependent outcomes in adults.

Although microcephaly is a feature of Fetal Alcohol Syndrome, it is currently unknown whether low-to-moderate prenatal alcohol exposure affects head circumference. Small magnitude associations reported in observational studies are likely to be misleading due to confounding and misclassification biases. Alternative analytical approaches such as the use of family negative controls (e.g. comparing the effects of maternal and paternal exposure) could help disentangle causal effects. We investigated the association of maternal and paternal alcohol drinking before and early in pregnancy with infant head circumference, using data from 68,244 mother-father-offspring trios from the Norwegian Mother and Child Cohort Study (MoBa) (1999–2009). In analyses adjusted for potential confounders, we found no consistent pattern of association between maternal or paternal alcohol intake before or during pregnancy and offspring head circumference modelled as a continuous outcome. However, we found higher odds of microcephaly at birth for higher paternal, but not maternal, alcohol consumption before pregnancy, and similar but weaker effect estimates for first trimester drinking. Associations with paternal drinking before pregnancy were unexpected and should be regarded as hypothesis generating, until independently replicated, although potentially important given the absence of guidelines on safe drinking levels for men in couples trying for a pregnancy.

Background Smoking during pregnancy is linked to having a small for gestational age (SGA) baby. We estimated SGA risk among women who smoked persistently, quit smoking or started smoking during their first two pregnancies. Methods Data from the population-based Medical Birth Registry of Norway was used to evaluate self-reported smoking at the beginning and end of two successive pregnancies among 118 355 Nordic women giving birth 1999–2014. Relative risks (RR) with 95% confidence intervals (CI) of SGA in the second pregnancy were estimated using adjusted generalised linear models with non-smokers during both pregnancies serving as referent category. Results Daily smokers throughout both pregnancies had almost threefold increased SGA risk in the second pregnancy (RR 2.9, 95% CI 2.7, 3.1). Daily smokers in the first pregnancy, who abstained in the second, had a 1.3-fold increased risk (95% CI 1.1, 1.5). Intermediate risks were found among persistent daily smokers who quit by the end of the second pregnancy (RR 2.0, 95% CI 1.6, 2.4) and non-smokers in first pregnancy who smoked daily throughout their second (RR 1.8, 95% CI 1.4, 2.3). Persistently smoking women without SGA in first pregnancy, had a 2.7-fold increased risk of SGA in second pregnancy (95% CI 2.5, 3.0). Conclusions Smoking throughout two successive pregnancies was associated with the greatest increased SGA risk compared with non-smokers, while cessation before or during the second pregnancy reduced this risk. Women who smoked in the first pregnancy without experiencing SGA are not protected against SGA in second pregnancy if they continue smoking.

Using individual participant data from six population-based case–control studies, we conducted pooled analyses to examine maternal alcohol consumption and the risk of clefts among >4600 infants with cleft lip only, cleft lip with cleft palate, or cleft palate only and >10,000 unaffected controls. We examined two first-trimester alcohol measures: average number of drinks/sitting and maximum number of drinks/sitting, with five studies contributing to each analysis. Study-specific odds ratios (ORs) were estimated using logistic regression and pooled to generate adjusted summary ORs. Across studies, 0.9–3.2 % of control mothers reported drinking an average of 5+ drinks/sitting, while 1.4–23.5 % reported drinking a maximum of 5+ drinks/sitting. Compared with non-drinkers, mothers who drank an average of 5+ drinks/sitting were more likely to deliver an infant with cleft lip only (pooled OR 1.48; 95 % confidence intervals 1.01, 2.18). The estimate was higher among women who drank at this level 3+ times (pooled OR 1.95; 1.23, 3.11). Ever drinking a maximum of 5+ drinks/sitting and non-binge drinking were not associated with cleft risk. Repeated heavy maternal alcohol consumption was associated with an increased risk of cleft lip only in offspring. There was little evidence of increased risk for other cleft types or alcohol measures. © 2016, The Author(s).

Hormones play an important role in breast cancer. Well-documented risk factors, such as early menarche, late age at first birth, late menopause, and long-term hormone therapy, are related to the duration of lifetime exposure to estrogen and progesterone (1,2). Treatment with ovulation-stimulating fertility drugs causes recruitment and maturation of multiple ovarian follicles, temporarily elevating estrogen; in women treated with clomiphene citrate (CC), the peak serum levels of estrogen are two- to threefold higher than normal (average: 200 pg/mL at peak) (3,4), and peak levels are even higher in women who undergo in vitro fertilization (IVF) treatment, which typically involves the use of follicle- stimulating hormone (FSH)-containing drugs (5,6). If pregnancy results, the supernumerary ovarian corpora lutea produce both estrogen and progesterone and raise the levels far above normal in the first 9 weeks (7,8). It is estimated that 6% of babies born in the United States in 2005 were conceived with ovulation-stimulating drugs (9). The widespread use of ovulation-stimulating fertility drugs has raised concern about possible implications for breast cancer. Some, but not all, studies report increased risk following infertility treatment (10–31). A recent meta-analysis was inconclusive, citing methodological limitations of previous studies, which included infrequent use of fertility drugs, unspecified treatments, incomplete control for confounding, and small numbers of case subjects (32). Breast cancers in women younger than age 50 years are rare but can be aggressive and carry a worse prognosis compared with those in older women (33), and distinct risk factors are associated with such young-onset disease. We conducted a sister-controlled study and examined whether use of ovulation-stimulating fertility drugs is associated with risk of breast cancer in women younger than age 50 years. To examine the possible consequences of the high hormonal exposures experienced in early pregnancy by women who conceive with ovarian hyperstimulation, we separated fertility-drug exposures according to whether or not that treatment had resulted in a pregnancy lasting at least 10 weeks.

Rheumatoid arthritis (RA) has been associated with lower socioeconomic status (SES), but the reasons for this are not known.To examine childhood SES measures, SES trajectory and other perinatal factors in relation to RA.The sample included 50 884 women, aged 35-74 (84% non-Hispanic white) enrolled 2004-9 in a US national cohort study. In baseline questionnaires, cases (N=424, 0.8%) reported RA diagnosis after age 16, ever use of disease-modifying antirheumatic drugs or steroids for RA and ≥6 weeks bilateral joint swelling. Childhood SES measures are presented as OR and 95% CI adjusted for age and race/ethnicity. Analyses of perinatal factors also adjusted for childhood SES, and joint effects of childhood and adult SES and smoking exposures were evaluated.Patients with RA reported lower childhood household education (12 years vs college degree; OR=1.7; 95% CI 1.1 to 2.5), food insecurity (OR=1.5, 95% CI 1.1 to 2.0) and young maternal age (20 vs 20-34 years; OR=1.7, 95% CI 1.2 to 2.5), with a trend (p0.0001) for increasing number of adverse factors (OR=3.0; 95% CI 1.3 to 7.0; 4 vs 0 factors) compared with non-cases. Low birth weight (2500 g) [corrected] and preconception paternal smoking were independently associated with RA. Together, lower childhood SES and adult education (college degree) were associated with RA (interaction p=0.03), with a joint effect magnitude similar to a history of paternal and adult smoking.RA was associated with low childhood SES sustained into adulthood, with cumulative effects across multiple measures, suggesting the importance of other unmeasured factors linking SES and RA.

Background: Uterine leiomyomata (fibroids) are hormonally responsive tumors, but little is known about risk factors. Early-life exposures may influence uterine development and subsequent response to hormones in adulthood. An earlier analysis of non-Hispanic white women who participated in the Sister Study found associations between several early-life factors and early-onset fibroids. Objectives: We evaluated associations of early-life and childhood exposures with early-onset fibroids among black women and compared the results with those found among white women. Methods: We analyzed baseline data from 3,534 black women, 35–59 years of age, in the Sister Study (a nationwide cohort of women who had a sister diagnosed with breast cancer) who self-reported information on early-life and childhood exposures. Early-onset fibroids were assessed based on self-report of a physician diagnosis of fibroids by the age of 30 years (n = 561). We estimated risk ratios (RR) and 95% confidence intervals (CI) from log-binomial regression models. Results: Factors most strongly associated with early-onset fibroids were in utero diethylstilbestrol (DES; RR = 2.02; 95% CI: 1.28, 3.18), maternal prepregnancy diabetes or gestational diabetes (RR = 1.54; 95% CI: 0.95, 2.49), and monozygotic multiple birth (RR = 1.94; 95% CI: 1.26, 2.99). We also found positive associations with having been taller or thinner than peers at the age of 10 years and with early-life factors that included being the firstborn child of a teenage mother, maternal hypertensive disorder, preterm birth, and having been fed soy formula. Conclusions: With the exception of monozygotic multiple birth and maternal hypertensive disorder, early-life risk factors for early-onset fibroids for black women were similar to those found for white women. However, in contrast to whites, childhood height and weight, but not low socioeconomic status indicators, were associated with early-onset fibroids in blacks. The general consistency of early-life findings for black and white women supports a possible role of early-life factors in fibroid development.

The authors conducted a meta-analysis of the association between smoking before a first pregnancy, when undifferentiated breast tissue may be vulnerable to tobacco carcinogens, and the risk of breast cancer. A search of the published literature through August 2010 identified 23 papers reporting on associations between smoking before a first pregnancy and breast cancer. Odds ratios or hazard ratios and 95% confidence intervals, adjusted for known or suspected breast cancer risk factors, were abstracted from each study. Data were pooled using both fixed- and random-effects models. The fixed-effect summary risk ratio for breast cancer among the women who smoked before their first pregnancy versus women who had never smoked was 1.10 (95% confidence interval: 1.07, 1.14); the random-effects estimate was similar. The separate fixed-effect risk ratios for smoking only before the first pregnancy (5 studies) or only after the first pregnancy (16 studies) were both 1.07, providing no evidence that breast tissue is more susceptible to malignant transformation from smoking before the first pregnancy. While these small summary risk ratios may represent causal effects, residual confounding could readily produce estimates of this size in the absence of any causal effect.

Oocytes are formed in utero; menopause occurs when the oocyte pool is depleted. The authors hypothesized that early-life events could affect the number of a woman's oocytes and determine age at menopause. To test their hypothesis, the authors conducted a secondary analysis of baseline data from 22,165 participants in the Sister Study (2003-2007) who were aged 35-59 years at enrollment. To estimate the association between early-life events and age at natural menopause, the authors used Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals, adjusting for current age, race/ethnicity, education, childhood family income, and smoking history. Earlier menopause was associated with in-utero diethylstilbestrol exposure (hazard ratio (HR) = 1.45, 95% confidence interval (CI): 1.27, 1.65). Suggestive associations included maternal prepregnancy diabetes (HR = 1.33, 95% CI: 0.89, 1.98) and low birth weight (HR = 1.09, 95% CI: 0.99, 1.20). Having a mother aged 35 years or older at birth appeared to be associated with a later age at menopause (HR = 0.95, 95% CI: 0.89, 1.01). Birth order, in-utero smoke exposure, and having been breastfed were not related to age at menopause. In-utero and perinatal events may subsequently influence age at menopause.

Background: Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation. Objective: The objective was to examine whether multivitamin use is associated with longer telomeres in women. Design: We performed a cross-sectional analysis of data from 586 early participants (age 35‐74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction. Results: After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend ¼ 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore, intakes of both nutrients were associated with telomere length among women who did not take multivitamins. Conclusion: This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women. Am J Clin Nutr 2009;89:1857‐63.

A fin de ahondar en la visión que predominaba a principios del siglo XX sobre el maltrato infantil, sus efectos sobre el comportamiento de los jóvenes y las estrategias para prevenir la delincuencia juvenil se ofrece una síntesis en inglés de la conferencia " La delincuencia infantil y la profilaxis del crimen" , presentada en 1929 por el pediatra e higienista social colombiano Jorge Bejarano Martínez y se resaltan sus teorías sobre el abuso y la desatención infantil, y la prevención del crimen. Mediante citas del texto original de 88 páginas, esta síntesis presenta los puntos de vista de Bejarano sobre las condiciones sociales que él consideraba cruciales en la etiología de la delincuencia infantil en Colombia (la falta de mecanismos sociales de protección y de oportunidades educacionales para los niños, la pobreza en el hogar, el trabajo infantil, el abandono, y el abuso y la desatención de los niños). Aunque en Colombia aún subsisten problemas de fondo similares, se han logrado avances en la protección de los niños contra el abuso y la desatención para prevenir la delincuencia en etapas posteriores de su vida. Esta conferencia demuestra que Bejarano fue un precursor de estos esfuerzos en América Latina y ofrece elementos sobre los orígenes de las estrategias actuales para reducir la violencia juvenil.

A fin de ahondar en la vision que predominaba a principios del siglo XX sobre el maltrato infantil, sus efectos sobre el comportamiento de los jovenes y las estrategias para prevenir la delincuencia juvenil se ofrece una sintesis en ingles de la conferencia " La delincuencia infantil y la profilaxis del crimen" , presentada en 1929 por el pediatra e higienista social colombiano Jorge Bejarano Martinez y se resaltan sus teorias sobre el abuso y la desatencion infantil, y la prevencion del crimen. Mediante citas del texto original de 88 paginas, esta sintesis presenta los puntos de vista de Bejarano sobre las condiciones sociales que el consideraba cruciales en la etiologia de la delincuencia infantil en Colombia (la falta de mecanismos sociales de proteccion y de oportunidades educacionales para los ninos, la pobreza en el hogar, el trabajo infantil, el abandono, y el abuso y la desatencion de los ninos). Aunque en Colombia aun subsisten problemas de fondo similares, se han logrado avances en la proteccion de los ninos contra el abuso y la desatencion para prevenir la delincuencia en etapas posteriores de su vida. Esta conferencia demuestra que Bejarano fue un precursor de estos esfuerzos en America Latina y ofrece elementos sobre los origenes de las estrategias actuales para reducir la violencia juvenil.

Use of complementary and alternative medicine (CAM) is high among U.S. women, yet information is limited on use among women at increased breast cancer risk. We analyzed CAM use among women with a family history of breast cancer. CAM use was analyzed among women enrolled 2003-2009 in the Sister Study cohort. Eligible women were aged 35-74, U.S. or Puerto Rican residents, no personal history of breast cancer, and had ≥1 sister with breast cancer. Baseline data on CAM use in the past year were available for 49,734 women. Logistic regression models examined the association between CAM use and Gail Model breast cancer risk score. Results were compared to female participants in the 2007 National Health Interview Survey (n = 7965). Among Sister Study participants, there was high use of vitamin/mineral supplements (79 %), mind-body practices (41 %), manipulative/body-based practices (32 %), and botanicals (23 %). Overall use was higher than the U.S. female population. No association was observed between familial breast cancer risk and CAM use. Black women were more likely to use spirituality/meditation-based CAM modalities, while non-Hispanic white and Asian women were high users of dietary supplements. In a cohort of women with increased breast cancer risk due to family history, CAM use is higher than women in the general U.S. population and is associated with race/ethnicity. Use was not associated with breast cancer risk. Given the high prevalence of CAM use among women at risk for breast caner, research on the effectiveness of CAM use for disease prevention is needed.

Migraine headache is often timed with the menstrual cycle. Some studies have reported reduced risk of breast cancer in migraineurs but most of those did not distinguish menstrually-related from non-menstrually-related migraine. To examine the possible associations between breast cancer and migraine overall and between cancer subcategories and the two migraine subtypes, we used a cohort study of 50,884 women whose sister had breast cancer and a sister-matched case-control study including 1,418 young-onset (in situ (HR = 0.77; 95% CI (0.62,0.96)). Also, women with non-menstrually-related migraine had increased risk (HR = 1.30, 95% CI (0.93,1.81)) while women with menstrually-related migraine had decreased risk (HR = 0.63, 95% CI (0.42,0.96)) of hormone-receptor-negative (ER−/PR−) cancer, with a significant contrast in estimated effects (P = 0.005). While replication of these subset-based findings will be needed, effect specificity could suggest that while migraine has little overall association with breast cancer, menstrual migraine may be associated with reduced risk of ER−/PR− breast cancer.

Summary Objective From August 1999 to July 2001, asylum seekers who had come to Switzerland from Kosovo were repatriated. The present study aimed to assess the relationship between living conditions during asylum in Switzerland and health status among returnees. Study design Cross-sectional survey of 319 ethnic Albanian families in Kosovo, selected from a list of 12 900 heads of households who had received repatriation aid. Methods Consenting household members aged 16 years or more who had received asylum in Switzerland were interviewed during the autumn of 2001. Questions explored living conditions during asylum, present socio-economic conditions (World Bank Kosovo Poverty Assessment Survey), subjective physical and mental health [Medical Outcomes Study 36-item Short Form Health Survey (SF-36)], traumatic events (Harvard Trauma Questionnaire) and symptoms of post-traumatic stress disorder (PTSD; Mini International Neuropsychiatric Interview). Results Ninety-four per cent of selected households were located. Among the 580 participants, 25.5% suffered from PTSD and 65% lived in extreme poverty. Subjective health scores, measured by SF-36, were low, particularly for those affected by PTSD. Among living conditions in the host country, duration of stay longer than 26 weeks was associated with lower mental health scores, particularly among people with PTSD. Conclusions Two years after the conflict, returnees had low health scores. The association between duration of stay and lower mental health scores may reflect the stress of adapting to asylum or the consequence of compulsory repatriation. This study has implications for the emerging healthcare system in Kosovo and for policies of asylum in host countries.

OBJECTIVE To assess the effects of socioeconomic factors on the association between parity and long-term maternal mortality. METHODS This was a population-based cohort study of mothers with births registered in the Medical Birth Registry of Norway during the period 1967-2009. We estimated age-specific (40-69 years) cardiovascular and noncardiovascular mortality ratios by number of births using Cox proportional hazard models. To assess effect modification by mothers' attained education, we stratified on low (less than 11 years) and high (11 years or greater) educational level. We further evaluated fathers' mortality by number of births using the same analytical approach. RESULTS Mothers with low education had higher mortality (cardiovascular: hazard ratio 2.62, 95% confidence interval [CI] 2.34-2.93, noncardiovascular: hazard ratio 1.67, 95% CI 1.62-1.73). Among mothers with low education, cardiovascular mortality increased linearly with each additional birth above one (P trend=.02). In contrast, among mothers with high education, cardiovascular mortality declined with added births (P trend=.045). For noncardiovascular mortality there was no association among mothers with low education, whereas mortality declined with increasing number of births among mothers with high education (P trend

Migraine headache is often timed with the menstrual cycle. Some studies have reported reduced risk of breast cancer in migraineurs but most of those did not distinguish menstrually-related from non-menstrually-related migraine. To examine the possible associations between breast cancer and migraine overall and between cancer subcategories and the two migraine subtypes, we used a cohort study of 50,884 women whose sister had breast cancer and a sister-matched case-control study including 1,418 young-onset (in situ (HR = 0.77; 95% CI (0.62,0.96)). Also, women with non-menstrually-related migraine had increased risk (HR = 1.30, 95% CI (0.93,1.81)) while women with menstrually-related migraine had decreased risk (HR = 0.63, 95% CI (0.42,0.96)) of hormone-receptor-negative (ER−/PR−) cancer, with a significant contrast in estimated effects (P = 0.005). While replication of these subset-based findings will be needed, effect specificity could suggest that while migraine has little overall association with breast cancer, menstrual migraine may be associated with reduced risk of ER−/PR− breast cancer.

Background: Some but not all past studies reported associations between components of air pollution and breast cancer, namely fine particulate matter ≤2.5 μm (PM2.5) and nitrogen dioxide (NO2). It is yet unclear whether risks differ according to estrogen receptor (ER) and progesterone receptor (PR) status. Methods: This analysis includes 47,591 women from the Sister Study cohort enrolled from August 2003 to July 2009, in whom 1,749 invasive breast cancer cases arose from enrollment to January 2013. Using Cox proportional hazards and polytomous logistic regression, we estimated breast cancer risk associated with residential exposure to NO2, PM2.5, and PM10. Results: Although breast cancer risk overall was not associated with PM2.5 [HR = 1.03; 95% confidence intervals (CI), 0.96–1.11], PM10 (HR = 0.99; 95% CI, 0.98–1.00), or NO2 (HR = 1.02; 95% CI, 0.97–1.07), the association with NO2 differed according to ER/PR subtype (P = 0.04). For an interquartile range (IQR) difference of 5.8 parts per billion (ppb) in NO2, the relative risk (RR) of ER+/PR+ breast cancer was 1.10 (95% CI, 1.02–1.19), while there was no evidence of association with ER−/PR− (RR = 0.92; 95% CI, 0.77–1.09; Pinteraction = 0.04). Conclusions: Within the Sister Study cohort, we found no significant associations between air pollution and breast cancer risk overall. But we observed an increased risk of ER+/PR+ breast cancer associated with NO2. Impact: Though these results suggest there is no substantial increased risk for breast cancer overall in relation to air pollution, NO2, a marker of traffic-related air pollution, may differentially affect ER+/PR+ breast cancer. Cancer Epidemiol Biomarkers Prev; 24(12); 1907–9. ©2015 AACR.

Maternal cigarette smoking is a well-established risk factor for oral clefts. Evidence is less clear for passive (secondhand) smoke exposure. We combined individual-level data from 4 population-based studies (the Norway Facial Clefts Study, 1996-2001; the Utah Child and Family Health Study, 1995-2004; the Norwegian Mother and Child Cohort Study, 1999-2009; and the National Birth Defects Prevention Study (United States), 1999-2007) to obtain 4,508 cleft cases and 9,626 controls. We categorized first-trimester passive and active smoke exposure. Multivariable logistic models adjusted for possible confounders (maternal alcohol consumption, use of folic acid supplements, age, body size, education, and employment, plus study fixed effects). Children whose mothers actively smoked had an increased risk of oral clefts (odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.11, 1.46). Children of passively exposed nonsmoking mothers also had an increased risk (OR = 1.14, 95% CI: 1.02, 1.27). Cleft risk was further elevated among babies of smoking mothers who were exposed to passive smoke (OR = 1.51, 95% CI: 1.35, 1.70). Using a large pooled data set, we found a modest association between first-trimester passive smoking and oral clefts that was consistent across populations, diverse study designs, and cleft subtypes. While this association may reflect subtle confounding or bias, we cannot rule out the possibility that passive smoke exposure during pregnancy is teratogenic.

Women with preeclamptic pregnancies have increased long-term cardiovascular disease (CVD) mortality. We explored this mortality risk among women with placental abruption, another placental pathology. We used linked Medical Birth Registry and Death Registry data to study CVD mortality among over two million women with a first singleton birth between 1967 and 2002 in Norway and 1973 and 2003 in Sweden. Women were followed through 2009 and 2010, respectively, to ascertain subsequent pregnancies and mortality. Cox regression analysis was used to estimate associations between placental abruption and cardiovascular mortality adjusting for maternal age, education, year of the pregnancy and country. There were 49,944 deaths after an average follow-up of 23 years, of which 5453 were due to CVD. Women with placental abruption in first pregnancy (n = 10,981) had an increased risk of CVD death (hazard ratio 1.8; 95 % confidence interval 1.3, 2.4). Results were essentially unchanged by excluding women with pregestational hypertension, preeclampsia or diabetes. Women with placental abruption in any pregnancy (n = 23,529) also had a 1.8-fold increased risk of CVD mortality (95 % confidence interval 1.5, 2.2) compared with women who never experienced the condition. Our findings provide evidence that placental abruption, like other placental complications of pregnancy, is associated with women’s increased risk of later CVD mortality. publishedVersion

An estimated 15% of US women age 35 to 79 years are eligible for breast cancer chemoprevention; however, less than 5% may have favorable risk-benefit profiles (1). Tamoxifen can decrease risk of invasive breast cancer up to 48% and was US Food and Drug Administration (FDA)–approved for primary prevention in 1998 for women 35 years and older at high risk of breast cancer (typically determined by a five-year probability of developing invasive breast cancer greater than 1.67%) and low risk of serious side effects (including endometrial cancer, stroke, pulmonary embolism, deep vein thrombosis, and cataract) (2–6). It is the only approved pharmacologic agent for breast cancer prevention available to premenopausal women (7). The US Preventive Services Task Force (USPSTF) recently published a recommendation statement for risk reduction of primary breast cancer that encourages clinicians to offer to prescribe tamoxifen or raloxifene to reduce breast cancer risk (8). National estimates indicate that less than 1% of eligible women use tamoxifen for prevention (9). It is unknown why few women use tamoxifen for breast cancer prevention, although vasomotor symptoms, increased risk of adverse health effects, and difficulties in estimating or communicating risk-benefit profiles can be deterrents. Whether women who do use tamoxifen for breast cancer prevention are among those most likely to benefit is also unknown. In previous studies, willingness to use tamoxifen has not consistently been associated with invasive breast cancer risk (10–13). Further, substantial nonadherence to the recommended five-year course of tamoxifen has been reported in prevention trials. To date, there has been no large study of tamoxifen users outside of a trial setting to evaluate risk-benefit profiles or early discontinuation. We examined risk-benefit profiles of women who used tamoxifen for primary breast cancer prevention and characteristics associated with initiation and discontinuation among a sample of adult US and Puerto Rican women with a first-degree family history of breast cancer.

The Norwegian Mother and Child Cohort Study (MoBa) is a valuable resource for the study of the effects of maternal alcohol consumption. MoBa’s strengths include a population-based sample of over 107,000 pregnancies, concurrent and retrospective assessment of maternal prenatal and postnatal alcohol consumption, and prospective follow-up for pregnancy and child outcomes. Direct questions were asked on the frequency, dose and timing of maternal alcohol consumption. Screening tools including the T-ACE and partial Rutgers Alcohol Problem Index were used to identify women at risk for drinking during pregnancy. Comprehensive information on potential confounders was collected including maternal medical history, reproductive history, smoking, and other substance use. The detailed alcohol data allow the differentiation between non-binge and binge-level drinking, important for studying different thresholds of exposure. The availability of maternal and infant DNA enables the study of genetic differences in alcohol metabolism. Besides conventional analyses, sibship studies of differentially exposed siblings can be conducted among the offspring of over 15,000 women who participated in the study for more than one pregnancy. Although there are low levels of social disadvantage in Norway (poverty increases the risk of harms from prenatal drinking), binge drinking is a common pattern of consumption and previous studies found that drinking alcohol during pregnancy is not uncommon. Here, I provide a brief review of prenatal alcohol literature and measurement issues, describe MoBa alcohol variables, and discuss how MoBa can contribute to maternal alcohol research within the context of Norway.

Limited prior data suggest an association between traffic-related air pollution and incident asthma in adults. No published studies assess the effect of long-term exposures to particulate matter less than 2.5 μm in diameter (PM2.5) on adult incident asthma.To estimate the association between ambient air pollution exposures (PM2.5 and nitrogen dioxide, NO2) and development of asthma and incident respiratory symptoms.The Sister Study is a U.S. cohort study of risk factors for breast cancer and other health outcomes (n = 50,884) in sisters of women with breast cancer (enrollment, 2003-2009). Annual average (2006) ambient PM2.5 and NO2 concentrations were estimated at participants' addresses, using a national land-use/kriging model incorporating roadway information. Outcomes at follow-up (2008-2012) included incident self-reported wheeze, chronic cough, and doctor-diagnosed asthma in women without baseline symptoms.Adjusted analyses included 254 incident cases of asthma, 1,023 of wheeze, and 1,559 of chronic cough. For an interquartile range (IQR) difference (3.6 μg/m(3)) in estimated PM2.5 exposure, the adjusted odds ratio (aOR) was 1.20 (95% confidence interval [CI] = 0.99-1.46, P = 0.063) for incident asthma and 1.14 (95% CI = 1.04-1.26, P = 0.008) for incident wheeze. For NO2, there was evidence for an association with incident wheeze (aOR = 1.08, 95% CI = 1.00-1.17, P = 0.048 per IQR of 5.8 ppb). Neither pollutant was significantly associated with incident cough (PM2.5: aOR = 0.95, 95% CI = 0.88-1.03, P = 0.194; NO2: aOR = 1.00, 95% CI = 0.93-1.07, P = 0.939).Results suggest that PM2.5 exposure increases the risk of developing asthma and that PM2.5 and NO2 increase the risk of developing wheeze, the cardinal symptom of asthma, in adult women.

Organic solvents are ubiquitous in occupational settings where they may contribute to risks for carcinogenesis. However, there is limited information on organic solvents as human breast carcinogens. We examined the relationship between occupational exposure to solvents and breast cancer in a prospective study of 47,661 women with an occupational history in the Sister Study cohort. Occupational solvent exposure was categorized using self-reported job-specific solvent use collected at baseline. Multivariable Cox regression analyses were used to assess breast cancer risk, adjusting for established breast cancer risk factors. A total of 1,798 women were diagnosed with breast cancer during follow-up, including 1,255 invasive cases. Overall the risk of invasive breast cancer was not associated with lifetime exposure to solvents [HR, 1.04; 95% confidence interval (CI), 0.88–1.24]. Parous women who worked with solvents before their first full-term birth had an increased risk of estrogen receptor–positive invasive breast cancer compared with women who never worked with solvents (HR, 1.39; 95% CI, 1.03–1.86). A significantly elevated risk for estrogen receptor–positive invasive breast cancer was associated with solvent exposure among clinical laboratory technologists and technicians (HR, 2.00; 95% CI, 1.07–3.73). Occupational exposure to solvents before first birth, a critical period of breast tissue differentiation, may result in increased vulnerability for breast cancer. Our findings suggest a need for future studies in this area to focus on exposure time windows and solvent types in different occupational settings. Cancer Res; 74(11); 3076–83. ©2014 AACR.

Aims. To examine the effectiveness of brief behavioral interventions adapting the principles and techniques of Motivational Interviewing (MI) to four behavioral domains: substance abuse, smoking, HIV risk and diet/exercise. Design. We conducted a systematic review of 29 randomized trials of MI interventions. Data on methodological quality were extracted and tabulated. Between-group behavior change effect sizes and confidence intervals were calculated for each study. Findings. Due to varying intervention time lengths, targeted problem behaviors, settings and interventionists' backgrounds and skill levels, outcomes were not combined meta-analytically. Sixty per cent of the 29 studies yielded at least one significant behavior change effect size. No significant association between length of follow-up time and magnitude of effect sizes was found across studies. There was substantial evidence that MI is an effective substance abuse intervention method when used by clinicians who are non-specialists in substance abuse treatment, particularly when enhancing entry to and engagement in more intensive substance abuse treatment treatment-as-usual. Data were inadequate to judge the effect of MI in the other domains. Client attribute-treatment interactions were understudied and the sparse and inconsistent findings revealed little about the mechanism by which MI works or for whom it works best. Conclusion. To determine more effectively how well MI works in domains other than substance abuse and for whom it works best in all domains, researchers should study MI with risk behaviors other than substance abuse, while examining both interactions and the theoretical components of MI.

Background Many women drink during pregnancy and lactation despite recommendations to abstain. In animals, alcohol exposure during pregnancy and lactation influences lung and immune development, plausibly increasing risk of asthma and lower respiratory tract infections (LRTIs). Studies in humans are few. Methods In the Norwegian Mother and Child Cohort Study, we examined maternal alcohol intake during pregnancy and lactation in relation to risk of current asthma at 36 months (49,138 children), recurrent LRTIs by 36 months (39,791 children), and current asthma at 7 years (13,253 children). Mothers reported frequency and amount of alcohol intake each trimester and the first 3 months following delivery. We calculated adjusted relative risk (aRR), comparing children of drinkers to nondrinkers, using Generalized Linear Models. Results A total of 31.8% of mothers consumed alcohol during first trimester, 9.7% during second trimester, and 15.6% during third trimester. Infrequent and low-dose prenatal alcohol exposure showed a modest statistically significant inverse association with current asthma at 36 months (aRRs ~ 0.85). No association was seen with the highest alcohol intakes during the first trimester when alcohol consumption was most common. RRs of maternal alcohol intake during pregnancy with recurrent LRTIs were ~1, with sporadic differences in risk for some metrics of intake, but without any consistent pattern. For current asthma at 7 years, similar inverse associations were seen as with current asthma at 36 months but were not statistically significant. Among children breastfed throughout the first 3 months of life, maternal alcohol intake during this time was not significantly associated with any of the 3 outcomes. Conclusions The low levels of alcohol exposure during pregnancy or lactation observed in this cohort were not associated with increased risk of asthma or recurrent LRTIs. The slight inverse associations of infrequent or low-dose prenatal alcohol exposure with asthma may not be causal.

Background Exposure to air pollution has been consistently associated with cardiovascular morbidity and mortality, but mechanisms remain uncertain. Associations with blood pressure (BP) may help to explain the cardiovascular effects of air pollution. Objective We examined the cross-sectional relationship between long-term (annual average) residential air pollution exposure and BP in the National Institute of Environmental Health Sciences’ Sister Study, a large U.S. cohort study investigating risk factors for breast cancer and other outcomes. Methods This analysis included 43,629 women 35–76 years of age, enrolled 2003–2009, who had a sister with breast cancer. Geographic information systems contributed to satellite-based nitrogen dioxide (NO2) and fine particulate matter (≤ 2.5 μm; PM2.5) predictions at participant residences at study entry. Generalized additive models were used to examine the relationship between pollutants and measured BP at study entry, adjusting for cardiovascular disease risk factors and including thin plate splines for potential spatial confounding. Results A 10-μg/m3 increase in PM2.5 was associated with 1.4-mmHg higher systolic BP (95% CI: 0.6, 2.3; p < 0.001), 1.0-mmHg higher pulse pressure (95% CI: 0.4, 1.7; p = 0.001), 0.8-mmHg higher mean arterial pressure (95% CI: 0.2, 1.4; p = 0.01), and no significant association with diastolic BP. A 10-ppb increase in NO2 was associated with a 0.4-mmHg (95% CI: 0.2, 0.6; p < 0.001) higher pulse pressure. Conclusions Long-term PM2.5 and NO2 exposures were associated with higher blood pressure. On a population scale, such air pollution–related increases in blood pressure could, in part, account for the increases in cardiovascular disease morbidity and mortality seen in prior studies. Citation Chan SH, Van Hee VC, Bergen S, Szpiro AA, DeRoo LA, London SJ, Marshall JD, Kaufman JD, Sandler DP. 2015. Long-term air pollution exposure and blood pressure in the Sister Study. Environ Health Perspect 123:951–958; http://dx.doi.org/10.1289/ehp.1408125