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We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine effectiveness against infection (VE-I) and death (VE-D) by vaccine type in 780,225 veterans in the Veterans Health Administration, covering 2.7% of the US population. From February to October 2021, VE-I declined for all vaccine types, and the decline was greatest for the Janssen vaccine, resulting in a VE-I of 13.1%. Although breakthrough infection increased risk of death, vaccination remained protective against death in persons who became infected during the Delta variant surge. From July to October 2021, VE-D for age

ObjectivesSARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use.DesignThis is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality.SettingMedical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality.Participants9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed.Outcome measureDeath from any cause within 60 days of COVID-19 diagnosis was examined.ResultsDiscontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2-1.7). Initiating (OR: 0.3; 95% CI 0.2-0.5) or continuous (OR: 0.6; 95% CI 0.5-0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment.ConclusionsRecent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.

BackgroundSerum DDTs during or just after pregnancy were associated with breast cancer in mothers (F0), and with breast cancer, mammographic density, and obesity in adult daughters (F1) in the Child Health and Development Studies multi-generational cohort in prior publications. Here, we investigate F0 perinatal serum DDT associations with granddaughters'(F2) measured obesity at a median age of 26 and self-reported age at menarche.MethodsF2 weight, height and waist circumference were measured by trained examiners. o,p'-DDT, p,p'-DDT and p,p'-DDE were measured in archived F0 perinatal serum. F0 DDT associations with F2 outcomes, accounting for F1 characteristics, were estimated in log-linear models adjusted for F0 and F1 body mass index (BMI), race, and menarche timing (N = 258 triads for obesity; N = 235 triads for early menarche). Interactions between F0 BMI and DDTs were estimated.ResultsF0 o,p'-DDT was associated with F2 obesity [Odds ratio (OR), 2.6; 95% confidence interval (CI), 1.3-6.7; tertile 3 vs. 1), among normal weight F0 (70%), but not among overweight and obese F0 (P interaction = 0.03), independent of other DDTs. F0 o,p'-DDT was also associated with F2 early menarche (OR, 2.1; 95% CI, 1.1-3.9, tertile 3 vs. 1) and this association was not modified by F0 BMI.ConclusionsAncestral exposure to environmental chemicals, banned decades ago, may influence the development of earlier menarche and obesity, which are established risk factors for breast cancer and cardiometabolic diseases.ImpactDiscovery of actionable biomarkers of response to ancestral environmental exposures in young women may provide opportunities for breast cancer prevention.See related commentary by Fenton and Boyles, p. 1459.

BackgroundObesity is a malnourishment epidemic worldwide. A meta-analysis of prospective human studies across the world demonstrated a consistent positive association between maternal exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE) and children with obesity. The present study evaluates the association of maternal exposure to DDT and DDE with the risk of obesity in daughters during their mid-life in a prospective birth cohort with up to 53 years of follow-up.MethodsGravidas' blood was collected during their 1959-1967 enrollment into the prospective Child Health and Development Studies birth cohort in California. Their daughters aged 44-53 years had their height, weight, and waist circumference measured during a home visit to evaluate associations of daughters' adiposity and relative risk of overweight and obesity with their mothers' prenatal serum levels of DDT and DDE quantified by gas chromatograph-tandem mass spectrometer (n = 511).ResultsMaternal o,p'-DDT was positively associated with body mass index (β = 0.59 kg/m2 per ln ng/ml (95th percentile confidence interval, 95% CI: 0.17, 1.00)) and waist circumference (β = 1.19 cm per ln ng/ml (95% CI: 0.26, 2.13)) in multivariable models. Maternal o,p'-DDT was positively associated with a 26% (95% CI: 6-49) to 31% (95% CI: 6-62) higher risk of overweight and the same magnitude of additional risk for obesity, based on waist circumference and BMI definitions respectively, in multivariable models.ConclusionsThese data indicate maternal DDT exposure is significantly associated with increased obesity risk among middle-aged women independent of the obesity definition, confounding, and obesity risk factors. Our findings suggest that policies supporting the use of DDT for malaria vector abatement need to consider the obesity risk as a health cost when weighing the benefits of using DDT in malaria vector control.

The advancement of high-resolution metabolomics (HRM) and metabolome-wide-association study (MWAS) enables the readout of environmental effects in human specimens. We used HRM to understand DDT-induced alterations of in utero environment and potential health effects. Endogenous metabolites were measured in 397 maternal perinatal serum samples collected during 1959-1967 in the Child Health and Development Studies (CHDS) and in 16 maternal postnatal serum samples of mice treated with or without DDT. MWAS was performed to assess associations between metabolites and p,p'-DDT, o,p'-DDT and p,p'-DDE levels, followed by pathway analysis. Distinct metabolic profiles were found with p,p'-DDT and p,p'-DDE. Amino acids such arginine had a strong association with p,p'-DDT and o,p'-DDT in both women and mice, whereas lipids and acyl-carnitine intermediates were found exclusively associated with p,p'-DDE in CHDS women indicating mitochondrial impairment. It suggests that the role of serine and fatty acid metabolism on the causal disease pathway should be examined.

Background: To make informed decisions about endocrine-disrupting chemicals (EDCs), people need functional understanding of exposures and health and an ability to act on their knowledge. The return of biomonitoring results is an opportunity to educate people about EDCs and motivate exposure reduction. Objectives: This study investigates environmental health knowledge about EDCs, concerns about health effects, and exposure-reducing behaviors before and after the return of individual-level exposure results or only study-wide results. Methods: Women in the Child Health and Development Studies who were biomonitored for 42 EDCs were randomly assigned to receive a report with personal chemical results or only study-wide findings. We interviewed participants before and after report- back about their knowledge and concerns about EDCs and how frequently they performed exposure-related behaviors. We investigated baseline differences by education and race and examined changes after report-back by race and report type. Results: Participants (n = 135) demonstrated general understanding of exposure pathways and health impacts of EDCs. For 9 out of 20 knowledge questions, more than 90% of participants (n [greater than or equal to] 124) gave correct responses at baseline, including for questions about chemicals' persistence in the body and effects of early-life exposure. Most participants held two misconceptions--about chemical safety testing in the United States and what doctors can infer from EDC results--although errors decreased after report-back. Initially, concern was higher for legacy pollutants, but report-back increased concern for consumer product chemicals. After report-back, participants took some actions to reduce exposures, particularly to per- and polyfluoroalkyl substances, and total behavior was associated with knowledge and concern but not race, education, or report type. Discussion: This study demonstrated that participants had foundational knowledge about EDCs and that report-back further built their environmental health literacy. We conclude that future communications should target misconceptions about chemicals regulation in the United States, because information about regulations is crucial for people to evaluate risks posed by consumer product chemicals and decide whether to engage with public policy. https://doi.org/10.1289/EHP12565, Introduction Endocrine-disrupting chemicals (EDCs) are ubiquitous in everyday environments and many consumer products. (1-3) Sources include some pesticides, flame retardants, ingredients in plastics and personal care products, and per- and [...]

Many suspected breast cancer risk factors, including the pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE), are stored in fat where they could influence carcinogenesis. We tested the hypothesis that the relationship of DDT and DDE (DDTs) with adiposity is modified by disposition to develop breast cancer. We predicted that concentrations of serum DDTs would be inversely correlated with body mass index (BMI) during active exposure when DDTs move into the larger fat pool. We described this correlation at an average of 17 years before breast cancer was diagnosed, in a prospective nested case-control study in the Child Health and Development Studies. Women entered the study during pregnancy from 1959 to 1966 when DDT was in active use. In total, 133 breast cancer cases were diagnosed under the age of 50 as of 1998. Mean time to diagnosis was 17 years. In total, 133 controls were matched to cases on birth year. We observed the expected inverse correlation of serum DDTs with BMI only in women who remained cancer-free and not in women who ultimately developed breast cancer (p for interaction

BackgroundExperimental and clinical evidence implicates testosterone in the aetiology of prostate cancer. Variation across the normal range of circulating free testosterone concentrations may not lead to changes in prostate biology, unless circulating concentrations are low. This may also apply to prostate cancer risk, but this has not been investigated in an epidemiological setting.ObjectiveTo examine whether men with low concentrations of circulating free testosterone have a reduced risk of prostate cancer.Design, setting, and participantsAnalysis of individual participant data from 20 prospective studies including 6933 prostate cancer cases, diagnosed on average 6.8 yr after blood collection, and 12 088 controls in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group.Outcome measurements and statistical analysisOdds ratios (ORs) of incident overall prostate cancer and subtypes by stage and grade, using conditional logistic regression, based on study-specific tenths of calculated free testosterone concentration.Results and limitationsMen in the lowest tenth of free testosterone concentration had a lower risk of overall prostate cancer (OR=0.77, 95% confidence interval [CI] 0.69-0.86; p

The authors examined the relationship of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with child neurodevelopment. Mother-child dyads were a subgroup (n = 2,084) of the Child Health and Development Studies from the Oakland, California, area enrolled during pregnancy from 1959 to 1966 and followed at child age 9 years. Linear regression was used to examine associations between prepregnancy BMI, GWG, and standardized Peabody Picture Vocabulary Test and Raven Progressive Matrices scores and to evaluate effect modification of GWG by prepregnancy BMI. Before pregnancy, 77% of women were normal weight, 8% were underweight, 11% were overweight, and 3% were obese. Associations between GWG and child outcomes did not vary by prepregnancy BMI, suggesting no evidence for interaction. In multivariable models, compared to normal prepregnancy BMI, prepregnancy overweight and obesity were associated with lower Peabody scores (b: -1.29; 95% CI [-2.6, -0.04] and b: -2.7; 95% CI [-5.0, -0.32], respectively). GWG was not associated with child Peabody score [b: -0.03 (95% CI: -0.13, 0.07)]. Maternal BMI and GWG were not associated with child Raven score (all P >0.05). Maternal prepregnancy overweight and obesity were associated with lower scores for verbal recognition in mid-childhood. These results contribute to evidence linking maternal BMI with child neurodevelopment. Future research should examine the role of higher prepregnancy BMI values and the pattern of pregnancy weight gain in child cognitive outcomes.

CorrectionAfter publication of the article [1], it has been brought to our attention that the thirteenth author of this article has had their name spelt incorrectly. In the original article the spelling "Laura Rizzir" was used. In fact the correct spelling should be "Laura Rizzi".

BackgroundEarly 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.MethodsWe 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).ResultsHighest 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 cm2, 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.ConclusionsWe did not observe consistent associations between different measures of early life SES and mammographic density in adulthood.

Extensive evidence leads us to expect that health disparities by race and socioeconomic status found in one generation might be reproduced in the next. To the extent that this occurs it is important to assess life course processes responsible for the reproduction. Prospective evidence concerning such life course processes is hard to come by as it requires long-term follow-up of individuals from childhood through adult life. We present data from the Child Health and Development Disparities study that provides evidence relevant to this issue with respect to self-rated health. Mothers and offspring recruited in California's Bay Area between 1959 and 1967 were assessed during pregnancy with follow-up exams of offspring along with in-person interviews with mothers (at offspring ages 5, 9-11, 15-17) and offspring (at ages 15-17, ∼50). Available data allow us to assess the importance of three potential life course pathways in the reproduction of inequalities in self-rated health - socioeconomic pathways, cognitive pathways and pathways involving emerging health itself. As expected we found that race and SES disparities in SRH are reproduced across generations. They are evident in mothers, not strong or significant in offspring at 15-17, but present once again in offspring at age ∼50. Concerning potential pathways, we found that indicators of child health were related to adult SRH and played some role in accounting for race but not SES disparities in adult SRH. Cognitive abilities were unrelated to adult SRH with childhood SES controlled. Childhood SES was associated with adult SRH independent of other childhood factors and is reduced to non-significance only when offspring college attainment is controlled. Race and SES disparities in self-reported health in one generation are re-expressed in the next with strongest support for SES pathways in this transmission.

IntroductionSex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.MethodsStatistical analyses of individual participant data from 12,330 male controls aged 25-85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.ResultsOlder age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.ConclusionCirculating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.

We tested the hypothesis that irregular menstruation predicts lower risk for ovarian cancer, possibly due to less frequent ovulation. We conducted a 50-year prospective study of 15,528 mothers in the Child Health and Development Studies cohort recruited from the Kaiser Foundation Health Plan from 1959 to 1966. Irregular menstruation was classified via medical record and self-report at age 26. We identified 116 cases and 84 deaths due to ovarian cancer through 2011 via linkage to the California Cancer Registry and Vital Statistics. Contrary to expectation, women with irregular menstrual cycles had a higher risk of ovarian cancer incidence and mortality over the 50-year follow-up. Associations increased with age (p

A multidisciplinary group of experts gathered in Parma Italy for a workshop hosted by the University of Parma, May 16-18, 2014 to address concerns about the potential relationship between environmental metabolic disrupting chemicals, obesity and related metabolic disorders. The objectives of the workshop were to: 1. Review findings related to the role of environmental chemicals, referred to as "metabolic disruptors", in obesity and metabolic syndrome with special attention to recent discoveries from animal model and epidemiology studies; 2. Identify conclusions that could be drawn with confidence from existing animal and human data; 3. Develop predictions based on current data; and 4. Identify critical knowledge gaps and areas of uncertainty. The consensus statements are intended to aid in expanding understanding of the role of metabolic disruptors in the obesity and metabolic disease epidemics, to move the field forward by assessing the current state of the science and to identify research needs on the role of environmental chemical exposures in these diseases. We propose broadening the definition of obesogens to that of metabolic disruptors, to encompass chemicals that play a role in altered susceptibility to obesity, diabetes and related metabolic disorders including metabolic syndrome.

ContextCurrently no direct evidence links in utero dichlorodiphenyltrichloroethane (DDT) exposure to human breast cancer. However, in utero exposure to another xenoestrogen, diethylstilbestrol, predicts an increased breast cancer risk. If this finding extends to DDT, it could have far-reaching consequences. Many women were heavily exposed in utero during widespread DDT use in the 1960s. They are now reaching the age of heightened breast cancer risk. DDT exposure persists and use continues in Africa and Asia without clear knowledge of the consequences for the next generation.HypothesisIn utero exposure to DDT is associated with an increased risk of breast cancer.DesignThis was a case-control study nested in a prospective 54-year follow-up of 9300 daughters in the Child Health and Development Studies pregnancy cohort (n = 118 breast cancer cases, diagnosed by age 52 y and 354 controls matched on birth year).Setting and participantsKaiser Foundation Health Plan members who received obstetric care in Alameda County, California, from 1959 to 1967, and their adult daughters participated in the study.Main outcome measureDaughters' breast cancer diagnosed by age 52 years as of 2012 was measured.ResultsMaternal o,p'-DDT predicted daughters' breast cancer (odds ratio fourth quartile vs first = 3.7, 95% confidence interval 1.5-9.0). Mothers' lipids, weight, race, age, and breast cancer history did not explain the findings.ConclusionsThis prospective human study links measured DDT exposure in utero to risk of breast cancer. Experimental studies are essential to confirm results and discover causal mechanisms. Findings support classification of DDT as an endocrine disruptor, a predictor of breast cancer, and a marker of high risk.