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BackgroundInvestigating the burden of access to infertility treatment has primarily been conducted in high-income countries, with little known for low- and middle-income countries, which comprise 80% of the world’s population. The objective of this study was to investigate access to infertility care in Mexico.MethodsThis was a cross-sectional analysis in the Mexican Teachers’ Cohort (MTC), a prospective cohort study of 115,307 Mexican female public school teachers from 12 states in Mexico. Log-binomial models, adjusted for age, hormonal contraceptive use, teaching in a rural school, and speaking an indigenous language, were used to estimate the prevalence ratio (PR) and 95% confidence intervals (95% CI) of accessing medical care for infertility among women reporting a history of infertility.Results19,580 (17%) participants reported a history of infertility. Of those who experienced infertility, 12,470 (63.7%) reported seeking medical care for infertility, among whom 8,467 (67.9%) reported undergoing fertility treatments. Among women who reported a history of infertility, women who taught in a rural school (PR:0.95;0.92-0.97), spoke an indigenous language (PR:0.88; 0.84-0.92), or had less than a university degree (PR:0.93; 0.90-0.97) were less likely to access medical care for fertility. Women who had ever had a mammogram (PR:1.07; 1.05-1.10), had a pap-smear in the past year (PR:1.08;1.06-1.10), or who had utilized private healthcare regularly or in times of illness were more likely to access medical care for fertility.ConclusionUtilization of infertility care varied by demographic and access characteristics, including speaking an indigenous language, teaching in a rural school, and having a private healthcare provider.

ObjectivesThis study aimed to identify whether differences exist in postpartum depression (PPD) in US and Korean nurses and its related factors. Identifying occupational and personal factors that underlie potential differences will be helpful for women’s occupational health.MethodsBaseline and postpartum survey data from employed nurses in the Korea Nurses’ Health Study and Nurses’ Health Study 3 (1244 Korean; 2742 US nurses) were analysed. Postpartum data collection was done via online survey. PPD was analysed based on cultural validation from prior studies using the Edinburgh Postnatal Depression Scale (cut-off of 10 for Korea and 13 for USA); depressive symptoms prior to pregnancy and childbirth, general characteristics and sleep satisfaction were also measured. Descriptive statistics, χ2tests and t-tests and multivariate ordinal logistic regression analysis were performed.Results45.9% of Korean participants had clinical symptoms of PPD (≥10), whereas US participants presented with 3.4% (≥13). Prior depressive symptoms were also higher in Korean participants (22.5%) compared with their US counterparts (4.5%). Prior depressive symptoms and poor sleep satisfaction were significant risk factors of PPD in both cohort groups, and vaginal birth was an additional influencing factor in Korean participants.ConclusionsDifferences in PPD rates and related factors suggest the role of stress, cultural variation and differing work systems. Nurses and other women shift-workers noted to have depressive symptoms before and during pregnancy and exhibit PPD symptoms should especially be followed closely and offered supportive mental health services that include greater flexibility in returning to work.

Maternal mortality is unusually high in the United States compared to other wealthy nations and is characterized by major disparities in race/ethnicity, geography, and socioeconomic factors. Similar to other developed nations, the United States has seen a shift in the underlying causes of pregnancy-related death, with a relative increase in mortality resulting from diseases of the cardiovascular system and preexisting medical conditions. Improved continuity of care aimed at identifying reproductive-age women with preexisting conditions that may heighten the risk of maternal death, preconception management of risk factors for major adverse pregnancy outcomes, and primary care visits within the first year after delivery may offer opportunities to address gaps in medical care contributing to the unacceptable rates of maternal mortality in the United States.

Background Adherence to healthy lifestyles can be beneficial for depression among adults, but the intergenerational impact of maternal healthy lifestyles on offspring depressive symptoms is unknown. Methods In total, 10 368 mothers in Nurses' Health Study II and 13 478 offspring in the Growing Up Today Study were paired. Maternal and offspring healthy lifestyles were defined as a composite score including a healthy diet, normal body mass index (BMI), never-smoking, light-to-moderate consumption of alcohol, and regular moderate-to-vigorous physical activity. Maternal lifestyles were assessed during their offspring's childhood. Offspring depressive symptoms were repeatedly assessed five times using the Center for Epidemiological Studies Depression Scale-10 (CESD-10); the offspring were between the ages of 14 and 30 when the first CESD-10 was assessed. Covariates included maternal variables (age at baseline, race/ethnicity, antidepressant use, pregnancy complications, etc.) and offspring age and sex. Results Children of mothers with the healthiest lifestyle had significantly fewer depressive symptoms (a 0.30 lower CESD-10 score, 95% confidence interval (CI) 0.09–0.50) in comparison with children of mothers with the least healthy lifestyle. The association was only found significant in female offspring but not in males. For individual maternal lifestyle factors, a normal BMI, never-smoking, and adherence to regular physical activity were independently associated with fewer depressive symptoms among the offspring. The association between maternal healthy lifestyles and offspring depressive symptoms was mediated by offspring's healthy lifestyles (mediation effect: 53.2%, 95% CI 15.8–87.3). Conclusions Our finding indicates the potential mechanism of intergenerational transmission of healthy lifestyles to reduce the risk of depressive symptoms in offspring.

To examine the association between the intake of fruits and vegetables with high- vs. low-pesticide residue burden and diagnosis of laparoscopically confirmed endometriosis. The etiology of endometriosis is not well understood, but dietary factors may influence the risk. Pesticides may act as endocrine disruptors, and the intake of pesticide-contaminated food is a common exposure pathway.Prospective cohort study. Hazard ratios and 95% confidence intervals were calculated using multivariable Cox proportional hazard models to evaluate the intake of fruits and vegetables with high- and low-pesticide residues in relation to the diagnosis of laparoscopically confirmed endometriosis.Not applicable.Premenopausal US women (N = 52,053) of the Nurses' Health Study II, aged 34-53 years at study baseline (1999), were followed until 2013. The diet was assessed every 4 years using a validated food frequency questionnaire. A previously developed and validated pesticide residue burden score (PRBS), on the basis of the US Department of Agriculture Pesticide Data Program, was used to assign fruits and vegetables to pesticide residue groups (high/low).Not applicable.Cases of laparoscopically confirmed endometriosis were identified from self-reports to validated questionnaires.During 14 years of follow-up, 956 incidences of laparoscopically confirmed endometriosis were reported. No association was observed between the intake of high- or low-PRBS fruit and vegetable intake and endometriosis (hazard ratio for 5th vs. 1st quintile: high-PRBS intake = 0.94, 95% confidence interval = 0.73-1.23; low-PRBS intake = 1.07, 95% confidence interval = 0.82-1.40). No associations were observed for high- or low-PRBS fruit and vegetable intake by fertility status.No clear associations were observed between high- or low-PRBS fruit and vegetable intake and endometriosis risk among premenopausal women. To our knowledge, this is the first study to evaluate the association between dietary pesticide residue intake and endometriosis. Further research is needed, particularly to evaluate this association among a younger population of women (adolescence or early adulthood) and assess the dietary exposure to specific pesticides or chemical families.

Published studies report inconsistent associations of polyunsaturated fatty acid (PUFA) intake with non-Hodgkin lymphoma (NHL) risk. We conducted a nested case-control study in Nurses' Health Study and Health Professionals Follow-Up Study participants to evaluate a hypothesis of inverse association of pre-diagnosis red blood cell (RBC) membrane PUFA levels with risk of NHL endpoints. We confirmed 583 NHL cases and matched 583 controls by cohort/sex, age, race and blood draw date/time. We estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL endpoints using logistic regression. RBC PUFA levels were not associated with all NHL risk

Objective: Energy drinks are consumed for a variety of reasons, including to boost mental alertness and energy. We assessed associations between demographic factors and various high-risky behaviours with energy drink consumption as they may be linked to adverse health events. Design: We conducted cross-sectional analysis including basic descriptive and multivariable-adjusted logistic regression analyses to characterise demographic and behavioural factors (including diet quality, binge drinking and illicit drug use, among others obtained via questionnaires) in relation to energy drink consumption. Setting: We used data from two large US-based cohorts. Participants: 46 390 participants from Nurses’ Health Study 3 (NHS3, n 37 302; ages 16–31) and Growing Up Today Study (GUTS, n 9088, ages 20–55). Results: Of the 46 390 participants, 13·2 % reported consuming ≥ 1 energy drink every month. Several risky behaviours were associated with energy drink use, including illegal drug use (pooled OR, pOR: 1·45, 95 % CI: 1·16, 1·81), marijuana use (pOR: 1·49, 95 % CI: 1·28, 1·73), smoking (pOR: 1·88. 95 % CI: 1·55, 2·29), tanning bed use (pOR: 2·31, 95 % CI: 1·96, 2·72) and binge drinking (pOR: 2·53, 95 % CI: 2·09, 3·07). Other factors, such as high BMI, e-cigarette use and poor diet quality were found to be significantly associated with higher energy drink consumption (P values < 0·001). Conclusions: Our findings show that energy drink consumption and high-risk behaviours may be related, which could potentially serve as not only as a talking point for providers to address in outreach and communications with patients, but also a warning sign for medical and other health practitioners.

To evaluate the association of a history of infertility with long-term weight, body composition, and blood pressure.We studied 1581 women from the prospective cohort Project Viva. History of infertility was based on self-reported time to pregnancy ≥12 months or use of medical treatment to conceive for the index or any prior pregnancy; a diagnosis of infertility; claims for infertility treatments/prescriptions abstracted from medical records. The outcomes were weight, waist circumference, and body fat assessed through 12 years postpartum; and blood pressure assessed through 3 years postpartum. We used linear mixed-effect models adjusted for age, race/ethnicity, income, education, marital status, parity, and age at menarche.Three hundred forty-two women (21.6%) had a history of infertility. In adjusted models, women with versus without infertility, had higher average weight (3.29 kg, 95% confidence interval [CI]: 1.35-5.24), waist circumference (2.46 cm, 95% CI: 0.78-4.13) and body fat (1.76 kg, 95% CI: 0.09-3.43). Among younger (18-29 years), but not older (≥30 years) women, infertility was associated with higher systolic (4.08 mmHg, 95% CI: 0.93, 7.23) and diastolic blood pressure (2.16 mmHg, 95% CI: 0.11-4.20).A history of infertility may serve as a marker to identify women at higher cardiometabolic risk.

We examined longitudinal associations of psychosocial stressors with menopausal symptoms and well-being of women in midlife in a longitudinal cohort.This study is based on 682 women from Project Viva, a prospective cohort enrolled in 1999 to 2002 during pregnancy (median age = 33.3 y) and followed for almost two decades. In pregnancy, women self-reported psychosocial stressors (history of physical and sexual abuse and financial instability, from childhood to the current pregnancy). In 2017 to 2021 (median age, 51.6 y), they reported their menopausal symptoms (0-44 point scale) and well-being (general health [good/fair/poor vs excellent/very good], generalized anxiety symptoms, and depressive symptoms [both-more than minimal levels vs none/minimal]). We performed multivariable and logistic regression models to examine associations of psychosocial stressors with outcomes, adjusting for covariates.History of physical abuse (reported by 37.3%) was associated with worse menopausal symptoms in the somatovegetative (odds ratio [OR], 0.46 points; 95% confidence interval [CI], 0.04-0.87 points) and psychological (OR, 0.52 points; 95% CI, 0.07-0.97 points) domains and with worse general health (OR, 1.73; 95% CI, 1.17-2.55) and greater depressive symptoms (OR, 1.74; 95% CI, 1.05-2.87). History of sexual abuse (7.7%) was associated with worse menopausal symptoms (OR, 2.81 points; 95% CI, 1.05-4.56) and worse general health (OR, 2.04; 95% CI, 1.04-4.03) but not with depressive symptoms. History of financial instability (10.8%) was associated with worse menopausal symptoms (1.92 points; 0.49 to 3.34), worse general health (OR, 2.16; 95% CI, 1.24-3.75), and greater depressive symptoms (OR, 2.68; 95% CI, 1.44-4.98). We observed no association between psychosocial stressors and generalized anxiety symptoms assessed at midlife.Psychosocial stressors were associated with worse menopausal symptoms and well-being decades after initial report.

BACKGROUND: The etiology of endometriosis is not well understood. Limited evidence suggests that dietary factors influence risk, but prospective data related to carbohydrate, fiber, and gluten consumption are scarce. Despite this, recommendations concerning fiber, gluten intake, and endometriosis are pervasive in the lay literature. OBJECTIVES: We aimed to investigate the associations of carbohydrate quality [glycemic index (GI) and glycemic load (GL)], fiber intake (total, legume, vegetable, cruciferous vegetable, fruit, cereal), and gluten intake with incident laparoscopically confirmed endometriosis. METHODS: This was a prospective cohort study using data collected from 81,961 premenopausal women in the Nurses’ Health Study II (mean age = 36 y in 1991). Diet was assessed with a validated FFQ every 4 y. Cox proportional hazards models were used to calculate rate ratios (RRs) and 95% CIs. RESULTS: A total of 3810 incident cases of laparoscopically confirmed endometriosis were reported over 24 y of follow-up. Women in the highest quintile of GI had 12% (95% CI: 1.01, 1.23; P(trend) = 0.03) higher risk of endometriosis diagnosis than those in the lowest quintile. Total vegetable and cruciferous vegetable fiber intakes were also associated with higher risk (highest compared with lowest quintile RR: 1.13; 95% CI: 1.02, 1.24; P(trend) = 0.004 and RR: 1.17; 95% CI: 1.06, 1.29; P(trend) = 0.02, respectively). Higher intake of fruit fiber was associated with lower risk of endometriosis but the association was not significant after adjusting for the Alternative Healthy Eating Index. Gluten intake was also associated with lower risk (highest compared with lowest quintile RR: 0.91; 95% CI: 0.80, 1.02; P(trend) = 0.01), but these results were not consistent in direction nor statistical significance across sensitivity analyses. No association was observed for GL or total, legume, or cereal fiber intake. CONCLUSIONS: Our findings suggest that carbohydrate quality and specific types of fiber—total vegetable and cruciferous vegetable fiber—are associated with endometriosis diagnosis in premenopausal women. These results also indicate it is unlikely that gluten intake is a strong factor in the etiology or symptomatology of endometriosis.

The aim of this study was to evaluate the associations of a lifetime history of hypertensive disorders of pregnancy (HDP) and gestational diabetes mellitus (GDM) with menopausal symptoms in midlife.This was a secondary analysis of women participating in Project Viva, an ongoing cohort enrolled during pregnancy. The exposure was lifetime history of HDP or GDM assessed for the index pregnancy by review of outpatient and hospital medical records and for all other pregnancies by interview or questionnaire at study entry (1999-2002) and the midlife visit (2017-2021). The primary outcome was the Menopause Rating Scale (MRS) applied at the midlife study visit. We used linear or logistic regression models adjusted for covariates such as baseline age, race/ethnicity, education, married/cohabiting, household income, baseline parity, age at menarche, and body mass index at midlife.Of the 676 included participants, 120 (18%) had a history of HDP, and 47 (7%) had a history of GDM. The mean (SD) age was 52 (3.9) years at the midlife visit, and 48% of the participants had experienced menopause. There were no consistent differences in total, domain-specific, or individual symptoms in women with a history of HDP or GDM. A history of HDP and/or GDM was not associated with age at the onset of natural menopause.Our findings do not support an association of a history of HDP or GDM with the severity of menopausal symptoms or age at the onset of natural menopause. Larger studies of women with a history of these pregnancy complications are needed to clarify their association with menopausal symptoms.

The associations between urinary phenol concentrations and markers of thyroid function and autoimmunity among potentially susceptible subgroups, such as subfertile women, have been understudied, especially when considering chemical mixtures. We evaluated cross-sectional associations of urinary phenol concentrations, individually and as a mixture, with serum markers of thyroid function and autoimmunity. We included 339 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2009–2015). We quantified four phenols in urine using isotope dilution high-performance liquid chromatography–tandem mass spectrometry, and biomarkers of thyroid function (thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4), and triiodothyronine (fT3, TT3)), and autoimmunity (thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (Ab)) in serum using electrochemoluminescence assays. We fit linear and additive models to investigate the association between urinary phenols—both individually and as a mixture—and serum thyroid function and autoimmunity, adjusted for confounders. As a sensitivity analysis, we also applied Bayesian Kernel Machine Regression (BKMR) to investigate non-linear and non-additive interactions. Urinary bisphenol A was associated with thyroid function, in particular, fT3 (mean difference for a 1 log unit increase in concentration: −0.088; 95% CI [−0.151, −0.025]) and TT3 (−0.066; 95% CI [−0.112, −0.020]). Urinary methylparaben and triclosan were also associated with several thyroid hormones. The overall mixture was negatively associated with serum fT3 concentrations (mean difference comparing all four mixture components at their 75th vs. 25th percentiles: −0.19, 95% CI [−0.35, −0.03]). We found no evidence of non-linearity or interactions. These results add to the current literature on phenol exposures and thyroid function in women, suggesting that some phenols may alter the thyroid system.

An epidemiological analysis assessing beverage consumption and risk factors for cardiovascular disease was conducted. Participants were 9-16 years old at enrolment, completed food frequency questionnaires in 1996-2001 and self-reported outcomes in 2010-2014. Exclusion criteria included missing data on relevant variables and covariates, prevalent disease before 2005, and implausible/extreme weight or energy intake. Intakes of orange juice, apple/other fruit juice, sugar-sweetened beverages and diet soda were related to the risk of incident hypertension or hyperlipidaemia using Cox proportional hazards regression, adjusting for diet, energy intake, age, smoking, physical activity and body mass index. There were 9,043 participants with 618 cases of hypertension and 850 of hyperlipidaemia in 17 years of mean follow-up. Sugar-sweetened beverage intake but not fruit juice nor diet soda was associated with hypertension (hazard ratio (95% confidence interval): 1.16 (1.03, 1.31)) in males. This study can guide beverage consumption as it relates to early predictors of cardiovascular disease.

Background Pre-pandemic psychological distress is associated with increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but associations with the coronavirus disease 2019 (COVID-19) severity are not established. The authors examined the associations between distress prior to SARS-CoV-2 infection and subsequent risk of hospitalization. Methods Between April 2020 (baseline) and April 2021, we followed 54 781 participants from three ongoing cohorts: Nurses' Health Study II (NHSII), Nurses' Health Study 3 (NHS3), and the Growing Up Today Study (GUTS) who reported no current or prior SARS-CoV-2 infection at baseline. Chronic depression was assessed during 2010–2019. Depression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at baseline. SARS-CoV-2 infection and hospitalization due to COVID-19 was self-reported. Relative risks (RRs) were calculated by Poisson regression. Results 3663 participants reported a positive SARS-CoV-2 test (mean age = 55.0 years, standard deviation = 13.8) during follow-up. Among these participants, chronic depression prior to the pandemic [RR = 1.72; 95% confidence interval (CI) 1.20–2.46], and probable depression (RR = 1.81, 95% CI 1.08–3.03), being very worried about COVID-19 (RR = 1.79; 95% CI 1.12–2.86), and loneliness (RR = 1.81, 95% CI 1.02–3.20) reported at baseline were each associated with subsequent COVID-19 hospitalization, adjusting for demographic factors and healthcare worker status. Anxiety and perceived stress were not associated with hospitalization. Depression, worry about COVID-19, and loneliness were as strongly associated with hospitalization as were high cholesterol and hypertension, established risk factors for COVID-19 severity. Conclusions Psychological distress may be a risk factor for hospitalization in patients with SARS-CoV-2 infection. Assessment of psychological distress may identify patients at greater risk of hospitalization. Future work should examine whether addressing distress improves physical health outcomes.

Men diagnosed with nonmetastatic prostate cancer have a long life expectancy, and many die of unrelated causes. It is therefore important to know to what extent post-diagnostic diet may affect disease-specific and overall mortality. A total of 926 men participating in the Physicians' Health Study diagnosed with nonmetastatic prostate cancer completed diet questionnaires for a median of 5.1 years after diagnosis, and were followed thereafter to assess mortality for a median of 9.9 years since questionnaire completion. Two post-diagnostic dietary patterns were identified: a Prudent pattern, characterized by higher intake of vegetables, fruits, fish, legumes, and whole grains; and a Western pattern, characterized by higher intake of processed and red meats, high-fat dairy and refined grains. Cox regression was used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). During 8,093 person-years of follow-up, 333 men died, 56 (17%) of prostate cancer. The Western pattern was significantly related to a higher risk of prostate cancer–specific and all-cause mortality. Comparing men in the highest versus the lowest quartile of the Western pattern, the HRs were 2.53 (95% CI, 1.00–6.42; Ptrend = 0.02) for prostate cancer–specific mortality and 1.67 (95% CI, 1.16–2.42; Ptrend = 0.01) for all-cause mortality. The Prudent pattern was associated with a significantly lower all-cause mortality (HRQuartile 4 vs. Quartile 1: 0.64; 95% CI, 0.44–0.93; Ptrend = 0.02); the relationship with prostate cancer–specific mortality was inverse but not statistically significant. A post-diagnostic Western dietary pattern was associated with higher prostate cancer–specific and all-cause mortality, whereas a Prudent dietary pattern was related to lower all-cause mortality after prostate cancer diagnosis. Cancer Prev Res; 8(6); 545–51. ©2015 AACR.

Supplementary tables

Several case–control studies have reported that mushroom consumption may be associated with reduced risk of certain cancers. However, epidemiologic studies have not yet prospectively examined the association of mushroom consumption with total and various site-specific cancer risks. This prospective cohort study included 68,327 women (Nurses' Health Study, 1986–2012) and 44,664 men (Health Professionals Follow-up Study, 1986–2012) who were free of cancer at baseline. Mushroom consumption was assessed at baseline using a validated food frequency questionnaire. Covariates were assessed using biennial questionnaires during the follow-up. We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) of total and 17 site-specific cancers associated with mushroom consumption. During up to 26 years of follow-up, we documented 22,469 incident cancer cases (15,103 in women and 7,366 in men). In the pooled multivariable analysis, participants who consumed five or more servings of mushrooms per week had no significantly different risk of total cancer (HR, 1.06; 95% CI, 0.98–1.14) than participants who almost never consumed mushrooms. We consistently found no association between mushroom consumption and risk of 16 site-specific cancers. However, there was a marginal positive association between mushroom consumption and risk of lung cancer (Ptrend = 0.05). In conclusion, we found no association between mushroom consumption and total and site-specific cancers in U.S. women and men. More prospective cohort studies are needed to examine the associations for specific cancer types in diverse racial/ethnic groups.

Supplemental Table S1. Food groupings used in the dietary pattern analysis. Supplemental Table S2. Comparisons of Cox proportional hazards regression model and competing risk model in associations between dietary patterns and prostate cancer-specific mortality among 926 men diagnosed with non-metastatic prostate cancer Supplemental Table S3. Relative risks between food groups with loading factor > 0.3 within each dietary pattern and prostate cancer-specific and all-cause mortality among men with non-metastatic prostate cancer (n=926)a.

Background Certain symptoms associated with infertility are associated with cardiovascular disease, including menstrual cycle irregularity, early menopause, and obesity; however, few studies have investigated the association between infertility and cardiovascular disease risk. Methods and Results Participants in the NHSII (Nurses' Health Study II) who reported infertility (12 months of trying to conceive without success, including women who subsequently conceived) or who were gravid, with no infertility were followed from 1989 until 2017 for development of incident, physician‐diagnosed coronary heart disease (CHD) (myocardial infarction, coronary artery bypass grafting, angioplasty, stent) and stroke. Time‐varying Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs and were adjusted a priori for potential confounding variables. Among 103 729 participants, 27.6% reported having ever experienced infertility. Compared with gravid women who had not reported infertility, women with a history of infertility had greater risk of CHD (HR, 1.13 [95% CI, 1.01–1.26]) but not stroke (HR, 0.91 [95% CI, 0.77–1.07]). The association between history of infertility and CHD was strongest among women who reported infertility at an earlier age (HR for infertility first reported at ≤25 years, 1.26 [95% CI, 1.09–1.46]; HR at 26–30 years, 1.08 [95% CI, 0.93–1.25]; HR at >30 years, 0.91 [95% CI, 0.70–1.19]). When we investigated specific infertility diagnoses, elevated risk of CHD was observed among women whose infertility was attributed to an ovulatory disorder (HR, 1.28 [95% CI, 1.05–1.55]) or endometriosis (HR, 1.42 [95% CI, 1.09–1.85]). Conclusions Women with infertility may be at an increased risk of CHD. Risk differed by age at first infertility diagnosis and was restricted to ovulatory‐ and endometriosis‐related infertility.

IntroductionSupplements sold with claims to promote weight loss, cleansing/detoxing, increased energy, or boosted immunity can be dangerous, and consumers experiencing extreme stressors may be especially vulnerable to deceptive claims. The purpose of our study was to investigate associations of financial strain and psychological distress during the COVID-19 pandemic with use of supplements sold for weight loss, cleanse/detox, energy, or immunity.MethodsWe used repeated-measures data gathered over five survey waves from April/May 2020–April 2021 from the COVID-19 Substudy (N = 54,951), within three prospective US national cohorts (Nurses' Health Study 2, Nurses' Health Study 3, and Growing Up Today Study), to investigate longitudinal associations between financial strain and psychological distress and risk of use of potentially dangerous types of supplements. Surveys assessed use of supplements prior to and during the first year of the pandemic, as well as financial precarity, food insecurity, depressive and anxiety symptoms, perceived stress, and daily hassles. We fit sociodemographic-adjusted modified Poisson GEE models to estimate risk ratios (RRs) and 95% confidence intervals (CIs) for associations between baseline or lagged time-varying predictors and prevalent or incident (i.e., new-onset) use of each supplement type.ResultsAt baseline in April/May 2020, soon after pandemic onset, current use of supplement types was: weight loss 2.7%; cleanse/detox 3.2%; energy 4.4%; immune 22.6%. By the end of the study period, cumulative incidence was: weight loss 3.5%; cleanse/detox 3.7%; energy 4.5%; immune 21.3%. In prevalent-use analyses, financial precarity, food insecurity, and psychological distress were associated with up to 2.4 times the risk of use of these types of supplements across the study period. Similarly, in incident-use analyses, financial precarity and psychological distress were associated with up to 2.1 times the risk of initiating use; whereas, high food insecurity was associated with nearly 1.8 times higher risk of onset of weight-loss supplements use but was not associated with onset of use of other types of supplements.DiscussionWe found consistent evidence that during the first year of the pandemic, participants experiencing elevated financial strain and psychological distress were at heightened risk of initiating use of potentially dangerous types of supplements. Our findings raise concerns about deceptive claims about the safety and product effectiveness by manufacturers of these supplements to profit from vulnerable consumers during the pandemic.

Objectives: Studies suggest that endogenous estrogen may be involved in regulating body weight. Dietary lignans can act as estrogen receptor agonists and may be beneficial for weight control. We prospectively examined the association between changes in dietary lignan intake with weight change. Methods: We analyzed data from 124,875 men and women in the Nurses’ Health Study (1986-2010), Nurses’ Health Study II (1991-2011), and the Health Professionals Follow-up Study (1986-2010). We calculated 4-year changes in total lignan intake as well as in four major individual lignans (matairesinol, secoisolariciresinol, pinoresinol, and lariciresinol) using data from a semi-quantitative food frequency questionnaire. Participants reported their height and weight at baseline and updated their current weight every 2 years thereafter, from which we calculated 4-year changes in weight as the primary study outcome. We used multivariable generalized linear regression models to examine the association between 4-year changes in lignan intake with 4-year weight changes over the same period, and these models were adjusted for age, baseline BMI in each period, and relevant lifestyle factors. Results: Each 1-standard deviation (SD) increase in total lignan intake was associated with a 4-year weight change of -0.36 lbs (95% confidence interval [CI] -0.40 to -0.33 lbs; P for trend (Figure) . The observed associations were stronger among certain subgroups, including those with BMI ≥25 kg/m 2 , below-median diet quality, or below-median physical activity level. Conclusions: Increases in dietary lignan intake were associated with less weight gain over the same 4-year period. Our findings support existing dietary recommendations to consume a healthy plant-based diet.

Introduction: Many women experience suboptimal cardiovascular health (CVH) during midlife and CVH is related to upstream social, behavioral and environmental factors. However, associations of adverse childhood experiences (ACEs) - more common among women - with CVH are understudied. Hypothesis: ACEs would be associated with poorer CVH among women in midlife. Methods: At mean (SD) 50.9 (5.1) years, participants in the Project Viva cohort completed questionnaires and research staff measured their height, weight, blood pressure, and blood levels of glucose, HbA1c and cholesterol. We calculated Life’s Essential 8 (LE8), a 0-100-point score that includes 8 components of CVH: heart healthy levels of diet, physical activity, sleep, avoidance of nicotine, body mass index (BMI), blood lipids, blood glucose and blood pressure. In 2021, women reported their personal history of ACEs (10 possible types) prior to age 18y. We used linear regression models adjusted for childhood SES measures (race/ethnicity, parental education, US birth) and age at outcome. Results: Among 319 participants, 114 (36%) reported 0 ACEs and 58 (18%) reported ≥4 ACEs. In midlife, mean (SD) LE8 score was 77 (12) points. In age-adjusted models, ACEs (4+ vs 0) were associated with poorer LE8 score (β -6.15; 95% CI -9.91, -2.40) and behavioral (β -5.84; CI -9.98, -1.69) and biological (β -6.47; CI -11.8, -1.12) domains; covariate adjustment attenuated the results, though the trends remained significant for LE8 and behavioral domain (Figure). In fully adjusted models, each additional ACE was associated with poorer LE8 score (β -0.74; CI -1.44, -0.04) and associations were stronger for ACEs related to abuse (β -2.72; CI -5.57, 0.12) and neglect (-2.48; CI -5.81, 0.85). Of the LE8 components (0-100-points), associations were strongest for glucose (β -1.76; CI -2.85, -0.67) and physical activity (β -1.86; CI -3.92, 0.20). Conclusions: Adverse childhood experiences may have persistent associations with several measures of cardiovascular health among women into midlife.

Background: A healthy lifestyle is associated with a lower risk of premature death. Metabolic pathways of a healthy lifestyle and their association with mortality remain to be understood. This study aimed to identify the metabolomic profile of a healthy lifestyle score and examine its prospective association with all-cause and cause-specific mortality, including death from cardiovascular disease (CVD) and cancer. Methods: The population included 12,146 participants from the Nurses’ Health Study (NHS), NHS II and Health Professionals Follow-Up Study (HPFS)(83% women, 97% white, aged 55±9y). Plasma metabolites were profiled using high-throughput liquid chromatography mass-spectrometry at baseline (NHS:1989-1990; NHSII:1996-1999; HPFS:1993-1995). The healthy lifestyle score was computed by summing the total number of healthy lifestyle factors participants adhered to from validated questionnaires at baseline: healthy diet (Alternative Healthy Eating Index, upper 40%), moderate alcohol intake (women: 5-15 g/d; men: 5-30 g/d), moderate-to-vigorous physical activity (≥30min/d), never smoking and normal BMI (18.5-24.9kg/m 2 ). Deaths were ascertained with death certificates and medical records. The metabolite profile was identified using elastic net regressions with train test validation split (70-30%). Metabolic pathways were determined using Metabolite Set Enrichment Analysis (MSEA). Multivariable-adjusted Cox proportional hazards regressions were used to estimate hazard ratios and 95% confidence intervals (HR[CI]) per unit of score of the healthy lifestyle metabolite profile with mortality risk. Results: The identified profile included 88 metabolites and correlated with the healthy lifestyle score (Pearson r=0.43-0.44; ppb =0.43; p Conclusions: In US adults, we identified a metabolite profile related to a healthy lifestyle largely reflecting lipid metabolism pathways. A higher metabolite score was associated with lower subsequent all-cause mortality risk, specifically from CVD. Findings provide novel insights into potential metabolic pathways underlying the association between a healthy lifestyle and lower premature mortality.

OBJECTIVE: To examine the association between dietary folate intake and antral follicle count (AFC) among women seeing treatment for infertility. DESIGN: Cohort study SETTING: Academic fertility center PATIENTS: 552 women attending the Massachusetts General Hospital Fertility Center (2007-2019) who participated in the Environment and Reproductive Health Study. INTERVENTION(S): None. Folate intake was measured using a validated food frequency questionnaire at study entry. Multivariable Poisson regression models with robust standard errors were used to estimate the association of folate intake with AFC adjusting for calorie intake, age, BMI, physical activity, education, smoking status, year of AFC, and intakes of vitamin B12, iron, and vitamin D. Non-linearity was assessed with restricted cubic splines. MAIN OUTCOME MEASURES: AFC as measured with transvaginal ultrasonography as part of routine care. RESULTS: Among the 552 women (median age 35.0 years, median folate intake 1,005 μg/day), total and supplemental folate intake had a significant non-linear relationship with AFC (P for non-linearity 0.05 and 0.02, respectively). There was a positive linear association with AFC up to approximately 1200 μg/day for total folate intake and up to 800 μg/day for supplemental folate intake; however, there was no additional benefit of higher folate intakes. The magnitude of association was modest – for example, the predicted adjusted difference in AFC between a woman consuming 400 versus 800 μg/day of supplemental folate was approximately 1.5 follicles. CONCLUSIONS: Higher intake of folate, particularly from supplements, was associated with modestly higher ovarian reserve as measured by AFC among women attending a fertility center. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT00011713

STUDY QUESTIONAre menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?SUMMARY ANSWERIrregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.WHAT IS KNOWN ALREADYLong and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear.STUDY DESIGN, SIZE, DURATIONProspective cohort study. Prospective follow-up of 78 943 women participating in the Nurses’ Health Study II between 1989 and 2015.PARTICIPANTS/MATERIALS, SETTING, METHODSWe followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14–17, 18–22 and 29–46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence.MAIN RESULTS AND THE ROLE OF CHANCEWe documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29–46 years had an 11% (95% CI: 2–21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9–39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09–1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14–17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02–1.81).LIMITATIONS, REASONS FOR CAUTIONOur study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White.WIDER IMPLICATIONS OF THE FINDINGSWomen with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood.STUDY FUNDING/COMPETING INTERESTThis work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare.TRIAL REGISTRATION NUMBERN/A.

Objective To examine the association between ambient temperature and antral follicle count (AFC), a standard measure of ovarian reserve. Design Prospective cohort study. Setting Fertility center at an academic hospital in the northeastern United States. Patient(s) 631 women attending the Massachusetts General Hospital Fertility Center (2005–2015) who participated in the Environment and Reproductive Health Study. Intervention(s) Daily temperature at the women’s residential address was estimated for the 90 days before their antral follicle scan using a spatially refined gridded climate data set. We evaluated the associations between temperature and AFC using Poisson regression with robust standard errors, adjusting for relative humidity, fine particulate matter exposure, age, education, smoking status, year and month of AFC, and diagnosis of diminished ovarian reserve and ovulation disorders. Main Outcome Measure(s) Antral follicle count as measured with transvaginal ultrasonography. Result(s) A 1°C increase in average maximum temperature during the 90 days before ovarian reserve testing was associated with a −1.6% (95% confidence interval [CI], −2.8, −0.4) lower AFC. Associations remained negative, but were attenuated, for average maximum temperature exposure in the 30 days (−0.9%, 95% CI, −1.8, 0.1) and 14 days (−0.8%, 95% CI, −1.6, 0.0) before AFC. The negative association between average maximum temperature and AFC was stronger in November through June than during the summer months, suggesting that timing of heat exposure and acclimatization to heat may be important factors to consider in future research. Conclusion(s) Exposure to higher temperatures was associated with lower ovarian reserve. These results raise concern that rising ambient temperatures worldwide may result in accelerated reproductive aging among women.

STUDY QUESTION Is intake of sugar-sweetened beverages (SSB) or artificially sweetened beverages (ASB) associated with testicular function in young men? SUMMARY ANSWER Among young men unaware of their semen quality and reproductive hormone levels, intake of SSBs was associated with lower sperm concentration, lower total sperm count, and a lower ratio of serum inhibin-B/FSH. WHAT IS KNOWN ALREADY SSBs may adversely impact testicular function, but results are not consistent across studies. Moreover, the associations of ASB, energy-drinks or fruit juices with testicular function are unclear. STUDY DESIGN, SIZE, DURATION Young healthy men and unselected for fertility status men enrolled in a cross-sectional study between 2008 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 2935 young (median age: 19 years) men enrolled in the study. Intake of SSBs, ASBs, fruit juices, and energy-drinks was assessed with a validated food frequency questionnaire. Testicular function was assessed through conventional semen quality parameters (semen volume, sperm concentration, total count, motility and morphology), testicular volume assessed with ultrasound, and serum reproductive hormone concentrations (total testosterone, free testosterone, E2, inhibin-B, LH, FSH, sex hormone-binding globulin) were measured. MAIN RESULTS AND THE ROLE OF CHANCE In multivariable-adjusted analyses, men in the highest category of SSB intake (median: 1.1 servings (∼220 ml)/day) had a 13.2 million/ml lower median sperm concentration (95% CI: –21.0, –5.5) than non-consumers. A similar pattern was observed with total sperm count (–28 million (95% CI: –48, –9)), serum inhibin-B (–12 pg/ml (95% CI: –21, –4)), and inhibin-B/FSH ratio (–9 (95% CI: –18, 0)). The adjusted median difference in sperm concentration and inhibin-B associated with increasing SSB intake by 1 serving (∼200ml)/day at the expense of water was –3.4 million sperm/ml (95% CI: –5.8, –1.0) and –7 pg/ml (95% CI: –11, –3), respectively. LIMITATIONS, REASONS FOR CAUTION Inferring causality is limited owing to the cross-sectional design. We adjusted for a number of potential confounders but cannot exclude that unmeasured lifestyle and behavior associated with soft drink intake is associated with testicular function in these young men. WIDER IMPLICATIONS OF THE FINDINGS In the largest study to date, intake of SSBs was associated with lower sperm concentration, total sperm count, and serum inhibin-B/FSH ratio, consistent with a direct suppressive effect of SSB intake on testicular function among otherwise healthy men, potentially affecting fertility. However, the observed association between higher SSB intake and lower semen quality does not necessarily imply a decrease in fertility. STUDY FUNDING/COMPETING INTEREST(S) Supported by research from the Danish Council for Strategic Research (2101-08-0058), Independent Research Fund Denmark (8020-00218B), European Union (212844), the Kirsten and Freddy Johansen’s Foundation (95-103-72087), the Research Fund of the Capital Region of Denmark (A6176), and the NIH (P30DK046200). The authors report no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

Objective This study examined the associations of central adiposity gain from midchildhood to early adolescence with cardiometabolic health markers in early adolescence. Methods A total of 620 participants were studied in Project Viva. In midchildhood (mean age = 7.8 years) and early adolescence (12.9 years), waist circumference and dual-energy x-ray absorptiometry-measured visceral adipose tissue, subcutaneous abdominal adipose tissue, and trunk fat were obtained. Central adiposity gain was calculated as change per year between visits. Cardiometabolic health markers, including blood pressure, lipids, markers of insulin resistance, inflammation, and adipokines, were collected in early adolescence. Results Greater waist circumference gain was associated with higher log triglycerides (β 0.07 mg/dL; 95% CI: 0.02-0.13), log alanine aminotransferase (0.07 U/L; 95% CI: 0.03-0.12), log high-sensitivity C-reactive protein (0.43 mg/L; 95% CI: 0.28-0.58), and other cardiometabolic markers in early adolescence. Directly measured central adiposity gains were associated with higher systolic blood pressure z score in early adolescence (visceral adipose tissue [0.13 SD units; 95% CI: 0.04-0.23], subcutaneous abdominal adipose tissue [0.18 SD units; 95% CI: 0.04-0.31], and trunk fat [0.21 SD units; 95% CI: 0.06-0.36]). These associations were independent of baseline and change in total adiposity from midchildhood to early adolescence. Conclusions Monitoring central adiposity gain may enable identification and intervention in children vulnerable to developing cardiometabolic health risks.

Background: Emerging evidence suggests beneficial impacts of plant-based diets on glucose metabolism among generally healthy individuals. Whether adherence to these diets is related to risk of gestational diabetes mellitus (GDM) is unknown. Objectives: We aimed to examine associations between plant-based diets and GDM in a large prospective study. Methods: We included 14,926 women from the Nurses' Health Study II (1991-2001), who reported ≥1 singleton pregnancy and without previous GDM before the index pregnancy. Prepregnancy adherence to plant-based diets was measured by an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) as assessed by FFQs every 4 y. Incident first-Time GDM was ascertained from a self-reported physician diagnosis, which was previously validated by review of medical records. We used log-binomial models with generalized estimating equations to calculate RRs and 95% CIs for associations of PDIs with GDM. Results: We documented 846 incident GDM cases over the 10-y follow-up among 20,707 pregnancies. Greater adherence to the PDI and hPDI was associated with lower GDM risk. For the PDI, the multivariable-Adjusted RR (95% CI) comparing the highest and lowest quintiles (Q5 compared with Q1) was 0.70 (0.56, 0.87) (Ptrend = 0.0004), and for each 10-point increment was 0.80 (0.71, 0.90). For the hPDI, the RR (95% CI) of Q5 compared with Q1 was 0.75 (0.59, 0.94) (Ptrend = 0.009) and for each 10-point increment was 0.86 (0.77, 0.95). After further adjustment for prepregnancy BMI, the associations were attenuated but remained significant: for the PDI, the RR (95% CI) for each 10-point increment was 0.89 (0.79, 1.00) and the corresponding RR (95% CI) was 0.89 (0.80, 0.99) for the hPDI. The uPDI was not associated with GDM. Conclusions: Our study suggests that greater prepregnancy adherence to a healthful plant-based diet was associated with lower risk of GDM, whereas an unhealthful plant-based diet was not related to GDM risk.

Objective To examine the impact of men’s diet on outcomes of infertility treatment with assisted reproductive technology (ART) using an empirical score representing the relation of diet with semen quality. Design Prospective cohort study. Setting Fertility center at an academic medical center. Patient(s) We included 296 men (688 semen samples) to identify an empirical dietary pattern and 231 couples (406 ART cycles) to investigate the association of this diet pattern with ART outcomes. Intervention(s) Men’s diet was assessed at baseline using a validated questionnaire. An empirical dietary pattern reflecting the overall relation of diet with semen quality was identified using reduced rank regression. Main Outcome Measure(s) The primary outcome was live birth per treatment cycle. The secondary outcomes were fertilization, implantation, and clinical pregnancy. Result(s) Men had a median baseline age and body mass index of 36.8 years and 26.9 kg/m2, respectively. Although the empirical diet pattern was significantly associated with all semen parameters, the empirical diet score was not related to any clinical outcome of infertility treatment after ART. The adjusted probabilities of relevant clinical outcomes in the lowest and highest quartiles of the empirical score were 0.62 (0.50–0.73) and 0.55 (0.45–0.66) for implantation, 0.57 (0.46–0.69) and 0.50 (0.40–0.61) for clinical pregnancy, and 0.49 (0.37–0.62) and 0.36 (0.25–0.48) for live birth. Analyses excluding couples with a diagnosis of male factor infertility and, separately, excluding intracytoplasmic sperm injection cycles yielded similar results. Conclusion(s) A dietary score representing the overall association of diet with semen quality parameters was not associated with ART outcomes.

ImportanceMenstrual cycle characteristics may be associated with an increased risk of cardiovascular disease (CVD). However, existing studies are limited, and few have explored the mediating role of established CVD risk factors.ObjectiveTo explore the associations of menstrual cycle characteristics across the reproductive lifespan with the risk of CVD and to what extent these associations were mediated by hypercholesterolemia, chronic hypertension, and type 2 diabetes.Design, Setting, and ParticipantsThis cohort study prospectively followed Nurses’ Health Study II participants between 1993 and 2017 who reported menstrual cycle regularity and length for ages 14 to 17 years and 18 to 22 years at enrollment in 1989 and updated current cycle characteristics in 1993 (at ages 29 to 46 years). Data analysis was performed from October 1, 2019, to January 1, 2022.ExposuresMenstrual cycle regularity and length across the reproductive lifespan.Main Outcomes and MeasuresIncident CVD events of interest, including fatal and nonfatal coronary heart disease (CHD; myocardial infarction [MI] or coronary revascularization) and stroke.ResultsA total of 80 630 Nurses’ Health Study II participants were included in the analysis, with a mean (SD) age of 37.7 (4.6) years and body mass index of 25.1 (5.6) at baseline. Over 24 years of prospective follow-up, 1816 women developed their first CVD event. Multivariable Cox proportional hazards models showed that, compared with women reporting very regular cycles at the same ages, women who had irregular cycles or no periods at ages 14 to 17, 18 to 22, or 29 to 46 years had hazard ratios for CVD of 1.15 (95% CI, 0.99-1.34), 1.36 (95% CI, 1.06-1.75), and 1.40 (95% CI, 1.14-1.71), respectively. Similarly, compared with women reporting a cycle length of 26 to 31 days, women reporting a cycle length 40 days or more or a cycle too irregular to estimate from ages 18 to 22 or 29 to 46 years had hazard ratios for CVD of 1.44 (95% CI, 1.13-1.84) and 1.30 (95% CI, 1.09-1.57), respectively. Mediation analyses showed that subsequent development of hypercholesteremia, chronic hypertension, and type 2 diabetes only explained 5.4% to 13.5% of the observed associations.Conclusions and RelevanceIn this cohort study, both irregular and long menstrual cycles were associated with increased rates of CVD, which persisted even after accounting for subsequently established CVD risk factors.

Objective To assess whether maternal ultra-processed food intake during peripregnancy and during the child rearing period is associated with offspring risk of overweight or obesity during childhood and adolescence. Design Population based prospective cohort study. Setting The Nurses’ Health Study II (NHSII) and the Growing Up Today Study (GUTS I and II) in the United States. Participants 19 958 mother-child (45% boys, aged 7-17 years at study enrollment) pairs with a median follow-up of 4 years (interquartile range 2-5 years) until age 18 or the onset of overweight or obesity, including a subsample of 2925 mother-child pairs with information on peripregnancy diet. Main outcome measures Multivariable adjusted, log binomial models with generalized estimating equations and an exchangeable correlation structure were used to account for correlations between siblings and to estimate the relative risk of offspring overweight or obesity defined by the International Obesity Task Force. Results 2471 (12.4%) offspring developed overweight or obesity in the full analytic cohort. After adjusting for established maternal risk factors and offspring’s ultra-processed food intake, physical activity, and sedentary time, maternal consumption of ultra-processed foods during the child rearing period was associated with overweight or obesity in offspring, with a 26% higher risk in the group with the highest maternal ultra-processed food consumption (group 5) versus the lowest consumption group (group 1; relative risk 1.26, 95% confidence interval 1.08 to 1.47, P for trendv group 1: relative risk 1.17, 95% confidence interval 0.89 to 1.53, P for trend=0.07). These associations were not modified by age, sex, birth weight, and gestational age of offspring or maternal body weight. Conclusions Maternal consumption of ultra-processed food during the child rearing period was associated with an increased risk of overweight or obesity in offspring, independent of maternal and offspring lifestyle risk factors. Further study is needed to confirm these findings and to understand the underlying biological mechanisms and environmental determinants. These data support the importance of refining dietary recommendations and the development of programs to improve nutrition for women of reproductive age to promote offspring health.

To examine the association between the consumption of fruits and vegetables and pesticide residue intake from consumption of fruits and vegetables and risk of ultrasound or hysterectomy-confirmed fibroids. Only a few studies have evaluated the association of fruit and vegetable intake with uterine fibroids with inconsistent results. No studies have examined pesticide exposure through fruits and vegetables with fibroid risk.Prospective cohort study. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI).Not applicable.81,782 premenopausal participants from the Nurses' Health Study II cohort were followed from 1991-2009 for the fruits and vegetable analysis, and 49,927 participants were followed from 1999-2009 for the pesticide residue burden analysis. Diet was assessed every four years with a food frequency questionnaire. Fruits and vegetables were classified into high- or low-pesticide-residues using a validated method based on surveillance data from the U.S. Department of Agriculture.Not applicable MAIN OUTCOME MEASURE(S): Cases of ultrasound or hysterectomy-confirmed fibroids were identified from self-reports to validated questionnaires.From 1991-2009, 9,706 incident cases of ultrasound or hysterectomy-confirmed fibroids were reported, and 4,195 incident cases were identified from 1999-2009. No association was observed between total fruit and vegetable consumption and uterine fibroid risk. Participants who consumed the highest intake of total fruits (≥4/day) were 10% less likely to develop uterine fibroids compared to participants who consumed1/day (95% CI=0.80-1.01; pOur findings suggest that pesticide residues on fruits and vegetables are not associated with a higher risk of uterine fibroids. Further, our results suggest that intake of fruits may be associated with a lower risk of fibroids. Future research in this area should focus on dietary exposures across the life course as well as assessment of class-specific pesticides.

The aim of this study was to investigate the extent to which self-reported menstrual cycle length during reproductive years is associated with menopausal symptoms and age at natural menopause at midlife.This analysis includes 634 women who enrolled in Project Viva during pregnancy (1999-2002) and completed the midlife visit approximately 18 years later. Women self-reported menstrual cycle length at enrollment (early pregnancy) and at midlife reported total and specific menopausal symptoms using the Menopause Rating Scale as well as age at natural menopause. We used linear and regression models to evaluate associations of cycle length with total and specific menopausal symptoms. We also applied a time-to-event Cox proportional hazards model to investigate the relationship between menstrual cycle length and onset of natural menopause. We adjusted models for age at midlife visit, prepregnancy body mass index, race/ethnicity, education, and parity.At enrollment (median age, 33.3 years), 90 (14%) women reported having short (≤25 days) and 39 (6%) reported long (≥35 days) menstrual cycles. Compared with women with a normal menstrual cycle length of 26 to 34 days, women whose cycles were short had a higher total Menopause Rating Scale at midlife ( β = 2.05; 95% confidence interval [CI], 0.73-3.38). Specifically, women with short menstrual cycles during their reproductive years had higher odds of midlife sleep problems (odds ratio [OR], 1.92; 95% CI, 1.10-3.37), heart discomfort (OR, 1.68; 95% CI, 1.03-2.73), and depressive symptoms (OR, 1.85; 95% CI, 1.16-2.96). In addition, compared with women with a normal cycle length of 26 to 34 days, women reporting short cycles had an earlier onset of natural menopause (hazard ratio, 1.67; 95% CI, 1.11-2.51).Compared with women with normal menstrual cycle length, those with short menstrual cycles during their reproductive years had a higher frequency of total and certain menopausal symptoms at midlife and reached menopause earlier.

ImportanceFew risk factors for long-lasting (≥4 weeks) COVID-19 symptoms have been identified.ObjectiveTo determine whether high levels of psychological distress before SARS-CoV-2 infection, characterized by depression, anxiety, worry, perceived stress, and loneliness, are prospectively associated with increased risk of developing post–COVID-19 conditions (sometimes called long COVID).Design, Setting, and ParticipantsThis prospective cohort study used data from 3 large ongoing, predominantly female cohorts: Nurses’ Health Study II, Nurses’ Health Study 3, and the Growing Up Today Study. Between April 2020 and November 2021, participants were followed up with periodic surveys. Participants were included if they reported no current or prior SARS-CoV-2 infection at the April 2020 baseline survey when distress was assessed and returned 1 or more follow-up questionnaires.ExposuresDepression, anxiety, worry about COVID-19, perceived stress, and loneliness were measured at study baseline early in the pandemic, before SARS-CoV-2 infection, using validated questionnaires.Main Outcomes and MeasuresSARS-CoV-2 infection was self-reported during each of 6 monthly and then quarterly follow-up questionnaires. COVID-19–related symptoms lasting 4 weeks or longer and daily life impairment due to these symptoms were self-reported on the final questionnaire, 1 year after baseline.ResultsOf 54 960 participants, 38.0% (n = 20 902) were active health care workers, and 96.6% (n = 53 107) were female; the mean (SD) age was 57.5 (13.8) years. Six percent (3193 participants) reported a positive SARS-CoV-2 test result during follow-up (1-47 weeks after baseline). Among these, probable depression (risk ratio [RR], 1.32; 95% CI = 1.12-1.55), probable anxiety (RR = 1.42; 95% CI, 1.23-1.65), worry about COVID-19 (RR, 1.37; 95% CI, 1.17-1.61), perceived stress (highest vs lowest quartile: RR, 1.46; 95% CI, 1.18-1.81), and loneliness (RR, 1.32; 95% CI, 1.08-1.61) were each associated with post–COVID-19 conditions (1403 cases) in generalized estimating equation models adjusted for sociodemographic factors, health behaviors, and comorbidities. Participants with 2 or more types of distress prior to infection were at nearly 50% increased risk for post–COVID-19 conditions (RR, 1.49; 95% CI, 1.23-1.80). All types of distress were associated with increased risk of daily life impairment (783 cases) among individuals with post–COVID-19 conditions (RR range, 1.15-1.51).Conclusions and RelevanceThe findings of this study suggest that preinfection psychological distress may be a risk factor for post–COVID-19 conditions in individuals with SARS-CoV-2 infection. Future work should examine the biobehavioral mechanism linking psychological distress with persistent postinfection symptoms.

To investigate whether history of comorbidities is associated with markers of ovarian reserve among subfertile women.This observational study includes 645 women seeking fertility care at the Massachusetts General Hospital who enrolled in the Environment and Reproductive Health (EARTH) study (2005-2019). Women completed a comprehensive questionnaire including medical diagnosis of comorbidities. Ovarian reserve markers including antral follicle count (AFC), assessed by transvaginal ultrasound, and circulating serum levels of day 3 FSH and AMH, are assessed by immunoassays. We fit linear regression models to evaluate the association between history of comorbidities and markers of ovarian reserve while adjusting for confounders.Self-reported history of hypertension, cancer, and neurological disorders was negatively associated with AFC in unadjusted models and in adjusted models for age, smoking, physical activity, comorbidity count, and BMI. Adjusted mean AFC (95% CI) was lower among women with history of hypertension, compared to women with no self-reported history of hypertension (11.5 vs 15.6, p value 0.0001). In contrast, day 3 FSH levels were positively related to history of eating disorders in both unadjusted and adjusted models (10.8 vs. 7.43 IU/L, p value ≤ 0.0001). Self-reported history of other comorbidities was unrelated to AFC, day 3 FSH, and AMH levels.History of hypertension, cancer, and neurological disorders was negatively associated with AFC, and eating disorders were positively related to day 3 FSH levels. The prevention of common comorbidities among women in reproductive age may help increase women's fertility given the declining birth rates and increasing use of assisted reproductive technologies in the past years.

ImportancePregnancy intention assessment is a key element of preconception and contraceptive care. The association between a single screening question and the incidence of pregnancy is unknown.ObjectiveTo prospectively evaluate the dynamics of pregnancy intention and pregnancy incidence.Design, Setting, and ParticipantsThis prospective cohort study (the Nurses’ Health Study 3) was conducted from June 1, 2010, to April 1, 2022, in 18 376 premenopausal, nonpregnant female nurses aged 19 to 44 years.Main Outcomes and MeasuresPregnancy intention and pregnancy status were assessed at baseline and approximately every 3 to 6 months thereafter. Cox proportional hazards regression models were used to estimate the association between pregnancy intention and pregnancy incidence.ResultsA total of 18 376 premenopausal, nonpregnant women (mean [SD] age, 32.4 [6.5] years) participated in the study. At baseline, 1008 women (5.5%) were trying to conceive, 2452 (13.3%) were contemplating pregnancy within 1 year, and the remaining 14 916 (81.2%) were neither trying to conceive nor thought they would be pregnant within 1 year. A total of 1314 pregnancies were documented within 12 months of pregnancy intention assessment. The cumulative incidence of pregnancy was 38.8% in women actively trying to conceive (median [IQR] time to pregnancy, 3.3 [1.5-6.7] months), 27.6% in women contemplating pregnancy (median [IQR] time to pregnancy, 6.7 [4.2-9.3] months), and 1.7% in women neither trying to conceive nor contemplating pregnancy (median [IQR] time to pregnancy, 7.8 [5.2-10.5] months) among those who became pregnant. Women who were actively trying to conceive were 23.1 times (95% CI, 19.5-27.4 times) and women who were contemplating pregnancy were 13.0 times (95% CI, 11.1-15.2 times) more likely to conceive within 12 months than women who were neither attempting nor contemplating pregnancy. Among women contemplating pregnancy at baseline who did not get pregnant during follow up, 18.8% were actively trying and 27.6% were not trying by 12 months. Conversely, only 4.9% of women neither trying to conceive nor contemplating pregnancy within 1 year at baseline changed pregnancy intention during follow up.Conclusions and RelevanceIn this cohort study of reproductive-aged nurses in North America, pregnancy intention was highly fluid among women who were contemplating pregnancy but relatively stable among women trying to conceive and women who were neither trying to conceive nor contemplating pregnancy. Pregnancy intention was strongly associated with pregnancy incidence, but the median time to pregnancy points to a relatively short time window to initiate preconception care.

Objective To explore associations between early life physical and sexual abuse and subsequent risk of premature mortality (death before age 70 years). Design Prospective cohort study. Setting The Nurses’ Health Study II (2001-19). Participants 67 726 female nurses aged 37-54 years when completing a violence victimization questionnaire in 2001. Main outcome measures Hazard ratios and 95% confidence intervals for total and cause specific premature mortality by childhood or adolescent physical and sexual abuse, estimated by multivariable Cox proportional hazard models. Results 2410 premature deaths were identified over 18 years of follow-up. Nurses who experienced severe physical abuse or forced sexual activity in childhood and adolescence had a higher crude premature mortality rate than nurses without such abuse in childhood or adolescence (3.15 v 1.83 and 4.00 v 1.90 per 1000 person years, respectively). The corresponding age adjusted hazard ratios for premature deaths were 1.65 (95% confidence interval 1.45 to 1.87) and 2.04 (1.71 to 2.44), respectively, which were materially unchanged after further adjusting for personal characteristics and early life socioeconomic status (1.53, 1.35 to 1.74, and 1.80, 1.50 to 2.15, respectively). Cause specific analyses indicated that severe physical abuse was associated with a greater risk of mortality due to external causes of injury and poisoning (multivariable adjusted hazard ratio 2.81, 95% confidence interval 1.62 to 4.89), suicide (3.05, 1.41 to 6.60), and diseases of the digestive system (2.40, 1.01 to 5.68). Forced sexual activity as a child and adolescent was associated with greater risk of mortality due to cardiovascular disease (2.48, 1.37 to 4.46), external injury or poisoning (3.25, 1.53 to 6.91), suicide (4.30, 1.74 to 10.61), respiratory disease (3.74, 1.40 to 9.99), and diseases of the digestive system (4.83, 1.77 to 13.21). The association of sexual abuse with premature mortality was stronger among women who smoked or had higher levels of anxiety during adulthood. Smoking, low physical activity, anxiety, and depression each explained 3.9-22.4% of the association between early life abuse and premature mortality. Conclusion Early life physical and sexual abuse could be associated with a greater risk of adult premature mortality.

Maternal fat intake during pregnancy affects fetal growth, but mechanisms underlying this relationship are unclear. We performed an exploratory study of the associations of fat consumption during pregnancy with cord blood DNA methylation of the insulin-like growth factor 2 (IGF2) and H19 genes. We used data from 96 uncomplicated full-term pregnancies of mothers of whom majority had normal body mass index (BMI) (66%) in Project Viva, a prospective pre-birth cohort. We assessed maternal diet with validated food frequency questionnaires during the first and second trimesters and measured DNA methylation in segments of the IGF2- and H19-differentially methylated regions (DMRs) by pyrosequencing DNA extracted from umbilical cord blood samples. Mean (SD) age was 32.8 (4.1) years and prepregnancy BMI was 24.0 (4.4) kg/m2 . Mean DNA methylation was 56.3% (3.9%) for IGF2-DMR and 44.6% (1.9%) for H19-DMR. Greater first trimester intake of omega-6 polyunsaturated fat (effect per 1% of calories at the expense of carbohydrates) was associated with lower DNA methylation of IGF2-DMR (-1.2%; 95% confidence interval [CI]: -2.2%, -0.2%) and higher DNA methylation at H19-DMR (0.8%; 95% CI: 0.3%, 1.3%). On the other hand, greater first trimester intake of omega-3 polyunsaturated fat was associated with lower DNA methylation of the H19-DMR (-4.3%; 95% CI: -7.9%, -0.8%). We did not find significant associations of IGF2 and H19 methylation with IGF2 cord blood levels. Our findings suggest that early prenatal fat intake (omega-3, omega-6, and saturated fatty acids) may influence DNA methylation at the IGF2 and H19 locus, which could impact fetal development and long-term health.

Objectives: To quantify adequacy of personal protective equipment (PPE) for U.S. healthcare personnel (HCP) at the outset of the COVID-19 pandemic and its association with infection risk. Methods: March–May 2020 survey of the national Nurses’ Health Studies and the Growing Up Today study regarding self-reported PPE access, use, and reuse. COVID-19 endpoints included SARS-CoV-2 tests and COVID-19 status predicted from symptoms. Results: Nearly 22% of 22,232 frontline HCP interacting with COVID-19 patients reported sometimes or always lacking PPE. Fifty percent of HCP reported not needing respirators, including 13% of those working in COVID-19 units. Lack of PPE was cross-sectionally associated with two-fold or greater odds of COVID-19 among those who interacted with infected patients. Conclusion: These data show the need to improve the U.S. infection prevention culture of safety when confronting a novel pathogen.

PURPOSE(S): To evaluate the relationship of men’s dietary patterns with outcomes of in vitro fertilization (IVF). METHODS: This is a prospective cohort study including 231 couples with 407 IVF cycles, presented at an academic fertility center from April 2007 to April 2018. We assessed diet with a validated food frequency questionnaire and identified Dietary Pattern 1 and Dietary Pattern 2 using principal component analysis. We evaluated adjusted probability of IVF outcomes across the quartiles of the adherence to two dietary patterns by generalized linear mixed models. RESULTS: Men had a median age of 36.8 years and BMI of 26.9 kg/m(2). Women’s median age and BMI were 35.0 years and 23.1 kg/m(2), respectively. Adherence to Dietary Pattern 1 (r(Pearson)=0.44) and Dietary Pattern 2 (r(Pearson)=0.54) was positively correlated within couples. Adherence to Dietary Pattern 1 was positively associated with sperm concentration. A 1-unit increase in this pattern was associated with a 13.33 (0.71–25.96) million/mL higher sperm concentration. However, neither Dietary Pattern 1 nor Dietary Pattern 2 was associated with fertilization, implantation, clinical pregnancy, or live birth probabilities. CONCLUSIONS: Data-derived dietary patterns were associated with semen quality but unrelated to the probability of successful IVF outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02251-9.

Background Infertility affects 15-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives Three overall questions will be studied: 1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? 2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And 3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up? Material and methods ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skane University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of bio-specimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem. This article is protected by copyright. All rights reserved.

ObjectivesTo examine the association of occupational exposure to high-level disinfectants (HLDs) with risk of miscarriage among nurses.MethodsOur study included women who enrolled in the Nurses’ Health Study 3 (2010–2020) and had at least one pregnancy during follow-up. Occupational exposure to HLDs was self-reported at baseline. Every 6 months, a follow-up questionnaire was sent to participants asking for detailed information on pregnancies. We used a discrete-time Cox model to calculate the HRs and 95% CIs of miscarriage according to exposure to HLDs.ResultsOur study included 2579 nurses with a median of 5.6 years of follow-up (range: 1–9 years), and we documented 768 (19%) cases of miscarriage among 3974 pregnancies. Compared with women with no HLD exposure, the HRs of miscarriage were 1.08 (95% CI: 0.87 to 1.34) for past users and 0.84 (95% CI: 0.68 to 1.04) for HLD users. Compared with women with no HLD exposure, duration, frequency, and type of HLD and use of exposure controls were not associated with risk of miscarriage. When restricting to pregnancies that occurred within 12 months of HLD use, occupational exposure to unspecified types of HLD was significantly associated with higher risk of miscarriage (HR=1.78; 95% CI: 1.08 to 2.93).ConclusionsWe observed no associations between occupational use of HLDs and miscarriage, except when we restricted to pregnancies occurring within 12 months of assessed baseline exposure. Given the observational design and limited sample size, results should be interpreted cautiously.