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Objectives. To describe longitudinal trends in the prevalence of mental distress across the first year of the COVID-19 pandemic (April 2020‒April 2021) among US women at the intersection of sexual orientation and racialized group. Methods. Participants included 49 805 cisgender women and female-identified people from the COVID-19 Sub-Study, a cohort of US adults embedded within the Nurses' Health Studies 2 and 3 and the Growing Up Today Study. We fit generalized estimating equation Poisson models to estimate trends in depressive and anxiety symptoms by sexual orientation (gay or lesbian, bisexual, mostly heterosexual, completely heterosexual); subsequent models explored further differences by racialized group (Asian, Black, Latine, White, other or unlisted). Results. Relative to completely heterosexual peers, gay or lesbian, bisexual, and mostly heterosexual women had a higher prevalence of depressive and anxiety symptoms at each study wave and experienced widening inequities over time. Inequities were largest for sexual minority women of color, although confidence intervals were wide. Conclusions. The COVID-19 pandemic may have exacerbated already-glaring mental health inequities affecting sexual minority women, especially those belonging to marginalized racialized groups. Future research should investigate structural drivers of these patterns to inform policy-oriented interventions. (Am J Public Health. 2024;114(5):511–522. https://doi.org/10.2105/AJPH.2024.307601) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

BACKGROUND: It remains unclear whether in utero and childhood exposure to air pollution affects pubertal development, particularly age of menarche in girls. OBJECTIVE: The aim of this study was to determine whether residential ambient particulate matter (PM) exposure in utero and during childhood is associated with age of menarche. METHODS: We studied 5,201 girls in the Growing Up Today Study 2 (2004-present) who were 10-17 y of age at enrollment (47.7% premenarchal; 52.3% postmenarchal). Exposure to three size fractions of PM [fine PM with aerodynamic diameter ≤ 2.5 μm (PM2.5), PM with aerodynamic diameters between 2.5 μm and 10 μm (PM2.5-10), and PM with aerodynamic diameter 10 μm (PM10)] was assigned based on maternal residential address, updated every 2 y, using nationwide spatiotemporal models. We estimated average PM exposure in utero, and time-varying windows: annual average exposure in the prior 1 and 2 y and cumulative average from birth. Age of menarche was self-reported on three surveys administered in 2004, 2006, and 2008. We calculated hazard ratios (HR) for menarche for an interquartile range (IQR) increase in PM exposure using Cox proportional hazard models adjusting for potential confounders. RESULTS: Girls attained menarche at 12.3 y of age on average. In the adjusted model, higher residential exposure to ambient PM2.5 during all time windows was associated with earlier age of menarche. The HRs of menarche for each IQR (4 μg/m³) increase in exposure to PM2.5 during the in utero period, 1 y prior to menarche, and throughout childhood were 1.03 [95% confidence interval (CI): 1.00, 1.06], 1.06 (95% CI: 1.02, 1.10) and 1.06 (95% CI: 1.02, 1.10), respectively. Effect estimates for PM10 exposure were similar, albeit attenuated, for all time windows. PM2.5-10 exposure was not associated with age of menarche. DISCUSSION: Among a large, nationwide, prospective cohort of U.S. girls, higher exposure to PM2.5 and PM10 in utero and throughout childhood was associated with an earlier age of menarche. Our results suggest that PM2.5 and PM10 may have endocrine-disrupting properties that could lead to altered timing of menarche. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Females with a history of gestational diabetes mellitus (GDM) are at higher risk of developing type 2 diabetes mellitus (T2D) later in life. Objective This study prospectively examined whether greater habitual coffee consumption was related to a lower risk of T2D among females with a history of GDM. Methods We followed 4522 participants with a history of GDM in the NHS II for incident T2D between 1991 and 2017. Demographic, lifestyle factors including diet, and disease outcomes were updated every 2–4 y. Participants reported consumption of caffeinated and decaffeinated coffee on validated FFQs. Fasting blood samples were collected in 2012–2014 from a subset of participants free of diabetes to measure glucose metabolism biomarkers (HbA1c, insulin, C-peptide; n  = 518). We used multivariable Cox regression models to calculate adjusted HRs and 95% CIs for the risk of T2D. We estimated the least squares mean of glucose metabolic biomarkers according to coffee consumption. Results A total of 979 participants developed T2D. Caffeinated coffee consumption was inversely associated with the risk of T2D. Adjusted HR (95% CI) for ≤1 (nonzero), 2–3, and 4+ cups/d compared with 0 cup/d (reference) was 0.91 (0.78, 1.06), 0.83 (0.69, 1.01), and 0.46 (0.28, 0.76), respectively (P -trend = 0.004). Replacement of 1 serving/d of sugar-sweetened beverage and artificially sweetened beverage with 1 cup/d of caffeinated coffee was associated with a 17% (risk ratio [RR] = 0.83, 95% CI: 0.75, 0.93) and 9% (RR = 0.91, 95% CI: 0.84, 0.99) lower risk of T2D, respectively. Greater caffeinated coffee consumption was associated with lower fasting insulin and C-peptide concentrations (all P -trend <0.05). Decaffeinated coffee intake was not significantly related to T2D but was inversely associated with C-peptide concentrations (P -trend = 0.003). Conclusions Among predominantly Caucasian females with a history of GDM, greater consumption of caffeinated coffee was associated with a lower risk of T2D and a more favorable metabolic profile. [ABSTRACT FROM AUTHOR]

Background Many studies have linked intakes of fat and of specific fatty acids during pregnancy with preeclampsia; however, information on the association of intake before pregnancy with hypertensive disorders of pregnancy (HDP) is scant. Objectives We evaluated the associations of intakes of major and specific types of fat before pregnancy with the risks of HDP, including preeclampsia and gestational hypertension (GHTN). Methods We followed 11,535 women without chronic disease participating in the Nurses' Health Study II from 1991 and 2009. Pre-pregnancy dietary fat was assessed by an FFQ. Intakes of total fat, saturated fat, trans fatty acid (TFA), MUFAs, PUFAs, and fat subtypes (omega-3 and omega-6) were categorized into quintiles of intake. HDP were self-reported. The RRs (95% CIs) of HDP were estimated by log-binomial generalized estimating equation regression models, with an exchangeable correlation matrix to account for repeated pregnancies while adjusting for potential confounders. Results During 19 years of follow-up, there were 495 cases of preeclampsia (2.9%) and 561 (3.3%) cases of GHTN in 16,892 singleton pregnancies. The mean age at pregnancy was 34.6 years (SD, 3.9 years). Among major fat types, only pre-pregnancy TFA was related to a higher risk of HDP (RR, 1.32; 95% CI: 1.05–1.66), and only for preeclampsia (RR, 1.50; 95% CI: 1.07–2.10) but not for GHTN (RR, 1.21; 95% CI: 0.87–1.70). Among specific types of PUFAs, intake of arachidonic acid was positively related with GHTN (RR, 1.43; 95% CI: 1.00–2.04) but not preeclampsia (RR, 1.08; 95% CI: 0.75–1.57). In analyses restricted to pregnancies 1 year after the diet assessment, women with the highest intake of long-chain omega-3 fatty acids had a 31% lower risk of HDP (95% CI: 3%–51%), which was driven by preeclampsia (RR, 0.55; 95% CI: 0.33–0.92). Conclusions Pre-pregnancy intakes of total fat, saturated fat, and MUFA were unrelated to HDP, whereas TFA was positively related to HDP. These findings highlight the importance of ongoing efforts to eliminate TFA from the global food supply. [ABSTRACT FROM AUTHOR]

We aimed to determine whether intake of pesticide residues from fruits and vegetables was associated with glioma. Within 3 prospective cohorts from 1998–2016—the Nurses' Health Study (NHS), Nurses' Health Study II (NHSII), and Health Professionals Follow-up Study—we computed multivariable-adjusted hazard ratios (MVHRs) and 95% confidence intervals (CI) for glioma by quintiles of intake of low- and high-pesticide-residue fruits and vegetables using Cox proportional hazards regression. Fruits and vegetables were categorized as high or low residue using a validated method based on pesticide surveillance data. We confirmed 275 glioma cases across 2,745,862 person-years. A significant association was observed between intake of high-residue fruits and vegetables and glioma in NHS (MVHR = 2.99, 95% CI: 1.38, 6.44 comparing highest with lowest quintile, P for trend = 0.02). This was not identified in NHSII (MVHR = 0.52, 95% CI: 0.19, 1.45, P for trend = 0.20) or Health Professionals Follow-up Study (MVHR = 1.01, 95% CI: 0.42, 2.45, P for trend = 0.39). No significant associations were observed by intake of low-residue fruits and vegetables; overall intake was not significantly associated with glioma in any cohort. We found no evidence for an inverse relationship of fruit and vegetable intake with glioma. Although limited in power, this study suggests a possible association between fruit-and-vegetable pesticide residue intake and risk of glioma that merits further study. [ABSTRACT FROM AUTHOR]

Background Male obesity has been related to poor semen quality and may also have a negative effect on assisted reproductive technologies (ART) outcomes. Whether male waist circumference (WC), as a measure of central obesity, impacts a couple's fertility independently of BMI is unclear. Objectives To examine the associations of male WC with semen quality and couples' outcomes of infertility treatment with ART. Methods Couples presenting to the Massachusetts General Hospital Fertility Center were invited to participate in the study. Between 2009 and 2019, 269 males provided 671 semen samples and 176 couples underwent 317 ART cycles. Height, weight, and WC were measured on site. We analyzed the association of male WC with semen quality and pregnancy outcomes using cluster-weighted regression models to account for repeated observations while adjusting for potential confounders. Models were also stratified by male BMI (<25 kg/m2 compared with ≥25 kg/m2). Results The median male age, WC, and BMI were 36.1 years, 96.0 cm, and 26.8 kg/m2, respectively. A 5-cm increase in WC was associated with a 6.3% (95% CI, 2.1–10.5%) lower sperm concentration after adjustment for potential confounders, including BMI. Male WC was also inversely related to the probability of achieving a live birth. For each 5-cm increase in male WC, the odds of a live birth per initiated cycle decreased by 9.0% (95% CI, 1.1%–16.4%) after accounting for several anthropometric and demographic characteristics of both partners. These associations were stronger among males in the normal BMI category (<25 kg/m2) than among overweight or obese males. Conclusions A higher male WC may be an additional risk factor for poor outcomes of infertility treatment, even after accounting for male and female partner BMIs, particularly in couples where the male partner has a normal BMI. [ABSTRACT FROM AUTHOR]

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) (P trend = 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) (P trend = 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. [ABSTRACT FROM AUTHOR]

Background Because randomized trials of sustained dietary changes are sometimes impractical for long-term outcomes, the explicit emulation of a (hypothetical) target trial using observational data may be an important tool for nutritional epidemiology. Objectives We describe a methodological approach that aims to emulate a target trial of dietary interventions sustained over many years using data from observational cohort studies. Methods We estimated the 20-y risk of all-cause mortality under the sustained implementation of the food-based goals of the American Heart Association (AHA) 2020 using data from 3 prospective observational studies of US men [Health Professionals Follow-up Study (HPFS)] and women [Nurses' Health Study (NHS) and Nurses' Health Study II (NHS II)]. We applied the parametric g-formula to estimate the 20-y mortality risk under a dietary intervention and under no dietary intervention. Results There were 165,411 participants who met the eligibility criteria. The mean age at baseline was 57.4 y (range, 43–82 y) in the HPFS, 52.4 y (range, 39–66 y) in the NHS, and 40.2 y (range, 30–50 y) in the NHS II. During 20 y of follow-up, 13,241 participants died. The estimated 20-y mortality risks under a dietary intervention versus no intervention were 21.9% compared with 25.8%, respectively, in the HPFS (risk difference, −3.9%; 95% CI: −4.9% to −3.2%); 10.0% compared with 12.6%, respectively, in the NHS (risk difference, −2.6%; 95% CI: −3.1% to −1.8%); and 2.1% compared with 2.5%, respectively, in the NHS II (risk difference, −0.35%; 95% CI: −0.56% to −0.09%). The corresponding risk ratios were 0.85 (95% CI: 0.81–0.88) in the HPFS, 0.79 (95% CI: 0.75–0.85) in the NHS, and 0.86 (95% CI: 0.78–0.96) in the NHS II. Conclusions We estimated that adherence to the food-based AHA 2020 Dietary Goals starting in midlife may reduce the 20-y risk of mortality. [ABSTRACT FROM AUTHOR]

Background Trans fatty acid (TFA) intake persists in much of the world, posing ongoing threats to public health that warrant further elucidation. Published evidence suggests a positive association of self-reported TFA intake with non-Hodgkin lymphoma (NHL) risk. Objectives To confirm those reports, we conducted a prospective study of prediagnosis RBC membrane TFA levels and risk of NHL and common NHL histologic subtypes. Methods We conducted a nested case–control study in Nurses' Health Study and Health Professionals Follow-Up Study participants with archived RBC specimens and no history of cancer at blood draw (1989–1090 and 1994–1995, respectively). We confirmed 583 incident NHL cases (332 women and 251 men) and individually matched 583 controls on cohort (sex), age, race, and blood draw date/time. We analyzed RBC membrane TFA using GLC (in 2013–2014) and expressed individual TFA levels as a percentage of total fatty acids. We used unconditional logistic regression adjusted for the matching factors to estimate ORs and 95% CIs for overall NHL risk per 1 SD increase in TFA level and assessed histologic subtype-specific associations with multivariable polytomous logistic regression. Results Total and individual TFA levels were not associated with risk of all NHL or most subtypes. We observed a positive association of total TFA levels with diffuse large B cell lymphoma (DLBCL) risk [ n  = 98 cases; OR (95% CI) per 1 SD increase: 1.30 (1.05, 1.61); P  = 0.015], driven by trans 18:1n–9(ω-9)/elaidic acid [OR (95% CI): 1.34 (1.08, 1.66); P  = 0.007], trans 18:1n–7/vaccenic acid [OR (95% CI): 1.28 (1.04, 1.58); P  = 0.023], and trans 18:2n–6 t,t [OR (95% CI): 1.26 (1.01, 1.57); P  = 0.037]. Conclusions Our findings extended evidence for TFA intake and DLBCL risk but not for other NHL subtypes. Reduced TFA consumption through dietary choices or health policy measures may support prevention of DLBCL, an aggressive NHL subtype. [ABSTRACT FROM AUTHOR]

Background It is unclear whether adherence to diet recommendations for the prevention of cardiovascular disease (CVD) in the general population is also related to the risk of hypertensive disorders of pregnancy, including pre-eclampsia and gestational hypertension (GHTN). Objectives The aim was to evaluate the relation of prepregnancy adherence to the American Heart Association (AHA) diet recommendations and the Dietary Approaches to Stop Hypertension (DASH) with the risk of pre-eclampsia and GHTN. Methods Between 1991 and 2009, we prospectively followed 16,892 singleton pregnancies among 11,535 women who participated in the Nurses' Health Study II. Prepregnancy diet was assessed every 4 y, from which we calculated dietary pattern scores from the DASH diet (8 components) and the diet recommendations from the AHA 2020 Strategic Impact Goals (primary score: 5 components; secondary score: primary score plus 3 components). Pregnancy outcomes were self-reported, and we estimated the RR (95% CI) of pre-eclampsia and GHTN with log-binomial regression using generalized estimating equations to account for repeat pregnancies and adjusting for potential confounders. Results Women had a mean (SD) age of 34.4 (34.0) y at pregnancy. Pre-eclampsia was reported in 495 (2.9%) pregnancies and GHTN in 561 (3.3%) pregnancies. The RR (95% CI) of pre-eclampsia for women in the highest quintile of the DASH was 0.65 (0.48, 0.87) compared with women in the lowest score quintile. A similar inverse trend was observed for the AHA primary (0.74; 95% CI: 0.55, 1.00) and secondary (0.81; 95% CI: 0.61, 1.07) scores comparing women in the highest versus the lowest score quintile. Neither the DASH nor the AHA scores were related to GHTN. Conclusions Women with higher adherence to dietary recommendations for the prevention of CVD in the general population had a lower risk of pre-eclampsia—a common pregnancy complication related to higher CVD risk among women—than women with lower adherence to these recommendations. [ABSTRACT FROM AUTHOR]

Objective: To characterize dietary patterns and physical activity in a diverse cohort of Midwestern reproductive-age women and to determine associations between these lifestyle factors, socioeconomic factors, and obesity. Methods: In this cross-sectional study, 185 women completed validated food frequency and physical activity questionnaires. Dietary patterns were identified through principal component analysis. Sociodemographic characteristics associated with dietary pattern adherence and physical activity participation were identified through linear regression. Associations between lifestyle factors and obesity were assessed through logistic regression. Results: Two dietary patterns were identified: a "Prudent" pattern characterized by consumption of fruits, vegetables, olive oil, and nuts and a "Western" pattern including meat, refined carbohydrates, and high-calorie drinks. African-American women and women without a college degree were more likely to adhere to the Western dietary pattern than other women. Women in areas with higher socioeconomic deprivation had lower levels of physical activity, especially leisure-time exercise. Women who completed college participated in more leisure-time exercise and had less physically demanding occupations. Obesity was associated with increasing adherence to the Western dietary pattern in a dose-dependent fashion (aOR range 2.68–4.33, 95% CI range 0.69–16.61) but was not associated with adherence to the Prudent pattern (aOR range 0.46–1.06, 95% CI range 0.13–3.41). Increased physical activity was associated with reduced odds of obesity (aOR range 0.28–0.30, 95% CI range 0.10–0.93). Conclusions for Practice: This study highlights dietary and physical activity patterns associated with obesity in reproductive-age women. Lifestyle interventions focused on minimizing consumption of the Western diet and increasing physical activity may provide an opportunity to reduce obesity among reproductive-age women. [ABSTRACT FROM AUTHOR]

BACKGROUND: Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women. OBJECTIVE: We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity. METHODS: This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using 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 and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores. RESULTS: We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of fT4, TT4, fT3, and TT3 [absolute difference: -0.62; 95% confidence interval (CI): -0.12, -0.01; 푝= 0.04; absolute difference: -8.31; 95% CI: -13.8, -2.85; 푝= 0.003; absolute difference: -0.37; 95% CI: 0.54, -0.19; 푝< 0.0001; and absolute difference: -0.21; 95% CI: -0.32, -0.10; 푝= 0.003, respectively]. Using BKMR, we observed that mono(2-ethyl-5 hydroxyhexyl) phthalate (MEHHP) was the primary contributor to these negative associations. DEHP and non-DEHP factor scores were not associated with serum TSH, TgAb, or TPOAb. CONCLUSIONS: Mixtures of urinary DEHP metabolites were inversely associated with serum biomarkers of thyroid function but not with autoimmunity, which were within normal ranges for healthy adult women. https://doi.org/10.1289/EHP6740 [ABSTRACT FROM AUTHOR]

We examined interactions between lifestyle factors and genetic risk of type 2 diabetes (T2D-GR), captured by genetic risk score (GRS) and family history (FH). Our initial study cohort included 20,524 European-ancestry participants, of whom 1,897 developed incident T2D, in the Nurses' Health Study (1984–2016), Nurses' Health Study II (1989–2016), and Health Professionals Follow-up Study (1986–2016). The analyses were replicated in 19,183 European-ancestry controls and 2,850 incident T2D cases in the Women's Genome Health Study (1992–2016). We defined 2 categories of T2D-GR: high GRS (upper one-third) with FH and low GRS or without FH. Compared with participants with the healthiest lifestyle and low T2D-GR, the relative risk of T2D for participants with the healthiest lifestyle and high T2D-GR was 2.24 (95% confidence interval (CI): 1.76, 2.86); for participants with the least healthy lifestyle and low T2D-GR, it was 4.05 (95% CI: 3.56, 4.62); and for participants with the least healthy lifestyle and high T2D-GR, it was 8.72 (95% CI: 7.46, 10.19). We found a significant departure from an additive risk difference model in both the initial and replication cohorts, suggesting that adherence to a healthy lifestyle could lead to greater absolute risk reduction among those with high T2D-GR. The public health implication is that a healthy lifestyle is important for diabetes prevention, especially for individuals with high GRS and FH of T2D. [ABSTRACT FROM AUTHOR]

Traffic-related air pollution has been linked to higher risks of infertility and miscarriage. We evaluated whether folate intake modified the relationship between air pollution and livebirth among women using assisted reproductive technology (ART). Our study included 304 women (513 cycles) presenting to a fertility center in Boston, Massachusetts (2005–2015). Diet and supplements were assessed by food frequency questionnaire. Spatiotemporal models estimated residence-based daily nitrogen dioxide (NO2), ozone, fine particulate, and black carbon concentrations in the 3 months before ART. We used generalized linear mixed models with interaction terms to evaluate whether the associations between air pollutants and livebirth were modified by folate intake, adjusting for age, body mass index, race, smoking, education, infertility diagnosis, and ART cycle year. Supplemental folate intake significantly modified the association of NO2 exposure and livebirth (P = 0.01). Among women with supplemental folate intakes of <800 μg/day, the odds of livebirth were 24% (95% confidence interval: 2, 42) lower for every 20-parts-per-billion increase in NO2 exposure. There was no association among women with intakes of ≥800 μg/day. There was no effect modification of folate on the associations between other air pollutants and livebirth. High supplemental folate intake might protect against the adverse reproductive consequences of traffic-related air pollution. [ABSTRACT FROM AUTHOR]

Background Mushrooms are good dietary sources of important vitamins, minerals, and bioactive compounds which may be important in the prevention of chronic diseases. However, studies have not prospectively evaluated the potential health effects of mushrooms with respect to major cardiometabolic diseases. Objectives The aim of this study was to examine the association of mushroom consumption with major cardiometabolic diseases and mediating biomarkers in 2 large prospective US cohorts. Methods We followed 67,139 women from the Nurses' Health Study (1986–2012) and 43,541 men from the Health Professionals Follow-up Study (1986–2012) who were free of chronic diseases. Mushroom consumption was assessed at baseline through the use of a food-frequency questionnaire. Cardiometabolic biomarkers were collected in subpopulations of the 2 cohorts. Cox proportional hazards models were used to estimate HRs and 95% CIs of cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, and type 2 diabetes (T2D), associated with mushroom consumption. Results We identified total 11,894 CVD (7,616 CHD; 4,278 stroke), and 10,206 T2D cases in >2 million person-years of follow-up. In the pooled multivariable-adjusted analysis, participants who consumed ≥5 servings of mushrooms per week had no significantly different risk of total CVD (HR: 1.02; 95% CI: 0.91, 1.14), CHD (HR: 1.00; 95% CI: 0.87, 1.16), stroke (HR: 1.05; 95% CI: 0.87, 1.25), or T2D (HR: 1.04; 95% CI: 0.93, 1.16) than participants who consumed mushrooms <1 time/mo. We consistently found no association between mushroom consumption and the aforementioned cardiometabolic diseases, in subgroups of sex, lifestyle factors, and medical conditions. Moreover, mushroom consumption was not associated with plasma biomarkers of lipids, insulin, and inflammation. Conclusions We found no association of mushroom consumption with biomarkers and risks of CVD and T2D in US adults. More large prospective cohort studies are warranted to investigate this association in other racial/ethnic groups. [ABSTRACT FROM AUTHOR]

BACKGROUND: A few studies suggest that air pollution may decrease fertility, but prospective studies and examinations of windows of susceptibility remain unclear. OBJECTIVE: We aimed to examine the association between time-varying exposure to nitrogen dioxide (NO2), ozone (O3), fine particulate matter <2:5 lm (PM2:5), and black carbon (BC) on in vitro fertilization (IVF) outcomes. METHODS: We included 345 women (522 IVF cycles) for the NO2, O3, and PM2:5 analyses and 339 women (512 IVF cycles) for the BC analysis enrolled in a prospective cohort at a Boston fertility center (2004-2015). We used validated spatiotemporal models to estimate daily residential exposure to NO2, O3, PM2:5, and BC. Multivariable discrete time Cox proportional hazards models with four periods [ovarian stimulation (OS), oocyte retrieval to embryo transfer (ET), ET to implantation, implantation to live birth] estimated odds ratios (OR) and 95% confidence intervals (CI) of failing at IVF. Time-dependent interactions were used to identify vulnerable periods. RESULTS: An interquartile range (IQR) increase in NO2, PM2:5, and BC throughout the IVF cycle was associated with an elevated odds of failing at IVF prior to live birth (OR=1:08, 95% CI: 0.95, 1.23 for NO2; OR=1:06, 95% CI: 0.88, 1.28 for PM2:5; and OR=1:16, 95% CI: 0.96, 1.41 for BC). This relationship significantly varied across the IVF cycle such that the association with higher exposure to air pollution during OS was strongest for early IVF failures. An IQR increase in NO2, PM2:5, and BC exposure during OS was associated with 1.42 (95% CI: 1.20, 1.69), 1.26 (95% CI: 0.96, 1.67), and 1.23 (95% CI: 0.96, 1.59) times the odds of failing prior to oocyte retrieval, and 1.32 (95% CI: 1.13, 1.54), 1.27 (95% CI: 0.98, 1.65), and 1.32 (95% CI: 1.10, 1.59) times the odds of failing prior to ET. CONCLUSION: Increased exposure to traffic-related pollutants was associated with higher odds of early IVF failure. [ABSTRACT FROM AUTHOR]

Background: Some dietary factors have been linked to outcomes of infertility treatment with assisted reproductive technology (ART), but the role of intake of meats and other protein-rich foods remains unclear. Objective: The aim of this manuscript was to study the relation between preconception intake of meat and other protein-rich foods and outcomes of infertility treatment with ART. Design: A total of 351 women enrolled in a prospective cohort at the Massachusetts General Hospital Fertility Center and underwent 598 ART cycles for infertility treatment. Meat intake was assessed with a validated food-frequency questionnaire, and ART outcomes were abstracted from electronic medical records. We estimated the associations between intake of protein-rich foods (meats, eggs, beans, nuts, and soy) and the outcome of live birth per initiated cycle using generalized linear mixed models. Results: The average total meat intake was 1.2 servings/d, with most coming from poultry (35%), fish (25%), processed meat (22%), and red meat (17%). Fish intake was positively related to the proportion of cycles resulting in live birth. The multivariableadjusted probabilities of live birth for women in increasing quartiles of fish intake were 34.2% (95% CI: 26.5%, 42.9%), 38.4% (95% CI: 30.3%, 47.3%), 44.7% (95% CI: 36.3%, 53.4%), and 47.7% (95% CI: 38.3%, 57.3%), respectively (P-trend = 0.04). In the estimated substitution analyses, the ORs of live birth associated with increasing fish intake by 2 servings/wk were 1.54 (95% CI: 1.14, 2.07) when fish replaced any other meat, 1.50 (95% CI: 1.13, 1.98) when fish replaced any other protein-rich food, and 1.64 (95% CI: 1.14, 2.35) when fish replaced processed meat. Conclusions: Fish consumption is related to a higher probability of live birth following infertility treatment with ART. This trial was registered at clinicaltrials.gov as NCT00011713. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the relation between pre-pregnancy caffeine and caffeinated beverage intake and risk of spontaneous abortion (SAB).Methods: Our prospective cohort study included 15,590 pregnancies from 11,072 women with no history of SAB in the Nurses’ Health Study II (1991–2009). Beverage intake was assessed every 4 years using a validated questionnaire. Pregnancies were self-reported with case pregnancies lost spontaneously at <20 weeks gestation. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the relative risks (RRs) and 95 % confidence intervals (CIs).Results: There was a positive linear trend across categories of pre-pregnancy caffeine intake and risk of SAB such that women consuming >400 mg/day had 1.11 (95 % CI 0.98, 1.25) times the risk of SAB compared to women consuming <50 mg/day (p trend = 0.05). Total coffee intake had a positive, linear association with SAB. Compared to women with no pre-pregnancy coffee intake, women consuming ≥4 servings/day had a 20 % (6, 36 %) increased risk of SAB (p trend = 0.01). There was no difference in the association between caffeinated and decaffeinated coffee and risk of SAB. Pre-pregnancy intake of caffeinated tea, caffeinated soda, and decaffeinated soda had no association with SAB.Conclusions: Pre-pregnancy coffee consumption at levels ≥4 servings/day is associated with increased risk of SAB, particularly at weeks 8–19. [ABSTRACT FROM AUTHOR]

Background: Refined grains, a major source of dietary carbohydrates, have been related to impaired glucose homeostasis and obesity. Emerging animal data suggest that in utero exposure to dietary refined carbohydrates may predispose offspring to an obese phenotype, indicating a potential role for nutritional programming in the early origins of obesity, but intergenerational human data are lacking. Objective: We prospectively investigated refined-grain intake during pregnancy in association with offspring growth through age 7 y among high-risk children born to women with gestational diabetes mellitus (GDM). Design: The analysis included 918 mother-singleton child dyads from the Danish National Birth Cohort. Offspring body mass index z scores (BMIZs) were calculated by using weight and length or height measured at birth, 5 and 12 mo, and 7 y. Overweight or obesity was defined by WHO cutoffs. Linear and Poisson regressions were used, with adjustment for maternal demographic, lifestyle, and dietary factors. Results: Refined-grain intake during pregnancy was positively associated with offspring BMIZ (adjusted β per serving increase per day: 0.09; 95% CI: 0.02, 0.15) and risk of overweight or obesity at age 7 y [adjusted RR (aRR) comparing the highest with the lowest quartile: 1.80; 95% CI: 1.09, 2.98; P-trend = 0.032]. The association appeared to be more pronounced among children who were breastfed <6 mo. The substitution of 1 serving refined grains/d with an equal serving of whole grains during pregnancy was related to a 10% reduced risk of offspring overweight or obesity at 7 y of age (aRR: 0.90; 95% CI: 0.82, 0.98). No associations were observed between refined-grain intake and infant growth. Conclusions: Higher maternal refined-grain intake during pregnancy was significantly related to a greater BMIZ and a higher risk of overweight or obesity at age 7 y among children born after pregnancies complicated by GDM. The findings highlight pregnancy as a potential window of susceptibility associated with off-spring growth and obesity risk among this high-risk population. Data with longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

The authors evaluated the validity of a 152-item semiquantitative food frequency questionnaire (SFFQ) by comparing it with two 7-day dietary records (7DDRs) or up to 4 automated self-administered 24-hour recalls (ASA24s) over a 1-year period in the women's Lifestyle Validation Study (2010-2012), conducted among subgroups of the Nurses' Health Studies. Intakes of energy and 44 nutrients were assessed using the 3 methods among 632 US women. Compared with the 7DDRs, SFFQ responses tended to underestimate sodium intake but overestimate intakes of energy, macronutrients, and several nutrients in fruits and vegetables, such as carotenoids. Spearman correlation coefficients between energy-adjusted intakes from 7DDRs and the SFFQ completed at the end of the data-collection period ranged from 0.36 for lauric acid to 0.77 for alcohol (mean r = 0.53). Correlations of the end-period SFFQ were weaker when ASA24s were used as the comparison method (mean r = 0.43). After adjustment for within-person variation in the comparison method, the correlations of the final SFFQ were similar with 7DDRs (mean r = 0.63) and ASA24s (mean r = 0.62). These data indicate that this SFFQ provided reasonably valid estimates for intakes of a wide variety of dietary variables and that use of multiple 24-hour recalls or 7DDRs as a comparison method provided similar conclusions if day-to-day variation was taken into account. [ABSTRACT FROM AUTHOR]

The glycaemic and insulin indices assess postprandial glycaemic and insulin response to foods, respectively, which may not reflect the long-term effects of diet on insulin response. We developed and evaluated the validity of four empirical indices to assess the insulinaemic potential of usual diets and lifestyles, using dietary, lifestyle and biomarker data from the Nurses’ Health Study (NHS, n 5812 for hyperinsulinaemia, n 3929 for insulin resistance). The four indices were as follows: the empirical dietary index for hyperinsulinaemia (EDIH) and the empirical lifestyle index for hyperinsulinaemia (ELIH); the empirical dietary index for insulin resistance (EDIR) and the empirical lifestyle index for insulin resistance (ELIR). We entered thirty-nine FFQ-derived food groups in stepwise linear regression models, and defined indices as patterns most predictive of fasting plasma C-peptide, for the hyperinsulinaemia pathway (EDIH and ELIH), and of theTAG:HDL-cholesterol ratio, for the insulin-resistance pathway (EDIR and ELIR). We evaluated the validity of indices in two independent samples from NHS-II and Health Professionals Follow-up Study (HPFS) using multivariable-adjusted linear regression analyses to calculate relative concentrations of biomarkers. The EDIH is comprised of eighteen food groups; thirteen were positively associated with C-peptide and five were inversely associated. The EDIR is comprised of eighteen food groups; ten were positively associated with TAG:HDL-cholesterol and eight were inversely associated. Lifestyle indices had fewer dietary components, and included BMI and physical activity as components. In the validation samples, all indices significantly predicted biomarker concentrations – for example, the relative concentrations of the corresponding biomarkers comparing extreme index quintiles in the HPFS were EDIH, 1·29 (95 % CI 1·22, 1·37); ELIH, 1·78 (95 % CI 1·68, 1·88); EDIR, 1·44 (95 % CI 1·34, 1·55); and ELIR, 2·03 (95 % CI 1·89, 2·19); all Ptrend<0·0001. The robust associations of these novel hypothesis-driven indices with insulin response biomarker concentrations suggest their usefulness in assessing the ability of whole diets and lifestyles to stimulate and/or sustain insulin secretion. [ABSTRACT FROM PUBLISHER]

A recent meta-analysis suggested that circulating fatty acids do not play an important role in prostate carcinogenesis. We hypothesized that the relation between circulating fatty acids and prostate cancer (PCa) risk is modified by time between blood draw and diagnosis. We tested this hypothesis in a prospective case-control study of 476 PCa cases and matched control subjects nested in the Physicians' Health Study. The previously reported associations between fatty acids and PCa in this cohort were dramatically stronger among men diagnosed 10 or more years after blood collection. Statistically significant effect modification by time since blood collection was identified for mono-unsaturated and poly-unsaturated fatty acids and was more pronounced for aggressive tumors. Among men diagnosed fewer than 10 years since blood collection, the relative risks per interquartile range were 1.03 (95% confidence interval [CI] = 0.86 to 1.25) for total mono-unsaturated fatty acids (MUFA) and 0.95 (95% CI = 0.78 to 1.15) for total poly-unsaturated fatty acids (PUFA) whereas among men diagnosed 10 or more years after blood draw the relative risks per interquartile range were 1.69 (95% CI = 1.21 to 2.34) for MUFA (Pheterogeneity = .01) and 0.59 (95% CI = 0.42 to 0.83) for PUFA (Pheterogeneity = .02). These data suggest that the results of the meta-analysis may be partly explained by insufficient follow-up time. Furthermore, they suggest that some environmental and metabolic factors may play a role in prostate carcinogenesis decades before clinical identification of this disease. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency impairs fertility in animal models, but the role of vitamin D in human fertility or treatment of infertility is less clear. Objective: We examined the association between circulating 25-hydroxyvitamin D [25(OH)D] concentrations and the outcome in women undergoing assisted reproduction technologies (ARTs). Design: We randomly selected 100 women undergoing infertility treatment with ART enrolled in an ongoing prospective cohort study who underwent 168 treatment cycles. Serum 25(OH)D concentrations were measured in samples collected from women between days 3 and 9 of gonadotropin treatment. Generalized linear mixed models were used to evaluate the association of 25(OH)D concentrations with ART outcomes while adjusting for potential confounders and accounting for repeated treatment cycles per woman. Results: Median (range) serum 25(OH)D concentrations were 86.5 (33.5-155.5) nmol/L. Ninety-one percent of participants consumed multivitamins. Serum 25(OH)D concentrations were positively related to fertilization rate. The adjusted fertilization rate for women in increasing quartiles of serum 25(OH)D were 0.62 (95% CI: 0.51, 0.72), 0.53 (95% CI: 0.43, 0.63), 0.67 (95% CI: 0.56, 0.76), and 0.73 (95% CI: 0.63, 0.80), respectively (P-trend = 0.03). This association persisted when analyses were restricted to women with serum 25(OH)D between 50 and 125 nmol/L when models were further adjusted for season of blood draw and when analyses were restricted to the first treatment cycle. However, 25(OH)D concentrations were unrelated to probability of pregnancy (P-trend = 0.83) or live birth after ART (P-trend = 0.47). Conclusion: Vitamin D may be associated with higher fertilization rates, but this apparent benefit does not translate into higher probability of pregnancy or live birth. This trial was registered at www.clinicaltrials.gov as NCT00011713. [ABSTRACT FROM AUTHOR]

Background: Given the long-term adverse sequelae of childhood obesity, identification of early life factors related to fetal growth and childhood obesity is warranted. Investigation on growth and obesity in early life in association with intrauterine exposure to maternal hyperglycemia, a common metabolic pregnancy complication, is of public health significance and clinical implications. Objective: We investigated the association of fasting plasma glucose (FPG) concentrations during pregnancy with offspring growth and risk of overweight/obesity through age 7 y, after adjustment for confounders, including maternal prepregnancy obesity status. Design: FPG concentrations at 28 gestational weeks (IQR: 22-32 wk) were extracted from medical records for 661 pregnancies complicated by gestational diabetes mellitus in the Danish National Birth Cohort (1996-2002). Offspring's ponderal index was derived from birth weight and length; age- and sex-specific body mass index (BMI) z scores at 5 mo, 12 mo, and 7 y were calculated based on WHO reference data. Relations between FPG and offspring growth and obesity were assessed by linear and Poisson regression with robust standard errors, adjusting for maternal prepregnancy BMI and sociodemographic and perinatal factors. Results: At birth, maternal FPG during pregnancy was significantly associated with offspring ponderal index (β = 0.46; 95% CI: 0.14, 0.78 per 1-mmol/L increase) and risk of macrosomia (birth weight >4000 g) (RR = 1.21; 95% CI: 1.07, 1.38 per 1-mmol/L increase). At 7 y, higher maternal FPG concentrations were significantly associated with increased BMI z scores (β = 0.20; 95% CI: 0.04, 0.36) and elevated risk of overweight/obesity (RR = 1.21; 95% CI: 1.01, 1.50). Additional adjustment for birth weight and childhood lifestyle factors did not appreciably alter results. No associations were observed at 5 or 12 mo. Conclusion: Among women with gestational diabetes mellitus, maternal FPG concentrations during pregnancy were significantly and positively associated with offspring birth size and overweight/obesity risk at 7 y, adjusting for maternal prepregnancy BMI. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests potential links between some dietary fatty acids and improved fertility, because specific fatty acids may affect prostaglandin synthesis and steroidogenesis. Objective: The objective of this exploratory study was to evaluate associations between total and specific types of dietary fat intake and 1) hormone concentrations and 2) the risk of sporadic anovulation in a cohort of 259 regularly menstruating women in the Bio-Cycle Study. Design: Endogenous reproductive hormones were measured up to 8 times/cycle for up to 2 cycles, with visits scheduled with the use of fertility monitors. Dietary intake was assessed with up to four 24-h recalls/cycle. Linear mixed models and generalized linear models were used to evaluate the associations between dietary fatty acids and both reproductive hormone concentrations and ovulatory status. All models were adjusted for total energy intake, age, body mass index, and race. Results: Relative to the lowest levels of percentage of energy from total fat, the highest tertile was associated with increased total and free testosterone concentrations (total: percentage change of 4.0%; 95% CI: 0.7%, 7.3%; free: percentage change of 4.1%; 95% CI: 0.5%, 7.7%). In particular, the percentage of energy from polyunsaturated fatty acids (PUFAs) in the highest tertile was associated with increases in total and free testosterone (total: percentage change of 3.7%; 95% CI: 0.6%, 6.8%; free: percentage change of 4.0%; 95% CI: 0.5%, 7.5%). The PUFA docosapentaenoic acid (22:5n-3) was not significantly associated with testosterone concentrations (P-trend = 0.86 in energy substitution models) but was associated with increased progesterone and a reduced risk of anovulation (highest tertile compared with the lowest tertile: RR: 0.42; 95% CI: 0.18, 0.95). Fat intakes were not associated with other reproductive hormone concentrations. Conclusions: These results indicate that total fat intake, and PUFA intake in particular, is associated with very small increases in testosterone concentrations in healthy women and that increased docosapentaenoic acid was associated with a lower risk of anovulation. [ABSTRACT FROM AUTHOR]

Background: Fetal exposure to parental smoking may have long-term impact on the development of disease in adulthood. We examined the association of parental smoking during pregnancy with risk of gestational diabetes mellitus (GDM) in the daughter.Methods: We included 15,665 singleton pregnancies from 10,152 women in the Nurses' Health Study II cohort whose mothers participated in the Nurses' Mothers' Cohort Study. Data on maternal and paternal smoking during pregnancy and associated covariates were recalled by the mothers. GDM diagnosis was self-reported by the daughters and was validated by medical record review in a previous study. We used log-binomial models with generalized estimating equations to estimate relative risks (RRs) and 95% confidence intervals (CIs).Results: We observed a positive association between maternal heavy smoking during pregnancy and risk of GDM in the daughter. The multivariable-adjusted RRs (95% CIs) of GDM among women whose mothers did not smoke during pregnancy, continued smoking 1-14, 15-24, and ≥ 25 cigarettes/day were 1.00 (reference), 1.05 (0.81-1.35), 1.27 (0.95-1.70) and 1.98 (1.18-3.30), respectively (P for trend = 0.01). Further adjustment for the women's perinatal variables, adult-life characteristics and body mass index during various periods of life modestly attenuated the association. No association was observed between paternal smoking during the pregnancy period and risk of GDM in the daughter.Conclusions: Maternal heavy smoking (≥ 25 cigarettes/day) during pregnancy was associated with higher risk of gestational diabetes in the daughter. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: An iron overload may induce pancreatic islet damage and increase risk of diabetes. Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM) after pregnancy. Objective: We aimed to examine the association of habitual iron intake with long-term risk of T2DM in this high-risk population. Design: We included 3976 women with a history of GDM from the Nurses' Health Study II cohort as part of the ongoing Diabetes & Women's Health Study. The women were followed up through 2009. Iron intake was assessed with the use of a validated food-frequency questionnaire in 1991 and every 4 y thereafter. We used Cox proportional hazards models to estimate HRs and 95% CIs. Results: We documented 641 incident T2DM cases during 57,683 person-years of observation. Adjusted HRs for T2DM for the highest quartile compared with the lowest quartile were 1.64 (95% CI: 1.20, 2.25; P-trend = 0.02) for total iron intake and 1.80 (95% CI: 1.18, 2.74; P-trend = 0.005) for dietary heme iron intake. In addition, women who consumed ≥30.0 mg supplemental Fe/d, compared with nonusers, had an adjusted HR of 1.83 (95% CI: 1.25, 2.70; P-trend = 0.002). Conclusion: In women with a history of GDM, greater intakes of total iron, dietary heme iron, and supplemental iron were associated with higher risk of T2DM. [ABSTRACT FROM AUTHOR]

Background: Preconceptional folate and vitamin B-12 have been linked to beneficial reproductive outcomes in both natural pregnancies and those after assisted reproductive technology (ART) treatment. Objective: The objective of the study was to evaluate the associations of serum folate and vitamin B-12 with ART outcomes. Design: This analysis included a random sample of 100 women (154 ART cycles) participating in a prospective cohort study [Environment and Reproductive Health (EARTH)] at the Massachusetts General Hospital Fertility Center (2007-2013). Serum folate and vitamin B-12 were measured in blood samples collected between days 3 and 9 of treatment. Generalized estimating equations with adjustment for age, BMI, and race were used to evaluate the association of serum folate and vitamin B-12 with ART outcomes. Results: Women in the highest quartile of serum folate (.26.3 ng/mL) had 1.62 (95% CI: 0.99, 2.65) times the probability of live birth compared with women in the lowest quartile (,16.6 ng/mL).Women in the highest quartile of serum vitamin B-12 (.701 pg/mL) had 2.04 (95% CI: 1.14, 3.62) times the probability of live birth compared with women in the lowest quartile (,439 pg/mL). Suggestive evidence of an interaction was observed; women with serum folate and vitamin B-12 concentrations greater than the median had 1.92 (95% CI: 1.12, 3.29) times the probability of live birth compared with women with folate and vitamin B-12 concentrations less than or equal to the median. This translated into an adjusted difference in live birth rates of 26% (95% CI: 10%, 48%; P = 0.02). Conclusion: Higher serum concentrations of folate and vitamin B-12 before ART treatment were associated with higher live birth rates among a population exposed to folic acid fortification. This trial was registered at clinicaltrials.gov as NCT00011713. [ABSTRACT FROM AUTHOR]

Background: Two previous case-control studies observed associations between specific food groups and risk of miscarriage; however, to our knowledge, no previous studies have investigated dietary patterns and risk of pregnancy loss. Objective: We aimed to assess prepregnancy adherence to the alternate Healthy Eating Index 2010 (aHEI-2010), alternate Mediterranean diet (aMED), and Fertility Diet (FD) and risk of pregnancy loss. Design: Our prospective cohort study included 15,950 pregnancies reported by 11,072 women in the Nurses' Health Study II between 1992 and 2009. Diet was assessed every 4 y starting in 1991 by using a validated food-frequency questionnaire. Prepregnancy dietary pattern scores were computed as the sum of a woman's score on each pattern's predefined components. Multivariable log-binomial regression models with generalized estimating equations were used to estimate RRs and 95% CIs. Results: Incident spontaneous abortions and stillbirths were reported in 2756 (17.3%) and 120 (0.8%) pregnancies, respectively. None of the 3 dietary patterns were associated with risk of pregnancy loss. In the multivariable model, RR of pregnancy loss for a 1-SD increase in score was 1.02 (95% CI: 0.98, 1.05) for the aMED pattern, 1.01 (95% CI: 0.98, 1.05) for the aHEI-2010 pattern, and 0.98 (95% CI: 0.95, 1.01) for the FD pattern. Results were consistent when pregnancy loss was classified as either a spontaneous abortion (loss at <20 wk) or a stillbirth (loss at ≥20 wk). Conclusion: Prepregnancy adherence to several dietary patterns was not associated with risk of pregnancy loss. [ABSTRACT FROM AUTHOR]

Studies of delayed conception and risk of gestational diabetes (GDM) are sparse, although common underlying mechanisms are plausible, including insulin resistance and inflammation. The association between a history of infertility and GDM was assessed prospectively among 40,773 eligible pregnancies in the US Nurses' Health Study II cohort (1989–2001). Biennial questionnaires provided updated information on infertility and several lifestyle and health-related characteristics. Multivariable log-binomial models with generalized estimating equations were used to compute risk ratios and 95% confidence intervals, adjusting for age, prepregnancy body mass index (weight (kg)/height (m)2), and additional potential confounders. GDM occurred among 1,405 (5.2%) women. A prepregnancy history of infertility was reported by 5,497 (20.5%) participants and was significantly associated with a 39% greater risk of GDM (risk ratio (RR) = 1.39, 95% confidence interval (CI): 1.24, 1.57; P < 0.001). Underlying reasons for infertility associated with GDM included ovulation disorders (RR = 1.52, 95% CI: 1.23, 1.87; P < 0.001) and tubal blockage (RR = 1.83, 95% CI: 1.20, 2.77; P = 0.005). The association of cervical mucus disorder with GDM was of borderline significance (RR = 1.70, 95% CI: 0.88, 3.30; P = 0.11). Endometriosis (RR = 1.27, 95% CI: 0.70, 2.31; P = 0.43) and male factor infertility (RR = 1.12, 95% CI: 0.78, 1.61; P = 0.55) were not associated with GDM risk. These novel findings suggest that infertility, particularly from ovulation disorders and tubal blockage, is associated with an increased GDM risk. Further research is needed to identify mechanisms or common underlying metabolic dysfunction explaining these observations. [ABSTRACT FROM PUBLISHER]

De novo lipogenesis has been implicated in prostate carcinogenesis, and blood levels of specific saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) could reflect activity of this pathway. We used gas chromatography to measure blood SFA and MUFA levels in prediagnostic samples from 476 incident prostate cancer cases (1982–1995) in the Physicians' Health Study and an equal number of controls matched on age and smoking status. Five tagging polymorphisms in the fatty acid synthase (FASN) gene (rs1127678, rs6502051, rs4246444, rs12949488, and rs8066956) were related to blood SFA and MUFA levels. Conditional logistic regression was used to estimate the rate ratios, with 95% confidence intervals, of prostate cancer across quintiles of blood fatty acid levels. The polymorphisms rs6502051 and rs4246444 were associated with lower levels of 14:1n-5, 16:1n-7, and 18:1n-9. Blood levels of 16:1n-7 were associated with higher prostate cancer incidence, with rate ratios for men in increasing quintiles of 1.00, 1.40, 1.35, 1.44, and 1.97 (95% confidence interval: 1.27–3.06; Ptrend = 0.003). Furthermore, 16:1n-7 levels were positively related to incidence of high-grade (Gleason score ≥7) tumors (rate ratioQ5–Q1 = 3.92; 95% confidence interval: 1.72–8.94) but not low-grade tumors (rate ratioQ5–Q1 = 1.51; 95% confidence interval: 0.87–2.62) (Pheterogeneity = 0.02). Higher activity of enzymes involved in de novo lipogenesis, as reflected in blood levels of 16:1n-7, could be involved in the development of high-grade prostate cancer. [ABSTRACT FROM PUBLISHER]

The etiology of endometriosis is poorly understood, and few modifiable risk factors have been identified. Dairy foods and some nutrients can modulate inflammatory and immune factors, which are altered in women with endometriosis. We investigated whether intake of dairy foods, nutrients concentrated in dairy foods, and predicted plasma 25-hydroxyvitamin D (25(OH)D) levels were associated with incident laparoscopically confirmed endometriosis among 70,556 US women in Nurses’ Health Study II. Diet was assessed via food frequency questionnaire. A score for predicted 25(OH)D level was calculated for each participant. During 737,712 person-years of follow-up over a 14-year period (1991–2005), 1,385 cases of incident laparoscopically confirmed endometriosis were reported. Intakes of total and low-fat dairy foods were associated with a lower risk of endometriosis. Women consuming more than 3 servings of total dairy foods per day were 18% less likely to be diagnosed with endometriosis than those reporting 2 servings per day (rate ratio = 0.82, 95% confidence interval: 0.71, 0.95; Ptrend = 0.03). In addition, predicted plasma 25(OH)D level was inversely associated with endometriosis. Women in the highest quintile of predicted vitamin D level had a 24% lower risk of endometriosis than women in the lowest quintile (rate ratio = 0.76, 95% confidence interval: 0.60, 0.97; Ptrend = 0.004). Our findings suggest that greater predicted plasma 25(OH)D levels and higher intake of dairy foods are associated with a decreased risk of endometriosis. [ABSTRACT FROM PUBLISHER]

Objective: To assess the relation between body mass index (BMI) and short-term weight change with assisted reproductive technology (ART) outcomes. Design: Prospective cohort study. Setting: Fertility center. Patient(s): A total of 170 women undergoing 233 ART cycles. Intervention(s): Baseline BMI and short-term weight change were related to ART outcomes. Regression models accounting for repeated observations were used to adjust data for potential confounders. Main Outcome Measure(s): Peak E2 levels, oocyte yield, MII yield, fertilization rate, embryo quality, postive [beta]-hCH, clinical pregnancy and live birth rates. Result(s): Overweight and obesity were associated with lower live birth rates. The adjusted live birth rate (95% confidence interval) was 42% (28%–58%) among women with a BMI between 20 and 22.4 kg/m2 and 23% (14%–36%) among overweight or obese women. Short-term weight loss was associated with a higher proportion of metaphase II (MII) oocytes retrieved. The adjusted proportion of MII eggs was 91% (87%–94%) for women who lost 3 kg or more and 86% (81%–89%) for women whose weight remained stable. This association was stronger among women who were overweight or obese at baseline. Short-term weight loss was unrelated to positive β-hCG, clinical pregnancy, or live birth rates. Conclusion(s): Overweight and obesity were related to lower live birth rates in women undergoing ART. Short-term weight loss was related to higher MII yield, particularly among overweight and obese women, but unrelated to clinical outcomes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Polycystic Ovary Syndrome (PCOS) is common among females, with significantmetabolic and reproductive comorbidities.We describe PCOS development in a pediatric population. METHODS: We assessed cardiometabolic biomarkers and adiposity at the midchildhood (mean 7.9 y), early teen (mean 13.1 y), and midteen (mean 17.8 y) visits among 417 females in the prospective Project Viva cohort. We defined PCOS via self-reported diagnosis or ovulatory dysfunction with hyperandrogenism in midlate adolescence. We used multivariable logistic regression to assess associations of metabolic and adiposity markers at each visit with PCOS. RESULTS: Adolescents with PCOS (n = 56, 13%) versus without had higher mean (SD) BMI z-score and truncal fat mass at the midchildhood (0.66 [0.99] vs 0.30 [1.04]; 3.5 kg [2.6] vs 2.7 [1.5]), early teen (0.88 [1.01] vs 0.25 [1.08]; 9.4 kg [6.7] vs 6.1 [3.4]), and midteen (0.78 [1.03] vs 0.33 [0.97]; 11.6 kg [7.2] vs 9.1 [4.9]) visits as well as lower adiponectin to leptin ratio at the early (0.65 [0.69] vs 1.04 [0.97]) and midteen (0.33 [0.26] vs 0.75 [1.21]) visits. In models adjusted for maternal PCOS, education and child race and ethnicity (social factors), we found higher odds of PCOS per 1-SD increase in truncal fat at midchildhood (odds ratio [OR] 1.42; 95% confidence interval [CI] 1.03-1.95) and early teen visits (OR 1.61; 95% CI 1.14-2.28) and lower odds per 1-SD increase in adiponectin/leptin ratio at the midteen visit (OR 0.14; 95% CI 0.03-0.58). CONCLUSIONS: Childhood excess adiposity and adipose tissue dysfunction may be a first signs of later PCOS risk. [ABSTRACT FROM AUTHOR]

The article focuses on a study conducted to analyze the association of healthy lifestyle profile before pregnancy with a reduced risk of gestational diabetes. It is noted that female nurses who had a singleton live birth during 1989 to 2001 were icnlduded in the study. It is stated that an 83% lower risk of gestational diabetes was observed in patients who met all four criteria inclduing healthy body weight, healthy diet, regular exercise, and not smoking.

Although much has been published in recent years on differences in Papanicolaou (Pap) tests across sexual orientation, other aspects of cervical cancer prevention remain underexplored, such as human papillomavirus (HPV) vaccination, HPV co-tests, or abnormal Pap tests. Data came from participants (aged 24–54 years) enrolled in an ongoing, longitudinal, U.S.-based cohort study, the Nurses' Health Study 3 (N = 12,175). Analyses were restricted to participants who met the current guidelines for care (e.g., ≥21 years of age for Pap tests). Mostly heterosexual women were more likely to initiate HPV vaccination than completely heterosexual women with no same-sex partners. All other comparisons across sexual orientation for HPV vaccination initiation and completion and the age of initiation were not statistically significant. Compared with completely heterosexual women with no same-sex partners, mostly heterosexual and lesbian women had lower odds of having a Pap test within the past 2 years. Completely heterosexual women with same-sex partners, mostly heterosexual women, and bisexual women had their first Pap test at an earlier age, had higher odds of having an HPV co-test, and had higher odds of having a positive HPV or abnormal Pap test compared with completely heterosexual women with no same-sex partners. In contrast, lesbian women had lower odds of having positive HPV or abnormal Pap results (odds ratio, 0.65; 95% confidence interval, 0.49–0.86) than completely heterosexual women with no same-sex partners. There are significant differences across sexual orientation groups in cervical cancer prevention for Pap test timing and positive HPV and abnormal Pap tests, but few differences in HPV vaccination initiation, completion, and age at initiation. Interventions should focus on increasing routine Pap testing among mostly heterosexual and lesbian women. [ABSTRACT FROM AUTHOR]

We examined sexual orientation-related differences in various pregnancy outcomes (e.g., teen pregnancy, abortion) across the lifespan. We collected data from 124,710 participants in three U.S. longitudinal cohort studies, the Nurses' Health Study 2 and 3 and Growing Up Today Study 1, followed from 1989 to 2017. Multivariate regression was used to calculate differences of each outcome—ever had pregnancy, teen pregnancy, ever had abortion, and age at first birth—by sexual orientation groups (e.g., heterosexual, mostly heterosexual, bisexual, lesbian), adjusting for potential confounders of age and race/ethnicity. All sexual minority groups—except lesbians—were generally more likely than heterosexual peers to have a pregnancy, a teen pregnancy, and an abortion. For example, Growing Up Today Study 1 bisexual participants were three times as likely as heterosexuals to have had an abortion (risk ratio, 3.21; 95% confident interval, 1.94–5.34). Lesbian women in all of the cohorts were approximately half as likely to have a pregnancy compared with heterosexual women. Few sexual orientation group differences were detected in age at first birth. The increased risk of unintended pregnancy among sexual minority women likely reflects structural barriers to sexual and reproductive health services. It is critical that sex education programs become inclusive of sexual minority individuals and medical education train health care providers to care for this population. Health care providers should not make harmful heteronormative assumptions about pregnant patients and providers must learn to take sexual histories as well as offer contraceptive counseling to all patients who want to prevent a pregnancy regardless of sexual orientation. [ABSTRACT FROM AUTHOR]

The dietary supplements industry disproportionately markets potentially harmful products promising weight loss, cleansing/detoxing, and boosted energy and immunity to women. The COVID-19 pandemic heightened consumer concerns around health and body weight, which may have increased women's risks of using supplements, particularly if they had a higher weight and experienced weight discrimination. This study aimed to estimate inequities in prevalence and change in use of weight-loss, cleanse/detox, immunity, and energy supplements in the first year of the pandemic and to assess the extent to which the relationship between weight and supplement use differs across discrimination experiences. We drew upon longitudinal data from cisgender women in the U.S. COVID-19 Pandemic Substudy of the Nurses' Health Study II and 3 and Growing Up Today Study cohorts, collected over 5 waves from April/May 2020 to April 2021 (N = 51,814). Modified Poisson generalized estimating equation models, adjusted for age, cohort, race/ethnicity, wave, and Census region, estimated the relative excess risk due to interaction (RERI) between weight status and weight discrimination on prevalence of supplement use. Weight status categories were derived from body mass index (BMI), and weight discrimination was assessed using the attributions item of the Everyday Discrimination Scale. Baseline prevalence of supplement use was 2.7% for weight-loss, 3.3% for cleanse/detox, 4.2% for energy, and 22.6% for immune. Respondents with BMIs of 25–29.9 kg/m2 and 30–34.9 kg/m2 who experienced weight discrimination had RERI values of 0.89 (95% CI 0.14, 1.65) and 1.00 (95% CI 0.25, 1.75) for weight-loss and 0.57 (95% CI 0.13, 1.02) and 0.60 (95% CI 0.19, 1.01) for energy supplements, respectively, indicating this group had excess risk of use compared to lower BMI respondents who experienced no weight discrimination. The findings demonstrate the disproportionate impact of weight discrimination on use of potentially harmful supplements among cisgender women with higher weights during the pandemic. • Disproportionate use of potentially harmful dietary supplements is well-documented • We assessed the influence of weight discrimination on supplement use among women • High weight women reporting weight discrimination have excess risk of supplement use • Excess risk was specific to potentially harmful weight-loss and energy supplements • Experiencing weight discrimination influenced supplement use during the pandemic [ABSTRACT FROM AUTHOR]

Objective: To evaluate the patterns of change in serum antimüllerian hormone (AMH) during controlled ovarian hyperstimulation (COH) and their relation to concurrent response and in vitro fertilization (IVF) pregnancy outcomes.Design: Prospective cohort study.Setting: Academic medical center.Patient(s): A total of 113 consecutive fresh IVF embryo transfer cycles from September 1, 2012 through January 1, 2013.Intervention(s): Serial serum AMH measurements were analyzed on each day that serum estradiol (E2) was drawn during COH.Main Outcome Measure(s): Relationship between the rate of COH AMH change [Δ ng/mL per day] (stratified into tertiles), and ovarian response, and pregnancy outcomes.Result(s): During COH, AMH declined. Age and ovarian reserve testing were associated with the rate of AMH decline (RAD). Women with intermediate and minimal RAD had statistically significantly fewer follicles ≥ 12 mm, lower peak serum E2, fewer oocytes, and inferior early embryo development compared with women with the greatest RAD. Compared with patients with the lowest RAD, clinical pregnancy was more likely in patients with the greatest RAD in the total population (adjusted odds ratio 3.51; 95% confidence interval, 1.03, 11.94) and among patients older than 35 years (adjusted odds ratio 6.95; 95% confidence interval, 1.09, 44.1).Conclusion(s): The rate of COH AMH decline was associated with ovarian reserve testing, oocyte yield, embryo progression, and clinical pregnancy rates, particularly in women older than 35 years. These results suggest that dynamic AMH levels may provide a novel intracycle approach to predict response and treatment outcomes after IVF. [ABSTRACT FROM AUTHOR]