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The Preconception Period Analysis of Risks and Exposures Influencing Health and Development (PrePARED) Consortium creates a novel resource for addressing preconception health by merging data from numerous cohort studies. In this paper, we describe our data harmonization methods and results. Individual-level data from 12 prospective studies were pooled. The crosswalk-cataloging-harmonization procedure was used. The index pregnancy was defined as the first postbaseline pregnancy lasting more than 20 weeks. We assessed heterogeneity across studies by comparing preconception characteristics in different types of studies. The pooled data set included 114,762 women, and 25,531 (22%) reported at least 1 pregnancy of more than 20 weeks' gestation during the study period. Babies from the index pregnancies were delivered between 1976 and 2021 (median, 2008), at a mean maternal age of 29.7 (standard deviation, 4.6) years. Before the index pregnancy, 60% of women were nulligravid, 58% had a college degree or more, and 37% were overweight or obese. Other harmonized variables included race/ethnicity, household income, substance use, chronic conditions, and perinatal outcomes. Participants from pregnancy-planning studies had more education and were healthier. The prevalence of preexisting medical conditions did not vary substantially based on whether studies relied on self-reported data. Use of harmonized data presents opportunities to study uncommon preconception risk factors and pregnancy-related events. This harmonization effort laid the groundwork for future analyses and additional data harmonization. [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 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: 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; Ptrend = 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; Ptrend = 0.004 and RR: 1.17; 95% CI: 1.06, 1.29; Ptrend = 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; Ptrend = 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. [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]

Study Question: Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?Summary Answer: Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.What Is Known Already: Long 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, Duration: Prospective cohort study. Prospective follow-up of 78 943 women participating in the Nurses' Health Study II between 1989 and 2015.Participants/materials, Setting, Methods: We 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 Chance: We 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 Caution: Our 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 Findings: Women 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 Interest: This 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 Number: N/A. [ABSTRACT FROM AUTHOR]

Objective: We examined lifestyle factors with midlife weight change according to history of gestational diabetes mellitus (GDM) in a large longitudinal female cohort.Research Design and Methods: In the Nurses' Health Study II, we categorized changes in lifestyle within 4-year periods and estimated their associations with concurrent changes in body weight (kilograms) among parous women after age 40 years by GDM history status (N = 54,062; 5.3% with a history of GDM) for the following: diet quality (Alternate Healthy Eating Index [AHEI]), leisure-time physical activity (PA), alcohol consumption, and smoking status.Results: Over a median follow-up of 13 years, average 4-year weight gain was 1.10 and 1.33 kg for women with and without prior GDM, respectively. Women with improved diet quality had favorable 4-year weight change, particularly those with a history of GDM (AHEI change [95% CI] from low to high -2.97 kg [-4.34, -1.60] vs. -1.19 kg [-1.41, -0.96] for GDM vs. non-GDM, respectively; P heterogeneity = 0.04). Increasing PA was associated with weight maintenance for GDM women only (PA increase [95% CI] from low to high 0.26 kg [-0.25, 0.77] vs. 0.90 kg [0.80, 1.01] for GDM vs. non-GDM, respectively; P heterogeneity = 0.02). For both GDM and non-GDM women, weight change did not differ significantly with change in alcohol consumption, while women who quit smoking had significant weight gain (4.38 kg for GDM and 3.85 kg for non-GDM).Conclusions: Improvements in diet quality and PA were related to less weight gain in midlife among parous women, and the benefit of such improvements on weight management was particularly pronounced among women with a history of GDM. [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]

Objective: Evaluate associations between orange juice (OJ) consumption and anthropometric parameters.Design: Prospective cohort study assessing the association between OJ intake and changes in BMI and height-for-age Z-score (HAZ) using mixed linear regression.Setting: 2004-2008, USA.Participants: Children from the Growing Up Today Study II (n 7301), aged 9-16 years at enrollment.Results: OJ consumption was positively associated with 2-year change in HAZ in girls (mean (se)): 0·03 (0·01) for non-consumers, 0·03 (0·02) for 1-3 glasses/month, 0·06 (0·01) for 1-6 glasses/week and 0·09 (0·02) for ≥1 glass/d after full adjustment (Ptrend = 0·02). However, OJ consumption was not associated with 2-year change in BMI percentile (kg/m2, mean (se)): -0·44 (0·36) for non-consumers, 0·20 (0·41) for 1-3 glasses/month, -0·04 (0·34) for 1-6 glasses/week and -0·77 (0·62) for ≥1 glass/d in girls, Ptrend = 0·81; -0·94 (0·53) for non-consumers, -1·68 (0·52) for 1-3 glasses/month, -0·81 (0·38) for 1-6 glasses per week and -1·12 (0·61) for ≥1 glass/d in boys, Ptrend = 0·49.Conclusion: OJ consumption was favourably associated with height growth but unrelated to excess weight gain. OJ may be a useful alternative to whole fruit in the event that whole fruit intake is insufficient. [ABSTRACT FROM AUTHOR]

Summary: Background: There are concerns that fruit juice and milk contribute to childhood obesity. Objective: Determine the relationship between fruit juice and milk intakes and body mass index (BMI) change among preadolescents/adolescents. Methods: Participants aged 9 to 16 years old from the Growing Up Today Study II completed surveys including validated food frequency questionnaires in 2004, 2006 and 2008. The contributions of one serving of juice or milk to total energy intake and 2‐year change in BMI were evaluated using multiple linear regression. Additional analyses were conducted with subgroups of juice (orange juice and other fruit juice) and milk (low fat and high fat). Missing values for BMI were imputed using a multiple imputation approach, after which data from 8173 participants and 13 717 2‐year interval observations were analysed. Results: Baseline fruit juice consumption was inversely associated with BMI change in girls (β = −.102 kg/m2, SE = 0.038, P value =.008) but not boys after controlling for race, age, baseline BMI, and baseline and 2‐year changes in total energy intake and physical activity. Orange juice was inversely associated with BMI change among girls (β = −.137 kg/m2, SE = 0.053, P value =.010) while other fruit juice, low fat and high fat milk were not associated with BMI change. Conclusion: Orange juice was inversely associated with 2‐year BMI change among preadolescent/adolescent girls but not boys and there were no significant associations with other juices or milk among either gender. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity among women have been associated with lower success of assisted reproduction technologies (ARTs). However, the relation of adolescent body weight and adult weight change to ART outcomes is not well understood.Objective: Our objective was to evaluate the associations of female BMI (in kg/m2) at 18 y and weight change from 18 y to current age with ART outcomes.Methods: We included 486 women in a prospective cohort at the Massachusetts General Hospital Fertility Center (2004-2018) who underwent 863 ART cycles. At study entry, height and weight were measured by research personnel. Women recalled their weight at 18 y. Restricted cubic splines were used to evaluate the associations between BMI at 18 y and weight change since 18 y and ART outcomes adjusting for age, race, education, smoking, and height and accounting for the correlated cycles within women.Results: Women had a median (range) BMI of 20.6 (14.8 to 36.4) at 18 y and 23.3 (16.1 to 45.8) at study entry. The median (range) weight change since 18 y was 7.4 kg (-12.1 to 60.1 kg). There was no association between BMI at 18 y and clinical ART outcomes. Long-term weight change had a nonlinear association with live birth such that higher weight gain since 18 y (particularly ≥15 kg) and weight loss were both associated with lower odds of live birth. The negative association between weight change and live birth was stronger in women ≥22.5 kg/m2 at 18 y such that each 10-kg increase was associated with a 30% (6%, 48%) lower odds of live birth.Conclusions: Weight gain in adulthood is negatively associated with ART success, particularly among women who were heavier at 18 y. These results add to the growing literature supporting the benefits of preventing weight gain in adulthood on female fertility. [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]

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]

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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: Randomized trials of supplementation with antioxidant mixtures during infertility treatment show no benefit on pregnancy or live birth rate. However, the roles of individual antioxidants are poorly understood. We examined the association of baseline intake of vitamins A, C, E, and carotenoids with outcomes of assisted reproductive technologies (ARTs).Methods: We followed 349 women undergoing a total of 588 ART cycles for infertility treatment at the Massachusetts General Hospital. We assessed antioxidant intakes from food and supplements before treatment using a validated food frequency questionnaire. We used generalized linear mixed models to account for multiple ART cycles per woman while adjusting for confounding.Results: Mean (SD) age and body mass index were 35.1 years (4.0 years) and 24.1 kg/m (4.3 kg/m), respectively. Total intake of vitamins A, C, and E was not associated with the probability of live birth. Women in the highest intake category of β-carotene from foods had a lower probability of live birth than women in the lowest intake quartile (50% vs. 22%; P trend = 0.03); for lutein and zeaxanthin, the probability for the highest intake group was 44% vs. 28% for the lowest. Intake of β-carotene from supplements and intakes of retinol and all other carotenoids were unrelated to live birth rates.Conclusions: We found unexpected inverse associations of β-carotene intake from foods and of lutein and zeaxanthin intake with live birth rates. Within the observed intake ranges, total consumption of vitamins A, C, and E before starting infertility treatment with ART was not associated with live birth rates. [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]

Objective: This study aimed to examine the associations of two obesity-related metabolite patterns with changes in metabolic biomarkers during early adolescence.Methods: Multivariable linear regression was used to examine associations of branched chain amino acid (BCAA) and androgen hormone patterns with changes in glycemia (fasting glucose, insulin, homeostatic model assessment of insulin resistance), adipokines (leptin, adiponectin), inflammation (C-reactive protein, interleukin-6), lipid profile, and blood pressure during ∼5 years of follow-up among 213 children aged 6 to 10 years at baseline. Covariates included baseline age, pubertal status, biomarker level, and BMI percentile, and age at follow-up. Interactions with sex and baseline BMI percentile were also considered.Results: The median age at baseline was 7.7 years; 48.8% were boys. In adjusted models, each 1 unit of the BCAA pattern corresponded with a 4.82 (95% CI: 0.92 to 8.71) mg/dL decrease in fasting glucose in boys. In girls, the BCAA pattern was associated with an increase in triglycerides (4.17 [0.03 to 8.32] mg/dL). The androgen pattern was associated with decreased leptin (-2.35 [-4.34 to -0.35] ng/dL) and increased C-reactive protein (0.28 [0.03 to 0.54] mg/dL) in girls. These relationships did not differ by baseline BMI percentile.Conclusions: The BCAA and androgen hormone metabolite patterns are related to changes in metabolic parameters in a sex-specific manner during early adolescence. [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]

Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19. This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19. We followed 46,579 women from 2 ongoing prospective cohort studies—the Nurses' Health Study II and the Nurses' Health Study 3—who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993–2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases). Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44–65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05–1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09–1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00–1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01–1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis. Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations. [ABSTRACT FROM AUTHOR]

Background: Animal data suggest sexually dimorphic programming of obesity in response to altered intrauterine environment, but the longitudinal impact of gestational diabetes mellitus (GDM) on sex-specific risk of offspring obesity in humans is unclear.Methods: We conducted a prospective analysis of 15 009 US individuals (7946 female and 7063 male) from the Growing-Up Today Study, who were followed from 1996 (ages 9-14 years) through 2010. Height and weight from validated questionnaires were used to derive body mass index (BMI) at different ages. Obesity during childhood (< 18 years) and adulthood (≥ 18 years) were defined using the International Obesity Task Force and the World Health Organization criteria. GDM exposure was identified through self-reported questionnaires from mothers. Relative risks were estimated using multivariable log-binomial regression models with generalized estimating equations accounting for clustering within the same family.Results: Male offspring born from pregnancies complicated by GDM had higher BMI compared with non-GDM offspring and had increased risk of obesity; the adjusted relative risk [RR, 95% confidence interval (CI)] was 1.47 (1.11-1.95) for all age groups, 1.59 (1.05-2.41) for late childhood, 1.48 (1.06-2.06) for adolescence and 1.39 (1.00-1.94) for early adulthood. No significant association between obesity and maternal GDM was observed among female participants (RR = 0.97, 95% CI: 0.71-1.33).Conclusions: The association of GDM with offspring obesity from late childhood through early adulthood may differ by sex; a significant association was observed among male but not female offspring. [ABSTRACT FROM AUTHOR]

Background: Artificial sweeteners are widely replacing caloric sweeteners. Data on long-term impact of artificially sweetened beverage (ASB) consumption during pregnancy on offspring obesity risk are lacking. We prospectively investigated intake of ASBs and sugar-sweetened beverages (SSBs) during pregnancy in relation to offspring growth through age 7 years among high-risk children born to women with gestational diabetes.Methods: In a prospective study of 918 mother-singleton child dyads from the Danish National Birth Cohort, maternal dietary intake was assessed by a food frequency questionnaire during pregnancy. Offspring body mass index z-scores (BMIZ) and overweight/obesity status were derived using weight and length/height at birth, 5 and 12 months and 7 years. Linear regression and Poisson regression with robust standard errors were used, adjusting for major risk factors.Results: Approximately half of women reported consuming ASBs during pregnancy and 9% consumed daily. Compared to never consumption, daily ASB intake during pregnancy was positively associated with offspring large-for-gestational age [adjusted relative risk (aRR) 1.57; 95% CI: 1.05, 2.35 at birth], BMIZ (adjusted β 0.59; 95% CI: 0.23, 0.96) and overweight/obesity (aRR 1.93; 95% CI; 1.24, 3.01) at 7 years. Per-serving-per-day substitution of ASBs with water during pregnancy was related to a lower overweight/obesity risk at 7 years (aRR 0.83; 95% CI: 0.76, 0.91), whereas SSB substitution with ASBs was not related to a lower risk (aRR 1.14; 95% CI: 1.00, 1.31).Conclusions: Our findings illustrated positive associations between intrauterine exposure to ASBs and birth size and risk of overweight/obesity at 7 years. Data with longer follow-up are warranted. [ABSTRACT FROM AUTHOR]

Background: The Korea Nurses' Health Study (KNHS) is a prospective cohort study of female nurses, focusing on the effects of occupational, environmental, and lifestyle risk factors on the health of Korean women. Materials and Methods: Female registered nurses aged 20-45 years and living in the Republic of Korea were invited to join the study, which began in July 2013. They were asked to complete a web-based baseline survey. The study protocols and questionnaires related to the KNHS are based on the Nurses' Health Study 3 (NHS3) in the United States, although they were modified to reflect the Korean lifestyle. Participants were asked about demographic, lifestyle factors, disease history, occupational exposure, reproductive factors, and dietary habits during their adolescence: Follow-up questionnaires were/will be completed at 6-8 month intervals after the baseline survey. If a participant became pregnant, she answered additional questionnaires containing pregnancy-related information. Results: Among 157,569 eligible female nurses, 20,613 (13.1%) completed the web-based baseline questionnaire. The mean age of the participants was 29.4 ± 5.9 years, and more than half of them were in their 20s. Eighty-eight percent of the participants had worked night shifts as a nurse (mean, 5.3 ± 4.3 nights per month). Approximately 80% of the participants had a body mass index below 23 kg/m2. Gastrointestinal diseases were the most prevalent health issues (25.9%). Conclusions: The findings from this prospective cohort study will help to identify the effects of lifestyle-related and occupational factors on reproductive health and development of chronic diseases in Korean women. [ABSTRACT FROM AUTHOR]

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: Circulating fatty acids are highly correlated with each other, and analyzing fatty acid patterns could better capture their interactions and their relation to prostate cancer. We aimed to assess the associations between data-derived blood fatty acid patterns and prostate cancer risk.Methods: We conducted a nested case-control study in the Physicians' Health Study. Fatty acids levels were measured in whole blood samples of 476 cases and their matched controls by age and smoking status. Fatty acid patterns were identified using principal component analysis. Conditional logistic regression was used to estimate odds ratio (OR) and 95 % confidence interval (CI).Results: Two patterns explaining 40.9 % of total variation in blood fatty acid levels were identified. Pattern 1, which mainly reflects polyunsaturated fatty acid metabolism, was suggestively positively related to prostate cancer risk (ORquintile 5 vs. quintile 1 = 1.37, 95 % CI = 0.91-2.05, P trend = 0.07). Pattern 2, which largely reflects de novo lipogenesis, was significantly associated with higher prostate cancer risk (ORquintile5 vs. quintile1 = 1.63, 95 % CI = 1.04-2.55, P trend = 0.02). This association was similar across tumor stage, grade, clinical aggressiveness categories and follow-up time.Conclusion: The two patterns of fatty acids we identified were consistent with known interactions between fatty acid intake and metabolism. A pattern suggestive of higher activity in the de novo lipogenesis pathway was related to higher risk of prostate cancer. [ABSTRACT FROM AUTHOR]

The article discusses the historical evolution of the Nurses' Health Study (NHS) which was launched in 1976, the NHS II project which began in 1989, and the NHS3 program which began in 2010 and has an ongoing enrollment as of 2016. According to the article, these studies involving married registered nurses have produced long-term, multidimensional data regarding lifestyle- and health-related information across the life course. U.S. public health recommendations are also assessed.

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]

Objective: Low-carbohydrate diets (LCDs) may improve short-term glycemic control in patients with gestational diabetes mellitus (GDM), but the long-term effect on progression from GDM to type 2 diabetes mellitus (T2DM) is unknown. We aimed to examine the long-term risk of T2DM in association with a low-carbohydrate dietary pattern among women with a history of GDM.Research Design and Methods: Overall, 4,502 women with a history of GDM from the Nurses' Health Study II (NHSII) cohort, as part of the Diabetes & Women's Health (DWH) study, were followed up from 1991 to 2011. Overall, animal, or vegetable LCD scores, which represent adherence to different low-carbohydrate dietary patterns, were calculated using diet intake information assessed every 4 years since 1991 by validated food-frequency questionnaires. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs.Results: We documented 722 incident cases of T2DM during 68,897 person-years of observation. The multivariable-adjusted HRs (95% CIs) of T2DM, comparing the highest with lowest quintiles, were 1.36 (1.04-1.78) for overall LCD score (P = 0.003 for trend), 1.40 (1.06-1.84) for animal LCD score (P = 0.004 for trend), and 1.19 (0.91-1.55) for vegetable LCD score (P = 0.50 for trend).Conclusions: Among women with a history of GDM, a low-carbohydrate dietary pattern, particularly with high protein and fat intake mainly from animal-source foods, is associated with higher T2DM risk, whereas a low-carbohydrate dietary pattern with high protein and fat intake from plant-source foods is not significantly associated with risk of T2DM. [ABSTRACT FROM AUTHOR]

Background: Long-chain omega-3 fatty acids and their food sources have garnered interest as a potential nutrient with wide-range health benefits, including fertility.Objective: This study aimed to investigate the association of women's and men's intake of omega-3 fatty acids and omega-3 rich-foods with semen quality and outcomes of infertility treatment with assisted reproductive technologies.Study Design: Couples presenting to the Massachusetts General Hospital were invited to enroll in a prospective cohort study (2007-2020). Male and female diets were assessed using a validated 131-item food frequency questionnaire. The primary outcomes were implantation, clinical pregnancy, and live birth probabilities. The secondary outcomes included total and clinical pregnancy loss and conventional semen parameters, for males only. We estimated the relationship between intakes of omega-3 fatty acids, nuts, and fish and the probability (95% confidence interval) of study outcomes using generalized linear mixed models to account for repeated treatment cycles per participant while simultaneously adjusting for age, body mass index, smoking status, education, dietary patterns, total energy intake, and male partner diet.Results: A total of 229 couples and 410 assisted reproductive technology cycles were analyzed for primary and secondary outcomes. Of note, 343 men contributing 896 semen samples were included in analyses for semen quality measures. Women's docosahexaenoic acid + eicosapentaenoic acid intake was positively associated with live birth. The multivariable-adjusted probabilities of live birth for women in the bottom and top quartiles of eicosapentaenoic acid + docosahexaenoic acid intake were 0.36 (95% confidence interval, 0.26-0.48) and 0.54 (95% confidence interval, 0.42-0.66) (P trend=.02). Eicosapentaenoic acid + docosahexaenoic acid intake was inversely related to the risk of pregnancy loss, which was 0.53 among women in the lowest quartile of eicosapentaenoic acid + docosahexaenoic acid intake and 0.05 among women in the highest quartile (P trend=.01). Men's intake of total omega-3 fatty acids was positively related to sperm count, concentration, and motility, but unrelated to any assisted reproductive technology outcomes. Similar associations were observed when evaluating the intake of primary food sources of these fatty acids.Conclusion: Women's consumption of omega-3 fatty acids and omega-3-rich foods may improve the probability of conception by decreasing the risk of pregnancy loss. In addition, men's intake of omega-3 fatty acids may influence semen quality. [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]

STUDY QUESTION: Are urinary BPA concentrations associated with in vitro fertilization (IVF) outcomes among women attending an academic fertility center? SUMMARY ANSWER: Urinary BPA concentrations were not associated with adverse reproductive and pregnancy outcomes among women from a fertility clinic. WHAT IS KNOWN ALREADY: Bisphenol A (BPA), an endocrine disruptor, is detected in the urine of most Americans. Although animal studies have demonstrated that BPA reduces female fertility through effects on the ovarian follicle and uterus, data from human populations are scarce and equivocal. STUDY DESIGN, SIZE AND DURATION: This prospective cohort study between 2004 and 2012 at the Massachusetts General Hospital Fertility Center included 256 women (n = 375 IVF cycles) who provided up to two urine samples prior to oocyte retrieval (total N = 673). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Study participants were women enrolled in the Environment and Reproductive Health (EARTH) Study. Intermediate and clinical end-points of IVF treatments were abstracted from electronic medical records. We used generalized linear mixed models with random intercepts to evaluate the association between urinary BPA concentrations and IVF outcomes adjusted by age, race, body mass index, smoking status and infertility diagnosis. MAIN RESULTS AND THE ROLE OF CHANCE: The specific gravity-adjusted geometric mean of BPA was 1.87 µg/l, which is comparable to that for female participants in the National Health and Nutrition Examination Survey, 2011-2012. Urinary BPA concentrations were not associated with endometrial wall thickness, peak estradiol levels, proportion of high quality embryos or fertilization rates. Furthermore, there were no associations between urinary BPA concentrations and implantation, clinical pregnancy or live birth rates per initiated cycle or per embryo transfer. Although we did not find any associations between urinary BPA concentrations and IVF outcomes, the relation between BPA and endometrial wall thickness was modified by age. Younger women (≥ 37 years old) had thicker endometrial thickness across increasing quartiles of urinary BPA concentrations, while older women (> 37 years old) had thinner endometrial thickness across increasing quartiles of urinary BPA concentrations. LIMITATIONS, REASONS FOR CAUTION: Limitations to this study include a possible misclassification of BPA exposure and difficulties in extrapolating the findings to the general population. WIDER IMPLICATIONS OF THE FINDINGS: Data on the relation between urinary BPA concentrations and reproductive outcomes remain scarce and additional research is needed to clarify its role in human reproduction. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by NIH grants R01ES022955, R0 1ES009718 and R01ES000002fromthe National Institute of Environmental Health Sciences (NIEHS) and grantT32DK00770316 from the National Institute of Child Health and Human Development (NICHD). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. [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]

Background: Endometriosis is a prevalent but enigmatic gynecologic disorder for which few modifiable risk factors have been identified. Fish oil consumption has been associated with symptom improvement in studies of women with primary dysmenorrhea and with decreased endometriosis risk in autotransplantation animal studies.Methods: To investigate the relation between dietary fat intake and the risk of endometriosis, we analyzed 12 years of prospective data from the Nurses' Health Study II that began in 1989. Dietary fat was assessed via food frequency questionnaire in 1991, 1995 and 1999. We used Cox proportional hazards models adjusted for total energy intake, parity, race and body mass index at age 18, and assessed cumulatively averaged fat intake across the three diet questionnaires.Results: During the 586 153 person-years of follow-up, 1199 cases of laparoscopically confirmed endometriosis were reported. Although total fat consumption was not associated with endometriosis risk, those women in the highest fifth of long-chain omega-3 fatty acid consumption were 22% less likely to be diagnosed with endometriosis compared with those with the lowest fifth of intake [95% confidence interval (CI) = 0.62-0.99; P-value, test for linear trend (Pt) = 0.03]. In addition, those in the highest quintile of trans-unsaturated fat intake were 48% more likely to be diagnosed with endometriosis (95% CI = 1.17-1.88; Pt = 0.001).Conclusion: These data suggest that specific types of dietary fat are associated with the incidence of laparoscopically confirmed endometriosis, and that these relations may indicate modifiable risk. This evidence additionally provides another disease association that supports efforts to remove trans fat from hydrogenated oils from the food supply. [ABSTRACT FROM AUTHOR]

Objective: To examine whether use of multivitamins and intake of specific nutrients in multivitamins is associated with ovulatory infertility.Design: A prospective cohort study.Setting: The Nurses' Health Study II.Patient(s): Eighteen thousand five hundred fifty-five married, premenopausal women without a history of infertility who attempted a pregnancy or became pregnant between 1991 and 1999.Intervention(s): None, observational study.Main Outcome Measure(s): Incident reports of infertility caused by anovulation.Result(s): During 8 years of follow-up, 438 women reported infertility caused by ovulatory disorder. There was an inverse association between frequency of multivitamin use and ovulatory infertility. The multivariate-adjusted relative risk (95% confidence interval) of ovulatory infertility was 0.88 (0.60, 1.28) for women consuming two tablets per week or less, 0.69 (0.51, 0.95) for women consuming three to five tablets per week, and 0.59 (0.46, 0.75) for women consuming six or more tablets per week, when compared with women who did not use these supplements (P, trend <.001). Folic acid appeared to explain part of the association between multivitamin supplement use and risk of ovulatory infertility.Conclusion(s): Regular use of multivitamin supplements may decrease the risk of ovulatory infertility. [ABSTRACT FROM AUTHOR]