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Background: Individual studies have suggested that some circulating fatty acids are associated with prostate cancer risk, but have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease. Methods: Principal investigators of prospective studies on circulating fatty acids and prostate cancer were invited to collaborate. Investigators provided individual participant data on circulating fatty acids (weight percent) and other characteristics of prostate cancer cases and controls. Prostate cancer risk by study-specific fifths of 14 fatty acids was estimated using multivariable-adjusted conditional logistic regression. All statistical tests were two-sided. Results: Five thousand and ninety-eight case patients and 6649 control patients from seven studies with an average follow-up of 5.1 (SD = 3.3) years were included. Stearic acid (18:0) was inversely associated with total prostate cancer (odds ratio [OR] Q5 vs Q1 = 0.88, 95% confidence interval [CI] = 0.78 to 1.00, P trend = .043). Prostate cancer risk was, respectively, 14% and 16% greater in the highest fifth of eicosapentaenoic acid (20:5n-3) (OR = 1.14, 95% CI = 1.01 to 1.29, P trend = .001) and docosapentaenoic acid (22:5n-3) (OR = 1.16, 95% CI = 1.02 to 1.33, P trend = .003), but in each case there was heterogeneity between studies (P = .022 and P < .001, respectively). There was heterogeneity in the association between docosapentaenoic acid and prostate cancer by grade of disease (P = .006); the association was statistically significant for low-grade disease but not high-grade disease. The remaining 11 fatty acids were not statistically associated with total prostate cancer risk. Conclusion: There was no strong evidence that circulating fatty acids are important predictors of prostate cancer risk. It is not clear whether the modest associations of stearic, eicosapentaenoic, and docosapentaenoic acid are causal.

Context: Concentration of circulating anti-Müllerian hormone (AMH) predicts short-term (3-5 years) bone loss around menopause. Whether AMH during mid-reproductive years predicts bone health over a decade later is unknown., Objective: To study the association of AMH levels in mid-reproductive years with bone density and turnover biomarkers measured after ∼14 years of follow-up., Methods: We assessed plasma AMH in 2003-2006 (mean 37.0 years, SD 5.1) among 450 parous women (71% White) in a US longitudinal cohort, and bone mineral density (BMD; spine, hip, and femoral neck, measured by dual-energy X-ray absorptiometry) in 2017-2021 (mean 51.0 years, SD 5.1). Secondary outcomes were plasma levels of procollagen type I N-propeptide (PINP) and C-terminal telopeptide I (CTX-I)., Results: In linear regression models adjusted for demographics and lifestyle, compared to women with AMH >3.5 ng/mL, those with AMH <1.0 ng/mL had lower BMD (g/cm2) at follow-up (beta [95% CI]: spine: -0.06 [-0.10, -0.02]; hip: -0.05 [-0.08, -0.02]; femoral neck: -0.03 [-0.06, 0.00]) and higher bone turnover markers (beta [95% CI]: PINP: 0.36 SD [0.10, 0.63]; CTX-I: 0.34 SD [0.07, 0.60]). The association of AMH with spine BMD was more pronounced among post-menopausal women, in contrast to associations with bone turnover markers which were more pronounced among women who had not yet reached menopause. The associations between AMH and BMD were primarily mediated by menopausal status at follow-up., Conclusions: Lower AMH during mid-reproductive years is associated with lower BMD and higher bone turnover 14 years later. Ovarian reserve during mid-reproductive years may be a valuable predictor of long-term bone health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Context: Evidence suggests that exposure to per- and polyfluoroalkyl substances (PFAS) increases the risk of developing cardiometabolic disease risk factors. Limited research has evaluated associations between PFAS, assessed during pregnancy, a sensitive window for maternal endocrine effects, and long-term maternal adiposity., Objective: Estimate associations of early pregnancy measures of individual PFAS, and PFAS mixtures, with maternal adiposity in midlife., Methods: We studied 547 Project Viva participants with measures of early pregnancy (mean gestation 10.0 weeks; mean age 32.5 years) plasma concentrations of 6 PFAS and midlife adiposity outcomes (mean follow-up 17.7 years; mean age 50.7 years), including weight, waist circumference (WC), trunk fat mass (TFM), and total body fat mass (TBFM). We used linear regression and Bayesian Kernel Machine Regression (BKMR)., Results: Linear regression estimated higher midlife weight per doubling of perfluorooctane sulfonate (PFOS) (3.8 kg [95% CI: 1.6, 5.9]) and 2-(N-ethyl-perfluorooctane sulfonamido) acetate (2.3 kg [95% CI: 0.9, 3.7]). BKMR analyses of single PFAS plasma concentrations (comparing the 25th percentile concentration to the 75th percentile) showed a positive association between PFOS and midlife adiposity (weight: 7.7 kg [95% CI: 4.0, 11.5]; TFM: 1.2 kg [95% CI: 0.0, 2.3]; TBFM: 3.0 kg [95% CI: 0.8, 5.2]), but inverse associations with perfluorononanoate (weight: -6.0 kg [95% CI: -8.5, -3.5]; WC: -1.8 cm [95% CI: -3.2, -0.3]; TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.7, -0.3]) and perfluorohexane sulfonate (TFM: -0.8 kg [95% CI: -1.5, -0.1]; TBFM: -1.4 kg [95% CI: -2.6, -0.2]). No associations were observed with the overall PFAS mixture., Conclusion: Select PFAS, assessed in pregnancy, may differentially affect maternal midlife adiposity, influencing later-life maternal cardiometabolic health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Objectives: To assess correlates of diagnosed and probable polycystic ovary syndrome (PCOS) among parous women., Methods: This study includes 557 women recruited from multi-specialty clinics in eastern Massachusetts. We categorized women as "diagnosed PCOS" based on medical records and self-reported clinician-diagnoses. Next, we constructed a category of "probable PCOS" for women without a diagnosis but with ≥2 of the following: ovulatory dysfunction (cycle length<21 or ≥35 days), hyperandrogenism (free testosterone>75th percentile), or elevated anti-Müllerian hormone (>75th percentile). We classified the remaining as "no PCOS," and compared characteristics across groups., Results: 9.7% had diagnosed and 9.2% had probable PCOS. The frequency of irregular cycles was similar for diagnosed and probable PCOS. Free testosterone and AMH were higher for probable than diagnosed PCOS. Frequency of irregular cycles and both hormones were higher for the two PCOS groups vs. the no PCOS group. Obesity prevalence for diagnosed PCOS was twice that of probable PCOS (43.9% vs. 19.6%), yet the two groups had similar HbA1c and adiponectin., Conclusions: Women with probable PCOS are leaner but have comparable glycemic traits to those with a formal diagnosis, highlighting the importance of assessing biochemical profiles among women with irregular cycles, even in the absence of overweight/obesity., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2023.)

Study Question: What metabolic pathways and metabolites in the serum and follicular fluid are associated with peak estradiol levels and the number of mature oocytes?, Summary Answer: In the serum metabolome, mostly fatty acid and amino acid pathways were associated with estradiol levels and mature oocytes while in the follicular fluid metabolome, mostly lipid, vitamin, and hormone pathways were associated with peak estradiol levels and mature oocytes., What Is Known Already: Metabolomics has identified several metabolic pathways and metabolites associated with infertility but limited data are available for ovarian stimulation outcomes., Study Design, Size, Duration: A prospective cohort study of women undergoing IVF from 2009 to 2015., Participants/materials, Setting, Methods: A total of 125 women undergoing a fresh IVF cycle at a fertility clinic in the Northeast United States who provided a serum and follicular fluid sample. Untargeted metabolomics profiling was conducted using liquid chromatography with high-resolution mass spectrometry in two chromatography columns (C18 and hydrophilic interaction chromatography (HILIC)). The main ovarian stimulation outcomes were peak serum estradiol levels and number of mature oocytes. We utilized adjusted generalized linear regression models to identify significant metabolic features. Models were adjusted for age,BMI, initial infertility diagnosis, and ovarian stimulation protocol. We then conducted pathway analysis using mummichog and metabolite annotation using level-1 evidence., Main Results and Role of Chance: In the serum metabolome, 480 and 850 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively. Additionally, 437 and 538 features were associated with mature oocytes in the C18 and HILIC columns, respectively. In the follicular fluid metabolome, 752 and 929 features were associated with peak estradiol levels in the C18 and HILIC columns, respectively, Additionally, 993 and 986 features were associated with mature oocytes in the C18 and HILIC columns, respectively. The most common pathways associated with peak estradiol included fatty acids (serum and follicular fluid), hormone (follicular fluid), and lipid pathways (follicular fluid). The most common pathways associated with the number of mature oocytes retrieved included amino acids (serum), fatty acids (serum and follicular fluid), hormone (follicular fluid), and vitamin pathways(follicular fluid). The vitamin D3 pathway had the strongest association with both ovarian stimulation outcomes in the follicularfluid. Four and nine metabolites were identified using level-1 evidence (validated identification) in the serum and follicular fluid metabolomes, respectively., Limitations, Reasons for Caution: Our sample was majority White and highly educated and may not be generalizable to thewider population. Additionally, residual confounding is possible and the flushing medium used in the follicular fluid could have diluted our results., Wider Implications of the Findings: The pathways and metabolites identified by our study provide novel insights into the biologicalmechanisms in the serum and follicular fluid that may underlie follicular and oocyte development, which could potentially be used to improve ovarian stimulation outcomes., Study Funding/competing Interest(s): This work was supported by the following grants from the National Institute of Environmental Health Sciences (P30-ES019776, R01-ES009718, R01-ES022955, P30-ES000002, R00-ES026648, and T32-ES012870), and National Institute of Diabetes and Digestive and Kidney Diseases (P30DK046200). The authors have no competing interests to disclose., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Question: Are occupational factors associated with markers of testicular function among men attending a fertility center?, Summary Answer: Men working non-daytime/rotating shifts and those with physically demanding jobs have higher sperm concentration and total sperm count as well as higher estradiol and total testosterone concentrations., What Is Known Already: Semen quality has declined during recent decades and has been negatively correlated with higher risks of common chronic diseases and mortality, highlighting its public health importance beyond fertility and reproduction. While most of the previous epidemiology literature on male fertility has focused on environmental exposures, dietary factors, and other related variables, little attention has been paid to occupational factors., Study Design, Size, Duration: This observational study included 377 men who were male partners in couples seeking infertility treatment at a fertility center, who enrolled in the Environment and Reproductive Health (EARTH) study between 2005 and 2019., Participants/materials, Setting, Methods: Self-reported information on lifting/moving heavy objects, typical shift, and physical level of exertion at work was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone concentrations. Linear regression models were used to evaluate the association between occupational factors and measures of testicular function, while adjusting for covariates such as age, BMI, education, race, smoking, and abstinence time, and accounting for multiple semen samples (mean = 2, min-max = 1-9) in analyses for semen parameters., Main Results and the Role of Chance: Men had a median (interquartile range) age of 36 (33, 39) years and were predominantly Caucasian (87%). Of the men who completed the survey, 12% reported often lifting or moving heavy objects at work, 6% reported heavy physical exertion at work, and 9% reported evening or rotating shifts. Men who reported often lifting or moving heavy objects at work had 46% higher sperm concentrations (P = 0.01) and 44% higher total counts (P = 0.01) compared with men who reported never lifting or moving heavy objects at work. Similar results were found for men working in rotating shifts compared to those in day shifts, as well as for men involved in heavy levels of physical exertion compared to those with light levels at work. We also found that men involved in heavy/moderate levels of physical exertion at work had higher circulating testosterone concentrations compared to those with lighter exertion (adjusted means of 515 and 427 ng/dl, respectively, P = 0.08), and men who often moved/lifted heavy objects at work had higher estradiol concentrations, compared to those who never did (adjusted means of 36.8 and 27.1 pg/ml, respectively, P = 0.07). Men working evening/rotating shifts had 24% higher testosterone (P = 0.04) and 45% higher estradiol concentrations (P = 0.01), compared to men working day shifts. No associations were observed for ejaculated volume, total motility, morphologically normal sperm, or serum FSH and LH concentrations., Limitations, Reasons for Caution: Due to our study design which recruited men from couples seeking fertility treatment, it may not be possible to generalize our findings to men from the general population. Also, as is the case of all studies based on self-reported questionnaires, measurement error and misclassification of the exposure are potential concerns., Wider Implications of the Findings: Physically demanding jobs and rotating or evening shift occupations may be associated with higher testicular function in men measured as higher sperm concentrations and counts as well as higher serum testosterone and estradiol levels. Confirmation of these findings in other non-fertility clinic study populations is warranted., Study Funding/competing Interest(s): NIH grants R01ES022955, R01ES009718, R01ES033651, and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and Legacy, Inc. R.A.G. works part time for Legacy, Inc., which provided funds to perform this analysis. There are no other conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders., Methods and Results: We followed 95 465 ever-gravid women participating in the Nurses' Health Study II between 1993 and 2017. Cox proportional hazards models were used to estimate the hazard ratios (HRs) of CVD, including coronary heart disease (CHD), and stroke, according to the occurrence of PL. A mediation analysis was conducted to explore the intermediating effect of subsequent type 2 diabetes, hypertension, or hypercholesterolaemia. During 2 205 392 person-years of follow-up (mean 23.10 years), 2225 (2.3%) incident CVD cases were documented. After adjusting for confounding factors, PL was associated with an HR of 1.21 [95% confidence interval (CI) 1.10-1.33] for CVD during follow-up. A similar association was observed for CHD (HR 1.20; 95% CI 1.07-1.35) and stroke (HR 1.23; 95% CI 1.04-1.44). The risk of CVD increased with the number of PLs [HR 1.18 (95% CI 1.06-1.31) for 1 and 1.34 (95% CI 1.13-1.59) for ≥2 times] and was greater for PL occurring early in reproductive lifespan [HR 1.40 (95% CI 1.21-1.62) for age ≤23 years, 1.25 (95% CI 1.09-1.43) for age 24-29 years, and 1.03 (95% CI 0.88-1.19) for age ≥30 years]. Hypertension, hypercholesterolaemia, and type 2 diabetes all explained <1.80% of the association between PL and CVD., Conclusion: PL was associated with a greater CVD risk, independently of subsequent development of metabolic disorders., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The literature on the relationship between adiposity and the onset of puberty is extensive, both in size and in the length of time this question has been alive in the biomedical literature. It is easy to wonder, then, whether there is anything new to be learned in this crowded field. In this issue of the Journal, Deardorff et al. (Am J Epidemiol. 2022;191(1):7-16) show that it is still possible to innovate in this area. The authors report on the relationship between body mass index at age 5 years and a variety of markers of the onset of puberty. Consistent with the current literature, they show no association between body mass index at age 5 and pubertal onset in boys. They also show an association between obesity at age 5 with earlier onset of secondary sexual characteristics in girls, making an important subject-matter contribution that addresses many of the concerns of the existing literature in assigning causality. At the same time, the authors make an important, although less evident contribution to the practice of epidemiology for studies where the assessment of pubertal status is of interest., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Question: Is cesarean delivery associated with earlier offspring pubertal development?, Summary Answer: We identified that boys born by cesarean delivery developed puberty earlier, evidenced by an earlier age at peak height velocity and earlier attainment of puberty score > 1, than boys born by vaginal delivery., What Is Known Already: Cesarean delivery is posited to have long-term effects on health outcomes. However, few studies have examined whether mode of delivery is related to pubertal development., Study Design, Size, Duration: Prospective pre-birth cohort study consisting of 1485 mother-child pairs enrolled during pregnancy from obstetric practices and followed up until early adolescence (median age 12.9 years). Participant inclusion required data on mode of delivery and at least one measure of pubertal development., Participants/materials, Setting, Methods: Participants are children from the Project Viva study. We abstracted information on delivery mode from electronic medical records from children followed since birth (1999-2002) and examined the following markers of pubertal development: age at peak height velocity (APHV); age at menarche (girls only); parent-reported pubertal development score; and child-reported pictograph Tanner pubic hair staging. We used multivariable regression models to examine associations of delivery mode with these four pubertal indices, adjusting for the following confounders: demographic and socioeconomic factors; maternal height, pre-pregnancy BMI, total gestational weight gain, pregnancy conditions, parity, and maternal age at menarche; paternal height and BMI; gestational age at delivery and birthweight-for-gestational-age z-score., Main Results and the Role of Chance: In this study, 23.2% of children were born by cesarean delivery. Girls had an earlier APHV, had a higher pubertal score throughout childhood and in early adolescence, and were more likely to attain puberty score >1 and Tanner pubic hair Stage >1 earlier compared to boys. Mean (SD) age at menarche in girls was 12.4 (1.0) years. Boys born by cesarean delivery had significantly earlier APHV (β -0.23 years; 95% CI -0.40, -0.05) and higher risk of earlier attainment of puberty score > 1 (hazard ratio 1.09; 95% CI 1.01, 1.19) than boys born by vaginal delivery, after adjusting for confounders. These associations were not mediated by pre-pubertal BMI and were similar for planned (no labor) and unplanned (labor) cesarean delivery. No associations were observed between delivery mode and time to attain Tanner pubic hair Stage > 1 in boys. In girls, mode of delivery was not associated with any of the measured pubertal development markers., Limitations, Reasons for Caution: This study used, as secondary outcomes, parent- and child-reported measures of pubertal development, which may be more prone to error and misclassification than information collected by trained observers or physicians during clinical examinations. The findings may also not be generalizable to populations from different settings, because all participants lived in one geographic area, were well educated, and had health care., Wider Implications of the Findings: Our findings provide support for cesarean delivery as a potential indicator of identifying children who are likely to experience earlier pubertal development; however, more studies are needed to confirm or refute these observations., Study Funding/competing Interest(s): The project was funded by grants from the National Institutes of Health. The authors have no financial relationships or competing interests to disclose., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Fetal exposure to gestational diabetes mellitus (GDM) increases the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 (FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposure to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposity and metabolic traits during childhood/adolescence., Design and Methods: The follow-up study included 504 GDM and 540 control offspring aged 9-16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concentrations of leptin, adiponectin, and FGF21 were measured by validated immune assays., Results: GDM offspring had 38% (95% CI: 22-55%) higher leptin, 0.6 mg/L (95% CI: -1.2, -0.04 mg/L) lower adiponectin, and 32% (95% CI: -47%, -12%) lower FGF21 concentrations than control offspring (P < 0.05). After adjustment for confounders including maternal pre-pregnancy BMI, GDM offspring had borderline higher leptin (P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concentrations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated with fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage., Conclusions: GDM offspring had higher leptin, lower adiponectin and FGF21 concentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.

Study Question: Is physical activity or sedentary time associated with semen quality parameters?, Summary Answer: Among healthy men screened as potential sperm donors, higher self-reported physical activity was associated with increased progressive and total sperm motility., What Is Known Already: Despite the claimed beneficial effect of moderate physical activity on semen quality, results from epidemiological studies have been inconclusive. Previous studies were mostly conducted among endurance athletes or male partners of couples who sought infertility treatment., Study Design, Size, Duration: Healthy men screened as potential sperm donors were recruited at the Hubei Province Human Sperm Bank of China. Between April 2017 and July 2018; 746 men completed the long-form International Physical Activity Questionnaire (IPAQ) and provided repeated semen samples (n = 5252) during an approximately 6-month period., Participants/materials, Setting, Methods: Total metabolic equivalents (METs), moderate-to-vigorous METs and sedentary time were abstracted from the IPAQ. Sperm concentration, total sperm count, progressive motility and total motility in repeated specimens were determined by trained clinical technicians. Mixed-effect models were applied to investigate the relationships between physical activity and sedentary time and repeated measures of semen quality parameters., Main Results and the Role of Chance: After adjusting for multiple confounders, total METs and moderate-to-vigorous METs were both positively associated with progressive and total sperm motility. Compared with men in the lowest quartiles, those in the highest quartiles of total and moderate-to-vigorous METs had increased progressive motility of 16.1% (95% CI: 6.4, 26.8%) and 17.3% (95% CI: 7.5, 27.9%), respectively, and had increased total motility of 15.2% (95% CI: 6.2, 24.9%) and 16.4% (95% CI: 7.4, 26.1%), respectively. Sedentary time was not associated with semen quality parameters., Limitations, Reasons for Caution: The IPAQ was reported only once from study participants; measurement errors were inevitable and may have biased our results. Furthermore, although we have adjusted for various potential confounders, the possibility of unmeasured confounding cannot be fully ruled out., Wider Implications of the Findings: Our findings suggest that maintaining regular exercise may improve semen quality parameters among healthy, non-infertile men. Specifically, we found that higher self-reported total and moderate-to-vigorous METs were associated with improved sperm motility, which reinforces the existing evidence that physical activity may improve male reproductive health., Study Funding/competing Interest(s): Y.-X.W was supported by the Initiative Postdocs Supporting Program (No. BX201700087). A.P. was supported by the National Key Research and Development Program of China (2017YFC0907504). C.-L.X. was supported by the National Key Research and Development Program of China (2016YFC1000206). The authors report no conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.For permissions, please e-mail: journals.permission@oup.com.)

Study Question: Is adherence to an a priori defined diet quality indices [Alternate Healthy Index 2010 (AHEI-2010), relative Mediterranean diet score (rMED) or dietary approaches to stop hypertension (DASH)] associated with semen quality and reproductive hormone levels in young men?, Summary Answer: Greater adherence to the DASH diet is related to higher sperm counts., What Is Known Already: Studies assessing the relationship between dietary intake and male reproductive function have mainly been focused on specific nutrients, food groups or data-driven dietary patterns, but the evidence on a priori defined dietary indices is still scarce., Study Design, Size, Duration: Cross-sectional study of 209 male university students recruited from October 2010 to November 2011 in Murcia Region (Southern Spain)., Participants/materials, Setting, Methods: Healthy young men aged 18-23 years were included in this study. Diet was assessed using a validated food frequency questionnaire and three a priori-defined dietary indices (AHEI-2010, rMED and DASH) were calculated. Linear regression was used to analyze the relation between the three dietary indices and semen quality parameters and reproductive hormone levels accounting for potential confounders and covariates., Main Results and the Role of Chance: We found statistically significant positive associations between the DASH index and sperm concentration (P, trend = 0.04), total sperm count (P, trend = 0.04) and total motile sperm count (P, trend = 0.02). No associations were observed for other semen parameters or male reproductive hormones., Limitations, Reasons for Caution: Even though we adjusted for several known and suspected confounders we cannot exclude the possibility of residual or unmeasured confounding or chance findings. Subjects were blinded to the study outcomes thus reducing the potential influence on their report of diet. Our sample size may be too small to rule out associations with other semen parameters or reproductive hormones. Causal inference is limited, as usual with all observational studies., Wider Implications of the Findings: The results suggest that greater adherence to the DASH may help improve sperm counts. This study was carried out on young men from the general population. However, results may differ among other populations (e.g. infertile men). Therefore, further research is needed to confirm these findings and extend these results to other populations., Study Funding/competing Interest(s): This work was supported by Fundación Séneca, grants No 08808/PI/08 and No 19443/PI/14; Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (AES), grants No PI10/00985 and No PI13/01237; and grant P30DK046200 from the National Institutes of Health. Authors have no competing interests to declare., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Study Question: What is the association of female and male partner marijuana smoking with infertility treatment outcomes with ART?, Summary Answer: Women who were marijuana smokers at enrollment had a significantly higher adjusted probability of pregnancy loss during infertility treatment with ART whereas, unexpectedly, there was a suggestion of more favorable treatment outcomes in couples where the man was a marijuana smoker at enrollment., What Is Known Already: Data on the relation of female and male partner marijuana use with outcomes of infertility treatment is scarce despite increased use and legalization worldwide., Study Design, Size, Duration: We followed 421 women who underwent 730 ART cycles while participating in a prospective cohort (the Environment and Reproductive Health Study) at a fertility center between 2004 and 2017. Among them, 200 women (368 cycles) were part of a couple in which their male partner also enrolled in the study., Participants/materials, Setting, Methods: Participants self-reported marijuana smoking at baseline. Clinical endpoints were abstracted from electronic medical records. We used generalized linear mixed models with empirical standard errors to evaluate the association of baseline marijuana smoking with ART outcomes adjusting for participants' age, race, BMI, tobacco smoking, coffee and alcohol consumption, and cocaine use. We estimated the adjusted probability of implantation, clinical pregnancy, and live birth per ART cycle, as well as the probability of pregnancy loss among those with a positive B-hCG., Main Results and the Role of Chance: The 44% of the women and 61% of the men had ever smoked marijuana; 3% and 12% were marijuana smokers at enrollment, respectively. Among 317 women (395 cycles) with a positive B-hCG, those who were marijuana smokers at enrollment (N = 9, cycles = 16) had more than double the adjusted probability of pregnancy loss than those who were past marijuana smokers or had never smoked marijuana (N = 308, 379 cycles) (54% vs 26%; P = 0.0003). This estimate was based on sparse data. However, couples in which the male partner was a marijuana smoker at enrollment (N = 23, 41 cycles) had a significantly higher adjusted probability of live birth than couples in which the male partner was a past marijuana smoker or had never smoked marijuana (N= 177, 327 cycles) (48% vs 29%; P = 0.04), independently of the women's marijuana smoking status. Treatment outcomes of past marijuana smokers, male and female, did not differ significantly from those who had never smoked marijuana., Limitations, Reasons for Caution: Marijuana smoking was self-reported with possible exposure misclassification. Chance findings cannot be excluded due to the small number of exposed cases. The results may not be generalizable to couples from the general population., Wider Implications of the Findings: Even though marijuana smoking has not been found in past studies to impact the ability to become pregnant among pregnancy planners in the general population, it may increase the risk of pregnancy loss among couples undergoing infertility treatment. Marijuana smoking by females and males may have opposing effects on outcomes of infertility treatment with ART., Study Funding/competing Interest(s): The project was financed by grants R01ES009718, P30ES000002, and K99ES026648 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Study Question: Is there an association between air pollution exposures and the risk of spontaneous abortion (SAB)?, Summary Answer: Higher exposure to particulate matter (PM) air pollution above and beyond a woman's average exposure may be associated with greater risk of SAB, particularly among women experiencing at least one SAB during follow-up., What Is Known Already: There is sufficient biologic plausibility to suggest that air pollution adversely affects early pregnancy outcomes, particularly pregnancy loss; however, the evidence is limited., Study Design, Size, Duration: Our prospective cohort study included 19 309 women in the Nurses' Health Study II who contributed a total of 35 025 pregnancies between 1990 and 2008. We also conducted a case-crossover analysis among 3585 women (11 212 pregnancies) with at least one SAB and one live birth during follow-up., Participants/materials, Setting, Methods: Proximity to major roadways and exposure to PM <10 microns (PM10), 2.5-10 microns (PM2.5-10) and <2.5 microns (PM2.5) were determined for residential addresses between 1989 and 2007. Pregnancy outcomes were self-reported biannually throughout follow-up and comprehensively in 2009. Multivariable log-binomial regression models with generalized estimating equations were used to estimate the risk ratios and 95% CIs of SAB. Conditional logistic regression was used for the case-crossover analysis., Main Results and the Role of Chance: During the 19 years of follow-up, 6599 SABs (18.8% of pregnancies) were reported. In the main analysis, living closer to a major roadway and average exposure to PM10, PM10-2.5 or PM2.5 in the 1 or 2 years prior to pregnancy were not associated with an increased risk of SAB. However, small positive associations between PM exposures and SAB were observed when restricting the analysis to women experiencing at least one SAB during follow-up. In the case-crossover analysis, an increase in PM10 (per 3.9 μg/m3), PM2.5-10 (per 2.3 μg/m3) and PM2.5 (per 2.0 μg/m3) in the year prior to pregnancy was associated with 1.12 (95% CI 1.06, 1.19), 1.09 (95% CI 1.03, 1.14) and 1.10 (95% CI 1.04, 1.17) higher odds of SAB, respectively., Limitations, Reasons for Caution: We did not have information on the month or day of SAB, which precluded our ability to examine specific windows of susceptibility or acute exposures. We also used ambient air pollution exposures as a proxy for personal exposure, potentially leading to exposure misclassification., Wider Implications of the Findings: In our case-crossover analysis (but not in the entire cohort) we observed positive associations between exposure to all size fractions of PM exposure and risk of SAB. This may suggest that changes in PM exposure confer greater risk of SAB or that women with a history of SAB are a particularly vulnerable subgroup., Study Funding/competing Interest(s): The authors are supported by the following NIH grants UM1CA176726, R00ES026648 and P30ES000002. The authors have no actual or potential competing financial interests to disclose., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Study Question: Is self-reported type of underwear worn associated with markers of testicular function among men at a fertility center?, Summary Answer: Men who reported most frequently wearing boxers had higher sperm concentration and total count, and lower FSH levels, compared to men who did not., What Is Known Already: Elevated scrotal temperatures are known to adversely affect testicular function. However, the epidemiologic literature on type of underwear, as a proxy of scrotal temperature, and male testicular function is inconsistent., Study Design, Size, Duration: This is a cross-sectional study including 656 male partners of couples seeking infertility treatment at a fertility center (2000-2017)., Participants/materials, Setting, Methods: Self-reported information on type of underwear worn was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone levels and neutral comet assays for sperm DNA damage. We fit linear regression models to evaluate the association between underwear type and testicular function, adjusting for covariates and accounting for multiple semen samples., Main Results and the Role of Chance: Men had a median (interquartile range) age of 35.5 (32.0, 39.3) years and BMI of 26.3 (24.4, 29.9) kg/m2. About half of the men (53%; n = 345) reported usually wearing boxers. Men who reported primarily wearing boxers had a 25% higher sperm concentration (95% CI = 7, 31%), 17% higher total count (95% CI = 0, 28%) and 14% lower serum FSH levels (95% CI = -27, -1%) than men who reported not primarily wearing boxers. Sperm concentration and total count were inversely related to serum FSH. Furthermore, the differences in sperm concentration and total count according to type of underwear were attenuated after adjustment for serum FSH. No associations with other measured reproductive outcomes were observed., Limitations, Reasons for Caution: Our results may not be generalizable to men from the general population. Underwear use was self-reported in a questionnaire and there may be misclassification of the exposure. The cross-sectional design limits causal inference, and residual confounding is still possible owing to lack of information on other modifiable life styles that can also modify scrotal heat (e.g. type of trousers worn, textile fabric of the underwear). Blood sampling was not limited to the morning and, as a result, we may have missed associations with testosterone or other hormones with significant circadian variation despite statistical adjustment for time of blood draw., Wider Implications of the Findings: Certain styles of male underwear may impair spermatogenesis and this may result in a compensatory increase in gonadotrophin secretion, as reflected by higher serum FSH levels among men who reported most frequently wearing tight underwear. Confirmation of these findings, and in particular the findings on FSH levels suggesting a compensatory mechanism, is warranted., Study Funding/competing Interest(s): The project was financed by Grants (R01ES022955, R01ES009718, P30ES000002, and K99ES026648) from the National Institutes of Health. None of the authors has any conflicts of interest to declare.

Context: Marine long-chain omega-3 fatty acids have been positively related to markers of fecundity in both men and women. However, seafood, their primary food source, can also be a source of toxicants, which could counteract the reproductive benefits., Objective: To examine the relationship of male and female seafood intake with time to pregnancy (TTP)., Design: Our prospective cohort study included 501 couples planning pregnancy, who participated in the Longitudinal Investigation of Fertility and the Environment study (2005 to 2009) and were followed up for ≤1 year or until pregnancy was detected. Seafood intake was collected daily during follow-up in journals., Setting: Couples residing in Michigan and Texas were recruited using population-based sampling frameworks., Main Outcome Measures: The primary outcome was the TTP, determined using an in-home pregnancy test. A secondary outcome was sexual intercourse frequency (SIF) as recorded in the daily journals., Results: Couples with male and female partners who consumed eight or more seafood servings per cycle had 47% (95% CI, 7% to 103%) and 60% (95% CI, 15% to 122%) greater fecundity (shorter TTP) than couples with male and female partners who consumed one or fewer seafood servings per cycle. Couples with both partners consuming eight or more seafood servings per cycle had 61% (95% CI, 17% to 122%) greater fecundity than couples consuming less. Male and female partners with the highest seafood intake (eight or more servings per cycle) also had 22% greater SIF., Conclusions: Greater male and female seafood intake was associated with a higher SIF and fecundity among a large prospective cohort of couples attempting pregnancy.

We evaluated the performance of a semiquantitative food frequency questionnaire (SFFQ), the Automated Self-Administered 24-Hour Dietary Recall (ASA24), and 7-day dietary records (7DDRs), in comparison with biomarkers, in the estimation of nutrient intakes among 627 women in the Women's Lifestyle Validation Study (United States, 2010-2012). Two paper SFFQs, 1 Web-based SFFQ, 4 ASA24s (beta version), 2 7DDRs, 4 24-hour urine samples, 1 doubly labeled water measurement (repeated among 76 participants), and 2 fasting blood samples were collected over a 15-month period. The dietary variables evaluated were energy, energy-adjusted intakes of protein, sodium, potassium, and specific fatty acids, carotenoids, α-tocopherol, retinol, and folate. In general, relative to biomarkers, averaged ASA24s had lower validity than the SFFQ completed at the end of the data-collection year (SFFQ2); SFFQ2 had slightly lower validity than 1 7DDR; the averaged SFFQs had validity similar to that of 1 7DDR; and the averaged 7DDRs had the highest validity. The deattenuated correlation of energy-adjusted protein intake assessed by SFFQ2 with its biomarker was 0.46, similar to its correlation with 7DDRs (deattenuated r = 0.54). These data indicate that the SFFQ2 provides reasonably valid measurements of energy-adjusted intake for most of the nutrients assessed in our study, consistent with earlier conclusions derived using 7DDRs as the comparison method. The ASA24 needs further evaluation for use in large population studies, but an average of 3 days of measurement will not be sufficient for some important nutrients.

Background: Little is known about the predictors of sexual intercourse frequency (SIF) among couples trying to conceive despite the well-established link between SIF and fecundity., Aim: To evaluate men's and women's demographic, occupational, and lifestyle predictors of SIF among couples., Methods: 469 Couples without a history of infertility participating in the Longitudinal Investigation of Fertility and the Environment Study (2005-2009) were followed up for ≤1 year while trying to conceive. At enrollment, both partners were interviewed about demographic, occupational, lifestyle, and psychological characteristics using standardized questionnaires. Multivariable generalized linear mixed models with Poisson distribution were used to estimate the adjusted percent difference in SIF across exposure categories., Outcomes: SIF was recorded in daily journals and summarized as average SIF/mo., Results: The median (interquartile range) SIF during follow-up was 6 (4-9) acts/mo. For every year increase in age for women and men, SIF decreased by -0.8% (95% CI -2.5 to 1.0%) and -1.7% (95% CI -3.1 to -0.3%). Women with high school education or less and those of non-white race had 34.4% and 16.0% higher SIF, respectively. A similar trend was seen for men's education and race. Only couples where both partners (but not just 1 partner) worked rotating shifts had -39.1% (95% CI -61.0 to -5.0%) lower SIF compared to couples where neither partner worked rotating shifts. Men's (but not women's) exercise was associated with 13.2% (95% CI 1.7-26.0%) higher SIF. Diagnosis of a mood or anxiety disorder in men (but not women) was associated with a 26.0% (95% CI -42.7 to -4.4%) lower SIF. Household income, smoking status, body mass index, night work, alcohol intake, and psychosocial stress were not associated with SIF., Clinical Translation: Even among couples trying to conceive, there was substantial variation in SIF. Both partners' age, education, race, and rotating shift work as well as men's exercise and mental health play an important role in determining SIF., Conclusions: As this was a secondary analysis of an existing study, we lacked information on many pertinent psychological and relationship quality variables and the hormonal status of participants, which could have affected SIF. The unique population-based couple design, however, captured both partners' demographics, occupational characteristics, and lifestyle behaviors in advance of their daily, prospective reporting of SIF, which was a major strength. Important predictors of SIF among couples attempting to conceive include men's exercise and mental health and both partners' age, education, race, and rotating shift work. Gaskins AJ, Sundaram R, Buck Louis GM, et al. Predictors of Sexual Intercourse Frequency Among Couples Trying to Conceive. J Sex Med 2018;15:519-528., (Copyright © 2018 International Society for Sexual Medicine. All rights reserved.)

Background: The Environment and Reproductive Health (EARTH) Study is an ongoing prospective preconception cohort designed to investigate the impact of environmental, nutritional, and lifestyle factors among both women and men on fertility and pregnancy outcomes., Methods: The EARTH Study recruits women 18 to 45 years and men 18 to 55 years seeking fertility evaluation and treatment at the Massachusetts General Hospital (MGH) Fertility Center, Boston, USA. Women and men are eligible to join either independently or as a couple. Participants are followed from study entry throughout each fertility treatment cycle, once per trimester of pregnancy (for those achieving pregnancy), and up to labor and delivery, or until they discontinue treatment or withdraw from the study. The study collects biological samples, self-reported questionnaire data (including a food frequency questionnaire) and clinically abstracted information., Results: As of June 2017, the study cohort included 799 women and 487 men (447 couples; 40 men joined without female partners). Women were on average 34.7 years old at time of enrolment and predominantly Caucasian (81%), educated (49% have a graduate degree), and nulliparous (83%). Men were on average 36.6 years at baseline and mostly Caucasian (86%) and never-smokers (67%)., Conclusions: The EARTH Study is one of the few cohorts designed to examine multiple potentially critical windows of vulnerability, including the paternal and maternal preconception windows and the periconception and prenatal windows in pregnancy. It is also one of the few human studies that has assessed potential interactions between environmental exposures and dietary factors., Competing Interests: Conflict of Interest: All authors declare no potential or actual competing interests.

Semen parameters are variable within individuals, but it is unclear whether 1 semen sample could represent a man's long-term average values in epidemiologic studies. Between 2005 and 2014, a total of 329 men from a fertility clinic in Boston, Massachusetts, provided 768 semen samples as part of the Environment and Reproductive Health (EARTH) Study. Total sperm count, sperm concentration, morphology, motility, and ejaculate volume were assessed. We used linear mixed models to compare values from men's first semen samples with their long-term averages and to calculate intraclass correlation coefficients for each parameter. We calculated positive predictive values (PPVs) and negative predictive values (NPVs) by comparing agreement in classification according to World Health Organization reference limits. There were no differences in mean semen parameters between men's first samples and the remaining replicates. Intraclass correlation coefficients ranged from 0.61 for morphology to 0.75 for concentration, indicating consistently greater between-man variability than within-man variability. Nevertheless, using 1 sample alone resulted in high NPVs but low PPVs (range, 43%-91%). The average of 2 samples was needed to achieve high PPVs (range, 86%-100%) and NPVs (range, 91%-100%). We conclude that 1 semen sample may suffice for studies aimed at identifying average differences in semen quality between individuals. Studies aimed at classifying men based on World Health Organization reference limits may benefit from collection of 2 or more samples., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

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., (Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.)

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., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Context: Experimental data in rodents suggest that the adverse reproductive health effects of bisphenol A (BPA) can be modified by intake of soy phytoestrogens. Whether the same is true in humans is not known., Objective: The purpose of this study was to evaluate whether soy consumption modifies the relation between urinary BPA levels and infertility treatment outcomes among women undergoing assisted reproduction., Setting: The study was conducted in a fertility center in a teaching hospital., Design: We evaluated 239 women enrolled between 2007 and 2012 in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study, who underwent 347 in vitro fertilization (IVF) cycles. Participants completed a baseline questionnaire and provided up to 2 urine samples in each treatment cycle before oocyte retrieval. IVF outcomes were abstracted from electronic medical records. We used generalized linear mixed models with interaction terms to evaluate whether the association between urinary BPA concentrations and IVF outcomes was modified by soy intake., Main Outcome Measure: Live birth rates per initiated treatment cycle were measured., Results: Soy food consumption modified the association of urinary BPA concentration with live birth rates (P for interaction = .01). Among women who did not consume soy foods, the adjusted live birth rates per initiated cycle in increasing quartiles of cycle-specific urinary BPA concentrations were 54%, 35%, 31%, and 17% (P for trend = .03). The corresponding live birth rates among women reporting pretreatment consumption of soy foods were 38%, 42%, 47%, and 49% (P for trend = 0.35). A similar pattern was found for implantation (P for interaction = .02) and clinical pregnancy rates (P for interaction = .03) per initiated cycle, where urinary BPA was inversely related to these outcomes among women not consuming soy foods but unrelated to them among soy consumers., Conclusion: Soy food intake may protect against the adverse reproductive effects of BPA. As these findings represent the first report suggesting a potential interaction between soy and BPA in humans, they should be further evaluated in other populations.

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., (Published by Oxford University Press on behalf of International Epidemiological Association 2016. This work is written by US Government employees and is in the public domain in the US.)

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 Interests: This work was supported by NIH grants R01ES022955, R01ES009718 and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and grant T32DK00770316 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., (© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Study Question: Is intake of fatty acids related to semen quality among young men?, Summary Answer: The intake of trans fatty acids is inversely related to total sperm count in healthy young men., What Is Known Already: Spain has seen an increase in the proportion of calories consumed as fat over the same period that a downward trend in semen quality has been observed. In addition, rodent models suggest that trans fat intake may severely affect testicular function., Study Design, Size, Duration: Cross-sectional study of 209 men recruited between October 2010 and November 2011., Participants/materials, Setting, Methods: A group of 209 healthy young university students 18-23 years of age provided a semen sample and completed a previously validated food frequency questionnaire. The association between intake of fatty acids with semen quality parameters (sperm concentration, motility, morphology and total count) was assessed using multivariate linear regression., Main Results and the Role of the Chance: Trans fatty acid intake was inversely related to total sperm count after adjusting for potential confounders (P, trend = 0.03). The multivariate adjusted mean (95% confidence interval) total sperm count in increasing quartiles of trans fat intake was 144 (110-190), 113 (87-148), 100 (18-130) and 89 (69-117). There also was an inverse association between cholesterol intake and ejaculate volume (P, trend = 0.04). No other statistically significant relations were observed., Limitations, Reasons for Caution: The cross-sectional design of the study limits causal inference, we cannot exclude the possibility of unmeasured confounding and there was insufficient statistical power to identify modest associations., Wider Implications of the Findings: The results of this study, together with previous experimental work in rodents and biomarker studies among infertility patients, suggest that intake of trans fatty acids may be related to lower semen quality. Although the data provide further evidence that diet is a modifiable factor that could impact male fertility, it is not known whether the observed differences in sperm count translate into differences in fertility., Study Funding/competing Interest(s): This work was supported by The Seneca Foundation, Regional Agency of Science and Technology, grant no 00694/PI/04, Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (FIS), grant no PI10/00985, and grant P30 DK46200 from the National Institutes of Health. The authors have no competing interests to declare.

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.

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.

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; P(trend) = 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; P(trend) = 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.

Study Question: Are different dietary patterns associated with semen parameters in young men?, Study Answer: The consumption of a Prudent dietary pattern was significantly associated with higher progressive sperm motility and unrelated to sperm concentration and morphology. The consumption of a Western dietary pattern was unrelated to conventional semen quality parameters., What Is Known Already: Over the past decades there has been evidence of a concomitant decline in sperm and diet quality. Yet whether diet composition influences semen quality remains largely unexplored., Study Design, Size, Duration: The Rochester Young Men's Study (n= 188) was a cross-sectional study conducted between 2009 and 2010 at the University of Rochester., Participants, Setting, Methods: Men aged 18-22 years were included in this analysis. Diet was assessed via food frequency questionnaire and dietary patterns were identified by factor analysis. Linear regression was used to analyze the relation between diet patterns and conventional semen quality parameters (sperm concentration, progressive motility and morphology) adjusting for abstinence time, multivitamin use, race, smoking status, BMI, recruitment period, moderate-to-intense exercise and total calorie intake., Results: Two dietary patterns were identified by factor analysis. The 'Western' pattern was characterized by high intake of red and processed meat, refined grains, pizza, snacks, high-energy drinks and sweets. The 'Prudent' pattern was characterized by high intake of fish, chicken, fruit, vegetables, legumes and whole grains. The Prudent pattern was positively associated with percent progressively motile sperm in multivariate models (P-trend = 0.04). Men in the highest quartile of the Prudent diet had 11.3% (95% CI 1.3, 21.3) higher % progressively motile sperm compared with men in the lowest quartile. The Prudent pattern was unrelated to sperm concentration and morphology. The Western pattern was not associated with any semen parameter., Limitations: This was a cross-sectional and observational study, which limited our ability to determine causality of diet on semen quality parameters., Wider Implications of the Findings: Our findings support the suggestion that a diet rich in fruits, vegetables, chicken, fish and whole grains may be an inexpensive and safe way to improve at least one measure of semen quality., Study Funding/competing Interests: The authors are supported by NIH grant T32DK007703-16 and P30DK46200 and European Union DEER Grant 212844. The authors have no competing interests to declare.

Background: The objective of this study was to examine the relation between dietary fats and semen quality parameters., Methods: Data from 99 men with complete dietary and semen quality data were analyzed. Fatty acid levels in sperm and seminal plasma were measured using gas chromatography in a subgroup of men (n = 23). Linear regression was used to determine associations while adjusting for potential confounders., Results: Men were primarily Caucasian (89%) with a mean (SD) age of 36.4 (5.3) years; 71% were overweight or obese; and 67% were never smokers. Higher total fat intake was negatively related to total sperm count and concentration. Men in the highest third of total fat intake had 43% (95% confidence interval (CI): 62-14%) lower total sperm count and 38% (95% CI: 58-10%) lower sperm concentration than men in the lowest third (P(trend) = 0.01). This association was driven by intake of saturated fats. Levels of saturated fatty acids in sperm were also negatively related to sperm concentration (r= -0.53), but saturated fat intake was unrelated to sperm levels (r = 0.09). Higher intake of omega-3 polyunsaturated fats was related to a more favorable sperm morphology. Men in the highest third of omega-3 fatty acids had 1.9% (0.4-3.5%) higher normal morphology than men in the lowest third (P(trend) = 0.02)., Conclusions: In this preliminary cross-sectional study, high intake of saturated fats was negatively related to sperm concentration whereas higher intake of omega-3 fats was positively related to sperm morphology. Further, studies with larger samples are now required to confirm these findings.

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.

Few studies have evaluated the validity of adolescent diet recall after many decades. Between 1943 and 1970, yearly diet records were completed by parents of adolescents participating in an ongoing US study. In 2005-2006, study participants who had been 13-18 years of age when the diet records were collected were asked to complete a food frequency questionnaire regarding their adolescent diet. Food frequency questionnaires and diet records were available for 72 participants. The authors calculated Spearman correlation coefficients between food, food group, and nutrient intakes from the diet records and food frequency questionnaire and deattenuated them to account for the effects of within-person variation measured in the diet records on the association. The median deattenuated correlation for foods was 0.30, ranging from -0.53 for a beef, pork, or lamb sandwich to 0.99 for diet soda. The median deattenuated correlation for food groups was 0.31 (range: -0.48 for breads to 0.70 for hot beverages); for nutrient intakes, it was 0.25 (range: -0.08 for iron to 0.82 for vitamin B(12)). Some dietary factors were reasonably recalled 3-6 decades later. However, this food frequency questionnaire did not validly measure overall adolescent diet when completed by middle-aged and older adults on average 48 years after adolescence.

Validation of early childhood diet recalls by surrogate responders decades later has not been possible because of a lack of diet records from the distant past. Between 1948 and 1970, parents of children participating in the Fels Longitudinal Study (Kettering, Ohio) completed a 7-day diet record for their children every year from birth to age 18 years. In 2005-2006, all surviving women (n = 59) with a child aged 3-5 years when diet records had been collected were asked to complete a 42-item food frequency questionnaire (FFQ) pertaining to 1 of their children's diets at age 3-5 years. One or more diet records were available for 48 children. The authors calculated Spearman correlation coefficients for correlations between food, food-group, and nutrient intakes from the diet records and the FFQ and deattenuated them to account for the effects of within-person variation in the diet records on the association. For foods, the median deattenuated correlation coefficient was 0.19 (range, -0.31 to 0.85); moderate-to-high correlations were found for some specific foods. Correlations for food groups were slightly higher (median, 0.27; range, -0.14 to 0.85). Correlations for nutrient intakes were consistently low (median, 0.06; range, -0.35 to 0.27). Overall, the FFQ did not validly reflect overall preschool diet when completed by mothers 4 decades later.

Background: High isoflavone intake has been related to decreased fertility in animal studies, but data in humans are scarce. Thus, we examined the association of soy foods and isoflavones intake with semen quality parameters., Methods: The intake of 15 soy-based foods in the previous 3 months was assessed for 99 male partners of subfertile couples who presented for semen analyses to the Massachusetts General Hospital Fertility Center. Linear and quantile regression were used to determine the association of soy foods and isoflavones intake with semen quality parameters while adjusting for personal characteristics., Results: There was an inverse association between soy food intake and sperm concentration that remained significant after accounting for age, abstinence time, body mass index, caffeine and alcohol intake and smoking. In the multivariate-adjusted analyses, men in the highest category of soy food intake had 41 million sperm/ml less than men who did not consume soy foods (95% confidence interval = -74, -8; P, trend = 0.02). Results for individual soy isoflavones were similar to the results for soy foods and were strongest for glycitein, but did not reach statistical significance. The inverse relation between soy food intake and sperm concentration was more pronounced in the high end of the distribution (90th and 75th percentile) and among overweight or obese men. Soy food and soy isoflavone intake were unrelated to sperm motility, sperm morphology or ejaculate volume., Conclusions: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration.