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Henrik Toft Sørensen,1 Tina Christensen,1 Hans Erik Bøtker,2 Christian Fynbo Christiansen,1 Cecilia H Fuglsang,1 Sigrid B Gribsholt,1 Frederik Pagh Bredahl Kristensen,1 Kristina Laugesen,1 Anne Sofie D Laursen,1 Mette Nørgaard,1 Morten Schmidt,1 Nils Skajaa,1 Frederikke S Troelsen,1 Lars Pedersen1 1Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Aarhus, Denmark; 2Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkCorrespondence: Henrik Toft Sørensen, Department of Clinical Epidemiology, Aarhus University Hospital and Aarhus University, Olof Palmes Allé 43-45, Aarhus, 8200, Denmark, Tel +45 87 16 82 15, Email hts@clin.au.dkPurpose: Humans are living longer and may develop multiple chronic diseases in later life. The Better Health in Late Life cohort study aims to improve our understanding of the risks and outcomes of multimorbidity in the Danish population.Methods: A randomly-selected sample of Danish residents who were 50– 65 years of age received a questionnaire and an invitation to participate in this study. Respondents completed an online survey between October 2021 and January 2022 which addressed topics that included self-assessed health, mental health, sleep, specific medical conditions, use of painkillers, diet, alcohol consumption, smoking, physical activity, and body composition. This information was linked to the Danish health and social registries (some established in 1943 and onwards) that maintain data on filled prescriptions, hospital records, socioeconomic status, and health care utilization.Results: Responses were received from 115,431 of the 301,244 residents invited to participate (38%). We excluded respondents who answered none of the questions as well as those who provided no information on sex or indicated an age other than 50– 65 years. Of the 114,283 eligible respondents, 54.8% were female, 30.3% were overweight, and 16.7% were obese. Most participants reported a weekly alcohol consumption of less than seven units and 13.3% were current smokers; 5.2% had a history of hospitalization for solid cancer, and 3.0%, 2.3%, 2.0%, and 0.9% reported chronic pulmonary disease, diabetes, stroke, and myocardial infarction, respectively. The most frequently filled prescriptions were for medications used to treat the nervous system and cardiovascular diseases (38.1% and 37.4%, respectively).Keywords: aging, epidemiology, health registries, life course epidemiology, multimorbidity, prospective cohort

Study Question: To what extent is male physical activity (PA) associated with fecundability (per-cycle probability of conception)?, Summary Answer: Preconception levels of vigorous, moderate, or total PA were not consistently associated with fecundability across Danish and North American cohorts, but there was suggestive evidence that bicycling with a 'soft, comfort seat' was associated with reduced fecundability in both cohorts, especially among males with greater BMI., What Is Known Already: Among males, some studies indicate that moderate PA might improve fertility, whereas vigorous PA, especially bicycling, might be detrimental., Study Design, Size, Duration: We assessed the association between male PA and fecundability among couples participating in two preconception cohort studies: SnartForaeldre.dk (SF) in Denmark (2011-2023) and Pregnancy Study Online (PRESTO) in North America (2013-2024). We restricted analyses to 4921 males (1088 in SF and 3833 in PRESTO) who had been trying to conceive with their partners for ≤6 cycles at enrollment., Participants/materials, Setting, Methods: At baseline, male partners reported data on medical history, lifestyle, behavioral, anthropometric factors, and their PA levels using different instruments [SF: International Physical Activity Questionnaire (IPAQ); PRESTO: average annual hours/week and type]. Both cohorts included additional questions on bicycling (frequency, bike seat type). After linking couple data at baseline, the female partner completed follow-up questionnaires to update their pregnancy status every 8 weeks for 12 months or until conception, whichever occurred first. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, controlling for potential confounders., Main Results and the Role of Chance: Average hours/week of vigorous PA, moderate PA, and total metabolic equivalents of task were generally inversely associated with fecundability in SF, but not PRESTO. While there was little association with bicycling overall in either cohort, we observed an inverse association for bicycling using a 'soft, comfort seat' (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.53-1.05; PRESTO: FR = 0.81, 95% CI: 0.62-1.07) but not a 'hard, racing-style seat' (≥3 vs 0 h/week: SF: FR = 1.16, 95% CI: 0.95-1.41; PRESTO: FR = 1.06, 95% CI: 0.89-1.28). Among males with BMI ≥25 kg/m2, associations with bicycling using a 'soft, comfort seat' were similar or stronger (≥3 vs 0 h/week: SF: FR = 0.75, 95% CI: 0.45-1.24; PRESTO: FR = 0.73, 95% CI: 0.52-1.03)., Limitations, Reasons for Caution: Misclassification of PA was likely the most important study limitation because we ascertained PA only once at enrollment using different instruments in each cohort. We would expect misclassification of PA to be non-differential given the prospective study design. Additional weaknesses include the narrow range of PA levels evaluated, reduced precision when stratifying the data by selected covariates, and limited generalizability due to the large percentage of non-Hispanic White participants and restriction of the cohort to pregnancy planners., Wider Implications of the Findings: Further evaluation of the potential deleterious effects of bicycling on male fertility, with additional consideration of the influence of bike seat type and BMI, may be warranted., Study Funding/competing Interest(s): This study was funded by NICHD Grants R21-HD072326, R01-HD086742, R01 HD105863, and R03-HD094117. These funding bodies had no involvement in the: study design; collection, analysis, and interpretation of data; writing of the report; or decision to submit the article for publication. L.A.W. serves as a paid consultant for AbbVie, Inc. and the Bill and Melinda Gates Foundation. She also receives in-kind donations for primary data collection in Pregnancy Study Online (PRESTO) from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility apps). All of these relationships are for work unrelated to this manuscript. M.L.E. is an advisor for and holds stock in Legacy, Doveras, VSeat, Hannah, Illumicell, HisTurn, & Next. The other authors have no competing interests to declare., Trial Registration Number: N/A., (© The Author(s) 2024. 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.)

Background: Epidemiologic studies have demonstrated that ambient concentrations of particulate matter < 2.5 μm (PM 2.5 ) are associated with reduced fecundability, the per cycle probability of conception. The specific constituents driving this association are unknown., Objectives: We examined the association between ambient concentrations of PM 2.5 constituents and fecundability in a Danish preconception cohort study., Methods: During 2007-2018, we enrolled female pregnancy planners in an Internet-based preconception cohort study. We included the 5905 participants who had been trying to conceive for < 3 cycles at study enrollment. Participants completed a baseline questionnaire and follow-up questionnaires every 8 weeks to update pregnancy status. We geocoded time-varying residential addresses to estimate ambient concentrations of total PM 2.5 and the following PM 2.5 constituents: elemental carbon (EC), primary organic aerosol (POA), secondary organic aerosols (SOA), sulfate (SO 4 2- ), ammonium (NH 4 + ), nitrate (NO 3 - ), and sea salt. We averaged concentrations of each pollutant across each menstrual cycle at risk. We fit proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI), adjusting for potential confounders and co-pollutants., Results: Total PM 2.5 concentrations were associated with reduced fecundability (the FR for an IQR increase, corresponding to 3.2 μg/m 3 , was 0.93 [95% CI 0.87, 0.99]). The association was strongest for POA: the FR for an IQR increase, corresponding to 1.3 μg/m 3 , was 0.92 (95% CI 0.84, 1.01). The corresponding FRs for the remaining PM 2.5 constituents were 0.96 (95% CI 0.87, 1.05) for EC (IQR = 0.5 μg/m 3 ), 0.98 (95% CI 0.91, 1.06) for SOA (IQR = 0.5), 0.97 (95% CI 0.92, 1.02) for SO 2 4- (IQR = 0.4), 0.95 (95% CI 0.91, 1.01) for NH 4 + (IQR = 0.5), 0.97 (95% CI 0.93, 1.01) for NO 3 - (IQR = 1.0), and 1.00 (95% CI 0.95, 1.06) for sea salt (IQR = 0.4)., Conclusions: In this Danish preconception cohort study, PM 2.5 constituents derived from biomass and transportation-related combustion may drive the association between PM 2.5 concentrations and fecundability., (© 2025 John Wiley & Sons Ltd.)

More than one million sexually transmitted infections (STIs) are acquired every day worldwide. They are commonly caused by Chlamydia trachomatis (CT), herpes simplex virus (HSV), or human papillomavirus (HPV) and are suggested to contribute to female infertility. This scoping review aims to map and summarize existing literature on the association between a pre-pregnancy infection with CT, genital HSV, or HPV and female fertility. We searched two databases (PubMed, Embase) to identify published literature on the association between CT, genital HSV, or HPV infection and female fertility. We included full-text articles, published from 2002 to 2022, on pre-pregnancy infection with either CT, genital HSV, or HPV within a population of women of reproductive age. The study endpoint was either pregnancy, time-to-pregnancy, or infertility. The included studies were evaluated according to the Critical Appraisal Tool by Joanna Briggs Institute. Eight studies were eligible for the review. All of them investigated the association between a CT infection and fertility, while none of them investigated infections with genital HSV or HPV. Three studies found that a CT infection was associated with poorer female fertility, and one study found a similar association in a subgroup analysis of women with a pregnancy intention. Four studies indicated no association, although methodological differences between the studies preclude firm conclusions. This review revealed sparse literature investigating the association between CT, HPV, and HSV and subsequent female fertility. Prospective cohort studies with preconception assessments of these STIs are needed to determine the relation between STIs and subsequent fertility., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility-promoting tools., Objective: To investigate the association between fertility indicators and fecundability in Danish women trying to conceive., Methods: Web-based preconception cohort study. We analysed data from 11,328 females aged 18-49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007-2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self-reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities regression models adjusted for age, socio-economic position, health indicators, reproductive history and gynaecological factors., Results: Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non-use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow-up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31)., Conclusion: In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator., (© 2024 The Author(s). Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Study Question: Is cervical intraepithelial neoplasia (CIN) associated with reduced fecundability, defined as the probability of conceiving per menstrual cycle?, Summary Answer: Overall, we observed no meaningful association between CIN and fecundability, regardless of surgical status, although a recent diagnosis of moderate or severe CIN might be associated with slightly reduced fecundability for 2 years after diagnosis., What Is Known Already: About 15% of couples experience infertility. Few studies have examined the influence of CIN on fertility, and the results have been inconsistent. No study has investigated the association between fecundability and pathologist-reported CIN diagnoses, particularly with respect to the recency of the specific CIN diagnoses., Study Design, Size, Duration: This prospective cohort study included 9586 women trying to conceive. The women were enrolled from 1 June 2007 to 3 February 2020., Participants/materials, Setting, Methods: Women were invited to complete a baseline questionnaire and bimonthly follow-up questionnaires for up to 12 months or until pregnancy occurred. Data on cervical cytologies and biopsies were retrieved from The National Pathology Registry (DNPR), which holds records of all cervical specimens examined in Denmark. Women were categorized based on their most severe diagnosis of CIN: no lesion, other cervical changes, mild CIN (CIN1), or moderate/severe CIN (CIN2+) with or without surgery. To investigate the association between CIN and fecundability, we computed fecundability ratios (FR) and 95% confidence intervals (CI) using a proportional probabilities regression model. We adjusted for age at study entry, partner age, body mass index, smoking status, timing of intercourse, parity, education, number of sexual partners, and household income., Main Results and the Role of Chance: Compared with no lesion, the adjusted FRs (95% CI) for the association between CIN and fecundability were: other cervical lesions, 0.97 (0.91-1.04); CIN1, 1.04 (0.96-1.13); CIN2+ no surgery, 1.00 (0.82-1.22); and CIN2+ with surgery 0.99 (0.89-1.10). The FRs (95% CI) for a recent diagnosis (<2 years) of CIN were 0.98 (0.86-1.11) for other cervical lesions; 1.13 (0.99-1.29) for CIN1; 0.89 (0.62-1.26) for CIN2+ no surgery and 0.91 (0.75-1.10) for CIN2+ with surgery compared with the no lesion group., Limitations, Reasons for Caution: In the analyses, we adjusted for several covariates related to the women. However, we had little information on the male partners which could lead to unmeasured confounding as fecundability is a couple-based measure of fertility. Furthermore, a CIN diagnosis may not be constant as it may regress or progress spontaneously; therefore, it is possible that we have misclassified some women, especially women categorized as having normal cells or CIN1., Wider Implications of the Findings: Our results contribute important knowledge to women who are concerned about their future fertility after receiving a CIN diagnosis., Study Funding/competing Interest(s): This study was funded by The Danish Cancer Society (R167-A11036-17-S2). The overall cohorts were funded by the National Institute of Child Health and Human Development (R01-HD086742 and R03-HD094117). The authors report no competing interests., Trial Registration Number: N/A., (© The Author(s) 2024. 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.)

Spontaneous abortion (SAB), defined as a pregnancy loss before 20 weeks of gestation, affects up to 30% of conceptions, yet few modifiable risk factors have been identified. We estimated the effect of ambient air pollution exposure on SAB incidence in Pregnancy Study Online (PRESTO), a preconception cohort study of North American couples who were trying to conceive. Participants completed questionnaires at baseline, every 8 weeks during preconception follow-up, and in early and late pregnancy. We analyzed data on 4643 United States (U.S.) participants and 851 Canadian participants who enrolled during 2013-2019 and conceived during 12 months of follow-up. We used country-specific national spatiotemporal models to estimate concentrations of particulate matter <2.5 μm (PM 2.5 ), nitrogen dioxide (NO 2 ), and ozone (O 3 ) during the preconception and prenatal periods at each participant's residential address. On follow-up and pregnancy questionnaires, participants reported information on pregnancy status, including SAB incidence and timing. We fit Cox proportional hazards regression models with gestational weeks as the time scale to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of time-varying prenatal concentrations of PM 2.5 , NO 2 , and O 3 with rate of SAB, adjusting for individual- and neighborhood-level factors. Nineteen percent of pregnancies ended in SAB. Greater PM 2.5 concentrations were associated with a higher incidence of SAB in Canada, but not in the U.S. (HRs for a 5 μg/m 3 increase = 1.29, 95% CI: 0.99, 1.68 and 0.94, 95% CI: 0.83, 1.08, respectively). NO 2 and O 3 concentrations were not appreciably associated with SAB incidence. Results did not vary substantially by gestational weeks or season at risk. In summary, we found little evidence for an effect of residential ambient PM 2.5 , NO 2 , and O 3 concentrations on SAB incidence in the U.S., but a moderate positive association of PM 2.5 with SAB incidence in Canada., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lauren A. Wise and Elizabeth E. Hatch reports financial support was provided by National Institute of Environmental Health Sciences. Lauren A. Wise reports a relationship with AbbVie Inc that includes: consulting or advisory. Dr. Lauren Wise serves as a consultant for AbbVie, Inc. and the Gates Foundation. She also receives in-kind donations for primary data collection in Pregnancy Study Online (PRESTO) from Swiss Precision Diagnostics (home pregnancy tests) and Kindara.com (fertility apps). All of these relationships are for work unrelated to this manuscript. The remaining authors report no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Study Question: To what extent is socioeconomic status (SES), as measured by educational attainment and household income, associated with fecundability in a cohort of Danish couples trying to conceive?, Summary Answer: In this preconception cohort, lower educational attainment and lower household income were associated with lower fecundability after adjusting for potential confounders., What Is Known Already: Approximately 15% of couples are affected by infertility. Socioeconomic disparities in health are well established. However, little is known about socioeconomic disparity and its relation to fertility., Study Design, Size, Duration: This is a cohort study of Danish females aged 18-49 years who were trying to conceive between 2007 and 2021. Information was collected via baseline and bi-monthly follow-up questionnaires for 12 months or until reported pregnancy., Participants/materials, Setting, Methods: Overall, 10 475 participants contributed 38 629 menstrual cycles and 6554 pregnancies during a maximum of 12 cycles of follow-up. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs., Main Results and the Role of Chance: Compared with upper tertiary education (highest level), fecundability was substantially lower for primary and secondary school (FR: 0.73, 95% CI: 0.62-0.85), upper secondary school (FR: 0.89, 95% CI: 0.79-1.00), vocational education (FR: 0.81, 95% CI: 0.75-0.89), and lower tertiary education (FR: 0.87, 95% CI: 0.80-0.95), but not for middle tertiary education (FR: 0.98, 95% CI: 0.93-1.03). Compared with a monthly household income of >65 000 DKK, fecundability was lower for household income <25 000 DKK (FR: 0.78, 95% CI: 0.72-0.85), 25 000-39 000 DKK (FR: 0.88, 95% CI: 0.82-0.94), and 40 000-65 000 DKK (FR: 0.94, 95% CI: 0.88-0.99). The results did not change appreciably after adjustment for potential confounders., Limitations, Reasons for Caution: We used educational attainment and household income as indicators of SES. However, SES is a complex concept, and these indicators may not reflect all aspects of SES. The study recruited couples planning to conceive, including the full spectrum of fertility from less fertile to highly fertile individuals. Our results may generalize to most couples who are trying to conceive., Wider Implications of the Findings: Our results are consistent with the literature indicating well-documented inequities in health across socioeconomic groups. The associations for income were surprisingly strong considering the Danish welfare state. These results indicate that the redistributive welfare system in Denmark does not suffice to eradicate inequities in reproductive health., Study Funding/competing Interest(s): The study was supported by the Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, and the National Institute of Child Health and Human Development (RO1-HD086742, R21-HD050264, and R01-HD060680). The authors declare no conflict 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.)

Objective: Adult overweight is associated with increased risk of diverticular disease (DD). We investigated associations between birthweight and childhood body mass index (BMI) and DD., Methods: Cohort study of 346,586 persons born during 1930-1996 with records in the Copenhagen School Health Records Register. Data included birthweight, and height and weight from ages 7 through 13. We used Cox proportional hazard regression to examine associations between birthweight and BMI z-scores and DD registered in the Danish National Patient Registry. Due to non-proportionality, we followed participants from age 18-49 and from age 50., Results: During follow-up, 5459 (3.2%) women and 4429 (2.5%) men had DD. For low and high BMI in childhood, we observed a higher risk of DD before age 50. Among women with z-scores <0 at age 13, the hazard ratio (HR) was 1.16 [95% confidence interval (CI): 0.98-1.39] per one-point lower z-score. For z-scores ≥0 at age 13, the HR was 1.30 (95% CI: 1.11-1.51) per one-point higher z-score. Among men with z-scores <0 at age 13, the HR was 1.02 (95% CI: 0.85-1.22). For z-scores ≥0 at age 13, the HR was 1.54 (95% CI: 1.34-1.78). Z-scores ≥0 were not associated with DD after age 50. Among women only, birthweight was inversely associated with DD before age 50 [HR = 0.90 (95% CI: 0.83-0.99) per 500 g higher birthweight]., Conclusion: BMI z-scores below and above zero in childhood were associated with higher risk of DD before age 50. In addition, we observed lower risk of DD among women, the higher their birthweight., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Spontaneous abortion (SAB)-pregnancy loss before the 20th week of gestation-has adverse psychological and physical sequelae. Some medical conditions known to affect insulin sensitivity, including polycystic ovary syndrome and diabetes, can affect the risk of SAB. No prior studies have examined glycemic load and incidence of SAB in populations without conditions known to affect insulin sensitivity., Objectives: We prospectively evaluated the association between preconception glycemic load and intake of carbohydrates, dietary fiber, and added sugar and risk of SAB., Methods: During 2013-2020, we recruited pregnancy planners from Denmark (SnartForaeldre.dk; SF) and the United States and Canada (Pregnancy Study Online; PRESTO). Participants completed a baseline questionnaire and a cohort-specific FFQ evaluated for validity. We estimated preconception glycemic load and intake of carbohydrates, dietary fiber, and added sugar from individual foods and mixed recipes. We included 2238 SF and 4246 PRESTO participants who reported a pregnancy during the course of the study. SAB data were derived from questionnaires and population registries. We used Cox proportional hazards regression to estimate HRs and 95% CIs., Results: In the study population, 15% of SF participants and 22% of PRESTO participants experienced SAB. Across both cohorts, there was no appreciable association between glycemic load, carbohydrate quality, dietary fiber, or added sugar intake and SAB. Compared with daily mean glycemic load <110, the HR for women with daily mean glycemic load ≥130 was 0.76 (95% CI: 0.52, 1.10) in SF and 1.01 (95% CI: 0.86, 1.19) in PRESTO., Conclusions: Diets with high glycemic load, carbohydrates, and added sugars were not consistently associated with risk of SAB in parallel analyses of 2 preconception cohort studies of women in North America and Denmark., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Little is known about potential health effects of eating organic food in relation to reproduction., Objective: We examined associations between organic food consumption and fecundability., Methods: Data were derived from a preconception cohort study of Danish couples trying to conceive (SnartForaeldre.dk, SF). Participants completed a baseline questionnaire on socio-demographics, anthropometrics and lifestyle and a validated food-frequency questionnaire, which included questions on proportions of organic food consumed within six food groups. Participants were followed up with bimonthly questionnaires for up to 12 months or until pregnancy. Analyses were restricted to 2061 participants attempting pregnancy for ≤6 cycles at enrollment and 1303 with <3 cycles. Fecundability ratios (FRs) and 95% confidence intervals (CI) were estimated by proportional probabilities regression models adjusted for potential confounders including age, lifestyle and socioeconomic factors. Associations were examined for vegetables, fruits, cereals, dairy products, eggs and meat, separately, and for the overall pattern of organic food consumption (organic sum score)., Results: The final analytic sample comprised 2069 participants. In the full cohort, organic food consumption was not meaningfully associated with fecundability. Among participants <3 cycles of pregnancy attempt at study entry (n = 1303), the FR was 1.11 (95% CI 0.93, 1.33) for the category 'less than half', for 'more than half' the FR was 1.17 (95% CI 0.99, 1.38) and for 'almost everything' the FR was 1.12 (95% CI 0.97, 1.28)., Conclusion: Higher consumption of organic foods was not meaningfully associated with fecundability, although slightly greater fecundability was seen among participants with <3 cycles of pregnancy attempt time., (© 2022 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Background: Psychological stress is prevalent among reproductive-aged men. Assessment of semen quality for epidemiological studies is challenging as data collection is expensive and cumbersome, and studies evaluating the effect of perceived stress on semen quality are inconsistent., Objective: To examine the association between perceived stress and semen quality., Material and Methods: We analyzed baseline data on 644 men (1,159 semen samples) from two prospective preconception cohort studies during 2015-2021: 592 in Pregnancy Study Online (PRESTO) and 52 in SnartForaeldre.dk (SF). At study entry, men aged ≥21 years (PRESTO) and ≥18 years (SF) trying to conceive without fertility treatment completed a questionnaire on reproductive and medical history, socio-demographics, lifestyle, and the 10-item version of the Perceived Stress Scale (PSS; interquartile range [IQR] of scores: 0-40). After enrollment (median weeks: 2.1, IQR: 1.3-3.7), men were invited to perform in-home semen testing, twice with 7-10 days between tests, using the Trak Male Fertility Testing System. Semen quality was characterized by semen volume, sperm concentration, and total sperm count. We fit generalized estimating equation linear regression models to estimate the percent difference in mean log-transformed semen parameters by four PSS groups (<10, 10-14, 15-19, ≥20), adjusting for potential confounders., Results: The median PSS score and IQR was 15 (10-19), and 136 men (21.1%) had a PSS score ≥20. Comparing men with PSS scores ≥20 with <10, the adjusted percent difference was -2.7 (95% CI: -9.8; 5.0) for semen volume, 6.8 (95% CI: -10.9; 28.1) for sperm concentration, and 4.3 (95% CI: -13.8; 26.2) for total sperm count., Conclusion: Our findings indicate that perceived stress is not materially associated with semen volume, sperm concentration, or total sperm count., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Purpose: Evidence on the influence of modifiable risk factors on spontaneous abortion (SAB) is scarce. We investigated associations for adherence to national dietary guidelines and a healthy Nordic diet with first-trimester (≤ 12 weeks' gestation) SAB in a Danish cohort of couples trying to conceive., Methods: Participants completed a questionnaire on sociodemographics, lifestyle and reproductive history and a validated food frequency questionnaire (FFQ). We ascertained pregnancies from follow-up questionnaires and restricted analyses to 3,043 women who became pregnant. We assessed adherence to the Danish Dietary Guidelines Index (DDGI, range of 0-6, from low to high), covering intake of fruit, vegetables, fish, red and processed meat, whole grains, saturated fat and added sugar. The Healthy Nordic Food Index (HNFI, range 0-6) covered intake of fish, cabbage, rye bread, apples, pears, root vegetables and oatmeal. Pregnancy outcomes were identified through Danish medical registries or self-reported. We used Cox proportional hazards regression to compute hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for sociodemographics and lifestyle., Results: Fifteen percent of participants had a first-trimester SAB. Compared with a DDGI score < 3, adjusted HRs (95% CIs) for scores 3 to < 4, 4 to  < 5 and ≥ 5 were 0.85 (0.59-1.23), 0.78 (0.54-1.12) and 0.71 (0.44-1.13), respectively. Compared with an HNFI score < 2, adjusted HRs (95% CIs) for scores 2 to < 3, 3 to < 4, 4 to < 5 and ≥ 5 were 0.84 (0.62-1.15), 0.88 (0.66-1.19), 0.94 (0.69-1.28) and 0.69 (0.49-0.96), respectively., Conclusion: Greater pre-pregnancy adherence to Danish dietary guidelines or a healthy Nordic diet was associated with a lower rate of first-trimester SAB, although estimates were imprecise., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Purpose: Diet quality is increasingly recognized as important for human reproductive capacity. We studied the association between intake of protein-rich foods and risk of spontaneous abortion (SAB)., Methods: During 2013-2020, we recruited pregnancy planners from the United States and Canada (Pregnancy Study Online; PRESTO) and Denmark (SnartForaeldre.dk; SF). Participants completed a baseline questionnaire and a validated cohort-specific food frequency questionnaire. We estimated preconception intake of red meat, poultry, processed meat, seafood, eggs, plant-based proteins, and dairy from individual foods and mixed recipes. We included 4,246 PRESTO and 2,953 SF participants who reported a pregnancy during the study. Data on SAB were derived from questionnaires and population registries. We used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI), representing the effect of substituting one type of protein-rich food for another., Results: SAB risk was 23% in PRESTO and 16% in SF. In PRESTO, substitution of seafood with other protein-rich foods was associated with higher SAB risk [for example, the HR for replacing 100 g of seafood/week with 100 g of red meat was 1.10 (95% CI 1.00, 1.20)]. In contrast, in SF, substituting seafood with other protein-rich foods was associated with lower SAB risk [HR for replacing 100 g of seafood/week with 100 g of red meat was 0.89 (95% CI 0.82, 0.98)]. Other protein-rich food substitutions were not meaningfully associated with SAB risk., Conclusions: Preconception intake of protein-rich foods was largely unrelated to SAB risk, with the exception of seafood, which was associated with higher risk of SAB in Denmark, but a lower risk in North America., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

A daily intake of dairy products is recommended in many countries in order to maintain optimal health throughout life. However, evidence regarding the association between intake of individual dairy products and mortality is limited. We therfore, explored associations between intake of different dairy products and all-cause and cause-specific mortality using specified theoretical substitution analyses. We analysed data from 55 775 Danish men and women aged 50-64 years between 1993 and 1997. Information about dairy product intake at baseline was collected using a validated food frequency questionnaire. Information about vital status and causes of death was obtained through national registers. Measures of associations were calculated using Cox proportional hazards regression. During a median follow-up of 19·0 years, 11 586 participants died. For all-cause mortality, we observed that the intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese was associated with a higher rate of death (hazard ratios between 1·03 and 1·12 per serving/d substituted). The same pattern was present for CVD mortality. For cancer mortality, whole-fat milk and low-fat yogurt products in place of cheese were also associated with a higher rate of death for men while for women, whole-fat milk in place of buttermilk was associated with a higher cancer mortality rate. The results appeared robust in several sensitivity analyses. Our results suggest that intake of low-fat milk, whole-fat milk or low-fat yogurt products in place of cheese is associated with a higher rate of all-cause and cause-specific mortality.

Study Question: To what extent is dietary folate intake and total folate intake (dietary and supplemental intakes) associated with fecundability, the per cycle probability of conception?, Summary Answer: Preconception dietary folate intake was positively associated with fecundability in a monotonic pattern., What Is Known Already: Supplemental folic acid has been associated with improved fertility, but little is known about the relation between dietary folate and fecundability., Study Design, Size, Duration: A prospective cohort study including 9559 women trying to conceive without fertility treatment and enrolled in the period 2013-2020., Participants/materials, Setting, Methods: We used data from two internet-based prospective cohort studies of pregnancy planners from Denmark, where folic acid fortification is not performed (SnartForældre.dk (SF); n = 3755) and North America, where the food supply is fortified with folic acid (Pregnancy Study Online (PRESTO); n = 5804). Women contributed menstrual cycles at risk until they reported conception or experienced a censoring event. We used proportional probabilities regression models to compute fecundability ratios (FRs) and 95% CI, adjusting for potential confounders., Main Results and the Role of Chance: Compared with a dietary folate intake ≥400 µg/day, the adjusted FRs for women in SF were 0.92 (95% CI: 0.85-0.99) for intake 250-399 µg/day, and 0.80 (95% CI: 0.68-0.94) for intake of <250 µg/day. The corresponding FRs in PRESTO were 0.95 (95% CI: 0.89-1.01) and 0.81 (95% CI: 0.65-1.00). Compared with the highest level of total folate intake (diet folate ≥400 µg/day plus folic acid supplementation), in both cohorts fecundability was lowest among women with the lowest dietary intake <250 µg/day dietary folate and no supplementation (FR: 0.76, 95% CI: 0.59-0.98 [SF] and 0.49, 95% CI: 0.31-0.77 [PRESTO]). Further, total intake dietary folate <250 µg/day plus supplementation was associated with reduced fecundability for SF participants (FR; 0.79, 95% CI: 0.65-0.98) and for PRESTO participants (FR; 0.92, 95% CI: 0.72-1.16)., Limitations, Reasons for Caution: It is unknown whether dietary folate and folic acid intake affect fecundability on its own or if there is an interaction with other micronutrients provided in healthy diet. Thus, the observed associations may not reflect dietary folate intake alone, but overall healthy diet., Wider Implications of the Findings: Recommendations for preconception dietary folate intake and folic acid supplementation are of importance not only to prevent neural tube defects but also to enhance fecundability., Study Funding/competing Interest(s): The study was supported by the National Institute of Child Health and Human Development (R01-HD086742). The authors report no competing interests., Trial Registration Number: N/A., (© The Author(s) 2022. 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.)

Background: Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. Epidemiologic studies have been restricted largely to couples undergoing fertility treatment or have retrospectively ascertained time-to-pregnancy among pregnant women., Objectives: We examined the association between residential ambient air pollution and fecundability, the per-cycle probability of conception, in a large preconception cohort of Danish pregnancy planners., Methods: During 2007-2018, we used the Internet to recruit and follow women who were trying to conceive without the use of fertility treatment. Participants completed an online baseline questionnaire eliciting socio-demographic characteristics, lifestyle factors, and medical and reproductive histories and follow-up questionnaires every 8 weeks to ascertain pregnancy status. We determined concentrations of ambient nitrogen oxides (NO x ), nitrogen dioxide (NO 2 ), carbon monoxide (CO), ozone (O 3 ), particulate matter <2.5 µm (PM 2.5 ) and <10 µm (PM 10 ), and sulphur dioxide (SO 2 ) at each participant's residential address. We calculated average exposure during the year before baseline, during each menstrual cycle over follow-up and during the entire pregnancy attempt time. We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders and co-pollutants. The analysis was restricted to the 10,183 participants who were trying to conceive for <12 cycles at study entry whose addresses could be geocoded., Results: During 12 months of follow-up, 73% of participants conceived. Higher concentrations of PM 2.5 and PM 10 were associated with small reductions in fecundability. For example, the FRs for a one interquartile range (IQR) increase in PM 2.5 (IQR = 3.2 µg/m 3 ) and PM 10 (IQR = 5.3 µg/m 3 ) during each menstrual cycle were 0.93 (95% CI: 0.87, 0.99) and 0.91 (95% CI: 0.84, 0.99), respectively. Other air pollutants were not appreciably associated with fecundability., Conclusions: In this preconception cohort study of Danish women, residential exposures to PM 2.5 and PM 10 were associated with reduced fecundability., (© 2021 John Wiley & Sons Ltd.)

Importance: The associations of maternal history of spontaneous abortion (SA) and stillbirth with congenital heart disease (CHD) remain elusive., Objective: To evaluate the associations of maternal history of pregnancy loss with CHD in offspring and the role of maternal type 2 diabetes., Design, Setting, and Participants: This population-based cohort study included singleton live offspring born between January 1, 1977, and December 31, 2016, identified through Danish national health registries. Statistical analysis was performed from October 1, 2019, through September 1, 2021., Exposures: Maternal history of SA, with frequency varying from 1 or 2 to 3 or more episodes, and maternal history of single and multiple stillbirths., Main Outcomes and Measures: Overall CHD identified by hospital diagnosis. Cox proportional hazard regression was used to estimate the hazard ratio (HR) of CHD. Diabetes was evaluated as a potential confounder and a potential effect modifier., Results: Among 1 642 534 included offspring (mean [SD] age, 14.11 [8.39] years; 843 265 male [51.35%]), 246 669 (15.02%) were born to mothers with a history of SA and 9750 (0.59%) were born to mothers with a history of stillbirth. The HRs of CHD were 1.16 (95% CI, 1.13-1.20) for offspring with a maternal history of SA and 1.49 (95% CI, 1.32-1.68) for offspring with a maternal history of stillbirth. Significant dose-response associations were observed among offspring with a maternal history of 3 or more episodes of SA (HR, 1.60; 95% CI, 1.39-1.84) and those with maternal history of multiple stillbirths (HR, 2.75; 95% CI, 1.63-4.65). If only inpatient CHD cases were included, the risk of CHD was higher than that found in the main analysis, with HRs of 1.24 (95% CI, 1.19-1.30) for maternal history of SA and 1.78 (95% CI, 1.51-2.11) for maternal history of stillbirth. The observed associations were strengthened by maternal prepregnancy type 2 diabetes (HR for maternal history of SA, 1.65 [95% CI, 1.37-1.97]; HR for maternal history of stillbirth, 1.74 [95% CI, 1.06-2.85])., Conclusions and Relevance: These findings suggest that offspring born to mothers with a previous SA or stillbirth, especially multiple episodes, or with prepregnancy type 2 diabetes were at a higher risk of being diagnosed with CHD. These findings may help identify women at increased risk in whom detailed fetal heart assessment may be cost-effective and highlight the importance of screening for type 2 diabetes in women of reproductive age.

Purpose: We investigated the association between an increased intake of one dairy product subgroup at the expense of another within a 5-year period and the subsequent 10-year risk of type 2 diabetes., Methods: The cohort included 39,393 adults with two measurements of diet assessed using food frequency questionnaires (FFQ) administered in 1993-1997 and 1999-2003. Dairy products were milk (skimmed, semi-skimmed, whole fat), buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Type 2 diabetes cases were ascertained from the Danish National Diabetes Register. The pseudo-observation method was used to calculate risk differences (RD) with 95% confidence intervals (CI). The data were analysed in age strata to fulfil the assumption of independent entry., Results: Among participants aged 56-59 years at completion of the follow-up FFQ, increased intake of whole-fat yogurt in place of skimmed, semi-skimmed or whole-fat milk was associated with a reduced risk (RD% [95% CI]: - 0.8% [- 1.3, - 0.2]; - 0.6% [- 1,1, - 0.1]; - 0.7 [- 1.2, - 0.1]; per 50 g/d, respectively). Among participants aged 60-64 and 65-72, substitution of skimmed milk for semi-skimmed milk was associated with an increased risk of type 2 diabetes (0.5% [0.2, 0.7]; 0.4% [0.1, 0.7]; per 50 g/d, respectively). Similar patterns of associations were found after adjustment for potential mediators., Conclusion: Our results suggest that substitution of whole-fat yogurt for milk among those aged 56-59 decreases risk of type 2 diabetes and substitution of skimmed milk for semi-skimmed milk may increase the risk among those aged 60-64 and 65-72., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Introduction: Information about temporal development of von Willebrand disease (VWD) incidence at a population level is scarce. To our knowledge, no study has described the incidence of VWD at a population level., Aim: To estimate overall and annual incidence rates of hospital diagnosed VWD in Denmark between 1995 and 2016 as well as the frequency of hospital treated bleeding episodes before and after VWD diagnosis., Methods: A registry-based cohort study that included all Danish patients with a first diagnosis of VWD in Denmark, identified in the Danish National Patient Registry through 1995-2016., Results: We identified 1,035 patients with a diagnosis of VWD. The overall incidence rate of VWD in 1995-2016 was 8.6 (95% CI: 8.1-9.2). The annual age-standardized incidence rate per 100 000 person-years varied between 4.1 (95% CI: 2.4-5.9) in 1998 and 16.7 (95% CI: 13.1-20.3) in 2005. A prominent peak in rates appeared from 2002 to 2008. One and five years before VWD diagnosis, 6% and 11.5% of the patients had at least one hospital treated bleeding episode. One and five years after diagnosis, the corresponding percentages were 7.9% and 13.4%., Conclusion: These results are the first population-based estimates of VWD incidence. The incidence may be underestimated because asymptomatic individuals may not be diagnosed. The observed peak in incidence from 2002-2008 may be explained by increased medical attention, leading to more patients being diagnosed, rather than an actual increase in VWD incidence. However, overall, we observed no systematic changes in VWD incidence over the study period., (© 2021 John Wiley & Sons Ltd.)

The advantage of using specified substitution analysis in nutritional epidemiology has been clearly demonstrated in studies of macronutrient intake and disease risk. However, the method has not been widely applied in studies of food intake. The aim of this article is to describe and compare the interpretation and application of different food substitution models in epidemiologic studies on diet and disease development. Both theoretically and in the context of a specific example, we discuss methodologic issues to be considered, including modeling of food substitutions using diet at a single time point or at multiple time points (focusing on dietary changes), choice of substitution unit, adjustment for total energy intake, and adjustment for confounding. We argue that specified food substitution analyses can be used to identify optimal food composition of the diet and that these analyses are thus highly relevant to inform public health policy decision makers., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Food-based dietary guidelines recommend replacement of whole-fat dairy products with low-fat variants based on data suggesting that diets high in saturated fat are associated with a higher risk of ischemic heart disease. However, the health effects of saturated fat may depend on the source., Objectives: The aim was to investigate substitutions between different subgroups of dairy products and the risk of myocardial infarction (MI)., Methods: Data were from the Danish Diet, Cancer and Health cohort and included 54,903 men and women aged 50-64 y at enrollment and without an MI diagnosis. Information about intake of dairy products was obtained by a semiquantitative food-frequency questionnaire. Incident MI cases were identified through nationwide registries. We used Cox proportional hazards regression to estimate associations between specified substitutions of dairy products and MI risk., Results: During a median follow-up of 15.9 y, 3033 cases were identified. Whole-fat yogurt products in place of low-fat or whole-fat milk were associated with a lower risk of MI (HR: 0.89; 95% CI: 0.80, 0.99 per 200 g/d replaced; and HR: 0.87; 95% CI: 0.78, 0.98 per 200 g/d replaced, respectively). Substitution of 20 g/d of cheese for 200 g/d of low-fat or whole-fat milk was also associated with a lower risk of MI (HR: 0.96; 95% CI: 0.92, 0.99; and HR: 0.95; 95% CI: 0.89, 0.99, respectively)., Conclusions: Among middle-aged Danish men and women, intake of whole-fat yogurt products or cheese in place of milk, regardless of fat content, was associated with a lower risk of development of MI., (Copyright © The Author(s) 2020.)

The association between intake of different dairy products and the risk of stroke remains unclear. We therefore investigated substitutions between dairy product subgroups and risk of stroke. We included 36 886 Dutch men and women. Information about dairy product intake was collected through a FFQ. Dairy products were grouped as low-fat milk, whole-fat milk, buttermilk, low-fat yogurt, whole-fat yogurt, cheese and butter. Incident stroke cases were identified in national registers. We used Cox proportional hazards regression to calculate associations for substitutions between dairy products with the rate of stroke. During a median follow-up of 15·2 years we identified 884 stroke cases (503 ischaemic and 244 haemorrhagic). Median intake of total dairy products was four servings/d. Low-fat yogurt substituted for whole-fat yogurt was associated with a higher rate of ischaemic stroke (hazard ratio (HR) = 2·58 (95 % CI 1·11, 5·97)/serving per d). Whole-fat yogurt as a substitution for any other subgroup was associated with a lower rate of ischaemic stroke (HR between 0·33 and 0·36/serving per d). We did not observe any associations for haemorrhagic stroke. In conclusion, whole-fat yogurt as a substitution for low-fat yogurt, cheese, butter, buttermilk or milk, regardless of fat content, was associated with a lower rate of ischaemic stroke.

Background: The effect of individual saturated fatty acids (SFAs) on serum cholesterol levels depends on their carbon-chain length. Whether the association with myocardial infarction (MI) also differs across individual SFAs is unclear. We examined the association between consumption of individual SFAs, differing in chain lengths ranging from 4 through 18 carbons, and risk of MI., Methods: We used data from 22,050 and 53,375 participants from EPIC-Norfolk (UK) and EPIC-Denmark, respectively. Baseline SFA intakes were assessed through validated, country-specific food frequency questionnaires. Cox regression analysis was used to estimate associations between intakes of individual SFAs and MI risk, for each cohort separately., Results: During median follow-up times of 18.8 years in EPIC-Norfolk and 13.6 years in Denmark, respectively, 1204 and 2260 MI events occurred. Mean (±SD) total SFA intake was 13.3 (±3.5) en% in EPIC-Norfolk, and 12.5 (±2.6) en% in EPIC-Denmark. After multivariable adjustment, intakes of C12:0 (lauric acid) and C14:0 (myristic acid) inversely associated with MI risk in EPIC-Denmark (HR upper versus lowest quintile: 0.80 (95%CI: 0.66, 0.96) for both SFAs). Intakes in the third and fourth quintiles of C4:0-C10:0 also associated with lower MI risk in EPIC-Denmark. Moreover, substitution of C16:0 (palmitic acid) and C18:0 (stearic acid) with plant proteins resulted in a reduction of MI risk in EPIC-Denmark (HR per 1 energy%: 0.86 (95%CI: 0.78, 0.95) and 0.87 (95%CI: 0.79, 0.96) respectively). No such associations were found in EPIC-Norfolk., Conclusion: The results from the present study suggest that the association between SFA and MI risk depends on the carbon chain-length of the SFA., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: The role of dairy fat for the risk of stroke is not yet clear. Adipose tissue reflects long-term fatty acid intake and metabolism. We, therefore, investigated associations for percentages of adipose tissue fatty acids, for which dairy products are a major source (12:0, 14:0, 14:1 cis-9, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans-11), with incident total stroke and stroke subtypes., Methods: We conducted a case-cohort study within the Danish Diet, Cancer and Health cohort, including all incident stroke cases (n = 2108) and a random sample of the total cohort (n = 3186). The fatty acid composition of adipose tissue biopsies was determined by gas chromatography and specific fatty acids were expressed as percentage of total fatty acids. Stroke cases were identified in the Danish National Patient Registry and the diagnoses were individually verified., Results: We recorded 2108 stroke cases of which 1745 were ischemic, 249 were intracerebral hemorrhages and 102 were subarachnoid hemorrhages. We observed a lower rate of ischemic stroke for a higher adipose tissue percentage of 12:0, 14:0, 15:0, 17:0, 18:1 trans-11 and 18:2 cis-9, trans-11. Adipose tissue percentages of 15:0 and 18:1 trans-11 were also inversely associated with intracerebral hemorrhage, whereas no associations between the adipose tissue fatty acids and subarachnoid hemorrhage were observed. No associations between 14:1 cis-9 and ischemic or hemorrhagic stroke were found., Conclusions: Our results suggest that a larger percentage in adipose tissue of fatty acids for which dairy products are a major source is associated with a lower rate of ischemic stroke.

Background: Studies have consistently found that obesity is associated with poor self-rated health, but how body mass index (BMI) developed in the lead up to poor self-rated health is unknown., Methods: We nested a longitudinal case-control study in the English Longitudinal Study of Ageing (1998-2015) to investigate BMI trajectories in the years preceding a first self-report of poor health. Participants rated their health at each data collection; every other collection included a BMI assessment by a nurse. Case status was defined as a first report of poor health during follow-up. Three age- and sex-matched controls were identified per case using density sampling. BMI trajectories were fitted to time backwards prior to first report of poor health using mixed-effects models. Age and sex were potential modifiers. We conducted subgroup analyses of those not reporting certain chronic diseases or smoking., Results: We identified 732 cases and 2195 controls. Age, but not sex, modified the association between BMI and self-rated health. Participants reporting poor health at age 60 had a 1.5 kg/m2 (95%CI: 0.8 to 2.1) higher BMI at the time of reporting than controls, and their BMI had previously increased markedly (1.3 kg/m2 95%CI: 0.9 to 1.8 over ten years). After age 75, cases no longer had higher BMI than controls, and their BMI had decreased sharply prior to reporting poor health (e.g. -2.0 kg/m2 95%CI: -2.6 to -1.5 per decade on average for those reporting poor health at age 90). Age was also an effect modifier among those without diabetes, however BMI trajectories were more similar among the middle-aged. The subgroup analysis of those without cardiovascular disease, cancer and chronic lung disease showed similar results to the main findings., Conclusion: Development of BMI was associated with poor self-rated health; however, the nature of the association depended markedly on age., Competing Interests: The authors have declared that no competing interests exist.

Low fat dairy products are part of dietary guidelines to prevent stroke. However, epidemiological evidence is inconclusive with regard to the association between dairy products and stroke. We therefore investigated associations for substitutions between dairy product subgroups and risk of total stroke and stroke subtypes. We included 55,211 Danish men and women aged 50-64 years without previous stroke. Baseline diet was assessed by a food frequency questionnaire. Cases were identified through a national register and subsequently verified. The associations were analyzed using Cox proportional hazard regression. During a median follow-up of 13.4 years, we identified 2272 strokes, of which 1870 were ischemic (318 large artery atherosclerotic, 839 lacunar, 102 cardioembolic, 98 other determined types, 513 of unknown type), 389 were hemorrhages (273 intracerebral, 116 subarachnoid) and 13 of unknown etiology. Substitution of semi-skimmed fermented milk or cheese for whole-fat fermented milk was associated with a higher rate of ischemic stroke [semi-skimmed fermented milk: hazard ratio (HR) = 1.20 (95% confidence interval (CI) 0.99-1.45), cheese: HR = 1.14 (95% CI 0.98-1.31) per serving/day substituted] and substitutions of whole-fat fermented milk for low-fat milk, whole-fat milk or buttermilk were associated with a lower rate [low-fat milk: HR = 0.85 (95% CI 0.74-0.99), whole-fat milk: HR = 0.84 (95% CI 0.71-0.98) and buttermilk: HR = 0.83 (95% CI 0.70-0.99)]. We observed no associations for substitutions between dairy products and hemorrhagic stroke. Our results suggest that intake of whole-fat fermented milk as a substitution for semi-skimmed fermented milk, cheese, buttermilk or milk, regardless of fat content, is associated with a lower rate of ischemic stroke.

The aim of this study was to investigate the associations for specified substitutions between different subgroups of dairy products and the risk of type 2 diabetes. We used data from the Danish Diet, Cancer and Health cohort including 54 277 men and women aged 50-64 years at baseline. Information regarding intake of dairy products was obtained from a validated FFQ, and cases of type 2 diabetes were identified through the Danish National Diabetes Register. Cox proportional hazards regressions were used to estimate associations. During a median follow-up of 15·3 years, 7137 cases were identified. Low-fat yogurt products in place of whole-fat yogurt products were associated with a higher rate of type 2 diabetes (hazard ratio (HR) 1·17; 95 % CI 1·06, 1·29) per serving/d substituted. Whole-fat yogurt products in place of low-fat milk, whole-fat milk or buttermilk were associated with a lower rate of type 2 diabetes (HR 0·89; 95 % CI 0·83, 0·96; HR 0·89; 95 % CI 0·82, 0·96; HR 0·89; 95 % CI 0·81, 0·97; per serving/d substituted, respectively). The pattern of associations was similar when intake was expressed as kJ/d (kcal/d). These findings suggest that intake of whole-fat yogurt products in place of low-fat yogurt products, low-fat milk, whole-fat milk and buttermilk are associated with a lower rate of type 2 diabetes.

Physical activity is associated with reduced cardiovascular disease risk. However, improvements in conventional risk factors due to physical activity do not explain its full benefit. Therefore, we examined associations of objectively measured physical activity energy expenditure and intensity with central hemodynamics to provide new insight into the link between physical activity and cardiovascular disease. We analyzed data from 1816 Danes (median age: 66 years) without cardiovascular disease. Physical activity was estimated using combined accelerometry and heart rate monitoring. Aortic stiffness was assessed by applanation tonometry, as aortic pulse wave velocity, and central blood pressure was estimated from radial waveforms. Associations between physical activity energy expenditure and central hemodynamics were examined by linear regression. Furthermore, the consequence of substituting 1 hour sedentary behavior with 1 hour light or moderate-to-vigorous physical activity on central hemodynamics was examined. Median physical activity energy expenditure was 28.0 kJ/kg/d (IQR: 19.8; 38.7). A 10 kJ/kg/d higher energy expenditure was associated with 0.75% lower aortic pulse wave velocity (CI: -1.47; -0.03). Associations with central systolic blood pressure and central pulse pressure were not statistically significant. We observed no difference in central hemodynamics when substituting 1 hour sedentary behavior with 1 hour light or moderate-to-vigorous physical activity. In this relatively inactive population, higher physical activity energy expenditure was associated with lower aortic stiffness, while there was no statistically significant association between substitution of activity intensity and central hemodynamics. This suggests that lower aortic stiffness is one of a number of health benefits attributed to higher habitual physical activity.