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Objectives: To better understand whether history of infertility is associated with anti-Müllerian hormone (AMH) levels later in life, outside of reproduction., Methods: Among 1,758 premenopausal women in the Nurses' Health Study II with measured AMH, we used multivariable generalized linear models to compare log-transformed plasma AMH for women with a history of infertility compared with fertile women. We investigated AMH levels by cause of infertility and effect modification by menstrual cycle regularity. Lastly, we investigated AMH levels by history of primary and secondary infertility and age at reported infertility., Results: Mean age at blood collection was 40 years. We observed no association between overall history of infertility and AMH levels (% difference AMH: -8.1% [CI, -19.4 to 4.8]). The association between overall infertility and AMH was strongest among women who first reported infertility at >30 years (-17.7% [CI, -32.1 to -0.3])., Conclusions: Overall, we observed no association between the history of infertility and AMH levels later in life. However, specific subgroups of women with a history of infertility may have lower AMH levels throughout life compared with fertile women. This association was observed among subgroups, such as those who first experienced infertility at >30 years. These findings have implications for mechanisms through which infertility may be associated with premature menopause and chronic disease risk., Competing Interests: Financial disclosure/conflicts of interest: S.A.M. receives ongoing institutional funding from the Department of Defense, Abbvie (grant), and Marriot Family Foundation (grant). She also receives honoraria from University of British Columbia, WERF, Huilun Shanghai, and University of Kansas Medical Center (honoraria). She receives coverage for travel to meetings by SRI, ESHRE, University of Michigan, Massachusetts Institute of Technology, ASRM, LIDEA Registry, Taiwan Endometriosis Society, SEUD, Japan Endometriosis Society, and NASEM. She receives personal fees for advisory board, roundtable, consultant, or editor role from AbbVie, Roche, Frontiers in Reproductive Health, Abbott, and LIDEA Registry. She holds unpaid board or leadership roles at Human Reproduction, SWHR, WERF, WES, ASRM, ESHRE. The other authors have nothing to disclose., (Copyright © 2024 by The Menopause Society.)

Background: Sexual minority (SM) individuals (e.g., those with same-sex attractions/partners or who identify as lesbian/gay/bisexual) experience a host of physical and mental health disparities. However, little is known about sexual orientation-related disparities in gestational diabetes mellitus (GDM) and hypertensive disorders of pregnancy (HDP; gestational hypertension [gHTN] and preeclampsia)., Objective: To estimate disparities in GDM, gHTN and preeclampsia by sexual orientation., Methods: We used data from the Nurses' Health Study II-a cohort of nurses across the US enrolled in 1989 at 25-42 years of age-restricted to those with pregnancies ≥20 weeks gestation and non-missing sexual orientation data (63,518 participants; 146,079 pregnancies). Our primary outcomes were GDM, gHTN and preeclampsia, which participants reported for each of their pregnancies. Participants also reported their sexual orientation identity and same-sex attractions/partners. We compared the risk of each outcome in pregnancies among heterosexual participants with no same-sex experience (reference) to those among SM participants overall and within subgroups: (1) heterosexual with same-sex experience, (2) mostly heterosexual, (3) bisexual and (4) lesbian/gay participants. We used modified Poisson models to estimate risk ratios (RR) and 95% confidence intervals (CI), fit via weighted generalised estimating equations, to account for multiple pregnancies per person over time and informative cluster sizes., Results: The overall prevalence of each outcome was ≤5%. Mostly heterosexual participants had a 31% higher risk of gHTN (RR 1.31, 95% CI 1.03, 1.66), and heterosexual participants with same-sex experience had a 31% higher risk of GDM (RR 1.31, 95% CI 1.13, 1.50), compared to heterosexual participants with no same-sex experience. The magnitudes of the risk ratios were high among bisexual participants for gHTN and preeclampsia and among lesbian/gay participants for gHTN., Conclusions: Some SM groups may be disparately burdened by GDM and HDP. Elucidating modifiable mechanisms (e.g., structural barriers, discrimination) for reducing adverse pregnancy outcomes among SM populations is critical., (© 2024 John Wiley & Sons Ltd.)

Background: Pregnant women with obesity face heightened focus on weight during pregnancy due to greater risk of medical complications. Closer follow-up in maternety care may contribute to reduce risk and promote health in these women. The aim of this study was to gain a deeper insight in how pregnant women with obesity experience encounters with healthcare providers in maternity care. How is the received maternity care affected by their weight, and how do they describe the way healthcare providers express attitudes towards obesity in pregnancy?, Methods: We conducted in-depth interviews with 14 women in Trøndelag county in Norway with pre-pregnancy BMI of ≥ 30 kg/m 2 , between 3 and 12 months postpartum. The study sample was strategic regarding age, relationship status, education level, obesity class, and parity. Themes were developed using reflexive thematic analysis. The analysis was informed by contextual information from a prior study, describing the same participants' weight history from childhood to motherhood along with their perceptions of childhood quality., Results: This study comprised of an overarching theme supported by three main themes. The overarching theme, Being pregnant with a high BMI: a vulnerable condition, reflected the challenge of entering maternity care with obesity, especially for women unprepared to be seen as "outside the norm". Women who had grown up with body criticism and childhood bullying were more prepared to have their weight addressed in maternity care. The first theme, Loaded conversations: a balancing act, emphasizes how pregnant women with a history of body criticism or obesity-related otherness proactively protect their integrity against weight bias, stigma and shame. The women also described how some healthcare providers balance or avoid weight and risk conversations for the same reasons. Dehumanization: an unintended drawback of standardized care makes apparent the pitfalls of prioritizing standardization over person-centered care. Finally, the third theme, The ambivalence of discussing weight and lifestyle, represent women's underlying ambivalence towards current weight practices in maternity care., Conclusions: Our findings indicate that standardized weight and risk monitoring, along with lifestyle guidance in maternity care, can place the pregnant women with obesity in a vulnerable position, contrasting with the emotionally supportive care that women with obesity report needing. Learning from these women's experiences and their urge for an unloaded communication to protect their integrity highlights the importance of focusing on patient-centered practices instead of standardized care to create a safe space for health promotion., (© 2024. The Author(s).)

Background: Preeclampsia history signals a higher risk for cardiovascular disease, but its value as a risk marker relies primarily on self-report. To identify the accuracy of maternal self-reports of recent preeclampsia, we conducted a validation study among women recruited to a web-based trial. Methods: Women with preeclampsia in the past 5 years were recruited to Heart Health 4 Moms. Preeclampsia was self-reported through an online recruitment questionnaire and affirmed via phone screen. Accuracy of maternal self-report was quantified using positive predictive value (PPV) versus medical record evidence of preeclampsia using three definitions: (1) documentation of clinician diagnosis, (2) American College of Obstetricians and Gynecologists (ACOG) 2002 diagnostic criteria (gestational hypertension and proteinuria), and (3) ACOG 2013 diagnostic criteria (gestational hypertension and proteinuria or systemic symptoms). Results: Complete medical records were received for 290 women who delivered from 2011 to 2016 and were predominantly non-Hispanic White (81.7%) with a mean age of 31.2 ± 4.8 years. Mean length of recall was 13.6 ± 14.7 months. The majority of women (92.1%) had medical record evidence of preeclampsia using ≥1 of the definitions. Maternal self-report of preeclampsia was validated for 88.3% based on clinician diagnosis, 59.0% with ACOG 2002, and 65.2% with ACOG 2013. Conclusions: In this validation study of U.S. women, the majority accurately self-reported their preeclampsia diagnosis based on medical record review. A higher proportion of self-reports validated by clinician diagnosis than ACOG criteria, suggesting women remember the diagnosis given by their provider and providers may not always follow or document criteria when making a diagnosis.

Background: Women with a history of adverse pregnancy outcomes have a higher risk of coronary heart disease. Emerging evidence suggests that women with a history of preeclampsia have a different pattern of overall coronary atherosclerosis and that they at the time of myocardial infarction (MI) more frequently present with ST-segment elevation MI (STEMI) compared to women with no such history., Objectives: The purpose of this study was to determine whether among women with MI, those with a history of adverse pregnancy outcomes are more likely to present with STEMI or other clinical characteristics indicating a more severe myocardial injury., Methods: The study sample consisted of 8,320 women aged ≤65 years with first MI in Sweden 2007 to 2022. Regression models were used to estimate the association between adverse pregnancy outcomes (hypertensive disorders of pregnancy [non-preeclamptic hypertension and preeclampsia], small for gestational age [SGA] infant, and preterm delivery) and STEMI, invasive revascularization, and high troponin, while considering known predictors of coronary heart disease., Results: In total, 3,128 (38%) of women suffered STEMI. The adjusted OR of presenting with STEMI were higher in women with a history of preterm preeclampsia (OR: 1.40; 95% CI: 1.05-1.88), or an SGA infant (OR: 1.30; 95% CI: 1.13-1.50) compared to women with no such history, as well as for in-hospital revascularization. Stratified by infarct type, troponin levels did not differ by adverse pregnancy outcome history., Conclusions: Among women with a first MI, a history of preterm preeclampsia or SGA infant were associated with STEMI and invasive revascularization., Competing Interests: This work was supported by grants awarded to Dr Timpka from the 10.13039/501100004359Swedish Research Council (2019-02082), The 10.13039/501100003793Swedish Heart-Lung Foundation (20180312), Public research support via the Faculty of Medicine at 10.13039/501100003252Lund University (ALF: YF-ALF, ALF project), The 10.13039/501100007687Swedish Society of Medicine (SLS-885331), The Jeansson Foundations, Stockholm, Sweden, and Åke Wiberg Foundation, Stockholm, Sweden. Dr Gonҫalves received grants from the 10.13039/501100004359Swedish Research Council, the Swedish Heart and Lung Foundation, 10.13039/501100011077Skåne University Hospital funds and Lund University Diabetes Center (10.13039/501100004359Swedish Research Council - Strategic Research Area Exodiab Dnr 2009-1039, Linnaeus grant Dnr 349-2006-23 and the 10.13039/501100001729Swedish Foundation for Strategic Research Dnr IRC15-006). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

During the COVID-19 pandemic, healthcare workers faced grave responsibilities amidst rapidly changing policies and material and staffing shortages. Moral injury, psychological distress following events where actions transgress moral beliefs/ expectations, increased among healthcare workers. We used a sequential mixed methods approach to examine workplace and contextual factors related to moral injury early in the pandemic. Using a Total Worker Health® framework, we 1) examined factors associated with moral injury among active healthcare professionals (N = 14,145) surveyed between May-August 2020 and 2) qualitatively analyzed open-ended responses from 95 randomly selected participants who endorsed moral injury on the survey. Compared to inpatient hospital, outpatient (OR = 0.74 [0.65, 0.85]) or school clinic settings (OR = 0.37 [0.18, 0.75]) were associated with lower odds of moral injury; while group care settings increased odds (OR = 1.36 [1.07, 1.74]). Working with COVID+ patients (confirmed+ OR = 1.27 [1.03, 1.55]), PPE inadequacy (OR = 1.54 [1.27, 1.87]), and greater role conflict (OR = 1.57 [1.53, 1.62]) were associated with greater odds of moral injury. Qualitative findings illustrate how outside factors as well as organizational policies and working conditions influenced moral injury. Moral injury experiences affected staff turnover and patient care, potentially producing additional morally injurious effects. Worker- and patient-centered organizational policies are needed to prevent moral injury among healthcare workers. The generalizability of these findings may be limited by our predominantly white and female sample. Further research is indicated to replicate these findings in minoritized samples., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Scoglio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Prepregnancy body mass index (BMI) is a well-established risk factor of adverse pregnancy outcomes (APOs). The associations of long-term and short-term weight trajectories with APOs are less clear., Objectives: This study aimed to determine the associations of weight trajectories during females' reproductive years, before and between pregnancies, with risk of APOs., Methods: We followed 16,241 females (25,386 singleton pregnancies) participating in a prospective cohort, the Nurses' Health Study II. Weight at age 18 y, current weight, and height were assessed at baseline (1989), and weight was updated biennially. Pregnancy history was self-reported in 2009. The primary outcome was a composite of hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), preterm birth, and stillbirth. Secondary outcomes were individual APOs. The associations of weight change with APOs were estimated using log-binomial regression, adjusting for demographic, lifestyle, reproductive factors, and baseline BMI (in kg/m 2 )., Results: The mean (standard deviation [SD]) age at first in-study pregnancy was 33.7 (4.1) y. The mean (SD) time from age 18 y to pregnancy, baseline to pregnancy, and between pregnancies was 16.3 (4.0), 6.1 (3.0), and 2.9 (1.6) y, with a corresponding weight change of 6.4 (9.1), 3.1 (5.8), and 2.3 (4.8) kg, respectively. Of the pregnancies, 4628 (18.2%) were complicated by ≥1 APOs. Absolute weight change since age 18 y was most strongly associated with APOs. Compared with females whose weight remained stable (0-2 kg) since age 18, females who gained >2 kg had higher risk of APO (2.1-9.9 kg, relative risk [RR]: 1.12; 95% confidence interval [CI]: 1.02, 1.23; 10.0-14.9 kg, RR: 1.43; 95% CI: 1.29, 1.60; ≥15 kg, RR: 1.87; 95% CI: 1.69, 2.08), primarily driven by HDP and GDM. The associations of per 1 kg weight gain before and between pregnancies with HDP were nearly identical., Conclusions: Weight trajectories prior to and between pregnancies were associated with the risk of APOs, particularly HDP. Longer periods of weight gain, corresponding to greater absolute weight gain, were most strongly associated with higher risk of APOs., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: Plant-based diets have been associated with a lower risk of cardiovascular disease in nonpregnant adults, but specific evidence for their effects on risk of hypertensive disorders of pregnancy is scarce., Objective: This study aimed to evaluate the prospective association between adherence to plant-based diets before pregnancy and the risk for hypertensive disorders of pregnancy. We hypothesized that women with higher adherence to plant-based diets would have a lower risk for hypertensive disorders of pregnancy., Study Design: We followed 11,459 parous women (16,780 singleton pregnancies) without chronic diseases, a history of preeclampsia, and cancers who participated in the Nurses' Health Study II (1991-2009), which was a prospective cohort study. Diet was assessed every 4 years using a validated food frequency questionnaire from which we calculated the plant-based diet index (higher score indicates higher adherence) to evaluate the health associations of plant-based diets among participants while accounting for the quality of plant-based foods. Participants self-reported hypertensive disorders of pregnancy, including preeclampsia and gestational hypertension. We estimated the relative risk of hypertensive disorders of pregnancy in relation to plant-based diet index adherence in quintiles using generalized estimating equations log-binomial regression while adjusting for potential confounders and accounting for repeated pregnancies for the same woman., Results: The mean (standard deviation) age at first in-study pregnancy was 35 (4) years. A total of 1033 cases of hypertensive disorders of pregnancy, including 482 cases of preeclampsia (2.9%) and 551 cases of gestational hypertension (3.3%) were reported. Women in the highest quintile of plant-based diet index were significantly associated with a lower risk for hypertensive disorders of pregnancy than women in the lowest quintile (relative risk, 0.76; 95% confidence interval, 0.62-0.93). There was an inverse dose-response relationship between plant-based diet index and risk for hypertensive disorders of pregnancy. The multivariable-adjusted relative risk (95% confidence interval) of hypertensive disorders of pregnancy for women in increasing quintiles of plant-based diet index were 1 (ref), 0.93 (0.78-1.12), 0.86 (0.72-1.03), 0.84 (0.69-1.03), and 0.76 (0.62-0.93) with a significant linear trend across quintiles (P trend=.005). This association was slightly stronger for gestational hypertension (relative risk, 0.77; 95% confidence interval, 0.60-0.99) than for preeclampsia (relative risk, 0.80; 95% confidence interval, 0.61-1.04). Mediation analysis suggested that body mass index evaluation for dietary assessment and pregnancy explained 39% (95% confidence interval, 15%-70%]) of the relation between plant-based diet index and hypertensive disorders of pregnancy and 48% (95% confidence interval, 12%-86%]) of the relation between plant-based diet index and gestational hypertension., Conclusion: Higher adherence to plant-based diets was associated with a lower risk of developing hypertensive disorders of pregnancy. Much of the benefit seems to be related to improved weight control., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Pre-pregnancy obesity increases the risk of perinatal complications. Post-pregnancy is a time of preparation for the next pregnancy and lifestyle advice in antenatal care and postpartum follow-up is therefore recommended. However, behavioral changes are difficult to achieve, and a better understanding of pregnant women's perspectives and experiences of pre-pregnancy weight development is crucial., Methods: We used a qualitative design and conducted semi-structured interviews with 14 women in Norway with pre-pregnancy obesity 3-12 months postpartum. Data were analyzed using thematic analysis., Results: Four themes addressing women's experiences and understanding of their weight development were generated: (1) Unmet essential needs, (2) Genetic predisposition for obesity, challenging life course transitions and turning points, (3) Under a critical eye: an ever-present negative bodily awareness, and (4) Wrestling with food. Parents' inability to meet children's essential needs caused weight gain through an unbalanced diet, increased stress, and emotional eating patterns. Body criticism and a feeling of not belonging led to negative body awareness that influenced behavioral patterns and relationships. Participants reporting having had a good childhood more often described their weight development as a result of genetic predisposition, challenging life course transitions and turning points, such as illness and injuries. Nevertheless, these participants also described how eating patterns were influenced by stress and negative emotions., Conclusions: Healthcare providers should pay attention to the insider perspectives of pre-pregnancy weight development. An open and shared understanding of the root causes of these women's weight development can form a basis for more successful lifestyle guidance., (© 2024. The Author(s).)

Objective: To investigate the association of healthy lifestyle factors before pregnancy (body mass index [BMI] 18.5-24.9, nonsmoking, 150 min/wk or more of moderate-to-vigorous physical activity, healthy eating [top 40% of Dietary Approaches to Stop Hypertension score], no or low-to-moderate alcohol intake [less than 15 g/d], and use of multivitamins) with risk of adverse pregnancy outcomes., Methods: We conducted a secondary analysis of prospectively collected data for women without chronic diseases who are participating in an ongoing cohort in the United States (the NHSII [Nurses' Health Study II]). Healthy lifestyle factors preceding pregnancy were prospectively assessed every 2-4 years from 1991 to 2009 with validated measures. Reproductive history was self-reported in 2001 and 2009. A composite outcome of adverse pregnancy outcomes that included miscarriage, ectopic pregnancy, gestational diabetes, gestational hypertension, preeclampsia, preterm birth, stillbirth, or low birth weight was assessed., Results: Overall, 15,509 women with 27,135 pregnancies were included. The mean maternal age was 35.1±4.2 years. Approximately one in three pregnancies (n=9,702, 35.8%) was complicated by one or more adverse pregnancy outcomes. The combination of six low-risk factors was inversely associated with risk of adverse pregnancy outcomes in a dose-dependent manner ( P for trend <.001). Compared with women who had zero or one healthy lifestyle factor, those with six had a 37% lower risk of adverse pregnancy outcomes (relative risk 0.63, 95% CI 0.55-0.72), driven primarily by lower risks of gestational diabetes, gestational hypertension, and low birth weight. All prepregnancy healthy lifestyle factors, except avoiding harmful alcohol consumption and regular physical activity, were independently associated with lower risk of adverse pregnancy outcomes after mutual adjustment for each other. Healthy BMI, high-quality diet, and multivitamin supplementation showed the strongest inverse associations with adverse pregnancy outcomes. If the observed relationships were causal, 19% of adverse pregnancy outcomes could have been prevented by the adoption of all six healthy lifestyle factors (population attributable risk 19%, 95% CI 13-26%)., Conclusion: Prepregnancy healthy lifestyle is associated with a substantially lower risk of adverse pregnancy outcomes and could be an effective intervention for the prevention of adverse pregnancy outcomes., Competing Interests: Financial Disclosure Makiko Mitsunami disclosed receiving payment from the Global Scholarship Rotary Foundation. Dr. Mitsunami's institution a grant for soy products research from the Fuji Protein for Research Foundation. The other authors did not report any potential conflicts of interest., (Copyright © 2023 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

To enhance inclusivity and rigor, many funding agencies and journals now mandate the inclusion of females as well as males in biomedical studies. These mandates have enhanced generalizability and created unprecedented opportunities to discover sex differences. However, education in sound methods to consider sex as a subgroup category has lagged behind, resulting in a problematic literature in which study designs, analyses, and interpretations of results are often flawed. Here, we outline best practices for complying with sex-inclusive mandates, both for studies in which sex differences are a primary focus and for those in which they are not. Our recommendations are organized within the "4 Cs of Studying Sex to Strengthen Science: Consideration, Collection, Characterization and Communication," a framework developed by the Office of Research on Women's Health at the National Institutes of Health in the United States. Following these guidelines should help researchers include females and males in their studies while at the same time upholding high standards of rigor., Competing Interests: JR, DM No competing interests declared, (© 2023, Rich-Edwards and Maney.)

Importance: Consumption of energy drinks has increased drastically in recent years, particularly among young people. It is unknown whether intake of energy drinks is associated with health during pregnancy., Objective: To examine associations of energy drink intake before and during pregnancy with risk of adverse pregnancy outcomes (APOs)., Design, Setting, and Participants: This prospective cohort study included data from women enrolled in the Nurses' Health Study 3 (NHS3) between June 1, 2010, and September 27, 2021, and the Growing Up Today Study (GUTS) who reported 1 or more singleton pregnancy from January 1, 2011, to June 1, 2019. Data were analyzed from October 1, 2021, to September 28, 2023., Exposure: Intake of energy drinks, assessed by food frequency questionnaire., Main Outcomes and Measures: The main outcomes were self-reported APOs, including pregnancy loss, gestational diabetes, gestational hypertension, preeclampsia, or preterm birth, and a composite APO, defined as development of any of the APOs. Risk of APOs was compared between consumers and nonconsumers of energy drinks., Results: This study included 7304 pregnancies in 4736 participants with information on prepregnancy energy drink intake and 4559 pregnancies in 4559 participants with information on energy drink intake during pregnancy. There were 1691 GUTS participants (mean [SD] age, 25.7 [2.9] years) and 3045 NHS3 participants (mean [SD] age, 30.2 [4.1] years). At baseline, 230 GUTS participants (14%) and 283 NHS3 participants (9%) reported any intake of energy drinks. While no associations were found for pregnancy loss (odds ratio [OR], 0.89; 95% CI, 0.71-1.11), preterm birth (OR, 1.07; 95% CI, 0.71-1.61), gestational diabetes (OR, 0.89; 95% CI, 0.58-1.35), preeclampsia (OR, 0.73; 95% CI, 0.41-1.30), or the composite APO (OR, 1.05; 95% CI, 0.87-1.26), prepregnancy energy drink use was associated with a higher risk of gestational hypertension (OR, 1.60; 95% CI, 1.12-2.29). A significant interaction was found between age and energy drink intake in relation to hypertensive disorders (P = .02 for interaction for gestational hypertension; P = .04 for interaction for any hypertensive disorders), with stronger associations for participants above the median age. No associations of energy drink intake during pregnancy with any of the APOs were found in NHS3 (eg, any APO: OR, 0.86; 95% CI, 0.41-1.79)., Conclusions and Relevance: In this study, energy drink intake before pregnancy was associated with an elevated risk of gestational hypertension. Given the low prevalence of energy drink intake and low consumption levels among users, the results should be interpreted cautiously.

Importance: Gestational diabetes has been associated with numerous chronic diseases. However, few studies have examined the association of gestational diabetes with long-term mortality risk., Objective: To investigate the associations between gestational diabetes and long-term risks of total and cause-specific mortality., Design, Setting, and Participants: This cohort study analyzed participants of the Nurses' Health Study II who were followed for 30 years (1989-2019). Participants included US female nurses aged 25 to 42 years who reported at least 1 pregnancy (≥6 months) at 18 years or older across their reproductive life span. Data were analyzed from May 1, 2022, to May 25, 2023., Exposure: Gestational diabetes across the reproductive life span., Main Outcomes and Measures: Hazard ratios (HRs with 95% CIs) for total and cause-specific mortality were estimated by Cox proportional hazards regression models., Results: A total of 91 426 parous participants were included, with a mean (SD) age of 34.9 (4.7) years and a body mass index of 24.1 (4.7) at baseline. During a follow-up period of 2 609 753 person-years, 3937 deaths were documented, including 255 deaths from cardiovascular disease and 1397 from cancer. Participants with a history of gestational diabetes had a higher crude mortality rate than those without a history of gestational diabetes (1.74 vs 1.49 per 1000 person-years; absolute difference = 0.25 per 1000 person-years). The corresponding HR for total mortality was 1.28 (95% CI, 1.13-1.44), which did not materially change after additional adjustment for potential confounders and lifestyle factors during the reproductive life span (HR, 1.25; 95% CI, 1.11-1.41). The association persisted regardless of the subsequent development of type 2 diabetes and was more robust among participants who adopted less healthy lifestyles; experienced gestational diabetes in 2 or more pregnancies (HR, 1.48; 95% CI, 0.99-2.19); had gestational diabetes both in the initial and subsequent pregnancies (HR, 1.71; 95% CI, 1.11-2.63); and concurrently reported hypertensive disorders in pregnancy (HR, 1.80; 95% CI, 1.21-2.67), preterm birth (HR, 2.46; 95% CI, 1.66-3.64), or low birth weight (HR, 2.11; 95% CI, 1.21-3.68). Cause-specific mortality analyses revealed that gestational diabetes was directly associated with the risk of mortality due to cardiovascular disease (HR, 1.59; 95% CI, 1.03-2.47). Additionally, gestational diabetes was inversely associated with cancer mortality (HR, 0.76; 95% CI, 0.59-0.98); however, it was only evident among participants who later developed type 2 diabetes., Conclusions and Relevance: Results of this cohort study suggest that participants who reported a history of gestational diabetes exhibited a small but elevated risk of subsequent mortality over 30 years. The findings emphasize the importance of considering gestational diabetes as a critical factor in later-life mortality risk.

Background: Preterm delivery (PTD) includes three main presenting subtypes: spontaneous preterm labour (sPTL), preterm premature rupture of membranes (pPROM) and clinician-initiated preterm delivery (ciPTD). PTD subtype data are rarely available from birth registries and are onerous to derive from medical records., Objectives: To develop and test the validity of a questionnaire to classify PTD subtype based on birthing parent recall of labour and delivery events., Methods: The questionnaire was sent in 2022 to 581 patients with PTD history documented in the LIFECODES study, a hospital-based birth cohort in Boston, Massachusetts. Eighty-two respondents reported 94 PTDs that could be linked to medical records. Data on PTD subtype were extracted from medical records as the reference standard., Results: Medical records indicated 47 spontaneous (24 sPTL, 23 pPROM) and 47 ciPTD deliveries occurring a median eight years earlier. The sensitivity and specificity of the recall questionnaire were 88% (95% confidence interval: 68, 97%) and 89% (79, 95%) for sPTL; 96% (78, 100%) and 94% (86, 98%) for pPROM; and 83% (69, 92%) and 100% (92, 100%) for ciPTD, respectively. Greater time since pregnancy did not degrade the sensitivity or specificity of the parental recall questionnaire., Conclusions: Although derived from a modest sample, the moderate-to-high sensitivity and specificity of the parental recall questionnaire to classify sPTL, pPROM and ciPTD demonstrates its potential for large studies of PTD and for correction of misclassification bias. Future studies are required to test the questionnaire in a variety of populations., (© 2023 The Authors. Paediatric and Perinatal Epidemiology published by John Wiley & Sons Ltd.)

Objective: To investigate the association between infertility and the incidence of invasive cancer., Design: Prospective cohort study (1989-2015)., Setting: Not applicable., Patient(s): A total of 103,080 women aged 25-42 years in the Nurses' Health Study II who were cancer-free at baseline (1989)., Intervention(s): The infertility status (failure to conceive after 1 year of regular, unprotected sex) and causes of infertility were self-reported at baseline and biennial follow-up questionnaires., Main Outcome Measure(s): 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 postmenopausal breast) or non-obesity-related (all other cancers). We fit the Cox proportional-hazards models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between infertility and cancer incidence., Result(s): During 2,149,385 person-years of follow-up, 26,208 women reported a history of infertility, and we documented 6,925 incident invasive cancer cases. After adjusting for body mass index and other risk factors, women who reported infertility had a higher risk of developing cancer than gravid women without a history of infertility (HR, 1.07; 95% CI, 1.02-1.13). This association was stronger among obesity-related cancers (HR, 1.13; 95% CI, 1.05-1.22; vs. non-obesity-related cancers, HR, 0.98; 95% CI, 0.91-1.06) and, in particular, obesity-related reproductive cancers (postmenopausal breast, endometrial, and ovarian cancers; HR, 1.17; 95% CI, 1.06-1.29) and was stronger among women who first reported infertility earlier in life (≤25 years, HR, 1.19; 95% CI, 1.07-1.33; 26-30 years, HR, 1.11; 95% CI, 0.99-1.25; >30 years, HR, 1.07; 95% CI, 0.94-1.22; P trend < .001)., Conclusion(s): A history of infertility may be associated with the risk of developing obesity-related reproductive cancers; further study is needed to elucidate the underlying mechanisms., (Copyright © 2023 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Hypertensive disorders of pregnancy (HDPs) have been associated with respiratory dysfunction during pregnancy and postpartum. In this study, we explored the associations between HDPs (gestational hypertension and preeclampsia) and the risk of incident asthma and chronic obstructive pulmonary disease (COPD) during adulthood and the potential mediating role of chronic hypertension., Methods: We included parous nurses in the Nurses' Health Study II reporting a pregnancy lasting no less than 6 months. The associations between HDPs and asthma and COPD were estimated using Cox proportional hazards models with adjustment for confounders., Findings: We included 73,807 nurses [92.5% (68,246 of 73,807) White] in asthma analyses and 79,843 [92.4% (73,746 of 79,843) White] in COPD analyses, whose mean (SD, range) age, at baseline, were both 34.8 (4.7, 25.0-44.0) years. During 24 years of follow-up, we identified 2663 incident cases of asthma and 537 COPD. Compared with nurses without HDPs, nurses reporting HDPs had an increased HR for incident asthma and COPD of 1.22 (95% CI 1.10-1.36) and 1.39 (95% CI 1.11-1.74), respectively. The risk of asthma was similar when gestational hypertension and preeclampsia were assessed separately [HR = 1.25 (95% CI 1.08-1.43) and 1.24 (95% CI 1.11-1.38), respectively]. However, only nurses with preeclampsia had a higher risk of COPD (HR = 1.41, 95% CI 1.11-1.78). Mediation analyses estimated that chronic hypertension explained 18.6% (95% CI 8.9-35.0%) and 10.7% (95% CI 2.9-32.4%) of the associations between HDPs and asthma and COPD, respectively., Interpretation: HDPs may serve as useful markers of increased susceptibility to chronic respiratory diseases during adulthood., Funding: The National Institutes of Health grants., Competing Interests: JEC and CAC report financial support from the 10.13039/100000002National Institutes of Health, outside the submitted work. All other authors declare no competing interests., (© 2023 The Authors.)

Introduction: Data on the associations of prepandemic physical activity and sedentary behavior with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity, particularly milder illness, have been limited., Methods: We used data from 43,913 participants within the Nurses' Health Study II and Health Professionals Follow-Up Study who responded to periodic COVID-related surveys from May 2020 through March 2021. History of physical activity from the prepandemic period was assessed as the metabolic equivalents of task (MET)-hours per week of various activities of different intensity and sedentary behavior assessed from reports of time spent sitting from questionnaires completed 2016-2017. Multivariable logistic regression models were fitted to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for risk of SARS-CoV-2 infection and COVID-19 severity, as well as predicted COVID-19 defined using a validated symptom-based algorithm., Results: Higher levels of prepandemic physical activity were associated with a lower risk for SARS-CoV-2 infection. Compared to participants with <3 MET-hours per week, the multivariable-adjusted OR was 0.86 (95% CI: 0.74, 0.99; P trend =.07) for those with ≥27 MET-hours per week. Higher physical activity levels were also associated with lower risk of symptomatic SARS-CoV-2 infection (OR: 0.84; 95% CI: 0.72, 0.99; P trend = .05) and predicted COVID-19 (OR: 0.87; 95% CI: 0.78, 0.97; P trend = .01). Longer time sitting at home watching TV (OR: 0.85; 95% CI: 0.73, 0.97) or for other tasks (OR: 0.78; 95% CI: 0.66, 0.92) was associated with a lower risk of SARS-CoV-2 infection., Conclusions: Our findings support a protective association between prepandemic physical activity and lower risk and severity of COVID-19., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Women are at greater risk than men of developing chronic inflammatory conditions and "long COVID." However, few gynecologic health risk factors for long COVID-19 have been identified. Endometriosis is a common gynecologic disorder associated with chronic inflammation, immune dysregulation, and comorbid presentation with autoimmune and clotting disorders, all of which are pathophysiological mechanisms proposed for long COVID-19. Therefore, we hypothesized that women with a history of endometriosis may be at greater risk of developing long COVID-19., Objective: This study aimed to investigate the association between history of endometriosis before SARS-CoV-2 infection and risk of long COVID-19., Study Design: We followed 46,579 women from 2 ongoing prospective cohort studies-the Nurses' Health Study II and the Nurses' Health Study 3-who participated in a series of COVID-19-related surveys administered from April 2020 to November 2022. Laparoscopic diagnosis of endometriosis was documented prospectively in main cohort questionnaires before the pandemic (1993-2020) with high validity. SARS-CoV-2 infection (confirmed by antigen, polymerase chain reaction, or antibody test) and long-term COVID-19 symptoms (≥4 weeks) defined by the Centers for Disease Control and Prevention were self-reported during follow-up. Among individuals with SARS-CoV-2 infection, we fit Poisson regression models to assess the associations between endometriosis and risk of long COVID-19 symptoms, with adjustment for potential confounding variables (demographics, body mass index, smoking status, history of infertility, and history of chronic diseases)., Results: Among 3650 women in our sample with self-reported SARS-CoV-2 infections during follow-up, 386 (10.6%) had a history of endometriosis with laparoscopic confirmation, and 1598 (43.8%) reported experiencing long COVID-19 symptoms. Most women were non-Hispanic White (95.4%), with a median age of 59 years (interquartile range, 44-65). Women with a history of laparoscopically-confirmed endometriosis had a 22% greater risk of developing long COVID-19 (adjusted risk ratio, 1.22; 95% confidence interval, 1.05-1.42) compared with those who had never been diagnosed with endometriosis. The association was stronger when we defined long COVID-19 as having symptoms for ≥8 weeks (risk ratio, 1.28; 95% confidence interval, 1.09-1.50). We observed no statistically significant differences in the relationship between endometriosis and long COVID-19 by age, infertility history, or comorbidity with uterine fibroids, although there was a suggestive trend indicating that the association may be stronger in women aged <50 years (<50 years: risk ratio, 1.37; 95% confidence interval, 1.00-1.88; ≥50 years: risk ratio, 1.19; 95% confidence interval, 1.01-1.41). Among persons who developed long COVID-19, women with endometriosis reported on average 1 additional long-term symptom compared with women without endometriosis., Conclusion: Our findings suggest that those with a history of endometriosis may be at modestly increased risk for long COVID-19. Healthcare providers should be aware of endometriosis history when treating patients for signs of persisting symptoms after SARS-CoV-2 infection. Future studies should investigate the potential biological pathways underlying these associations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Qualitative research methods, while rising in popularity, are still a relatively underutilized tool in public health research. Usually reserved for small samples, qualitative research techniques have the potential to enhance insights gained from large questionnaires and cohort studies, both deepening the interpretation of quantitative data and generating novel hypotheses that might otherwise be missed by standard approaches; this is especially true where exposures and outcomes are new, understudied, or rapidly changing, as in a pandemic. However, methods for the conduct of qualitative research within large samples are underdeveloped. Here, we describe a novel method of applying qualitative research methods to free-text comments collected in a large epidemiologic questionnaire. Specifically, this method includes: 1) a hierarchical system of coding through content analysis; 2) a qualitative data management application; and 3) an adaptation of Cohen's κ and percent agreement statistics for use by a team of coders, applying multiple codes per record from a large codebook. The methods outlined in this paper may help direct future applications of qualitative and mixed methods within large cohort studies., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objective: To explore associations between early life physical and sexual abuse and subsequent risk of premature mortality (death before age 70 years)., Design: Prospective cohort study., Setting: The Nurses' Health Study II (2001-19)., Participants: 67 726 female nurses aged 37-54 years when completing a violence victimization questionnaire in 2001., Main Outcome Measures: Hazard ratios and 95% confidence intervals for total and cause specific premature mortality by childhood or adolescent physical and sexual abuse, estimated by multivariable Cox proportional hazard models., Results: 2410 premature deaths were identified over 18 years of follow-up. Nurses who experienced severe physical abuse or forced sexual activity in childhood and adolescence had a higher crude premature mortality rate than nurses without such abuse in childhood or adolescence (3.15 v 1.83 and 4.00 v 1.90 per 1000 person years, respectively). The corresponding age adjusted hazard ratios for premature deaths were 1.65 (95% confidence interval 1.45 to 1.87) and 2.04 (1.71 to 2.44), respectively, which were materially unchanged after further adjusting for personal characteristics and early life socioeconomic status (1.53, 1.35 to 1.74, and 1.80, 1.50 to 2.15, respectively). Cause specific analyses indicated that severe physical abuse was associated with a greater risk of mortality due to external causes of injury and poisoning (multivariable adjusted hazard ratio 2.81, 95% confidence interval 1.62 to 4.89), suicide (3.05, 1.41 to 6.60), and diseases of the digestive system (2.40, 1.01 to 5.68). Forced sexual activity as a child and adolescent was associated with greater risk of mortality due to cardiovascular disease (2.48, 1.37 to 4.46), external injury or poisoning (3.25, 1.53 to 6.91), suicide (4.30, 1.74 to 10.61), respiratory disease (3.74, 1.40 to 9.99), and diseases of the digestive system (4.83, 1.77 to 13.21). The association of sexual abuse with premature mortality was stronger among women who smoked or had higher levels of anxiety during adulthood. Smoking, low physical activity, anxiety, and depression each explained 3.9-22.4% of the association between early life abuse and premature mortality., Conclusion: Early life physical and sexual abuse could be associated with a greater risk of adult premature mortality., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from the National Institutes of Health for the submitted work; no financial relationships with any organizations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Investigate the association between adverse childhood experiences and pre-pregnancy body mass index (BMI) in a population-based cohort in Trøndelag county, Norway., Materials and Methods: We linked data from the third (2006-2008) or fourth (2017-2019) survey of the Trøndelag Health Study (HUNT) and the Medical Birth Registry of Norway for 6679 women. Multiple logistic regression models were used to examine the association between adverse childhood experiences and pre-pregnancy BMI. Adverse childhood experiences were self-reported in adulthood and included perceiving childhood as difficult, parental divorce, parental death, dysfunctional family environment, bad childhood memories and lack of support from a trusted adult. Pre-pregnancy BMI was derived from the Medical Birth Registry of Norway or BMI measurement from the HUNT survey conducted within 2 years prior to the woman's pregnancy., Results: Perceiving childhood as difficult was associated with higher odds of pre-pregnancy underweight (OR 1.78, 95%CI 0.99-3.22) and obesity (OR 1.58, 95%CI 1.14-2.2). A difficult childhood was positively associated with obesity with an adjusted OR of 1.19, 95%CI 0.79-1.81 (class I obesity), 2.32, 95%CI 1.35-4.01 (class II obesity) and 4.62, 95%CI 2.0-10.65 (class III obesity). Parental divorce was positively associated obesity (OR 1.34, 95%CI 1.10-1.63). Bad childhood memories were associated with both overweight (OR 1.34, 95%CI 1.01-1.79) and obesity (OR 1.63, 95%CI 1.13-2.34). Parental death was not associated with pre-pregnancy BMI., Conclusions: Childhood adversities were associated with pre-pregnancy BMI. Our results suggest that the positive associations between childhood adversities and pre-pregnancy obesity increased with increasing obesity level., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sandsæter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Research on infertility and risk of breast cancer has been conflicting, potentially because many well-established breast cancer risk factors, such as pregnancy history, are strongly correlated with infertility., Methods: We followed participants in the Nurses' Health Study II from 1989 to 2015 (n = 103,080) for the development of invasive breast cancer and calculated Hazard Ratios (HR) and 95% confidence intervals (CI) using Cox regression. Participants with a self-reported history of infertility (12 months of trying without conception) were compared to gravid women with no history of infertility. We classified breast cancer by menopausal status and investigated mediation by reproductive factors., Results: Over 26 years of follow-up, 26,208 (25.4%) women reported a history of infertility, and 3,201 women were newly diagnosed with invasive breast cancer. We observed no association between infertility history and risk of overall breast cancer (HR: 1.05, 95% CI: 0.97-1.14) or premenopausal breast cancer (RR: 0.93, 95% CI: 0.83-1.03). However, we observed a modest association between history of infertility and risk of postmenopausal breast cancer (HR: 1.13, 95% CI: 1.00-1.28), approximately 50% of which could be attributed to lower total parity and later age at first birth (95% CI: 8.2%-91.0%)., Conclusions: Women with a history of infertility were at increased risk of postmenopausal breast cancer. Older age at first birth and lower total parity explained approximately half of the association between infertility and risk of postmenopausal breast cancer., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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

Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Objective: Migraine is a highly prevalent neurovascular disorder among reproductive-aged women. Whether migraine history and migraine phenotype might serve as clinically useful markers of obstetric risk is not clear. The primary objective of this study was to examine associations of prepregnancy migraine and migraine phenotype with risks of adverse pregnancy outcomes., Methods: We estimated associations of self-reported physician-diagnosed migraine and migraine phenotype with adverse pregnancy outcomes in the prospective Nurses' Health Study II (1989-2009). Log-binomial and log-Poisson models with generalized estimating equations were used to estimate relative risks (RRs) and 95% CIs for gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension, preterm delivery, and low birthweight., Results: The analysis included 30,555 incident pregnancies after cohort enrollment among 19,694 participants without a history of cardiovascular disease, diabetes, or cancer. After adjusting for age, adiposity, and other health and behavioral factors, prepregnancy migraine (11%) was associated with higher risks of preterm delivery (RR = 1.17; 95% CI = 1.05-1.30), gestational hypertension (RR = 1.28; 95% CI = 1.11-1.48), and preeclampsia (RR = 1.40; 95% CI = 1.19-1.65) compared with no migraine. Migraine was not associated with low birthweight (RR = 0.99; 95% CI = 0.85-1.16) or GDM (RR = 1.05; 95% CI = 0.91-1.22). Risk of preeclampsia was somewhat higher among participants with migraine with aura (RR vs no migraine = 1.51; 95% CI = 1.22-1.88) than migraine without aura (RR vs no migraine = 1.30; 95% CI = 1.04-1.61; p- heterogeneity = 0.32), whereas other outcomes were similar by migraine phenotype. Participants with migraine who reported regular prepregnancy aspirin use had lower risks of preterm delivery (<2×/week RR = 1.24; 95% CI = 1.11-1.38; ≥2×/week RR = 0.55; 95% CI = 0.35-0.86; p -interaction < 0.01) and preeclampsia (<2×/week RR = 1.48; 95% CI = 1.25-1.75; ≥2×/week RR = 1.10; 95% CI = 0.62-1.96; p -interaction = 0.39); however, power for these stratified analyses was limited., Discussion: Migraine history, and to a lesser extent migraine phenotype, appear to be important considerations in obstetric risk assessment and management. Future research should determine whether aspirin prophylaxis may be beneficial for preventing adverse pregnancy outcomes among pregnant individuals with a history of migraine., (© 2023 American Academy of Neurology.)

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

Importance: During the COVID-19 pandemic, the prevalence and severity of intimate partner violence (IPV) increased. Associations between IPV and mental health symptoms and modifiable health factors early in the pandemic have yet to be explored., Objective: To prospectively investigate the association of IPV with greater risk of mental health symptoms and adverse health factors during the COVID-19 pandemic in 3 cohorts of female participants., Design, Setting, and Participants: This cohort study used observational data from 3 prospective, population-based, longitudinal cohorts in the US: the Nurses' Health Study II, Growing Up Today Study, and Nurses' Health Study 3. Data analyzed included baseline and follow-up survey responses about IPV experiences early in the pandemic (March-September 2020); mental health domains of depression, anxiety, and posttraumatic stress symptoms (PTSS); and modifiable health factors (May 2020-October 2021). Female participants (both health care professionals and non-health care workers) aged 21 to 60 years from the 3 cohorts were included in the full analytic sample., Exposures: Experience of IPV measured by the Relationship Assessment Tool and fear of partner., Main Outcomes and Measures: Mental health symptoms, including depression, anxiety, and PTSS, and modifiable health factors, including sleep duration, sleep quality, physical activity, alcohol use, and use of alcohol or other substances to cope with stress., Results: The full analytic sample included 13 597 female participants with a mean (SD) age of 44 (10.6) years. Accounting for sociodemographic factors and prepandemic mental health symptoms and correcting for multiple testing, experiencing IPV was associated with higher endorsement of depression (odds ratio [OR], 1.44; 95% CI, 1.38-1.50), anxiety (OR, 1.31; 95% CI, 1.26-1.36), and PTSS (OR, 1.22; 95% CI, 1.15-1.29) in random-effects meta-analyses across the 3 cohorts. The IPV experience was also associated with poorer sleep quality (OR, 1.21; 95% CI, 1.16-1.26), shorter sleep duration (OR, 1.13; 95% CI, 1.08-1.19), increased use of alcohol (OR, 1.10; 95% CI, 1.06-1.14), and use of alcohol or other substances to cope with stress (OR, 1.13; 95% CI, 1.08-1.18) across all cohorts as well as decreased physical activity (OR, 1.17; 95% CI, 1.09-1.26) in the Nurses' Health Study II only., Conclusions and Relevance: Results of the study showed that IPV experiences at the start of the pandemic were associated with worse mental health symptoms and modifiable health factors for female participants younger than 60 years. Screening and interventions for IPV and related health factors are needed to prevent severe, long-term health consequences.

Background: Women's pregnancy history is associated with incident risk of coronary artery disease with some evidence also suggesting a relevance for prognosis following treatment., Objectives: To study the associations between maternal history of preterm delivery, a history of small for gestational age infant, parity and age at first delivery with clinical restenosis after percutaneous coronary intervention (PCI)., Methods: In this prospective cohort study, we included 6027 women < 65 years undergoing their first PCI 2006-2017, merging clinical register data on PCI procedures in Sweden with comprehensive registry data on deliveries since 1973. We used proportional hazards regression to study the association between aspects of pregnancy history and clinical restenosis in per-segment analyses, and with target lesion revascularisation (TLR) in per-patient analyses. We adjusted models for procedural-related and patient-related predictors of restenosis., Results: During 15 981 segment-years of follow-up, 343 (3.7%) events of clinical restenosis occurred. We found no strong evidence of associations between the studied aspects of pregnancy history and clinical restenosis following PCI. For example, the restenosis HR for a history of preterm delivery in the fully adjusted model was 1.09 (95% CI 0.77 to 1.55) and the TLR HR was 1.18 (95% CI 0.91 to 1.52)., Conclusion: Risk of restenosis following treatment with PCI did not differ by the studied aspects of pregnancy history, including preterm delivery, in young and middle-aged women. Larger studies are needed to obtain more precise estimates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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

There is a dearth of qualitative studies exploring the lived experiences of frontline healthcare personnel (HCP) during the coronavirus disease (COVID-19) pandemic. We examined workplace stressors, psychological manifestations of said stressors, and coping strategies reported through coded open-text responses from 1024 online surveys completed over two months by 923 HCP participating in three nationwide cohorts from Spring 2020. Our findings suggest that risk, job insecurity, frustration with hospital administration, inadequate access to personal protective equipment, and witnessing patient suffering and death contributed to deteriorating mental and physical health. Negative health impacts included the onset or exacerbation of anxiety, depression, and somatic symptoms, including weight fluctuation, fatigue, and migraines. Coping mechanisms included substance use and food consumption, meditation and wellness, fitness, socializing with loved ones, and religious activities. Insights garnered from participants' responses will enable more personalized and effective psychosocial crisis prevention and intervention for frontline HCP in future health crises., (© 2022 The Authors.)

Background: Women are at a greater risk of a major adverse cardiovascular event (MACE) after percutaneous coronary intervention than men. A history of preterm delivery is a female-specific risk factor for coronary artery disease, but its relevance in the treatment of coronary artery disease is unknown., Objectives: The purpose of this study was to analyze the association between a history of preterm delivery and MACE after the first coronary artery stenting., Methods: We included a nationwide sample of 5,766 Swedish women aged ≤65 years receiving their first coronary stent during 2006 to 2017. To adjust for periprocedural characteristics and estimate the association between a history of preterm delivery and MACE at >30 days from stenting, we used proportional hazards regression. We also investigated mortality by history of preterm delivery., Results: During a median follow-up time of 3.7 years (IQR: 1.3-6.7 years), 1,200 (20.8%) women had a MACE. In total, 963 (16.7%) women had a history of preterm delivery. A history of preterm delivery was associated with a higher risk of MACE (adjusted HR: 1.19; 95% CI: 1.03-1.38) and mortality (adjusted HR ratio: 1.38; 95% CI: 1.02-1.85). Similar associations were observed when excluding women with a history of hypertensive disorders of pregnancy or diabetes. Subgroup analyses suggested that women with a history of early preterm delivery had lower risk of MACE than those who had late preterm delivery ( P  = 0.04)., Conclusions: History of preterm delivery is associated with worse prognosis following the first coronary artery stenting in women and warrants consideration as a risk factor also in the secondary prevention setting., Competing Interests: This work was supported by grants awarded to Simon Timpka from the 10.13039/501100004359Swedish Research Council (2019-02082); The 10.13039/501100003793Swedish Heart-Lung Foundation (20180312); public research support via the Faculty of Medicine at 10.13039/501100003252Lund University (ALF [Avtal om Läkarutbildning och Forskning]: YF-ALF, ALF project); The 10.13039/501100007687Swedish Society of Medicine (SLS-885331); The 10.13039/100008738Jeansson Foundations, Stockholm, Sweden; and 10.13039/100007435Åke Wiberg Foundation, Stockholm, Sweden. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Background: Weight at birth has been associated with the development of various adult diseases, but its association with mortality remains unclear., Methods: We included 22,389 men from the Health Professionals Follow-up Study (1994-2018) and 162,231 women from the Nurses' Health Study (1992-2018) and the Nurses' Health Study II (1991-2019). The hazard ratios (HRs) of mortality according to birth weight were estimated by Cox proportional hazards regression models with adjustment for potential confounders., Findings: Compared to women reporting a birth weight of 3.16-3.82 kg, the pooled HRs for all-cause mortality were 1.13 (95% CI, 1.08 to 1.17), 0.99 (95% CI, 0.96 to 1.02), 1.04 (95% CI, 1.00 to 1.08), and 1.03 (95% CI, 0.96 to 1.10), respectively, for women with a birth weight of <2.5, 2.5-3.15, 3.83-4.5, and >4.5 kg. In cause-specific mortality analyses, women reporting birth weight >4.5 kg had a higher risk of cancer mortality (HR=1.15, 95% CI: 1.00 to 1.31), whereas women with a birth weight <2.5 kg had an elevated risk of mortality from cardiovascular diseases (HR=1.15; 95% CI, 1.05 to 1.25) and respiratory diseases (HR=1.35; 95% CI, 1.18 to 1.54). Birth weight was unrelated to all-cause mortality among men, but cause-specific mortality analyses showed an inverse association with cardiovascular disease mortality and a positive association with cancer mortality ( p for linear trend = 0.012 and 0.0039, respectively)., Interpretation: low birth weight was associated with a greater risk of cardiovascular and respiratory disease mortality among women, while large birth weight was associated with a greater cancer mortality risk in both men and women., Funding: The National Institutes of Health grants U01-HL145386, U01-CA176726, R01-HL034594, R01-HL088521, UM-CA186107, P01-CA87969, R01-CA49449, R01-CA67262, U01-HL145386, U01-CA167552, R01-HL35464, and R24-ES028521-01 support this study., Competing Interests: Declaration of interests JEC and JEM report financial support from the National Institutes of Health, outside the submitted work. All other authors declare no competing interests.

Objectives. To characterize COVID-19 vaccine uptake and hesitancy among US nurses. Methods. We surveyed nurses in 3 national cohorts during spring 2021. Participants who indicated that they did not plan to receive or were unsure whether they planned to receive the vaccine were considered vaccine hesitant. Results. Among 32 426 female current and former nurses, 93% had been or planned to be vaccinated. After adjustment for age, race/ethnicity, and occupational variables, vaccine hesitancy was associated with lower education, living in the South, and working in a group care or home health setting. Those who experienced COVID-19 deaths and those reporting personal or household vulnerability to COVID-19 were less likely to be hesitant. Having contracted COVID-19 doubled the risk of vaccine hesitancy (95% confidence interval [CI] = 1.85, 2.53). Reasons for hesitancy that were common among nurses who did not plan to receive the vaccine were religion/ethics, belief that the vaccine was ineffective, and lack of concern about COVID-19; those who were unsure often cited concerns regarding side effects or medical reasons or reported that they had had COVID-19. Conclusions. Vaccine hesitancy was unusual and stemmed from specific concerns. Public Health Implications. Targeted messaging and outreach might reduce vaccine hesitancy. ( Am J Public Health . 2022;112(11):1620-1629. https://doi.org/10.2105/AJPH.2022.307050).

Background: Despite anecdotal reports, the impacts of SARS-CoV-2 infection or COVID-19 vaccination on menstrual health have not been systemically investigated., Objective: This study aimed to examine the associations of SARS-CoV-2 infection and COVID-19 vaccination with menstrual cycle characteristics., Study Design: This study prospectively observed 3858 premenopausal women in the Nurses' Health Study 3 living in the United States or Canada who received biannual follow-up questionnaires between January 2011 and December 2021 and completed additional monthly and quarterly surveys related to the COVID-19 pandemic between April 2020 and November 2021. History of positive SARS-CoV-2 test, COVID-19 vaccination status, and vaccine type were self-reported in surveys conducted in 2020 and 2021. Current menstrual cycle length and regularity "before COVID-19" were reported at baseline between 2011 and 2016, and current menstrual cycle length and regularity "after COVID-19" were reported in late 2021. Pre- to post-COVID change in menstrual cycle length and regularity was calculated between reports. Logistic or multinomial logistic regression models were used to assess the associations between SARS-CoV-2 infection and COVID-19 vaccination and change in menstrual cycle characteristics., Results: The median age at baseline and the median age at end of follow-up were 33 years (range, 21-51) and 42 years (range, 27-56), respectively, with a median follow-up time of 9.2 years. This study documented 421 SARS-CoV-2 infections (10.9%) and 3527 vaccinations (91.4%) during follow-up. Vaccinated women had a higher risk of increased cycle length than unvaccinated women (odds ratio, 1.48; 95% confidence interval, 1.00-2.19), after adjusting for sociodemographic and behavioral factors. These associations were similar after in addition accounting for pandemic-related stress. COVID-19 vaccination was only associated with change to longer cycles in the first 6 months after vaccination (0-6 months: odds ratio, 1.67 [95% confidence interval, 1.05-2.64]; 7-9 months: odds ratio, 1.43 [95% confidence interval, 0.96-2.14]; >9 months: odds ratio, 1.41 [95% confidence interval, 0.91-2.18]) and among women whose cycles were short, long, or irregular before vaccination (odds ratio, 2.82 [95% confidence interval, 1.51-5.27]; odds ratio, 1.10 [95% confidence interval, 0.68-1.77] for women with normal length, regular cycles before vaccination). Messenger RNA and adenovirus-vectored vaccines were both associated with this change. SARS-CoV-2 infection was not associated with changes in usual menstrual cycle characteristics., Conclusion: COVID-19 vaccination may be associated with short-term changes in usual menstrual cycle length, particularly among women whose cycles were short, long, or irregular before vaccination. The results underscored the importance of monitoring menstrual health in vaccine clinical trials. Future work should examine the potential biological mechanisms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pregnancy is associated with physiological changes to meet the metabolic demands of the growing fetus. To understand adverse pregnancy outcomes it is important to establish vascular changes throughout pregnancy. We examined longitudinal changes in vascular measurements from prepregnancy through postpartum. Materials and Methods: Seventy women planning to conceive in Ulaanbaatar, Mongolia enrolled in this prospective study. Within 6 months, 44 (63%) had conceived; of which 36 (82%) delivered. Ten (28%) developed complex pregnancies and were analyzed separately. Vascular measures included central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), augmentation index corrected for heart rate of 75 beats/minute (AIx-75), and pulse wave velocity (PWV). Measurements were performed at prepregnancy, second trimester (22-24 weeks), third trimester (34-36 weeks), and 2 months postpartum. Missing values ( n  = 0-6 per time period) were replaced by multiple imputation. A repeated measures analysis of variance analyzed changes within individual women over the four time points adjusted for age, parity, and body mass index. Results: We observed significant reductions from prepregnancy to second trimester for mean Alx-75 (17.1%-12.6%; p  = 0.006) and cSBP (91.7-86.8 mmHg; p  = 0.03) but not for cDBP or PWV. Both mean AIx-75 and cSBP increased in third trimester. In the postpartum, cSBP returned to prepregnancy levels, whereas AIx-75 exceeded prepregnancy levels, although this fell short of significance ( p  = 0.09). Similar vascular patterns were observed in women with complex pregnancies for AIx-75; however, PWV increased from the second trimester and remained higher through postpartum, although not significant. Conclusion: In Mongolian women, we observed a decrease in AIx-75 and cSBP from prepregnancy through second trimester, which resolved postpartum. These results provide an understanding of changes across pregnancies in an Asian country. Future studies should assess vascular changes across pregnancies to determine if it can predict conditions such as pre-eclampsia.

Background: Breastfeeding has been associated with a reduced maternal long-term risk of chronic diseases, but its association with mortality is poorly known., Methods: We included 166,708 female United States (US) nurses from the Nurses' Health Study (1986-2016) and the Nurses' Health Study II (1989-2019) who experienced at least one pregnancy lasting at least six months across their reproductive lifespan. Hazard ratios and 95% confidence intervals (CI) for mortality according to lifetime breastfeeding duration were estimated with time-dependent Cox proportional hazards regression models., Findings: During 4,705,160 person-years of follow-up, 36,634 deaths were documented in both cohorts, including 9880 from cancer and 7709 from cardiovascular disease (CVD). Lifetime total breastfeeding duration was associated with a lower subsequent risk of all-cause mortality in a non-linear manner (p-value for non-linearity=0.0007). The pooled multivariable-adjusted hazard ratios of all-cause mortality were 0.95 (95% CI: 0.92 to 0.98), 0.94 (95% CI: 0.91 to 0.98), 0.93 (95% CI: 0.90 to 0.97), and 0.93 (95% CI: 0.89 to 0.97), respectively, for women reporting lifetime total breastfeeding duration of 4-6, 7-11, 12-23, and ≥24 months, compared to women who breastfed for ≤3 months over their reproductive lifespan. Cause-specific analysis showed a similar pattern of non-linear inverse associations between lifetime total breastfeeding duration and CVD and cancer mortality (both p-values for non-linearity <0.01). There was no evidence of interactions between breastfeeding duration and pre-pregnancy lifestyle factors on mortality risk., Interpretation: Parous women with longer lifetime breastfeeding duration had a modestly lower risk of mortality., Funding: The National Institutes of Health grants., Competing Interests: JEM reports financial support from the National Institutes of Health outside the submitted work. SAM reports personal fees from AbbVie and Roche outside the submitted work. J.E.C. reports grants from the National Institutes of Health, Centres for Disease Control and Prevention, and Food and Drug Administration, outside the submitted work., (© 2022 The Authors.)

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

Background A history of preeclampsia is associated with increased risk of coronary artery disease and experimental evidence suggests that a history of preeclampsia also increases the risk of restenosis. However, the extent to which a history of preeclampsia is associated with risk of restenosis after percutaneous coronary intervention in women is unknown. Methods and Results We included 6065 parous women aged ≤65 years with first percutaneous coronary intervention on 9452 segments 2006 to 2017, linking nationwide data on percutaneous coronary intervention and delivery history in Sweden. Main outcomes were clinical restenosis and target lesion revascularization within 2 years. We accounted for segment-, procedure-, and patient-related potential predictors of restenosis in proportional hazards regression models. Restenosis occurred in 345 segments (3.7%) and target lesion revascularization was performed on 383 patients (6.3%). A history of preeclampsia was neither significantly associated with risk of restenosis (predictor-accounted hazard ratio [HR], 0.71 [95% CI, 0.41-1.23]) nor target lesion revascularization (0.74 [95% CI, 0.51-1.07]) compared with a normotensive pregnancy history. When term and preterm preeclampsia were investigated separately, segments in women with a history of term preeclampsia had a lower risk of restenosis (predictor-accounted HR, 0.45 [95% CI, 0.21-0.94]). A history of preeclampsia was not significantly associated with death by any cause within 2 years of the index procedure (predictor-accounted HR 1.06, [95% CI, 0.62-1.80]). Conclusions A history of preeclampsia was not associated with increased risk of restenosis but instead some evidence pointed to a decreased risk. To facilitate future studies and allow for replication, concomitant collection of data on pregnancy complication history and percutaneous coronary intervention outcomes in women is warranted.

Background: Many studies have linked intakes of fat and of specific fatty acids during pregnancy with preeclampsia; however, information on the association of intake before pregnancy with hypertensive disorders of pregnancy (HDP) is scant., Objectives: We evaluated the associations of intakes of major and specific types of fat before pregnancy with the risks of HDP, including preeclampsia and gestational hypertension (GHTN)., Methods: We followed 11,535 women without chronic disease participating in the Nurses' Health Study II from 1991 and 2009. Pre-pregnancy dietary fat was assessed by an FFQ. Intakes of total fat, saturated fat, trans fatty acid (TFA), MUFAs, PUFAs, and fat subtypes (omega-3 and omega-6) were categorized into quintiles of intake. HDP were self-reported. The RRs (95% CIs) of HDP were estimated by log-binomial generalized estimating equation regression models, with an exchangeable correlation matrix to account for repeated pregnancies while adjusting for potential confounders., Results: During 19 years of follow-up, there were 495 cases of preeclampsia (2.9%) and 561 (3.3%) cases of GHTN in 16,892 singleton pregnancies. The mean age at pregnancy was 34.6 years (SD, 3.9 years). Among major fat types, only pre-pregnancy TFA was related to a higher risk of HDP (RR, 1.32; 95% CI: 1.05-1.66), and only for preeclampsia (RR, 1.50; 95% CI: 1.07-2.10) but not for GHTN (RR, 1.21; 95% CI: 0.87-1.70). Among specific types of PUFAs, intake of arachidonic acid was positively related with GHTN (RR, 1.43; 95% CI: 1.00-2.04) but not preeclampsia (RR, 1.08; 95% CI: 0.75-1.57). In analyses restricted to pregnancies 1 year after the diet assessment, women with the highest intake of long-chain omega-3 fatty acids had a 31% lower risk of HDP (95% CI: 3%-51%), which was driven by preeclampsia (RR, 0.55; 95% CI: 0.33-0.92)., Conclusions: Pre-pregnancy intakes of total fat, saturated fat, and MUFA were unrelated to HDP, whereas TFA was positively related to HDP. These findings highlight the importance of ongoing efforts to eliminate TFA from the global food supply., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Objective: To investigate the association between subfertility and risk of cardiovascular disease (CVD) outcomes., Design: Prospective study., Setting: Population-based cohort., Patient(s): We studied 31,629 women and 17,630 men participating in the Trøndelag Health Study., Intervention(s): Self-reported subfertility. As men were not directly asked about fertility, male partners of female participants were identified through linkage to the Medical Birth Registry of Norway and assigned the fertility information obtained from their partners., Main Outcome Measure(s): The primary outcomes were stroke and coronary heart disease in women and men with and without a history of subfertility. The secondary outcomes were myocardial infarction and angina (subgroups of coronary heart disease) and any CVD (stroke or coronary heart disease). Information on CVD was available by linkage to hospital records. We used Cox proportional hazards models adjusted for age at participation in the Trøndelag Health Study (linear + squared), birth year, smoking history, cohabitation, and education. Cardiometabolic factors were assessed in separate models., Result(s): A total of 17% of women and 15% of men reported subfertility. In women, subfertility was modestly associated with an increased risk of stroke (age-adjusted hazard ratio [aaHR], 1.19; 95% confidence interval [CI], 1.02-1.39; adjusted hazard ratio [aHR]; 1.18; 95% CI, 1.01-1.37) and coronary heart disease (aaHR, 1.19; 95% CI, 1.06-1.33; aHR, 1.16; 95% CI, 1.03-1.30) compared with fertile women. In men, we observed a weak positive association for stroke (aaHR, 1.11; 95% CI, 0.91-1.34; aHR, 1.10; 95% CI, 0.91-1.33) and a weak inverse association for coronary heart disease (aaHR, 0.92; 95% CI, 0.81-1.05; aHR, 0.93; 95% CI, 0.81-1.06)., Conclusion(s): We observed modestly increased risks of CVD outcomes in women and some weak associations in men, although with no strong statistical evidence on sex differences. We acknowledge that we were only able to include men linked to pregnancies ending at 12 completed gestational weeks or later, potentially resulting in selection bias and misclassification of history of subfertility in analyses of male partners. Despite the large sample size, our results indicate the need for larger studies to obtain precise results in both sexes and determine whether there are true sex differences., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Low birth weight has been associated with a greater risk of cardiovascular disease (CVD). However, the interaction between low birth weight and adult lifestyle factors on the risk of CVD remains unclear., Methods: We included 20,169 men from the Health Professionals Follow-up Study (HPFS, 1986-2016), 52,380 women from the Nurses' Health Study (NHS, 1980-2018), and 85,350 women from the Nurses' Health Study II (NHS II, 1991-2017) in the USA who reported birth weight and updated data on adult body weight, smoking status, physical activity, and diet every 2-4 years. Incident cases of CVD, defined as a combined endpoint of fatal and nonfatal coronary heart disease (CHD) and stroke, were self-reported and confirmed by physicians through reviewing medical records., Findings: During 4,370,051 person-years of follow-up, 16,244 incident CVD cases were documented, including 12,126 CHD and 4118 stroke cases. Cox proportional hazards regression models revealed an increased risk of CHD during adulthood across categories of decreasing birth weight in all cohorts (all  P  for linear trend <0.001). Additionally, we found an additive interaction between decreasing birth weight and unhealthy lifestyles on the risk of CHD among women, with a pooled relative excess risk due to interaction of 0.06 (95% CI: 0.04-0.08). The attributable proportions of the joint effect were 23.0% (95% CI: 11.0-36.0%) for decreasing birth weight alone, 67.0% (95% CI: 58.0-75.0%) for unhealthy lifestyle alone, and 11.0% (95% CI: 5.0-17.0%) for their additive interaction. Lower birth weight was associated with a greater stroke risk only among women, which was independent of later-life lifestyle factors., Interpretation: Lower birth weight may interact synergistically with unhealthy lifestyle factors in adulthood to further increase the risk of CHD among women., Funding: The National Institutes of Health grants., Competing Interests: E.B.R. reports financial support from USDA/United States Highbush Blueberry Council, outside the submitted work. J.E.C. reports financial support from the National Institutes of Health, US Food and Drug Administration, US Centers for Disease Control and Prevention, Harvard Health Publications, Caixa Foundation, American Society for Reproductive Medicine, Northwestern University, Pacific Coast Reproductive Society, Medical University of Vienna, outside the submitted work. All other authors declare no competing interests., (© 2022 The Authors.)

Objective: Women who experience adverse pregnancy outcomes (APO) are at increased risk for cardiovascular disease (CVD); however, their knowledge of CVD risk is not well characterized. We aimed to evaluate knowledge and perception of CVD risk in young women and to determine whether these factors differ based on experience of an APO., Methods: We conducted a cross-sectional study among women with a recent live birth at an urban medical center. Knowledge and perception of CVD risk were assessed through a self-administered online survey adapted from the American Heart Association Survey of Women's CVD Awareness., Results: Of 5612 individuals contacted between 3/1/21 and 4/18/21, 714 completed the survey; the mean (SD) age was 34 (4) years and 25% reported an APO. While 62% of respondents identified CVD as the leading cause of death in women, there was no significant difference in CVD knowledge scores between participants who reported experiencing an APO and those who did not (6.9 vs 6.8 out of 10; p = 0.51). Participants who reported experiencing an APO had higher perception of personal risk for CVD (adjusted odds ratio, 2.64 [95% CI 1.83-3.80]) compared with participants who did not. Half of participants who experienced an APO reported perceiving average, or below average, risk for CVD and only 41 (22.5%) reported speaking with a healthcare professional about CVD within the past year., Conclusions: Gaps remain in knowledge of CVD risk among young women, particularly after an APO. The peripartum period may represent a unique opportunity for targeted education when healthcare engagement is high., Competing Interests: 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., (© 2022 Published by Elsevier B.V.)

Background: Appropriate gestational weight gain (GWG) is important for optimal pregnancy outcomes. This study prospectively evaluated the associations between GWG during the second and third trimesters of pregnancy and adverse pregnancy outcomes in an urban Tanzanian pregnancy cohort., Methods: We used data from a randomized clinical trial conducted among pregnant women recruited by 27 weeks of gestation in Dar es Salaam, Tanzania (N = 1230). Women's gestational weight was measured at baseline and at monthly antenatal visits. Weekly GWG rate during the second and third trimesters was calculated and characterized as inadequate, adequate, or excessive, in conjunction with measured or imputed early-pregnancy BMI status according to the 2009 Institute of Medicine (IOM) GWG guidelines. We used multivariable Poisson regression with a sandwich variance estimator to calculate risk ratios (RR) for associations of GWG with low birth weight, preterm birth, small for gestational age (SGA), and large for gestational age (LGA). Degree of appropriate GWG defined using additional metrics (i.e., percentage of adequacy, z-score) and potential effect modification by maternal BMI were additionally evaluated., Results: According to the IOM guidelines, 517 (42.0%), 270 (22.0%), and 443 (36.0%) women were characterized as having inadequate, adequate, and excessive GWG, respectively. Overall, compared to women with adequate GWG, women with inadequate GWG had a lower risk of LGA births (RR = 0.54, 95% CI: 0.36-0.80) and a higher risk of SGA births (RR = 1.32, 95% CI: 0.95-1.81). Women with inadequate GWG as defined by percentage of GWG adequacy had a higher risk of LBW (OR = 1.93, 95% CI: 1.03-3.63). In stratified analyses by early-pregnancy BMI, excessive GWG among women with normal BMI was associated with a higher risk of preterm birth (RR = 1.59, 95% CI: 1.03-2.44)., Conclusions: A comparatively high percentage of excessive GWG was observed among healthy pregnant women in Tanzania. Both inadequate and excessive GWGs were associated with elevated risks of poor pregnancy outcomes. Future studies among diverse SSA populations are warranted to confirm our findings, and clinical recommendations on optimal GWG should be developed to promote healthy GWG in SSA settings., Trial Registration: This trial was registered as "Prenatal Iron Supplements: Safety and Efficacy in Tanzania" (NCT01119612; http://clinicaltrials.gov/show/NCT01119612 )., (© 2022. The Author(s).)

Background: Hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia, are associated with an increased risk of CVD., Objectives: The purpose of this study was to evaluate associations between HDP and long-term CVD and identify the proportion of the association mediated by established CVD risk factors., Methods: Parous participants without CVD in the Nurses' Health Study II (n = 60,379) were followed for incident CVD from first birth through 2017. Cox proportional hazards models estimated HRs and 95% CIs for the relationship between HDP and CVD, adjusting for potential confounders, including prepregnancy body mass index, smoking, and parental history of CVD. To evaluate the proportion of the association jointly accounted for by chronic hypertension, hypercholesterolemia, type 2 diabetes, and changes in body mass index, we used the difference method., Results: Women with HDP in first pregnancy had a 63% higher rate of CVD (95% CI: 1.37-1.94) compared with women with normotensive pregnancies. This association was mediated by established CVD risk factors (proportion mediated = 64%). The increased rate of CVD was higher for preeclampsia (HR: 1.72; 95% CI: 1.42-2.10) than gestational hypertension (HR: 1.41; 95% CI: 1.03-1.93). Established CVD risk factors accounted for 57% of the increased rate of CVD for preeclampsia but 84% for gestational hypertension (both P < 0.0001)., Conclusions: Established CVD risk factors arising after pregnancy explained most (84%) of the increased risk of CVD conferred by gestational hypertension and 57% of the risk among women with preeclampsia. Screening for chronic hypertension, hypercholesterolemia, type 2 diabetes, and overweight/obesity after pregnancy may be especially helpful in CVD prevention among women with a history of HDP., Competing Interests: Funding Support and Author Disclosures This research was funded by the following grants from the National Institutes of Health: U01 CA176726, R01 HL088521, R01 HL34594, and U01 HL145386. This work was supported by awards from the American Heart Association (12PRE9110014, 13GRNT17070022). Dr Stuart was supported by Training Grant T32HL098048 from the National Heart, Lung, and Blood Institute and by Training Grant T32HD060454 from the National Institute of Child Health and Human Development. Dr Tanz was supported by F31HL131222 from the National Heart, Lung, and Blood Institute under the Ruth L. Kirschstein National Research Service Award. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Historically, females have been underrepresented in clinical trials evaluating the safety and efficacy of investigational drugs and devices. We assessed participation by sex in recent clinical trials., Methods: We extracted data over a 4-year period (2016-2019) from ClinicalTrials.gov on US-based, pharmaceutical industry or government-funded Phase 1-3 clinical trials of drugs and devices. We included trials with adult cardiovascular, psychiatric, and cancer endpoints whose protocol planned to enroll both sexes. Average proportions of females enrolled per trial were described overall and by disease area., Results: Across 1433 trials including 302,664 participants in our analysis, on average, 41.2% were female. Females were underrepresented compared with their proportion of the disease population in cardiovascular disease trials (41.9% female participants vs. 49% female population with cardiovascular disease). In psychiatry, where females comprise 60% of patients, the mean participation of females in clinical trials was 42.0%. Similarly, for cancer trials, where 51% of patients are female, only 41.0% of cancer clinical trial participants were female. For each therapeutic area analyzed, the participation of females in clinical trials fell short of the benchmark derived from national prevalence data., Conclusions: While the participation of females in clinical trials has improved compared to previous reports, sex-based gaps still persist between trial populations and those expected to use these drugs/devices based on distributions of diseases in the population. Given potential sex-based differences in treatment responses and toxicities, adequate inclusion of females in clinical trials remains critical., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Healthy maternal diets during pregnancy are an important protective factor for pregnancy-related outcomes, including gestational weight gain (GWG) and birth outcomes. We prospectively examined the associations of maternal dietary diversity and diet quality, using Minimum Dietary Diversity for Women (MDD-W) and Prime Diet Quality Score (PDQS), with GWG and birth outcomes among women enrolled in a trial in Tanzania (n = 1190). MDD-W and PDQS were derived from a baseline food frequency questionnaire. Women were monthly followed until delivery, during which weight was measured. GWG was classified based on the 2009 Institute of Medicine guidelines. Adverse birth outcomes were classified as low birth weight (LBW), small for gestational age, large for gestational age, and preterm birth. 46.2% participants had MDD-W ≥ 5. Mean score of PDQS was 23.3. Maternal intakes of nuts, poultry, and eggs were low, whereas intakes of sugar-sweetened beverages and refined grains were high. MDD-W was not associated with GWG or birth outcomes. For PDQS, compared to the lowest tertile, women in the highest tertile had lower risk of inappropriate GWG (risk ratio [RR] = 0.93, 95% confidence interval [CI]: 0.87-1.00). Women in the middle tertile group of PDQS (RR = 0.72, 95% CI: 0.51-1.00) had lower risk of preterm birth. After excluding women with prior complications, higher PDQS was associated with lower risk of LBW (middle tertile: RR = 0.55, 95% CI: 0.31-0.99, highest tertile: RR = 0.52, 95% CI: 0.29-0.94; continuous per SD: RR = 0.77, 95% CI: 0.60-0.99). Our findings support continuing efforts to improve maternal diet quality for optimal GWG and infant outcomes among Tanzanian women., (© 2021 The Authors. Maternal & Child Nutrition published by John Wiley & Sons Ltd.)

Background: Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) severity have been limited and inconsistent., Objective: We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infection and COVID-19 severity., Methods: We used data from periodic surveys (May 2020 to March 2021) within the Nurses' Health Study II. Among 39,315 participants, 1768 reported a positive test for SARS-CoV-2 infection. Usual vitamin D intake from foods and supplements were measured using a semiquantitative, pre-pandemic food-frequency questionnaire in 2015. Predicted 25-hydroxyvitamin D [25(OH)D] concentration were calculated based on a previously validated model including dietary and supplementary vitamin D intake, UV-B, and other behavioral predictors of vitamin D status., Results: Higher predicted 25(OH)D concentrations, but not vitamin D intake, were associated with a lower risk of SARS-CoV-2 infection. Comparing participants in the highest quintile of predicted 25(OH)D concentrations with the lowest, the multivariable-adjusted OR was 0.76 (95% CI: 0.58, 0.99; P-trend = 0.04). Participants in the highest quartile of UV-B (OR: 0.76; 95% CI: 0.66, 0.87; P-trend = 0.002) and UV-A (OR: 0.76; 95% CI: 0.66, 0.88; P-trend < 0.001) also had a lower risk of SARS-CoV-2 infection compared with the lowest. High intake of vitamin D from supplements (≥400 IU/d) was associated with a lower risk of hospitalization (OR: 0.51; 95% CI: 0.29, 0.91; P-trend = 0.04)., Conclusions: Our study provides suggestive evidence on the association between higher predicted circulating 25(OH)D concentrations and a lower risk of SARS-CoV-2 infection. Greater intake of vitamin D supplements was associated with a lower risk of hospitalization. Our data also support an association between exposure to UV-B or UV-A, independently of vitamin D and SARS-CoV-2 infection, so results for predicted 25(OH)D need to be interpreted cautiously., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)