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OBJECTIVE: To examine the association between dietary folate intake and antral follicle count (AFC) among women seeing treatment for infertility. DESIGN: Cohort study SETTING: Academic fertility center PATIENTS: 552 women attending the Massachusetts General Hospital Fertility Center (2007-2019) who participated in the Environment and Reproductive Health Study. INTERVENTION(S): None. Folate intake was measured using a validated food frequency questionnaire at study entry. Multivariable Poisson regression models with robust standard errors were used to estimate the association of folate intake with AFC adjusting for calorie intake, age, BMI, physical activity, education, smoking status, year of AFC, and intakes of vitamin B12, iron, and vitamin D. Non-linearity was assessed with restricted cubic splines. MAIN OUTCOME MEASURES: AFC as measured with transvaginal ultrasonography as part of routine care. RESULTS: Among the 552 women (median age 35.0 years, median folate intake 1,005 μg/day), total and supplemental folate intake had a significant non-linear relationship with AFC (P for non-linearity 0.05 and 0.02, respectively). There was a positive linear association with AFC up to approximately 1200 μg/day for total folate intake and up to 800 μg/day for supplemental folate intake; however, there was no additional benefit of higher folate intakes. The magnitude of association was modest – for example, the predicted adjusted difference in AFC between a woman consuming 400 versus 800 μg/day of supplemental folate was approximately 1.5 follicles. CONCLUSIONS: Higher intake of folate, particularly from supplements, was associated with modestly higher ovarian reserve as measured by AFC among women attending a fertility center. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT00011713

Background: Emerging evidence suggests beneficial impacts of plant-based diets on glucose metabolism among generally healthy individuals. Whether adherence to these diets is related to risk of gestational diabetes mellitus (GDM) is unknown. Objectives: We aimed to examine associations between plant-based diets and GDM in a large prospective study. Methods: We included 14,926 women from the Nurses' Health Study II (1991-2001), who reported ≥1 singleton pregnancy and without previous GDM before the index pregnancy. Prepregnancy adherence to plant-based diets was measured by an overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI) as assessed by FFQs every 4 y. Incident first-Time GDM was ascertained from a self-reported physician diagnosis, which was previously validated by review of medical records. We used log-binomial models with generalized estimating equations to calculate RRs and 95% CIs for associations of PDIs with GDM. Results: We documented 846 incident GDM cases over the 10-y follow-up among 20,707 pregnancies. Greater adherence to the PDI and hPDI was associated with lower GDM risk. For the PDI, the multivariable-Adjusted RR (95% CI) comparing the highest and lowest quintiles (Q5 compared with Q1) was 0.70 (0.56, 0.87) (Ptrend = 0.0004), and for each 10-point increment was 0.80 (0.71, 0.90). For the hPDI, the RR (95% CI) of Q5 compared with Q1 was 0.75 (0.59, 0.94) (Ptrend = 0.009) and for each 10-point increment was 0.86 (0.77, 0.95). After further adjustment for prepregnancy BMI, the associations were attenuated but remained significant: for the PDI, the RR (95% CI) for each 10-point increment was 0.89 (0.79, 1.00) and the corresponding RR (95% CI) was 0.89 (0.80, 0.99) for the hPDI. The uPDI was not associated with GDM. Conclusions: Our study suggests that greater prepregnancy adherence to a healthful plant-based diet was associated with lower risk of GDM, whereas an unhealthful plant-based diet was not related to GDM risk.

Objective To examine the impact of men’s diet on outcomes of infertility treatment with assisted reproductive technology (ART) using an empirical score representing the relation of diet with semen quality. Design Prospective cohort study. Setting Fertility center at an academic medical center. Patient(s) We included 296 men (688 semen samples) to identify an empirical dietary pattern and 231 couples (406 ART cycles) to investigate the association of this diet pattern with ART outcomes. Intervention(s) Men’s diet was assessed at baseline using a validated questionnaire. An empirical dietary pattern reflecting the overall relation of diet with semen quality was identified using reduced rank regression. Main Outcome Measure(s) The primary outcome was live birth per treatment cycle. The secondary outcomes were fertilization, implantation, and clinical pregnancy. Result(s) Men had a median baseline age and body mass index of 36.8 years and 26.9 kg/m2, respectively. Although the empirical diet pattern was significantly associated with all semen parameters, the empirical diet score was not related to any clinical outcome of infertility treatment after ART. The adjusted probabilities of relevant clinical outcomes in the lowest and highest quartiles of the empirical score were 0.62 (0.50–0.73) and 0.55 (0.45–0.66) for implantation, 0.57 (0.46–0.69) and 0.50 (0.40–0.61) for clinical pregnancy, and 0.49 (0.37–0.62) and 0.36 (0.25–0.48) for live birth. Analyses excluding couples with a diagnosis of male factor infertility and, separately, excluding intracytoplasmic sperm injection cycles yielded similar results. Conclusion(s) A dietary score representing the overall association of diet with semen quality parameters was not associated with ART outcomes.

Objectives: To quantify adequacy of personal protective equipment (PPE) for U.S. healthcare personnel (HCP) at the outset of the COVID-19 pandemic and its association with infection risk. Methods: March–May 2020 survey of the national Nurses’ Health Studies and the Growing Up Today study regarding self-reported PPE access, use, and reuse. COVID-19 endpoints included SARS-CoV-2 tests and COVID-19 status predicted from symptoms. Results: Nearly 22% of 22,232 frontline HCP interacting with COVID-19 patients reported sometimes or always lacking PPE. Fifty percent of HCP reported not needing respirators, including 13% of those working in COVID-19 units. Lack of PPE was cross-sectionally associated with two-fold or greater odds of COVID-19 among those who interacted with infected patients. Conclusion: These data show the need to improve the U.S. infection prevention culture of safety when confronting a novel pathogen.

PURPOSE(S): To evaluate the relationship of men’s dietary patterns with outcomes of in vitro fertilization (IVF). METHODS: This is a prospective cohort study including 231 couples with 407 IVF cycles, presented at an academic fertility center from April 2007 to April 2018. We assessed diet with a validated food frequency questionnaire and identified Dietary Pattern 1 and Dietary Pattern 2 using principal component analysis. We evaluated adjusted probability of IVF outcomes across the quartiles of the adherence to two dietary patterns by generalized linear mixed models. RESULTS: Men had a median age of 36.8 years and BMI of 26.9 kg/m(2). Women’s median age and BMI were 35.0 years and 23.1 kg/m(2), respectively. Adherence to Dietary Pattern 1 (r(Pearson)=0.44) and Dietary Pattern 2 (r(Pearson)=0.54) was positively correlated within couples. Adherence to Dietary Pattern 1 was positively associated with sperm concentration. A 1-unit increase in this pattern was associated with a 13.33 (0.71–25.96) million/mL higher sperm concentration. However, neither Dietary Pattern 1 nor Dietary Pattern 2 was associated with fertilization, implantation, clinical pregnancy, or live birth probabilities. CONCLUSIONS: Data-derived dietary patterns were associated with semen quality but unrelated to the probability of successful IVF outcomes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10815-021-02251-9.

Background Infertility affects 15-25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives Three overall questions will be studied: 1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? 2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And 3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up? Material and methods ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skane University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of bio-specimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem. This article is protected by copyright. All rights reserved.

ObjectivesTo examine the association of occupational exposure to high-level disinfectants (HLDs) with risk of miscarriage among nurses.MethodsOur study included women who enrolled in the Nurses’ Health Study 3 (2010–2020) and had at least one pregnancy during follow-up. Occupational exposure to HLDs was self-reported at baseline. Every 6 months, a follow-up questionnaire was sent to participants asking for detailed information on pregnancies. We used a discrete-time Cox model to calculate the HRs and 95% CIs of miscarriage according to exposure to HLDs.ResultsOur study included 2579 nurses with a median of 5.6 years of follow-up (range: 1–9 years), and we documented 768 (19%) cases of miscarriage among 3974 pregnancies. Compared with women with no HLD exposure, the HRs of miscarriage were 1.08 (95% CI: 0.87 to 1.34) for past users and 0.84 (95% CI: 0.68 to 1.04) for HLD users. Compared with women with no HLD exposure, duration, frequency, and type of HLD and use of exposure controls were not associated with risk of miscarriage. When restricting to pregnancies that occurred within 12 months of HLD use, occupational exposure to unspecified types of HLD was significantly associated with higher risk of miscarriage (HR=1.78; 95% CI: 1.08 to 2.93).ConclusionsWe observed no associations between occupational use of HLDs and miscarriage, except when we restricted to pregnancies occurring within 12 months of assessed baseline exposure. Given the observational design and limited sample size, results should be interpreted cautiously.

PURPOSE: Extensive prior research has shown that sexual minority women are more likely to have a number of cancer risk factors, thereby putting them at higher risk for cancer than heterosexual women. However, there has been little research evaluating the association between sexual orientation and diet quality. METHODS: Data come from participants (aged 24–54 years) enrolled in Nurses’ Health Study 3, an ongoing, U.S.-based cohort study (N=15,941). We measured diet using recommendations from the Dietary Approach to Stop Hypertension (DASH) and American Health Association (AHA) 2020 Strategic Impact Goals. RESULTS: We found limited evidence of differences across diet quality by sexual orientation. When examining predicted DASH scores, mostly heterosexual [predicted mean score (95% confidence interval), 24.0 (23.8, 24.3)] and lesbian [24.3 (23.8, 24.9)] women had healthier predicted DASH scores than the reference group of completely heterosexual women with no same-sex partners [23.6 (23.5, 23.7)]. Even though certain sexual minority women had overall healthier predict DASH scores, their consumption of certain food groups—low-fat dairy and fruit—was lower than completely heterosexual women with no same-sex partners. When measuring AHA scores, most sexual minority groups (completely heterosexual women with same-sex partners, mostly heterosexual women, and lesbian women) had higher diet quality compared to the reference group of completely heterosexual women with no same-sex partners. CONCLUSION: Sexual minority women, particularly mostly heterosexual women and lesbian women, had healthier diet quality than completely heterosexual women with no same-sex partners. These data suggest that cancer risk factors (e.g., smoking, drinking, and inactivity) other than diet would drive higher cancer rates among sexual minority compared to heterosexual women. Nonetheless, it is critical for all women to improve their diet quality since diet quality was poor among participants of all sexual orientations.

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

BACKGROUND Cesarean delivery has been linked with childhood obesity. Few studies have examined if this association is attenuated if there is labor prior to delivery. The objective of this current analysis was to examine the association of cesarean vs. vaginal delivery with measures of childhood adiposity, and whether the association differs by labor type (spontaneous, induced, or absent) preceding cesarean delivery. METHODS We ascertained delivery mode and type of labor from medical records in 1443 mother-child dyads from Project Viva with adiposity measures from at least one follow-up visit (3369 total observations) in early childhood (median age 3.2 y), mid-childhood (median 7.7 y), or early teen (median 12.9 y). Child adiposity outcomes were CDC age- and sex-specific body mass index (BMI) z-scores, sum of subscapular and triceps skinfold thicknesses (SS + TR; mm), and waist circumference (cm). We used linear regression models with generalized estimating equation estimates and adjusted for maternal age, education, race/ethnicity, prepregnancy BMI, rate of gestational weight gain, and child sex and age at outcome. RESULTS A total of 333 (23%) women delivered via cesarean, including 155 (11%) with spontaneous labor, 74 (5%) with induced labor, 99 (7%) with no labor, and 5 (

Secular trends in earlier initiation of puberty have been observed in recent decades. One risk factor appears to be increases in adiposity, as measured by body mass index. This trend is particularly notable among Latino populations, who have higher rates of overweight/obesity compared with non-Latino White youth. Previous research has focused primarily on White girls, resulting in data gaps regarding male puberty and among potentially high-risk populations. Using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, we examined body mass index at age 5 years (2005–2006) and multiple markers of pubertal onset, assessed repeatedly and longitudinally at 7 in-person visits, starting at age 9 and continuing through age 14 (2009–2015), among 336 Mexican Americans in Salinas, California. We observed no associations among boys, but found significantly earlier thelarche in overweight (HR = 1.7, 95% CI: 1.1, 2.7) and obese girls (HR = 1.5, 95% CI: 1.0, 2.4), menarche in overweight girls (HR = 1.6; CI: 1.0, 2.4), and pubarche in obese girls (HR = 1.9; CI: 1.2, 3.0), compared with normal-weight girls. This study examined an understudied population and included key covariates, such as birth weight and early adverse events, which are typically omitted in studies.

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

The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; COVID-19) pandemic presents challenges to the real-time collection of population-scale data to inform near-term public health needs as well as future investigations. We established the COronavirus Pandemic Epidemiology (COPE) consortium to address this unprecedented crisis on behalf of the epidemiology research community. As a central component of this initiative, we have developed a COVID Symptom Study (previously known as the COVID Symptom Tracker) mobile application as a common data collection tool for epidemiologic cohort studies with active study participants. This mobile application collects information on risk factors, daily symptoms, and outcomes through a user-friendly interface that minimizes participant burden. Combined with our efforts within the general population, data collected from nearly 3 million participants in the United States and United Kingdom are being used to address critical needs in the emergency response, including identifying potential hot spots of disease and clinically actionable risk factors. The linkage of symptom data collected in the app with information and biospecimens already collected in epidemiology cohorts will position us to address key questions related to diet, lifestyle, environmental, and socioeconomic factors on susceptibility to COVID-19, clinical outcomes related to infection, and long-term physical, mental health, and financial sequalae. We call upon additional epidemiology cohorts to join this collective effort to strengthen our impact on the current health crisis and generate a new model for a collaborative and nimble research infrastructure that will lead to more rapid translation of our work for the betterment of public health.

Background: Physical activity and sleep are behavioral risk factors for cancer that may be influenced by environmental exposures, including built and natural environments. However, many studies in this area are limited by residence-based exposure assessment and/or self-reported, time-aggregated measures of behavior. Methods: The Nurses' Health Study 3 (NHS3) Mobile Health Substudy is a pilot study of 500 participants in the prospective NHS3 cohort who use a smartphone application and a Fitbit for seven-day periods, four times over a year, to measure minute-level location, physical activity, heart rate, and sleep. Results: We have collected data on 435 participants, comprising over 6 million participant-minutes of heart rate, step, sleep, and location. Over 90% of participants had five days of ≥600 minutes of Fitbit wear-time in their first sampling week, and this percentage dropped to 70% for weeks 2 to 4. Over 819 sampling weeks, we observed an average of 7,581 minutes of heart rate and step data [interquartile range (IQR): 6,651–9,645] per participant-week, and >2 million minutes of sleep in over 5,700 sleep bouts. We have recorded location data for 5,237 unique participant-days, averaging 104 location observations per participant-day (IQR: 103–107). Conclusions: This study describes a protocol to incorporate mobile health technology into a nationwide prospective cohort to measure high-resolution objective data on environment and behavior. Impact: This project could provide translational insights into interventions for urban planning to optimize opportunities for physical activity and healthy sleep patterns to reduce cancer risk. See all articles in this CEBP Focus section, “Modernizing Population Science.”

BACKGROUND The role of diet on hypertensive disorders of pregnancy (HDPs), including preeclampsia and gestational hypertension (GHTN), remains unclear. OBJECTIVES We evaluated whether adherence during pregnancy to dietary recommendations that reduce cardiovascular disease (CVD) in the general population is related to the risk of HDPs. METHODS We followed 66,651 singleton pregnancies from 62,774 women participating in the Danish National Birth Cohort. Diet was assessed during week of gestation 25 with an FFQ from which we created 2 dietary pattern scores: 1) AHA, based on the diet recommendations from the AHA 2020 Strategic Impact Goals; and 2) the Dietary Approaches to Stop Hypertension (DASH) diet. Cases of HDPs were identified through linkage with the Danish National Patient Registry. RRs and 95% CIs of HDPs were estimated by increasing quintiles of adherence to the AHA and DASH scores using log-Poisson regression models with generalized estimating equations-to account for repeated pregnancies per woman-while adjusting for potential confounders. RESULTS We identified 1809 cases of HDPs: n = 1310 preeclampsia (n = 300 severe preeclampsia) and n = 499 cases of GHTN. Greater adherence to AHA or DASH scores was not related to the risk of HDPs. However, when each component of the scores was separately evaluated, there were positive linear relations of sodium intake with HDPs (P-linearity

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

This cohort study investigates associations between the mode of obstetric delivery and body composition measured by dual-energy x-ray absorptiometry among offspring during middle childhood and early adolescence., Key Points Question Are there differences in body composition measured by dual-energy x-ray absorptiometry during middle childhood and early adolescence among children born by cesarean delivery vs vaginal delivery? Findings In this cohort study of 975 mother-child pairs, adolescents born by cesarean delivery had significantly higher measures of lean mass, fat mass, and central adiposity compared with those born by vaginal delivery, but associations did not remain after adjustment for the mothers’ self-reported prepregnancy body mass index. Meaning The findings suggest that prepregnancy body mass index may partly explain the association between birth by cesarean delivery and adiposity in adolescence., Importance Although the literature on the association between birth by cesarean delivery and children’s anthropometry has continued to increase, only a few studies have examined the association of cesarean delivery with measures of body composition assessed using dual-energy x-ray absorptiometry (DXA), which allows the differentiation of fat and lean mass overall and in specific regions of the body. Objective To investigate whether differences exist in DXA-measured body composition between children and adolescents born by cesarean delivery and those born by vaginal delivery. Design, Setting, and Participants This prospective cohort study included singleton children of mothers enrolled between April 1999 and July 2002 in Project Viva, a longitudinal prebirth cohort of mother-child pairs in Massachusetts. The children had at least 1 DXA scan at a follow-up visit during middle childhood (2007-2010) and/or early adolescence (2013-2016). Data analysis was performed from October 16, 2020, to May 9, 2021. Exposures Mode of delivery (cesarean vs vaginal). Main Outcomes and Measures Total lean mass index, total and truncal fat mass indexes, visceral adipose tissue (VAT), subcutaneous abdominal adipose tissue, and total abdominal adipose tissue (TAAT) were estimated using DXA. Multivariable linear regression models were used to estimate the association between mode of delivery and DXA-derived outcomes with adjustment for confounders. Stabilized inverse probability weights were used to control for potential selection bias owing to loss to follow-up. Results A total of 975 mother-child pairs were included in the study. The mean (SD) maternal age at study entry was 32.0 (5.5) years, and the mean (SD) self-reported prepregnancy body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) was 25.0 (5.4). Of the children included in the study, 491 (50%) were female; 212 (22%) were born by cesarean delivery and 763 (78%) by vaginal delivery. Body composition in middle childhood as measured by DXA did not differ by mode of delivery. In early adolescence, participants born by cesarean delivery had a significantly greater total lean mass index (β, 0.4; 95% CI, 0.0-0.7), total fat mass index (β, 0.6; 95% CI, 0.1-1.1), truncal fat mass index (β, 0.3; 95% CI, 0.0-0.5), VAT area (β, 4.7; 95% CI, 0.9-8.6), and TAAT area (β, 23.8; 95% CI, 0.8-46.8) in a model adjusted for child sex and age at the time of DXA measurements; maternal age, educational level, race and ethnicity, total gestational weight gain, and smoking status during pregnancy; birth-weight-per-gestational-age z score; and paternal BMI. Associations between mode of delivery and measures of adiposity were found for cesarean deliveries performed in the absence of labor (total fat mass index: β, 1.3; 95% CI, 0.3-2.3; truncal fat mass index: β, 0.6; 95% CI, 0.1-1.0; VAT area: β, 10.7; 95% CI, 3.1-18.3; TAAT area: β, 47.3; 95% CI, 2.3-92.2). There were no associations after adjustment for maternal self-reported prepregnancy BMI (total lean mass index: β, 0.2; 95% CI, –0.1 to 0.6; total fat mass index: β, 0.4; 95% CI, –0.1 to 0.9; truncal fat mass index: β, 0.2; 95% CI, –0.1 to 0.4; VAT area: β, 3.0; 95% CI, –0.6 to 6.7; TAAT area: β, 13.6; 95% CI, –8.2 to 35.3). Conclusions and Relevance In this cohort study, adolescents born by cesarean delivery had significantly higher measures of lean mass, fat mass, and central adiposity compared with those born by vaginal delivery, but associations did not remain after adjustment for the mothers’ self-reported prepregnancy BMI. The findings suggest that the association between birth by cesarean delivery and adolescent adiposity may partly be explained by maternal self-reported prepregnancy BMI.

This cohort study uses data from the Nurses’ Health Study II to assess the association between habitual alcohol consumption and subsequent risk for type 2 diabetes among women with a history of gestational diabetes., Key Points Question Among women with a history of gestational diabetes, is there an association of habitual alcohol intake with subsequent risk for type 2 diabetes? Findings In this cohort study of 4740 women with a history of gestational diabetes, after adjustment for major dietary and lifestyle factors and body mass index, women who consumed 5.0-14.9 g/d had a 41% lower risk for developing incident type 2 diabetes compared with those who did not consume any alcohol. Meaning These findings should be interpreted in the context of other known risks and benefits of alcohol consumption when considering clinical recommendations for individual women with a history of gestational diabetes., Importance Women with gestational diabetes are at high risk for type 2 diabetes. Identifying modifiable dietary and lifestyle factors, such as alcohol intake, that can be useful in delaying or preventing progression to overt type 2 diabetes is of particular interest. Objective To evaluate the association between alcohol consumption and risk for type 2 diabetes among women with a history of gestational diabetes. Design, Setting, and Participants This cohort study included women from the Nurses’ Health Study II cohort who reported a history of gestational diabetes and were followed up from January 1, 1991, to December 31, 2017, as part of the Diabetes & Women’s Health Study. Data analysis was performed from 2020 to 2021. Exposures Dietary intakes, including alcohol, were assessed every 4 years using validated food-frequency questionnaires. Main Outcomes and Measures Multivariable Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs for the association of alcohol intake with risk for incident type 2 diabetes after a pregnancy during which gestational diabetes was diagnosed. Results A total of 4740 women were included in the study; the mean (SD) age at baseline was 38.2 (5.0) years, and the median follow-up time was 24 years (interquartile range, 18-28 years), resulting in 78 328 person-years of follow-up. During this period, 897 incident cases of type 2 diabetes were reported. After adjustment for major dietary and lifestyle factors, compared with women who did not consume any alcohol, only alcohol consumption of 5.0 to 14.9 g/d was associated with decreased risk for incident type 2 diabetes (HR, 0.45; 95% CI, 0.33-0.61); there was no association of alcohol consumption of 0.1 to 4.9 g/d or 15.0 g/d or more (maximum, 74.2 g/d) with risk of type 2 diabetes (0.1 to 4.9 g/d: HR, 0.87 [95% CI, 0.73-1.03]; ≥15.0 g/d: HR, 0.62 [95% CI, 0.37-1.04]). After additional adjustment for body mass index, women who reported alcohol consumption of 5.0 to 14.9 g/d had a 41% lower risk for developing incident type 2 diabetes (HR, 0.59; 95% CI, 0.42-0.81); consumption of 0.1 to 4.9 g/d and consumption of 15.0 g/d or more were still not associated with risk of type 2 diabetes, but the results were attenuated (0.1-4.9 g/d: HR, 1.02 [95% CI, 0.85-1.23]; ≥15.0 g/d: HR, 0.75 [95% CI, 0.42-1.33]). Conclusions and Relevance In this cohort study, among women with a history of gestational diabetes, usual alcohol intake of 5.0 to 14.9 g/d (approximately 0.5-1 drinks per day) was associated with a lower risk for type 2 diabetes. These findings should be interpreted in the context of other known risks and benefits of alcohol consumption when considering clinical recommendations for individual women with a history of gestational diabetes.

AIMS/HYPOTHESIS: Menstrual cycle dysfunction has been associated with many endocrine-related diseases, but evidence linking menstrual cycle dysfunction with gestational diabetes mellitus (GDM) is scant. The current study investigated the association of pre-pregnancy menstrual cycle regularity and length during adolescence, early adulthood and mid-adulthood with the subsequent risk of GDM. METHODS: Between 1993 and 2009, we followed 10 906 premenopausal women participating in the Nurses' Health Study II who reported menstrual cycle characteristics during adolescence (age 14-17 years), early adulthood (age 18-22 years) and mid-adulthood (age 29-46 years). Incident GDM was ascertained from a self-reported questionnaire regarding physician diagnosis. Log-binomial models with generalised estimating equations were used to estimate the RRs and 95% CI for the associations between menstrual cycle characteristics and GDM. RESULTS: We documented 578 incident cases of GDM among 14 418 pregnancies over a 16 year follow-up. After adjusting for potential confounders, women reporting always having irregular menstrual cycles during mid-adulthood had a 65% (95% CI 21, 125%) higher risk of GDM than women reporting very regular cycles. GDM risk was also greater among women reporting that their cycles were usually ≥32 days during mid-adulthood, compared with women reporting cycles between 26 and 31 days (RR 1.42 [95% CI 1.15, 1.75]). The risk of GDM was greater for women whose cycles changed from regular early in their reproductive years to irregular or from

ObjectivePoor metabolic health and certain lifestyle factors have been associated with risk and severity of coronavirus disease 2019 (COVID-19), but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its intersection with socioeconomic deprivation.DesignWe used data from 592,571 participants of the smartphone-based COVID Symptom Study. Diet quality was assessed using a healthful plant-based diet score, which emphasizes healthy plant foods such as fruits or vegetables. Multivariable Cox models were fitted to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for COVID-19 risk and severity defined using a validated symptom-based algorithm or hospitalization with oxygen support, respectively.ResultsOver 3,886,274 person-months of follow-up, 31,815 COVID-19 cases were documented. Compared with individuals in the lowest quartile of the diet score, high diet quality was associated with lower risk of COVID-19 (HR, 0.91; 95% CI, 0.88-0.94) and severe COVID-19 (HR, 0.59; 95% CI, 0.47-0.74). The joint association of low diet quality and increased deprivation on COVID-19 risk was higher than the sum of the risk associated with each factor alone (Pinteraction=0.005). The corresponding absolute excess rate for lowest vs highest quartile of diet score was 22.5 (95% CI, 18.8-26.3) and 40.8 (95% CI, 31.7-49.8; 10,000 person-months) among persons living in areas with low and high deprivation, respectively.ConclusionsA dietary pattern characterized by healthy plant-based foods was associated with lower risk and severity of COVID-19. These association may be particularly evident among individuals living in areas with higher socioeconomic deprivation.

OBJECTIVES: To examine the association of adherence to a healthy diet with risk and severity of SARS-CoV-2 infections. METHODS: We included participants from the COVID Symptom Study smartphone application enrolled in March 2020 from the UK and the US who provided information about their sociodemographic characteristics and risk factors for COVID-19 at baseline, and subsequently reported any symptoms they were experiencing over follow-up. We administered a supplementary diet and lifestyle survey between August and September 2020 to ascertain diet quality before the pandemic using a validated 35-item short food frequency questionnaire. We defined incident predicted cases of COVID-19 over follow-up using a validated symptom-based model and a severe case of COVID-19 as a report of hospitalization with requirement of oxygen support. We used Cox models to calculate hazard ratios (HR) and 95% confidence intervals (95% CI) for predicted COVID-19 and severe COVID-19 after adjusting for potential sociodemographic and behavioral confounders. RESULTS: Over 4,044,344 person-months of follow-up, we recorded 33,360 incident COVID-19 cases. Compared with individuals in the lowest quartile of the diet quality score, high diet quality was associated with a reduced risk of predicted COVID-19 (adjusted HR 0.94, 95% CI 0.91 to 0.97) and reduced risk of severe COVID-19 (adjusted HR 0.80, 95% CI 0.65 to 0.99). We found evidence of significant interactions between diet quality and socioeconomic status on COVID-19 risk, in which the attributable risk proportion of the joint effect due to the interaction was 30% (95% CI 2.8 to 57.2). Among participants with higher levels of socioeconomic deprivation, COVID-19 incidence rate per 1,000 person-months was 7.5% for those with low diet quality (95% CI 7.1 to 7.8) compared with 5.5% for those with a high diet quality (95% CI 5.2 to 5.9). CONCLUSIONS: These findings suggest that adherence to a healthy diet is associated with lower risk of COVID-19 infection and severity. The apparent beneficial association of a high-quality diet may be particularly evident among individuals with a higher levels of socioeconomic deprivation. FUNDING SOURCES: Zoe Global, UK Government Department of Health and Social Care, Wellcome Trust, Massachusetts Consortium on Pathogen Readiness

IRET Following a 2019 workshop led by the Center for Global Health Studies at the Fogarty International Center on the topic of childhood obesity prevention and research synergies transpiring from cross-border collaborations, we convened a group of experts in the United States and Latin America to conduct a narrative review of the epidemiological literature on the role of obesogenic endocrine disrupting chemicals (EDCs) in the etiology of childhood obesity among Latino youth in the United States and Latin America. In addition to summarizing and synthesizing results from research on this topic published within the last decade, we place the findings within a lifecourse biobehavioral framework to aid in identification of unique exposure-outcome relationships driven by both biological and behavioral research, identify inconsistencies and deficiencies in current literature, and discuss the role of policy regulations, all with the goal of identifying viable avenues for prevention of early life obesity in Latino/Hispanic populations. Luego de un taller de 2019 dirigido por el Centro de Estudios de Salud Global en el Centro Internacional Fogarty sobre el tema de la prevención de la obesidad infantil y las sinergias de investigación que surgen de las colaboraciones transfronterizas, reunimos a un grupo de expertos en los Estados Unidos y América Latina para llevar a cabo un revisión narrativa de la literatura epidemiológica sobre el papel de los disruptores endocrinos (EDC) obesogénicos en la etiología de la obesidad infantil entre los jóvenes latinos en los Estados Unidos y América Latina. Además de resumir y sintetizar los resultados de la investigación sobre este tema publicada en la última década, colocamos los hallazgos dentro de un marco bioconductual del ciclo de vida para ayudar en la identificación de relaciones únicas de exposición-resultado impulsadas por investigaciones tanto biológicas como conductuales, identificar inconsistencias y deficiencias en literatura actual y discutir el papel de las regulaciones políticas, todo con el objetivo de identificar vías viables para la prevención de la obesidad en la vida temprana en las poblaciones latinas / hispanas. University of Colorado Denver Anschutz Medical Campus, USA Instituto Nacional de Salud Pública, México School of Public Health and Health Professions, USA Brown University, USA University of California Berkeley, USA Universidad Nacional, Costa Rica Universidad de Chile, Chile Universidad de São Paulo, Brasil Harvard T.H. Chan School of Public Health, USA University of Southern California Keck School of Medicine, USA University of Michigan School of Public Health, USA Instituto Regional de Estudios en Sustancias Tóxicas

Background We examined the association between the administration of antineoplastic drugs (AD) and fecundity among female nurses. Methods AD administration and use of exposure controls (EC) such as gloves, gowns, and needleless systems were self-reported at baseline among 2649 participants of the Nurses' Health Study 3, who were actively attempting pregnancy. Every 6 months thereafter, the nurses reported the current duration of their pregnancy attempt. Multivariable accelerated failure time models were used to estimate time ratios (TR) and 95% confidence intervals (CI) adjusted for age, race, body mass index, smoking, marital status, hours of work, and other occupational risk factors. Results Mean (standard deviation) age and BMI at baseline were 30.7 years (4.7) and 26.0 kg/m2 (6.4). Forty-one percent of nurses reported ever administering AD; 30% only in the past and 11% currently. The former administration of AD (TR = 1.02, 95% CI, 0.93-1.12) was unrelated to the ongoing duration of pregnancy attempt. Among nurses currently administering AD, those who had administered AD for 6 years and above had a 27% (95% CI, 6%-53%) longer duration of pregnancy attempt than nurses who never handled ADs in unadjusted analyses. This difference disappeared in multivariable analyses (TR = 1.01, 95% CI, 0.85-1.21). 93% (n = 270) of the nurses currently administering ADs reported consistent use of EC. These nurses had a similar median duration of pregnancy attempt to those who never handled AD (TR = 1.00, 95% CI, 0.87-1.15). Conclusions Administration of ADs did not appear to have an impact on fecundity in a cohort of nurses planning for pregnancy with a high prevalence of consistent ECs. Our results may not be generalizable to women who are less compliant with PPE use or with less availability to ECs. Therefore, it is possible that we did not observe an association between occupational exposure to AD and reduced fecundity because of lower exposure due to the more prevalent use of effective ECs.

Background: Many antineoplastic (chemotherapeutic) drugs are known or probable human carcinogens, and many have been shown to be reproductive toxicants in cancer patients. Evidence from occupational exposure studies suggests that health care workers who have long-term, low-level occupational exposure to antineoplastic drugs have an increased risk of adverse reproductive outcomes. It's recommended that, at minimum, nurses who handle or administer such drugs should wear double gloves and a nonabsorbent gown to protect themselves. But it's unclear to what extent nurses do.This study assessed glove and gown use by female pregnant and nonpregnant nurses who administer antineoplastic drugs in the United States and Canada.We used data collected from more than 40,000 nurses participating in the Nurses' Health Study 3. The use of gloves and gowns and administration of antineoplastic drugs within the past month (among nonpregnant nurses) or within the first 20 weeks of pregnancy (among pregnant nurses) were self-reported via questionnaire.Administration of antineoplastic drugs at any time during their career was reported by 36% of nonpregnant nurses, including 27% who reported administering these drugs within the past month. Seven percent of pregnant nurses reported administering antineoplastic drugs during the first 20 weeks of pregnancy. Twelve percent of nonpregnant nurses and 9% of pregnant nurses indicated that they never wore gloves when administering antineoplastic drugs, and 42% of nonpregnant nurses and 38% of pregnant nurses reported never using a gown. The percentage of nonpregnant nurses who reported not wearing gloves varied by type of administration: 32% of those who administered antineoplastic drugs only as crushed pills never wore gloves, compared with 5% of those who administered such drugs only via infusion.Despite longstanding recommendations for the safe handling of antineoplastic and other hazardous drugs, many nurses-including those who are pregnant-reported not wearing protective gloves and gowns, which are considered the minimum protective equipment when administering such drugs. These findings underscore the need for further education and training to ensure that both employers and nurses understand the risks involved and know which precautionary measures will minimize such exposures.

ObjectivesOccupational use of disinfectants among healthcare workers has been associated with asthma. However, most studies are cross-sectional, and longitudinal studies are not entirely consistent. To limit the healthy worker effect, it is important to conduct studies among early- to mid-career workers. We investigated the prospective association between use of disinfectants and asthma incidence in a large cohort of early- to mid-career female nurses.MethodsThe Nurses’ Health Study 3 is an ongoing, prospective, internet-based cohort of female nurses in the USA and Canada (2010–present). Analyses included 17 280 participants without a history of asthma at study entry (mean age: 34 years) and who had completed ≥1 follow-up questionnaire (sent every 6 months). Occupational use of high-level disinfectants (HLDs) was evaluated by questionnaire. We examined the association between HLD use and asthma development, adjusted for age, race, ethnicity, smoking status and body mass index.ResultsDuring 67 392 person-years of follow-up, 391 nurses reported incident clinician-diagnosed asthma. Compared with nurses who reported ≤5 years of HLD use (89%), those with >5 years of HLD use (11%) had increased risk of incident asthma (adjusted HR (95% CI), 1.39 (1.04 to 1.86)). The risk of incident asthma was elevated but not statistically significant in those reporting >5 years of HLD use and current use of ≥2 products (1.72 (0.88 to 3.34)); asthma risk was significantly elevated in women with >5 years of HLD use but no current use (1.46 (1.00 to 2.12)).ConclusionsOccupational use of HLDs was prospectively associated with increased asthma incidence in early- to mid-career nurses.

Background Few epidemiologic studies have evaluated the impact of paternal environmental exposures, particularly as mixtures, on couples’ pregnancy outcomes. Objective We investigated whether mixtures of paternal urinary bisphenol A (BPA), paraben, and phthalates were associated with pregnancy outcomes among couples attending a fertility center. Methods We included 210 couples undergoing 300 in vitro fertilization (IVF) between 2004 and 2017 in this prospective analysis. We quantified paternal urinary biomarker concentrations in one sample per cycle using isotope-dilution tandem mass spectrometry. We used principal component analysis (PCA) to identify correlations of biomarker concentrations and multivariable Cox proportional hazards models for discrete survival time to estimate the hazard ratios (HRs) and 95% CIs for the associations between PCA-derived factor scores and probability of failing to achieve a live birth. Interactions were also included in the models to examine strength of associations over three vulnerable periods [embryo transfer to implantation, implantation to clinical pregnancy, and clinical pregnancy to live birth]. Models were adjusted for paternal and maternal ages and body mass indexes, urinary dilution (specific gravity) and year of collection, infertility diagnosis, and other PCA factor scores. Sensitivity analyses with further adjustment for maternal PCA factor scores were performed. Results We identified three factors, representing di-2-ethylhexyl phthalate (DEHP) metabolites, BPA and non-DEHP metabolites, and parabens, accounting for 56%, 15% and 10%, respectively, of the total variance explained. An interquartile range (25th and 75th percentiles) increase in the DEHP-related factor score was associated with elevated probability of failing prior to live birth (HR = 1.41, 95% CI: 1.08, 1.81) and the association was stronger between implantation and clinical pregnancy as well as between clinical pregnancy and live birth compared to before implantation. The overall HRs of failure for the BPA/non-DEHP-related and paraben-related factor scores were HR = 1.24 (95% CI: 0.97, 1.59) and HR = 0.99 (95% CI: 0.80, 1.24). We found similar HRs when additionally adjusting for maternal PCA factor scores. Conclusion Paternal mixtures of urinary concentrations of DEHP metabolites were related to higher infertility treatment failure.

Background We assessed differences in plasma levels of metabolic health and inflammation biomarkers during mid-childhood and early adolescence between children born by cesarean section vs. vaginal delivery. Methods Mother–child pairs (N = 942) enrolled during pregnancy in obstetric practices and child follow-up started at birth. Risk biomarkers were assessed in blood samples collected at the mild-childhood (median = 7 years) and early adolescence (median = 13 years) in-person visits. Results Two hundred and six children (22%) were born by cesarean section. There were no significant differences in biomarker levels between children born by cesarean and children born vaginally in mid-childhood. However, adolescents born by cesarean section had significantly lower adiponectin [% difference (95% confidence interval (CI)) = −11.3 (−18.1, −4.0) µg/mL] compared to vaginal delivery. We also found some suggestion of higher insulin resistance [insulin levels % difference (95% CI) = 11.5 (−0.40, 25.0) µU/mL and HOMA-IR (homeostatic model assessment of insulin resistance) % difference (95% CI) = 9.1 (−2.30, 21.8) U] in adolescents born by cesarean section compared to those born vaginally. Conclusions We found suggestive evidence that adolescents born by cesarean section show differences in certain metabolic health biomarkers relative to adolescents born by vaginal delivery. Further studies are needed to reevaluate these associations since the clinical significance of these differences is unclear. Impact Multiple studies show that children born by cesarean section are at higher risk of obesity compared to those born vaginally. It is unclear yet to what extent this elevated risk may extend to a more adverse profile of biomarkers of metabolic health and inflammation. Adolescents born by cesarean section show small differences in adiponectin and insulin relative to adolescents born by vaginal delivery. Adolescents born by cesarean section may be at higher risk to a more adverse profile of biomarkers of metabolic health and inflammation, but the clinical significance of these differences is uncertain.

Summary Background Infertility has been associated with common chronic non-communicable diseases. However, the association of infertility with long-term mortality is unclear. Methods We followed 101,777 women aged 25–42 years at enrollment between 1989 and 2017. Biennial questionnaires updated participants’ infertility status and underlying reasons for infertility throughout their reproductive lifespan. Hazard ratios (HRs) for the associations of infertility with the risk of premature mortality (death before age 70 years) were estimated using Cox proportional hazards models. Findings During 28 years of follow-up, 2174 women died before age 70 years. Infertility was associated with an HR of 1.26 (95% confidence interval: 1.15 to 1.38) for premature death. This relation was largely driven by deaths from cancer (HR = 1.22, 1.08 to 1.39) and was stronger among women reporting infertility at a younger age (HR = 1.35, 1.19 to 1.52 for age ≤ 25 years; 1.23, 1.10 to 1.38 for age 26–30 years; and 1.10, 0.91 to 1.32 for age > 30 years, compared to no infertility). The premature mortality risk was also higher for women who didn't become pregnant after their first report of infertility (HR = 1.39, 1.25 to 1.54) than among women who reported at least one pregnancy after infertility (HR = 1.12, 1.00 to 1.26). When contributing diagnoses of infertility were evaluated, a greater risk of all-cause mortality was associated with infertility due to ovulatory disorders (HR = 1.28, 1.09 to 1.51) and endometriosis (HR = 1.50, 1.22 to 1.83). Interpretation Infertility may be associated with a greater risk of premature mortality, particularly cancer mortality. Funding The National Institutes of Health grants.

IntroductionLonger duration of lactation is associated with lower cardiometabolic disease risk, but pathogenic pathways involved in the disease progression are unclear, especially among high-risk women. We aimed to examine the associations of lifetime lactation duration with cardiometabolic biomarkers among middle-aged women with a history of gestational diabetes (GDM).Research design and methodsWomen with a history of GDM participating in the Nurses’ Health Study II, a prospective cohort study, were identified and followed through biennial questionnaires beginning in 1991. Lactation history was asked in three follow-up questionnaires to calculate lifetime duration. In 2012–2014, fasting blood samples were collected through the Diabetes & Women’s Health Study to measure inflammatory (C-reactive protein (CRP), interleukin (IL) 6), liver enzyme (alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transferase), and lipid biomarkers (total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol).ResultsAt follow-up blood collection, women were at median age 58.2 (95% CI 51 to 65) years and 26.3 (95% CI 15.7 to 34.1) years since GDM index pregnancy. After multiple adjustment including prepregnancy body mass index (BMI), longer duration of lactation was significantly associated with lower CRP (least squares (LS) mean 1.90 mg/L (95% CI 1.47 to 2.45) for 0-month lactation, 1.98 mg/L (95% CI 1.68 to 2.32) for up to 12-month lactation, 1.67 mg/L (95% CI 1.42 to 1.97) for 12–24 month lactation, and 1.39 mg/L (95% CI 1.19 to 1.62) for >24-month lactation; p trend=0.003) and IL-6 (1.25 pg/L (95% CI 0.94 to 1.68), 1.19 pg/L (95% CI 0.99 to 1.42), 1.04 pg/L (95% CI 0.87 to 1.25), and 0.93 pg/L (95% CI 0.78 to 1.11); p trend=0.04). Longer duration of lactation was associated with lower risk for chronic inflammation using CRP 3 mg/L cut-off in middle-aged women (OR 0.81 (95% CI 0.69 to 0.940 per 1-year increase) with multiple adjustment.ConclusionsLonger lifetime duration of lactation was associated with favorable inflammatory biomarker concentrations in middle-aged women with a history of GDM. Chronic inflammatory pathways may be responsible for previously reported associations between lactation and long-term risk for cardiometabolic diseases.

Hypertensive disorders of pregnancy (HDPs) are leading causes of maternal and perinatal morbidity and mortality. However, it is uncertain whether HDPs are associated with long-term risk of premature mortality (before age 70 years).The objective of this study was to evaluate whether HDPs were associated with premature mortality.Between 1989 and 2017, the authors followed 88,395 parous female nurses participating in the Nurses' Health Study II. The study focused on gestational hypertension and pre-eclampsia within the term HDPs. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between HDPs and premature mortality were estimated by using Cox proportional hazards models, with adjustment for relevant confounders.The authors documented that 2,387 women died before age 70 years, including 1,141 cancer deaths and 212 CVD deaths. The occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an HR of 1.31 (95% CI: 1.18 to 1.46) for premature death during follow-up. When specific causes of death were examined, these relations were strongest for CVD-related mortality (HR: 2.26; 95% CI: 1.67 to 3.07). The association between HDPs and all-cause premature death persisted, regardless of the subsequent development of chronic hypertension (HR: 1.20 [95% CI: 1.02 to 1.40] for HDPs only and HR: 2.02 [95% CI: 1.75 to 2.33] for both HDPs and subsequent chronic hypertension).An occurrence of HDPs, either gestational hypertension or pre-eclampsia, was associated with an increased risk of premature mortality, particularly CVD mortality, even in the absence of chronic hypertension.

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

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

BackgroundData for frontline healthcare workers (HCWs) and risk of SARS-CoV-2 infection are limited and whether personal protective equipment (PPE) mitigates this risk is unknown. We evaluated risk for COVID-19 among frontline HCWs compared to the general community and the influence of PPE.MethodsWe performed a prospective cohort study of the general community, including frontline HCWs, who reported information through the COVID Symptom Study smartphone application beginning on March 24 (United Kingdom, U.K.) and March 29 (United States, U.S.) through April 23, 2020. We used Cox proportional hazards modeling to estimate multivariate-adjusted hazard ratios (aHRs) of a positive COVID-19 test.FindingsAmong 2,035,395 community individuals and 99,795 frontline HCWs, we documented 5,545 incident reports of a positive COVID-19 test over 34,435,272 person-days. Compared with the general community, frontline HCWs had an aHR of 11·6 (95% CI: 10·9 to 12·3) for reporting a positive test. The corresponding aHR was 3·40 (95% CI: 3·37 to 3·43) using an inverse probability weighted Cox model adjusting for the likelihood of receiving a test. A symptom-based classifier of predicted COVID-19 yielded similar risk estimates. Compared with HCWs reporting adequate PPE, the aHRs for reporting a positive test were 1·46 (95% CI: 1·21 to 1·76) for those reporting PPE reuse and 1·31 (95% CI: 1·10 to 1·56) for reporting inadequate PPE. Compared with HCWs reporting adequate PPE who did not care for COVID-19 patients, HCWs caring for patients with documented COVID-19 had aHRs for a positive test of 4·83 (95% CI: 3·99 to 5·85) if they had adequate PPE, 5·06 (95% CI: 3·90 to 6·57) for reused PPE, and 5·91 (95% CI: 4·53 to 7·71) for inadequate PPE.InterpretationFrontline HCWs had a significantly increased risk of COVID-19 infection, highest among HCWs who reused PPE or had inadequate access to PPE. However, adequate supplies of PPE did not completely mitigate high-risk exposures.FundingZoe Global Ltd., Wellcome Trust, EPSRC, NIHR, UK Research and Innovation, Alzheimer’s Society, NIH, NIOSH, Massachusetts Consortium on Pathogen ReadinessRESEARCH IN CONTEXTEvidence before this studyThe prolonged course of the coronavirus disease 2019 (COVID-19) pandemic, coupled with sustained challenges supplying adequate personal protective equipment (PPE) for frontline healthcare workers (HCW), have strained global healthcare systems in an unprecedented fashion. Despite growing awareness of this problem, there are few data to inform policy makers on the risk of COVID-19 among HCWs and the impact of PPE on their disease burden. Prior reports of HCW infections are based on cross sectional data with limited individual-level information on risk factors for infection. A PubMed search for articles published between January 1, 2020 and May 5, 2020 using the terms “covid-19”, “healthcare workers”, and “personal protective equipment,” yielded no population-scale investigations exploring this topic.Added value of this studyIn a prospective study of 2,135,190 individuals, frontline HCWs may have up to a 12-fold increased risk of reporting a positive COVID-19 test. Compared with those who reported adequate availability of PPE, frontline HCWs with inadequate PPE had a 31% increase in risk. However, adequate availability of PPE did not completely reduce risk among HCWs caring for COVID-19 patients.Implications of all the available evidenceBeyond ensuring adequate availability of PPE, additional efforts to protect HCWs from COVID-19 are needed, particularly as lockdown is lifted in many regions of the world.

Background: Women with a history of GDM are at exceptionally high risk of T2D but adopting a healthy lifestyle may mitigate this risk. Methods: We analyzed 4,287 women with a prior clinician diagnosis of GDM from the Nurses’ Health Study II cohort as part of the Diabetes and Women’s Health Study. Healthy lifestyle factors, which were assessed every 2-4 years, included no current smoking, normal body mass index (500 MET-min/week), high-quality diet (above median for the Alternative Healthy Eating Index), and moderate alcohol consumption (>0-15 g/day). Self-reported incident T2D was confirmed via validated supplementary questionnaire (98% concordance with medical records). Multivariate-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI), adjusting for demographic, reproductive, and clinical characteristics. Results: We ascertained 835 incident T2D cases during a median 27.9 years of follow-up. Compared to women reporting no healthy lifestyle factors, HR (95% CI) for risk of T2D among those with 1, 2, 3, 4, or 5 factors were 0.91 (0.64, 1.30), 0.62 (0.44, 0.87), 0.45 (0.31, 0.64), 0.33 (0.22, 0.48), and 0.13 (0.06, 0.28), respectively (P86% (population attributable risk [PAR]%: 86.3%; 95% CI: 70.6%, 93.7%) of T2D cases were theoretically preventable if participants had adherence to all 5 healthy lifestyle factors. Conclusion: Adherence to healthy lifestyle factors was associated with a substantially lower likelihood of progressing to T2D in women with a history of GDM, and strategies to improve long-term adherence are warranted. Disclosure F. Qian: None. J.E. Chavarro: None. S.H. Ley: None. D. Tobias: None. E. Yeung: None. M. Li: None. A. Liu: None. J. Mills: None. Q. Sun: None. F. Hu: None. C. Zhang: None.

Objective: To identify novel modifiable factors that may help prevent gestational diabetes mellitus (GDM) by examining associations of plant-based diet indices with GDM risk. Methods: We included 15,999 women (22,524 singleton pregnancies) in the Nurses’ Health Study II (1991-2001), who reported at least one singleton pregnancy between 1991 and 2001. Pre-pregnancy plant-based diets (i.e., overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI)) were assessed every 4 years using a food frequency questionnaire. Incident first time GDM was ascertained from a self-reported physician diagnosis of GDM, which was previously validated to have high concordance with medical records. We used log-binomial models with generalized estimating equations to estimate relative risks (RR) and 95% confidence intervals (CI) for quartiles of PDI, hPDI, and uPDI and GDM with adjustment for demographic, lifestyle, and other factors. Results: We documented 891 GDM cases over the 10 years of follow-up. Both PDI and hPDI were significantly and inversely associated with GDM (PDI: adjusted RR for extreme quartiles (highest vs. lowest) 0.75, (95% CI: 0.62, 0.92), p trend = 0.01; hPDI: RR for extreme quartiles 0.76, (0.61, 0.94), p trend = 0.01). Further adjustment for pre-pregnancy BMI attenuated the associations (RR for extreme quartiles for PDI: 0.87 (0.71, 1.06); for hPDI: 0.81 (0.65, 1.00)). We estimated that pre-pregnancy BMI mediated 61.3% (95% CI: 21.7%, 90.1%) of the association between PDI and GDM, and 44.4% (18.1%, 74.3%) of the association between hPDI and GDM. uPDI was not significantly associated with GDM. Conclusions: Our study suggests that pre-pregnancy adherence to overall and healthful plant-based diets may be associated with a lower risk of GDM. These associations were substantially mediated through pre-pregnancy BMI. Disclosure Z. Chen: None. F. Qian: None. G. Liu: None. M. Li: None. T. Voortman: None. S.H. Ley: None. J.E. Chavarro: None. S. Bhupathiraju: None. Q. Sun: None. F. Hu: None. C. Zhang: None.

OBJECTIVES: While there is significant literature on the relation between intake of fat and of specific fatty acids during pregnancy with the risk of preeclampsia, the relation of pre-pregnancy intake with preeclampsia and GHTN has not been extensively evaluated. METHODS: In the Nurses’ Health Study II, 11,660 women without a history of chronic disease reported 17,114 singleton pregnancies between 1992 and 2009. Pre-pregnancy diet was assessed every four years, starting in 1991 using a 131-item food frequency questionnaire. GHTN and preeclampsia were self-reported biennially. The relative risk (RR) and 95% confidence intervals (CI) of GHTN and preeclampsia were estimated with log-binomial regression, employing generalized estimating equations to account for repeated pregnancies, and adjusting for total energy intake, protein intake, age at pregnancy, marital status, history of infertility, gestational diabetes, parity, multivitamin use, race, and co-adjustment for major types of fat. RESULTS: Mean (SD) age at pregnancy was 34.6 (3.9) years. Hypertensive disorders of pregnancy (HDP) were reported in 1066 (6%) pregnancies (564 [3%] GHTN; 502 [3%] preeclampsia). Total fat intake before pregnancy was not associated with the risk of GHTN or preeclampsia. When intakes of major types of fats (saturated, monounsaturated, polyunsaturated, and trans) were evaluated, only intake of trans fats was associated with a higher risk of preeclampsia. Women in the highest quartile of trans fat intake (median [range], 2.18 [1.84–5.75] % of calories) had a 45% (CI: 7%, 97%; p-trend = 0.01) greater risk of preeclampsia than women with the lowest quartile of intake (median [range]: 0.91 [0.11–1.09] % of calories). A similar, albeit attenuated, association was observed with trans fat intake and GHTN (p-trend = 0.12). Intakes of major types of fat were unrelated to GHTN. CONCLUSIONS: Greater intake of trans fats before pregnancy was associated with a higher risk of preeclampsia, but not GHTN. However, the extent to which these findings are generalizable to current intake levels in the general US population remains to be determined. Intakes of all other major fat types were unrelated to the risk of HDP. FUNDING SOURCES: Supported by National Institutes of Health grants UM1-CA176726, P30-DK046200, R00ES026648, U54-CA155626, and T32-DK007703–16.

OBJECTIVES: Nearly 1.3 million cesarean deliveries are performed each year in the United States, resulting in the birth of one third of all children nationwide. A higher risk of childhood obesity has been observed among children born by cesarean, but this literature is inconsistent. We investigated differences in total and truncal fat mass during early adolescence among offspring born by cesarean compared to those born by vaginal delivery. METHODS: This prospective study includes adolescents (median age 12.8 years) whose mothers enrolled in while pregnant in Project Viva between 1999 and 2002, and who have been followed since birth. A total of 740 adolescents had available total and truncal fat mass measured using Dual Energy X-Ray Absorptiometry (DXA) at the early adolescent in-person visit. We abstracted delivery mode from electronic medical records. We used multivariable linear regression models to estimate the difference in total and truncal fat mass indices (FMI, kg/m,(2)) among adolescents born by cesarean compared to those born by vaginal delivery while adjusting for confounders. We used stabilized inverse probability weights to account for censoring. RESULTS: Mean (SD) maternal age was 32.2 (5.4) years and pre-pregnancy BMI was 25.0 (5.3) kg/m,(2). A total of 157 (21%) of the adolescents were born by cesarean delivery and 51%were female; mean (SD) total and truncal FMI were 6.3 (3.1) and 2.4 (1.5) kg/m,(2) respectively. Adolescents born by cesarean vs. vaginal delivery had significantly higher total [β (95% CI) = 0.78 (0.23, 1.33) kg/m,(2)] and truncal [β (95% CI) = 0.35 (0.08, 0.61) kg/m,(2)] FMI than those born by vaginal delivery in models adjusted for child age and sex, and maternal age, education and race/ethnicity. These associations were attenuated and no longer statistically significant after further adjusting for maternal pre-pregnancy BMI [β (95% CI) = 0.45 (−0.06, 0.96) kg/m,(2) for total and 0.19 (−0.05, 0.44) kg/m,(2) for truncal FMI]. Additional adjustment for gestational weight gain, smoking and paternal BMI did not substantially change the results. CONCLUSIONS: These data suggest that the association between birth by cesarean delivery and adolescent adiposity is largely explained by maternal pre-pregnancy BMI. FUNDING SOURCES: NIH grants R01HD093761, R01HD034568, R01ES024765, and UH3 OD023286.

Background: Women with a history of gestational diabetes mellitus (GDM) are at increased risk for cardiovascular disease (CVD). Whether healthy lifestyle practices can mitigate this risk is unclear. Aims: To prospectively assess associations of healthy lifestyle factors with CVD risk in women with a history of GDM. Methods: We included 4,372 women from the Nurses’ Health Study II with a prior clinician diagnosis of GDM who were free of cancer or CVD at the time of the index pregnancy. Healthy lifestyle factors, which were updated every 2-4 years, included non-current smoking, body mass index2 , regular physical activity (>500 MET-min/week), high-quality diet (above median on the Alternative Healthy Eating Index), and moderate alcohol consumption (>0-15 g/day). A composite outcome of CVD was defined as the combination of nonfatal/fatal myocardial infarction (MI), stroke, angiographically confirmed angina, and coronary artery bypass surgery or angioplasty/stenting. Multivariate-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI). Results: During a median 28 years of follow-up, 179 incident CVD events were ascertained. Compared to women with 0 or 1 healthy lifestyle factor, HR (95% CI) for risk of CVD among those who had 2, 3, and ≥4 factors were 1.02 (0.68, 1.53), 0.45 (0.28, 0.74), and 0.32 (0.18, 0.60), respectively ( P trend < 0.001) ( Table 1 ). Similar results were observed for clinical CVD events (nonfatal/fatal MI or stroke) and total MI. When modeled continuously, each additional healthy lifestyle factor was associated with a lower risk of the composite outcome, HR (95% CI): 0.67 (0.57, 0.80); clinical CVD, HR (95% CI): 0.74 (0.58, 0.94); and MI, HR (95% CI): 0.61 (0.43, 0.86). We estimated that 62.5% (95% CI: 34.9%, 79.0%) of the CVD risk in this population was potentially avoidable with adherence to ≥4 healthy lifestyle factors. Conclusion: Greater adherence to healthy lifestyle factors was associated with a significant reduction in CVD risk in women with a history of GDM.

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

Background: Menstrual cycle dysfunction is associated with insulin resistance; however, the evidence linking irregular/long menstrual cycles with type 2 diabetes (T2D) is scarce and inconsistent. It is also unclear whether this relation can be modified by lifestyle factors. Methods: Between 1993 and 2017, we followed 75,546 premenopausal women without T2D at baseline who reported the usual length and regularity of their menstrual cycles at ages of 14-17, 18-22, and 29-46 years, as well as data on body weight, smoking status, physical activity, and diet every 2-4 years during follow-up. Time-dependent Cox proportional hazards regression models were constructed to estimate the hazard ratios (HRs) and 95% confidential intervals (CI) for the associations between menstrual cycle characteristics and T2D risk. Findings: We documented 5,608 new cases of T2D. After adjusting for potential confounders including BMI and lifestyle factors, women reporting always having irregular menstrual cycles between the ages of 14-17, 18-22, and 29-46 years were, respectively, 33% (95% CI: 23, 45%), 42% (95% CI: 23, 63%), and 66% (95% CI: 49, 84%) more likely to develop T2D than women reporting very regular cycles in the same age range. Similarly, women reporting usual cycle length ≥40 days between the ages of 18-22 and 29-46 years also had a higher risk of T2D than women reporting a usual cycle length of 26-31 days in the same age range (HRs=1.37; 95% CI: 1.20, 1.58 and 1.49; 95% CI: 1.36, 1.64, respectively). These relations were stronger for women with overweight/obesity and a lower level of physical activity when additive interaction was evaluated. Interpretation : Irregular and long menstrual cycles throughout life are associated with a higher risk of T2D, with a particularly elevated risk among women who were overweight/obesity and physical inactivity. Funding Statement: The National Institutes of Health grants U01-HL145386, U01-CA176726, R01-HL034594, R01-HL088521, DK120870, and DK112940. Declaration of Interests: The authors declare no competing interest. Ethics Approval Statement: Study procedures have been approved by the institutional review boards of the Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health.

Background: Although previous epidemiological studies have explored associations of phthalate metabolites with thyroid function, no studies to date have assessed associations of mixtures with thyroid function and autoimmunity among potentially susceptible subgroups such as subfertile women. Objective: We aimed to explore associations of mixtures of urinary phthalate metabolites with serum markers of thyroid function and autoimmunity. Methods: This cross-sectional study included 558 women attending a fertility center who provided one spot urine and one blood sample at enrollment (2005–2015). We quantified urinary concentrations of eight phthalate metabolites using mass spectrometry, and biomarkers of thyroid function [thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, TT4) and triiodothyronine (fT3, TT3), and autoimmunity [thyroid peroxidase and thyroglobulin antibodies (TPOAb and TgAb, respectively)] in serum using electrochemiluminescence assays. We applied principal component analysis (PCA) and Bayesian kernel machine regression (BKMR) to identify the main patterns of urinary phthalate metabolites. We used linear mixed models to assess the association between PCA-derived factor scores in quintiles and serum thyroid function and autoimmunity, adjusting for age, body mass index (BMI), specific gravity (SG), and, for the PCA, other factor scores. Results: We observed two factors using PCA, one representing the di(2-ethylhexyl) (DEHP) and another non-DEHP metabolites. Compared to women in the lowest quintile of the DEHP factor scores, women in the highest quintile had significantly lower serum concentrations of fT4, TT4, fT3, and TT3 [absolute difference: −0.62; 95% confidence interval (CI): −0.12, −0.01; p=0.04; absolute difference: −8.31; 95% CI: −13.8, −2.85; p=0.003; absolute difference: −0.37; 95% CI: 0.54, −0.19; p

Background: Intake of conventionally grown fruits and vegetables (FVs) is an important route of exposure to pesticide residues in the general population. However, whether health risk stemming from exposure to pesticides through diet could offset benefits of consuming FVs is unclear. Objective: We assessed the association of FV intake, classified according to their pesticide residue status, with total and cause-specific mortality. Methods: We followed 137,378 women (NHS, 1998-2019, and NHSII, 1999-2019) and 23,502 men (HPFS, 1998-2020) without cardiovascular disease, cancer, or diabetes at baseline. FV intake was assessed using validated food frequency questionnaires and categorized as having high- or low-pesticide-residues using data from the USDA Pesticide Data Program. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) for total and cause-specific mortality associated with high- and low-pesticide-residue FV intake. Results: A total of 27,026 deaths, including 4,318 from CVD and 6,426 from cancer, were documented during 3,081,360 person-years of follow-up. In multivariable-adjusted analyses, participants who consumed ≥4 servings/day of low-pesticide-residue FVs had 36% (95CI: 32%-41%) lower mortality risk compared to participants who consumed

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

Circulating saturated (SFA) and monounsaturated fatty acids (MUFA), which are predominantly derived from endogenous metabolism, may influence non-Hodgkin lymphoma (NHL) risk by modulating inflammation or lymphocyte membrane stability. However, few biomarker studies have evaluated NHL risk associated with these fats. We conducted a prospective study of 583 incident NHL cases and 583 individually matched controls with archived pre-diagnosis red blood cell (RBC) specimens in the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). RBC membrane fatty acid levels were measured using gas chromatography. Using multivariable logistic regression, we estimated odds ratios (OR) and 95% confidence intervals (CI) for risk of NHL and major NHL subtypes including T cell NHL (T-NHL), B cell NHL (B-NHL) and three individual B-NHLs: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. RBC SFA and MUFA levels were not associated with NHL risk overall. However, RBC very long chain SFA levels (VLCSFA; 20:0, 22:0, 23:0) were inversely associated with B-NHLs other than CLL/SLL; ORs (95% CIs) per standard deviation (SD) increase in level were 0.81 (0.70, 0.95) for 20:0, 0.82 (0.70, 0.95) for 22:0, and 0.82 (0.70, 0.96) for 23:0 VLCSFA. Also, both VLCSFA and MUFA levels were inversely associated with T-NHL [ORs (95% CIs) per SD: VLCSFA, 0.63 (0.40, 0.99); MUFA, 0.63 (0.40, 0.99)]. The findings of inverse associations for VLCSFAs with B-NHLs other than CLL/SLL and for VLCSFA and MUFA with T-NHL suggest an influence of fatty acid metabolism on lymphomagenesis.

OBJECTIVE We examined the association of lactation duration with incident type 2 diabetes among women with a history of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We monitored 4,372 women with a history of GDM participating in the Nurses’ Health Study II for incident type 2 diabetes over 25 years up to 2017. Lactation history was obtained through follow-up questionnaires to calculate lactation duration. Follow-up blood samples were collected from a subset of these women at median age of 58 years through the Diabetes & Women’s Health Study. RESULTS We documented 873 incident cases of type 2 diabetes during 87,411 person-years of follow-up. Longer duration of lactation was associated with lower risk of type 2 diabetes for both total lactation (hazard ratio 1.05 [95% CI 0.83–1.34] for up to 6 months, 0.91 [0.72–1.16] for 6–12 months, 0.85 [0.67–1.06] for 12–24 months, and 0.73 [0.57–0.93] for >24 months, compared with 0 months; P-trend = 0.003) and exclusive breastfeeding (P-trend = 0.002) after adjustment for age, ethnicity, family history of diabetes, parity, age at first birth, smoking, diet quality, physical activity, and prepregnancy BMI. Longer duration of lactation was also associated with lower HbA1c, fasting plasma insulin, and C-peptide concentrations among women without type 2 diabetes at follow-up (all adjusted P-trend ≤0.04). CONCLUSIONS Longer duration of lactation is associated with a lower risk of type 2 diabetes and a favorable glucose metabolic biomarker profile among women with a history of GDM. The underlying mechanisms and impact on diabetes complications, morbidity, and mortality remain to be determined.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication which has substantial short- and long-term adverse health implications for women and their children. However, large-scale studies on genetic risk loci for GDM remain sparse. METHODS: We conducted a case-control study among 2,636 GDM cases and 6,086 non GDM controls from the Nurses’ Health Study II (NHSII) and the Danish National Birth Cohort (DNBC). One hundred and twelve susceptibility genetic variants confirmed by genome-wide association studies for type 2 diabetes (T2D) were selected and measured. A weighted genetic risk score (GRS) was created based on variants that were significantly associated with risk of GDM after correcting for false discovery rate (FDR). RESULTS: For the first time, we identified eight variants associated with GDM, namely rs7957197 (HNF1A), rs10814916 (GLIS3), rs3802177 (SLC30A8), rs9379084 (RREB1), rs34872471 (TCF7L2), rs7903146 (TCF7L2), rs11787792 (GPSM1), and rs7041847 (GLIS3). Additionally, we confirmed three variants, rs10830963 (MTNR1B), rs1387153 (MTNR1B), and rs4506565 (TCF7L2), that were previously significantly associated with GDM risk. Furthermore, compared to participants in the first (lowest) quartile of weighted GRS based on these 11 SNPs, the odds ratios of GDM were 1.07 (95% CI: 0.93, 1.22), 1.23 (95% CI 1.07, 1.41), and 1.53 (95% CI 1.34, 1.74) in the second, third, and fourth (highest) quartile, respectively. The significant positive associations between the weighted GRS and risk of GDM persisted across most of the strata of major risk factors for GDM including family history of type 2 diabetes, smoking status, body mass index, and age. CONCLUSION: In this large-scale case-control study with women from two independent populations, eight novel GDM SNPs were identified, which offers potential to improve our understanding on GDM etiology, particularly biological mechanisms related to beta cell function.

BACKGROUND We sought to identify regional and seasonal variation in not meeting physical activity (PA) recommendations of ≥ 60 minutes a day of moderate-to-vigorous physical activity (MVPA) and 3 hours of vigorous physical activity per week (VPA) in a longitudinal cohort of U.S. adolescents. METHODS Participants in the Growing Up Today Study 2, a prospective study of 10,918 adolescents, self-reported season-specific weekly hours of MVPA and VPA from 2004 through 2011. To assess variation in PA by climate, we grouped the contiguous U.S. into nine climatically consistent geographic regions. We also examined MVPA and VPA by season, sex, ethnicity, weight status, and age group. RESULTS The majority (85%) of adolescents did not meet the MVPA recommendation, and 91% did not meet the VPA recommendation, for one or more seasons over the four study years. Across all climate regions, adolescents were two times more likely to not meet the MVPA recommendation during the winter compared to summer (OR 2.02, 95% CI 1.96-2.08). CONCLUSION Regardless of climate region, gender, ethnicity, or age group, adolescents were more likely not to meet MVPA or VPA recommendations in the winter than the summer. Adolescents may benefit from interventions aimed at increasing PA in the winter.