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Dysregulation of the immune system and dietary patterns that increase inflammation can increase the risk for cognitive decline, but the mechanisms by which inflammatory nutritional habits may affect the development of cognitive impairment in aging are not well understood. To determine whether plasma proteins linked to inflammatory diet predict future cognitive impairment, we applied high-throughput proteomic assays to plasma samples from a subset (n = 1528) of Women’s Health Initiative Memory Study (WHIMS) participants (mean [SD] baseline age, 71.3 [SD 3.8] years). Results provide insights into how inflammatory nutritional patterns are associated with an immune-related proteome and identify a group of proteins (CXCL10, CCL3, HGF, OPG, CDCP1, NFATC3, ITGA11) related to future cognitive impairment over a 14-year follow-up period. Several of these inflammatory diet proteins were also associated with dementia risk across two external cohorts (ARIC, ESTHER), correlated with plasma biomarkers of Alzheimer’s disease (AD) pathology (Aβ42/40) and/or neurodegeneration (NfL), and related to an MRI-defined index of neurodegenerative brain atrophy in a separate cohort (BLSA). In addition to evaluating their biological relevance, assessing their potential role in AD, and characterizing their immune-tissue/cell-specific expression, we leveraged published RNA-seq results to examine how the in vitro regulation of genes encoding these candidate proteins might be altered in response to an immune challenge. Our findings indicate how dietary patterns with higher inflammatory potential relate to plasma levels of immunologically relevant proteins and highlight the molecular mediators which predict subsequent risk for age-related cognitive impairment.

BACKGROUND: The associations of red and processed meat with chronic disease risk remain to be clarified, in part because of measurement error in self-reported diet. OBJECTIVES: We sought to develop metabolomics-based biomarkers for red and processed meat, and to evaluate associations of biomarker-calibrated meat intake with chronic disease risk among postmenopausal women. METHODS: Study participants were women who were members of the Women's Health Initiative (WHI) study cohorts. These participants were postmenopausal women aged 50–79 y when enrolled during 1993–1998 at 40 US clinical centers with embedded human feeding and nutrition biomarker studies. Literature reports of metabolomics correlates of meat consumption were used to develop meat intake biomarkers from serum and 24-h urine metabolites in a 153-participant feeding study (2010–2014). Resulting biomarkers were used in a 450-participant biomarker study (2007–2009) to develop linear regression calibration equations that adjust FFQ intakes for random and systematic measurement error. Biomarker-calibrated meat intakes were associated with cardiovascular disease, cancer, and diabetes incidence among 81,954 WHI participants (1993–2020). RESULTS: Biomarkers and calibration equations meeting prespecified criteria were developed for consumption of red meat and red plus processed meat combined, but not for processed meat consumption. Following control for nondietary confounding factors, hazard ratios were calculated for a 40% increment above the red meat median intake for coronary artery disease (HR: 1.10; 95% CI: 1.07, 1.14), heart failure (HR: 1.26; 95% CI: 1.20, 1.33), breast cancer (HR: 1.10; 95% CI: 1.07, 1.13) for, total invasive cancer (HR: 1.07; 95% CI: 1.05, 1.09), and diabetes (HR: 1.37; 95% CI: 1.34, 1.39). HRs for red plus processed meat intake were similar. HRs were close to the null, and mostly nonsignificant following additional control for dietary potential confounding factors, including calibrated total energy consumption. CONCLUSIONS: A relatively high-meat dietary pattern is associated with somewhat higher chronic disease risks. These elevations appear to be largely attributable to the dietary pattern, rather than to consumption of red or processed meat per se.

We investigated the association of coffee and caffeine with breast cancer (BCa) risk, overall and by ER/PR status. We also examined potential interactions of coffee and caffeine with postmenopausal hormone use.Our study included 77,688 postmenopausal participants from the Women's Health Initiative observational study cohort without a history of any cancer at baseline (except non-melanoma skin) and with valid Food Frequency Questionnaire data and complete data on dietary caffeine. Regular coffee (none, 1, 2-3, 4-5, and ≥ 6 cups/day) and caffeine (tertiles) were assessed at baseline. Information on BCa risk factors was collected at baseline. The associations were examined using survival analysis, accounting for death as a competing risk.The median follow-up time for our cohort was 18.3 years. During the follow-up, 5005 women developed invasive breast cancer. In multivariable analysis, coffee was not associated with the overall invasive BCa risk. Higher caffeine intake was mildly associated with increased BCa risk (2nd vs. 1st tertile SHR = 1.10, 95% CI 1.03-1.18, 3rd vs. 1st tertile SHR-1.05, 95% CI 0.98-1.13, overall p = 0.03). We found no interaction of coffee/caffeine with postmenopausal hormone use (p interaction = 0.44 and 0.42, respectively). In the exploratory analysis by ER/PR status, we found a positive association of caffeine with ER+ /PR+ BCa (2nd vs. 1st tertile SHR = 1.17, 95% CI 1.07-1.28, 3rd vs. 1st tertile SHR = 1.13, 95% CI 1.03-1.24, overall p = 0.002); no associations were observed for ER-/PR- tumors. Coffee was not associated with the risk of ER+ /PR+ or ER-/PR- tumors.We found no associations of coffee with BCa risk, overall and for ER/PR-defined tumor subtypes. The higher caffeine consumption was mildly and positively associated with the overall BCa risk and with ER+ /PR+ tumors.

Pancreatic cancer (PC) is the fourth leading cause of cancer mortality among women in the United States. Obesity is positively associated with PC risk. Current health recommendations focus on weight maintenance for healthy-weight individuals and weight loss for overweight/obese individuals; however, little research has assessed associations between PC risk and changes in weight throughout the life course. Using prospective cohort study data, we examined the relationship between baseline adulthood weight patterns self-reported between 1993 and 1998 and PC risk in 136,834 postmenopausal women with 873 incident PC cases through September 30, 2015, in the Women’s Health Initiative. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards models, adjusting for age, smoking habits, heavy alcohol consumption, and body mass index. Compared with women with stable weight, no significant associations were found between steady weight gain (HR = 1.01, 95% CI: 0.83, 1.22), sustained weight loss (HR = 1.26, 95% CI: 0.85, 1.87), or weight cycling patterns (HR = 1.08, 95% CI: 0.89, 1.30) and PC. Results were similar when the outcome definition was restricted to pancreatic adenocarcinoma cases. Overall, we did not find evidence to suggest that weight changes in adulthood significantly impact PC risk among postmenopausal women.

Background and ObjectivesThe mortality from Parkinson disease (PD) and its long-term trends in the United States in recent decades remains unknown. This study aimed to describe the trends in PD mortality in the United States from 1999 to 2019.MethodsWe used data from the National Vital Statistics System, a nationwide, population-based death registry, to determine national trends in PD mortality, overall and by age, sex, race/ethnicity, urban-rural classification, and geographic location. Analyses focused on the data from 479,059 deaths due to PD from 1999 to 2019. Joinpoint regression was performed to examine temporal trends in age-adjusted death rates.ResultsThe age-adjusted mortality from PD increased from 5.4 (95% confidence interval [CI] 5.3–5.5) per 100,000 population in 1999 to 8.8 (95% CI, 8.7–8.9) per 100,000 population in 2019, with an average annual percent change of 2.4% (95% CI, 1.8%–3.0%). From 1999 to 2019, PD mortality increased significantly across all age groups, both sexes, various racial/ethnic groups, and different urban-rural classifications. The US states and District of Columbia with reported death rates all experienced an increase in PD mortality. Significant differences by sex and race/ethnicity were noted. Age-adjusted PD mortality rates were twice as high in men as in women and were greater in White individuals than those from other racial/ethnic groups.DiscussionFrom 1999 to 2019, the mortality from PD in the United States has increased significantly. The increase was regardless of age, sex, race/ethnicity, urban-rural classification, and geographic location. A comprehensive evaluation of long-term trends in PD mortality is important for health care priority setting.

Background Cardiometabolic diseases are prevalent in aging Americans. Although some studies have implicated greater intake of dairy products, it is not clear how dairy intake is related to biomarkers of cardiometabolic health. Objective Our aim was to test the hypothesis that associations of dairy foods with biomarkers of lipid metabolism, insulin-like growth factor signaling, and chronic inflammation may provide clues to understanding how dairy can influence cardiometabolic health. Design This was a cross-sectional study in the Women's Health Initiative using baseline food frequency questionnaire data to calculate dairy intake. Participants/setting Participants were 35,352 postmenopausal women aged 50 to 79 years at 40 clinical centers in the United States. Main outcome measures Baseline (1993-1998) concentrations of 20 circulating biomarkers were measured. Statistical analyses Multivariable-adjusted linear regression was used to estimate percent difference in biomarker concentrations per serving of total dairy and individual foods (milk, cheese, yogurt, butter, and low-fat varieties). Results Lower triglyceride concentrations were associated with greater intake of total dairy (–0.8% [95% CI –1.2% to –0.3%]), mainly driven by full-fat varieties. Individual dairy foods had specific associations with circulating lipid components. For example, greater total milk intake was associated with lower concentrations of total cholesterol (–0.4% [95% CI –0.7% to –0.2%]) and high-density lipoprotein cholesterol (–0.5% [95% CI –0.9% to –0.1%]), whereas greater butter intake was associated with higher total cholesterol (0.6% [95% CI 0.2% to 1.0%]) and high-density lipoprotein cholesterol (1.6% [95% CI 1.1% to 2.0%]) concentrations. In contrast, higher total yogurt intake was associated with lower total cholesterol (–1.1% [95% CI –2.0% to –0.2%]) and higher high-density lipoprotein cholesterol (1.8% [95% CI 0.5% to 3.1%]). Greater total dairy intake (regardless of fat content), total cheese, full-fat cheese, and yogurt were consistently associated with lower concentrations of glucose, insulin, and C-reactive protein. However, milk and butter were not associated with these biomarkers. Conclusions Higher dairy intake, except butter, was associated with a favorable profile of lipids, insulin response, and inflammatory biomarkers, regardless of fat content. Yet, specific dairy foods might influence these markers uniquely. Findings do not support a putative role of dairy in cardiometabolic diseases observed in some previous studies.

The potential role of nutritional factors in the development of peripheral arterial disease (PAD) remains poorly understood. We evaluated multiple recommended eating patterns as reflected by predefined diet quality indices in relation to long-term risk of PAD. We included 138 506 US postmenopausal women in the Women’s Health Initiative who had no known PAD at baseline (1993–1998). Four diet quality indices, including alternate Mediterranean diet index, alternate Healthy Eating Index-2010, Dietary Approaches to Stop Hypertension diet index, and Healthy Eating Index-2015, were derived using dietary information collected by a validated food frequency questionnaire at baseline. Incident cases of symptomatic PAD in the lower extremities were ascertained and adjudicated through March 2019 via medical record review. During a median 18.6 years of follow-up, 1036 incident PAD cases were identified. After multivariable adjustment, all diet quality scores were significantly and inversely associated with 21% (for alternate Healthy Eating Index 2010) to 34% (for Dietary Approaches to Stop Hypertension index) lower risk of PAD when comparing the highest with the lowest quartiles (all P -for-trend values ≤0.010). Among contributing food groups and nutrients, intakes of legumes, dietary fiber, and vegetable protein were associated lower risk of PAD, while intakes of unprocessed red meat, processed meat, and regular soft drinks were associated with higher risk. In a broad sample of US postmenopausal women, adhering to different recommended eating patterns is associated with lower risk of PAD. Our findings suggest that current clinical and public health strategies that recommend healthful eating patterns may also be applicable to PAD prevention.

The National Academy of Sciences, Engineering, and Medicine (NASEM) recommended steps to redesign the process of developing the Dietary Guidelines for Americans (DGA) are based on 5 guiding principles (enhance transparency; promote diversity of expertise and experience; support a deliberative process; manage biases and conflicts of interest; and adopt state-of-the-art processes and methods). Using these principles and recommendations, the USDA and HHS updated the process for developing the 2020-2025 Dietary Guidelines, including the process for appointing members and managing the work of the 2020 Dietary Guidelines Advisory Committee. Modifications included having public comment on the topics and questions to be addressed by the Federal Advisory Committee, reviewing professional and financial activities on potential appointees to the committee prior to their appointment, redesigning the website to provide status updates on the work of the committee as analytical frameworks and draft conclusions were developed, strengthening the approaches for conducting systematic reviews, and adding a public meeting for discussion of the final report before its submission to the Secretaries of the USDA and HHS. Because the DGA is reviewed and updated every 5 y, it is possible to learn from each cycle what works well and where improvements in the process can be implemented. The current article illustrates, from the perspective of the advisory committee, the impact of the NASEM report on the development of the scientific report by examining changes in the process consistent with the 5 principles.

Background Epidemiological studies have been inconsistent regarding the relations between diabetes risk and the consumption of eggs and nutrients in eggs, such as choline, betaine, and cholesterol. There have been few studies among elderly women. Objectives The objective of this study was to examine associations between consumption of eggs, cholesterol, choline, and betaine and the risk of diabetes among elderly US women. Methods Multivariable Cox regression was used with data from the prospective Women's Health Initiative. Population attributable risks were calculated. Consumption of eggs alone (not mixed in foods) and nutrients were assessed with an FFQ. Diabetes incidence was defined as the first incidence of self-reported diabetes treated with oral diabetes medication or insulin injections. Results There were 46,263 women at follow-up baseline. During 13.3 y and 592,984 person-years of follow-up, there were 5480 incident diabetes cases. Higher egg, cholesterol, and choline consumption were each significantly associated with increases in diabetes risk. The associations for eggs and choline were not significant after adjustment for cholesterol consumption. The association for eggs was attenuated after adjustment for non-egg cholesterol consumption, with 1 significant HR in the top consumption quintile (≥3 eggs/wk) of 1.15 (95% CI: 1.05, 1.27; P for linear trend = 0.0001). The population attributable risks for obesity, overweight, consumption of ≥3 eggs/wk, inadequate exercise, and poor diet were 25.0 (95% CI: 22.3, 27.6), 12.8 (95% CI: 11.1, 14.5), 4.2 (95% CI: 2.3, 6.1), 3.5 (95% CI: 1.2, 5.8), and 3.1 (95% CI: 0.5, 5.7), respectively. Conclusions As egg consumption increased to ≥3 eggs/wk, there was a steady increase in diabetes risk that may have been due to the cholesterol in the eggs. The population attributable risk for ≥3 eggs/wk was far lower than that for being obese or overweight.

BackgroundIdentification of nutrients of public health concern has been a hallmark of the Dietary Guidelines for Americans (DGA); however, a formal systematic process for identifying them has not been published.ObjectivesWe aimed to propose a framework for identifying "nutrients or food components" (NFCs) of public health relevance to inform the DGA.MethodsThe proposed framework consists of 1) defining terminology; 2) establishing quantitative thresholds to identify NFCs; and 3) examining national data. The proposed framework utilizes available data from 3 key data sources or "prongs": 1) dietary intakes; 2) biological endpoints; and 3) clinical health consequences such as prevalence of health conditions, directly or indirectly through validated surrogate markers.ResultsIn identifying potential NFCs of public health concern, the 2020 DGA Committee developed a decision-tree framework with suggestions for combining the 3 prongs. The identified NFCs of public health concern for Americans ≥1y old included fiber, calcium (≥2y old), vitamin D, and potassium for low intakes and sodium, added sugars, and saturated fats (≥2y old) for high intakes that were associated with adverse health consequences. Iron was identified among infants ages 6-12mo fed human milk. For reproductive-aged and pregnant females, iron (all trimesters) and folate (first trimester) were identified for low intake, based on dietary and biomarker data (iron) or the severity of the consequence (folic acid and neural tube defects). Among pregnant women, low iodine was of potential public health concern based on biomarker data. Other NFCs that were underconsumed, overconsumed, and pose special challenges were identified across the life course.ConclusionsThe proposed decision-tree framework was intended to streamline and add transparency to the work of this and future Dietary Guidelines Advisory Committees to identify NFCs that need to be encouraged or discouraged in order to help reduce risk of chronic disease and promote health and energy balance in the population.

BackgroundThe potential cardiovascular impact of dietary cholesterol intake has been actively debated for decades.ObjectivesWe aimed to evaluate associations of dietary cholesterol and egg intakes with incident cardiovascular disease (CVD) and all-cause and cause-specific mortality.MethodsWe included 96,831 US postmenopausal women aged 50-79 y without known CVD or cancer during baseline enrollment (1993-1998) of the Women's Health Initiative. Dietary information was collected using a validated FFQ. Incident CVD [i.e., ischemic heart disease (IHD) and stroke] and all-cause and cause-specific mortality were ascertained and adjudicated through February 2018.ResultsA total of 9808 incident CVD cases and 19,508 all-cause deaths occurred during a median follow-up of 17.8 y and 18.9 y, respectively. After multivariable adjustment for traditional risk factors and key dietary nutrients including dietary saturated fat, there were modest associations of dietary cholesterol intake with incident CVD (HRQ5versusQ1: 1.12; 95% CI: 1.03, 1.21; P-trend0.05). Higher egg consumption was also associated with modestly higher risk of incident CVD (P-trend=0.004) and all-cause mortality (P-trend&nbsp

Although adherence to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity for Cancer Prevention associates with lower risk of obesity-related cancer (ORC) incidence and mortality, evidence in Black and Latina women is limited. This association was examined in Black and Latina participants in the Women's Health Initiative (WHI).Semi-Markov multistate model examined the association between ACS guideline adherence and ORC incidence and mortality in the presence of competing events, combined and separately, for 9301 Black and 4221 Latina postmenopausal women. Additionally, ACS guideline adherence was examined in a subset of less common ORCs and potential effect modification by neighborhood socioeconomic status and smoking.Over a median of 11.1, 12.5, and 3.7 years of follow-up for incidence, nonconditional mortality, and conditional mortality, respectively, 1191 ORCs (Black/Latina women: 841/269), 1970 all-cause deaths (Black/Latina women: 1576/394), and 341 ORC-related deaths (Black/Latina women: 259/82) were observed. Higher ACS guideline adherence was associated with lower ORC incidence for both Black (cause-specific hazard ratio [CSHR]Adherence to the ACS guidelines was associated with lower risk of ORCs and less common ORCs but was not for conditional ORC-related mortality.Evidence on the association between the American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention and cancer remains scarce for women of color. Adherence to the guidelines and risk of developing one of 13 obesity-related cancers among Black and Latina women in the Women's Health Initiative was examined. Women who followed the lifestyle guidelines had 28% to 42% lower risk of obesity-related cancer. These findings support public health interventions to reduce growing racial/ethnic disparities in obesity-related cancers.

Training to ensure good documentation practices and adherence to regulatory requirements in human nutrition randomized controlled trials has not been given sufficient attention. Furthermore, it is difficult to find this information conveniently organized or in a form relevant to nutrition protocols. Current gaps in training and research surveillance exist in clinical nutrition research because training modules emphasize drugs and devices, promote reliance on monitoring boards, and lack nutrition expertise on human nutrition research teams. Additionally, because eating is essential, ongoing, and highly individualized, it is difficult to distinguish risks associated with interventions from eating under free-living conditions. Controlled-feeding trials provide an option to gain more experimental control over food consumed, but at a price of less external validity, and may pose human behavior issues that are unrelated to the intervention. This paper covers many of the expected practices for documentation and regulation that may be encountered in planning and conducting nutrition intervention trials with examples and references that should be useful to clinical nutrition researchers, funders of research, and research institutions. Included are definitions and guidance on clinical nutrition research oversight (institutional review boards, data safety and monitoring boards, US FDA); participant safety; standard operating procedures; training of investigators, staff, and students; and local culture and reporting requirements relevant to diet-related clinical research conduct and documentation.

Previous dietary studies and current dietary guidelines have mainly focused on dietary intake and food patterns. Little is known about the association between eating behaviors such as meal frequency, skipping and intervals, and mortality.The objective was to examine the associations of meal frequency, skipping, and intervals with all-cause and cardiovascular disease (CVD) mortality.This was a prospective study.A total of 24,011 adults (aged ≥40 years) who participated in the National Health and Nutrition Examination Survey 1999-2014 were included in this study. Eating behaviors were assessed using 24-hour recall. Death and underlying causes of death were ascertained by linkage to death records through December 31, 2015.The outcomes were all-cause and CVD mortality.Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) of all-cause and CVD mortality.During 185,398 person-years of follow-up period, 4,175 deaths occurred, including 878 cardiovascular deaths. Most participants ate three meals per day. Compared with participants eating three meals per day, the multivariable-adjusted HRs for participants eating one meal per day were 1.30 (95% CI 1.03 to 1.64) for all-cause mortality, and 1.83 (95% CI 1.26 to 2.65) for CVD mortality. Participants who skipped breakfast have multivariable-adjusted HRs 1.40 (95% CI 1.09 to 1.78) for CVD mortality compared with those who did not. The multivariable-adjusted HRs for all-cause mortality were 1.12 (95% CI 1.01 to 1.24) for skipping lunch and 1.16 (95% CI 1.02 to 1.32) for skipping dinner compared with those who did not. Among participants eating three meals per day, the multivariable-adjusted HR for participants with an average interval of ≤4.5 hours in two adjacent meals was 1.17 (95% CI 1.04 to 1.32) for all-cause mortality, comparing with those having a meal interval of 4.6 to 5.5 hours.In this large, prospective study of US adults aged 40 years or older, eating one meal per day was associated with an increased risk of all-cause and CVD mortality. Skipping breakfast was associated with increased risk of CVD mortality, whereas skipping lunch or dinner was associated with increased risk of all-cause mortality. Among participant with three meals per day, a meal interval of ≤4.5 hours in two adjacent meals was associated with higher all-cause mortality.

Poor diet quality is a leading risk factor for death in the United States. We examined the association between Healthy Eating Index-2015 (HEI-2015) scores and death from all causes, cardiovascular disease (CVD), cancer, Alzheimer disease, and dementia not otherwise specified (NOS) among postmenopausal women in the Women’s Health Initiative Observational Study (1993–2017). This analysis included 59,388 participants who completed a food frequency questionnaire and were free of cancer, CVD, and diabetes at enrollment. Stratified Cox proportional hazards models were fit using person-years from enrollment as the underlying time metric. We estimated multivariable adjusted hazard ratios and 95% confidence intervals for risk of death associated with HEI-2015 quintiles, with higher scores reflecting more optimal diet quality. Over a median of 18.2 years, 9,679 total deaths 3,303 cancer deaths, 2,362 CVD deaths, and 488 deaths from Alzheimer disease and dementia NOS occurred. Compared with those with lower scores, women with higher HEI-2015 scores had an 18% lower risk of all-cause death and 21% lower risk of cancer death. HEI-2015 scores were not associated with death due to CVD, Alzheimer disease, and dementia NOS. Consuming a diet aligned with 2015–2020 US dietary guidelines may have beneficial impacts for preventing overall causes of death and death from cancer.

BACKGROUND: Asian Americans are among the fastest growing subpopulations in the United States. However, evidence about maternal prepregnancy body mass index (BMI) and preterm birth among Asian Americans is lacking. METHODS: This population-based study used nationwide birth certificate data from the US National Vital Statistics System 2014 to 2018. All Asian American mothers who had a singleton live birth were included. According to Asian-specific cutoffs, maternal prepregnancy BMI was classified into underweight (BMI < 18.5 kg/m(2)), normal weight (BMI 18.5–22.9 kg/m(2)), overweight (BMI 23.0–27.4 kg/m(2)), class I obesity (BMI 27.5–32.4 kg/m(2)), class II obesity (BMI 32.5–37.4 kg/m(2)), and class III obesity (BMI ≥37.5 kg/m(2)). Preterm birth was defined as gestational age less than 37 weeks. Multivariable logistic regression models were used to estimate the odds ratio (OR) of preterm birth. RESULTS: We included 1 081 341 Asian American mother-infant pairs. The rate of preterm birth was 6.51% (n = 70 434). The rate of maternal prepregnancy overweight and obesity was 46.80% (n = 506 042). Compared with mothers with normal weight, the adjusted OR of preterm delivery was 1.04 (95% CI, 1.01–1.07) for underweight mothers, 1.18 (95% CI, 1.16–1.20) for overweight mothers, 1.41 (95% CI, 1.37–1.44) for mothers with class I obesity, 1.69 (95% CI, 1.63–1.76) for mothers with class II obesity, and 1.78 (95% CI, 1.66–1.90) for mothers with class III obesity. Similar patterns of associations were observed in Asian American mothers across different country origins. CONCLUSIONS: Among Asian American mothers, maternal prepregnancy overweight or obesity, defined by Asian-specific, lower BMI cutoffs, was significantly associated with an increased risk of preterm birth. The risk of preterm birth increased with increasing obesity severity. These findings highlight the importance of using Asian-specific BMI cutoffs in assessing risk of preterm birth among Asian American mothers.

Objective To determine if premature menopause and early menarche are associated with increased risk of AAA, and to explore potential effect modification by smoking history. Summary of background data Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific risk factors, such as premature menopause and early menarche, with risk of AAA in a large, ethnically diverse cohort of women. Methods This was a post-hoc analysis of Women's Health Initiative participants who were beneficiaries of Medicare Parts A&B fee-for-service. AAA cases and interventions were identified from claims data. Follow-up period included Medicare coverage until death, end of follow-up or end of coverage inclusive of 2017. Results Of 101,119 participants included in the analysis, the mean age was 63 years and median follow-up was 11.3 years. Just under 10,000 (9.4%) women experienced premature menopause and 22,240 (22%) experienced early menarche. Women with premature menopause were more likely to be overweight, Black, have ≥20 pack years of smoking, history of cardiovascular disease, hypertension, and early menarche. During 1,091,840 person-years of follow-up, 1125 women were diagnosed with AAA, 134 had premature menopause (11.9%), 93 underwent surgical intervention and 45 (48%) required intervention for ruptured AAA. Premature menopause was associated with increased risk of AAA [hazard ratio 1.37 (1.14, 1.66)], but the association was no longer significant after multivariable adjustment for demographics and cardiovascular disease risk factors. Amongst women with ≥20 pack year smoking history (n = 19,286), 2148 (11.1%) had premature menopause, which was associated with greater risk of AAA in all models [hazard ratio 1.63 (1.24, 2.23)]. Early menarche was not associated with increased risk of AAA. Conclusions This study finds that premature menopause may be an important risk factor for AAA in women with significant smoking history. There was no significant association between premature menopause and risk of AAA amongst women who have never smoked. These results suggest an opportunity to develop strategies for better screening, risk reduction and stratification, and outcome improvement in the comprehensive vascular care of women.

OBJECTIVE To examine the association of maternal prepregnancy diabetes, gestational diabetes mellitus (GDM), and 12 subtypes of congenital anomalies of the newborn. RESEARCH DESIGN AND METHODS We included 29,211,974 live births with maternal age ranging from 18 to 49 years old documented in the National Vital Statistics System in the U.S. from 2011 to 2018. Information on prepregnancy diabetes, GDM, and congenital anomalies was retrieved from birth certificates. Log-binomial regression was used to estimate risk ratios (RRs) and 95% CIs for congenital anomalies overall and by subtypes. RESULTS Of the 29,211,974 live births, there were 90,061 infants who had congenital anomalies identified at birth. The adjusted RRs of congenital anomalies at birth were 2.44 (95% CI 2.33–2.55) for prepregnancy diabetes and 1.28 (95% CI 1.24–1.31) for GDM. The associations were generally consistent across subgroups by maternal age, race/ethnicity, prepregnancy obesity status, and infant sex. For specific subtypes of congenital anomalies, maternal prepregnancy diabetes or GDM was associated with an increased risk of most subtypes. For example, the adjusted RRs of cyanotic congenital heart disease were 4.61 (95% CI 4.28–4.96) for prepregnancy diabetes and 1.50 (95% CI 1.43–1.58) for GDM; the adjusted RRs of hypospadias were 1.88 (95% CI 1.67–2.12) for prepregnancy diabetes and 1.29 (95% CI 1.21–1.36) for GDM. CONCLUSIONS Prepregnancy diabetes and, to a lesser extent, GDM were associated with several subtypes of congenital anomalies of the newborn. These findings suggest potential benefits of preconception counseling in women with preexisting diabetes or at risk for GDM for the prevention of congenital anomalies.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder that usually persists into adulthood. However, limited evidence is available regarding its influence on adult health outcomes beyond neuropsychiatric comorbidities. This study aimed to examine the association of ADHD with diabetes in US adults.We analyzed data from the National Health Interview Survey (NHIS), a leading health survey of a nationally representative sample in the United States. We included adults aged 20-79 years who participated in the NHIS 2007 and 2012. Physician-diagnosed ADHD and diabetes were reported during an in-person household interview. Logistic regression with survey sampling weights was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of diabetes.This analysis included 52 821 adults (weighted mean age 45.5 years; 48.6% males). Among them, 1642 participants reported a diagnosis of ADHD and 4631 reported a diagnosis of diabetes. In the multivariable analysis adjusting for age, sex, race/ethnicity, education level, family income level, smoking, alcohol drinking, physical activity, and body mass index, the OR of diabetes among adults with ADHD vs those without ADHD was 1.54 (95% CI, 1.16-2.04). In the stratified analyses, the significant association of ADHD with diabetes remained in most strata, and the associations were not significantly modified by age, sex, race/ethnicity, or obesity status.In a nationally representative sample of US adults, we found a significant association between a history of ADHD diagnosis and diabetes.背景: 注意缺陷力/多动症(ADHD)是一种儿童期出现并通常持续到成年的一种神经发育障碍。除外神经精神病合并症以外, ADHD对患者长期健康结局影响的研究证据非常有限。本项研究旨在了解美国成人ADHD与糖尿病的关系。 方法: 美国国家健康访谈调查(NHIS)是一项针对美国全国代表性样本的健康调查。我们纳入了2007年和2012参加这项调查的20-79岁成年人。在面对面的家庭访谈中收集了ADHD和糖尿病的诊断信息。用纳入了调查样本权重的逻辑回归分析来估计糖尿病的优势比(OR)和95%置信区间(CI)。 结果: 这项分析包括52821名成年人(加权平均年龄45.5岁；48.6%为男性)。其中, 有1642名受试者报告了ADHD的诊断, 4631名受试者报告了糖尿病的诊断。在对年龄, 性别, 种族/族裔, 教育程度, 家庭收入水平, 吸烟, 饮酒, 体育锻炼和体重指数进行校正的多变量分析中, 患有ADHD的成年人与未患ADHD的成年人相比, 其糖尿病OR为1.54(95 % CI:1.16-2.04)。在分层分析中, ADHD与糖尿病之间的显著关联存在于大多数层级中, 并且该关联并未因年龄, 性别, 种族/民族或肥胖状况有明显改变。 结论: 在美国成年人的全国代表性样本中, 我们发现了ADHD的诊断历史与糖尿病之间存在显著关联。.

Chocolate contains both potentially harmful components (i.e., stearic acid and added sugar) and beneficial components (i.e., phenolics and flavonoids). Despite its popularity, long-term health effects of chocolate consumption remain unclear.The aim of this study was to examine the association of chocolate consumption with all-cause and cause-specific mortality.This is a prospective cohort study./setting This study included 84,709 postmenopausal women free of cardiovascular disease (CVD) and cancer at baseline in the Observational Study and Clinical Trials control arm of the prospective Women's Health Initiative cohort who were enrolled during 1993-1998. These women were followed through March 2018.The outcomes included all-cause mortality and cause-specific mortality from CVD, cancer and dementia.Multivariable Cox proportional hazards models were used to estimate adjusted HRs of all-cause mortality and cause-specific mortality.During 1,608,856 person-years of follow up (19.0 years on average [SD=4.2]), 25,388 deaths occurred, including 7,069 deaths from CVD, 7,030 deaths from cancer, and 3,279 deaths from dementia. After adjustment for a variety of covariates, compared to no chocolate consumption, the HRs (95% CIs) for all-cause mortality were 0.95 (0.92, 0.98), 0.93 (0.89, 0.96), 0.97 (0.90, 1.04) and 0.90 (0.84, 0.97) for1 serving/week, 1-3 servings/week, 4-6 servings/week, and ≥1 serving/day of chocolate consumption, respectively (P for trend = 0.02). For CVD mortality, compared to no chocolate consumption, the HRs (95% CIs) were 0.96 (0.91, 1.01), 0.88 (0.82, 0.95), 1.06 (0.93, 1.21) and 0.92 (0.80, 1.05) for1 serving/week, 1-3 servings/week, 4-6 servings/week, and ≥1 serving/day of chocolate consumption, respectively (P for trend = 0.45). For dementia mortality, compared to no chocolate consumption, the HRs (95% CIs) were 0.91 (0.84, 0.99), 0.89 (0.80, 0.99), 0.97 (0.79, 1.18) and 0.97 (0.80, 1.18) for1 serving/week, 1-3 servings/week, 4-6 servings/week, and ≥1 serving/day of chocolate consumption, respectively (P for trend = 0.95). Chocolate consumption was not associated with cancer mortality.The results suggested modest inverse association of chocolate consumption with mortality from all causes, CVD or dementia, specifically for a moderate chocolate consumption of 1-3 servings/week.

INTRODUCTION: Particulate air pollutants may induce neurotoxicity by increasing homocysteine levels, which can be lowered by high B vitamin intakes. Therefore, we examined whether intakes of three B vitamins (folate, B(12), and B(6)) modified the association between PM(2.5) exposure and incidence of all-cause dementia. METHODS: This study included 7183 women aged 65 to 80 years at baseline. B vitamin intakes from diet and supplements were estimated by food frequency questionnaires at baseline. The 3-year average PM(2.5) exposure was estimated using a spatiotemporal model. RESULTS: During a mean follow-up of 9 years, 342 participants developed all-cause dementia. We found that residing in locations with PM(2.5) exposure above the regulatory standard (12 μg/m(3)) was associated with a higher risk of dementia only among participants with lower intakes of these B vitamins. DISCUSSION: This is the first study suggesting that the putative neurotoxicity of PM(2.5) exposure may be attenuated by high B vitamin intakes.

BACKGROUND: We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, whereas protein density associations were mixed. OBJECTIVES: To elucidate and extend this earlier work through biomarker development for protein and carbohydrate components, including animal protein and fiber. METHODS: Prospective disease association analyses were undertaken in Women's Health Initiative (WHI) cohorts of postmenopausal US women, aged 50–79 y when enrolled at 40 US clinical centers. Biomarkers were developed using an embedded human feeding study (n = 153). Calibration equations for protein and carbohydrate components were developed using a WHI nutritional biomarker study (n = 436). Calibrated intakes were associated with chronic disease incidence in WHI cohorts (n = 81,954) over a 20-y (median) follow-up period, using HR regression methods. RESULTS: Previously reported elevations in cardiovascular disease (CVD) with higher-protein diets tended to be explained by animal protein density. For example, for coronary heart disease a 20% increment in animal protein density had an HR of 1.20 (95% CI: 1.02, 1.42) relative to the HR for total protein density. In comparison, cancer and diabetes risk showed little association with animal protein density beyond that attributable to total protein density. Inverse carbohydrate density associations with total CVD were mostly attributable to fiber density, with a 20% increment HR factor of 0.89 (95% CI: 0.83, 0.94). Cancer risk showed little association with fiber density, whereas diabetes risk had a 20% increment HR of 0.93 (95% CI: 0.88, 0.98) relative to the HRs for total carbohydrate density. CONCLUSIONS: In a population of postmenopausal US women, CVD risk was associated with high-animal-protein and low-fiber diets, cancer risk was associated with low-carbohydrate diets, and diabetes risk was associated with low-fiber/low-carbohydrate diets.

The Dietary Guidelines for Americans, 2020–2025 was issued jointly by the US Departments of Agriculture and of Health and Human Services in December 2020. It is the ninth edition of the Dietary Guidelines and is the first to provide recommendations by life stage, from birth to older adulthood. The Dietary Guidelines is grounded in the current body of scientific evidence on diet and health outcomes and aims to promote health and prevent chronic diseases. The process to develop the Dietary Guidelines involved 4 steps: (1) identifying the topics and supporting scientific questions, (2) appointing a Dietary Guidelines Advisory Committee (Committee) to review current scientific evidence, (3) developing the new edition of the Dietary Guidelines, and (4) implementing the Dietary Guidelines. The 2020-2025 edition provides 4 overarching guidelines and supporting key recommendations that encourage healthy dietary patterns across the life span. The foods and beverages that people consume have a profound impact on health, and it is never too late or too early to eat healthfully.

Interval breast cancers (IBCs) emerge after a non-suspicious mammogram and before the patient’s next scheduled screen. Risk factors associated with IBC have not been identified. This study evaluated if the empirical dietary inflammatory pattern (EDIP) or empirical dietary index for hyperinsulinemia (EDIH) scores are associated with IBC compared to screen-detected breast cancer. Data were from women 50–79 years-old in the Women’s Health Initiative cohort who completed food frequency questionnaires at baseline (1993–98) and were followed through March 31, 2019 for breast cancer detection. Women were identified as having either IBC diagnosed within 1-year after their last negative screening mammogram (N = 317) or screen-detected breast cancer (N = 1,928). Multivariable-adjusted logistic regression analyses were used to estimate odds ratios for risk of IBC compared to screen-detected cancer in dietary index tertiles. No associations were observed between EDIP or EDIH and IBC. Odds ratios comparing the highest to the lowest dietary index tertile were 1.08; 95%CI, 0.78–1.48 for EDIP and 0.92; 95%CI, 0.67–1.27 for EDIH. The null associations persisted when stratified by BMI categories. Findings suggest that diet-driven inflammation or insulinemia may not be substantially associated with IBC risk among postmenopausal women. Future studies are warranted to identify modifiable factors for IBC prevention.

AIM: To investigate the association between dietary patterns and total and obesity-related cancers risk. Additionally, to examine if acculturation modifies this relationship. SUBJECT AND METHODS: Dietary intake of postmenopausal Hispanic women (N=5,482) enrolled in the Women’s Health Initiative was estimated from a Food Frequency Questionnaire and used to calculate dietary pattern scores; Healthy Eating Index-2015 (HEI-2015), Mexican Diet (MexD) score, alternate Mediterranean Diet Score (aMED), and the energy adjusted-Dietary Inflammatory Index (E-DII™). Associations were evaluated using Cox proportional hazards regression models. RESULTS: 631 cancers and 396 obesity-related cancers were diagnosed over a mean-follow up of 12 years. Across dietary scores, there were no significant associations with cancer risk or mortality. Trend analysis suggest a potentially lower risk for total cancer related to the highest MexD score (HR 0.68, 95% CI 0.45–1.04, P-trend=0.03), and lower risk for obesity-related cancer mortality related to the highest score category for MexD (HR 0.65, 95% CI 0.37–1.16, P-trend=0.02), and aMED (HR 0.87, 95% CI 0.45–1.67, P-trend=0.04). Further analysis suggests less acculturated women with higher MexD scores had 56% lower risk for any cancer (HR 0.44, 95% CI 0.22–0.88, P-trend=0.03) and 83% lower risk for cancer mortality (HR 0.17, 95% CI 0.04–0.76, P-trend=0.01) compared to more acculturated Hispanic women. CONCLUSIONS: Dietary patterns were not associated with cancer risk and mortality in postmenopausal Hispanic women. Less-acculturated, Spanish-preferred speakers, who reported consuming a more traditional Mexican diet may experience a lower risk for cancer and cancer mortality.

BACKGROUND: Multiple methods of correcting nutrient intake for misreported energy intake have been proposed but have not been extensively compared. The availability of the Women's Health Initiative (WHI) data set, which includes several objective recovery biomarkers, offers an opportunity to compare these corrections with respect to protein intake. OBJECTIVE: We compared 5 energy-correction methods for self-reported dietary protein against urinary nitrogen–derived protein intake. METHODS: As part of the WHI Nutritional Biomarkers Study (NBS) 544 participants (50- to 80-y-old women) completed a FFQ and biomarker assessments using doubly labeled water (DLW) for total energy expenditure (TEE) and 24-h urinary nitrogen. Correction methods evaluated were as follows: 1) DLW-TEE; 2) the Institute of Medicine's (IOM's) estimated energy requirement (EER) TEE prediction equation based on sex, height, weight, and age; 3) published NBS total energy TEE prediction (WHI-NBS-TEE) using age, BMI, race, and income; 4) reported protein versus reported energy linear regression–based residual method; and 5) a Goldberg cutoff to exclude subjects reporting energy intakes

PURPOSE: Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol-breast cancer association. METHODS: A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25-29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol-metabolite associations were evaluated using multivariable linear mixed effects regression. RESULTS: Alcohol was significantly (FDR p

ObjectiveTo examine the association between prediagnostic plasma polyunsaturated fatty acids levels (PUFA) and amyotrophic lateral sclerosis (ALS).MethodsWe identified 275 individuals who developed ALS while enrolled in 5 US prospective cohorts, and randomly selected 2 controls, alive at the time of the case diagnosis, matched on cohort, birth year, sex, ethnicity, fasting status, and time of blood draw. We measured PUFA, expressed as percentages of total fatty acids, using gas liquid chromatography and used conditional logistic regression to estimate risk ratios (RR) and 95% confidence intervals (CI) for the association between PUFA and ALS.ResultsThere was no association between total, n-3, and n-6 PUFA, eicosapentaenoic acid, or docosapentaenoic acid levels and ALS. Higher plasma α-linolenic acid (ALA) in men was associated with lower risk of ALS in age- and matching factor-adjusted analyses (top vs bottom quartile: RR = 0.21 [95% CI 0.07, 0.58], p for trend = 0.004). In women, higher plasma arachidonic acid was associated with higher risk (top vs bottom quartile: RR = 1.65 [95% CI 0.99, 2.76], p for trend = 0.052). Multivariable adjustment, including correlated PUFA, did not change the findings for ALA and arachidonic acid. In men and women combined, higher plasma docosahexaenoic acid (DHA) was associated with higher risk of ALS (top vs bottom quartile: RR = 1.56 [95% CI 1.01, 2.41], p for trend = 0.054), but in multivariable models the association was only evident in men.ConclusionsThe majority of individual PUFAs were not associated with ALS. In men, ALA was inversely and DHA was positively related to risk of ALS, while in women arachidonic acid was positively related. These findings warrant confirmation in future studies.

Background: Contemporary energy expenditure data are crucial to inform and guide nutrition policy in older adults to optimize nutrition and health.Objective: The aim was to determine the optimal method of estimating total energy expenditure (TEE) in adults (aged >= 65 y) through 1) establishing which published predictive equations have the closest agreement between measured resting metabolic rate (RMR) and predicted RMR and 2) utilizing the RMR equations with the best agreement to predict TEE against the reference method of doubly labeled water (DLW).Methods: A database consisting of international participant-level TEE data from DLW studies was developed to enable comparison with energy requirements estimated by 17 commonly used predictive equations. This database included 31 studies comprising 988 participant-level RMR data and 1488 participant-level TEE data. Mean physical activity level (PAL) was determined for men (PAL = 1.69, n = 320) and women (PAL = 1.66, n = 668). Bland-Altman plots assessed agreement of measured RMR and TEE with predicted RMR and TEE in adults aged >= 65 y, and subgroups of 65-79 y and >= 80 y. Linear regression assessed proportional bias.Results: The Ikeda, Livingston, and Mifflin equations most closely agreed with measured RMR and TEE in all adults aged >= 65 y and in the 65-79 y and >= 80 y subgroups. In adults aged >= 65 y, the Ikeda and Livingston equations overestimated TEE by a mean +/- SD of 175 +/- 1362 kJ/d and 86 +/- 1344 kJ/d, respectively. The Mifflin equation underestimated TEE by a mean +/- SD of 24 +/- 1401 kJ/d. Proportional bias was present as energy expenditure increased.Conclusions: The Ikeda, Livingston, or Mifflin equations are recommended for estimating energy requirements of older adults. Future research should focus on developing predictive equations to meet the requirements of the older population with consideration given to body composition and functional measures.

BackgroundEarlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are associated with adult breast density, which could mediate the increased risk.MethodsFrom 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006–2008, 182 participants then aged 25–29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV.ResultsThe mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2–86.1. Age at thelarche was negatively associated with %DBV (ptrend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (ptrend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2–26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9–17.5%)).ConclusionsOur results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.

High consumption of soft drinks has been associated with lower bone mineral density among postmenopausal women. This study explores the association of soft drink consumption, osteoporosis, and incidental fractures in this population.Cross-sectional (at baseline) and cohort combined designs, over 11.9 years of median follow-up for 72,342 postmenopausal women participating in the Women's Health Initiative Observational Study. Multiple linear regression models were used to examine the cross-sectional associations between soft drink consumption and hip and lumbar spine bone mineral density. Cox proportional hazards regression models were used to examine the association of soft drink consumption with incident hip fractures.There were no associations between soft drink consumption and hip or lumbar spine t scores. During 700,388 person-years of follow-up, 2,578 hip fractures occurred. Adjusted hazard ratios for incident hip fracture for the highest consumption category compared with no consumption were 1.26 (95% confidence interval [CI] 1.01-1.56) for total soda and 1.32 (95% CI 1.00-1.75) for caffeine-free soda. There was no association between caffeinated soda and incident hip fracture (hazard ratio = 1.16; 95% CI 0.86-1.57). There was no apparent linear trend in the risk of hip fracture across categories of soda consumption in the fully adjusted models, suggesting a threshold effect. A sensitivity analysis using adjudicated hip fractures showed significant associations for all three soda exposures in the highest intake groups.Consuming more than two servings of soft drinks per day on average showed potential associations with higher risk of hip fracture among postmenopausal women.

Complementary foods and beverages (CFBs) are key components of an infant's diet in the second 6 months of life. This article summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFBs sometime before 6 months. The primary mode of feeding (ie, human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFBs is associated with the timing of introduction and types of CFBs reported. FMF infants (42%) are more likely to be introduced to CFBs before 4 months compared with HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed, including fruit, grains, dairy, proteins, and solid fats. Compared with HMF infants of the same age, FMF infants consume more total energy (845 vs 631 kcal) and protein (22 vs 12 g) from all sources, and more energy (345 vs 204 kcal) and protein (11 vs 6 g) from CFBs alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs 7%), zinc (54% vs3%), and protein (27% vs3%). FMF infants are more likely to have an early introduction (12 months) to fruit juice (45% vs 20%) and cow's milk (36% vs 24%). Registered dietitian nutritionists and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could refine findings from this analysis.

BackgroundMaternal nutrition during pregnancy and lactation has profound effects on the development and lifelong health of the child. Long-chain PUFAs are particularly important for myelination and the development of vision during the perinatal period.ObjectivesWe conducted a systematic review to examine the relationship between supplementation with omega-3 fatty acids during pregnancy and/or lactation and neurodevelopment in children, to inform the Scientific Report of the 2020 Dietary Guidelines Advisory Committee.MethodsWe identified articles on omega-3 fatty acid supplementation in pregnant and lactating women that included measures of neurodevelopment in their children (0-18 y) by searching PubMed, CENTRAL, Embase, and CINAHL Plus. After dual screening articles for inclusion, we qualitatively synthesized and graded the strength of evidence using pre-established criteria for assessing risk of bias, consistency, directness, precision, and generalizability.ResultsWe included 33 articles from 15 randomized controlled trials (RCTs) and 1 prospective cohort study. Of the 8 RCTs that delivered omega-3 fatty acid dietary supplements during pregnancy alone (200-2200mg/d DHA and 0-1100mg/d EPA for approximately 20 wk), 5 studies reported ≥1 finding that supplementation improved measures of cognitive development in the infant or child by 6%-11% (P0.05) result. There was inconsistent or insufficient evidence for other outcomes (language, social-emotional, physical, motor, or visual development; academic performance; risks of attention deficit disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, anxiety, or depression) and for supplementation during lactation or both pregnancy and lactation. Populations with a lower socioeconomic status and adolescents were underrepresented and studies lacked racial and ethnic diversity.ConclusionsLimited evidence suggests that omega-3 fatty acid supplementation during pregnancy may result in favorable cognitive development in the child. There was insufficient evidence to evaluate the effects of omega-3 fatty acid supplementation during pregnancy and/or lactation on other developmental outcomes.

Background The plant‐based Dietary Portfolio combines established cholesterol‐lowering foods (plant protein, nuts, viscous fiber, and phytosterols), plus monounsaturated fat, and has been shown to improve low‐density lipoprotein cholesterol and other cardiovascular disease (CVD) risk factors. No studies have evaluated the relation of the Dietary Portfolio with incident CVD events. Methods and Results We followed 123 330 postmenopausal women initially free of CVD in the Women's Health Initiative from 1993 through 2017. We used Cox proportional‐hazard models to estimate adjusted hazard ratios (HRs) and 95% CI of the association of adherence to a Portfolio Diet score with CVD outcomes. Primary outcomes were total CVD, coronary heart disease, and stroke. Secondary outcomes were heart failure and atrial fibrillation. Over a mean follow‐up of 15.3 years, 13 365 total CVD, 5640 coronary heart disease, 4440 strokes, 1907 heart failure, and 929 atrial fibrillation events occurred. After multiple adjustments, adherence to the Portfolio Diet score was associated with lower risk of total CVD (HR, 0.89; 95% CI, 0.83–0.94), coronary heart disease (HR, 0.86; 95% CI, 0.78–0.95), and heart failure (HR, 0.83; 95% CI, 0.71–0.99), comparing the highest to lowest quartile of adherence. There was no association with stroke (HR, 0.97; 95% CI, 0.87–1.08) or atrial fibrillation (HR, 1.10; 95% CI, 0.87–1.38). These results remained statistically significant after several sensitivity analyses. Conclusions In this prospective cohort of postmenopausal women in the United States, higher adherence to the Portfolio Diet was associated with a reduction in incident cardiovascular and coronary events, as well as heart failure. These findings warrant further investigation in other populations.

Supplemental Digital Content is available in the text., Background: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia. Methods: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63 599) and the UK Biobank (N=59 220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake. Results: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (β, 2.12 [95% CI, 1.16–3.07] mg/dL per allele; P

Background Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions compared with a spot urine sample, if comparable, could reduce participant burden in epidemiologic and clinical studies. Objectives In a 2-week controlled-feeding study, Na and K excretions from a 24-h urine collection were compared with a first-void spot urine sample, applying established algorithms and enhanced models to estimate 24-h excretion. Actual and estimated 24-h excretions were evaluated relative to mean daily Na and K intakes in the feeding study. Methods A total of 153 older postmenopausal women ages 75.4 ± 3.5 y participated in a 2-wk controlled-feeding study with a 4-d repeating menu cycle based on their usual intake (ClinicalTrials.gov Identifier: NCT00000611). Of the 150 participants who provided both a first-void spot urine sample and a 24-h urine collection on the penultimate study day, statistical methods included Pearson correlations for Na and K between intake, 24-h collections, and the 24-h estimated excretions using 4 established algorithms: enhanced biomarker models by regressing ln-transformed intakes on ln-transformed 24-h excretions or ln-transformed 24-h estimated excretions plus participant characteristics and sensitivity analyses for factors potentially influencing Na or K excretion (e.g., possible kidney disease estimated glomerular filtration rate, Twenty-four-hour urine excretion measurement performs better than estimated 24-h excretion from a spot urine as a biomarker for Na and K intake among a sample of primarily white postmenopausal women.

OBJECTIVES: To evaluate the association of the ketogenic ratio of macronutrients (KR) with incidence of diabetes (DM). METHODS: Dietary information was obtained at baseline from postmenopausal women enrolled in the Women's Health Initiative (WHI) clinical trials (not including the intervention arm of dietary modification trial) and observational study. Participants were excluded if they had prevalent diabetes or unknown status of diabetes at baseline or reported energy intakes 5000 kilocalories. The KR was calculated as follows: (0.9*grams fat + 0.46*grams protein) divided by (0.1*grams fat + 0.58*grams protein + grams total carbohydrate – grams total fiber). A KR value 1.5 is considered the minimum threshold to predict a ketogenic diet. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between KR and risk of DM. Follow-up time was the number of days from enrollment to the first instance of incident DM. RESULTS: Among 128 752 participants, there were 19 439 incident cases of DM with median follow-up time of 20.7 years. The median KR was 0.36 and 12 participants (

OBJECTIVES: To inform the Dietary Guidelines for Americans, 2020–2025, the USDA and HHS identified important public health questions to be examined by the 2020 Dietary Guidelines Advisory Committee. The Committee conducted a systematic review with support from USDA's Nutrition Evidence Systematic Review (NESR) team to answer the question: What is the relationship between seafood consumption during pregnancy and lactation and neurocognitive development in the child? METHODS: The Committee developed a protocol that described how they would use NESR's systematic review methodology to examine evidence related to seafood intake during pregnancy and lactation and child neurocognitive development. NESR librarians conducted a literature search (2000–2019) and NESR analysts dual-screened the results using pre-defined inclusion and exclusion criteria. NESR analysts extracted data and assessed risk of bias of included studies. The Committee synthesized the evidence, developed conclusion statements, and graded the strength of evidence underlying the conclusion statements. RESULTS: Twenty-six articles (from 18 prospective cohort studies [PCS]) met inclusion criteria; all assessed prenatal seafood intake and none assessed seafood intake during lactation. Evidence from 15 PCS suggests that prenatal seafood intake has beneficial associations with cognitive development, particularly in young children. Evidence from 12 PCS suggests that there may be a beneficial association between prenatal seafood intake and language/communication development. Less consistent evidence and/or scant to no evidence was available for movement/physical or social-emotional/behavioral development, attention-deficit/hyperactivity disorder, autism, academic performance, anxiety, and depression. CONCLUSIONS: Moderate evidence indicates that seafood intake during pregnancy is associated favorably with measures of cognitive development in young children. Limited evidence suggests that seafood intake during pregnancy may be associated favorably with measures of language and communication development in the child. Insufficient or no evidence was available for all other relationships assessed. FUNDING SOURCES: USDA, Food and Nutrition Service, Center for Nutrition Policy and Promotion, Alexandria, VA.