Principles and Practices of Returning Individual Research Results to Participants in Large Studies of Pregnancy and Childhood.

Investigators conducting human subject research have typically conveyed only clinically actionable results back to individual participants. Shifting scientific culture around viewing participants as partners in research, however, is prompting investigators to consider returning as much data or results as the participant would like, even if they are not clearly actionable. Expanding return of individual results may add value for individual participants and their communities, refine future research questions and methods, build trust, and enhance retention of participants. Yet, gaps remain in understanding the implications of these changes for groups of 'vulnerable' participants, including pregnant and pediatric participants. We present the findings of a National Institutes of Health workshop on returning individual research results, particularly as applicable to pregnant and pediatric participants. Research participants who were panelists at the workshop agreed that they desire to receive their results. Workshop findings and current literature indicate that participants have differing preferences for what results they receive. One way to address the limits of current practice is to develop flexible digital platforms that convey individual results along with researchers' availability to answer questions, and to provide as much information as possible about actionable steps to control environmental exposures associated with disease risk.

A Decade of Dietary Assessment Methodology Research at the National Institutes of Health, 2012-2021.

BACKGROUND: Assessment of individual and population-level dietary intake is critical for public health surveillance, epidemiology, and dietary intervention research. In recognition of that need, the National Insitutes of Health (NIH) has a history of funding research projects designed to support the development, implementation, and refinement of tools to assess dietary intake in humans. OBJECTIVES: This report provides data and information on NIH-funded dietary intake assessment methodological research over the period of 2012-2021. METHODS: Data were extracted from an internal NIH data system using the Research, Condition, and Disease Categorization (RCDC) spending category for Nutrition. Data were then examined to identify research focused on dietary assessment tools or methods to capture or analyze dietary intake. RESULTS: Over the decade of 2012-2021, NIH supported 46 grants and 2 large contracts specific to dietary assessment methods development. The top 6 Institutes and Offices funding dietary assessment methods research were identified. Most projects were limited to adults. Projects ranged from novel methods to capture dietary intake, and refinement of analytical methods, to biomarkers of dietary intake. One key contract supported the automated self-administered 24-h dietary assessment tool (ASA24), a widely used, free tool available to the research community for assessing dietary intake. CONCLUSIONS: NIH's support for dietary assessment methods development over this 10-y period was small but grew over time with an expanding number and variety of methods, data sources, and technological advancements in the assessment of dietary intake. NIH remains committed to supporting research seeking to advance the field of dietary assessment methods research.

Nonfood Prebiotic, Probiotic, and Synbiotic Use Has Increased in US Adults and Children From 1999 to 2018.

BACKGROUND & AIMS: Public interest in pre-, pro-, and synbiotic products is increasing because of interactions between gut microbiota and human health. Our aim was to describe nonfood (from dietary supplements or medication) pre-, pro-, and synbiotic use by US adults and children and reported reasons. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES), we text-mined dietary supplement and prescription medication labels and ingredients to identify pre-, pro-, and synbiotic products used in the past 30 days. We describe trends in use from 1999 to 2018 (n = 101,199) and prevalence in 2015-2016 and 2017-2018 (n = 19,215) by age groups, sex, ethnicity/race, education, income, self-reported diet and health quality, and prescription gastrointestinal medication use stratified by children (<19 years) and adults (19+ years). RESULTS: Nonfood pre-, pro-, and synbiotic use increased up to 3-fold in recent cycles. Prevalence of use for all ages for prebiotics was 2.4% (95% confidence interval [CI], 2.0-2.9), for probiotics was 4.5% (95% CI, 3.5-5.6), and for synbiotics was 1.1% (95% CI, 0.8-1.5). Use was highest among older adults (8.8% [95% CI, 5.4-13.3] among those aged 60-69 years for probiotics), non-Hispanic Whites, those with higher educational attainment and income, those with more favorable self-reported diet or health quality, and those with concurrent prescription gastrointestinal medication use. The top reasons for use were for digestive health and to promote/maintain general health. Less than 30% reported using these products based on a health care provider's recommendation. CONCLUSIONS: One in 20 US adults or children use nonfood pre-, pro-, or synbiotic products, and use has sharply increased in recent years. Most individuals voluntarily take these products for general digestive or overall health reasons.

Improving Nutrition in the First 1000 Days in the United States: A Federal Perspective.

The first 1000 days begins with pregnancy and ends at the child's second birthday. Nutrition throughout the life course, and especially during the first 1000 days, supports maternal health and optimal growth and development for children. We give a high-level summary of the state of nutrition in the first 1000 days in the United States. We provide examples where continued efforts are needed. We then discuss select opportunities to strengthen federal research and surveillance, programs, and communication and dissemination efforts aimed at improving nutrition and positively, and equitably, influencing the health and well-being of mothers and children. (Am J Public Health. 2022;112(S8):S817-S825. https://doi.org/10.2105/AJPH.2022.307028).

Diet-induced weight loss leads to a switch in gene regulatory network control in the rectal mucosa.

BACKGROUND: Weight loss may decrease risk of colorectal cancer in obese individuals, yet its effect in the colorectum is not well understood. We used integrative network modeling, Passing Attributes between Networks for Data Assimilation, to estimate transcriptional regulatory network models from mRNA expression levels from rectal mucosa biopsies measured pre- and post-weight loss in 10 obese, pre-menopausal women. RESULTS: We identified significantly greater regulatory targeting of glucose transport pathways in the post-weight loss regulatory network, including "regulation of glucose transport" (FDR=0.02), "hexose transport" (FDR=0.06), "glucose transport" (FDR=0.06) and "monosaccharide transport" (FDR=0.08). These findings were not evident by gene expression analysis alone. Network analysis also suggested a regulatory switch from NFΚB1 to MAX control of MYC post-weight loss. CONCLUSIONS: These network-based results expand upon standard gene expression analysis by providing evidence for a potential mechanistic alteration caused by weight loss.

Diet Quality and Colorectal Cancer Risk in the Women's Health Initiative Observational Study.

Diet quality index scores on Healthy Eating Index 2010 (HEI-2010), Alternative HEI-2010, alternative Mediterranean Diet Index, and the Dietary Approaches to Stop Hypertension (DASH) index have been inversely associated with all-cause and cancer-specific death. This study assessed the association between these scores and colorectal cancer (CRC) incidence as well as CRC-specific mortality in the Women's Health Initiative Observational Study (1993-2012), a US study of postmenopausal women. During an average of 12.4 years of follow-up, there were 938 cases of CRC and 238 CRC-specific deaths. We estimated multivariate hazard ratios and 95% confidence intervals for relationships between quintiles of diet scores (from baseline food frequency questionnaires) and outcomes. HEI-2010 score (hazard ratios were 0.81, 0.77, and 0.73 with P values of 0.04, 0.01, and <0.01 for quintiles 3-5 vs. quintile 1, respectively) and DASH score (hazard ratios were 0.72, 0.74, and 0.78 with P values of <0.01, <0.01, and 0.03 for quintiles 3-5 vs. quintile 1, respectively), but not other diet scores, were associated with a lower risk of CRC in adjusted models. No diet scores were significantly associated with CRC-specific mortality. Closer adherence to HEI-2010 and DASH dietary recommendations was inversely associated with risk of CRC in this large cohort of postmenopausal women.

Meta-analysis of Egg Consumption and Risk of Coronary Heart Disease and Stroke.

The possible relationship between dietary cholesterol and cardiac outcomes has been scrutinized for decades. However, recent reviews of the literature have suggested that dietary cholesterol is not a nutrient of concern. Thus, we conducted a meta-analysis of egg intake (a significant contributor to dietary cholesterol) and risk of coronary heart disease (CHD) and stroke. A comprehensive literature search was conducted through August 2015 to identify prospective cohort studies that reported risk estimates for egg consumption in association with CHD or stroke. Random-effects meta-analysis was used to generate summary relative risk estimates (SRREs) for high vs low intake and stratified intake dose-response analyses. Heterogeneity was examined in subgroups where sensitivity and meta regression analyses were conducted based on increasing egg intake. A 12% decreased risk (SRRE = 0.88, 95% confidence interval [CI], 0.81-0.97) of stroke was observed in the meta-analysis of 7 studies of egg intake (high vs low; generally 1/d vs <2/wk), with little heterogeneity (p-H = 0.37, I2 = 7.50). A nonstatistically significant SRRE of 0.97 (95% CI, 0.88-1.07, p-H = 0.67, I2 = 0.00) was observed in the meta-analysis of 7 studies of egg consumption and CHD. No clear dose-response trends were apparent in the stratified intake meta-analyses or the meta regression analyses. Based on the results of this meta-analysis, consumption of up to one egg daily may contribute to a decreased risk of total stroke, and daily egg intake does not appear to be associated with risk of CHD. Key Teaching Points: • The role of egg consumption in the risk of stroke and coronary heart disease has come under scrutiny over many years. • A comprehensive meta-analysis of prospective cohort studies that reported risk estimates for egg consumption in association with CHD or stroke was performed on the peer-reviewed epidemiologic literature through August 2015. • Overall, summary associations indicate that intake of up to 1 egg daily may be associated with reduced risk of total stroke. • Overall, summary associations show no clear association between egg intake and increased or decreased risk of CHD. • Eggs are a relatively low-cost and nutrient-dense whole food that provides a valuable source of protein, essential fatty acids, antioxidants, choline, vitamins, and minerals.

Dairy consumption and CVD: a systematic review and meta-analysis.

Inverse associations between dairy consumption and CVD have been reported in several epidemiological studies. Our objective was to conduct a meta-analysis of prospective cohort studies of dairy intake and CVD. A comprehensive literature search was conducted to identify studies that reported risk estimates for total dairy intake, individual dairy products, low/full-fat dairy intake, Ca from dairy sources and CVD, CHD and stroke. Random-effects meta-analyses were used to generate summary relative risk estimates (SRRE) for high v. low intake and stratified intake dose-response analyses. Additional dose-response analyses were performed. Heterogeneity was examined in sub-group and sensitivity analyses. In total, thirty-one unique cohort studies were identified and included in the meta-analysis. Several statistically significant SRRE below 1.0 were observed, namely for total dairy intake and stroke (SRRE=0·91; 95% CI 0·83, 0·99), cheese intake and CHD (SRRE=0·82; 95% CI 0·72, 0·93) and stroke (SRRE=0·87; 95% CI 0·77, 0·99), and Ca from dairy sources and stroke (SRRE=0·69; 95% CI 0·60, 0·81). However, there was little evidence for inverse dose-response relationships between the dairy variables and CHD and stroke after adjusting for within-study covariance. The results of this meta-analysis of prospective cohort studies have shown that dairy consumption may be associated with reduced risks of CVD, although additional data are needed to more comprehensively examine potential dose-response patterns.

Dietary polyamine intake and polyamines measured in urine.

Dietary polyamines have recently been associated with increased risk of pre-malignant colorectal lesions. Because polyamines are synthesized in cells and taken up from dietary sources, development of a biomarker of exposure is challenging. Excess polyamines are primarily excreted in the urine. This pilot study seeks to identify dietary correlates of excreted urinary polyamines as putative biomarkers of exposure. Dietary polyamines/other nutrients were estimated from a food frequency questionnaire (FFQ) and correlated with urinary levels of acetylated polyamines in 36 men using 24-h urine samples. Polyamines, abundant in cheese and citrus, were highly positively correlated with urinary N(8)-acetylspermidine (correlation coefficient; r = 0.37, P = 0.03), but this correlation was attenuated after adjustment for total energy intake (r = 0.07, P = 0.68). Dietary energy intake itself was positively correlated with urinary total acetylated polyamine output (r = .40, P = 0.02). In energy-adjusted analyses, folic acid and folate from food were associated with urinary N(1),N(12)-diacetylspermine (r = 0.34, P = 0.05 and r = -0.39, P = 0.02, respectively). Red meat negatively correlated with total urinary acetylated polyamines (r = -0.42, P = 0.01). Our findings suggest that energy, folate, folic acid, saturated fat, and red meat intake, as opposed to FFQ-estimated dietary polyamines, are correlated with urinary polyamines.

Perspective: Early-Life Nutrition Research Supported by the US National Institutes of Health from 2018 to 2020.

The Dietary Guidelines for Americans, 2020-2025, included guidelines for pregnancy, lactation, and children from birth to age 24 mo (B-24) to reflect the growing body of evidence about appropriate nutrition during the earliest stages of life. Guidelines were based on a thorough review of the existing scientific evidence by the 2020 Dietary Guidelines Advisory Committee (DGAC). This study's objective was to enumerate early-life (pregnancy, lactation, and B-24) nutrition research needs that are already being addressed by the scientific community and to identify remaining research gaps. The Scientific Report of the 2020 Dietary Guidelines Advisory Committee was reviewed, and 138 research gaps relevant to early life were identified. Research gaps were consolidated into 13 topic areas. A total of 1632 nutrition- and early-life-focused research projects funded by the NIH between 2018 and 2020 were manually coded using title, abstract, and public health relevance statement available on NIH RePORTER. Projects were coded as affirmative if they addressed a research gap within 1 of the 13 research gap topic areas. Of coded projects, 235 (14.4%) addressed any early-life nutrition research gap. Between fiscal years 2018 to 2020, total costs of projects addressing any gap represented only 15% of total costs for all projects reviewed. Complementary foods, breastfeeding (never vs. ever), and frequency of eating were research gap areas most frequently coded as being addressed by a funded project. Iron supplementation, seafood consumption, and maternal diet food allergens were research gap areas least frequently coded as being potentially addressed by a funded project. This analysis highlights opportunities for changes in the federal government investment in maternal and child nutrition research to support development of effective, evidence-based dietary guidelines for improvement in early-life nutrition practices and overall public health.

Perspective: Human Milk Composition and Related Data for National Health and Nutrition Monitoring and Related Research.

National health and nutrition monitoring is an important federal effort in the United States and Canada, and the basis for many of their nutrition and health policies. Understanding of child exposures through human milk (HM) remains out of reach due to lack of current and representative data on HM's composition and intake volume. This article provides an overview of the current national health and nutrition monitoring activities for HM-fed children, HM composition (HMC) and volume data used for exposure assessment, categories of potential measures in HM, and associated variability factors. In this Perspective, we advocate for a framework for collection and reporting of HMC data for national health and nutrition monitoring and programmatic needs, including a shared vision for a publicly available Human Milk Composition Data Repository (HMCD-R) to include essential metadata associated with HMC. HMCD-R can provide a central, integrated platform for researchers and public health officials for compiling, evaluating, and sharing HMC data. The compiled compositional and metadata in HMCD-R would provide pertinent measures of central tendency and variability and allow use of modeling techniques to approximate compositional profiles for subgroups, providing more accurate exposure assessments for purposes of monitoring and surveillance. HMC and related metadata could facilitate understanding the complexity and variability of HM composition, provide crucial data for assessment of infant and maternal nutritional needs, and inform public health policies, food and nutrition programs, and clinical practice guidelines.

The need to study human milk as a biological system.

Critical advancement is needed in the study of human milk as a biological system that intersects and interacts with myriad internal (maternal biology) and external (diet, environment, infections) factors and its plethora of influences on the developing infant. Human-milk composition and its resulting biological function is more than the sum of its parts. Our failure to fully understand this biology in a large part contributes to why the duration of exclusive breastfeeding remains an unsettled science (if not policy). Our current understanding of human-milk composition and its individual components and their functions fails to fully recognize the importance of the chronobiology and systems biology of human milk in the context of milk synthesis, optimal timing and duration of feeding, and period of lactation. The overly simplistic, but common, approach to analyzing single, mostly nutritive components of human milk is insufficient to understand the contribution of either individual components or the matrix within which they exist to both maternal and child health. There is a need for a shift in the conceptual approach to studying human milk to improve strategies and interventions to support better lactation, breastfeeding, and the full range of infant feeding practices, particularly for women and infants living in undernourished and infectious environments. Recent technological advances have led to a rising movement towards advancing the science of human-milk biology. Herein, we describe the rationale and critical need for unveiling the multifunctionality of the various nutritional, nonnutritional, immune, and biological signaling pathways of the components in human milk that drive system development and maturation, growth, and development in the very early postnatal period of life. We provide a vision and conceptual framework for a research strategy and agenda to change the field of human-milk biology with implications for global policy, innovation, and interventions.

New NIH Primary and Secondary Prevention Research During 2012-2019.

INTRODUCTION: This manuscript characterizes primary and secondary prevention research in humans and related methods research funded by NIH in 2012‒2019. METHODS: The NIH Office of Disease Prevention updated its prevention research taxonomy in 2019‒2020 and applied it to a sample of 14,523 new extramural projects awarded in 2012-2019. All projects were coded manually for rationale, exposures, outcomes, population focus, study design, and type of prevention research. All results are based on that manual coding. RESULTS: Taxonomy updates resulted in a slight increase, from an average of 16.7% to 17.6%, in the proportion of prevention research awards for 2012‒2017; there was a further increase to 20.7% in 2019. Most of the leading risk factors for death and disability in the U.S. were observed as an exposure or outcome in <5% of prevention research projects in 2019 (e.g., diet, 3.7%; tobacco, 3.9%; blood pressure, 2.8%; obesity, 4.4%). Analysis of existing data became more common (from 36% to 46.5%), whereas randomized interventions became less common (from 20.5% to 12.3%). Randomized interventions addressing a leading risk factor in a minority health or health disparities population were uncommon. CONCLUSIONS: The number of new NIH awards classified as prevention research increased to 20.7% in 2019. New projects continued to focus on observational studies and secondary data analysis in 2018 and 2019. Additional research is needed to develop and test new interventions or develop methods for the dissemination of existing interventions, which address the leading risk factors, particularly in minority health and health disparities populations.

Effect of Incorporating Genetic Testing Results into Nutrition Counseling and Care on Dietary Intake: An Evidence Analysis Center Systematic Review-Part I.

Consumer interest in personalized nutrition based on nutrigenetic testing is growing. Recently, multiple, randomized controlled trials have sought to understand whether incorporating genetic information into dietary counseling alters dietary outcomes. The objective of this systematic review was to examine how incorporating genetic information into nutrition counseling and care, compared to an alternative intervention or control group, impacts dietary outcomes. This is the first of a 2-part systematic review series. Part II reports anthropometric, biochemical, and disease-specific outcomes. Peer-reviewed randomized controlled trials were identified through a systematic literature search of multiple databases, screened for eligibility, and critically reviewed and synthesized. Conclusion statements were graded to determine quality of evidence for each dietary outcome reported. Reported outcomes include intake of total energy and macronutrients, micronutrients, foods, food groups, food components (added sugar, caffeine, and alcohol), and composite diet scores. Ten articles representing 8 unique randomized controlled trials met inclusion criteria. Of 15 conclusion statements (evidence grades: Weak to Moderate), 13 concluded there was no significant effect of incorporating genetic information into nutrition counseling/care on dietary outcomes. Limited data suggested that carriers of higher-risk gene variants were more likely than carriers of low-risk gene variants to significantly reduce intake of sodium and alcohol in response to nutrition counseling that incorporated genetic results. Included studies differed in quality, selected genetic variants, timing and intensity of intervention, sample size, dietary assessment tools, and population characteristics. Therefore, strong conclusions could not be drawn. Collaboration between the Academy of Nutrition and Dietetics and professional nutrigenetic societies would likely prove valuable in prioritizing which genetic variants and targeted nutrition messages have the most potential to alter dietary outcomes in a given patient subpopulation and, thus, should be the targets of future research.

Effect of Incorporating Genetic Testing Results into Nutrition Counseling and Care on Health Outcomes: An Evidence Analysis Center Systematic Review-Part II.

In recent years, literature examining implementation of nutritional genomics into clinical practice has increased, including publication of several randomized controlled trials (RCTs). This systematic review addressed the following question: In children and adults, what is the effect of incorporating results of genetic testing into nutrition counseling and care compared with an alternative intervention or control group, on nutrition-related health outcomes? A literature search of MEDLINE, Embase, PsycINFO, CINAHL, and other databases was conducted for peer-reviewed RCTs published from January 2008 until December 2018. An international workgroup consisting of registered dietitian nutritionists, systematic review methodologists, and evidence analysts screened and reviewed articles, summarized data, conducted meta-analyses, and graded conclusion statements. The second in a two-part series, this article specifically summarizes evidence from RCTs that examined health outcomes (ie, quality of life, disease incidence and prevention of disease progression, or mortality), intermediate health outcomes (ie, anthropometric measures, body composition, or relevant laboratory measures routinely collected in practice), and adverse events as reported by study authors. Analysis of 11 articles from nine RCTs resulted in 16 graded conclusion statements. Among participants with nonalcoholic fatty liver disease, a diet tailored to genotype resulted in a greater reduction of percent body fat compared with a customary diet for nonalcoholic fatty liver disease. However, meta-analyses for the outcomes of total cholesterol, low-density lipoprotein cholesterol, body mass index, and weight yielded null results. Heterogeneity between studies and low certainty of evidence precluded development of strong conclusions about the incorporation of genetic information into nutrition practice. Although there are still relatively few well-designed RCTs to inform integration of genetic information into the Nutrition Care Process, the field of nutritional genomics is evolving rapidly, and gaps in the literature identified by this systematic review can inform future studies.

Substance use prevention research funded by the NIH.

BACKGROUND: Substance use is a leading preventable cause of death in the U.S. The National Institutes of Health (NIH) provides public funding to advance understanding on the causes of substance use disorders and apply that knowledge to improve public health through research that develops new and improved strategies to prevent substance use. The purpose of this study was to characterize substance use prevention research funded by the NIH. METHODS: Leveraging a dataset of NIH-funded prevention research, we identified grants studying substance use during 2012-2017. We coded the substances and types of prevention research studied in these grants. We generated descriptive statistics and estimated trends using weighted data representing the entire NIH substance use prevention research portfolio. RESULTS: Approximately 2.4% of all NIH research awards focused on substance use prevention during 2012-2017, with most focused on Epidemiologic Research. Alcohol and Nicotine were the top two substance categories studied. Marijuana prevention research showed a significant upward trend in funding over time (p = 0.002). Among studies of College Students and Military/Veterans, over three-quarters focused on Alcohol. Studies of Pregnant/Port-partum Women mostly focused on Nicotine. CONCLUSIONS: While substance use is a leading cause for morbidity and mortality, substance use prevention grants comprised a small portion of NIH's research portfolio during 2012-2017. These grants demonstrated breadth in the substances studied and the types of prevention research. Opportunities for further study are discussed.

Assessment of Prevention Research Measuring Leading Risk Factors and Causes of Mortality and Disability Supported by the US National Institutes of Health.

Importance: No studies to date have examined support by the National Institutes of Health (NIH) for primary and secondary prevention research in humans and related methods research that measures the leading risk factors or causes of death or disability as outcomes or exposures. Objective: To characterize NIH support for such research. Design and Setting: This serial cross-sectional study randomly sampled NIH grants and cooperative agreements funded during fiscal years 2012 through 2017. For awards with multiple subprojects, each was treated as a separate project. Study characteristics, outcomes, and exposures were coded from October 2015 through February 2019. Analyses weighted to reflect the sampling scheme were completed in March through June 2019. Using 2017 data from the Centers for Disease Control and Prevention and 2016 data from the Global Burden of Disease project, the leading risk factors and causes of death and disability in the United States were identified. Main Outcomes and Measures: The main outcome was the percentage of the NIH prevention research portfolio measuring a leading risk factor or cause of death or disability as an outcome or exposure. Results: A total of 11 082 research projects were coded. Only 25.9% (95% CI, 24.0%-27.8%) of prevention research projects measured a leading cause of death as an outcome or exposure, although these leading causes were associated with 74.0% of US mortality. Only 34.0% (95% CI, 32.2%-35.9%) measured a leading risk factor for death, although these risk factors were associated with 57.3% of mortality. Only 31.4% (95% CI, 29.6%-33.3%) measured a leading risk factor for disability-adjusted life-years lost, although these risk factors were associated with 42.1% of disability-adjusted life-years lost. Relatively few projects included a randomized clinical trial (24.6%; 95% CI, 22.5%-26.9%) or involved more than 1 leading cause (3.3%; 95% CI, 2.6%-4.1%) or risk factor (8.8%; 95% CI, 7.9%-9.8%). Conclusions and Relevance: In this cross-sectional study, the leading risk factors and causes of death and disability were underrepresented in the NIH prevention research portfolio relative to their burden. Because so much is already known about these risk factors and causes, and because randomized interventions play such a vital role in the development of clinical and public health guidelines, it appears that greater attention should be given to develop and test interventions that address these risk factors and causes, addressing multiple risk factors or causes when possible.