The Journal of Nutrition

Introduction: Infant neurodevelopment is associated with maternal nutritional status, yet few studies have evaluated the effects of balanced energy-protein (BEP) supplementation during pregnancy and/or lactation. Methods: The Maternal Infant Nutrition Trial (NCT03668977) was a 2x2 factorial, household randomized, unblinded, efficacy trial conducted in Sarlahi District, Nepal. Pregnant women were randomized to daily fortified BEP supplementation or no supplementation, and those with a live birth were re-randomized after delivery to supplementation or not until 6-months postpartum. The first 100 infants in each of the four intervention groups were enrolled in a neurodevelopment substudy. At 6-months, these infants underwent a cognitive, motor, language, and socioemotional assessment using the Bayley Scales of Infant and Toddler Development, fourth edition. Results: Baseline characteristics were similar across the four trial groups. A significant interaction (p< 0.05) between pregnancy and lactation supplementation groups was observed in the language domain only. Infants born to mothers who received BEP supplementation during pregnancy did not differ in standard scores for cognitive (mean difference (MD): 2.0, 95% confidence interval (CI): -0.29, 4.29), motor (MD: 0.98, 95% CI: -1.41, 3.36), or socioemotional (MD: -2.35, 95% CI: -5.27, 0.57) domains compared to the pregnancy control group. Similarly, for these three domains, there were no significant differences among infants whose mothers received BEP in lactation period vs. not. Infants born to mothers supplemented in both pregnancy and lactation had significantly higher mean language standard scores of 2.12 (95% CI: 0.16, 4.08; p-interaction = 0.015), driven by the expressive communication subtest, compared to those with no BEP supplementation in either period. Conclusion: BEP supplementation during pregnancy and/or lactation was not associated with improvements in cognitive, motor, or socioemotional domains at 6 months; however, infants of women supplemented in pregnancy and lactation had significant improvements in the language domain. Evaluation at later ages is warranted.

Background: Yeast (Saccharomyces cerevisiae) is a model organism in agricultural and industrial fermentation with nutritional benefits, yet less is understood about its nutritional value for supporting whole-body protein synthesis in vivo, and its comparison to animal-based protein. Objective: This study aimed to determine the effect of microbial-based protein (yeast) compared to a high (whey) and low (collagen) quality animal-based protein on the ability to support whole-body protein synthesis using the indicator amino acid oxidation technique. Methods: Thirteen healthy participants (M: n=6, 24{+/-}4 yr; F: n=7, 27{+/-}7 yr) consumed eight hourly yeast (Y), whey (W), or collagen (CH) protein beverages at 0.9 g{middle dot}kg-1{middle dot}d-1 supplemented with L-[1-13C]phenylalanine in a randomized, cross-over, counterbalanced design. Breath and urine were collected to measure fraction of expired 13CO2 (F13CO2) and [1-13C]Phe oxidation (PheOx) as inverse correlates of whole-body protein synthesis. An a priori 20% noninferiority margin was used to determine equivalency between protein sources. A Visual Analog Scale (VAS) was provided to assess fullness and hunger by protein sources. Results: Protein source had no effect on F13CO2 (P=0.15) or PheRa (P=0.10). PheOx was greater in CH compared to both Y (14.94{+/-}2.16 vs. 12.93{+/-}2.80 mol{middle dot}kg BM-1{middle dot}h-1, P<0.05) and W (14.94{+/-}2.16 vs. 12.50{+/-}2.75 mol{middle dot}kg BM-1{middle dot}h-1, P<0.05) whereas there was no significant difference between Y and W (P=0.59). Change in PheOx (mean difference [90% CI]) between CH and W (2.44 mol{middle dot}kg BM-1{middle dot}h-1 [0.98, 3.90], P<0.05) and between Y and W (0.44 mol{middle dot}kg BM-1{middle dot}h-1 [-1.34, 2.21], P>0.99) confirmed respective inferiority and noninferiority to W compared to the 20% noninferiority margin (2.50 mol{middle dot}kg BM-1{middle dot}h-1), while Y was superior to CH (-2.00 mol{middle dot}kg BM-1{middle dot}h-1 [-3.01, -0.99], P<0.05). Protein source did not significantly influence satiety (P=0.32) or hunger scores (P=0.15). Conclusion: EAA-enriched whey and yeast protein similarly reduced PheOx as compared to EAA-deficient collagen hydrolysate, suggesting these proteins were similarly superior in supporting whole-body protein synthesis.

Purpose: Iron deficiency impairs sports performance, and female athletes are particularly vulnerable. High-dose iron supplements, commonly used to prevent iron depletion and performance impairments, may cause gastrointestinal side effects and disrupt the gut microbiota. Whether lower doses can improve iron status without adverse effects remains unclear. The aim of this study was to characterize iron intake and iron status in female soccer players during the competitive season and investigate effects of low-dose iron supplementation on iron status, safety-related outcomes and gut microbiota. Methods: In a two-arm parallel randomized controlled trial, female soccer players (median age 21) were randomized to an intervention group (n=12) receiving 3-month low-dose iron supplementation (27 mg elemental iron/day) or a control group (n=11) without supplementation. Blood/fecal samples were collected at baseline and 3-month follow-up. Dietary intake was estimated using 7-day food diaries. Between-group differences were analyzed per protocol (n=18) using ANCOVA with baseline adjustment. Results: The players had inadequate baseline iron intake (median 11.2 mg/day) and 43% had serum ferritin indicating iron depletion (<35 g/L). At follow-up, no significant between-group difference was found for serum ferritin, but fewer athletes in the intervention group experienced decreases from baseline to follow-up (P<0.05). Moreover, serum iron was higher in the intervention group (Pgroup=0.05). No between-group differences were observed for gastrointestinal symptoms or liver damage biomarkers. On the contrary, the intervention led to lower IL-6 (Pgroup=0.04) and higher gut microbial -diversity (Pgroup=0.01) compared to controls. Conclusions: The low-dose iron supplementation was well tolerated, attenuated decreases in iron stores, increased gut microbial diversity and attenuated systemic inflammation in female soccer players with suboptimal dietary iron intake. However, potential adverse effects of long-term exposure cannot be excluded.

Background: Iron deficiency (ID) affects up to 40% of pregnant women in the third trimester, even in highly resourced and iron-supplemented populations, with adverse consequences for maternal health and long-term offspring development. Psychological stress may compromise iron status through hypothalamic-pituitary-adrenocortical (HPA) axis dysregulation and inflammation, but no study has directly examined cortisol in relation to iron status across human pregnancy. Objective: This longitudinal study examined associations between HPA function and maternal iron status across pregnancy and tested whether IL-6 and CRP mediated the relationship between cortisol and ferritin across gestation. Methods: One hundred sixty-eight pregnant Black women with Medicaid insurance completed up to four laboratory assessments across pregnancy. Salivary cortisol was measured before and in response to the Trier Social Stress Test, yielding basal and reactive cortisol indices. Serum ferritin, IL-6, and CRP were collected at each visit. Trimester-specific regression models examined cortisol reactivity in relation to ferritin; linear mixed-effects models with moderated mediation tested whether basal cortisol predicted ferritin via inflammation. Results: Higher cortisol reactivity was associated with lower ferritin specifically in the third trimester (std. {beta} = -0.197, p = .004). Higher basal cortisol predicted a steeper IL-6 rise across gestation (p = .002), and IL-6 was positively associated with ferritin (b = 0.236, p = .006), consistent with inflammatory iron sequestration. The indirect effect of basal cortisol on ferritin via IL-6 was statistically significant, and higher basal cortisol was negatively associated with cortisol reactivity in the third trimester. No pathway was observed through CRP. Conclusion: Greater cortisol reactivity predicted lower third-trimester ferritin, a pattern that suggests cumulative iron depletion, atypically sustained HPA reactivity in late pregnancy, or both. To our knowledge, this is the first prospective study linking cortisol reactivity to iron status across human pregnancy, identifying maternal stress physiology as a novel target for understanding and addressing gestational iron deficiency.

Background: Short-chain fatty acids (SCFAs) are microbial metabolites with immunoregulatory properties. Human milk contains SCFAs which have been proposed as potential modulators of infant immune development. We aimed to examine associations between human milk SCFA concentrations and infant allergic disease outcomes in a high-risk cohort of infants of atopic mothers. Methods: SCFAs were measured by targeted liquid chromatography-mass spectrometry in human milk samples collected at 3 and 6 months postpartum from atopic mothers enrolled in the Infant Fish Oil Supplementation (IFOS) Study (n=147). Associations between milk SCFA concentrations and early childhood allergic disease outcomes (atopic dermatitis, food allergy, allergic rhinitis, and allergen sensitisation at 1 and 2-3 years) were examined using logistic regression. Results: Human milk SCFA concentrations were broadly stable between 3 and 6 months postpartum, except for acetate which was significantly elevated at 6 months. No significant associations were observed between human milk SCFA concentrations and any allergic disease outcome after correction for multiple comparisons (all p>0.05). Conclusions: Human milk SCFA concentrations are not associated with allergic disease outcomes up to 4 years of age. These findings suggest that oral SCFA exposure via human milk is insufficient to reduce infant allergy risk, and that gut SCFA production may be a more relevant target for future allergy prevention research.

Systemic inflammatory diseases can be influenced by dietary intake, with gastrointestinal dysfunction driving both metabolic and behavioural changes mirroring the altered inflammatory profile. Additionally, the use of live biotherapeutic products (LBPs) shows promise for treating metabolic and inflammatory diseases, but their efficacy is limited by poor persistence in inflamed gut environments. Designed to utilize inflammatory byproducts, the LBP EcN::ttr has proven efficacy in the treatment of acute and chronic colitis, however its effects on the metabolic and behavioural patterns remain uncharacterized. We evaluated the effects of EcN::ttr on mice fed a proinflammatory omega-6 PUFA-rich diet. EcN::ttr-treated mice exhibited notable changes in the gut, including an improved expression of tight junction protein occludin, accompanied by reduced serum lipopolysaccharide (LPS) - binding protein, indicating protection against endotoxemia. EcN::ttr improved insulin sensitivity compared to the parental strain, associated with increased hepatic insulin receptor expression and reduced GSK3{beta} activation and endoplasmic reticulum stress. Secondary bile acids in mice treated with EcN::ttr were more abundant, with increases in those associated with resolving diarrhea and bile acid detoxification. Behavioural assessment highlighted a normalization of long-term memory along with a reduction of stress management behaviours. Altogether, EcN::ttr restores gut-liver-brain axis function through coordinated modulation of inflammation, barrier integrity, and bile acid metabolism. HighlightsO_LILive Biotherapeutic Product EcN::ttr, designed with a fitness advantage to survive inflammation, and provides protection against a proinflammatory omega 6-rich diet C_LIO_LIAdministration of EcN::ttr improved metabolic outcomes including increasing insulin sensitivity C_LIO_LIEcN::ttr increased the abundance of secondary bile acids including those that modulate bile acid detoxification C_LIO_LIBehavioural parameters were normalized in mice given EcN::ttr C_LIO_LIEcN::ttr partially normalizes gut-liver-brain axis through restoring barrier integrity, modulating inflammation and improving secondary bile acid metabolism C_LI

BackgroundAlthough human milk (HM) confers important health benefits, how bioactive milk components (e.g., microbiota, oligosaccharides, and fatty acids) interact with infant genetics to influence childhood atopy remains poorly understood. ObjectiveWe investigated interactions between infant genomic susceptibility and exposure to maternal human milk components (HMCs) and assessed whether integrating these genetic and milk features improves prediction of childhood atopy. MethodsLeveraging infant genomic and maternal HMC data from the CHILD Cohort Study, we conducted gene-milk interaction analysis using linear regression models that integrated polygenic risk scores (PRS) of nursing infants with multiple HMC types. Gradient-boosting machines (GBMs) were used to evaluate predictive performance of HMCs and infant PRS for childhood atopy. ResultsChildhood atopy was associated with interactions between infant genomics (e.g., PRS associated with atopy) and exposure to specific human milk microbes (e.g., Abiotrophia, PBonf=0.005, {beta}=0.29), as well as networks of co-occurring HMCs (e.g., a module containing Bifidobacterium longum, 2-fucosyllactose, and eicosapentaenoic acid, P=0.009, {beta}=-12.3). A GBM integrating HMCs and infant PRS achieved the highest predictive performance for childhood atopy with an area under the curve (AUC) of 0.78, outperforming models based on individual HMC types or PRS alone (AUC range: 0.54-0.63). ConclusionIntegration of maternal HMC exposures with infant genomics reveals interaction effects that contribute to prediction of childhood atopy. Understanding how early-life exposures such as HMCs impact the health of children differently depending on their genomic profiles may facilitate the development of personalized intervention strategies to reduce the burden of these health outcomes during childhood. Key messagesO_LIInteractions between infant polygenic risk and exposure to human milk components are associated with childhood atopy. C_LIO_LINetworks of co-occurring human milk microbiota, oligosaccharides, and fatty acids may influence childhood atopy, with effects varying by infant genomic susceptibility. C_LIO_LIIntegration of human milk components with infant genomics improves prediction of childhood atopy compared with individual milk components or genomics alone. C_LI Capsule SummaryThis study demonstrates that interactions between infant polygenic risk and maternal milk components improve prediction of childhood atopy, highlighting opportunities for personalized early-life prevention strategies.

BackgroundDespite the advancements in infant nutrition, a gap still exists in the nutritional composition bioactive ingredients between infant formula and human milk. We developed a next-generation, proof-of-concept infant formula that contains recombinant human milk proteins. ObjectiveTo determine the impact of a novel infant formula (H1) on organ growth and development, and intestinal function compared to donor human milk (DHM) and standard infant formula (S) in a term piglet model. MethodsTerm piglets delivered via cesarean section were fed either a donor human milk (DHM) control, the investigational formula (H1), or infant formula (S) for 10 days. On d 10, a blood sample and tissues were collected. ResultsThere was no difference (P > 0.05) in piglet growth, although H1 piglets had a smaller relative stomach and liver than DHM and S piglets. H1 piglets had higher (P < 0.05) interleukins in the distal ileum, but no other systemic cytokines were elevated compared to the DHM and S piglets. H1 piglet small intestinal histology was similar (P > 0.05) to that of DHM and S piglets. Additionally, H1 piglets had either the same (P > 0.05) or higher (P < 0.05) amino acids in circulation compared to DHM and S piglets. Recombinant human proteins had either similar (P > 0.05) or lower (P < 0.05) activity compared to the native human proteins when assessing the individual ingredients in the H1 formula. ConclusionH1 formula was noninferior to DHM and S based on growth, small intestinal histology and plasma amino acid endpoints when fed to neonatal piglets. These findings warrant further studies to use the neonatal piglet as a model to evaluate more in-depth outcomes of health and safety for new infant formulas. Lay SummaryA novel piglet study shows a hypoallergenic, next-generation infant formula containing recombinant human milk proteins rivals donor human milk and standard formula for growth, gut health, and nutrient status.

While substantial research has examined the role of infant nutrition in early brain and cognitive development, the links between later childhood nutrition, brain development, and cognitive and academic skills remain less explored. In this work, we investigated for the first time the direct and indirect associations between nutrition intake, white matter microstructure and structural connectivity, and cognitive and academic outcomes. Using longitudinal data from typically developing children aged 2 to 14 years, we combined neuroimaging, dietary, and cognitive measures to test direct associations between nutrition and brain structure and connectivity, as well as cognitive and learning outcomes, and to assess whether brain development mediated these relationships. We found that specific nutrients, including DHA, sphingomyelin, iron, niacin, choline, and palmitoleic acid (omega-7), were associated with improved brain structure and connectivity, as well as better cognitive and learning outcomes. We also found that brain development partly mediated the association between childhood nutrition and learning outcomes. To our knowledge, this is the first study to show such a pathway in school-age children. These results add to the growing literature demonstrating the ongoing importance of nutrition beyond infancy in supporting childhood brain and cognitive development.

Background & Aims The adoption of plant-based diets in the United Kingdom (UK) is increasing, which has potential health benefits, but may increase risk of inadequate intakes of some nutrients. We aimed to assess differences in biomarkers of nutritional status and disease across diet groups in UK adults. Methods This cross-sectional analysis included 124 omnivores, 131 flexitarians, 71 pescatarians, 124 vegetarians, and 183 vegans from the Feeding the Future (FEED) follow-up study (2024-2025). Capillary blood samples were collected and analysed for: haemoglobin; lipid measures (low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), non-HDL-C, total cholesterol, and triglycerides); vitamins B12 and D. We estimated age- and sex-adjusted arithmetic or geometric mean concentrations and 95% confidence intervals of these biomarkers across diet groups. Participants taking lipid-lowering medications were excluded for analysis of lipid markers (n = 85). Results We observed differences in concentrations of cholesterol, triglycerides, and vitamin B12 across diet groups (P heterogeneity for all [&le;] 0.03). Cholesterol markers (mmol/L) were lower with greater exclusion of animal foods (omnivores vs vegans, total cholesterol = -0.8; LDL-C = -0.7; HDL-C = -0.2). Triglyceride concentrations (mmol/L) were similar across groups, with slightly higher values in vegetarians (+0.2) and vegans (+0.1) compared with omnivores. Vitamin B12 concentrations (pmol/L) were highest in vegans and lowest in vegetarians compared to omnivores. Supplement users had higher vitamin B12 and D concentrations in all groups (P heterogeneity between strata = <0.001), while non-supplementing vegetarians and vegans had lower, but not deficient, vitamin B12 concentrations compared to omnivores (P heterogeneity between diet groups = <0.001). Conclusions In this contemporary UK cohort, those following plant-based diets had more favourable blood lipid profiles, with little evidence of vitamin B12 or D deficiency, or anaemia. Supplement use was associated with higher vitamin B12 and D concentrations, particularly among vegetarians and vegans.

Low dietary diversity is a risk factor for micronutrient deficiencies. Agricultural interventions that support crop production and livestock rearing may promote dietary diversity and achieve better nutritional outcomes, particularly among low-income households. Their effectiveness may be strengthened when integrated within microfinance platforms. The objective of this study was to estimate the association between an agricultural intervention delivered within a group-based microfinance program and dietary diversity in rural Western Kenya, and determined effect modification by sex. We conducted a cross-sectional design from June to August 2025 in two village wards of Webuye sub-County in rural Western Kenya, using a validated dietary diversity scale to assess the total number of food groups consumed in the previous 24 hours. We interviewed 312 microfinance participants, 156 of whom were in agricultural intervention comprised of farm input subsidies and training, while 156 were not in the intervention. We specified modified Poisson models to estimate the association between intervention receipt and dietary diversity, and tested whether the estimated association differed by sex. Participation in the agricultural intervention was associated with higher diversity among microfinance program members [adjusted PR (95% CI): 1.46 (1.02, 2.06)]. We did not find evidence that the association differed by sex (Wald p-value for interaction term=0.83). Participation in an agricultural intervention was associated with improved dietary diversity. Future prospective using large samples studies should build on these findings to establish temporal ordering, and assess the feasibility and sustainability of integrating agricultural support into microfinance platforms to improve dietary diversity in low-resource settings.

Background: Evidence regarding the double burden of malnutrition (DBM) among hospitalized patients in Vietnam remains limited. This study examined nutritional status at admission and its association with length of hospital stay among adults in Hanoi. Methods: This prospective observational cohort study was conducted in eight public hospitals in Hanoi between September 2018 and November 2019. Adults aged 18-60 years were assessed within 48 hours of admission using interviews, physical examination, anthropometric measurements, and medical records. Nutritional status was classified using the Subjective Global Assessment (SGA) and body mass index (BMI): undernourished (SGA-B or SGA-C or BMI <18.5 kg/m2) and overnourished (SGA-A and BMI [&ge;]25.0 kg/m2). Length of stay was compared across nutritional-status groups using the Kruskal-Wallis test. Results: Among 1,183 registered patients, 1,115 had sufficient data for analysis. Overall, 24% were undernourished and 16% overnourished. Weight loss during the preceding six months was reported by 54%, although most losses were <5%. SGA-B or SGA-C was identified in 20%, whereas 11% had BMI <18.5 kg/m2. The median hospital stay was 8 days, with no significant difference across nutritional status groups. Conclusions DBM was prevalent among hospitalized adults in Hanoi. Indicators of recent nutritional deterioration were more common than low BMI, suggesting that BMI alone may overlook early disease-related nutritional decline. Nutritional status was not associated with length of stay in this relatively young, predominantly mild-to-moderate patient population. Hospital nutritional screening should therefore assess recent nutritional changes across the full BMI spectrum.

Background and aims: Maternal overweight and obesity are increasing worldwide, including Nepal. This study assessed BMI trajectories from early pregnancy to one year postpartum and trends in overweight and obesity over the past two decades in Bhaktapur, Nepal. Methods: In the most recent study, BMI was measured in 800 Nepalese women at three time points: at early pregnancy, 6 and 12 months postpartum (2017-2021). The prevalence of undernutrition, overweight, and obesity was estimated using the World Health Organization and the Asian specific cut-offs. Long-term trends were assessed by comparing these findings with three population-based studies conducted in Bhaktapur between 2001 and 2021 among 2400 women at similar life stages. Results: Mean (SD) BMI increased from 23.7 (3.0) kg/m^2 in early pregnancy to 26.1 (3.3) kg/meter squre at 6 and 25.2 (3.3) kg/m^2 and 12 months. The prevalence of overweight increased from 32.9% in early pregnancy to 48% at 6 months. Using the Asia-specific cut-offs, the prevalences were higher. Results from the three previous population-based studies demonstrated an upward trend where postpartum overweight increased from 11.4% in 2001- 2002 to 44.6% in 2017- 2021. The obesity prevalence rose from 1.8% to 10.9% during this period. Conclusion: Overweight and obesity among Nepalese women have risen dramatically over the past two decades, with postpartum overweight increasing nearly fourfold and obesity more than sixfold. These findings highlight the need for interventions to prevent excessive weight retention and reduce adverse health outcomes.

Background: Chronic kidney disease (CKD) is associated with alterations in the gut microbiome that promote the accumulation of gut-derived uremic solutes and contribute to systemic inflammation, vascular dysfunction, and disease progression. Dietary fiber has emerged as a promising modulator of gut microbial metabolism, yet the influence of fiber physicochemical properties, particularly fermentability and viscosity, on uremic metabolite production in CKD remains poorly understood. Objective: To systematically evaluate the effects of isolated dietary fiber interventions, classified by fermentability and viscosity, on gut microbial metabolites in CKD across experimental rodent models and randomized clinical trials, and to determine whether these fiber properties modify microbial metabolites. Methods: A systematic search of PubMed, Embase, CINAHL, and Cochrane Library (through June 2026) identified randomized controlled trials and controlled rodent studies assessing isolated dietary fiber in CKD. Eligible studies reported at least one gut-derived metabolite (i.e., indoxyl sulfate (IS), p-cresyl sulfate (PCS), trimethylamine-N-oxide (TMAO), tryptophan-derived indoles, or short-chain fatty acids (SCFAs)). Random-effects models were used for pooled estimates using weighted mean differences (WMD) for human studies and standardized mean differences (SMD) for animal studies. Subgroup analyses evaluated fiber fermentability, viscosity, intervention dose, duration, and CKD stage. Risk of bias was assessed with ROB-2 and SYRCLE, and evidence certainty with GRADE. Results: Twenty-eight studies (13 human, 15 animal) met eligibility criteria, comprising 511 participants and 312 animals with CKD. Isolated fiber supplementation, primarily fermentable and non-viscous fibers, reduced IS (human: -0.13 mg/dL; 95% CI: -0.25, -0.01; p = 0.03; animal: -1.99; 95% CI: -3.06, -0.92; p < 0.0001) and pCS (human: -0.23 mg/dL; 95% CI: -0.46, 0.001; p = 0.051; animal: -1.56; 95% CI: -2.08, -1.03; p < 0.0001). SCFAs increased in animal studies, including cecal acetate (2.00, 95% CI: 0.78 to 3.22; p = 0.001) and circulating propionate (1.51, 95% CI: 0.054 to 2.96; p=0.04). There were no dose-dependent effects, but longer interventions (>8 weeks) tended to lower pCS (-0.26 mg/dL, 95% CI: -0.55 to 0.02; p=0.06). Some heterogeneity and low-to-moderate certainty were observed. Conclusion: Isolated dietary fiber reduces major gut-derived uremic solutes in CKD, with fermentability influencing metabolic responsiveness, but with minimal studies on viscous fibers. Larger, longer-duration trials with standardized reporting of total fiber intake and clinical endpoints are needed to guide evidence-based dietary recommendations in CKD.

Background: Iron Deficiency Anemia (IDA) is one of the most prevalent nutritional disorders globally and a leading cause of Disability Adjusted Life Years (DALYs). Conventional diagnostic methods fail to detect deficiencies at an early stage and rarely account for individual genetic5 predisposition. Methods: This study proposes an end-to-end AI-driven precision nutrition pipeline integrating public Genome-Wide Association Study (GWAS) data and NHANES phenotypic data encompassing demographics, dietary intake, anthropometrics, and hematology. A synthetic genotype matrix was simulated for 400 GWAS-filtered SNPs using Hardy-Weinberg Equilibrium. Data preprocessing included missing value imputation, feature engineering, and SMOTE class balancing. Four machine learning models namely, Logistic Regression, Random Forest, Artificial Neural Network (ANN), and XGBoost were implemented and evaluated for both IDA classification and haemoglobin regression tasks. Results: XGBoost achieved state-of-the-art performance with ROC-AUC = 0.9981 for classification and R2 = 0.9903 for haemoglobin prediction. Polygenic Risk Score (PRS) stratification classified participants into low (73%), moderate (18%), and high (9%) risk tiers. Pathway burden analysis identified the Hepcidin Regulation pathway as the highest burden pathway in high-risk individuals. Conclusion: The integration of genomics, machine learning, and nutritional science through a Pathway-Burden Precision Nutrition Engine produced gene-specific, evidence-graded dietary recommendations, demonstrating significant potential for early and personalised IDA prevention.

Background: The U.S. Food and Nutrient Database for Dietary Studies (FNDDS) is updated across NHANES dietary cycles and is central to U.S. nutrition surveillance. However, multi-cycle food-code-level changes in nutrient composition have not been comprehensively characterized across the full WWEIA nutrient panel. Objective: To characterize ten-year temporal patterns in nutrient composition across five FNDDS cycles, evaluate pandemic-period food-code compositional stability, and distinguish exploratory mean-level signals from distributional heterogeneity that may reflect reformulation, database coverage, or food-code definition changes. Methods: We analyzed five consecutive FNDDS biennial releases: 2013-14, 2015-16, 2017-18, 2019-20, and 2021-23. Nutrient values were extracted from the public FNDDS/FoodData Central release files and standardized to per-100-g food-code-level records. Cycle midpoints, 2013.5, 2015.5, 2017.5, 2019.5, and 2022.0, served as the independent variable in an exploratory ordinary least squares (OLS) regression. Mann-Kendall testing assessed monotonic rank trends, Welch's ANOVA assessed food-code-level distributional heterogeneity, and pairwise Welch comparisons with Cohen's d summarized pre-pandemic, pandemic-period, and post-pandemic differences. Equivalence testing using TOST with +/-10% bounds was restricted to the 2019-20 versus 2021-23 stability comparison. OLS sensitivity analyses were repeated after excluding the structurally atypical 2017-18 cycle. Results: Sixty-three nutrients were analyzed. Eight nutrients showed nominal OLS trends, p < 0.05, but none remained significant after Bonferroni correction. Mann-Kendall testing identified two nominal monotonic signals, and none after adjustment. Welch's ANOVA detected cycle-level distributional differences for 61 of 63 nutrients at nominal p < 0.05 and 57 of 63 after adjustment. Pairwise pandemic-period analyses showed many adjusted differences when the pre-pandemic baseline was compared with 2019-20 or 2021-23, but standardized effects were small, with all absolute Cohen's d values < 0.20. No nutrient differed after adjustment between 2019-20 and 2021-23, and 39 of 48 primary analytes met +/-10% TOST equivalence criteria for that comparison. Slope estimates were directionally stable after excluding 2017-18, but nominal significance status remained sensitive to the short time series. Conclusions: FNDDS food composition varied across cycles, but there was no clear decade-long linear trend for most nutrients. The main signal was a possible increase in total PUFA and linoleic acid, which may reflect changes in fat quality. The 2021-23 cycle was very similar to 2019-20, suggesting no major post-pandemic shift in the foods represented. These findings should be interpreted as food-database signals, not as direct estimates of what people consumed.

Background Indias maternal nutrition profile is undergoing a dual-direction shift, with persistent undernutrition coexisting alongside rising overweight and micronutrient deficiencies. Despite national efforts through Integrated Child Development Services (ICDS) and the National Health Mission (NHM), maternal dietary diversity remains suboptimal in India. Frontline health workers (FLWs) play a central role in delivering nutrition counselling; however, gaps remain between knowledge and its translation into practice, highlighting the need to strengthen training, applied competencies, and health system support within primary care settings. Objective To assess knowledge, attitudes, and practices (KAP) regarding maternal nutrition counselling among FLWs and to explore contextual factors influencing counselling delivery. Methods A sequential explanatory mixed-methods study was conducted in Udupi, Karnataka, India. In phase one, 46 FLWs- Accredited Social Health Activists (ASHA), Community Health Officers (CHO), and Primary Health Care Officers (PHCO) completed a validated Knowledge, Attitudes, and Practices (KAP) questionnaire. Data were analysed using descriptive statistics, Kruskal-Wallis test, Spearman correlation, and exploratory multiple linear regression. In phase two, one focus group discussion with 21 participants was conducted and analysed using reflexive thematic analysis. Results FLWs demonstrated moderate KAP scores (37.50 {+/-} 5.09), with lower scores observed in dietary diversity knowledge and counselling practices. CHOs and PHCOs had significantly higher knowledge (p < 0.001) and practice scores (p = 0.002) compared to ASHAs, while attitudes were similar across cadres. Knowledge was positively associated with practice ({rho} = 0.389, p = 0.008). Exploratory regression indicated that cadre and knowledge were associated with practice, while attitude was not statistically significant. Qualitative findings suggested that counselling was largely protocol-based and constrained by workload, limited counselling tools, economic barriers, and cultural food practices. Conclusion Despite positive attitudes towards maternal nutrition counselling, frontline health workers demonstrated gaps in knowledge and counselling practices. Mixed-methods findings suggest that counselling delivery is shaped by both provider competencies and health-system constraints, highlighting the need for implementation-focused strategies to strengthen maternal nutrition counselling in routine antenatal care.

Background: Early trophic feeding promotes gut maturation, feeding tolerance, and growth in preterm neonates. However, delays remain common despite recommendations for initiation within 24 hours of birth, especially in resource-limited settings. Evidence on feeding initiation timing and predictors among Ethiopian preterm neonates is limited. Objective: To determine time to trophic feeding initiation and identify predictors among preterm neonates admitted to Adama Hospital Medical College, Ethiopia. Methods: A hospital-based retrospective cohort study was performed on 436 randomly chosen preterm neonates admitted to NICU. Data extraction was performed using a structured checklist. Time to trophic feeding initiation was analyzed using Kaplan-Meier estimates, log-rank tests, and bivariable and multivariable Cox regression models . Adjusted hazard ratios with 95% CIs were reported. Results:The sample comprised 416 preterm neonates, of whom 311 (74.8%) started trophic feeding during follow-up, and 105 (25.2%) were censored. The rate of initiation of trophic feeding was 1.92 per 100 person-hours (95% CI 1.72 to 2.15). Median time to initiation was 42 hours (interquartile range 24 to 50). Independent predictors of feeding initiation were determined by multivariable analysis and included gestational age, birth weight, maternal anaemia, respiratory distress syndrome and necrotising enterocolitis. Neonates born at 34-36 weeks had earlier initiation than those born at <34 weeks (AHR 1.39; 95 % CI 1.09 to 1.78). Similarly, neonates with a birth weight of [&ge;]1500 g had an earlier initiation than those with a birth weight of <1500 g (AHR 1.41; 95% CI 1.04 to 1.91). Delayed initiation was associated with maternal anaemia (AHR 0.70; 95% CI 0.51-0.95), respiratory distress syndrome (AHR 0.67; 95% CI 0.51-0.88) and necrotising enterocolitis (AHR 0.48; 95% CI 0.33-0.69). Conclusions: Delayed trophic feeding remains common among preterm neonates. Standardized feeding protocols, strengthened maternal care, and individualized nutrition strategies are needed to improve neonatal outcomes in study area.

Background: The Dietary Inflammatory Index (DII) is widely used to assess the inflammatory potential of diet, but it relies on self-reported dietary assessment and does not directly capture individual differences in metabolism as an intermediate connection to inflammation. High-resolution metabolomics provides objective measurements that complement dietary assessment to support precision nutrition to control inflammation. Objective: We developed, tested, and applied a Dietary Metabolite Inflammatory Index (DMII) to assess diet-related chronic inflammation using metabolites measured by liquid chromatography high-resolution mass spectrometry. Methods: DII was calculated using dietaryindex R package with Block Food Frequency Questionnaire (FFQ) data. To develop the DMII, chronic inflammation-related dietary metabolites corresponding to the DII food parameters were found through a literature review. Dietary metabolites were identified and quantified by authentic standards by our established laboratory procedures. DMII uses the same inflammatory effect scores as the DII. Three DMII versions were developed: concentration-based, median-based, and quintile-based DMII. Mean and standard deviation of 29 dietary metabolites were calculated by using 3025 human plasma samples from 3 studies. DMII was tested in the Center for Health Discovery and Well-Being cohort (CHDWB) and the Atlanta African American Maternal and Child cohort (ATLAA) using chronic inflammation biomarkers, including high-sensitivity C-reactive protein (hsCRP), CRP, and IL6. The median-based DMII was further applied to four Alzheimers disease metabolomics datasets as a proof-of-concept application. Results: In the CHDWB study, concentration-based DMII had a weak positive correlation with Block FFQ-derived DII and strongly correlated with median-based and quintile-based DMII. In the same study, all three DMII versions had significant positive correlations with hsCRP and IL6. In the ATLAA study, only concentration-based DMII was positively associated with CRP and IL6. Higher median-based DMII was associated with higher odds of Alzheimers disease. Conclusions: DMII provides a metabolomics-based framework for assessing diet-related chronic inflammation using metabolomics data. This metabolomics approach may complement self-reported dietary assessment to use diet and nutrition to help protect against chronic disease linked to inflammation.

Background: Pregnancy loss has important implications for womens health. Although maternal age is a well-established risk factor, the contribution of routinely measured cardiometabolic and behavioral markers at population-scale remains incompletely characterized. Objective: To examine associations between cardiometabolic, nutritional, and behavioral risk markers and pregnancy loss among U.S. women of reproductive age. Methods: We conducted a cross-sectional analysis of 4,842 U.S. women aged 20-44 years with [&ge;]1 pregnancy using the National Health and Nutrition Examination Survey data (2013-2023). Pregnancy loss was defined as [&ge;]1 prior miscarriages. Exposures included body mass index, smoking exposure (cotinine), lipid biomarkers, vitamin D and folate, and a composite cardiometabolic-nutritional risk score. Survey-weighted logistic regression estimated adjusted odds ratios (aORs) and 95% confidence intervals, with bootstrap resampling for predictor robustness. Results: The weighted prevalence of pregnancy loss was 23%. Higher odds of pregnancy loss were associated with increasing age (aOR per year=1.02; 95% CI: 1.00-1.04), Non-Hispanic Black race (aOR=1.32; 95% CI: 1.00-1.74), overweight (aOR=1.56; 95% CI: 1.16-2.11), obesity (aOR=2.06; 95% CI: 1.39-3.05), and smoking (aOR=1.58; 95% CI: 1.19-2.10). Adverse lipid profiles, particularly elevated triglycerides (aOR=1.83; 95% CI: 1.16-2.90) and high low-density lipoprotein (aOR=2.97; 95% CI: 1.45-6.61), were independently associated with pregnancy loss. Vitamin D/folate were not stable predictors. Higher composite cardiometabolic-nutritional risk scores were observed among women with pregnancy loss (P=0.026). Conclusion: Pregnancy loss clustered with adverse cardiometabolic and behavioral risk markers in a nationally representative population. These findings highlight pregnancy loss as a marker of broader metabolic vulnerability supporting the need for longitudinal studies and cardiometabolic profiling to inform preconception care and risk stratification.