Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study.

BACKGROUND: Overnutrition in utero may increase offspring risk of nonalcoholic fatty liver disease (NAFLD), but the specific contribution of maternal diet quality during pregnancy to this association remains understudied in humans. OBJECTIVES: This study aimed to examine the associations of maternal diet quality during pregnancy with offspring hepatic fat in early childhood (median: 5 y old, range: 4-8 y old). METHODS: Data were from 278 mother-child pairs in the longitudinal, Colorado-based Healthy Start Study. Multiple 24-h recalls were collected from mothers during pregnancy on a monthly basis (median: 3 recalls, range: 1-8 recalls starting after enrollment), and used to estimate maternal usual nutrient intakes and dietary pattern scores [Healthy Eating Index-2010 (HEI-2010), Dietary Inflammatory Index (DII), and Relative Mediterranean Diet Score (rMED)]. Offspring hepatic fat was measured in early childhood by MRI. Associations of maternal dietary predictors during pregnancy with offspring log-transformed hepatic fat were assessed using linear regression models adjusted for offspring demographics, maternal/perinatal confounders, and maternal total energy intake. RESULTS: Higher maternal fiber intake and rMED scores during pregnancy were associated with lower offspring hepatic fat in early childhood in fully adjusted models [Back-transformed ß (95% CI): 0.82 (0.72, 0.94) per 5 g/1000 kcal fiber; 0.93 (0.88, 0.99) per 1 SD for rMED]. In contrast, higher maternal total sugar and added sugar intakes, and DII scores were associated with higher offspring hepatic fat [Back-transformed ß (95% CI): 1.18 (1.05, 1.32) per 5% kcal/d added sugar; 1.08 (0.99, 1.18) per 1 SD for DII]. Analyses of dietary pattern subcomponents also revealed that lower maternal intakes of green vegetables and legumes and higher intake of "empty calories" were associated with higher offspring hepatic fat in early childhood. CONCLUSIONS: Poorer maternal diet quality during pregnancy was associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for the primordial prevention of pediatric NAFLD.

Identifying Foods That Optimize Intake of Key Micronutrients During Pregnancy.

BACKGROUND: Most pregnant women in the United States are at risk of inadequate intake of vitamin A, vitamin D, folic acid, calcium, iron, and omega-3 fatty acids from foods alone. Very few United States dietary supplements provide sufficient doses of all 6 nutrients without inducing excess intake. OBJECTIVE: We aimed to identify energy-efficient foods that provide sufficient doses of these nutrients and could be consumed in lieu of dietary supplements to achieve the recommended intake in pregnancy. METHODS: In a previous analysis of 2,450 pregnant women, we calculated the range of additional intake needed to shift 90% of participants to intake above the estimated average requirement and keep 90% below the tolerable upper level for these 6 nutrients. Here, we identified foods and beverages from the 2019 to 2020 Food and Nutrient Database for Dietary Studies that provide target levels of these nutrients without exceeding the additional energy intake recommended for pregnancy beginning in the second trimester (340 kilocalories). RESULTS: We identified 2358 candidate foods meeting the target intake range for at least one nutrient. No candidate foods provided target amounts of all 6 nutrients. Seaweed (raw or cooked without fat) provided sufficient vitamin A, folate, calcium, iron, and omega-3s (5 of 6 nutrients) but would require an intake of >5 cups/d. Twenty-one other foods/beverages (mainly fish, vegetables, and beverages) provided target amounts of 4 of the 6 nutrients. Few foods met targets for vitamin D (n = 54) or iron (n = 93). CONCLUSIONS: Results highlight the difficulty in meeting nutritional requirements from diet alone and imply that dietary supplements are likely necessary to meet vitamin D and iron targets in pregnancy, as well as omega-3 fatty acid targets for individuals who do not consume fish products. Other foods could be added in limited amounts to help meet intake targets without exceeding caloric recommendations or nutrient safety limits.

Untargeted, High-Resolution Metabolomics in Pediatric Eosinophilic Esophagitis.

BACKGROUND/OBJECTIVES: Eosinophilic esophagitis (EoE) is an inflammatory disease of unclear etiology. The aim of this study was to use untargeted plasma metabolomics to identify metabolic pathway alterations associated with EoE to better understand the pathophysiology. METHODS: This prospective, case-control study included 72 children, aged 1-17 years, undergoing clinically indicated upper endoscopy (14 diagnosed with EoE and 58 controls). Fasting plasma samples were analyzed for metabolomics by high-resolution dual-chromatography mass spectrometry. Analysis was performed on sex-matched groups at a 2:1 ratio. Significant differences among the plasma metabolite features between children with and without EoE were determined using multivariate regression analysis and were annotated with a network-based algorithm. Subsequent pathway enrichment analysis was performed. RESULTS: Patients with EoE had a higher proportion of atopic disease (85.7% vs 50%, P = 0.019) and any allergies (100% vs 57.1%, P = 0.0005). Analysis of the dual chromatography features resulted in a total of 918 metabolites that differentiated EoE and controls. Glycerophospholipid metabolism was significantly enriched with the greatest number of differentiating metabolites and overall pathway enrichment ( P < 0.01). Multiple amino and fatty acid pathways including linoleic acid were also enriched, as well as pyridoxine metabolism ( P < 0.01). CONCLUSIONS: In this pilot study, we found differences in metabolites involved in glycerophospholipid and inflammation pathways in pediatric patients with EoE using untargeted metabolomics, as well as overlap with amino acid metabolome alterations found in atopic disease.

Health Information Technology Adoption at U.S. Home Health Care Agencies: Results from a Multi-Methods Study.

Health information technology (HIT) holds potential to transform Home Health Care (HHC), yet, little is known about its adoption in this setting. In the context of infection prevention and control, we aimed to: (1) describe challenges associated with the adoption of HIT, for example, electronic health records (EHR) and telehealth and (2) examine HHC agency characteristics associated with HIT adoption. We conducted in-depth interviews with 41 staff from 13 U.S. HHC agencies (May-October 2018), then surveyed a stratified random sample of 1506 agencies (November 2018-December 2019), of which 35.6% participated (N = 536 HHC agencies). We applied analytic weights, generating nationally-representative estimates, and computed descriptive statistics, bivariate and multivariable analyses. Four themes were identified: (1) Reflections on providing HHC without EHR; (2) Benefits of EHR; (3) Benefits of other HIT; (4) Challenges with HIT and EHR. Overall, 10% of the agencies did not have an EHR; an additional 2% were in the process of acquiring one. Sixteen percent offered telehealth, and another 4% were in the process of acquiring telehealth services. In multivariable analysis, EHR use varied significantly by geographic location and ownership, and telehealth use varied by geographic location, ownership, and size. Although HIT use has increased, our results indicate that many HHC agencies still lack the HIT needed to implement technological solutions to improve workflow and quality of care. Future research should examine the impact of HIT on patient outcomes and the impact of the COVID-19 pandemic on HIT use in HHC.

Associations of Nutrient Intake Changes During Childhood with Adolescent Hepatic Fat: The Exploring Perinatal Outcomes Among CHildren Study.

OBJECTIVE: To examine associations of dietary changes from childhood to adolescence with adolescent hepatic fat and whether the PNPLA3 rs738409 risk allele, a strong genetic risk factor for hepatic fat, modifies associations. STUDY DESIGN: Data were from 358 participants in the Exploring Perinatal Outcomes among CHildren (EPOCH) study, a longitudinal cohort in Colorado. Diet was assessed by food frequency questionnaire in childhood (approximately 10 years of age) and adolescence (approximately 16 years of age) and converted to nutrient densities. Hepatic fat was assessed in adolescence by magnetic resonance imaging. Linear regression was used to test associations of dietary changes from childhood to adolescence with adolescent hepatic fat. RESULTS: Increases in fiber, vegetable protein, and polyunsaturated fat intake from childhood to adolescence were associated with lower adolescent hepatic fat, and increases in animal protein were associated with higher hepatic fat (ß per 5-unit increase on log-hepatic fat: -0.12 [95% CI, -0.21 to -0.02] for ▵fiber; -0.26 [95% CI, -0.45 to -0.07] for ▵vegetable protein; -0.18 [95% CI, -0.35 to -0.02] for ▵polyunsaturated fat; 0.13 [95% CI, 0.04-0.22] for ▵animal protein). There was evidence of effect modification by PNPLA3 variant, whereby inverse associations of ▵fiber and ▵vegetable protein and positive associations of ▵saturated fat with adolescent hepatic fat were stronger in risk allele carriers. Most conclusions were similar after adjusting for obesity in adolescence, but associations of ▵saturated fat with hepatic fat were attenuated toward the null. CONCLUSIONS: Our results suggest that nutrient intake changes between childhood and adolescence, particularly decreases in fiber and vegetable protein and increases in saturated fat intake, interact with the PNPLA3 variant to predict higher hepatic fat in adolescence, and may be targets for reducing hepatic fat in high-risk youth.

Community-Based Advance Care Planning Interventions for Minority Older Adults: A Systematic Review.

Racial/ethnic minority older adults in the United States often experience access, language, and cultural barriers to advance care planning. For the current study, a systematic review was conducted to summarize and appraise the current science on community-based interventions aimed at increasing advance care planning in racial/ethnic minority older adults. Five articles met the inclusion criteria, which represented four unique interventions in Asian American (n = 2) and Hispanic (n = 2) communities. Two interventions were nurse-led workshops and two were one-onone social worker-led sessions. Outcomes measured were intention to or completion of advance directive or advance care planning discussion; and improvement in advance directive knowledge, beliefs, attitudes, and comfort related to advance care planning. Interventions increased intention to or completion of advance directives and improved advance care planning knowledge, beliefs, and attitudes. Results were inconclusive regarding promoting advance care planning discussions. Further research is needed to address the diverse needs of racial/ethnic minority older adults and barriers to advance care planning. [Journal of Gerontological Nursing, 47(5), 26-36.].

Organizational Capacity and Readiness to Provide Medication for Individuals with Co-Occurring Alcohol Use Disorders in Public Mental Health Settings.

Alcohol use disorders (AUD) in individuals with mental illness are largely untreated. The purpose of this study was to identify gaps in organizational capacity and readiness to provide medications for AUD in outpatient public mental health clinics. We selected a purposive sample of eight publicly funded outpatient mental health clinics operated by the Los Angeles County Department of Mental Health; clinics were chosen to maximize heterogeneity. Guided by theories of organizational capacity and readiness and research on the adoption of pharmacotherapy for AUD in primary and specialty care treatment settings, we conducted semi-structured interviews and focus groups with administrators, providers and staff, and a qualitative analysis of the results. Respondents described significant organizational capacity and behavioral readiness constraints to providing medication treatment for AUD. Both groups articulated a perception that mental health clinics were not designed to provide co-occurring AUD treatment because of large caseloads, staffing configurations, and time constraints that did not support the delivery of appropriate treatment, and a lack of protocols and workflow procedures. We documented organizational capacity and readiness constraints which impede the delivery of medication treatment for AUD in a large mental helth system. While some constraints have straightforward solutions, others require structural changes to the way care is delivered, and state-level funding and policy changes.

Relationship Between State Policy and Anesthesia Provider Supply in Rural Communities.

BACKGROUND: There is a significant geographic variation in anesthesia provider supply. Lower supply in rural communities raises concerns about access to procedures that require anesthesia in rural areas. State policies related to certified registered nurse anesthetist (CRNA) practice may help to alleviate rural supply concerns. OBJECTIVES: To estimate the association between state CRNA policy and anesthesia provider supply especially in rural communities. RESEARCH DESIGN: Repeated cross-sectional design using ordinary least squares and 2-stage least squares regressions. SUBJECTS: All counties in the United States from 2010 to 2015. MEASURES: Dependent variables include anesthesia provider counts per 100,000 people, calculated separately for anesthesiologists, CRNAs, and their sum. Key variables of interest include state-level CRNA policy based on scope of practice (SOP) regulations and Medicare opt-out status. RESULTS: Opt-out status and less restrictive SOP regulations were consistently correlated with a greater supply of CRNAs, especially in rural counties. Furthermore, we found that anesthesiologists and CRNAs tend to be complements to each other, but less restrictive SOP and opt-out status tend to weaken the importance of this relationship. CONCLUSIONS: State regulations may lead to increased supply of CRNAs in rural communities. However, the design of our study makes causality difficult to assert. So, it is also possible that states set CRNA policy as a response to counts of anesthesia providers in rural areas. Furthermore, given supply of anesthesiologists and CRNAs are complementary to one another, improving access to anesthesia services may require addressing issues pertaining to the supply of all anesthesia provider types.

Costs of Infection Prevention Practices in Long-Term Care Settings: A Systematic Review.

Long-term care demographic and industry trends challenge provision of effective care and infection prevention. A systematic review was conducted to identify and evaluate cost estimates reported in the scientific literature of structure and processes intended to prevent infection among residents and staff of long-term care facilities (LTCFs). The small volume of publications regarding cost of infection prevention in LTCFs does not lead to recommendations for specific infection prevention practices. Cost-effectiveness research is needed to inform nurse executives' decisions on how best to prevent infections. Nurse executives should consider costs as well as health outcomes when generating new policy regarding procedures or products related to infection prevention. Administrators should cautiously evaluate the recommendations of published studies containing a cost estimation based on the quality of the estimate in addition to assessing applicability of the results to their own facility and resident population.

"Striving for Excellence": Minimum Data Set Coordinators' Perceptions of Their Role in the Nursing Home.

The purpose of the current study was to explore how Minimum Data Set (MDS) coordinators perceive their role and the assessment process. Eleven MDS coordinators from 10 geographically dispersed nursing homes (NHs) were interviewed between May and September 2013. Four broad themes emerged from content analysis: (a) information gathering, (b) interdisciplinary coordination, (c) role challenges, and (d) resources. The first two themes referred to key components and competencies in the MDS coordinators' role, the third theme dealt with certain challenges inherent in the role, and the fourth theme highlighted resources that helped address these challenges. The current study provides insight into how MDS coordinators perceive their role, as well as some of the challenges they face to successfully enact that role. The current findings can help inform NH management staff, such as directors of nursing and NH administrators, and policy makers, on how best to support MDS coordinators' work to enable efficient and accurate resident assessment processes.

Perceived barriers to infection prevention and control for nursing home certified nursing assistants: a qualitative study.

Healthcare-associated infections, while preventable, result in increased morbidity and mortality in nursing home (NH) residents. Frontline personnel, such as certified nursing assistants (CNAs), are crucial to successful implementation of infection prevention and control (IPC) practices. The purpose of this study was to explore barriers to implementing and maintaining IPC practices for NH CNAs as well as to describe strategies used to overcome these barriers. We conducted a multi-site qualitative study of NH personnel important to infection control. Audio-recorded interviews were transcribed verbatim and transcripts were analyzed using conventional content analysis. Five key themes emerged as perceived barriers to effective IPC for CNAs: 1) language/culture; 2) knowledge/training; 3) per-diem/part-time staff; 4) workload; and 5) accountability. Strategies used to overcome these barriers included: translating in-services, hands on training, on-the-spot training for per-diem/part-time staff, increased staffing ratios, and inclusion/empowerment of CNAs. Understanding IPC barriers and strategies to overcome these barriers may better enable NHs to achieve infection reduction goals.

Understanding infection prevention and control in nursing homes: A qualitative study.

Infections have been identified as a priority issue in nursing homes (NHs). We conducted a qualitative study purposively sampling 10 NHs across the country where 6-8 employees were recruited (N = 73). Semi-structured, open-ended guides were used to conduct in-depth interviews. Data were audiotaped, transcribed and a content analysis was performed. Five themes emerged: 'Residents' Needs', 'Roles and Training' 'Using Infection Data,' 'External Resources' and 'Focus on Hand Hygiene.' Infection prevention was a priority in the NHs visited. While all sites had hand hygiene programs, other recommended areas were not a focus and many sites were not aware of available resources. Developing ways to ensure effective, efficient and standardized infection prevention and control in NHs continues to be a national priority.

Associations of infant feeding practices with abdominal and hepatic fat measures in childhood in the longitudinal Healthy Start Study.

BACKGROUND: Infant feeding patterns have been linked with obesity risk in childhood, but associations with precise measures of body fat distribution are unclear. OBJECTIVE: We examined associations of infant feeding practices with abdominal fat and hepatic fat trajectories in childhood. METHODS: This study included 356 children in the Healthy Start Study, a prospective prebirth cohort in Colorado. Infant feeding practices were assessed by postnatal interviews and categorized as any human milk <6 mo compared with ≥6 mo; complementary foods introduced ≤4 mo compared with >4 mo; soda introduced ≤18 mo compared with >18 mo. Abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) areas and hepatic fat (%) were assessed by magnetic resonance imaging in early and middle childhood (median 5 and 9 y old, respectively). We examined associations of infant feeding with adiposity trajectories across childhood using linear mixed models. RESULTS: In the sample of children, 67% consumed human milk ≥6 mo, 75% were introduced to complementary foods at >4 mo, and 81% were introduced to soda at >18 mo. We did not find any associations between duration of any human milk consumption and childhood adiposity trajectories. Early introduction to complementary foods (≤4 mo) was associated with faster rates of change for SAT and VAT during childhood (Slope [95% CI]: 15.1 [10.7,19.4] cm2/y for SAT; 2.5 [1.9,2.9] cm2/y for VAT), compared with introduction at >4 mo (5.5 [3.0,8.0] cm2/y and 1.6 [1.3,1.9] cm2/y, respectively). Similarly, early introduction to soda (≤18 mo) was associated with faster rates of change for all 3 outcomes during childhood (Slope [95% CI]: 20.6 [15.0,26.1] cm2/y for SAT, 2.7 [2.0,3.3] cm2/y for VAT, 0.3 [0.1,0.5] %/year for hepatic fat) compared with delayed introduction (5.4 [2.8,8.0] cm2/y, 1.7 [1.3, 2.0] cm2/y, -0.1 [-0.2,0.0] %/y, respectively). CONCLUSIONS: The timing of introduction and quality of complementary foods in infancy was associated with rates of abdominal and hepatic fat accrual during childhood. Experimental studies are needed to assess underlying mechanisms.

Understanding uptake of information about innovations among emergency department clinicians during the COVID-19 pandemic.

Objectives: Early in the COVID-19 pandemic, little was known about managing sick patients, but emergency department (ED) clinicians had to decide which treatments and care processes to adopt. Our objective was to describe how ED clinicians learned about innovations and how they assessed them for credibility during the pandemic. Methods: We purposively sampled clinicians from hospital-based EDs to conduct focus groups with ED clinicians and staff. We used both inductive and deductive approaches to conduct thematic analysis of transcripts. Results: We conducted focus groups with clinicians from eight EDs across the United States. We found that ED clinicians in our sample relied on friends and colleagues or departmental and institutional leadership for information on innovations. They used social media sources when they came from credible accounts but did not directly seek information from professional societies. Clinicians reported a range of challenges to obtain credible information during the pandemic, including a fractured and changing information environment, policies misaligned across clinical sites or that conflicted with clinical knowledge, high patient volume, fear of harming patients, and untimely information. Facilitators included access to experienced and trusted colleagues and leaders and practicing at multiple EDs. Conclusion: Participants cited anecdotal evidence, institutional practice, and word-of-mouth-rather than peer-reviewed evidence and professional society communications-as their primary sources of information about care innovations during the early phases of the pandemic. These results underscore the importance of developing trusted local mechanisms and wider networks to identify and vet information for frontline clinicians during rapidly emerging public health emergencies.

Validation of a screening panel for pediatric metabolic dysfunction-associated steatotic liver disease using metabolomics.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as NAFLD, is the most common liver disease in children. Liver biopsy remains the gold standard for diagnosis, although more efficient screening methods are needed. We previously developed a novel NAFLD screening panel in youth using machine learning applied to high-resolution metabolomics and clinical phenotype data. Our objective was to validate this panel in a separate cohort, which consisted of a combined cross-sectional sample of 161 children with stored frozen samples (75% male, 12.8±2.6 years of age, body mass index 31.0±7.0 kg/m2, 81% with MASLD, 58% Hispanic race/ethnicity). METHODS: Clinical data were collected from all children, and high-resolution metabolomics was performed using their fasting serum samples. MASLD was assessed by MRI-proton density fat fraction or liver biopsy and cardiometabolic factors. Our previously developed panel included waist circumference, triglycerides, whole-body insulin sensitivity index, 3 amino acids, 2 phospholipids, dihydrothymine, and 2 unknowns. To improve feasibility, a simplified version without the unknowns was utilized in the present study. Since the panel was modified, the data were split into training (67%) and test (33%) sets to assess the validity of the panel. RESULTS: Our present highest-performing modified model, with 4 clinical variables and 8 metabolomics features, achieved an AUROC of 0.92, 95% sensitivity, and 80% specificity for detecting MASLD in the test set. CONCLUSIONS: Therefore, this panel has promising potential for use as a screening tool for MASLD in youth.

Lipidome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys with Metabolic Dysfunction-Associated Steatotic Liver Disease.

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention (p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET (p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.

The Impact of Nurse Practitioner-Led Primary Care on Quality and Cost for Medicaid-Enrolled Patients in States With Pay Parity.

Studies have established that nurse practitioners (NPs) deliver primary care comparable to physicians in quality and cost, but most focus on Medicare, a program that reimburses NPs less than physicians. In this retrospective cohort study, we evaluated the quality and cost implications of receiving primary care from NPs compared to physicians in 14 states that reimburse NPs at the Medicaid fee-for-service (FFS) physician rate (i.e., pay parity). We linked national provider and practice data with Medicaid data for adults with diabetes and children with asthma (2012-2013). We attributed patients to primary care NPs and physicians based on 2012 evaluation & management claims. Using 2013 data, we constructed claims-based primary care quality measures and condition-specific costs of care for FFS enrollees. We estimated the effect of NP-led care on quality and costs using: (1) weighting to balance observable confounders and (2) an instrumental variable (IV) analysis using differential distance from patients' residences to primary care practices. Adults with diabetes received comparable quality of care from NPs and physicians at similar cost. Weighted results showed no differences between NP- and physician-attributed patients in receipt of recommended care or diabetes-related hospitalizations. For children with asthma, costs of NP-led care were lower but quality findings were mixed: NP-led care was associated with lower use of appropriate medications and higher rates of asthma-related emergency department visits but similar rates of asthma-related hospitalization. IV analyses revealed no evidence of differences in quality between NP- and physician-led care. Our findings suggest that in states with Medicaid pay parity, NP-led care is comparable to physician-led care for adults with diabetes, while associations between NP-led care and quality were mixed for children with asthma. Increased use of NP-led primary care may be cost-neutral or cost-saving, even under pay parity.

Metabolome × Microbiome Changes Associated with a Diet-Induced Reduction in Hepatic Fat among Adolescent Boys.

Dietary sugar reduction is one therapeutic strategy for improving nonalcoholic fatty liver disease (NAFLD), and the underlying mechanisms for this effect warrant further investigation. Here, we employed metabolomics and metagenomics to examine systemic biological adaptations associated with dietary sugar restriction and (subsequent) hepatic fat reductions in youth with NAFLD. Data/samples were from a randomized controlled trial in adolescent boys (11-16 years, mean ± SD: 13.0 ± 1.9 years) with biopsy-proven NAFLD who were either provided a low free-sugar diet (LFSD) (n = 20) or consumed their usual diet (n = 20) for 8 weeks. Plasma metabolomics was performed on samples from all 40 participants by coupling hydrophilic interaction liquid chromatography (HILIC) and C18 chromatography with mass spectrometry. In a sub-sample (n = 8 LFSD group and n = 10 usual diet group), 16S ribosomal RNA (rRNA) sequencing was performed on stool to examine changes in microbial composition/diversity. The diet treatment was associated with differential expression of 419 HILIC and 205 C18 metabolite features (p < 0.05), which were enriched in amino acid pathways, including methionine/cysteine and serine/glycine/alanine metabolism (p < 0.05), and lipid pathways, including omega-3 and linoleate metabolism (p < 0.05). Quantified metabolites that were differentially changed in the LFSD group, compared to usual diet group, and representative of these enriched metabolic pathways included increased serine (p = 0.001), glycine (p = 0.004), 2-aminobutyric acid (p = 0.012), and 3-hydroxybutyric acid (p = 0.005), and decreased linolenic acid (p = 0.006). Microbiome changes included an increase in richness at the phylum level and changes in a few genera within Firmicutes. In conclusion, the LFSD treatment, compared to usual diet, was associated with metabolome and microbiome changes that may reflect biological mechanisms linking dietary sugar restriction to a therapeutic decrease in hepatic fat. Studies are needed to validate our findings and test the utility of these "omics" changes as response biomarkers.

Association of Maternal BMI and Rapid Infant Weight Gain With Childhood Body Size and Composition.

OBJECTIVES: Maternal prepregnancy BMI (ppBMI) and an infant's rapid weight gain (RWG) are each associated with increased risk for childhood obesity. We hypothesized that ppBMI and RWG interact to further raise childhood obesity risk. METHODS: Mother-infant dyads (n = 414) from the Healthy Start Study, an observational prebirth cohort, were included. RWG was defined as a weight-for-age z score increase of ≥0.67 from birth to 3 to 7 months. Body composition was measured by air displacement plethysmography at age 4 to 7 years. General linear regression models were fit to characterize associations between ppBMI, RWG, and their interaction with the outcomes of childhood BMI-for-age z score and percent fat mass (%FM). RESULTS: A total of 18.6% (n = 77) of offspring experienced RWG. Maternal ppBMI and RWG were both positively associated with offspring BMI z score and %FM. RWG amplified the association between ppBMI and BMI z score, especially among females. Females exposed to maternal obesity and RWG had an average BMI at the 94th percentile (1.50 increase in childhood BMI z score) compared with those exposed to normal ppBMI and no RWG (average childhood BMI at the 51st percentile). RWG had a weaker effect on the association between ppBMI and %FM. Adjustment for breastfeeding status or childhood daily caloric intake did not significantly alter findings. CONCLUSIONS: Rapid infant weight gain interacts with maternal ppBMI to jointly exacerbate risk of childhood obesity. Pediatric providers should monitor infants for RWG, especially in the context of maternal obesity, to reduce future risk of obesity.