Michele Mietus-Snyder

Etiologies of congenital heart disease (CHD) are multifactorial. The role of maternal nutrition and environmental factors among these CHD etiologies remain insufficiently understood. This pilot study evaluated the potential association between maternal diet quality, nutrient intake, and food security to fetal CHD in a cohort of 100 pregnant individuals, including 20 with CHD-affected pregnancies identified in a fetal cardiology clinic at an urban tertiary care hospital. A Diet Quality Photo Navigation (DQPN) tool assessed dietary quality and nutrient intake, while a survey collected data on demographics, health history, and food security. Comparison tests assessed for differences between CHD- and non-CHD-affected pregnancies. CHD-affected pregnancies demonstrated descriptively lower Healthy Eating Index scores, reduced prenatal multivitamin use, and lower intake of iron, manganese, fiber, and vitamin C. The non-CHD group demonstrated a significantly higher consumption of healthier snacks (p = 0.03), plant-based meat alternatives (p = 0.05), and unsweetened beverages (p = 0.05), while descriptively showing greater fruit and vegetable intake as compared to the CHD-affected group. No statistically significant differences in food security or socioeconomic indicators were identified. These findings demonstrate the feasibility of applying a DQPN tool in fetal health research and describe maternal dietary patterns that may inform the design of future hypothesis-driven studies. Continued investigation into maternal diet quality is critical to understand its potential role in mitigating CHD risk through targeted nutritional interventions.

Background: Myriad roles for high-density lipoprotein (HDL) beyond atheroprotection include immunologic functions implicated in the severity of coronavirus disease-2019 (COVID-19) in adults. We explored whether there is an association between HDL and COVID-19 severity in youth.Methods: A pediatric cohort (N = 102), who tested positive for COVID-19 across a range of disease manifestations from mild or no symptoms, to acute severe symptoms, to the multisystem inflammatory syndrome of children (MIS-C) was identified. Clinical data were collected from the medical record and reserve plasma aliquots were assessed for lipoproteins by NMR spectroscopy and assayed for HDL functional cholesterol efflux capacity (CEC). Findings were compared by COVID-19 status and symptom severity. Lipoprotein, NMR spectroscopy and CEC data were compared with 30 outpatient COVID negative children.Results: Decreasing HDL cholesterol (HDL-c), apolipoprotein AI (ApoA-I), total, large and small HDL particles and HDL CEC showed a strong and direct linear dose-response relationship with increasing severity of COVID-19 symptoms. Youth with mild or no symptoms closely resembled the uninfected. An atypical lipoprotein that arises in the presence of severe hepatic inflammation, lipoprotein Z (LP-Z), was absent in COVID-19 negative controls but identified more often in youth with the most severe infections and the lowest HDL parameters. The relationship between HDL CEC and symptom severity and ApoA-I remained significant in a multiply adjusted model that also incorporated age, race/ethnicity, the presence of LP-Z and of GlycA, a composite biomarker reflecting multiple acute phase proteins.Conclusion: HDL parameters, especially HDL function, may help identify youth at risk of more severe consequences of COVID-19 and other novel infectious pathogens.

Sugar intake, particularly fructose, is implicated as a factor contributing to insulin resistance via hepatic de novo lipogenesis (DNL). A nine-day fructose reduction trial, controlling for other dietary factors and weight, in children with obesity and metabolic syndrome, decreased DNL and mitigated cardiometabolic risk (CMR) biomarkers. Ceramides are bioactive sphingolipids whose dysregulated metabolism contribute to lipotoxicity, insulin resistance, and CMR. We evaluated the effect of fructose reduction on ceramides and correlations between changes observed and changes in traditional CMR biomarkers in this cohort. Analyses were completed on data from 43 participants. Mean weight decreased (−0.9 ± 1.1 kg). The majority of total and subspecies ceramide levels also decreased significantly, including dihydroceramides, deoxyceramides and ceramide-1-phoshates. Change in each primary ceramide species correlated negatively with composite insulin sensitivity index (CISI). Change in deoxyceramides positively correlated with change in DNL. These results suggest that ceramides decrease in response to dietary fructose restriction, negatively correlate with insulin sensitivity, and may represent an intermediary link between hepatic DNL, insulin resistance, and CMR.

Poor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT). Overweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured. In the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia. Nutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.

Background. Central arterial stiffness is a surrogate of cardiovascular risk and predicts cardiovascular mortality. Apolipoprotein B lipoproteins are also established cardiovascular risk factors. It is not known whether specific lipoprotein subclasses measured in the Malm Diet and Cancer Study and previously shown to be associated with coronary heart disease also predict arterial stiffening after a mean period of 17 years. Methods. Lipoprotein particle analysis was performed on 2,505 men and women from Malm, Sweden, from 1991 to 1994, and arterial stiffness was assessed by carotid-femoral pulse wave velocity (c-fPWV) on this same cohort from 2007 to 2012. Associations between c-fPWV and lipoprotein particles were determined with multiple linear regression, controlling for sex, presence of diabetes, waist-to-hip circumference, and smoking status at baseline, as well as heart rate (measured at the carotid artery), mean arterial pressure, antihypertensive and lipid-lowering medications, C-reactive protein (CRP), and age at the time of c-fPWV measurement. Results. The results confirm that triglycerides (TG) and high-density lipoprotein cholesterol (HDL-c) but not low-density lipoprotein cholesterol (LDL-c) predict c-fPWV. We identify a positive predictive association for very small, small, and medium (high risk), but not large LDL particles. There was a negative association for large HDL particles. The relationships between c-fPWV and high-risk LDL particles were unaffected by adjusting for LDL-c or CRP and were only mildly attenuated by adjusting for the homeostatic model for insulin resistance (HOMA-IR). Due to the collinearity of very small, small, and medium LDL particles and dyslipidemia (elevated TG and decreased HDL-c), the observed relationship between c-fPWV and high-risk LDL particles became insignificant after controlling for the concentration of HDL-c, large cholesterol-rich HDL particles, and TG. Conclusions. The development of central arterial stiffness previously associated with combined dyslipidemia may be mediated in part by LDL particles, particularly the very small-, small-, and medium-sized LDL particles.

Preventing Chronic Disease (PCD) is a peer-reviewed electronic journal established by the National Center for Chronic Disease Prevention and Health Promotion. PCD provides an open exchange of information and knowledge among researchers, practitioners, policy makers, and others who strive to improve the health of the public through chronic disease prevention.

This scientific statement presents considerations for clinical management regarding the assessment and risk reduction of select pediatric populations at high risk for premature cardiovascular disease, including acquired arteriosclerosis or atherosclerosis. For each topic, the evidence for accelerated acquired coronary artery disease and stroke in childhood and adolescence and the evidence for benefit of interventions in youth will be reviewed. Children and adolescents may be at higher risk for cardiovascular disease because of significant atherosclerotic or arteriosclerotic risk factors, high-risk conditions that promote atherosclerosis, or coronary artery or other cardiac or vascular abnormalities that make the individual more vulnerable to the adverse effects of traditional cardiovascular risk factors. Existing scientific statements and guidelines will be referenced when applicable, and suggestions for risk identification and reduction specific to each setting will be described. This statement is directed toward pediatric cardiologists, primary care providers, and subspecialists who provide clinical care for these young patients. The focus will be on management and justification for management, minimizing information on pathophysiology and epidemiology.

Asthma in the obese is often severe, difficult to treat, and characterized by less eosinophilic inflammation than asthma in the nonobese. Obesity‐associated metabolic dysregulation may be a causal factor. We previously reported that a nutrient‐ and fiber‐dense bar [Children's Hospital Oakland Research Institute (CHORI)‐bar], which was designed to fill gaps in poor diets, improved metabolism in healthy overweight/obese (OW/OB) adults. In this pilot trial, OW/OB adolescents with poorly controlled asthma were randomized to weekly nutrition/exercise classes with or without twice‐daily CHORI‐bar consumption. Intent‐to‐treat analysis did not indicate CHORI‐bar‐specific effects. However, restricting the analysis to participants with acceptable compliance and a relatively low fraction of exhaled nitric oxide (FENO; n = 16; controls, n = 15) indicated that CHORI‐bar‐specific, significant improvements in lung function (forced vital capacity, percent‐predicted forced expiratory volume in 1 s, and percent‐predicted forced expiratory flow between 25 and 75% of forced vital capacity), primarily in participants with low chronic inflammation (high‐sensitivity C‐reactive protein FASEB J . 32, 6643–6654 (2018). www.fasebj.org

Objective: Neurocognitive deficits in pediatric obesity relate to poor developmental outcomes. We sought preliminary evidence for changes in brain and cognitive functioning relevant to obesogenic behavior following vertical sleeve gastrectomy (VSG) in adolescents relative to wait‐listed (WL) and healthy controls (HC).Methods: Thirty‐six adolescents underwent fMRI twice 4 months apart, during executive, reward, and episodic memory encoding, in addition to behavioral testing for reward‐related decision making.Results: VSG adolescents lost weight, while WL gained weight and HC did not change between time points. Gains in executive and reward‐related performance were larger in VSG than control groups. Group × Time interaction (P < 0.05 corrected) in left prefrontal cortex during N‐back showed greater presurgical activation and postsurgical reduction comparable to HC levels but increased in WL between time points. Similarly, left striatal parametric response to reward value reduced after surgery to HC levels; WL did not change. Memory‐related medial temporal activation did not change in any group.Conclusions: Results provide pilot evidence for functional brain changes induced by VSG in adolescents with severe obesity. Weight loss and gain were paralleled by reduced and increased prefrontal activation, respectively, suggesting neural plasticity related to metabolic change.