Complementary food exposure and children's early understanding of food words: the approaching eating through language (APPEAL) study.

Introduction: Language skills, such as the ability to understand words (receptive language), develop during infancy and are built through interactions with the environment, including eating. Exposure to complementary foods also begins in infancy and may play a significant role in language development, especially in understanding of food-related words. However, the relationship between the complementary foods to which a child is exposed and early language acquisition has not been previously studied. We hypothesized that young children's food-related receptive language (FRL) would reflect the complementary foods to which they were frequently offered by caregivers. Methods: Caregivers of young children (4-26 months; n = 408) in the Approaching Eating through Language (APPEAL) Study in the US were surveyed via Qualtrics. FRL was assessed by caregiver-report via a modified MacArthur-Bates Communicative Development Inventory. Complementary foods offered (CFO) by caregivers were assessed using a modified Food Frequency Questionnaire. Latent Class Analysis (LCA) was implemented to identify, 1) groupings of foods frequently offered (>1x/week) and 2) groupings of food-related words understood by the young children. Results: A 5-class best fit LCA model was identified for CFO (-log likelihood [-llik]=-8727) and for FRL (-llik=-5476). Cross-classification of the CFO and FRL derived classes revealed that children with higher exposure to complementary foods were perceived by caregivers to be most likely to also understand a greater number of food-related words (Probability=0.48). As expected, children having been offered a greater number of complementary foods and who understood a greater number of food-related words were older, compared to those with less complementary food exposure and food-related language acquisition (p < 0.001). Discussion: These findings support the potential role of introduction to complementary foods in development of food-related language.

Biomarkers of Neurodegeneration and Alzheimer's Disease Neuropathology in Adolescents and Young Adults with Youth-Onset Type 1 or Type 2 Diabetes: A Proof-of-Concept Study.

Adult-onset diabetes increases one's risk of neurodegenerative disease including Alzheimer's disease (AD); however, the risk associated with youth-onset diabetes (Y-DM) remains underexplored. We quantified plasma biomarkers of neurodegeneration and AD in participants with Y-DM from the SEARCH cohort at adolescence and young adulthood (Type 1, n = 25; Type 2, n = 25; 59% female; adolescence, age = 15 y/o [2.6]; adulthood, age = 27.4 y/o [2.2]), comparing them with controls (adolescence, n = 25, age = 14.8 y/o [2.7]; adulthood, n = 21, age = 24.9 y/o [2.8]). Plasma biomarkers, including glial fibrillary acidic protein (GFAP), neurofilament light chain protein (NfL), phosphorylated tau-181 (pTau181), and amyloid beta (Aß40, Aß42), were measured via Simoa. A subset of participants (n = 7; age = 27.5 y/o [5.7]) and six controls (age = 25.1 y/o [4.5]) underwent PET scans to quantify brain amyloid and tau densities in AD sensitive brain regions. Y-DM adolescents exhibited lower plasma levels of Aß40, Aß42, and GFAP, and higher pTau181 compared to controls (p < 0.05), a pattern persisting into adulthood (p < 0.001). All biomarkers showed significant increases from adolescence to adulthood in Y-DM (p < 0.01), though no significant differences in brain amyloid or tau were noted between Y-DM and controls in adulthood. Preliminary evidence suggests that preclinical AD neuropathology is present in young people with Y-DM, indicating a potential increased risk of neurodegenerative diseases.

The association of insulin responses and insulin sensitivity with cognition in adults with pre-diabetes: The Diabetes Prevention Program Outcomes Study.

OBJECTIVE: Dysglycemia is a significant risk factor for cognitive impairment. However, which pathophysiologic determinant(s) of dysglycemia, impaired insulin sensitivity (ISens) or the islet ß-cell's response (IResp), contribute to poorer cognitive function, independent of dysglycemia is not established. Among 1052 adults with pre-diabetes from the Diabetes Prevention Program Outcomes Study (DPPOS), we investigated the relationship between IResp, ISens and cognitive function. RESEARCH DESIGN AND METHODS: IResp was estimated by the insulinogenic index (IGI; pmol/mmol) and ISens as 1/fasting insulin from repeated annual oral glucose tolerance tests. The mean IResp and mean ISens were calculated over approximately 12 years of follow-up. Verbal learning (Spanish-English Verbal Learning Test [SEVLT]) and executive function (Digital Symbol Substitution Test [DSST]) were assessed at the end of the follow-up period. Linear regression models were run for each cognitive outcome and were adjusted for dysglycemia and other factors. RESULTS: Higher IResp was associated with poorer performance on the DSST (-0.69 points per 100 unit increase in IGI, 95 % CI: -1.37, -0.01). ISens was not associated with DSST, nor were IResp or ISens associated with performance on the SEVLT. CONCLUSIONS: These results suggest that a greater ß-cell response in people at high risk for type 2 diabetes is associated with poorer executive function, independent of dysglycemia and ISens.

Maternal education prospectively predicts child neurocognitive function: An environmental influences on child health outcomes study.

A large body of research has established a relation between maternal education and children's neurocognitive functions, such as executive function and language. However, most studies have focused on early childhood and relatively few studies have examined associations with changes in maternal education over time. Consequently, it remains unclear if early maternal education is longitudinally related to neurocognitive functions in children, adolescents, and young adults. In addition, the associations between changes in maternal education across development and more broadly defined neurocognitive outcomes remain relatively untested. The current study leveraged a large multicohort sample to examine the longitudinal relations between perinatal maternal education and changes in maternal education during development with children's, adolescents', and young adults' neurocognitive functions (N = 2,688; Mage = 10.32 years; SDage = 4.26; range = 3-20 years). Moreover, we examined the differential effects of perinatal maternal education and changes in maternal education across development on executive function and language performance. Perinatal maternal education was positively associated with children's later overall neurocognitive function. This longitudinal relation was stronger for language than executive function. In addition, increases in maternal education were related to improved language performance but were not associated with executive functioning performance. Our findings support perinatal maternal education as an important predictor of neurocognitive outcomes later in development. Moreover, our results suggest that examining how maternal education changes across development can provide important insights that can help inform policies and interventions designed to foster neurocognitive development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Associations between Prenatal and Postnatal Exposure to Cannabis with Cognition and Behavior at Age 5 Years: The Healthy Start Study.

BACKGROUND: Prenatal exposure to cannabis may influence childhood cognition and behavior, but the epidemiologic evidence is mixed. Even less is known about the potential impact of secondhand exposure to cannabis during early childhood. OBJECTIVE: This study sought to assess whether prenatal and/or postnatal exposure to cannabis was associated with childhood cognition and behavior. STUDY DESIGN: This sub-study included a convenience sample of 81 mother-child pairs from a Colorado-based cohort. Seven common cannabinoids (including delta 9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD)) and their metabolites were measured in maternal urine collected mid-gestation and child urine collected at age 5 years. Prenatal and postnatal exposure to cannabis was dichotomized as exposed (detection of any cannabinoid) and not exposed. Generalized linear models examined the associations between prenatal or postnatal exposure to cannabis with the NIH Toolbox and Child Behavior Checklist T-scores at age 5 years. RESULTS: In this study, 7% (n = 6) of the children had prenatal exposure to cannabis and 12% (n = 10) had postnatal exposure to cannabis, with two children experiencing this exposure at both time points. The most common cannabinoid detected in pregnancy was Δ9-THC, whereas the most common cannabinoid detected in childhood was CBD. Postnatal exposure to cannabis was associated with more aggressive behavior (ß: 3.2; 95% CI: 0.5, 5.9), attention deficit/hyperactivity problems (ß: 8.0; 95% CI: 2.2, 13.7), and oppositional/defiant behaviors (ß: 3.2; 95% CI: 0.2, 6.3), as well as less cognitive flexibility (ß: -15.6; 95% CI: -30.0, -1.2) and weaker receptive language (ß: -9.7; 95% CI: -19.2, -0.3). By contrast, prenatal exposure to cannabis was associated with fewer internalizing behaviors (mean difference: -10.2; 95% CI: -20.3, -0.2) and fewer somatic complaints (mean difference: -5.2, 95% CI: -9.8, -0.6). CONCLUSIONS: Our study suggests that postnatal exposure to cannabis is associated with more behavioral and cognitive problems among 5-year-old children, independent of prenatal and postnatal exposure to tobacco. The potential risks of cannabis use (including smoking and vaping) during pregnancy and around young children should be more widely communicated to parents.

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.

Household Food Insecurity and Cognition in Youth and Young Adults with Youth-Onset Diabetes.

Objective: We evaluated the association of household food insecurity (FI) with cognition in youth and young adults with type 1 diabetes (T1D) or type 2 diabetes (T2D). Design: In this cross-sectional study, age-adjusted scores for composite Fluid Cognition, and sub-domain scores for Receptive Language and Inhibitory Control and Attention, were modeled stratified by diabetes-type using linear regression, with FI in the past year as the predictor, controlling for covariates. Tests for processing speed, inhibitory control/attention, working memory, episodic memory, and cognitive flexibility were administered to measure composite Fluid Cognition score. The NIHT-CB Picture Vocabulary Test was used to assess Crystallized Cognition score and rapid identification of congruent versus noncongruent items were used to assess Inhibitory Control and Attention score. Setting: The SEARCH for Diabetes in Youth study, representative of 5 U.S. states. Participants: Included 1574 youth and young adults with T1D or T2D, mean age of 21 years, mean diabetes duration of 11 years, 51% non-Hispanic white, and 47% had higher HbA1c levels (>9% HbA1c). Results: Approximately 18% of the 1,240 participants with T1D and 31% of the 334 with T2D experienced FI. The food-insecure group with T1D had a lower composite Fluid Cognition score (ß= -2.5, 95% confidence interval (CI)= -4.8, -0.1) and a lower Crystallized Cognition score (ß= -3.4, CI= -5.6, -1.3) than food-secure peers. Findings were attenuated to non-significance after adjustment for demographics. Among T2D participants, no associations were observed. In participants with T1D effect modification by glycemic levels were found in the association between FI and composite Fluid Cognition score but adjustment for socioeconomic characteristics attenuated the interaction (p=0.0531). Conclusions: Food-insecure youth and young adults with T1D or T2D did not have different cognition compared to those who were food-secure after adjustment for confounders. Longitudinal research is needed to further understand relations amongst these factors.

Diabetes complications and cognitive function in young adults with youth-onset type 1 or type 2 diabetes: the SEARCH for Diabetes in Youth Study.

Aims/hypotheses: People with type 1 (T1D) or type 2 diabetes (T2D) who also have diabetes complications can have pronounced cognitive deficits. It remains unknown, however, whether and how multiple diabetes complications co-occur with cognitive dysfunction, particularly in youth-onset diabetes. Methods: Using data from the SEARCH for Diabetes in Youth study cohort, a prospective longitudinal cohort, we examined clustering of complications and their underlying clinical factors with performance on cognitive tests in young adults with youth-onset T1D or T2D. Cognition was assessed via the NIH Toolbox Cognition Battery. The main cognitive variables were age-corrected scores for composite fluid cognition and associated cognitive subdomains. Diabetes complications included retinopathy, microalbuminuria, and peripheral neuropathy (PN). Lipids, systolic blood pressure (SBP), hemoglobin A1c, and other clinical factors were included in the analyses. Clustering was applied separately to each group (T1D=646; T2D=165). A three-cluster(C) solution was identified for each diabetes type. Mean values and frequencies of all factors were compared between resulting clusters. Results: The average age-corrected score for composite fluid cognition differed significantly across clusters for each group (p<0.001). People with T1D and the lowest average fluid cognition scores had the highest frequency of self-reporting at least one episode of hypoglycemia in the year preceding cognitive testing and the highest prevalence of PN. Persons with T2D and the lowest average fluid cognition scores had the highest SBP, the highest central systolic and diastolic blood pressures, and highest prevalence of PN. Conclusions/interpretations: These findings highlight shared (PN) and unique factors (hypoglycemia in T1D; SBP in T2D) that could be targeted to potentially mitigate cognitive issues in young people with youth-onset diabetes.

Acceptance of a Novel Food is Related to Caregiver Perceptions of Infant and Toddler Food-related Receptive Language.

OBJECTIVE: Language development, both what is understood (receptive language) and spoken (expressive language), is considered critical to a child's ability to understand and interact with their environment. However, little research has investigated the role children's early language skills might play in their food acceptance. The objective of this study was to explore the relationships between young children's food-related receptive language (FRL) and food-related expressive language (FEL) and acceptance of novel food. METHODS: Caregivers (n = 54) reported their perceptions of children's (aged 7-24 months) FRL and FEL using the MacArthur-Bates Communicative Development Inventory. Novel food acceptance was observed (grams consumed) during a laboratory visit. Multivariable linear regression tested associations between FRL, FEL, and novel food acceptance, by child age (infants [aged from 7 to < 12 months], toddlers [aged 12-24 months]), and at a significance level of P < 0.1 for hypothesis-generating research. RESULTS: Children's FRL and food acceptance differed by age (F = 8.08, P = 0.01). Among toddlers, greater FRL was associated with greater novel food acceptance (0.22 g [95% confidence interval, -0.04 to 0.49]), P = 0.09). In infants, greater FRL was associated with lower novel food acceptance (-0.80 g [95% confidence interval, -1.53 to -0.07], P = 0.03). No association between FEL and novel food acceptance was noted in either group. CONCLUSIONS AND IMPLICATIONS: Toddlers' understanding of food-related vocabulary may facilitate food acceptance; however, young infants may not yet have sufficient FRL to facilitate novel food acceptance.

Fetal Exposure to Cannabis and Childhood Metabolic Outcomes: The Healthy Start Study.

OBJECTIVE: To assess the impact of fetal exposure to cannabis on adiposity and glucose-insulin traits in early life. RESEARCH DESIGN AND METHODS: We leveraged a subsample of 103 mother-child pairs from Healthy Start, an ethnically diverse Colorado-based cohort. Twelve cannabinoids/metabolites of cannabis (including Δ9-tetrahydrocannabinol and cannabidiol) were measured in maternal urine collected at ~27 weeks' gestation. Fetal exposure to cannabis was dichotomized as exposed (any cannabinoid > limit of detection [LOD]) and not exposed (all cannabinoids < LOD). Fat mass and fat-free mass were measured via air displacement plethysmography at follow-up (mean age: 4.7 years). Glucose and insulin were obtained after an overnight fast. Generalized linear models estimated the associations between fetal exposure to cannabis with adiposity measures (fat mass [kg], fat-free mass [kg], adiposity [fat mass percentage], body mass index [BMI], and BMI z-scores) and metabolic measures (glucose [mg/dL], insulin [uIU/mL], and homeostatic model assessment of insulin resistance [HOMA-IR]). RESULTS: Approximately 15% of the women had detectable levels of any cannabinoid, indicating fetal exposure to cannabis. Exposed offspring had higher fat mass (1.0 kg; 95% CI, 0.3-1.7), fat-free mass (1.2 kg; 95% CI, 0.4-2.0), adiposity (2.6%; 95% CI, 0.1-5.2), and fasting glucose (5.6 mg/dL; 95% CI, 0.8-10.3) compared with nonexposed offspring. No associations were found with fasting insulin (in the fully adjusted model), HOMA-IR, BMI, or BMI z-scores. CONCLUSIONS: We provide novel evidence to suggest an association between fetal exposure to cannabis with increased adiposity and fasting glucose in childhood, a finding that should be validated in other cohorts.

Early microvascular complications in type 1 and type 2 diabetes: recent developments and updates.

The prevalence of youth-onset diabetes is progressing rapidly worldwide, and poor glycemic control, in combination with prolonged diabetes duration and comorbidities including hypertension, has led to the early development of microvascular complications including diabetic kidney disease, retinopathy, and neuropathy. Pediatric populations with type 1 (T1D) and type 2 (T2D) diabetes are classically underdiagnosed with microvascular complications, and this leads to both undertreatment and insufficient attention to the mitigation of risk factors that could help attenuate further progression of complications and decrease the likelihood for long-term morbidity and mortality. This narrative review aims to present a comprehensive summary of the epidemiology, risk factors, symptoms, screening practices, and treatment options, including future opportunities for treatment advancement, for microvascular complications in youth with T1D and T2D. We seek to uniquely focus on the inherent challenges of managing pediatric populations with diabetes and discuss the similarities and differences between microvascular complications in T1D and T2D, while presenting a strong emphasis on the importance of early identification of at-risk youth. Further investigation of possible treatment mechanisms for microvascular complications in youth with T1D and T2D through dedicated pediatric outcome trials is necessary to target the brief window where early pathological vascular changes may be significantly attenuated.

Infant and Toddler Consumption of Sweetened and Unsweetened Lipid Nutrient Supplements After 2-Week Home Repeated Exposures.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to address undernutrition during the complementary feeding period. SQ-LNS contains added sugars, but limited research has assessed whether infants' acceptance varies between versions with and without sugars. OBJECTIVES: Our objective was to examine the effects of repeated exposure on children's acceptance of sweetened and unsweetened SQ-LNS. We aimed to understand caregivers' perceptions of children's liking of the 2 SQ-LNS versions and their influences on infant acceptance of SQ-LNS. METHODS: Caregivers (86% non-Hispanic White) and children (7-24 mo), participated in a randomized, 2-week home-exposure study and baseline and post-home exposure assessments. Children were randomized to receive sweetened or unsweetened SQ-LNS versions, mixed with infant oatmeal. At in-person visits, caregivers fed both SQ-LNS versions to children and rated their child's liking for each. Caregivers fed the SQ-LNS version to which their child was randomized until the child refused to eat more. Acceptance was measured as total grams consumed. Mixed-effects linear models tested the change in SQ-LNS consumed between baseline and postexposure by the SQ-LNS version and number of home exposures. Covariates included the amount of SQ-LNS consumed at baseline, child BMI z-score, child age, and breastfeeding experience. RESULTS: Children's acceptance of both SQ-LNS versions increased from baseline to postexposure (ß, 0.71 g; 95% CI: 0.54-0.89 g; P = 0.04), regardless of SQ-LNS version (P = 0.88) or number of home exposures (P = 0.55). Caregivers rated children's liking of unsweetened SQ-LNS higher at baseline (P = 0.02). Children with lower liking ratings at baseline showed the greatest increases in acceptance between baseline and postexposure (P = 0.01). CONCLUSIONS: Children's acceptance of SQ-LNS increased with repeated exposure, whether offered the sweetened or unsweetened version, providing preliminary support that adding sugar to SQ-LNS may not improve acceptance in young children. Children who initially like the supplement less may need repeated experience to learn to accept SQ-LNS. This trial was registered at clinicaltrials.gov as NCT04544332.

Cognitive Function in Adolescents and Young Adults With Youth-Onset Type 1 Versus Type 2 Diabetes: The SEARCH for Diabetes in Youth Study.

OBJECTIVE: Poor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D (n = 1,095) or T2D (n = 285). RESEARCH DESIGN AND METHODS: Cognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition. RESULTS: Having T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model (P < 0.01 for all, respectively). CONCLUSIONS: These data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors.

In Utero Exposure to Maternal Overweight or Obesity is Associated with Altered Offspring Brain Function in Middle Childhood.

OBJECTIVE: The impact of in utero exposure to maternal overweight and obesity on offspring metabolic health is well documented. Neurodevelopmental outcomes among these children are, however, less well studied. To address this gap, the current study investigated brain function among 4- to 6-year-old children exposed to maternal overweight or obesity during gestation compared with that of children born to mothers with healthy BMI in pregnancy. METHODS: Resting-state functional magnetic resonance imaging was used to study neuronal activity and connectivity during a passive viewing task (movie) among 101 typically developing children enrolled in the Healthy Start study, a longitudinal prebirth cohort in Colorado. RESULTS: Forty-nine children (48%) were exposed to maternal overweight or obesity in utero (mean age = 5 years, SD = 0.9). Children born to mothers with overweight or obesity demonstrated hyperactivity in the left posterior cingulate cortex and hypoactivity in the dorsal anterior cingulate and the supplementary motor area (P < 0.05 for all). Children born to mothers with overweight or obesity also showed ubiquitously weaker brain connectivity (P < 0.05 for all). CONCLUSIONS: These novel results suggest altered brain function among children exposed to maternal overweight and obesity in utero.

Childhood Metabolic Biomarkers Are Associated with Performance on Cognitive Tasks in Young Children.

OBJECTIVE: To evaluate the hypothesis that metabolic measures (fasting glucose, insulin, and Homeostatic Model of Assessment for Insulin Resistance [HOMA-IR] levels) are inversely associated with performance on cognitive tasks using data from young (4- to 6-year-old), typically developing, healthy children. STUDY DESIGN: Data were obtained from children participating in the Healthy Start study, a pre-birth cohort in Colorado. HOMA-IR, glucose, and insulin values were centered and scaled using the study sample means and SD. Thus, they are reported in number of SD units from the mean. Fully corrected T scores for inhibitory control (Flanker task), cognitive flexibility (Dimensional Change Card Sort test), and receptive language (Picture Vocabulary test) were obtained via the National Institutes of Health Toolbox cognition battery. RESULTS: Children included in this analysis (n = 137) were 4.6 years old, on average. Per 1-SD unit, fasting glucose (B = -2.0, 95% CI -3.5, -0.5), insulin (B = -1.7, 95% CI -3.0, -0.4), and HOMA-IR values (B = -1.8, 95% CI -3.1, -0.5) were each significantly and inversely associated with inhibitory control (P < .05 for all, respectively). Fasting glucose levels were also inversely associated with cognitive flexibility (B = -2.0, 95% CI -3.7, -0.2, P = .03). CONCLUSIONS: Our data suggest that metabolic health may impact fluid cognitive function in healthy, young children.

Eating in the absence of hunger in young children is related to brain reward network hyperactivity and reduced functional connectivity in executive control networks.

BACKGROUND: Recent work has implicated disinhibited eating behaviours (DEB) as a potential pathway toward obesity development in children. However, the underlying neurobiology of disinhibited eating behaviours in young, healthy weight children, prior to obesity development, remains unknown. OBJECTIVES: This study tested the relationship between DEB and intrinsic neuronal activity and connectivity in young children without obesity. METHODS: Brain networks implicated in overeating including reward, salience and executive control networks, and the default mode network were investigated. DEB was measured by the eating in the absence of hunger (EAH) paradigm with postlunch kilocalories consumed from highly palatable foods (EAH kcal) used as the predictor. Intrinsic neuronal activity within and connectivity between specified networks were measured via resting-state functional magnetic resonance imaging. Eighteen typically developing children (mean age = 5.8 years) were included. RESULTS: EAH kcal was positively associated with activity of the nucleus accumbens, a major reward network hub (P < 0.05, corrected). EAH kcal was negatively associated with intrinsic prefrontal cortex connectivity to the striatum (P < 0.01, corrected). CONCLUSIONS: These results suggest that neural aspects of DEB are detectable in young children without obesity, providing a potential tool to better understand the development of obesity in this population.

Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain.

The intrauterine period is a critical time wherein developmental exposure can influence risk for chronic disease including childhood obesity. Using umbilical cord-derived mesenchymal stem cells (uMSC) from offspring born to normal-weight and obese mothers, we tested the hypothesis that changes in infant body composition over the first 5 months of life correspond with differences in cellular metabolism and transcriptomic profiles at birth. Higher long-chain acylcarnitine concentrations, lipid transport gene expression, and indicators of oxidative stress in uMSC-adipocytes were related to higher adiposity at 5 months of age. In uMSC-myocytes, lower amino acid concentrations and global differential gene expression for myocyte growth, amino acid biosynthesis, and oxidative stress were related to lower infant percent fat-free mass at 5 months of age, particularly in offspring of obese mothers. This is the first evidence of human infant adipocyte- or myocyte-related alterations in cellular metabolic pathways that correspond with increased adiposity and lower fat-free mass in early infancy. These pathways might reflect the effects of an adverse maternal metabolic environment on the fetal metabolome and genome. Our findings suggest that programmed differences in infant stem cell metabolism correspond with differences in body composition in early life, a known contributor to obesity risk.

Maternal obesity alters fatty acid oxidation, AMPK activity, and associated DNA methylation in mesenchymal stem cells from human infants.

OBJECTIVE: Infants born to mothers with obesity have greater adiposity, ectopic fat storage, and are at increased risk for childhood obesity and metabolic disease compared with infants of normal weight mothers, though the cellular mechanisms mediating these effects are unclear. METHODS: We tested the hypothesis that human, umbilical cord-derived mesenchymal stem cells (MSCs) from infants born to obese (Ob-MSC) versus normal weight (NW-MSC) mothers demonstrate altered fatty acid metabolism consistent with adult obesity. In infant MSCs undergoing myogenesis in vitro, we measured cellular lipid metabolism and AMPK activity, AMPK activation in response to cellular nutrient stress, and MSC DNA methylation and mRNA content of genes related to oxidative metabolism. RESULTS: We found that Ob-MSCs exhibit greater lipid accumulation, lower fatty acid oxidation (FAO), and dysregulation of AMPK activity when undergoing myogenesis in vitro. Further experiments revealed a clear phenotype distinction within the Ob-MSC group where more severe MSC metabolic perturbation corresponded to greater neonatal adiposity and umbilical cord blood insulin levels. Targeted analysis of DNA methylation array revealed Ob-MSC hypermethylation in genes regulating FAO (PRKAG2, ACC2, CPT1A, SDHC) and corresponding lower mRNA content of these genes. Moreover, MSC methylation was positively correlated with infant adiposity. CONCLUSIONS: These data suggest that greater infant adiposity is associated with suppressed AMPK activity and reduced lipid oxidation in MSCs from infants born to mothers with obesity and may be an important, early marker of underlying obesity risk.

Prenatal Vitamin D Intake, Cord Blood 25-Hydroxyvitamin D, and Offspring Body Composition: The Healthy Start Study.

Vitamin D deficiency in pregnancy may be associated with increased offspring adiposity, but evidence from human studies is inconclusive. We examined associations between prenatal vitamin D intake, 25-hydroxyvitamin D (25(OH)D) in cord blood, and offspring size and body composition at birth and 5 months. Participants included 605 mother-offspring dyads from the Healthy Start study, an ongoing, pre-birth prospective cohort study in Denver, Colorado, USA. Prenatal vitamin D intake was assessed with diet recalls and questionnaires, and offspring body composition was measured via air displacement plethysmography at birth and 5 months. General linear univariate models were used for analysis, adjusting for maternal age, race/ethnicity, pre-pregnancy body mass index (BMI), offspring sex, and gestational age at birth. Non-Hispanic white race, lower pre-pregnancy BMI, higher prenatal vitamin D intake, and summer births were associated with higher cord blood 25(OH)D. Higher 25(OH)D was associated with lower birthweight (ß = -6.22, p = 0.02), but as maternal BMI increased, this association became increasingly positive in direction and magnitude (ß = 1.05, p = 0.04). Higher 25(OH)D was also associated with lower neonatal adiposity (ß = -0.02, p < 0.05) but not after adjustment for maternal BMI (ß = -0.01, p = 0.25). Cord blood 25(OH)D was not associated with offspring size or body composition at 5 months. Our data confirm the hypothesis that vitamin D exposure in early life is associated with neonatal body size and composition. Future research is needed to understand the implications of these associations as infants grow.

Exposure to maternal diabetes in utero and offspring eating behavior: The EPOCH study.

The risk of becoming overweight among offspring exposed to gestational diabetes (GDM) in utero is two-fold higher than in the general population. The responsible mechanisms are likely multifactorial, with some evidence that GDM exposure alters brain satiety signaling, which may impact eating behavior. To better understand these effects, we investigated the relationship between GDM exposure, eating behavior, and total energy intake in 268 adolescents from the Exploring Perinatal Outcomes among Children cohort, who were exposed (n = 50) or not exposed (n = 217) to GDM in utero. Eating behavior was measured by the Eating in the Absence of Hunger in Children and Adolescents (EAH-C) questionnaire, which included subscale scores for Negative Affect, External Stimuli, and Fatigue/Boredom. Total energy intake (kcal/day) was derived from the Block Kid's Food Questionnaire. The associations between GDM exposure and the outcomes of total score and each EAH-C subscale were evaluated in separate multivariable models. In addition to the main predictor, GDM, the models included a GDM-by-sex interaction term and were adjusted for important covariates. The associations between EAH-C total and subscale scores and the outcome of total energy intake were also tested in separate multivariable models. Female offspring exposed to GDM in utero (vs unexposed males and females) were more likely to continue eating beyond satiation due to feelings of boredom and fatigue (ß = 0.47, 95% CI: 0.11, 0.83), and in general (EAH-C total score; ß = 4.20, 95% CI: 0.56, 7.86) compared to unexposed males. All EAH-C subscale and total scores were significantly, positively associated with higher energy intake (p < 0.05 for all, respectively). Our findings highlight the need for further investigation into the possible early life programming of eating behaviors by GDM exposure in utero.