Elucidating pathways to pediatric obesity: a study evaluating obesity polygenic risk scores related to appetitive traits in children.

BACKGROUND/OBJECTIVES: Obesity polygenic risk scores (PRS) explain substantial variation in body mass index (BMI), yet associations between PRSs and appetitive traits in children remain unclear. To better understand pathways leading to pediatric obesity, this study aimed to assess the association of obesity PRSs and appetitive traits. SUBJECTS/METHODS: This study included 248 unrelated children aged 9-12 years. DNA from the children was genotyped (236 met quality control thresholds) and four weighted polygenic risk scores from previous studies were computed and standardized: a 97 SNP PRS, 266 SNP pediatric-specific PRS, 466 SNP adult-specific PRS, and ~2 million SNP PRS. Appetitive traits were assessed using a parent-completed Child Eating Behavior Questionnaire, which evaluated food approach/avoidance traits and a composite obesogenic appetite score. BMI was directly measured and standardized by age and sex. Three associations were evaluated with linear regression: (1) appetitive traits and BMI, (2) PRSs and BMI, and (3) PRSs and appetitive traits, the primary association of interest. RESULTS: Expected positive associations were observed between obesogenic appetitive traits and BMI and all four PRSs and BMI. Examining the association between PRSs and appetitive traits, all PRSs except for the 466 SNP adult PRS were significantly associated with the obesogenic appetite score. Each standard deviation increase in the 266 SNP pediatric PRS was associated with an adjusted 2.1% increase in obesogenic appetite score (95% CI: 0.6%, 3.7%, p = 0.006). Significant partial mediation of the PRS-BMI association by obesogenic appetite score was found for these PRSs; for example, 21.3% of the association between the 266 SNP pediatric PRS and BMI was explained by the obesogenic appetite score. CONCLUSIONS: Genetic obesity risk significantly predicted appetitive traits, which partially mediated the association between genetic obesity risk and BMI in children. These findings build a clearer picture of pathways leading to pediatric obesity.

Associations between behavioral self-regulation and external food cue responsiveness (EFCR) in preschool-age children and evidence of modification by parenting style.

Decreased behavioral regulation is hypothesized to be a risk factor for excess weight gain among children, possibly via reduced appetite-specific regulation. Little research has specifically focused on behavioral regulation and food cue responsiveness, a conditioned precursor to eating, at a young age. This study examined the association between behavioral regulation and external food cue responsiveness among preschool-age children and explored if a more structured parenting style moderated that association. Baseline data from a prospective study on media use among preschool-age children (n = 83) in Northern New England were used. Parents reported on three domains of children's behavioral regulation (attentional focusing, inhibitory control, and emotional self-regulation), the children's external food cue responsiveness (EFCR), and their parenting styles (authoritative and permissive) via validated questionnaires. Mean age among children was 4.31 (SD 0.91) years, 57% of children were male, 89% were non-Hispanic white, and 26.2% had overweight or obesity. In a series of adjusted linear regression models, lower attentional focusing (standardized ß, ßs = -0.35, p = 0.001), inhibitory control (ßs = -0.30, p = 0.008), and emotional self-regulation (standardized beta, ßs = -0.38, p < 0.001) were each significantly associated with greater EFCR. In exploratory analyses, a more structured parenting style (more authoritative or less permissive) mitigated the associations between inhibitory control and EFCR (Bonferroni-adjusted p-interaction < 0.017). Findings support that lower attentional focusing, inhibitory control, and emotional self-regulation relate to greater ECFR in preschool-age children. The association between inhibitory control and EFCR may be modified by parenting style. Further research is needed to understand if children's responsiveness to external food cues may account for reported associations between lower behavioral regulation and adiposity gain over time.

Measurement of external food cue responsiveness in preschool-age children: Preliminary evidence for the use of the external food cue responsiveness scale.

BACKGROUND: Conditioned eating in response to external food cues may contribute to obesity risk in young children. OBJECTIVES: To develop a brief, parent-reported scale to measure external food cue responsiveness for preschool-age children. METHODS: Focus groups with parents of preschool-age children were conducted to create an initial pool of items reflecting children's behavioral responses to external food cues. Items were included in a nationally-distributed online survey of parents of preschool-age children (n = 456). Factor analysis was used to reduce the initial item pool, the scale's psychometric properties were assessed, and scores were correlated with reported snacking behaviors. RESULTS: Nine items met inclusion criteria in the final scale, which had high internal consistency (alpha = 0.86). Final scores were the mean across the nine items. External food cue responsiveness was greater among children with, versus without, usual TV advertisement exposure. Furthermore, greater external food cue responsiveness mediated the relationship between children's usual TV advertisement exposure and snacking during TV viewing. Findings remained statistically significant when adjusted for food responsiveness as measured with the Child Eating Behavior Questionnaire. CONCLUSIONS: Findings provide preliminary evidence that external food cue responsiveness is measurable by parental report in preschool-age children.

Household chaos and screen media use among preschool-aged children: a cross-sectional study.

BACKGROUND: Excess screen media use is a robust predictor of childhood obesity. Understanding how household factors may affect children's screen use is needed to tailor effective intervention efforts. The preschool years are a critical time for obesity prevention, and while it is likely that greater household disorder influences preschool-aged children's screen use, data on that relationship are absent. In this study, our goal was to quantify the relationships between household chaos and screen use in preschool-aged children. METHODS: A cross-sectional, online survey was administered to 385 parents of 2-5 year-olds recruited in 2017. Household chaos was measured with the Confusion, Hubbub and Order Scale (i.e., the chaos scale), a validated, parent-reported scale. The scale consists of 15 items, each scored on a 4-point Likert scale. Final scores were the sum across the 15 items and modeled as quartiles for analyses. Parents reported their children's screen use for nine electronic media activities. Adjusted linear and Poisson regression were used to model associations between household chaos and children's total weekly screen use, screen use within one hour of bedtime and screen use in the bedroom. RESULTS: Children averaged 31.0 (SD = 23.8) hours per week with screens, 49.6% used screens within one hour of bedtime and 41.0% used screens in their bedrooms. In adjusted regression models, greater household chaos was positively associated with weekly screen use (P = 0.03) and use of screens within one hour of bedtime (P < 0.01) in a dose-dependent manner. Children in the fourth versus the first quartile of household chaos were more likely to use screens in their bedroom (P = 0.03). CONCLUSIONS: Greater household chaos was associated with increased total screen use as well as screen use behaviors that are related to disrupted nighttime sleep. Findings suggest that household chaos may be an obesity risk factor during the preschool years because of such effects on screen use, and highlight the need to consider household chaos when implementing home-based obesity prevention programs for young children.

FTO genotype and weight status among preadolescents: Assessing the mediating effects of obesogenic appetitive traits.

Polymorphisms in the Fat Mass and Obesity Associated (FTO) gene are robustly associated with overweight and obesity among children, although the underlying mechanisms are poorly understood. We tested if appetitive traits partially mediated the association between FTO genotype and increased BMI among a sample of US preadolescents. Data were from 178 unrelated 9-10 year olds who participated in an experimental study between 2013 and 2015. Children's DNA was isolated from buccal swabs, and the rs9939609 SNP in the FTO gene was genotyped. Children's age- and sex-adjusted BMI z-scores were computed using height and weight measured at the laboratory. Parents completed the Child Eating Behavior Questionnaire that includes three validated scales of habitual appetitive traits related to drive and regulation: satiety responsiveness, enjoyment of food and food responsiveness. Structural equation modeling was used to assess if those traits mediated the relationship between FTO and BMI z-score. The sample of children was 48.9% male and 91.0% non-Hispanic white. FTO distribution was in Hardy Weinberg equilibrium, and 16.3% of participants were homozygous for the high-risk allele. Mean BMI z-score was greatest among those with the high-risk genotype (ANOVA P < 0.01). In separate structural equation models adjusted for the child's sex and maternal education, decreased satiety responsiveness and increased food responsiveness each partially mediated the positive association between the high-risk genotype and increased BMI z-score (P-value for each indirect effect <0.05). Continued research is needed to better understand how other known genetic obesity risk factors may impact appetitive traits among children.

Understanding eating in the absence of hunger among young children: a systematic review of existing studies.

BACKGROUND: Eating in the Absence of Hunger (EAH), or consuming highly palatable foods when satiated, is one behavioral pathway that may lead to childhood obesity. EAH is an objective, laboratory-based measure. A more comprehensive understanding of potential determinants of EAH could inform childhood obesity programs outside of a laboratory setting. OBJECTIVE: Systematic review of EAH experiments to identify individual, familial, and societal-level correlates of EAH among children 12 years of age or younger. DESIGN: 1487 studies were retrieved from five electronic databases (Medline [PubMed], Web of Science, Cochrane Library, CINAHL, PsycINFO). Eligible studies were those that measured EAH as initially operationalized in a laboratory setting enrolling children ≤12 years or reporting age-specific results for children ≤12 years. Only articles written in English were included. RESULTS: 12 cross-sectional, six prospective, and one behavioral-intervention studies were included in the review. EAH was observable among boys and girls; absolute levels of EAH increased with age; and maternal feeding styles were associated with EAH among girls. The most consistent evidence supported increased levels of EAH among overweight and obese versus normal weight children, both cross-sectionally and prospectively. Two studies supported a genetic component to EAH. CONCLUSIONS: Studies enrolling independent samples support a positive association between weight status and EAH among children; studies addressing causality are needed. Other various individual, genetic, and familiar characteristics were associated with EAH, yet studies among more heterogeneous sample populations are needed to confirm findings. Studies addressing societal-level factors related to EAH were absent.

Genetic associations with consumption of palatable foods in the absence of hunger in response to food cues in children.

OBJECTIVE: The objective of this study is to evaluate obesity-related genetic factors in relation to excess consumption and assess if food cues modify associations. METHODS: Children (9-12 years) completed a randomized crossover experiment. During two visits, children ate a preload and then snacks ad libitum while watching television, embedded with food or non-food advertisements to assess eating in the absence of hunger (EAH). Primary exposures were obesity-associated genotypes, FTO rs9939609 and MC4R rs571312, and a paediatric-specific polygenic risk score (PRS). Outcomes included consumption of all snacks (total EAH) and gummy candy only (gummy candy EAH). Linear mixed-effects models tested whether genetic exposures related to EAH outcomes. We tested for effect modification by food cues using multiplicative interaction terms. RESULTS: Among 177 children, each FTO risk allele was associated with a 30% increase in gummy candy EAH (p = 0.025) in adjusted models. Food cue exposure exacerbated associations between the FTO variant with gummy candy EAH (p = 0.046). No statistically significant associations were found between MC4R and EAH. CONCLUSION: The results suggest children with the FTO rs9939609 risk allele may be predisposed to excess consumption of candy and that this association may be exacerbated by food cues.

Genetic associations with neural reward responsivity to food cues in children.

Objective: To test associations of candidate obesity-related single nucleotide polymorphisms (SNPs) and obesity polygenic risk scores (PRS) with neural reward reactivity to food cues. Methods: After consuming a pre-load meal, 9-12-year-old children completed a functional magnetic resonance imaging (fMRI) paradigm with exposure to food and non-food commercials. Genetic exposures included FTO rs9939609, MC4R rs571312, and a pediatric-specific obesity PRS. A targeted region-of-interest (ROI) analysis for 7 bilateral reward regions and a whole-brain analysis were conducted. Independent associations between each genetic factor and reward responsivity to food cues in each ROI were evaluated using linear models. Results: Analyses included 151 children (M = 10.9 years). Each FTO rs9939609 obesity risk allele was related to a higher food-cue-related response in the right lateral hypothalamus after controlling for covariates including the current BMI Z-score (p < 0.01), however, the association did not remain significant after applying the multiple testing correction. MC4R rs571312 and the PRS were not related to heightened food-cue-related reward responsivity in any examined regions. The whole-brain analysis did not identify additional regions of food-cue-related response related to the examined genetic factors. Conclusion: Children genetically at risk for obesity, as indicated by the FTO genotype, may be predisposed to higher food-cue-related reward responsivity in the lateral hypothalamus in the sated state, which, in turn, could contribute to overconsumption. Clinical trial registration: https://clinicaltrials.gov/study/NCT03766191, identifier NCT03766191.

Differential neural reward reactivity in response to food advertising medium in children.

Introduction: Food cues including food advertisements (ads) activate brain regions related to motivation and reward. These responses are known to correlate with eating behaviors and future weight gain. The objective of this study was to compare brain responses to food ads by different types of ad mediums, dynamic (video) and static (images), to better understand how medium type impacts food cue response. Methods: Children aged 9-12 years old were recruited to complete a functional magnetic resonance imaging (fMRI) paradigm that included both food and non-food dynamic and static ads. Anatomical and functional images were preprocessed using the fMRIPrep pipeline. A whole-brain analysis and a targeted region-of-interest (ROI) analysis for reward regions (nucleus accumbens, orbitofrontal cortex, amygdala, insula, hypothalamus, ventral tegmental area, substantia nigra) were conducted. Individual neural responses to dynamic and static conditions were compared using a paired t-test. Linear mixed-effects models were then constructed to test the differential response by ad condition after controlling for age, sex, BMI-z, physical activity, and % of kcal consumed of a participant's estimated energy expenditure in the pre-load prior to the MRI scan. Results: A total of 115 children (mean=10.9 years) completed the fMRI paradigm. From the ROI analyses, the right and left hemispheres of the amygdala and insula, and the right hemisphere of the ventral tegmental area and substantia nigra showed significantly higher responses for the dynamic food ad medium after controlling for covariates and a false discovery rate correction. From the whole-brain analysis, 21 clusters showed significant differential responses between food ad medium including the precuneus, middle temporal gyrus, superior temporal gyrus, and inferior frontal gyrus, and all regions remained significant after controlling for covariates. Discussion: Advertising medium has unique effects on neural response to food cues. Further research is needed to understand how this differential activation by ad medium ultimately affects eating behaviors and weight outcomes.

Corrigendum: Differential neural reward reactivity in response to food advertising medium in children.

[This corrects the article DOI: 10.3389/fnins.2023.1052384.].

Randomized Exposure to Food Advertisements and Eating in the Absence of Hunger Among Preschoolers.

BACKGROUND: Preschoolers in the United States are heavily exposed to unhealthy food advertisements. Whether such exposure promotes cued eating has not been documented in this age group. METHODS: Randomized experiment among 60 children, aged 2 to 5 years, recruited in 2015-2016 from New Hampshire and Vermont. Children completed the experiment at a behavioral laboratory. Children were provided with a healthy snack to consume upon arrival then randomized to view a 14-minute TV program embedded with advertisements for either a food or a department store. Children were provided 2 snack foods to consume ad libitum while viewing the TV program; 1 of those snacks was the food advertised. Eating in the absence of hunger (EAH) was operationalized as the kilocalories of snack foods consumed. t tests were used to compare EAH by advertisement condition; linear regression models assessed effect modification by the child's age, sex, BMI percentile, and parental feeding restriction. RESULTS: Mean age was 4.1 (SD 0.9) years, 55% of children were male, 80% were non-Hispanic white, and 20% were overweight or obese. There were no differences in child or socioeconomic characteristics by advertisement condition. Child BMI was not related to EAH. Mean kilocalories consumed during the EAH phase was greater among children exposed to the food advertisements (126.8, SD: 58.5) versus those exposed to the nonfood advertisements (97.3, SD: 52.3; P = .04), an effect driven by greater consumption of the advertised food (P < .01). There was no evidence of effect modification. CONCLUSIONS: Findings suggest that food advertisement exposure may encourage obesogenic-eating behaviors among the very young.