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Abstract Background Identifying children and adolescents with cardiometabolic risk at an early stage is crucial for effective treatment and prevention. From a practical perspective, this could be accomplished by assessing the presence of abdominal obesity, which serves as a surrogate indicator of increased cardiometabolic risk and is easy to measure. However, the assessment of abdominal obesity via waist circumference has not yet become a standard procedure in pediatric healthcare. The present study aimed to analyze the secular trends in increased cardiometabolic risk, as indicated by waist circumference among Spanish children and adolescents. Methods This study included 4861 children and adolescents aged 8 to 16 years from two nationwide representative cross-sectional surveys, the EnKid study and the PASOS study, conducted in 1998–2000 and 2019–2020, respectively. Anthropometric variables were measured in both surveys by trained personnel. Three different waist-to-height (WHtR) cutoffs were used to define abdominal obesity as criteria for cardiometabolic risk. BMI categories were defined according to the IOTF and WHO growth charts. Results Abdominal obesity [waist to height ratio (cm/cm) > 0.49] significantly increased from 40.7 to 56.1% and 93.8 to 97.2% in participants with overweight and obesity, respectively, between 1998–2000 and 2019–2020 (p

IntroductionHuman milk contains human milk oligosaccharides (HMOs) and microRNAs (miRNAs), which are key bioactive components. HMOs are indigestible carbohydrates that impact infant growth and development. miRNAs are small, non-coding RNAs that regulate post-transcriptional gene expression. miRNAs are abundant in human milk and can be contained in extracellular vesicles (EVs). There is evidence that miRNAs are synthesized in the mammary epithelium and may influence mammary gland development and milk synthesis. However, the relationships between miRNAs and HMOs have yet to be fully characterized.MethodsThis study examined the associations between 210 human milk EV-miRNAs and 19 HMOs in a cohort of 98 Latina mothers. HMO measures included summary measures and concentrations of 19 HMOs. Relationships between EV-miRNAs and HMOs were examined using principal components analysis and associations between individual EV-miRNAs and HMOs were assessed.ResultsOverall patterns of EV-miRNA levels, summarized using principal components, were associated with HMO summary measures and concentrations. Levels of individual EV-miRNAs were associated with HMO summary measures and individual concentrations of 2’FL, 3FL, 3’SL, 6’SL, FLNH, LNFP I, and LNH.DiscussionResults from this study suggest that human milk EV-miRNAs are associated with the concentration of HMOs, which may have important effects on infant growth and development.

Background: Exposure to ambient air pollutants has emerged as a risk for metabolic-dysfunction associated steatotic liver disease (MASLD). Objectives: We sought to examine associations between short-term (prior month) and long-term (prior year) ambient air pollution exposure with hepatic fat fraction (HFF) and liver stiffness in Latino youth with obesity. A secondary aim was to investigate effect modification by patatin-like phospholipase domain-containing protein 3 (PNPLA3) genotype and liver disease severity. Methods: Data was analyzed from 113 Latino youth (age 11–19) with obesity in Southern California. Individual exposure to particulate matter with aerodynamic diameter ≤ 2.5μm (PM2.5), ≤ 10μm (PM10), nitrogen dioxide (NO2), 8-hour maximum ozone (8hrMax-O3), 24-hr O3, and redox-weighted oxidative capacity (Oxwt) were estimated using residential address histories and United States Environmental Protection Agency air quality observations. HFF and liver stiffness were measured using magnetic resonance imaging. Linear models were used to determine associations between short-term and long-term exposure to air pollutants with HFF and liver stiffness. Modification by PNPLA3 and liver disease severity was then examined. Results: Short-term exposure to 8hrMax-O3 was positively associated with HFF. Relationships between air pollution exposure and HFF were not impacted by PNPLA3 genotype or liver disease severity. Long-term exposure to 8hrMax-O3 and Oxwt were positively associated with liver stiffness. Associations between air pollution exposure and liver stiffness depended on PNPLA3 genotype, such that individuals with GG genotypes exhibited stronger, more positive relationships between short-term exposure to PM10, 8hrMax-O3, 24-hr O3, and Oxwt and liver stiffness than individuals with CC/CG genotypes. In addition, relationships between short-term exposure to NO2 and liver stiffness were stronger in those with severe liver disease. Discussion: Air pollution exposure may be a risk factor for liver disease among Latino youth with obesity, particularly in those with other preexisting risks for liver damage.

Abstract Background The Special Supplemental Nutrition Program for Women, Infants and Children (WIC) issues infant formula to infants who are not fully breastfed, and prior research found elevated obesity risk among children receiving lactose-reduced infant formula with corn syrup solids (CSSF) issued by WIC. This study was conducted to evaluate associations between a broader set of specialty infant formulas issued by WIC and child obesity risk, whether neighborhood context (e.g. neighborhood food environment) modifies associations, and whether racial/ethnic disparities in obesity are partly explained by infant formula exposure and neighborhood context. Methods WIC administrative data, collected from 2013–2020 on issued amount (categorical: fully formula fed, mostly formula fed, mostly breastfed, fully breastfed) and type of infant formula (standard cow’s milk formula, and three specialty formulas: any CSSF, any soy-based formula, and any cow's milk-based formula with added rice starch) and obesity at ages 2–4 years (defined as a Body Mass Index z-score ≥ 95th percentile according to World Health Organization growth standard) were used to construct a cohort (n = 59,132). Associations of infant formula exposures and race/ethnicity with obesity risk were assessed in Poisson regression models, and modification of infant feeding associations with obesity by neighborhood context was assessed with interaction terms. Results Any infant formula exposure was associated with significantly higher obesity risk relative to fully breastfeeding. Receipt of a CSSF was associated with 5% higher obesity risk relative to the standard and other specialty infant formulas (risk ratio 1.05, 95% confidence interval 1.02, 1.08) independent of breastfeeding duration and receipt of other specialty infant formulas. The association between CSSF and obesity risk was stronger in neighborhoods with healthier food environments (10% higher risk) compared to less healthy food environments (null). Racial/ethnic disparities in obesity risk were robust to adjustment for infant formula exposure and neighborhood environment. Conclusions Among specialty infant formulas issued by WIC, only CSSFs were associated with elevated obesity risk, and this association was stronger in healthier food environments. Future research is needed to isolate the mechanism underlying this association.

Abstract Human milk oligosaccharides (HMOs) impact neonate immunity and health outcomes. However, the environmental factors influencing HMO composition remain understudied. This study examined the associations between ambient air pollutant (AAP) exposure and HMOs at 1-month postpartum. Human milk samples were collected at 1-month postpartum (n = 185). AAP (PM2.5, PM10, NO2) exposure included the 9-month pregnancy period through 1-month postpartum. Associations between AAP with (1) HMO diversity, (2) the sum of sialylated and fucosylated HMOs, (3) 6 a priori HMOs linked with infant health, and (4) all HMOs were examined using multivariable linear regression and principal component analysis (PCA). Exposure to AAP was associated with lower HMO diversity. PM2.5 and PM10 exposure was positively associated with the HMO 3-fucosyllactose (3FL); PM2.5 exposure was positively associated with the sum of total HMOs, sum of fucosylated HMOs, and the HMO 2′-fucosyllactose (2′FL). PCA indicated the PM2.5, PM10, and NO2 exposures were associated with HMO profiles. Individual models indicated that AAP exposure was associated with five additional HMOs (LNFP I, LNFP II, DFLNT, LNH). This is the first study to demonstrate associations between AAP and breast milk HMOs. Future longitudinal studies will help determine the long-term impact of AAP on human milk composition.

Background: Per- and polyfluoroalkyl substances (PFAS) are pollutants linked to adverse health effects. Diet is an important source of PFAS exposure, yet it is unknown how diet impacts longitudinal PFAS levels. Objective: To determine if dietary intake and food sources were associated with changes in blood PFAS concentrations among Hispanic young adults at risk of metabolic diseases. Methods: Predominantly Hispanic young adults from the Children’s Health Study who underwent two visits (CHS; n = 123) and young adults from NHANES 2013–2018 who underwent one visit (n = 604) were included. Dietary data at baseline was collected using two 24-hour dietary recalls to measure individual foods and where foods were prepared/consumed (home/restaurant/fast-food). PFAS were measured in blood at both visits in CHS and cross-sectionally in NHANES. In CHS, multiple linear regression assessed associations of baseline diet with longitudinal PFAS; in NHANES, linear regression was used. Results: In CHS, all PFAS except PFDA decreased across visits (all p

ABSTRACT The postpartum period represents a dynamic time for women’s health, particularly when it comes to changes in weight, which can disproportionately affect Latina women. Weight change, particularly weight gain, has been associated with pronounced changes in host gut microbiome profiles and composition. This study aimed to evaluate changes in the gut microbiome among Latina mothers who gained or lost weight in the first 6 months after delivery by characterizing changes in gut microbial co-occurrence networks, alpha- and beta-diversity measures, and relative abundances of bacterial taxa. This study characterized the gut microbiomes of 105 Latina mothers at 1 and 6 months postpartum, comparing mothers who gained weight (n = 65) with those who lost weight (n = 40) during the 6-month period following delivery. Stool samples were collected for 16S rRNA gene sequencing. Statistical analysis was conducted using microbial co-occurrence network analysis as well as paired two-sided t-tests. Mothers who gained weight postpartum had significant changes in their co-occurrence network density, alpha- and beta-diversity, and relative abundances of certain microbial taxa compared to those who lost weight. Microbial co-occurrence networks, representing measures of differences in community structure dynamics, of the weight gain group decreased in density by 2%, while there was no change in density in the weight loss group. Additionally, the weight gain group had lower Shannon entropy after 6 months and significant changes in the relative abundances of 17 bacterial families and genera, while there were no significant changes in any of these metrics in the weight loss group.IMPORTANCEPrevious research has reported differences in the gut microbiome associated with varying body compositions. More specifically, within populations of mothers, the focus has been on the impact of gestational weight gain. This is the first study to examine postpartum weight change and its association with changes in the gut microbiome, similarly, it is the first to use a Latina cohort to do so. The results support the idea that weight gain may be an important factor in reducing gut microbiome network connectivity, diversity, and changing abundances of specific microbial taxa, all measures thought to impact host health. These results suggest that weight gain dynamically alters mothers’ gut microbial communities in the first 6 months postpartum, with comparatively little change in mothers who lost weight; further research is needed to examine the health consequences of such changes.

Abstract During the first 2 years of life, the infant gut microbiome is rapidly developing, and gut bacteria may impact host health through the production of metabolites that can have systemic effects. Thus, the fecal metabolome represents a functional readout of gut bacteria. Despite the important role that fecal metabolites may play in infant health, the development of the infant fecal metabolome has not yet been thoroughly characterized using frequent, repeated sampling during the first 2 years of life. Here, we described the development of the fecal metabolome in a cohort of 101 Latino infants with data collected at 1-, 6-, 12-, 18-, and 24-months of age. We showed that the fecal metabolome is highly conserved across time and highly personalized, with metabolic profiles being largely driven by intra-individual variability. Finally, we also identified several novel metabolites and metabolic pathways that changed significantly with infant age, such as valerobetaine and amino acid metabolism, among others.

Abstract Background Social determinants of health (SDoH) describe the complex network of circumstances that impact an individual before birth and across the lifespan. SDoH contextualize factors in a community that are associated with chronic disease risk and certain health disparities. The main objective of this study was to explore the impact of SDoH on the prevalence of obesity and diabetes, and whether these factors explain disparities in these health outcomes among Latinos in Southern California. Methods We utilized three composite indices that encompass different SDoH: the Healthy Places Index (HPI), Social Vulnerability Index (SVI), and CalEnviroScreen (CES). Univariate linear regression models explored the associations between index scores with adult obesity, adult diabetes, and childhood obesity. Results Communities with lower HPI scores were associated with higher prevalence of metabolic disease and a greater proportion of Latino residents. Cities in the lowest decile of HPI scores had 71% of the population identifying as Latino compared to 12% in the highest decile. HPI scores explained 61% of the variability in adult obesity (p

Abstract Background Higher prenatal ambient air pollution exposure has been associated with impaired neurodevelopment in preschoolers and school-aged children. The purpose of this study was to explore the relationships between prenatal ambient air pollution exposure and neurodevelopment during infancy. Methods This study examined 161 Latino mother-infant pairs from the Southern California Mother’s Milk Study. Exposure assessments included prenatal nitrogen dioxide (NO2) and particulate matter smaller than 2.5 and 10 microns in diameter (PM2.5 and PM10, respectively). The pregnancy period was also examined as three windows, early, mid, and late, which describe the first, middle, and last three months of pregnancy. Infant neurodevelopmental outcomes at 2 years of age were measured using the Bayley-III Scales of Infant and Toddler Development. Multivariable linear models and distributed lag linear models (DLM) were used to examine relationships between prenatal exposures and neurodevelopmental scores, adjusting for socioeconomic status, breastfeeding frequency, time of delivery, pre-pregnancy body mass index, and infant birthweight and sex. Results Higher prenatal exposure to PM10 and PM2.5 was negatively associated with composite cognitive score (β = -2.01 [-3.89, -0.13] and β = -1.97 [-3.83, -0.10], respectively). In addition, higher average prenatal exposure to PM10 was negatively associated with composite motor (β = -2.35 [-3.95, -0.74]), scaled motor (β = -0.77 [-1.30, -0.24]), gross motor (β = -0.37 [-0.70, -0.04]), fine motor (β = -0.40 [-0.71, -0.09]), composite language (β = -1.87 [-3.52, -0.22]), scaled language (β = -0.61 [-1.18, -0.05]) and expressive communication scaled scores (β = -0.36 [-0.66, -0.05]). DLMs showed that higher prenatal air pollution exposure during mid and late pregnancy was inversely associated with motor, cognitive, and communication language scores. Conclusions Higher exposure to air pollutants during pregnancy, particularly in the mid and late prenatal periods, was inversely associated with scaled and composite motor, cognitive, and language scores at 2 years. These results indicate that prenatal ambient air pollution may negatively impact neurodevelopment in early life.

Breast milk contains thousands of bioactive compounds including extracellular vesicle microRNAs (EV-miRNAs), which may regulate pathways such as infant immune system development and metabolism. We examined the associations between the expression of EV-miRNAs and laboratory variables (i.e., batch effects, sample characteristics), sequencing quality indicators, and maternal-infant characteristics. The study included 109 Latino mother-infant dyads from the Southern California Mother’s Milk Study. Mothers were age 28.0 ± 5.6 and 23-46 days postpartum. We used principal components analysis to evaluate whether EV-miRNA expression was associated with factors of interest. Then, we used linear models to estimate relationships between these factors and specific EV-miRNA counts and analyzed functional pathways associated with those EV-miRNAs. Finally, we explored which maternal-infant characteristics predicted sequencing quality indicators. Sequencing quality indicators, predominant breastfeeding, and breastfeedings/day were associated with EV-miRNA principal components. Maternal body mass index and breast milk collection timing predicted proportion of unmapped reads. Expression of 2 EV-miRNAs were associated with days postpartum, 23 EV-miRNAs were associated with breast milk collection time, 23 EV-miRNAs were associated with predominant breastfeeding, and 38 EV-miRNAs were associated with breastfeedings/day. These EV-miRNAs were associated with pathways including Hippo signaling pathway and ECM-receptor interaction, among others. This study identifies several important factors that may contribute to breast milk EV-miRNA expression. Future studies should consider these findings in the design and analysis of breast milk miRNA research.

The prevalence of obesity and type 2 diabetes is growing at an alarming rate, including among pregnant women. Low-calorie sweeteners (LCSs) have increasingly been used as an alternative to sugar to deliver a sweet taste without the excessive caloric load. However, there is little evidence regarding their biological effects, particularly during development. Here, we used a mouse model of maternal LCS consumption to explore the impact of perinatal LCS exposure on the development of neural systems involved in metabolic regulation. We report that adult male, but not female, offspring from both aspartame- and rebaudioside A–exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal LCS consumption reorganized hypothalamic melanocortin circuits and disrupted parasympathetic innervation of pancreatic islets in male offspring. We then identified phenylacetylglycine (PAG) as a unique metabolite that was upregulated in the milk of LCS-fed dams and the serum of their pups. Furthermore, maternal PAG treatment recapitulated some of the key metabolic and neurodevelopmental abnormalities associated with maternal LCS consumption. Together, our data indicate that maternal LCS consumption has enduring consequences on the offspring’s metabolism and neural development and that these effects are likely to be mediated through the gut microbial co-metabolite PAG.

Epidemiological studies in adults have shown that exposure to ambient air pollution (AAP) is associated with the composition of the adult gut microbiome, but these relationships have not been examined in infancy. We aimed to determine if 6-month postnatal AAP exposure was associated with the infant gut microbiota at 6 months of age in a cohort of Latino mother-infant dyads from the Southern California Mother’s Milk Study (n = 103). We estimated particulate matter (PM2.5 and PM10) and nitrogen dioxide (NO2) exposure from birth to 6-months based on residential address histories. We characterized the infant gut microbiota using 16S rRNA amplicon sequencing at 6-months of age. At 6-months, the gut microbiota was dominated by the phyla Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Our results show that, after adjusting for important confounders, postnatal AAP exposure was associated with the composition of the gut microbiota. As an example, PM10 exposure was positively associated with Dialister, Dorea, Acinetobacter, and Campylobacter while PM2.5 was positively associated with Actinomyces. Further, exposure to PM10 and PM2.5 was inversely associated with Alistipes and NO2 exposure was positively associated with Actinomyces, Enterococcus, Clostridium, and Eubacterium. Several of these taxa have previously been linked with systemic inflammation, including the genera Dialister and Dorea. This study provides the first evidence of significant associations between exposure to AAP and the composition of the infant gut microbiota, which may have important implications for future infant health and development.

BackgroundRandomized controlled trials of time restricted eating (TRE) in adults have demonstrated improvements in glucose variability as captured by continuous glucose monitors (CGM). However, little is known about the feasibility of CGM use in TRE interventions in adolescents, or the expected changes in glycemic profiles in response to changes in meal-timing. As part of a pilot trial of TRE in adolescents with obesity, this study aimed to 1) assess the feasibility of CGM use, 2) describe baseline glycemic profiles in adolescents with obesity, without diabetes, and 3) compare the difference between glycemic profiles in groups practicing TRE versus control.MethodsThis study leverages data from a 12-week pilot trial (ClinicalTrials.gov Identifier: NCT03954223) of late TRE in adolescents with obesity compared to a prolonged eating window. Feasibility of CGM use was assessed by monitoring 1) the percent wear time of the CGM and 2) responses to satisfaction questionnaires. A computation of summary measures of all glycemic data prior to randomization was done using EasyGV and R. Repeat measures analysis was conducted to assess the change in glycemic variability over time between groups. Review of CGM tracings during periods of 24-hour dietary recall was utilized to describe glycemic excursions.ResultsFifty participants were enrolled in the study and 43 had CGM and dietary recall data available (16.4 + 1.3 years, 64% female, 64% Hispanic, 74% public insurance). There was high adherence to daily CGM wear (96.4%) without negative impacts on daily functioning. There was no significant change in the glycemic variability as measured by standard deviation, mean amplitude glycemic excursion, and glucose area under the curve over the study period between groups.ConclusionsCGM use appears to be a feasible and acceptable tool to monitor glycemic profiles in adolescents with obesity and may be a helpful strategy to confirm TRE dosage by capturing glycemic excursions compared to self-reported meal timing. There was no effect of TRE on glucose profiles in this study. Further research is needed to investigate how TRE impacts glycemic variability in this age group and to explore if timing of eating window effects these findings.

The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in childhood (median 10 yrs) and adolescence (median 16 yrs). We used a multi-step approach: first, mixed models were used to examine the associations of SSB intake in childhood with CM measures across childhood and adolescence, which revealed a positive association between SSB intake and fasting triglycerides (β (95% CI) for the highest vs. lowest SSB quartile: 8.1 (−0.9,17.0); p-trend = 0.057). Second, least absolute shrinkage and selection operator (LASSO) regression was used to select 180 metabolite features (out of 767 features assessed by untargeted metabolomics) that were associated with SSB intake in childhood. Finally, 13 of these SSB-associated metabolites (from step two) were also prospectively associated with triglycerides across follow-up (from step one) in the same direction as with SSB intake (Bonferroni-adj. p < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids. In this diverse cohort, we identified a panel of lipid metabolites that may serve as intermediary biomarkers, linking SSB intake to dyslipidemia risk in youth.

Exposure to ambient and near-roadway air pollution during pregnancy has been linked with several adverse health outcomes for pregnant women and their babies. Emerging research indicates that microRNA (miRNA) expression can be altered by exposure to air pollutants in a variety of tissues. Additionally, miRNAs from breast tissue and circulating miRNAs have previously been proposed as a biomarker for breast cancer diagnosis and prognosis. Therefore, this study sought to evaluate the associations between pregnancy exposures to ambient (PM _10 , PM _2.5 , NO _2 , O _3 ) and near-roadway air pollution (total NO _x , freeway NO _x , non-freeway NO _x ) with breast milk extracellular vesicle miRNA (EV-miRNA), measured at 1-month postpartum, in a cohort of 108 Latina women living in Southern California. We found that PM _10 exposure during pregnancy was positively associated with hsa-miR-200c-3p, hsa-miR-200b-3p, and hsa-let-7c-5p, and was negatively associated with hsa-miR-378d. We also found that pregnancy PM _2.5 exposure was positively associated with hsa-miR-200c-3p and hsa-miR-200b-3p. First and second trimester exposure to PM _10 and PM _2.5 was associated with several EV-miRNAs with putative messenger RNA targets related to cancer. This study provides preliminary evidence that air pollution exposure during pregnancy is associated with human milk EV-miRNA expression.