Socioeconomic position and executive functioning from childhood to young adulthood: Evidence from Santiago, Chile.

BACKGROUND: Optimizing cognitive development through early adulthood has implications for population health. This study aims to understand how socioeconomic position (SEP) across development relates to executive functioning. We evaluate three frameworks in life-course epidemiology - the sensitive period, accumulation, and social mobility hypotheses. METHODS: Participants were young adults from Santiago, Chile who were studied from 6 months to 21 years. Family SEP was measured at ages 1 y, 10 y, and 16 y with the modified Graffar Index. Executive functioning was assessed at ages 16 y and 21 y by the Trail Making Test Part B (Trails B). Analyses estimating 16 y and 21 y executive function involved 581 and 469 participants, respectively. Trails B scores were modeled as a function of SEP at 1 y, 10 y, and 16 y, as the total accumulation of disadvantage, and as change in SEP between 1 y and 10 y and between 10 y and 16 y. RESULTS: Participants were low- to middle-income in infancy and, on average, experienced upwards mobility across childhood. Half of participants (58%) improved Trails B scores from 16 y and 21 y. Most (68%) experienced upward social mobility between infancy and 16 y. When examined independently, worse SEP measured at 10 y and 16 y related to worse (longer time to complete) Trails B scores at Age 21 but did not relate to the other outcomes. After mutual adjustment as a test of the sensitivity hypothesis, no SEP measure was independently related to any outcome. Testing the accumulation hypothesis, cumulative low SEP was associated with worse cognitive performance at 21 y (ß = 3.6, p = 0.04). Results for the social mobility hypothesis showed no relation to cognitive scores or to change in cognitive scores. Comparing all hypotheses, SEP at 16 y explained the most variability in executive functioning at 21 y, providing support for the sensitive period hypothesis. CONCLUSIONS: Results indicate that experiencing cumulatively low socioeconomic position from infancy to adolescence can have a negative impact on cognitive functioning in young adulthood. Findings also provide evidence in support of adolescence as a key developmental period during which SEP can most strongly impact cognitive functioning.

[A prospective cohort study on visual development in infants and young children].

Objective: This study aimed to analyze the trends and characteristics of early visual development in infants and young children. Methods: A prospective cohort study was conducted, including full-term infants born between 2008 and 2013 at the Maternal and Child Health Hospital in Sanhe City, Hebei Province, China. Visual acuity was assessed at three time points 42 days after birth, 9 months of age, and 18 months of age, using the Teller Acuity Card Ⅱ (TAC Ⅱ) grating visual acuity test. At 3 years of age, visual acuity was assessed using the Lea Symbols chart and converted to grating visual acuity. Visual acuity of both eyes was measured at 42 days, 9 months, and 18 months. For children at 9 and 18 months, monocular visual acuity was also assessed, while at 3 years of age, monocular visual acuity was measured. Visual acuity measurements at different time points and changes in visual acuity within each period were recorded. The visual development of the participants was analyzed and compared with previous literature results. Results: A total of 1 496 children were included in the study, including 773 males (51.67%) and 723 females (48.33%). The binocular visual acuity at 42 days, 9 months, and 18 months was 0.9 (0.6, 1.1), 6.4 (6.4, 9.6), and 9.6 (9.6, 9.6) cycles per degree (cpd), respectively, with statistically significant differences (P<0.001). Visual acuity increased by a factor of 3.21±0.70 between 42 days and 9 months, and by a factor of 0.23±0.48 between 9 and 18 months. At 9 months of age, the monocular visual acuity in the right and left eyes was 6.4 (4.8, 6.4) cpd, which remained the same at 18 months, and the median visual acuity at 3 years of age for both eyes was 18.75 cpd, with a Snellen visual acuity of 20/32 (20/40, 20/32). The differences in binocular visual acuity at each time point were not statistically significant (all P>0.05). At 9 months of age, 68.7%(633/921) of children had visual acuity of ≥6.5 cpd, which increased to 92.7%(342/369) at 18 months. Monocular visual acuity increased by a factor of 0.26±0.46 between 9 and 18 months, and by a factor of 1.36±0.52 between 18 months and 3 years. At 9 months of age, 72.01% (921 out of 1 279) of children who completed binocular visual acuity testing also underwent monocular visual acuity testing, while this proportion decreased to 35.83% (369 out of 1 030) at 18 months. Visual acuity improved with increasing age (P<0.001). The visual acuity of children at each age group in this study was higher than that reported in the literature for children in Guangzhou (P<0.001). Conclusions: The visual acuity of healthy infants and young children below 3 years of age improves with age. Visual development progresses rapidly before 9 months of age, slows down afterward, and then resumes rapid growth at 18 months of age.

Breastfeeding Duration and Timing of Bottle Supplementation: Associations with Body Mass Index from Childhood to Young-Adulthood.

Evidence for the association between breastfeeding (BF) duration and later body mass index (BMI) is inconsistent. We explored how BF duration and BF type (exclusive or partial) related to BMI from childhood to young adulthood in a Chilean cohort. Infants were recruited at 6 months between 1994 and 1996 in Santiago, Chile (n = 821). Mothers reported date of first bottle and last BF; anthropometry was measured at 1, 5, 10, 16, and 23 years. We tested whether: (1) type of BF at 6 months (none, partial, exclusive) and (2) duration of exclusive BF (<1 month, 1 to <3 months, 3 to <6 months, and ≥6 months) related to BMI. At 6 months, 35% received both breastmilk and formula ("partial BF") and 38% were exclusively breastfed. We found some evidence of an association between longer BF and lower BMI z-scores at young ages but observed null effects for later BMI. Specifically, BF for 3 to <6 months compared to <1 month related to lower BMI z-scores at 1 and 5 years (both p < 0.05). Our results are in partial accordance with others who have not found a protective effect of longer BF for lower BMI.

Differentiation between fetal and postnatal iron deficiency in altering brain substrates of cognitive control in pre-adolescence.

BACKGROUND: Early iron deficiency (ID) is a common risk factor for poorer neurodevelopment, limiting children's potential and contributing to global burden. However, it is unclear how early ID alters the substrate of brain functions supporting high-order cognitive abilities and whether the timing of early ID matters in terms of long-term brain development. This study aimed to examine the effects of ID during fetal or early postnatal periods on brain activities supporting proactive and reactive cognitive control in pre-adolescent children. METHODS: Participants were part of a longitudinal cohort enrolled at birth in southeastern China between December 2008 and November 2011. Between July 2019 and October 2021, 115 children aged 8-11 years were invited to participate in this neuroimaging study. Final analyses included 71 children: 20 with fetal ID, 24 with ID at 9 months (postnatal ID), and 27 iron-sufficient at birth and 9 months. Participants performed a computer-based behavioral task in a Magnetic Resonance Imaging scanner to measure proactive and reactive cognitive control. Outcome measures included accuracy, reaction times, and brain activity. Linear mixed modeling and the 3dlme command in Analysis of Functional NeuroImages (AFNI) were separately used to analyze behavioral performance and neuroimaging data. RESULTS: Faster responses in proactive vs. reactive conditions indicated that all groups could use proactive or reactive cognitive control according to contextual demands. However, the fetal ID group was lower in general accuracy than the other 2 groups. Per the demands of cues and targets, the iron-sufficient group showed greater activation of wide brain regions in proactive vs. reactive conditions. In contrast, such condition differences were reversed in the postnatal ID group. Condition differences in brain activation, shown in postnatal ID and iron-sufficient groups, were not found in the fetal ID group. This group specifically showed greater activation of brain regions in the reward pathway in proactive vs. reactive conditions. CONCLUSIONS: Early ID was associated with altered brain functions supporting proactive and reactive cognitive control in childhood. Alterations differed between fetal and postnatal ID groups. The findings imply that iron supplement alone is insufficient to prevent persisting brain alterations associated with early ID. Intervention strategies in addition to the iron supplement should consider ID timing.

A single night of moderate at-home sleep restriction increases hunger and food intake in overweight young adults.

OBJECTIVES: Experimental studies under laboratory conditions have shown a close link between acute sleep restriction and metabolic disorders. The aim of this study was to assess the effect of a single night of moderate sleep restriction implemented under ambulatory settings on sleep organization, food intake, blood pressure, and heart rate in overweight young adults. METHODS: In a non-randomized experimental study, we evaluated 15 young, overweight adults (mean age [± SEM] 20.8 ± 0.6 y) with a mean body mass index (BMI) 27.5 ± 6.2 kg/m2 (BMI range 18.9-36.6 kg/m2). Each participant was recorded at home during two successive nights under: 1) Regular sleep routine (from 2330 to 0730 h, 'night1') and 2) Restricted sleep (6 h in bed, from 0300 to 0900 h, "night2"). Sleep was assessed by a non-invasive mobile system (Watch-PAT200) placed on the non-dominant wrist, measuring peripheral arterial tonometry. We measured sleep duration, rapid eye movement sleep (REM), light sleep (LS), deep sleep (DS), and waking. Starting 2 d before night1, four consecutive food records assessed daily food intake. Preceding and succeeding each night, hunger/satiety feelings (measured by self-reported visual analog scales), blood pressure, and heart rate were also evaluated. RESULTS: Total sleep time was reduced in night2 (P = 0.007), with higher DS percentage (P = 0.03). Sleep onset and REM sleep latencies, LS time, and the number of wake episodes did not differ between nights. Energy intake was increased the day after night2 (P = 0.007), with increased fat and protein intakes (both P < 0.01) and feelings of hunger (P = 0.002). Systolic blood pressure was higher and heart rate faster in the morning after night2 (both P < 0.05). CONCLUSIONS: An acute moderate at-home sleep restriction exacerbated food intake and feelings of hunger, and impaired blood pressure and heart rate regulation in young, overweight adults.

Iron supplementation given to nonanemic infants: neurocognitive functioning at 16 years.

OBJECTIVE: There is concern that high iron uptake during the critical period of early brain development carries potential risks, especially for nonanemic infants. This study examined the neurocognitive functioning of 16-year-olds who were nonanemic as infants and received iron supplementation. METHODS: We studied 562 Chilean adolescents (M 16.2 years; 52.7% female) who participated in a randomized controlled iron supplementation trial in infancy. Between 6 and 12 months, 346 consumed an iron-fortified formula (12.7 Fe mg/L) or, if primarily breastfed, liquid vitamins with 15 mg elemental iron as ferrous sulfate, and 216 consumed unmodified cow milk without iron or liquid vitamins without iron if primarily breastfed. RESULTS: Compared to adolescents in the no-added iron condition in infancy, those in the iron-supplemented condition had poorer visual-motor integration, quantitative reasoning skills, and incurred more errors on neurocognitive tasks. Consuming larger amounts of iron-fortified formula in infancy was associated with lower arithmetic achievement. Of adolescents who had high hemoglobin at 6 months (Hb ≥ 125 g/L), those in the iron supplemented condition had poorer performance on arithmetic, quantitative reasoning, and response inhibition tests than those in the no-added iron condition. Of adolescents who had marginally low 6-month hemoglobin (Hb > 100 and < 110 g/L), those who received no-added iron incurred more errors on a visual searching task than those in the iron-supplemented condition. CONCLUSION: The physiologic need for iron during the period of rapid and critical brain development in young infants should be considered vis-à-vis the risks associated with supplementing nonanemic infants with high levels of iron.Clinical Trials number: NCT01166451.

Iron Deficiency in Infancy and Sluggish Cognitive Tempo and ADHD Symptoms in Childhood and Adolescence.

OBJECTIVE: To determine whether iron deficiency in infancy is associated with sluggish cognitive tempo (SCT) or attention-deficit/hyperactive-impulsive (AD-HI) symptoms in childhood and adolescence, and whether such behaviors contribute concurrently and predictively to lower verbal and mathematical abilities. METHOD: Chilean children (N = 959; 50% male, of Spanish or indigenous descent from working-class backgrounds) were rated by mothers for SCT or AD-HI symptoms at ages 5, 10, and 16 years. Children completed standardized tests assessing verbal and mathematical abilities at ages 5, 10, and 16. At ages 12 and 18 months, children were assessed for iron deficiency. RESULTS: Adjusting for a comprehensive panel of covariates, greater severity of iron deficiency in infancy was associated with more frequent SCT and AD-HI symptoms at all ages studied. Most effects of iron deficiency on children's verbal and math skills were indirect, mediated through AD-HI behaviors. Children's AD-HI symptoms related to lower verbal and math test scores within age and across age. CONCLUSIONS: The long-term associations found between infant iron deficiency and SCT and AD-HI behaviors suggest that the neurodevelopmental alterations that stem from postnatal iron deficiency might play an etiological role in the development of ADHD. Screening for early-life nutritional deficiencies among children with SCT or ADHD symptoms might prove useful, and behavioral screening of children with a history of iron deficiency seems warranted. Interventions that support brain development after early nutritional deprivation also would be beneficial.

Early-life adversity is associated with poor iron status in infancy.

Exposure to early-life adversity (ELA) and iron deficiency early in life are known risk factors for suboptimal brain and socioemotional development. Iron deficiency may arise from and co-occur with ELA, which could negatively affect development. In the present study, we investigated whether ELA is associated with iron deficiency in infants receiving no iron supplementation. This study is a secondary analysis of extant data collected in the 1990s; participants were healthy infants from working-class communities in Santiago, Chile (N = 534, 45.5% female). We measured stressful life events, maternal depression, and low home support for child development during infancy and assessed iron status when the infant was 12 months old. Slightly more than half of the infants were iron-deficient (51%), and 25.8% were iron-deficient anemic at 12 months. Results indicated that ELA was associated with lower iron levels and iron deficiency at 12 months. The findings are consistent with animal and human prenatal models of stress and iron status and provide evidence of the association between postnatal ELA and iron status in humans. The findings also highlight a nutritional pathway by which ELA may impact development and present a nutritionally-focused avenue for future research on ELA and psychopathology.

Nighttime Sleep Characteristics and White Matter Integrity in Young Adults.

Purpose: Sleep is essential for life and plays a key role for optimal physiology, brain functioning, and health. Evidence suggests a relation between sleep and cerebral white matter integrity. Human studies report that sleep duration shows a U-shaped association with brain functioning. We hypothesized that participants with longer or shorter sleep time in the nighttime period show altered microstructural white matter integrity. Participants and Methods: Seventy-three young adult participants were evaluated. Sleep-wake cycle parameters were assessed objectively using actigraphy. Diffusion tensor imaging studies were performed to assess white matter integrity using fractional anisotropy and mean, axial, and radial diffusivities. Relations between white matter microstructure indexes and sleep parameters were investigated through tract-based spatial statistics. Participants were grouped according to their nocturnal total sleep time: 27 in the Reference sleep group (6.5-8.0 h), 23 in the Short sleep group (<6.5 h) and 23 in the Long sleep group (>8.0 h). Results: Compared with the Reference sleep group, participants in the Long sleep group showed lower fractional anisotropy (p < 0.05) and higher radial diffusivity (p < 0.05) values in white matter tracts linked to sleep regulation (corona radiata, body of the corpus callosum, superior longitudinal fasciculus, and anterior thalamic radiation). Conclusion: This pattern of reduced fractional anisotropy and increased radial diffusivity in the Long sleep group indicates an association between sleep duration and lower integrity of myelin sheaths. Because myelin is continuously remodeled in the brain, nighttime sleep characteristics appear to be a key player for its quality and maintenance.

Cognitive control inhibition networks in adulthood are impaired by early iron deficiency in infancy.

Iron deficiency, a common form of micronutrient deficiency, primarily affects children and women. The principal cause of iron deficiency is undernutrition in low-income countries and malnutrition in middle to upper income regions. Iron is a key element for myelin production, neuronal metabolism, and dopamine functions. Iron deficiency in early life can alter brain development and exert long-lasting effects. Control inhibition is an executive function that involves several brain regions, including the prefrontal cortex and caudate and sub-thalamic nuclei. Dopamine is the prevalent neurotransmitter underlying cognitive inhibition. We followed cohort study participants who had iron deficiency anemia in infancy as well non-anemic controls. At 22 years of age, the participants were subjected to functional magnetic resonance imaging (fMRI) to evaluate the correlation between functional connectivity and performance on an inhibitory cognitive task (Go/No-Go). We hypothesized that former iron deficient anemic (FIDA) participants demonstrate less strength in functional connectivity compared with controls (C). There were not significant group differences in the behavioral results in terms of accuracy and response time. A continuous covariate interaction analysis of functional connectivity and the Go/No-Go scores demonstrated significant differences between the FIDA and C groups. The FIDA participants demonstrated less strength in connectivity in brain regions related to control inhibition, including the medial temporal lobe, impairment in the integration of the default mode network (indicating decreased attention and alertness), and an increase in connectivity in posterior brain areas, all of which suggest slower circuitry maturation. The results support the hypothesis that FIDA young adults show differences in the connectivity of networks related to executive functions. These differences could increase their vulnerability to develop cognitive dysfunctions or mental disorders in adulthood.

Infant Growth Trajectories and Lipid Levels in Adolescence: Evidence From a Chilean Infancy Cohort.

Growth in early infancy is hypothesized to affect chronic disease risk factors later in life. To date, most reports draw on European-ancestry cohorts with few repeated observations in early infancy. We investigated the association between infant growth before 6 months and lipid levels in adolescents in a Hispanic/Latino cohort. We characterized infant growth from birth to 5 months in male (n = 311) and female (n = 285) infants from the Santiago Longitudinal Study (1991-1996) using 3 metrics: weight (kg), length (cm), and weight-for-length (g/cm). Superimposition by translation and rotation (SITAR) and latent growth mixture models (LGMMs) were used to estimate the association between infant growth characteristics and lipid levels at age 17 years. We found a positive relationship between the SITAR length velocity parameter before 6 months of age and high-density lipoprotein cholesterol levels in adolescence (11.5, 95% confidence interval; 3.4, 19.5), indicating higher high-density lipoprotein cholesterol levels occurring with faster length growth. The strongest associations from the LGMMs were between higher low-density lipoprotein cholesterol and slower weight-for-length growth, following a pattern of associations between slower growth and adverse lipid profiles. Further research in this window of time can confirm the association between early infant growth as an exposure and adolescent cardiovascular disease risk factors.

Dynamic relationships between body fat and circulating adipokine levels from adolescence to young adulthood: The Santiago Longitudinal Study.

BACKGROUND AND AIMS: Adipose tissue secretes adipokines such as adiponectin and leptin, playing important roles in energy metabolism. The longitudinal associations between such adipokines and body fat accumulation have not been established, especially during adolescence and young adulthood and in diverse populations. The study aims to assess the longitudinal association between body fat measured with dual X-ray absorptiometry and plasma adipokines from adolescence to young adulthood. METHODS AND RESULTS: Among Hispanic/Latino participants (N = 537) aged 16.8 (SD: 0.3) years of the Santiago Longitudinal Study, we implemented structural equation modeling to estimate the sex-specific associations between adiposity (body fat percent (BF%) and proportion of trunk fat (PTF)) and adipokines (adiponectin and leptin levels) during adolescence (16 y) and these values after 6 years of follow-up (22 y). In addition, we further investigated whether the associations differed by baseline insulin resistance (IR) status. We found evidence for associations between 16 y BF% and 22 y leptin levels (ß (SE): 0.58 (0.06) for females; 0.53 (0.05) for males), between 16 y PTF and 22 y adiponectin levels (ß (SE): -0.31 (0.06) for females; -0.18 (0.06) for males) and between 16 y adiponectin levels and 22 y BF% (ß (SE): 0.12 (0.04) for both females and males). CONCLUSION: We observed dynamic relationships between adiposity and adipokines levels from late adolescence to young adulthood in a Hispanic/Latino population further demonstrating the importance of this period of the life course in the development of obesity.

Adjusting Ferritin Concentrations for Nonclinical Inflammation in Adolescents with Overweight or Obesity.

OBJECTIVE: To compare approaches for adjusting serum ferritin concentrations for inflammation in Chilean adolescents with overweight and obesity. STUDY DESIGN: Cross-sectional data from 518 adolescents (aged 16-17 years; 48% females) from Santiago, Chile were analyzed. Several approaches were compared for estimating the prevalence of depleted iron stores (defined as serum ferritin <15 µg/L), including unadjusted prevalence and higher cutoffs for various subgroups (excluding participants with inflammation), correction factors, and regression corrections. A "reference" prevalence estimate was calculated as the prevalence of serum ferritin <15 µg/L in normal weight individuals without inflammation. Each adjustment approach was compared with this reference prevalence. RESULTS: The sample comprised 61.2% normal weight, 23.7% overweight, and 15.1% obese individuals. The prevalence of inflammation (marked by C-reactive protein level >5.0 mg/L) was 6.3%, 8.1%, and 14.1% in the 3 groups, respectively. The correction factor approaches produced adjusted estimates closest to the reference estimate (24.1%-24.7% vs 22.9%), followed by the regression corrections (24.7%-25.1% vs 22.9%). Applying a higher serum ferritin cutoff (30 µg/L) to all participants or to participants with overweight/obesity produced adjusted estimates farthest from the reference (59.5% and 35.3%, respectively). CONCLUSIONS: Adjusting serum ferritin concentration may be necessary when assessing iron status in populations with high rates of overweight/obesity. After reviewing 6 approaches for adjusting for the influence of inflammation, this study suggests that using correction factors may be the most appropriate approach for adjusting serum ferritin in Chilean adolescents. Further research is needed to determine the optimal approach for adjusting serum ferritin concentrations for weight-related inflammation in broader populations.

Young adult outcomes associated with lower cognitive functioning in childhood related to iron-fortified formula in infancy.

Objective: This study examined how the lower cognitive skills in children who consumed iron-fortified formula in infancy relate to outcomes in young adulthood.Methods: Participants were 443 Chilean young adults (M age = 21.2y, 55% female) who took part in a randomized controlled iron-deficiency anemia preventive trial during infancy (6-12 m). Slightly over half of participants (n = 237) received iron-fortified formula (12.7 mg/L) and 206 received a low-iron formula (2.3 mg/L). Spatial memory, IQ, and visual-motor integration were measured at age 10, and neurocognition, emotion regulation, educational level, and attainment of adult developmental milestones were assessed at age 21.Results: Consumption of iron-fortified formula in infancy was associated with poorer performance on neurocognitive tests in childhood, and these effects related to poorer neurocognitive, emotional, and educational outcomes in young adulthood. Dosage effects associated with consumption of iron-fortified formula were found for lower educational attainment and, marginally, slower mental processing. Those who received iron-fortified formula and had low age 10 cognitive abilities performed most poorly on neurocognitive tests at age 21.Conclusion: Findings suggest that the long-term development of infants who consume iron-fortified formula may be adversely affected.Clinical Trials number: NCT01166451.

Timing of iron deficiency and recognition memory in infancy.

Objective: To determine the relationship between iron deficiency (or iron-deficient, ID) and neural correlates of recognition memory depending on ID timing (gestation vs. infancy) and infant age at testing (9 vs. 18 months).Study design: Event-related potentials (ERP) were used in a visual recognition memory task (mother vs. stranger face) to compare healthy term infants according to iron status at birth and 9 months. Fetal-neonatal ID was defined as cord serum ferritin < 75 µg/l or zinc protoporphrin/heme ratio > 118 µmol/mol, postnatal ID as ≥ 2 abnormal iron measures at 9 months with normal cord-blood iron status, and iron-sufficient as not ID at birth or 9 months. Recognition of mother faces was measured by negative component (Nc) and late slow wave (LSW). These ERP components reflect attention and memory updating processes, respectively.Results: All groups showed differences in Nc amplitude elicited by mother and stranger faces at 9 months. At 18 months, only postnatal ID and iron-sufficient groups showed condition differences in Nc amplitude. However, the 2 groups were different in the involved brain regions. For LSW, only the 2 ID groups showed condition differences in amplitude at 9 months. At 18 months, condition differences were not observed in any group.Conclusions: This study indicates that the timing of ID in early life (fetal-neonatal vs. postnatal) modulates the impact of ID on recognition memory. Such impact also varies depending on the age of infants at testing (9 vs. 18 months).

Genetic determinants of metabolic biomarkers and their associations with cardiometabolic traits in Hispanic/Latino adolescents.

BACKGROUND: Metabolic regulation plays a significant role in energy homeostasis, and adolescence is a crucial life stage for the development of cardiometabolic disease (CMD). This study aims to investigate the genetic determinants of metabolic biomarkers-adiponectin, leptin, ghrelin, and orexin-and their associations with CMD risk factors. METHODS: We characterized the genetic determinants of the biomarkers among Hispanic/Latino adolescents of the Santiago Longitudinal Study (SLS) and identified the cumulative effects of genetic variants on adiponectin and leptin using biomarker polygenic risk scores (PRS). We further investigated the direct and indirect effect of the biomarker PRS on downstream body fat percent (BF%) and glycemic traits using structural equation modeling. RESULTS: We identified putatively novel genetic variants associated with the metabolic biomarkers. A substantial amount of biomarker variance was explained by SLS-specific PRS, and the prediction was improved by including the putatively novel loci. Fasting blood insulin and insulin resistance were associated with PRS for adiponectin, leptin, and ghrelin, and BF% was associated with PRS for adiponectin and leptin. We found evidence of substantial mediation of these associations by the biomarker levels. CONCLUSIONS: The genetic underpinnings of metabolic biomarkers can affect the early development of CMD, partly mediated by the biomarkers. IMPACT: This study characterized the genetic underpinnings of four metabolic hormones and investigated their potential influence on adiposity and insulin biology among Hispanic/Latino adolescents. Fasting blood insulin and insulin resistance were associated with polygenic risk score (PRS) for adiponectin, leptin, and ghrelin, with evidence of some degree of mediation by the biomarker levels. Body fat percent (BF%) was also associated with PRS for adiponectin and leptin. This provides important insight on biological mechanisms underlying early metabolic dysfunction and reveals candidates for prevention efforts. Our findings also highlight the importance of ancestrally diverse populations to facilitate valid studies of the genetic architecture of metabolic biomarker levels.

Associations between adverse home environments and appetite hormones, adipokines, and adiposity among Chilean adolescents.

Little is known regarding the relationship between adverse home environments and hormones important in regulation of appetite and their impact on obesity in children and adolescents. In this study, we examined the impact of socioeconomic economic status, family stress and maternal depressive symptoms on appetite hormones, adipokines and adiposity. To determine whether adverse home environments in childhood and adolescence relate to adiposity in adolescence and disruptions in appetite hormones and adipokines, specifically lower levels of adiponectin and ghrelin and elevated levels of leptin and orexin. Adversity in the home (maternal depressive symptoms, family stress, socioeconomic disadvantage) was measured in the households of 593 Chilean youth at age 10 years (52.3% male) and in 606 youth at 16 years. At 16 years, participants provided fasting blood samples for assessment of adipokines and appetite hormones. Waist-to-height ratio was used to assess central adiposity. Correlational analyses examined associations between continuous levels of adversity in childhood and adolescence and appetite hormones and adiposity in adolescence. Multinomial logistic regressions compared hormone levels by tertiles of adversity. Participants were 52% male, with average age at the 16 years hormone assessment being 16.8 (n = 606, SD = 0.26). Those with highest maternal depression at age 10 had lower adiponectin OR = 0.95 [95% CI: 0.91, 0.99], p = 0.005) and ghrelin levels (OR = 0.98 [95% CI: 0.98, 1.00), p = 0.022) than those in the lowest maternal depression group at age 16. Those with the highest family stress at 16 years had lower adiponectin levels (OR = 0.93 [95% CI: 0.89, 0.98), p = 0.004) and higher central adiposity (OR = 1.05 [1.01, 1.08], p = 0.009) than the lowest family stress group. There were no significant associations found between socioeconomic status at either 10 or 16 years and appetite hormones. Results add new evidence regarding the relationship between household adversity to appetite hormones and adipokines, with the most consistent results for adiponectin. Current findings suggest that the relationship between home environment and adipokines and appetite hormones may play a role in altered adiposity in children and adolescents.

Resolving early obesity leads to a cardiometabolic profile within normal ranges at 23 years old in a two-decade prospective follow-up study.

Obesity is the most important predisposing factor for cardiovascular disease and type-2 diabetes. We explored the relationship between the age at onset of obesity and selected cardiometabolic parameters in young adults. Longitudinal study of n = 1,039 participants (48% males) in their early twenties. BMI was measured at birth, 1-5-10-12-14-16-23 years. BMI trajectories were interpolated. Five groups were identified: never obese (never-OB); early childhood obesity transitioning to non-obesity before adolescence (former-OB); obesity starting in preadolescence transitioning to non-obesity as adolescents (transient-OB); obesity from adolescence into early adulthood (recent-onset-OB); participants who were obese in early childhood and remained obese into adulthood (persistent-OB). Waist circumference (WC), blood pressure, lipids, glucose, and insulin were measured at 23 years. HOMA-IR and the Metabolic Syndrome Risk Z-Score were estimated. In the sample, 47% were obese during at least one time-point. Mean obesity duration was 20.7 years, 8.5 years, 6.2 years, and 3.3 years in persistent-OBs, recent-onset-OBs, former-OBs, and transient-OBs, respectively. The cardiometabolic profile was more adverse in recent-onset-OBs (12%) and persistent-OBs (15%) compared to never-OB participants (53%). Although former-OBs (15%) and transient-OBs (4%) had higher WC values than never-OBs, no differences were seen in other biomarkers. Both persistent and recent-onset obesity led to a cardiometabolic profile of risk in early adulthood, as suggested by values of WC, HOMA-IR, and hs-CRP above normal limits and HDL-chol values below normal limits. Participants who had obesity in early childhood or preadolescence but transitioned to a non-obesity status had a cardiometabolic profile similar to participants who were never obese and within normal limits. Obesity leads to risky values in a number of cardiometabolic biomarkers in young adulthood independent of age at obesity onset. Likewise, overcoming obesity during the pediatric age leads to a cardiometabolic profile within normal ranges at 23 years of age.

Iron deficiency in infancy and neurocognitive and educational outcomes in young adulthood.

This study examines the extent to which iron deficiency in infancy contributes to adverse neurocognitive and educational outcomes in young adulthood directly and indirectly, through its influence on verbal cognition and attention problems in childhood. Young adults (N = 1,000, M age = 21.3 years, 52% female; of Spanish or indigenous descent) from working-class families in Santiago, Chile, completed instruments assessing memory, processing speed, mental flexibility, and educational attainment. Iron status was assessed at ages 6, 12, and 18 months, and verbal intelligence, inattention, and sluggish cognitive tempo (SCT) symptoms were assessed at age 10. Results indicated that young adults who had iron-deficiency in infancy had poor executive control at age 21. Severity of iron deficiency during infancy was associated with lower verbal IQ and more frequent inattention and SCT symptoms in childhood, and with lower educational attainment in young adulthood through its effect on inattention. No additional indirect effects were found. Interventions directed toward improving cognitive and attention deficits linked to early-life iron deficiency appear warranted and could alter the course to adult functioning. Further research on the impact of such interventions would be helpful. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Maternal Overweight and Obesity during Pregnancy Are Associated with Neonatal, but Not Maternal, Hepcidin Concentrations.

BACKGROUND: Overweight or obesity among pregnant women may compromise maternal and neonatal iron status by upregulating hepcidin. OBJECTIVES: This study determined the association of 1) maternal and neonatal iron status with maternal and neonatal hepcidin concentrations, and 2) maternal prepregnancy weight status with maternal and neonatal hepcidin concentrations. METHODS: We examined hematologic data from 405 pregnant women and their infants from the placebo treatment group of a pregnancy iron supplementation trial in rural China. We measured hepcidin, serum ferritin (SF), soluble transferrin receptor (sTfR), and high-sensitivity C-reactive protein in maternal blood samples at mid-pregnancy and in cord blood at delivery. We used regression analysis to examine the association of maternal prepregnancy overweight or obese status with maternal hepcidin concentration in mid-pregnancy and cord hepcidin concentrations. We also used path analysis to examine mediation of the association of maternal prepregnancy overweight or obese status with maternal iron status by maternal hepcidin, as well as with neonatal hepcidin by neonatal iron status. RESULTS: Maternal iron status was positively correlated with maternal hepcidin at mid-pregnancy (SF: r = 0.63, P < 0.001; sTfR: r = -0.37, P < 0.001). Neonatal iron status was also positively correlated with cord hepcidin (SF: r = 0.61, P < 0.001; sTfR: r = -0.39, P < 0.001). In multiple linear regression models, maternal prepregnancy overweight or obese status was not associated with maternal hepcidin at mid-pregnancy but was associated with lower cord hepcidin (coefficient = -0.21, P = 0.004). Using path analysis, we observed a significant indirect effect of maternal prepregnancy overweight or obese status on cord hepcidin, mediated by neonatal iron status. CONCLUSIONS: In both pregnant women and neonates, hepcidin was responsive to iron status. Maternal prepregnancy overweight status, with or without including obese women, was associated with lower cord blood hepcidin, likely driven by lower iron status among the neonates of these mothers.