Epigenome-wide meta-analysis of BMI in nine cohorts: Examining the utility of epigenetically predicted BMI.

This study sought to examine the association between DNA methylation and body mass index (BMI) and the potential of BMI-associated cytosine-phosphate-guanine (CpG) sites to provide information about metabolic health. We pooled summary statistics from six trans-ethnic epigenome-wide association studies (EWASs) of BMI representing nine cohorts (n = 17,034), replicated these findings in the Women's Health Initiative (WHI, n = 4,822), and developed an epigenetic prediction score of BMI. In the pooled EWASs, 1,265 CpG sites were associated with BMI (p < 1E-7) and 1,238 replicated in the WHI (FDR < 0.05). We performed several stratified analyses to examine whether these associations differed between individuals of European and African descent, as defined by self-reported race/ethnicity. We found that five CpG sites had a significant interaction with BMI by race/ethnicity. To examine the utility of the significant CpG sites in predicting BMI, we used elastic net regression to predict log-normalized BMI in the WHI (80% training/20% testing). This model found that 397 sites could explain 32% of the variance in BMI in the WHI test set. Individuals whose methylome-predicted BMI overestimated their BMI (high epigenetic BMI) had significantly higher glucose and triglycerides and lower HDL cholesterol and LDL cholesterol compared to accurately predicted BMI. Individuals whose methylome-predicted BMI underestimated their BMI (low epigenetic BMI) had significantly higher HDL cholesterol and lower glucose and triglycerides. This study confirmed 553 and identified 685 CpG sites associated with BMI. Participants with high epigenetic BMI had poorer metabolic health, suggesting that the overestimation may be driven in part by cardiometabolic derangements characteristic of metabolic syndrome.

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

Maternal and Offspring Fatty Acid Desaturase Variants, Prenatal DHA Supplementation, and Dietary n-6:n-3 Fatty Acid Ratio in Relation to Cardiometabolic Health in Mexican Children.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in fatty acid desaturase (FADS) genes may modify dietary fatty acid requirements and influence cardiometabolic health (CMH). OBJECTIVES: We evaluated the role of selected variants in maternal and offspring FADS genes on offspring CMH at the age of 11 y and assessed interactions of genotype with diet quality and prenatal docosahexaenoic acid (DHA) supplementation. METHODS: We used data from offspring (n = 203) born to females who participated in a randomized controlled trial of DHA supplementation (400 mg/d) from midgestation to delivery. We generated a metabolic syndrome (MetS) score from body mass index, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and fasting glucose and identified 6 distinct haplotypes from 5 offspring FADS SNPs. Dietary n-6 (ω-6):n-3 fatty acid ratios were derived from 24-h recall data (n = 141). We used generalized linear models to test associations of offspring diet and FADS haplotypes with MetS score and interactions of maternal and offspring FADS SNP rs174602 with prenatal treatment group and dietary n-6:n-3 ratio on MetS score. RESULTS: Associations between FADS haplotypes and MetS score were null. Offspring SNP rs174602 did not modify the association of prenatal DHA supplementation with MetS score. Among children with TT or TC genotype for SNP rs174602 (n = 88), those in the highest n-6:n-3 ratio tertile (>8.61) had higher MetS score relative to the lowest tertile [<6.67) (Δ= 0.36; 95% confidence interval (CI): 0.03, 0.69]. Among children with CC genotype (n = 53), those in the highest n-6:n-3 ratio tertile had a lower MetS score relative to the lowest tertile (Δ= -0.23; 95% CI: -0.61, 0.16). CONCLUSIONS: There was evidence of an interaction of offspring FADS SNP rs174602 with current dietary polyunsaturated fatty acid intake, but not with prenatal DHA supplementation, on MetS score. Further studies may help to determine the utility of targeted supplementation strategies and dietary recommendations based on genetic profile.

Effects of early-life poverty on health and human capital in children and adolescents: analyses of national surveys and birth cohort studies in LMICs.

The survival and nutrition of children and, to a lesser extent, adolescents have improved substantially in the past two decades. Improvements have been linked to the delivery of effective biomedical, behavioural, and environmental interventions; however, large disparities exist between and within countries. Using data from 95 national surveys in low-income and middle-income countries (LMICs), we analyse how strongly the health, nutrition, and cognitive development of children and adolescents are related to early-life poverty. Additionally, using data from six large, long-running birth cohorts in LMICs, we show how early-life poverty can have a lasting effect on health and human capital throughout the life course. We emphasise the importance of implementing multisectoral anti-poverty policies and programmes to complement specific health and nutrition interventions delivered at an individual level, particularly at a time when COVID-19 continues to disrupt economic, health, and educational gains achieved in the recent past.

Health and development from preconception to 20 years of age and human capital.

Optimal health and development from preconception to adulthood are crucial for human flourishing and the formation of human capital. The Nurturing Care Framework, as adapted to age 20 years, conceptualises the major influences during periods of development from preconception, through pregnancy, childhood, and adolescence that affect human capital. In addition to mortality in children younger than 5 years, stillbirths and deaths in 5-19-year-olds are important to consider. The global rate of mortality in individuals younger than 20 years has declined substantially since 2000, yet in 2019 an estimated 8·6 million deaths occurred between 28 weeks of gestation and 20 years of age, with more than half of deaths, including stillbirths, occurring before 28 days of age. The 1000 days from conception to 2 years of age are especially influential for human capital. The prevalence of low birthweight is high in sub-Saharan Africa and even higher in south Asia. Growth faltering, especially from birth to 2 years, occurs in most world regions, whereas overweight increases in many regions from the preprimary school period through adolescence. Analyses of cohort data show that growth trajectories in early years of life are strong determinants of nutritional outcomes in adulthood. The accrual of knowledge and skills is affected by health, nutrition, and home resources in early childhood and by educational opportunities in older children and adolescents. Linear growth in the first 2 years of life better predicts intelligence quotients in adults than increases in height in older children and adolescents. Learning-adjusted years of schooling range from about 4 years in sub-Saharan Africa to about 11 years in high-income countries. Human capital depends on children and adolescents surviving, thriving, and learning until adulthood.

Growth in Infancy and Childhood and Age at Menarche in Five Low- or Middle-Income Countries: Consortium of Health Orientated Research in Transitional Societies (COHORTS).

BACKGROUND: Earlier age at menarche is associated with behavioral and noncommunicable disease risks. The influence of birth weight (BW) (intrauterine) and postnatal growth on age at menarche is not well studied in low- and middle-income countries (LMICs). OBJECTIVE: Therefore, we investigated these associations in 5 LMIC birth cohorts. METHODS: We analyzed data from Brazil, Guatemala, India, the Philippines, and South Africa (n = 3983). We derived stunting (< -2 SD scores) at 24 mo using the WHO child growth standards. We generated interaction terms with categorized BW and conditional weight (lighter < 0 or heavier ≥ 0), and height (shorter < 0 or taller ≥ 0) z-scores. We categorized early-, modal-, and late-onset menarche and used multilevel ordinal regression. We used multilevel linear regression on continuous age at menarche. RESULTS: Mean age at menarche was 12.8 y (95% CI: 12.7 12.9). BW was not associated with age at menarche. Conditional height at 24 mo and mid-childhood (OR: 1.35; 95% CI: 1.27, 1.44 and 1.32; 1.25, 1.41, respectively) and conditional weight at 24 mo and mid-childhood (OR: 1.15; 1.08, 1.22 and 1.18; 1.11, 1.25, respectively) were associated with increased likelihood of early-onset menarche. Being heavier at birth and taller at 24 mo was associated with a 4-mo (95% CI: 0.8, 7.6) earlier age at menarche than being lighter at birth and shorter at 24 mo. Being heavier at birth but lighter in mid-childhood was associated with a 3-mo (95% CI: 0.8, 4.8) later age at menarche than being lighter at birth and mid-childhood. Age at menarche was 7 mo later in stunted than nonstunted girls. CONCLUSION: Age at menarche is inversely related to relative weight gain but also to rapid linear growth among those born shorter but remained stunted, and those born taller and grew excessively. These findings do not deter the global health goal to reduce growth faltering but emphasize the potential adverse effects of an obesogenic environment on adolescent development.

Early life predictors of body composition trajectories from adolescence to mid-adulthood.

OBJECTIVES: Guatemala has experienced rapid increases in adult obesity. We characterized body composition trajectories from adolescence to mid-adulthood and determined the predictive role of parental characteristics, early life factors, and a nutrition intervention. METHODS: One thousand three hundred and sixty-four individuals who participated as children in a nutrition trial (1969-1977) were followed prospectively. Body composition characterized as body mass index (BMI), fat mass index (FMI), and fat-free mass indices (FFMI), was available at four ages between 10 and 55 years. We applied latent class growth analysis to derive sex-specific body composition trajectories. We estimated associations between parental (age, height, schooling) and self-characteristics (birth order, socioeconomic status, schooling, and exposure to a nutrition supplement) with body composition trajectories. RESULTS: In women, we identified two latent classes of FMI (low: 79.6%; high: 20.4%) and BMI (low: 73.0%; high: 27.0%), and three of FFMI (low: 20.2%; middle: 55.9%; high: 23.9%). In men, we identified two latent classes of FMI (low: 79.6%; high: 20.4%) and FFMI (low: 62.4%; high: 37.6%), and three of BMI (low: 43.1%; middle: 46.9%; high: 10.0%). Among women, self's schooling attainment inversely predicted FMI (OR [being in a high latent class]: 0.91, 95% CI: 0.85, 0.97), and maternal schooling positively predicted FFMI (OR: 1.16, 95% CI: 0.97, 1.39). Among men, maternal schooling, paternal age, and self's schooling attainment positively predicted FMI. Maternal schooling positively predicted FFMI, whereas maternal age and paternal schooling were inverse predictors. The nutrition intervention did not predict body composition class membership. CONCLUSIONS: Parents' age and schooling, and self's schooling attainment are small but significant predictors of adult body composition trajectories.

Participation in the Georgia Food for Health programme and CVD risk factors: a longitudinal observational study.

OBJECTIVE: To assess the relationship between programme attendance in a produce prescription (PRx) programme and changes in cardiovascular risk factors. DESIGN: The Georgia Food for Health (GF4H) programme provided six monthly nutrition education sessions, six weekly cooking classes and weekly produce vouchers. Participants became programme graduates attending at least 4 of the 6 of both the weekly cooking classes and monthly education sessions. We used a longitudinal, single-arm approach to estimate the association between the number of monthly programme visits attended and changes in health indicators. SETTING: GF4H was implemented in partnership with a large safety-net health system in Atlanta, GA. PARTICIPANTS: Three hundred thirty-one participants living with or at-risk of chronic disease and food insecurity were recruited from primary care clinics. Over three years, 282 participants graduated from the programme. RESULTS: After adjusting for programme site, year, participant sex, age, race and ethnicity, Supplemental Nutrition Assistance Program participation and household size, we estimated that each additional programme visit attended beyond four visits was associated with a 0·06 kg/m2 reduction in BMI (95 % CI -0·12, -0·01; P = 0·02), a 0·37 inch reduction in waist circumference (95 % CI -0·48, -0·27; P < 0·001), a 1·01 mmHg reduction in systolic blood pressure (95 % CI -1·45, -0·57; P < 0·001) and a 0·43 mmHg reduction in diastolic blood pressure (95 % CI -0·69, -0·17; P = 0·001). CONCLUSIONS: Each additional cooking and nutrition education visit attended beyond the graduation threshold was associated with modest but significant improvements in CVD risk factors, suggesting that increased engagement in educational components of a PRx programme improves health outcomes.

Protein-Energy Supplementation in Early-Life Decreases the Odds of Mental Distress in Later Adulthood in Guatemala.

BACKGROUND: The prevalence of mental health concerns is growing worldwide, along with lack of access to and receipt of needed treatment. Current gaps in treatment provision have led to exploring alternative methods of prevention, with research linking nutrition and mental health, of particular relevance in low- and middle-income countries, with a high prevalence of undernutrition. OBJECTIVES: To examine whether exposure to a protein-energy nutritional supplement during the first 1000 d of life decreased odds of mental distress in adulthood among men and women in Guatemala compared with receiving a low energy-no protein supplement or supplementation outside the 1000-d window. METHODS: Data from participants (n = 1249) in a longitudinal cohort protein-energy supplementation trial (early-life, supplementation data from 1969 to 1977, ages 0-7 y; life course, outcome data from 2017-2018 follow-up, ages 40-57 y) were analyzed for associations between nutrition in the first 1000 d and mental distress in adulthood (WHO Self-Reporting Questionnaire 20 [SRQ-20]), controlling for early-life variables and current life stress; life course variables (e.g. education) were examined as potential mediators of this relation. Generalized linear mixed models and zero-inflated Poisson generalized linear mixed models were utilized. RESULTS: Both partial and full supplementation with Atole during the first 1000 d were associated with 63% (95% CI: 0.16, 0.87) and 56% (95% CI: 0.19, 1.03) lower odds, respectively, of experiencing mental distress in adulthood. Results did not differ by sex. These inverse relations remained relatively unchanged (partial OR = 0.34 [95% CI: 0.14, 0.83]; full OR = 0.38 [95% CI: 0.16, 0.92]) after controlling for early-life and life course variables, including life stress. CONCLUSIONS: Protein-energy supplementation during the first 1000 d of life in Guatemala, where undernutrition is prevalent, may reduce the prevalence of later mental distress in adulthood. This effect appears to occur directly, rather than indirectly, through pathways of life course variables such as education, wealth, and marital status.

Protein-Energy Supplementation in Early-Life Decreases the Odds of Mental Distress in Later Adulthood in Guatemala.

BACKGROUND: The prevalence of mental health concerns is growing worldwide, along with lack of access to and receipt of needed treatment. Current gaps in treatment provision have led to exploring alternative methods of prevention, with research linking nutrition and mental health, of particular relevance in low- and middle-income countries, with a high prevalence of undernutrition. OBJECTIVES: To examine whether exposure to a protein-energy nutritional supplement during the first 1000 d of life decreased odds of mental distress in adulthood among men and women in Guatemala compared with receiving a low energy-no protein supplement or supplementation outside the 1000-d window. METHODS: Data from participants (n = 1249) in a longitudinal cohort protein-energy supplementation trial (early-life, supplementation data from 1969 to 1977, ages 0-7 y; life course, outcome data from 2017-2018 follow-up, ages 40-57 y) were analyzed for associations between nutrition in the first 1000 d and mental distress in adulthood (WHO Self-Reporting Questionnaire 20 [SRQ-20]), controlling for early-life variables and current life stress; life course variables (e.g. education) were examined as potential mediators of this relation. Generalized linear mixed models and zero-inflated Poisson generalized linear mixed models were utilized. RESULTS: Both partial and full supplementation with Atole during the first 1000 d were associated with 63% (95% CI: 0.16, 0.87) and 56% (95% CI: 0.19, 1.03) lower odds, respectively, of experiencing mental distress in adulthood. Results did not differ by sex. These inverse relations remained relatively unchanged (partial OR = 0.34 [95% CI: 0.14, 0.83]; full OR = 0.38 [95% CI: 0.16, 0.92]) after controlling for early-life and life course variables, including life stress. CONCLUSIONS: Protein-energy supplementation during the first 1000 d of life in Guatemala, where undernutrition is prevalent, may reduce the prevalence of later mental distress in adulthood. This effect appears to occur directly, rather than indirectly, through pathways of life course variables such as education, wealth, and marital status.

Conditional wealth to estimate association of wealth mobility with health and human capital in low- and middle-income country cohorts.

Temporally harmonized asset indices allow the study of changes in relative wealth (mean, variance, social mobility) over time and its association with adult health and human capital in cohort studies. Conditional measures are the unexplained residuals of an indicator regressed on its past values. Using such measures, previously used to study the relative importance of key life stages for anthropometric growth, we can identify specific life stages during which changes in relative wealth are important for adult health in longitudinal studies. We discuss the assumptions, strengths and limitations of this methodology as applied to relative wealth. We provide an illustrative example using a publicly-available longitudinal dataset and show how relative wealth changes at different life stages are differentially associated with body mass index in adulthood.

Age at childbirth and change in BMI across the life-course: evidence from the INCAP Longitudinal Study.

BACKGROUND: Parity has been associated with both short- and long-term weight gain in women. However, it is not clear if timing of parity across the reproductive age has different associations with BMI. METHODS: To prospectively assess the association between age at childbirth and maternal change in BMI, we analyzed data from the ongoing INCAP Longitudinal Study, which started in 1969 in four villages in Guatemala. Cohort women (n=778) provided information on reproductive history and anthropometric measures were measured in 1988-89 (adolescence, 15 to 25y), 2002-04 (early adulthood, 26 to 36y) and 2015-17 (mid adulthood, 37 to 55y). We evaluated the associations of number of live births in the period preceding each study wave (1969-77 to 1988-89, 1988-89 to 2002-04 and 2002-04 to 2015-17) with BMI change in the same period using multivariable linear regression models. RESULTS: Number of live births between 1988 and 89 and 2002-04 was positively associated with increased BMI, while there was not an association between number of live births and BMI in the other intervals. Women who had one, two, or three or more children between 1988 and 89 and 2002-04 had 0.90 (kg/m2, 95% CI: -0.55, 2.35), 2.39 (kg/m2, 95% CI: 1.09, 3.70) and 2.54 (kg/m2, 95% CI: 1.26, 3.82) higher BMI, respectively, than women who did not give birth in the same period. CONCLUSIONS: Our findings suggest that women who had three or more children during early adulthood gained more weight compared to women who had no children in the same period. In contrast, women who had children earlier or later in their reproductive lives did not gain additional weight compared to those who did not have children during that period. Childbirth may have different associations with BMI based on the mother's age.

Measuring Postprandial Metabolic Flexibility to Assess Metabolic Health and Disease.

Metabolic abnormalities substantially increase the risk of noncommunicable diseases, which are among the leading causes of mortality globally. Mitigating and preventing these adverse consequences remains challenging due to a limited understanding of metabolic health. Metabolic flexibility, a key tenet of metabolic health, encompasses the responsiveness of interrelated pathways to maintain energy homeostasis throughout daily physiologic challenges, such as the response to meal challenges. One critical underlying research gap concerns the measurement of postprandial metabolic flexibility, which remains incompletely understood. We concisely review the methodology for assessment of postprandial metabolic flexibility in recent human studies. We identify 3 commonalities of study design, specifically the nature of the challenge, nature of the response measured, and approach to data analysis. Primary interventions were acute short-term nutrition challenges, including single- and multiple-macronutrient tolerance tests. Postmeal challenge responses were measured via laboratory assays and instrumentation, based on a diverse set of metabolic flexibility indicators [e.g., energy expenditure (whole-body indirect calorimetry), glucose and insulin kinetics, metabolomics, transcriptomics]. Common standard approaches have been diabetes-centric with single-macronutrient challenges (oral-glucose-tolerance test) to characterize the postprandial response based on glucose and insulin metabolism; or broad measurements of energy expenditure with calculated macronutrient oxidation via indirect calorimetry. Recent methodological advances have included the use of multiple-macronutrient meal challenges that are more representative of physiologic meals consumed by free-living humans, combinatorial approaches for assays and instruments, evaluation of other metabolic flexibility indicators via precision health, systems biology, and temporal perspectives. Omics studies have identified potential novel indicators of metabolic flexibility, which provide greater granularity to prior evidence from canonical approaches. In summary, recent findings indicate the potential for an expanded understanding of postprandial metabolic flexibility, based on nonclassical measurements and methodology, which could represent novel dynamic indicators of metabolic diseases.

Early-Life Nutrition and Subsequent International Migration: A Prospective Study in Rural Guatemala.

BACKGROUND: It is generally accepted that migrants are favorably self-selected for labor market skills such as higher schooling and greater cognitive capacity, which are highly correlated with early-life nutrition. However, the influence of early-life nutrition on later-life migration is understudied. OBJECTIVE: The objective of this study was to examine prospectively the association between height-for-age z scores (HAZ) at 24 mo and subsequent international migration in a cohort of 2392 participants born between 1962 and 1977 in 4 rural villages in eastern Guatemala. METHODS: Information on nutritional status and covariates was collected between 1969 and 1977 and migration status was determined as of 2017 (at ages 40-57 y). We used proportional hazards and logistic regression models to assess whether HAZ was associated with international migration, adjusting for early-life and adult characteristics. RESULTS: Between 1978 and 2017 there were 297 international migrants (12.4% of the original cohort) during 99,212 person-y of follow-up. In pooled models that were adjusted for early-life characteristics, a 1-SD increase in HAZ was associated with a 19% increase in the risk of international migration (HR: 1.19; 95% CI: 1.02, 1.38). Further adjustment for village characteristics did not alter the estimate substantively (HR: 1.18; 95% CI: 1.02, 1.37), while additional adjustment for schooling attainment attenuated the estimate somewhat (HR: 1.14; 95% CI: 0.98, 1.33). In all models, effect sizes were stronger for men than for women. CONCLUSIONS: Our results indicate that early-life nutrition is positively associated with subsequent international migration.

Metabolomic Profiling Demonstrates Postprandial Changes in Fatty Acids and Glycerophospholipids Are Associated with Fasting Inflammation in Guatemalan Adults.

BACKGROUND: Metabolic flexibility is the responsiveness to heterogeneous physiological conditions, such as food ingestion. A key unresolved question is how inflammation affects metabolic flexibility. OBJECTIVES: Our study objective was to compare metabolic flexibility, specifically the metabolomic response to a standardized meal, by fasting inflammation status. METHODS: Participants in Guatemala (n = 302, median age 44 y, 43.7% men) received a standardized, mixed-macronutrient liquid meal. Plasma samples (fasting, 2 h postmeal) were assayed by dual-column LC [reverse phase (C18) and hydrophilic interaction LC (HILIC)] with ultra-high-resolution MS, for concentrations of 6 inflammation biomarkers: high-sensitivity C-reactive protein (hsCRP), leptin, resistin, IL-10, adiponectin, and soluble TNF receptor II (TNFsR). We summed the individual inflammation biomarker z-scores, after reverse-coding of anti-inflammation biomarkers. We identified features with peak areas that differed between fasting and postmeal (false discovery rate-adjusted q <0.05) and compared median log2 postprandial/fasting peak area ratios by inflammation indicators. RESULTS: We found 1397 C18 and 974 HILIC features with significant postprandial/fasting feature ratios (q <0.05). Overall inflammation z-score was directly associated with the postprandial/fasting feature ratios of arachidic acid, and inversely associated with the feature ratio of lysophosphatidic acid (LPA), adjusting for age and sex (all P < 0.05). The postprandial/fasting ratio of arachidic acid was negatively correlated with resistin, IL-10, adiponectin, and TNFsR concentrations (all P < 0.05). Feature ratios of several fatty acids-myristic acid [m/z 227.2018, retention time (RT) 229], heptadecanoic acid (m/z 269.2491, RT 276), linoleic acid (m/z 280.2358, RT 236)-were negatively correlated with fasting plasma concentrations of leptin (nanograms per milliliter) and adiponectin (micrograms per milliliter), respectively (all P < 0.05). The postprandial/fasting ratio of LPA was positively correlated with IL-10 and adiponectin (both P < 0.05); and the ratio of phosphatidylinositol was positively correlated with hsCRP (P < 0.05). CONCLUSIONS: Postprandial responses of fatty acids and glycerophospholipids are associated with fasting inflammation status in adults in Guatemala.

Infant Metabolome in Relation to Prenatal DHA Supplementation and Maternal Single-Nucleotide Polymorphism rs174602: Secondary Analysis of a Randomized Controlled Trial in Mexico.

BACKGROUND: Although DHA (22:6n-3) is critical for fetal development, results from randomized controlled trials (RCTs) of prenatal DHA supplementation report inconsistent effects on offspring health. Variants in fatty acid desaturase (FADS) genes that regulate the conversion of n-3 and n-6 essential fatty acids into their biologically active derivatives may explain this heterogeneity. OBJECTIVES: We investigated the effect of prenatal DHA supplementation on the offspring metabolome at age 3 mo and explored differences by maternal FADS single-nucleotide polymorphism (SNP) rs174602. METHODS: Data were obtained from a double-blind RCT in Mexico [POSGRAD (Prenatal Omega-3 Fatty Acid Supplementation and Child Growth and Development)] in which women (18-35 y old) received DHA (400 mg/d) or placebo from mid-gestation until delivery. Using high-resolution MS with LC, untargeted metabolomics was performed on 112 offspring plasma samples. Discriminatory metabolic features were selected via linear regression (P < 0.05) with false discovery rate (FDR) correction (q = 0.2). Interaction by SNP rs174602 was assessed using 2-factor ANOVA. Stratified analyses were performed, where the study population was grouped into carriers (TT, TC; n = 70) and noncarriers (CC; n = 42) of the minor allele. Pathway enrichment analysis was performed with Mummichog (P < 0.05). RESULTS: After FDR correction, there were no differences in metabolic features between infants whose mothers received prenatal DHA (n = 58) and those whose mothers received placebo (n = 54). However, we identified 343 differentially expressed features in the interaction analysis after FDR correction. DHA supplementation positively enriched amino acid and aminosugars metabolism pathways and decreased fatty acid metabolism pathways among offspring of minor allele carriers and decreased metabolites within the tricarboxylic acid cycle and galactose metabolism pathways among offspring of noncarriers. CONCLUSIONS: Our findings demonstrate differences in infant metabolism in response to prenatal DHA supplementation by maternal SNP rs174602 and further support the need to incorporate genetic analysis of FADS polymorphisms into DHA supplementation trials.This trial was registered at clinicaltrials.gov as NCT00646360.

Linear Growth Trajectories in Early Childhood and Adult Cognitive and Socioemotional Functioning in a Guatemalan Cohort.

BACKGROUND: Growth faltering in early childhood is associated with poor human capital attainment, but associations of linear growth in childhood with executive and socioemotional functioning in adulthood are understudied. OBJECTIVES: In a Guatemalan cohort, we identified distinct trajectories of linear growth in early childhood, assessed their predictors, and examined associations between growth trajectories and neurodevelopmental outcomes in adulthood. We also assessed the mediating role of schooling on the association of growth trajectories with adult cognitive outcomes. METHODS: In 2017-2019, we prospectively followed 1499 Guatemalan adults who participated in a food supplementation trial in early childhood (1969-1977). We derived height-for-age sex-specific growth trajectories from birth to 84 mo using latent class growth analysis. RESULTS: We identified 3 growth trajectories (low, intermediate, high) with parallel slopes and intercepts already differentiated at birth in both sexes. Children of taller mothers were more likely to belong to the high and intermediate trajectories [relative risk ratio (RRR): 1.21; 95% CI: 1.15, 1.26, and RRR: 1.11; 95% CI: 1.07, 1.15, per 1-cm increase in height, respectively] compared with the low trajectory. Children in the wealthiest compared with the poorest socioeconomic tertile were more likely to belong to the high trajectory compared with the low trajectory (RRR: 2.24; 95% CI: 1.29, 3.88). In males, membership in the high compared with low trajectory was positively associated with nonverbal fluid intelligence, working memory, inhibitory control, and cognitive flexibility at ages 40-57 y. Sex-adjusted results showed that membership in the high compared with low trajectory was positively associated with meaning and purpose scores at ages 40-57 y. Associations of intermediate compared with low growth trajectories with study outcomes were also positive but of lesser magnitude. Schooling partially mediated the associations between high and intermediate growth trajectories and measures of cognitive ability in adulthood. CONCLUSIONS: Modifiable and nonmodifiable risk factors predicted growth throughout childhood. Membership in the high and intermediate growth trajectories was positively associated with adult cognitive and socioemotional functioning.

Patterns of Growth in Childhood in Relation to Adult Schooling Attainment and Intelligence Quotient in 6 Birth Cohorts in Low- and Middle-Income Countries: Evidence from the Consortium of Health-Oriented Research in Transitioning Societies (COHORTS).

BACKGROUND: Growth faltering has been associated with poor intellectual performance. The relative strengths of associations between growth in early and in later childhood remain underexplored. OBJECTIVES: We examined the association between growth in childhood and adult human capital in 5 low- and middle-income countries (LMICs). METHODS: We analyzed data from 9503 participants in 6 prospective birth cohorts from 5 LMICs (Brazil, Guatemala, India, the Philippines, and South Africa). We used linear and quasi-Poisson regression models to assess the associations between measures of height and relative weight at 4 age intervals [birth, age ∼2 y, midchildhood (MC), adulthood] and 2 dimensions of adult human capital [schooling attainment and Intelligence Quotient (IQ)]. RESULTS: Meta-analysis of site- and sex-specific estimates showed statistically significant associations between size at birth and height at ∼2 y and the 2 outcomes (P < 0.001). Weight and length at birth and linear growth from birth to ∼2 y of age (1 z-score difference) were positively associated with schooling attainment (ß: 0.13; 95% CI: 0.08, 0.19, ß: 0.17; 95% CI: 0.07, 0.32, and ß: 0.25, 95% CI: 0.10, 0.40, respectively) and adult IQ (ß: 0.74, 95% CI: 0.35, 1.14, ß: 0.73, 95% CI: 0.35, 1.10, and ß: 1.52, 95% CI: 0.96, 2.08, respectively). Linear growth from age 2 y to MC and from MC to adulthood was not associated with higher school attainment or IQ. Change in relative weight in early childhood, MC, and adulthood was not associated with either outcome. CONCLUSIONS: Linear growth in the first 1000 d is a predictor of schooling attainment and IQ in adulthood in LMICs. Linear growth in later periods was not associated with either of these outcomes. Changes in relative weight across the life course were not associated with schooling and IQ in adulthood.

Development of a temporally harmonized asset index: evidence from across 50 years of follow up of a birth cohort in Guatemala.

BACKGROUND: Asset-based indices are widely-used proxy measures of wealth in low and middle-income countries (LMIC). The stability of these indices within households over time is not known. METHODS: We develop a harmonized household asset index using Principal Component Analysis for the participants (n = 2392) of INCAP Longitudinal Study, Guatemala using data from six waves of follow-up over the period of 1965-2018. We estimate its cross-sectional association with parental schooling (in 1967-75) and attained schooling (in 2015-18) of cohort members. We study how patterns of cross-sectional loadings change over time and between urban-rural settings. We assess its robustness to omission of assets or study waves and alternate specifications of factor extraction procedure (exploratory factor analysis, multiple correspondence analysis). RESULTS: The harmonized index constructed using 8 assets and 11 housing characteristics explained 32.4% of the variance. Most households increased in absolute wealth over time with median wealth (25th percentile, 75th percentile; households) increasing from - 3.74 (- 4.42, - 3.07; 547) in 1967 to 2.08 (1.41, 2.67; 1145) in 2017-18. Ownership of television, electricity, quality of flooring and sanitary installation explained the largest proportion of variance. The index is positively associated with measures of schooling (maternal: r = 0.16; paternal: r = 0.10; attained: r = 0.35, all p < 0.001). In 2015-18, house ownership versus housing characteristics and ownership of electronic goods differentiate households in urban and rural areas respectively. The index is robust for omission of assets or study waves, indicator categorization and factor extraction method. CONCLUSION: A temporally harmonized asset index constructed from consistently administered surveys in a cohort setting over time may allow study of associations of life-course social mobility with human capital outcomes in LMIC contexts. The approach permits exploration of trends in household wealth of the sample over a follow-up period against repeated cross-sectional surveys which permit the estimation of only the mean trajectory.

Postprandial glycemic response differed by early life nutritional exposure in a longitudinal cohort: a single- and multi-biomarker approach.

PURPOSE: Populations malnourished in early life are at increased risk for cardiometabolic diseases. We assessed if improved nutrition predicts cardiometabolic function, as assessed by postprandial biomarker responses. METHODS: Participants had been randomized at the village level to receive one of two nutritional supplements as children. At mean age 44 y (range 37-53 years), we obtained plasma samples before and 2 h after a mixed-component meal challenge. We assayed biomarkers including lipids, glycemic measurements, and inflammatory cytokines. We compared postprandial biomarker responses among those who received the improved nutrition intervention from conception through to their second birthday (the first 1000 days) to those with other exposure status, including those who received the improved nutrition intervention at other ages, and those who received the less nutritious supplement. RESULTS: Among 1027 participants (59.4% female), 22.9% were exposed to improved nutrition in the first 1000 days. Insulin increased the most in response to the meal challenge (over twofold), and non-esterified fatty acids decreased the most (by half). Glucose increased postprandial by 11.4% in the exposed group, compared with 15.7% in the other exposure group (p < 0.05), which remained significant after adjusting for confounders (- 4.7%; 95% confidence interval: - 9.3%, - 0.01%). Responses to the prandial challenges for the other biomarkers did not differ by intervention group (all p > 0.05). CONCLUSION: Early life exposure to improved nutrition was associated with a more favorable postprandial glucose response in this population. We did not observe a difference in overall cardiometabolic responses between the exposure groups.