Novel signals and polygenic score for height are associated with pubertal growth traits in Southwestern American Indians.

Most genetic variants associated with adult height have been identified through large genome-wide association studies (GWASs) in European-ancestry cohorts. However, it is unclear how these variants influence linear growth during adolescence. This study uses anthropometric and genotypic data from a longitudinal study conducted in an American Indian community in Arizona between 1965-2007. Growth parameters (i.e. height, velocity, and timing of growth spurt) were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, in 787 participants with height measurements spanning the whole period of growth. Heritability estimates suggested that genetic factors could explain 25% to 71% of the variance of pubertal growth traits. We performed a GWAS of growth parameters, testing their associations with 5 077 595 imputed or directly genotyped variants. Six variants associated with height at peak velocity (P < 5 × 10-8, adjusted for sex, birth year and principal components). Implicated genes include NUDT3, previously associated with adult height, and PACSIN1. Two novel variants associated with duration of growth spurt (P < 5 × 10-8) in LOC105375344, an uncharacterized gene with unknown function. We finally examined the association of growth parameters with a polygenic score for height derived from 9557 single nucleotide polymorphisms (SNPs) identified in the GIANT meta-analysis for which genotypic data were available for the American Indian study population. Height polygenic score was correlated with the magnitude and velocity of height growth that occurred before and at the peak of the adolescent growth spurt, indicating overlapping genetic architecture, with no influence on the timing of adolescent growth.

Adolescent Growth Spurt and Type 2 Diabetes Risk in Southwestern American Indians.

Early puberty onset is associated with higher risk of diabetes, but most studies have not accounted for childhood factors that may confound the association. Using data from a study conducted in an Indigenous community in Arizona (1965-2007), we examined associations of timing and velocity of the adolescent growth spurt with type 2 diabetes, and whether these associations are mediated by childhood body mass index and insulinemia. Adolescent growth parameters were derived from the Preece-Baines growth model, a parametric growth curve fitted to longitudinal height data, for 861 participants with height measurements spanning the whole period of growth. In males, older age at take-off, age at peak velocity, and age at maturation were associated with decreased prevalence of diabetes (odds ratio (OR) = 0.43 per year, 95% confidence interval (CI): 0.27, 0.69; OR = 0.50, 95% CI: 0.35, 0.72; OR = 0.58, 95% CI: 0.41, 0.83, respectively), while higher velocity at take-off was associated with increased risk (OR = 3.47 per cm/year, 95% CI: 1.87, 6.42) adjusting for age, birth year, and maternal diabetes. Similar results were observed with incident diabetes. Our findings suggest that an early and accelerated adolescent growth spurt is a risk factor for diabetes, at least in males. These associations are only partially explained by measures of adiposity and insulinemia.

Increased Adiposity and Low Height-for-Age in Early Childhood Are Associated With Later Metabolic Risks in American Indian Children and Adolescents.

BACKGROUND: Growth abnormalities in childhood have been related to later cardiometabolic risks, but little is known about these associations in populations at high risk of type 2 diabetes. OBJECTIVES: We examined the associations of patterns of growth, including weight and height at ages 1-59 months, with cardiometabolic risk factors at ages 5-16 years. METHODS: We linked anthropometric data collected at ages 1-59 months to cardiometabolic data obtained from a longitudinal study in a southwestern American Indian population at high risk of diabetes. Analyses included 701 children with ≥1 follow-up examination at ages 5-16 years. We derived age- and sex-specific weight-for-height z-scores (WHZ) and height-for-age z-scores (HAZ) at ages 1-59 months. We selected the highest observed WHZ and the lowest observed HAZ at ages 1-59 months and analyzed associations of z-scores and categories of WHZ and HAZ with cardiometabolic outcomes at ages 5-16 years. We used linear mixed-effects models to account for repeated measures. RESULTS: Overweight/obesity (WHZ >2) at ages 1-59 months was significantly associated with increased BMI, fasting and 2-hour postload plasma glucose, fasting and 2-hour insulin, triglycerides, systolic blood pressure, diastolic blood pressure, and decreased HDL cholesterol at ages 5-16 years relative to normal weight (WHZ ≤1). For example, at ages 5-9 years, 2-hour glucose was 10.4 mg/dL higher (95% CI: 5.6-15.3 mg/dL) and fasting insulin was 4.29 µU/mL higher (95% CI: 2.96-5.71 µU/mL) in those with overweight/obesity in early childhood. Associations were attenuated and no longer significant when adjusted for concurrent BMI. A low height-for-age (HAZ < -2) at ages 1-59 months was associated with 5.37 mg/dL lower HDL (95% CI: 2.57-8.17 mg/dL) and 27.5 µU/mL higher 2-hour insulin (95% CI: 3.41-57.6 µU/mL) at ages 10-16 years relative to an HAZ ≥0. CONCLUSIONS: In this American Indian population, findings suggest a strong contribution of overweight/obesity in early childhood to cardiometabolic risks in later childhood and adolescence, mediated through persistent overweight/obesity into later ages. Findings also suggest potential adverse effects of low height-for-age, which require confirmation.

Cognitive and socio-emotional correlates of psychological well-being and mental health in Guatemalan adults.

BACKGROUND: Little is known about associations of psychological and mental well-being with cognitive and socioemotional factors in low and middle-income countries, particularly among vulnerable populations born in adverse environments that may restrict developmental potential. This study aimed to examine the cognitive and socioemotional correlates of psychological well-being and mental health in a cohort of Guatemalan adults born in contexts of poverty and malnutrition. METHODS: From Dec 2017 to Apr 2019, data were collected from 704 women and 564 men ages 40-57 years living in four rural villages in eastern Guatemala and Guatemala City. We measured latent domains of psychological well-being, spirituality and religion, emotional support, and executive function using Confirmatory Factor Analysis (CFA). Under a Structural Equation Modeling framework, we examined intercorrelations among latent domains and observed measures of intelligence and mental health. RESULTS: CFA supported the construct validity of factor structures in this population. Correlations of psychological well-being with spirituality and religion were moderate in women (r = 0.68, p < 0.001) and men (r = 0.70, p < 0.001). Executive function was weakly correlated with psychological well-being in men (r = 0.23, p < 0.001) and showed no association in women. Correlations of psychological well-being with emotional support and IQ were weak in women (r = 0.34, and r = 0.15, respectively; p < 0.001 for both) and men (r = 0.35, and r = 0.25, respectively; p < 0.001 for both). Mental health and IQ were weakly correlated in men (r = 0.09, p < 0.05) and showed no association in women. Mental health showed weak correlations with emotional support (r = 0.18, p < 0.001 in women; r = 0.09, p < 0.05 in men), psychological well-being (r = 0.32 and r = 0.35, in women and men respectively; p < 0.001 for both) and showed no association with executive function in both sexes. CONCLUSIONS: Of all examined factors, spirituality and religion made the greatest contribution to psychological well-being. These findings support the notion that in populations experiencing difficult circumstances, religion can perhaps make a greater contribution to well-being and aid coping. More research is needed to examine mediators of this association.

Influence of enhanced nutrition and psychosocial stimulation in early childhood on cognitive functioning and psychological well-being in Guatemalan adults.

RATIONALE: Early-life nutrition interventions in low and middle-income countries have demonstrated long-term benefits on cognitive skills, however, their influence on socioemotional outcomes has not been fully explored. Moreover, the mediating processes through which nutrition intervention effects operate and are maintained over time are understudied. METHODS: We followed-up a cohort of Guatemalan adults who participated as children in a community randomized food-supplementation trial. We examined associations of exposure to nutritional supplementation from conception to age 2 years with executive function (measured using three sub-tests of the NIH Toolbox Cognition Battery) and psychological well-being (measured using two sub-scales of the NIH Toolbox Emotion Battery) at ages 40-57 years (n = 1268). We used structural equation modeling to investigate the mediating role of psychosocial stimulation (measured in childhood using parent reports and ratings of home environments), cognitive ability (measured at ages 26-42 years using standardized tests), and executive function on the association of early-life exposure to nutritional supplementation with adult psychological well-being (n = 1640). RESULTS: We found positive but inconsistent associations of nutritional supplementation in childhood with executive function and psychological well-being in adulthood. Psychosocial stimulation, cognitive ability, and executive function did not mediate the association of early-life nutritional supplementation with adult psychological well-being. We found strong and positive associations of psychosocial stimulation in childhood with cognitive ability, executive function, and psychological well-being in adulthood. Moreover, we observed no interaction of exposure to nutritional supplementation and psychosocial stimulation in childhood with cognitive and psychological well-being outcomes in adulthood. CONCLUSION: Our findings suggest that childhood nutrition interventions have long-lasting effects on cognitive ability and psychological well-being outcomes.

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.

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.

Malnutrition inequalities in Ecuador: differences by wealth, education level and ethnicity.

OBJECTIVE: To describe and quantify the magnitude and distribution of stunting, wasting, anaemia, overweight and obesity by wealth, level of education and ethnicity in Ecuador. DESIGN: We used nationally representative data from the 2012 Ecuadorian National Health and Nutrition Survey. We used the Multidimensional Poverty Index (MPI) as a proxy of wealth. The MPI identifies deprivations across three dimensions (health, education and standard of living). We defined education by years of schooling and ethnicity as a social construct, based on shared social, cultural and historical experiences, using Ecuadorian census categories. SETTING: Urban and rural Ecuador, including the Amazon rainforest and the Galapagos Islands. PARTICIPANTS: Children aged <5 years (n 8580), adolescent women aged 11-19 years (n 4043) and adult women aged 20-49 years (n 15 203). RESULTS: Among children <5 years, stunting and anaemia disproportionately affected low-wealth, low-education and indigenous groups. Among adolescent and adult women, higher rates of stunting, overweight and obesity were observed in the low-education and low-wealth groups. Stunting and short stature rates were higher in indigenous women, whereas overweight and obesity rates were higher in Afro-Ecuadorian women. CONCLUSIONS: Malnutrition differs significantly across sociodemographic groups, disproportionately affecting those in the low wealth tertile and ethnic minorities. Rates of stunting remain high compared with other countries in the region with similar economic development. The effective implementation of double-duty actions with the potential to impact both sides of the double burden is urgently required.

Effects of increased hemoglobin on child growth, development, and disease: a systematic review and meta-analysis.

In children under 5, a hemoglobin (Hb) cutoff of 11 g/dL is recommended by the World Health Organization to define anemia, yet few studies have examined whether this cut point accurately coincides with negative functional consequences. This systematic review and meta-analysis of iron intervention and observational studies aimed to clarify the consequences of low Hb concentration in children under age 5 years on growth, development, and chronic disease (functional outcomes) across the full range of Hb values. A literature search returned 5049 studies; of these, 56 intervention and 20 observational studies fit the inclusion criteria. Among iron supplementation trials, a metaregression indicated significant associations between intervention effects on Hb and their effects on motor and mental development. For each 1 standard deviation (SD) increase in Hb, motor scores increased by 0.28 SD and mental scores increased by 0.24 SD. Iron supplementation trials among children with lower Hb concentrations at baseline showed stronger associations between their effects on Hb and their effects on mental development (P-interaction = 0.008). Heterogeneity among observational studies precluded calculation of pooled associations between Hb and functional outcomes. Available evidence was not able to establish an inflection point at which decreasing Hb begins to be associated with negative functional outcomes. Future research is needed to examine associations of Hb with growth and development in populations with varying levels of Hb, inflammation, and in different ages and settings.

Impact of Double-Fortified Salt with Iron and Iodine on Hemoglobin, Anemia, and Iron Deficiency Anemia: A Systematic Review and Meta-Analysis.

Double-fortified salt (DFS) containing iron and iodine has been proposed as a feasible and cost-effective alternative for iron fortification in low- and middle-income countries (LMICs). We conducted a systematic review and meta-analysis from randomized and quasi-randomized controlled trials to 1) assess the effect of DFS on biomarkers of iron status and the risk of anemia and iron deficiency anemia (IDA) and 2) evaluate differential effects of DFS by study type (efficacy or effectiveness), population subgroups, iron formulation (ferrous sulfate, ferrous fumarate, and ferric pyrophosphate), iron concentration, duration of intervention, and study quality. A systematic search with the use of MEDLINE, EMBASE, Cochrane, Web of Science, and other sources identified 221 articles. Twelve efficacy and 2 effectiveness studies met prespecified inclusion criteria. All studies were conducted in LMICs: 10 in India, 2 in Morocco, and 1 each in Côte d'Ivoire and Ghana. In efficacy studies, DFS increased hemoglobin concentrations [standardized mean difference (SMD): 0.28; 95% CI: 0.11, 0.44; P < 0.001] and reduced the risk of anemia (RR: 0.59; 95% CI: 0.46, 0.77; P < 0.001) and IDA (RR 0.37; 95% CI: 0.25, 0.54; P < 0.001). In effectiveness studies, the effect size for hemoglobin was smaller but significant (SMD: 0.03; 95% CI: 0.01, 0.05; P < 0.01). Stratified analyses of efficacy studies by population subgroups indicated positive effects of DFS among women and school-age children. For the latter, DFS increased hemoglobin concentrations (SMD: 0.32; 95% CI: 0.03, 0.60; P < 0.05) and reduced the risk of anemia (SMD: 0.48; 95% CI: 0.34, 0.67; P < 0.001) and IDA (SMD: 0.37; 95% CI: 0.25, 0.54; P < 0.001). Hemoglobin concentrations, anemia prevalence and deworming at baseline, sample size, and study duration were not associated with effect sizes. The results indicate that DFS is efficacious in increasing hemoglobin concentrations and reducing the risk of anemia and IDA in LMIC populations. More effectiveness studies are needed.

A Food Transfer Program without a Formal Education Component Modifies Complementary Feeding Practices in Poor Rural Mexican Communities.

BACKGROUND: Inadequate complementary feeding partially explains micronutrient deficiencies in the first 2 y of life. To prevent malnutrition, the Mexican government implemented the Programa de Apoyo Alimentario (PAL), which transferred either food baskets containing micronutrient-fortified milk and animal food products or cash to beneficiary families along with educational sessions. OBJECTIVE: This study evaluated the impact of PAL on 2 indicators of complementary feeding: minimum dietary diversity and consumption of iron-rich or iron-fortified foods in children aged 6-23 mo. METHODS: A secondary analysis of the original PAL evaluation design was conducted through a randomized community trial implemented with 3 intervention groups (food basket with education, food basket without education, and cash transfer with education) and a control. The impact of PAL after 14 mo of exposure was estimated in 2 cross-sectional groups of children aged 6-23 mo at baseline and at follow-up in a panel of 145 communities by using difference-in-difference models. Only children who lived in households and communities that were similar between treatment groups at baseline were included in the analysis. These children were identified by using a propensity score. RESULTS: Of the 3 intervention groups, when compared with the control, only the food basket without education group component increased the consumption of iron-rich or iron-fortified foods by 31.2 percentage points (PP) (P < 0.01) and the prevalence of minimum dietary diversity by 21.6 PP (P < 0.01). CONCLUSION: These findings suggest that in order to improve dietary quality in children, food baskets that include fortified complementary foods may be more effective than cash transfers. The fact that the 2 food basket groups differed in the observed impact does not allow for more convincing conclusions to be made about the education component of the program. This trial was registered at clinicaltrials.gov as NCT01304888.

The double burden of undernutrition and excess body weight in Ecuador.

BACKGROUND: Ecuador's current nutrition policies have not taken adequate notice of the double burden of malnutrition and continue to focus on stunting and to a lesser extent on overweight, without addressing the simultaneous presence of undernutrition, micronutrient deficiencies, and overweight or obesity (OW/OB). OBJECTIVE: The aim of this article was to describe the prevalence and distribution of undernutrition (stunting, anemia, and zinc deficiency), overweight, and obesity in Ecuador to explore the evolving double burden of malnutrition at the national, household, and individual levels and to discuss whether current public health policies are addressing the double burden. DESIGN: Data from the 2012 Ecuadorian National Health and Nutrition Survey (ENSANUT-ECU) was used to estimate the dual burden of malnutrition at the national, household, and individual levels in children <5 y old, school-aged children, and women of reproductive age. RESULTS: In 13.1% of households, mothers with excess body weight coexist with a stunted child <5 y old. Moreover, among households with overweight or obese mothers, 12.6% have an anemic child and 14% have a zinc-deficient child. At the individual levels, the coexistence of OW/OB and stunting, anemia, or zinc deficiency was found in 2.8%, 0.7%, and 8.4% of school-aged children, respectively. In addition, 8.9% and 32.6% of women aged 12-49 y have excess body weight and anemia or zinc deficiency, respectively. CONCLUSIONS: This article shows the coexistence of high rates of undernutrition and OW/OB at the individual, household, and national levels in Ecuador. Although integrated approaches to address the emerging double burden are required, public health policies to date have not responded adequately.