Adolescent Levers for a Diet and Physical Activity Intervention Across Socioecological Levels in Kenya, South Africa, Cameroon, and Jamaica: Mixed Methods Study Protocol.

BACKGROUND: The increasing burden of noncommunicable diseases that are prevalent in low- and middle-income countries (LMICs) is largely attributed to modifiable behavioral risk factors such as unhealthy diets and insufficient physical activity (PA). The adolescent stage, defined as 10 to 24 years of age, is an important formative phase of life and offers an opportunity to reduce the risk of noncommunicable diseases across the life course and for future generations. OBJECTIVE: The aim of this paper is to describe a protocol for a study using a convergent mixed methods design to explore exposures in the household, neighborhood, school, and the journey from home to school that may influence diet and PA behaviors in adolescents from LMICs. METHODS: Male and female adolescents (n≥150) aged between 13 and 24 years will be recruited from selected high schools or households in project site countries to ensure the socioeconomic diversity of perspectives and experiences at the individual, home, and neighborhood levels. The project will be conducted at 5 sites in 4 countries: Kenya, Cameroon, Jamaica, and South Africa (Cape Town and Johannesburg). Data on anthropometric measures, food intake, and PA knowledge and behavior will be collected using self-report questionnaires. In addition, a small number of learners (n=30-45) from each site will be selected as citizen scientists to capture data (photographs, audio notes, text, and geolocations) on their lived experiences in relation to food and PA in their homes, the journey to and from school, and the school and neighborhood environments using a mobile app, and for objective PA measurements. In-depth interviews will be conducted with the citizen scientists and their caregivers to explore household experiences and determinants of food intake and foodways, as well as the PA of household members. RESULTS: The study described in this protocol paper was primarily funded through a UK National Institute for Health Research grant in 2017 and approved by the relevant institutional ethics review boards in the country sites (South Africa, Cameroun, and Jamaica in 2019, and Kenya in 2020). As of December 23, 2020, we had completed data collection from adolescents (n≥150) in all the country sites, except Kenya, and data collection for the subgroup (n=30-45) is ongoing. Data analysis is ongoing and the output of findings from the study described in this protocol is expected to be published by 2022. CONCLUSIONS: This project protocol contributes to research that focuses on adolescents and the socioecological determinants of food intake and PA in LMIC settings. It includes innovative methodologies to interrogate and map the contexts of these determinants and will generate much-needed data to understand the multilevel system of factors that can be leveraged through upstream and downstream strategies and interventions to improve health outcomes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/26739.

Admixture/fine-mapping in Brazilians reveals a West African associated potential regulatory variant (rs114066381) with a strong female-specific effect on body mass and fat mass indexes.

BACKGROUND/OBJECTIVES: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil. SUBJECTS/METHODS: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas). RESULTS: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects. CONCLUSIONS: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

Nutrient Patterns and Body Composition Parameters of Black South African Women.

Obesity is more prevalent in black South African women than men. However, little is known about the nutrient patterns associated with body composition indices in black African women. Principle Component Analysis (PCA) was applied to 25 nutrients derived from quantified food frequency questionnaires (QFFQs) in 498 middle aged black South African women. Three nutrient patterns, the plant driven, animal driven and Vitamin C, sugar and potassium driven nutrient patterns, accounted for 59% of the variance of nutrient intake. Linear models of the body composition parameters as outcome variables indicated that a standard deviation increase in the animal driven nutrient pattern was significantly associated with increases in body mass index (BMI) (1.29 kg·m-2 (95% CI, 0.54-2.04; p = 0.001), subcutaneous adipose tissue (SAT) (26.30 cm2 (7.97-44.63); p = 0.005), visceral adipose tissue (VAT) (9.88 cm2 (5.13-14.63); p < 0.001), VAT/SAT ratio (0.01 (0.00-0.02); p = 0.018), whole body fat mass index (0.74 kg·m-2 (0.25-1.22); p = 0.003), and whole body lean mass index (0.53 kg·m-2 (0.23-0.83); p = 0.001). An increase in plant driven nutrient pattern was significantly associated with an increase in SAT of 20.45 cm2 (0.47-40.43); p = 0.045. This study demonstrates that animal driven nutrient pattern, characterised by the consumption of more animal protein and fat nutrients, similar to the western diet is associated with increased body fat and lean mass.

International gestational age-specific centiles for umbilical artery Doppler indices: a longitudinal prospective cohort study of the INTERGROWTH-21st Project.

BACKGROUND: Reference values for umbilical artery Doppler indices are used clinically to assess fetal well-being. However, many studies that have produced reference charts have important methodologic limitations, and these result in significant heterogeneity of reported reference ranges. OBJECTIVES: To produce international gestational age-specific centiles for umbilical artery Doppler indices based on longitudinal data and the same rigorous methodology used in the original Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. STUDY DESIGN: In Phase II of the INTERGROWTH-21st Project (the INTERBIO-21st Study), we prospectively continued enrolling pregnant women according to the same protocol from 3 of the original populations in Pelotas (Brazil), Nairobi (Kenya), and Oxford (United Kingdom) that had participated in the Fetal Growth Longitudinal Study. Women with a singleton pregnancy were recruited at <14 weeks' gestation, confirmed by ultrasound measurement of crown-rump length, and then underwent standardized ultrasound every 5±1 weeks until delivery. From 22 weeks of gestation umbilical artery indices (pulsatility index, resistance index, and systolic/diastolic ratio) were measured in a blinded fashion, using identical equipment and a rigorously standardized protocol. Newborn size at birth was assessed using the international INTERGROWTH-21st Standards, and infants had detailed assessment of growth, nutrition, morbidity, and motor development at 1 and 2 years of age. The appropriateness of pooling data from the 3 study sites was assessed using variance component analysis and standardized site differences. Umbilical artery indices were modeled as functions of the gestational age using an exponential, normal distribution with second-degree fractional polynomial smoothing; goodness of fit for the overall models was assessed. RESULTS: Of the women enrolled at the 3 sites, 1629 were eligible for this study; 431 (27%) met the entry criteria for the construction of normative centiles, similar to the proportion seen in the original fetal growth longitudinal study. They contributed a total of 1243 Doppler measures to the analysis; 74% had 3 measures or more. The healthy low-risk status of the population was confirmed by the low rates of preterm birth (4.9%) and preeclampsia (0.7%). There were no neonatal deaths and satisfactory growth, health, and motor development of the infants at 1 and 2 years of age were documented. Only a very small proportion (2.8%-6.5%) of the variance of Doppler indices was due to between-site differences; in addition, standardized site difference estimates were marginally outside this threshold in only 1 of 27 comparisons, and this supported the decision to pool data from the 3 study sites. All 3 Doppler indices decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age for each of the 3 indices are provided, as well as equations to allow calculation of any value as a centile and z scores. The mean pulsatility index according to gestational age = 1.02944 + 77.7456*(gestational age)-2 - 0.000004455*gestational age3. CONCLUSION: We present here international gestational age-specific normative centiles for umbilical artery Doppler indices produced by studying healthy, low-risk pregnant women living in environments with minimal constraints on fetal growth. The centiles complement the existing INTERGROWTH-21st Standards for assessment of fetal well-being.

Comparative Models of Biological and Social Pathways to Predict Child Growth through Age 2 Years from Birth Cohorts in Brazil, India, the Philippines, and South Africa.

Background: Early growth faltering accounts for one-third of child deaths, and adversely impacts the health and human capital of surviving children. Social as well as biological factors contribute to growth faltering, but their relative strength and interrelations in different contexts have not been fully described. Objective: The aim of this study was to use structural equation modelling to explore social and biological multidetermination of child height at age 2 y in longitudinal data from 4 birth cohort studies in low- and middle-income countries. Methods: We analyzed data from 13,824 participants in birth cohort studies in Brazil, India, the Philippines, and South Africa. We used exploratory structural equation models, with height-for-age at 24 mo as the outcome to derive factors, and path analysis to estimate relations among a wide set of social and biological variables common to the 4 sites. Results: The prevalence of stunting at 24 mo ranged from 14.0% in Brazil to 67.7% in the Philippines. Maternal height and birthweight were strongly predictive of height-for-age at 24 mo in all 4 sites (all P values <0.001). Three social-environmental factors, which we characterized as "child circumstances," "family socioeconomic status," and "community facilities," were identified in all sites. Each social-environmental factor was also strongly predictive of height-for-age at 24 mo (all P values <0.001), with some relations partly mediated through birthweight. The biological pathways accounted for 59% of the total explained variance and the social-environmental pathways accounted for 41%. The resulting path coefficients were broadly similar across the 4 sites. Conclusions: Early child growth faltering is determined by both biological and social factors. Maternal height, itself a marker of intergenerational deprivation, strongly influences child height at 2 y, including indirect effects through birthweight and social factors. However, concurrent social factors, many of which are modifiable, directly and indirectly contribute to child growth. This study highlights opportunities for interventions that address both biological and social determinants over the long and short term.

Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies.

BACKGROUND: Fast weight gain and linear growth in children in low-income and middle-income countries are associated with enhanced survival and improved cognitive development, but might increase risk of obesity and related adult cardiometabolic diseases. We investigated how linear growth and relative weight gain during infancy and childhood are related to health and human capital outcomes in young adults. METHODS: We used data from five prospective birth cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa. We investigated body-mass index, systolic and diastolic blood pressure, plasma glucose concentration, height, years of attained schooling, and related categorical indicators of adverse outcomes in young adults. With linear and logistic regression models, we assessed how these outcomes relate to birthweight and to statistically independent measures representing linear growth and weight gain independent of linear growth (relative weight gain) in three age periods: 0-2 years, 2 years to mid-childhood, and mid-childhood to adulthood. FINDINGS: We obtained data for 8362 participants who had at least one adult outcome of interest. A higher birthweight was consistently associated with an adult body-mass index of greater than 25 kg/m(2) (odds ratio 1·28, 95% CI 1·21-1·35) and a reduced likelihood of short adult stature (0·49, 0·44-0·54) and of not completing secondary school (0·82, 0·78-0·87). Faster linear growth was strongly associated with a reduced risk of short adult stature (age 2 years: 0·23, 0·20-0·52; mid-childhood: 0·39, 0·36-0·43) and of not completing secondary school (age 2 years: 0·74, 0·67-0·78; mid-childhood: 0·87, 0·83-0·92), but did raise the likelihood of overweight (age 2 years: 1·24, 1·17-1·31; mid-childhood: 1·12, 1·06-1·18) and elevated blood pressure (age 2 years: 1·12, 1·06-1·19; mid-childhood: 1·07, 1·01-1·13). Faster relative weight gain was associated with an increased risk of adult overweight (age 2 years: 1·51, 1·43-1·60; mid-childhood: 1·76, 1·69-1·91) and elevated blood pressure (age 2 years: 1·07, 1·01-1·13; mid-childhood: 1·22, 1·15-1·30). Linear growth and relative weight gain were not associated with dysglycaemia, but a higher birthweight was associated with decreased risk of the disorder (0·89, 0·81-0·98). INTERPRETATION: Interventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors, with few adverse trade-offs. FUNDING: Wellcome Trust and Bill & Melinda Gates Foundation.

Maternal height and child growth patterns.

OBJECTIVE: To examine associations between maternal height and child growth during 4 developmental periods: intrauterine, birth to age 2 years, age 2 years to mid-childhood (MC), and MC to adulthood. STUDY DESIGN: Pooled analysis of maternal height and offspring growth using 7630 mother-child pairs from 5 birth cohorts (Brazil, Guatemala, India, the Philippines, and South Africa). We used conditional height measures that control for collinearity in height across periods. We estimated associations between maternal height and offspring growth using multivariate regression models adjusted for household income, child sex, birth order, and study site. RESULTS: Maternal height was associated with birth weight and with both height and conditional height at each age examined. The strongest associations with conditional heights were for adulthood and 2 years of age. A 1-cm increase in maternal height predicted a 0.024 (95% CI: 0.021-0.028) SD increase in offspring birth weight, a 0.037 (95% CI: 0.033-0.040) SD increase in conditional height at 2 years, a 0.025 (95% CI: 0.021-0.029 SD increase in conditional height in MC, and a 0.044 (95% CI: 0.040-0.048) SD increase in conditional height in adulthood. Short mothers (<150.1 cm) were more likely to have a child who was stunted at 2 years (prevalence ratio = 3.20 (95% CI: 2.80-3.60) and as an adult (prevalence ratio = 4.74, (95% CI: 4.13-5.44). There was no evidence of heterogeneity by site or sex. CONCLUSION: Maternal height influences offspring linear growth over the growing period. These influences likely include genetic and non-genetic factors, including nutrition-related intergenerational influences on growth that prevent the attainment of genetic height potential in low- and middle-income countries.

Size at birth, weight gain in infancy and childhood, and adult diabetes risk in five low- or middle-income country birth cohorts.

OBJECTIVE: We examined associations of birth weight and weight gain in infancy and early childhood with type 2 diabetes (DM) risk in five cohorts from low- and middle-income countries. RESEARCH DESIGN AND METHODS: Participants were 6,511 young adults from Brazil, Guatemala, India, the Philippines, and South Africa. Exposures were weight at birth, at 24 and 48 months, and adult weight, and conditional weight gain (CWG, deviation from expected weight gain) between these ages. Outcomes were adult fasting glucose, impaired fasting glucose or DM (IFG/DM), and insulin resistance homeostasis model assessment (IR-HOMA, three cohorts). RESULTS: Birth weight was inversely associated with adult glucose and risk of IFG/DM (odds ratio 0.91[95% CI 0.84-0.99] per SD). Weight at 24 and 48 months and CWG 0-24 and 24-48 months were unrelated to glucose and IFG/DM; however, CWG 48 months-adulthood was positively related to IFG/DM (1.32 [1.22-1.43] per SD). After adjusting for adult waist circumference, birth weight, weight at 24 and 48 months and CWG 0-24 months were inversely associated with glucose and IFG/DM. Birth weight was unrelated to IR-HOMA, whereas greater CWG at 0-24 and 24-48 months and 48 months-adulthood predicted higher IR-HOMA (all P < 0.001). After adjusting for adult waist circumference, birth weight was inversely related to IR-HOMA. CONCLUSIONS: Lower birth weight and accelerated weight gain after 48 months are risk factors for adult glucose intolerance. Accelerated weight gain between 0 and 24 months did not predict glucose intolerance but did predict higher insulin resistance.

Rapid infant weight gain and advanced skeletal maturation in childhood.

OBJECTIVE: To test the hypothesis that rapid infant weight gain is associated with advanced skeletal maturity in children from the United States and South Africa. STUDY DESIGN: Longitudinal data from 467 appropriate-for-gestational-age infants in the Fels Longitudinal Growth Study (Dayton, Ohio) and 196 appropriate-for-gestational-age infants in the Birth to Twenty birth cohort study (Johannesburg, South Africa) were used. Multiple linear regression models tested the association between internal SD score change in weight from 0 to 2 years and relative skeletal age at 9 years, adjusting for body mass index, stature, and other covariates. RESULTS: In both studies, faster infant weight gain was associated with more advanced skeletal maturity (approximately 0.2 years or 2.4 months per SD score) at age 9 years (P <.0001-.005), even when adjusting for the positive associations of both birth weight and body mass index at age 9 years. This effect appeared to be accounted for by the greater childhood stature of subjects with more rapid infant weight gain. CONCLUSIONS: Relatively rapid infant weight-gain is associated with advanced skeletal development in late childhood, perhaps via effects on stature.

Size at birth, weight gain in infancy and childhood, and adult blood pressure in 5 low- and middle-income-country cohorts: when does weight gain matter?

BACKGROUND: Promoting catch-up growth in malnourished children has health benefits, but recent evidence suggests that accelerated child weight gain increases adult chronic disease risk. OBJECTIVE: We aimed to determine how birth weight (BW) and weight gain to midchildhood relate to blood pressure (BP) in young adults. DESIGN: We pooled data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa. We used conditional weight (CW), a residual of current weight regressed on prior weights, to represent deviations from expected weight gain from 0 to 12, 12 to 24, 24 to 48 mo, and 48 mo to adulthood. Adult BP and risk of prehypertension or hypertension (P/HTN) were modeled before and after adjustment for adult body mass index (BMI) and height. Interactions of CWs with small size-for-gestational age (SGA) at birth were tested. RESULTS: Higher CWs were associated with increased BP and odds of P/HTN, with coefficients proportional to the contribution of each CW to adult BMI. Adjusted for adult height and BMI, no child CW was associated with adult BP, but 1 SD of BW was related to a 0.5-mm Hg lower systolic BP and a 9% lower odds of P/HTN. BW and CW associations with systolic BP and P/HTN were not different between adults born SGA and those with normal BW, but higher CW at 48 mo was associated with higher diastolic BP in those born SGA. CONCLUSIONS: Greater weight gain at any age relates to elevated adult BP, but faster weight gains in infancy and young childhood do not pose a higher risk than do gains at other ages.