Growth dynamics of Indian infants using latent trajectory models in pooled survey datasets

Mertens A., Benjamin-Chung J., Colford J.M., Coyle J., van der Laan M.J., Hubbard A.E., Rosete S., Malenica I., Hejazi N., Sofrygin O., Cai W., Li H., Nguyen A., Pokpongkiat N.N., Djajadi S., et. al.

AbstractGrowth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions.

Benjamin-Chung J., Mertens A., Colford J.M., Hubbard A.E., van der Laan M.J., Coyle J., Sofrygin O., Cai W., Nguyen A., Pokpongkiat N.N., Djajadi S., Seth A., Jilek W., Jung E., Chung E.O., et. al.

AbstractGlobally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards)1,2. Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering—a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries (n = 32 cohorts, 52,640 children, ages 0–24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children’s linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age.

Lai A., Velez I., Ambikapathi R., Seng K., Cumming O., Brown J.

ObjectiveThis study aimed to determine risk factors of growth faltering by assessing childhood nutrition and household water, sanitation, and hygiene (WASH) variables and their association with nutritional status of children under 24 months in rural Cambodia.DesignWe conducted surveys in 491 villages (clusters) randomised across 55 rural communes in Cambodia in September 2016 to measure associations between child, household and community-level risk factors for stunting and length-for-age z-score (LAZ). We measured 4036 children under 24 months of age from 3877 households (491 clusters). We analysed associations between nutrition/WASH practices and child growth (LAZ, stunting) using generalised estimating equations (GEEs) to fit linear regression models with robust SEs in a pooled analysis and in age-stratified analyses; child-level and household-level variables were modelled separately from community-level variables.ResultsAfter adjustment for potential confounding, we found household-level and community-level water, sanitation and hygiene factors to be associated with child growth among children under 24 months: presence of water and soap at a household’s handwashing station was positively associated with child growth (adjusted mean difference in LAZ +0.10, 95% CI 0.03 to 0.16); household-level use of an improved drinking water source and adequate child stool disposal practices were protective against stunting (adjusted prevalence ratio (aPR) 0.80, 95% CI 0.67 to 0.97; aPR 0.82, 95% CI 0.64 to 1.03). In our age-stratified analysis, we found associations between child growth and community-level factors among children 1–6 months of age: shared sanitation was negatively associated with growth (−0.47 LAZ, 95% CI −0.90 to –0.05 compared with children in communities with no shared facilities); improved sanitation facilities were protective against stunting (aPR 0.43, 95% CI 0.21 to 0.88 compared with children in communities with no improved sanitation facilities); and open defecation was associated with more stunting (aPR 2.13, 95% CI 1.10 to 4.11 compared with children in communities with no open defecation). These sanitation risk factors were only measured in the youngest age strata (1–6 months). Presence of water and soap at the household level were associated with taller children in the 1–6 month and 6–12 month age strata (+0.10 LAZ, 95% CI −0.02 to 0.22 among children 1–6 months of age; +0.11 LAZ, 95% CI −0.02 to 0.25 among children 6–12 months of age compared with children in households with no water and soap). Household use of improved drinking water source was positively associated with growth among older children (+0.13 LAZ, 95% CI −0.01 to 0.28 among children 12–24 months of age).ConclusionIn rural Cambodia, water, sanitation and hygiene behaviours were associated with growth faltering among children under 24 months of age. Community-level sanitation factors were positively associated with growth, particularly for infants under 6 months of age. We should continue to make effort to: investigate the relationships between water, sanitation, hygiene and human health and expand WASH access for young children.

Tariqujjaman M., Hasan M.M., Mahfuz M., Hossain M., Ahmed T.

The association between mother’s education and the World Health Organization’s (WHO’s) eight Infant and Young Child Feeding (IYCF) core indicators has yet to be explored in South Asia (SA). This study aimed to explore the association between mother’s education and the WHO’s eight IYCF core indicators in SA. We analyzed data from the most recent nationally representative Demographic and Health Surveys of six South Asian Countries (SACs)—Afghanistan, Bangladesh, India, Maldives, Nepal, and Pakistan. We found significantly higher odds (adjusted odds ratio, AOR, 1.13 to 1.47) among mothers who completed secondary or higher education than among mothers with education levels below secondary for the following seven IYCF indicators: early initiation of breastfeeding (EIBF), exclusive breastfeeding under 6 months (EBF), the introduction of solid, semisolid or soft foods (ISSSF), minimum dietary diversity (MDD), minimum meal frequency (MMF), minimum acceptable diet (MAD), and consumption of iron-rich or iron-fortified foods (CIRF); the exception was for the indicator of continued breastfeeding at one year. Country-specific analyses revealed significantly higher odds in EIBF (AOR 1.14; 95% CI: 1.11, 1.18) and EBF (AOR 1.27; 95% CI: 1.19, 1.34) among mothers with secondary or higher education levels in India. In contrast, the odds were lower for EIBF in Bangladesh and for EBF in Pakistan among mothers with secondary or higher education levels. For country-specific analyses for complementary feeding indicators such as ISSSF, MDD, MMF, MAD, and CIRF, significantly higher odds (AOR, 1.15 to 2.34) were also observed among mothers with secondary or higher education levels. These findings demonstrate a strong positive association between mother’s education and IYCF indicators. Strengthening national policies to educate women at least to the secondary level in SACs might be a cost-effective intervention for improving IYCF practices.

Ramírez-Luzuriaga M.J., Hoddinott J., Martorell R., Patel S.A., Ramírez-Zea M., Waford R., Stein A.D.

ABSTRACT 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.

Rodriguez-Martinez A., Zhou B., Sophiea M.K., Bentham J., Paciorek C.J., Iurilli M.L., Carrillo-Larco R.M., Bennett J.E., Di Cesare M., Taddei C., Bixby H., Stevens G.A., Riley L.M., Cowan M.J., Savin S., et. al.

Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents.For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5-19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence.We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9-10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes-gaining too little height, too much weight for their height compared with children in other countries, or both-occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls.The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks.Wellcome Trust, AstraZeneca Young Health Programme, EU.

Childhood malnutrition is associated with high morbidity and mortality globally1. Undernourished children are more likely to experience cognitive, physical, and metabolic developmental impairments that can lead to later cardiovascular disease, reduced intellectual ability and school attainment, and reduced economic productivity in adulthood2. Child growth failure (CGF), expressed as stunting, wasting, and underweight in children under five years of age (0–59 months), is a specific subset of undernutrition characterized by insufficient height or weight against age-specific growth reference standards3–5. The prevalence of stunting, wasting, or underweight in children under five is the proportion of children with a height-for-age, weight-for-height, or weight-for-age z-score, respectively, that is more than two standard deviations below the World Health Organization’s median growth reference standards for a healthy population6. Subnational estimates of CGF report substantial heterogeneity within countries, but are available primarily at the first administrative level (for example, states or provinces)7; the uneven geographical distribution of CGF has motivated further calls for assessments that can match the local scale of many public health programmes8. Building from our previous work mapping CGF in Africa9, here we provide the first, to our knowledge, mapped high-spatial-resolution estimates of CGF indicators from 2000 to 2017 across 105 low- and middle-income countries (LMICs), where 99% of affected children live1, aggregated to policy-relevant first and second (for example, districts or counties) administrative-level units and national levels. Despite remarkable declines over the study period, many LMICs remain far from the ambitious World Health Organization Global Nutrition Targets to reduce stunting by 40% and wasting to less than 5% by 2025. Large disparities in prevalence and progress exist across and within countries; our maps identify high-prevalence areas even within nations otherwise succeeding in reducing overall CGF prevalence. By highlighting where the highest-need populations reside, these geospatial estimates can support policy-makers in planning interventions that are adapted locally and in efficiently directing resources towards reducing CGF and its health implications. High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

Budge S., Parker A.H., Hutchings P.T., Garbutt C.

In 2017, an estimated 1 in every 4 (23%) children aged < 5 years were stunted worldwide. With slow progress in stunting reduction in many regions and the realization that a large proportion of stunting is not due to insufficient diet or diarrhea alone, it remains that other factors must explain continued growth faltering. Environmental enteric dysfunction (EED), a subclinical state of intestinal inflammation, can occur in infants across the developing world and is proposed as an immediate causal factor connecting poor sanitation and stunting. A result of chronic pathogen exposure, EED presents multiple causal pathways, and as such the scope and sensitivity of traditional water, sanitation, and hygiene (WASH) interventions have possibly been unsubstantial. Although the definite pathogenesis of EED and the mechanism by which stunting occurs are yet to be defined, this paper reviews the existing literature surrounding the proposed pathology and transmission of EED in infants and considerations for nutrition and WASH interventions to improve linear growth worldwide.

Lennon H., Kelly S., Sperrin M., Buchan I., Cross A.J., Leitzmann M., Cook M.B., Renehan A.G.

ObjectivesLatent class trajectory modelling (LCTM) is a relatively new methodology in epidemiology to describe life-course exposures, which simplifies heterogeneous populations into homogeneous patterns or classes. However, for a given dataset, it is possible to derive scores of different models based on number of classes, model structure and trajectory property. Here, we rationalise a systematic framework to derive a ‘core’ favoured model.MethodsWe developed an eight-step framework: step 1: a scoping model; step 2: refining the number of classes; step 3: refining model structure (from fixed-effects through to a flexible random-effect specification); step 4: model adequacy assessment; step 5: graphical presentations; step 6: use of additional discrimination tools (‘degree of separation’; Elsensohn’s envelope of residual plots); step 7: clinical characterisation and plausibility; and step 8: sensitivity analysis. We illustrated these steps using data from the NIH-AARP cohort of repeated determinations of body mass index (BMI) at baseline (mean age: 62.5 years), and BMI derived by weight recall at ages 18, 35 and 50 years.ResultsFrom 288 993 participants, we derived a five-class model for each gender (men: 177 455; women: 111 538). From seven model structures, the favoured model was a proportional random quadratic structure (model F). Favourable properties were also noted for the unrestricted random quadratic structure (model G). However, class proportions varied considerably by model structure—concordance between models F and G were moderate (Cohen κ: men, 0.57; women, 0.65) but poor with other models. Model adequacy assessments, evaluations using discrimination tools, clinical plausibility and sensitivity analyses supported our model selection.ConclusionWe propose a framework to construct and select a ‘core’ LCTM, which will facilitate generalisability of results in future studies.

Roth D.E., Krishna A., Leung M., Shi J., Bassani D.G., Barros A.J.

The causes of early childhood linear growth faltering (known as stunting) in low-income and middle-income countries remain inadequately understood. We aimed to determine if the progressive postnatal decline in mean height-for-age Z score (HAZ) in low-income and middle-income countries is driven by relatively slow growth of certain high-risk children versus faltering of the entire population.Distributions of HAZ (based on WHO growth standards) were analysed in 3-month age intervals from 0 to 36 months of age in 179 Demographic and Health Surveys from 64 low-income and middle-income countries (1993-2015). Mean, standard deviation (SD), fifth percentiles, and 95th percentiles of the HAZ distribution were estimated for each age interval in each survey. Associations between mean HAZ and SD, fifth percentile, and 95th percentile were estimated using multilevel linear models. Stratified analyses were performed in consideration of potential modifiers (world region, national income, sample size, year, or mean HAZ in the 0-3 month age band). We also used Monte Carlo simulations to model the effects of subgroup versus whole-population faltering on the HAZ distribution.Declines in mean HAZ from birth to 3 years of age were accompanied by declines in both the fifth and 95th percentiles, leading to nearly symmetrical narrowing of the HAZ distributions. Thus, children with relatively low HAZ were not more likely to have faltered than taller same-age peers. Inferences were unchanged in surveys regardless of world region, national income, sample size, year, or mean HAZ in the 0-3 month age band. Simulations showed that the narrowing of the HAZ distribution as mean HAZ declined could not be explained by faltering limited to a growth-restricted subgroup of children.In low-income and middle-income countries, declines in mean HAZ with age are due to a downward shift in the entire HAZ distribution, revealing that children across the HAZ spectrum experience slower growth compared to the international standard. Efforts to mitigate postnatal linear growth faltering in low-income and middle-income countries should prioritise action on community-level determinants of childhood HAZ trajectories.Bill & Melinda Gates Foundation.

Proust-Lima C., Philipps V., Liquet B.

Zhang Y., Zhou J., Niu F., Donowitz J.R., Haque R., Petri W.A., Ma J.Z.

Early childhood is a critical stage of physical and cognitive growth that forms the foundation of future wellbeing. Stunted growth is presented in one of every 4 children worldwide and contributes to developmental impairment and under-five mortality. Better understanding of early growth patterns should allow for early detection and intervention in malnutrition. We aimed to characterize early child growth patterns and quantify the change of growth curves from the World Health Organization (WHO) Child Growth Standards. In a cohort of 626 Bangladesh children, longitudinal height-for-age z-scores (HAZ) were modelled over the first 24 months of life using functional principal component analysis (FPCA). Deviation of individual growth from the WHO standards was quantified based on the leading functional principal components (FPCs), and growth faltering was detected as it occurred. The risk factors associated with growth faltering were identified in a linear regression. Ninety-eight percent of temporal variation in growth trajectories over the first 24 months of life was captured by two leading FPCs (FPC1 for overall growth and FPC2 for change in growth trajectory). A derived index, adj-FPC2, quantified the change in growth trajectory (i.e., growth faltering) relative to the WHO standards. In addition to HAZ at birth, significant risk factors associated with growth faltering in boys included duration of breastfeeding, family size and income and in girls maternal weight and water source. The underlying growth patterns of HAZ in the first 2 years of life were delineated with FPCA, and the deviations from the WHO standards were quantified from the two leading FPCs. The adj-FPC2 score provided a meaningful measure of growth faltering in the first 2 years of life, which enabled us to identify the risk factors associated with poor growth that would have otherwise been missed. Understanding faltering patterns and associated risk factors are important in the development of effective intervention strategies to improve childhood growth globally. ClinicalTrials.gov Identifier: NCT02734264 , registered 22 March, 2016.

Cumming O., Cairncross S.

Stunting is a complex and enduring challenge with far-reaching consequences for those affected and society as a whole. To accelerate progress in eliminating stunting, broader efforts are needed that reach beyond the nutrition sector to tackle the underlying determinants of undernutrition. There is growing interest in how water, sanitation and hygiene (WASH) interventions might support strategies to reduce stunting in high-burden settings, such as South Asia and sub-Saharan Africa. This review article considers two broad questions: (1) can WASH interventions make a significant contribution to reducing the global prevalence of childhood stunting, and (2) how can WASH interventions be delivered to optimize their effect on stunting and accelerate progress? The evidence reviewed suggests that poor WASH conditions have a significant detrimental effect on child growth and development resulting from sustained exposure to enteric pathogens but also due to wider social and economic mechanisms. Realizing the potential of WASH to reduce stunting requires a redoubling of efforts to achieve universal access to these services as envisaged under the Sustainable Development Goals. It may also require new or modified WASH strategies that go beyond the scope of traditional interventions to specifically address exposure pathways in the first 2 years of life when the process of stunting is concentrated.

Sudfeld C.R., McCoy D.C., Fink G., Muhihi A., Bellinger D.C., Masanja H., Smith E.R., Danaei G., Ezzati M., Fawzi W.W.

A large volume of literature has shown negative associations between stunting and child development; however, there is limited evidence for associations with milder forms of linear growth faltering and determinants of malnutrition in developing countries.The objective of this study was to assess the association between anthropometric growth indicators across their distribution and determinants of malnutrition with development of Tanzanian children.We used the Bayley Scales of Infant Development III to assess a cohort of 1036 Tanzanian children between 18 and 36 mo of age who were previously enrolled in a neonatal vitamin A trial. Linear regression models were used to assess standardized mean differences in child development for anthropometry z scores, along with pregnancy, delivery, and early childhood factors.Height-for-age z score (HAZ) was linearly associated with cognitive, communication, and motor development z scores across the observed range in this population (all P values for linear relation < 0.05). Each unit increase in HAZ was associated with +0.09 (95% CI: 0.05, 0.13), +0.10 (95% CI: 0.07, 0.14), and +0.13 (95% CI: 0.09, 0.16) higher cognitive, communication, and motor development z scores, respectively. The relation of weight-for-height z score (WHZ) was nonlinear with only wasted children (WHZ

Giles L.C., Whitrow M.J., Davies M.J., Davies C.E., Rumbold A.R., Moore V.M.

In an era where around one in four children in the United Kingdom, the United States, and Australia are overweight or obese, the development of obesity in early life needs to be better understood. We aimed to identify groups of children with distinct trajectories of growth in infancy and early childhood, to examine any association between these trajectories and body size at age 9, and to assess the relative influence of antenatal and postnatal exposures on growth trajectories. Prospective Australian birth cohort study. In total, 557 children with serial height and weight measurements from birth to 9 years were included in the study. Latent class growth models were used to derive distinct groups of growth trajectories from birth to age 3½ years. Multivariable logistic regression models were used to explore antenatal and postnatal predictors of growth trajectory groups, and multivariable linear and logistic regression models were used to examine the relationships between growth trajectory groups and body size at age 9 years. We identified four discrete growth trajectories from birth to age 3½ years, characterised as low, intermediate, high, or accelerating growth. Relative to the intermediate growth group, the low group had reduced z-body mass index (BMI) (−0.75 s.d.; 95% confidence interval (CI) −1.02, −0.47), and the high and accelerating groups were associated with increased body size at age 9 years (high: z-BMI 0.70 s.d.; 95% CI 0.49, 0.62; accelerating: z-BMI 1.64 s.d.; 95% CI 1.16, 2.11). Of the antenatal and postnatal exposures considered, the most important differentiating factor was maternal obesity in early pregnancy, associated with a near quadrupling of risk of membership of the accelerating growth trajectory group compared with the intermediate growth group (odds ratio (OR) 3.72; 95% CI 1.15, 12.05). Efforts to prevent childhood obesity may need to be embedded within population-wide strategies that also pay attention to healthy weight for women in their reproductive years.