Child stunting starts in utero: Growth trajectories and determinants in Ugandan infants.

Childhood stunting remains a public health burden worldwide. Although many studies have examined early life and in-utero risk factors; most have been observational and have used analytic techniques that make inferences limited to population means, thereby obscuring important within-group variations. This study addressed that important gap. Using data from a birth cohort of Ugandan infants (n = 4528), we applied group-based trajectory modelling to assess diverse patterns of growth among children from birth to 1-year old. A multinomial regression model was conducted to understand the relationship between risk factors and observed patterns across groups. We found that the onset of stunting occurred before birth and followed four distinct growth patterns: chronically stunted (Group 1), recovery (Group 2), borderline stunted (Group 3) and normal (Group 4). The average length-for-age z-score (LAZ) at birth was -2.6, -3.9, -0.6 and 0.5 for Groups 1-4, respectively. Although both Groups 1 and 2 were stunted at birth, stunting persisted in Group 1 while children in Group 2 recovered by the fourth month. Group 3 exhibited mild stunting while Group 4 was normal. Wasting and underweight were observed in all groups, with the highest prevalence of underweight in Group 1. Wasting gradually increased among children born already stunted (Groups 1 and 2). This showed the importance of distinguishing children by their growth patterns rather than aggregating them and only comparing population averages against global growth standards. The design of nutrition interventions should consider the differential factors and potential for growth gains relative to different risks within each group.

Prenatal dietary diversity may influence underweight in infants in a Ugandan birth-cohort.

Growth faltering in early childhood is prevalent in many low resource countries. Poor maternal dietary diversity during pregnancy has been linked with increased risk of fetal growth failure and adverse birth outcomes but may also influence subsequent infant growth. Our aim is to assess the role of prenatal maternal dietary diversity in infant growth in rural Uganda. Data from 3291 women and infant pairs enrolled in a birth cohort from 2014 to 2016 were analysed (NCT04233944). Maternal diets were assessed using dietary recall in the second or third trimesters of pregnancy. Maternal dietary diversity scores (DDS) were calculated using the FAO Minimum Dietary Diversity for Women (MDD-W). Cox regression models were used to evaluate associations of the DDS with the incidence of underweight, stunting and wasting in infants from 3 to 12 months, adjusting for confounding factors. The median DDS for women was low, at 3.0 (interquartile range 3.0-4.0), relative to the threshold of consuming five or more food groups daily. Infants of women in highest quartile of DDS (diverse diets) were less likely to be underweight (adjusted hazard ratio: 0.70, 95% confidence interval: 0.61, 0.80) compared with infants of women in Quartile 1 (p for trend <0.001) in models controlling for maternal factors. There was no significant association between DDS and stunting or wasting. Our findings suggest a relationship between higher maternal dietary diversity and lower risk of underweight in infancy. These findings suggest that programmes to improve infant growth could additionally consider strengthening prenatal dietary diversity to improve child outcomes globally.

Sustained intake of animal-sourced foods is associated with less stunting in young children.

The value of animal-sourced foods (ASFs) in providing key nutrients, particularly for child growth and where diets are of low quality, is understood mainly from cross-sectional assessment of current consumption. Longitudinal panel data from Nepal, Bangladesh and Uganda were used here to assess associations among previous (lagged) and contemporaneous ASF intake with linear growth of children aged 6-24 months. Lagged ASF consumption was significantly correlated with a 10% decline in stunting in Nepali children who consumed any ASF in the previous year, while current intake was associated with a 9% decline in stunting in Uganda. Previous consumption of two or more ASFs showed a stronger association, ranging from a 10% decline in stunting in Bangladesh to a 16% decline in Nepal. This novel lagged analysis emphasizes the need for regular and appropriate levels of ASF intake by young children to support healthy growth in resource-constrained settings.

Predictors of low birth weight and preterm birth in rural Uganda: Findings from a birth cohort study.

BACKGROUND: Approximately 20.5 million infants were born weighing <2500 g (defined as low birthweight or LBW) in 2015, primarily in low- and middle-income countries (LMICs). Infants born LBW, including those born preterm (<37 weeks gestation), are at increased risk for numerous consequences, including neonatal mortality and morbidity as well as suboptimal health and nutritional status later in life. The objective of this study was to identify predictors of LBW and preterm birth among infants in rural Uganda. METHODS: Data were derived from a prospective birth cohort study conducted from 2014-2016 in 12 districts across northern and southwestern Uganda. Birth weights were measured in triplicate to the nearest 0.1 kg by trained enumerators within 72 hours of delivery. Gestational age was calculated from the first day of last menstrual period (LMP). Associations between household, maternal, and infant characteristics and birth outcomes (LBW and preterm birth) were assessed using bivariate and multivariable logistic regression with stepwise, backward selection analyses. RESULTS: Among infants in the study, 4.3% were born LBW (143/3,337), and 19.4% were born preterm (744/3,841). In multivariable analysis, mothers who were taller (>150 cm) (adjusted Odds Ratio (aOR) = 0.42 (95% CI = 0.24, 0.72)), multigravida (aOR = 0.62 (95% CI = 0.39, 0.97)), or with adequate birth spacing (>24 months) (aOR = 0.60 (95% CI = 0.39, 0.92)) had lower odds of delivering a LBW infant Mothers with severe household food insecurity (aOR = 1.84 (95% CI = 1.22, 2.79)) or who tested positive for malaria during pregnancy (aOR = 2.06 (95% CI = 1.10, 3.85)) had higher odds of delivering a LBW infant. In addition, in multivariable analysis, mothers who resided in the Southwest (aOR = 0.64 (95% CI = 0.54, 0.76)), were ≥20 years old (aOR = 0.76 (95% CI = 0.61, 0.94)), with adequate birth spacing (aOR = 0.76 (95% CI = 0.63, 0.93)), or attended ≥4 antenatal care (ANC) visits (aOR = 0.56 (95% CI = 0.47, 0.67)) had lower odds of delivering a preterm infant; mothers who were neither married nor cohabitating (aOR = 1.42 (95% CI = 1.00, 2.00)) or delivered at home (aOR = 1.25 (95% CI = 1.04, 1.51)) had higher odds. CONCLUSIONS: In rural Uganda, severe household food insecurity, adolescent pregnancy, inadequate birth spacing, malaria infection, suboptimal ANC attendance, and home delivery represent modifiable risk factors associated with higher rates of LBW and/or preterm birth. Future studies on interventions to address these risk factors may be warranted.

Markers of Environmental Enteric Dysfunction Are Associated with Poor Growth and Iron Status in Rural Ugandan Infants.

BACKGROUND: Environmental enteric dysfunction (EED), characterized by altered intestinal permeability/inflammation, microbial translocation, and systemic inflammation (SI), may be a significant contributor to micronutrient deficiencies and poor growth in infants from low-resource settings. OBJECTIVE: We examined associations among EED, SI, growth, and iron status at 6 mo of age. METHODS: We performed a cross-sectional analysis of 6-mo-old infants (n = 548) enrolled in a Ugandan birth-cohort study (NCT04233944). EED was assessed via serum concentrations of anti-flagellin and anti- LPS immunoglobulins (Igs); SI was assessed via serum concentrations of ɑ1-acid glycoprotein (AGP) and C-reactive protein (CRP); iron status was assessed via serum concentrations of hemoglobin (Hb), soluble transferrin receptor (sTfR), and ferritin. Associations were assessed using adjusted linear regression analysis. RESULTS: At 6 mo, ∼35% of infants were stunted [length-for-age z score (LAZ) < -2] and ∼53% were anemic [hemoglobin (Hb) <11.0 g/dL]. Nearly half (∼46%) had elevated AGP (>1 g/L) and ∼30% had elevated CRP (>5 mg/L). EED and SI biomarkers were significantly correlated (r = 0.142-0.193, P < 0.001 for all). In adjusted linear regression models, which included adjustments for SI, higher anti-flagellin IgA, anti-LPS IgA, and anti-LPS IgG concentrations were each significantly associated with lower LAZ [ß (95% CI): -0.21 (-0.41, 0.00), -0.23 (-0.44, -0.03), and -0.33 (-0.58, -0.09)]. Furthermore, higher anti-flagellin IgA, anti-flagellin IgG, and anti-LPS IgA concentrations were significantly associated with lower Hb [ß (95% CI): -0.24 (-0.45, -0.02), -0.58 (-1.13, 0.00), and -0.26 (-0.51, 0.00)] and higher anti-flagellin IgG and anti-LPS IgG concentrations were significantly associated with higher sTfR [ß (95% CI): 2.31 (0.34, 4.28) and 3.13 (0.75, 5.51)]. CONCLUSIONS: EED is associated with both low LAZ and iron status in 6-mo-old infants. Further research on the mechanisms by which EED affects growth and micronutrient status is warranted.

Unsafe Drinking Water Is Associated with Environmental Enteric Dysfunction and Poor Growth Outcomes in Young Children in Rural Southwestern Uganda.

Environmental enteric dysfunction (EED), a subclinical disorder of the small intestine, and poor growth are associated with living in poor water, sanitation, and hygiene (WASH) conditions, but specific risk factors remain unclear. Nested within a birth cohort study, this study investigates relationships among water quality, EED, and growth in 385 children living in southwestern Uganda. Water quality was assessed using a portable water quality test when children were 6 months, and safe water was defined as lacking Escherichia coli contamination. Environmental enteric dysfunction was assessed using the lactulose:mannitol (L:M) test at 12-16 months. Anthropometry and covariate data were extracted from the cohort study, and associations were assessed using linear and logistic regression models. Less than half of the households (43.8%) had safe water, and safe versus unsafe water did not correlate with improved versus unimproved water source. In adjusted linear regression models, children from households with safe water had significantly lower log-transformed (ln) L:M ratios (ß: -0.22, 95% confidence interval (CI): -0.44, -0.00) and significantly higher length-for-age (ß: 0.29, 95% CI: 0.00, 0.58) and weight-for-age (ß: 0.20, 95% CI: 0.05, 0.34) Z-scores at 12-16 months. Furthermore, in adjusted linear regression models, ln L:M ratios at 12-16 months significantly decreased with increasing length-for-age Z-scores at birth, 6 months, and 9 months (ß: -0.05, 95% CI: -0.10, -0.004; ß: -0.06, 95% CI: -0.11, -0.006; and ß: -0.05, 95% CI: -0.09, -0.005, respectively). Overall, our data suggest that programs seeking to improve nutrition should address poor WASH conditions simultaneously, particularly related to household drinking water quality.