Predictors of change in early child development among children with stunting: Secondary analysis of a randomized trial in Uganda.

Millions of children under 5 years in low- and middle-income countries fail to attain their development potential with accruing short- and long-term consequences. Low length/height for age (stunting) is known to be a key factor, but there is little data on how child characteristics are linked with developmental changes among children with stunting. We assessed the socioeconomic, household, anthropometric, and clinical predictors of change in early child development (ECD) among 1-5-year-old children with stunting. This was a prospective cohort study nested in a randomized trial testing effects of lipid-based nutrient supplementation among children with stunting in Uganda. Development was assessed using the Malawi Development Assessment Tool (MDAT). Multiple linear regression analysis was used to assess for predictors of change. We included 750 children with mean ±SD age of 30.2 ±11.7 months 45% of whom were female. After 12 weeks, total MDAT z-score increased by 0.40 (95%CI: 0.32; 0.48). Moderate vs severe stunting, higher fat-free mass, negative malaria test and no inflammation (serum α-1-acid glycoprotein <1 g/l) at baseline predicted greater increase in ECD scores. Older age and fat mass gain predicted a lesser increase in ECD. Our findings reinforce the link between stunting and development with more severely stunted children having a lesser increase in ECD scores over time. Younger age, freedom from malaria and inflammation, and higher fat-free mass at baseline, as well as less gain of fat mass during follow-up predicted a higher increase in developmental scores in this study. Thus, supporting fat-free mass accretion, focusing on younger children, and infection prevention may improve development among children with stunting.

Correlates of Body Composition in Children with Stunting: A Cross-sectional Study in Uganda.

BACKGROUND: Development of body composition (BC) may be disrupted in children with stunting. Such disruption may affect the later risk of excess adiposity and metabolic health, yet few studies have investigated correlates of BC in children with stunting. OBJECTIVES: We aimed to investigate nutritional status, infection and inflammation, breastfeeding behaviors, and other factors as correlates of BC in children with stunting. METHODS: Among Ugandan children with a height-for-age z-score <-2, BC was estimated using bioelectrical impedance analysis and compared with United Kingdom references. We used multiple linear regression analysis to identify correlates of fat mass (FM), fat-free mass (FFM), FM-index (FMI), and FFM index (FFMI) and height, adjusting for gender and age. RESULTS: In 750 children aged 1-5 y, FMI was 0.46 (95% confidence interval [CI]: 0.38, 0.54] and FFMI 0.18 [95% CI: 0.11, 0.26) z-scores lower than United Kingdom references. Elevated serum α1-acid glycoprotein was associated with 1.14 [0.76, 1.52] cm lower height, 0.50 [0.35, 0.65] kg/m2 less FFMI, and 0.48 [0.31, 0.66] kg/m2 greater FMI. Similar, weaker, associations for elevated serum C-reactive protein were detected. A positive malaria rapid test was associated with 0.64 [0.25, 1.02] cm shorter height, but 0.36 [0.18, 0.54] kg/m2 greater FMI. Anemia (according to hemoglobin) was associated with 0.20 [0.07, 0.33] kg less FFM in proportion to shorter height. Longer breastfeeding duration was associated with 0.03 [0.02, 0.04] kg greater FFM per month, in proportion to greater height. CONCLUSIONS: These children exhibited deficits in FM and FFM, proportionally to their stunted height, compared with United Kingdom references. Systemic inflammation correlated inversely with linear growth and FFM but positively with fatness, making it a possible target for intervention where fat-free tissue accretion is desirable. Longer breastfeeding may offer protection to lean linear growth, but findings for micronutrients were less clear. Longitudinal studies are warranted to support these findings. The study was registered at www.isrctn.com (Ref. ISRCTN13093195).

The incretin effect in type 2 diabetes in a Sub-Saharan African population.

AIM: Type 2 diabetes is increasing in Sub-Saharan Africa, but the pathophysiology in this population is poorly investigated. In Western populations, the incretin effect is reduced in type 2 diabetes, leading to lowered insulin secretion. The aim of this study was to investigate the incretin effect in a group of Sub-Saharan Africans with type 2 diabetes. METHODS: Twenty adults diagnosed with type 2 diabetes, based on either an oral glucose tolerance test (n = 10) or on glycated hemoglobin A1c (n = 10), and 10 non-diabetic controls were included in an interventional study in Tanzania. We investigated the incretin effect as the difference between the plasma insulin area under the curve during an oral glucose tolerance test and that obtained during an intravenous glucose infusion. Differences between diabetes groups were analyzed by Kruskal-Wallis one-way analysis of variance. RESULTS: The incretin effect did not differ between groups (p = 0.45), and there was no difference in plasma concentrations of the incretin hormones during the OGTT. CONCLUSION: A reduced incretin effect appears not to contribute to hyperglycemia in type 2 diabetes in this Tanzanian population. More research is needed to explain the diabetes phenotype often seen in Sub-Saharan Africa. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03106480 , date of registration: 04/10/2017.

Developmental and Nutritional Changes in Children with Severe Acute Malnutrition Provided with n-3 Fatty Acids Improved Ready-to-Use Therapeutic Food and Psychosocial Support: A Pilot Study in Tanzania.

Children with severe acute malnutrition (SAM) are at high risk of impaired development. Contributing causes include the inadequate intake of specific nutrients such as polyunsaturated fatty acids (PUFAs) and a lack of adequate stimulation. We conducted a pilot study assessing developmental and nutritional changes in children with SAM provided with a modified ready-to-use therapeutic food and context-specific psychosocial intervention in Mwanza, Tanzania. We recruited 82 children with SAM (6-36 months) and 88 sex- and age-matched non-malnourished children. We measured child development, using the Malawi Development Assessment Tool (MDAT), measures of family and maternal care for children, and whole-blood PUFA levels. At baseline, the mean total MDAT z-score of children with SAM was lower than non-malnourished children; -2.37 (95% confidence interval: -2.92; -1.82), as were their total n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. After 8 weeks of intervention, MDAT z-scores improved in all domains, especially fine motor, among children with SAM. Total n-3 and EPA levels increased, total n-6 fatty acids decreased, and DHA remained unchanged. Family and maternal care also improved. The suggested benefits of the combined interventions on the developmental and nutritional status of children with SAM will be tested in a future trial.

Associations of early childhood body mass index trajectories with body composition and cardiometabolic markers at age 10 years: the Ethiopian infant anthropometry and body composition (iABC) birth cohort study.

BACKGROUND: Variability in body mass index (BMI) (kg/m2) trajectories is associated with body composition and cardiometabolic markers in early childhood, but it is unknown how these associations track to later childhood. OBJECTIVES: We aimed to assess associations of BMI trajectories from 0 to 5 y with body composition and cardiometabolic markers at 10 y. METHODS: In the Ethiopian infant anthropometry and body composition (iABC) birth cohort, we previously identified 4 distinct BMI trajectories from 0 to 5 y: stable low BMI (19.2%), normal BMI (48.8%), rapid growth to high BMI (17.9%), and slow growth to high BMI (14.1%). At 10 y, we obtained data from 320 children on anthropometry, body composition, abdominal subcutaneous and visceral fat, and cardiometabolic markers. Associations of BMI trajectories and 10-y outcomes were analyzed using multiple linear regression. RESULTS: Compared with children with the normal BMI trajectory, those with rapid growth to high BMI had 1.7 cm (95% CI: 0.1, 3.3) larger waist circumference and those with slow growth to high had 0.63 kg/m2 (95% CI: 0.09, 1.17) greater fat mass index and 0.19 cm (95% CI: 0.02, 0.37) greater abdominal subcutaneous fat, whereas those with stable low BMI had -0.28 kg/m2 (95% CI: -0.59, 0.03) lower fat-free mass at 10 y. Although the confidence bands were wide and included the null value, children with rapid growth to high BMI trajectory had 48.6% (95% CI: -1.4, 123.8) higher C-peptide concentration and those with slow growth to high BMI had 29.8% (95% CI: -0.8, 69.8) higher insulin and 30.3% (95% CI: -1.1, 71.6) higher homeostasis model assessment of insulin resistance, whereas those with rapid growth to high BMI had -0.23 mmol/L (95% CI: -0.47, 0.02) lower total cholesterol concentration. The trajectories were not associated with abdominal visceral fat, blood pressure, glucose, and other lipids at 10 y. CONCLUSIONS: Children with rapid and slow growth to high BMI trajectories before 5 y tend to show higher measures of adiposity and higher concentrations of markers related to glucose metabolism at 10 y. CLINICAL TRIAL REGISTRY: ISRCTN46718296 (https://www.isrctn.com/ISRCTN46718296).

Correlates of early child development among children with stunting: A cross-sectional study in Uganda.

Many children in low- and middle-income countries are not attaining their developmental potential. Stunting is associated with poor child development, but it is not known which correlates of stunting are impairing child development. We explored potential socioeconomic, nutritional, clinical, and household correlates of early child development among 12-59-month-old children with stunting in a cross-sectional study in Uganda. Development was assessed using the Malawi Development Assessment Tool (MDAT) across four domains of gross and fine motor, language, and social skills. Linear regression analysis was used to assess correlates of development in the four domains and total MDAT score. Of 750 children included, the median [interquartile range] age was 30 [23-41] months, 55% of the children resided in rural settings with 21% from female-headed households and 47% of mothers had no schooling. The mean ± standard deviation height-for-age z-score (HAZ) was -3.02 ± 0.74, 40% of the children had a positive malaria test and 65% were anaemic (haemoglobin < 110 g/L). One-third had children's books at home, majority (96%) used household objects to play with and most of them (70%) used toys as pretence items like those to mimic cooking. After age, sex, and site adjustments, HAZ (0.24, 95% confidence interval [CI]: 0.14-0.33) and head circumference (0.07, 95% CI: 0.02-0.12) were positive correlates of total MDAT score, whereas weight-for-height z-score (WHZ) was not. Current breastfeeding was associated with 0.41 (95% CI: 0.17-0.65) lower total MDAT score. Children from households with a single income earner had 0.22 (95% CI: 0.06-0.37) lower total MDAT score. Furthermore, severe food insecurity, inflammation and positive malaria test were associated with lower scores for motor development. All family care indicator subscales (FCIs) positively correlated with the total MDAT score and this association was independent of household's socioeconomic status. In conclusion, stunting degree, head circumference, number of household income earners and stimulation by improved FCIs correlate with early child development among stunted children. The negative association with prolonged breastfeeding is likely due to reverse causality. Identified correlates may inform initiatives to support children with stunting attain their development potential.

Effect of lipid-based nutrient supplements on micronutrient status and hemoglobin among children with stunting: secondary analysis of a randomized controlled trial in Uganda.

BACKGROUND: Micronutrient deficiencies and anemia are widespread among children with stunting. OBJECTIVES: We assessed the effects of lipid-based nutrient supplements (LNS) containing milk protein (MP) and/or whey permeate (WP) on micronutrient status and hemoglobin (Hb) among children with stunting. METHODS: This was a secondary analysis of a randomized controlled trial. Children aged 12-59 mo with stunting were randomly assigned to LNS (100 g/d) with milk or soy protein and WP or maltodextrin for 12 wk, or no supplement. Hb, serum ferritin (S-FE), serum soluble transferrin receptor (S-TfR), plasma cobalamin (P-Cob), plasma methylmalonic acid (P-MMA), plasma folate (P-Fol), and serum retinol-binding protein (S-RBP) were measured at inclusion and at 12 wk. Data were analyzed using linear and logistic mixed-effects models. RESULTS: Among 750 children, with mean age ± SD of 32 ± 11.7 mo, 45% (n = 338) were female and 98% (n = 736) completed follow-up. LNS, compared with no supplementation, resulted in 43% [95% confidence interval (CI): 28, 60] greater increase in S-FE corrected for inflammation (S-FEci), 2.4 (95% CI: 1.2, 3.5) mg/L greater decline in S-TfR, 138 (95% CI: 111, 164) pmol/L greater increase in P-Cob, 33% (95% CI: 27, 39) reduction in P-MMA, and 8.5 (95% CI: 6.6, 10.3) nmol/L greater increase in P-Fol. There was no effect of LNS on S-RBP. Lactation modified the effect of LNS on markers of cobalamin status, reflecting improved status among nonbreastfed and no effects among breastfed children. LNS increased Hb by 3.8 (95% CI: 1.7, 6.0) g/L and reduced the odds of anemia by 55% (odds ratio: 0.45, 95% CI: 0.29, 0.70). MP compared with soy protein increased S-FEci by 14% (95% CI: 3, 26). CONCLUSIONS: LNS supplementation increases Hb and improves iron, cobalamin, and folate status, but not vitamin A status among children with stunting. LNS should be considered for children with stunting. This trial was registered at ISRCTN as 13093195.

Correlates of Plasma Citrulline, a Potential Marker of Enterocyte Mass, among Children with Stunting: A Cross-Sectional Study in Uganda.

BACKGROUND: Environmental enteric dysfunction (EED) is associated with stunting. Citrulline, produced in mature enterocytes, may be a valuable biomarker of small intestinal enterocyte mass in the context of EED. OBJECTIVES: We aimed to explore the correlates of plasma citrulline (p-cit) in children with stunting. METHODS: In a cross-sectional study using baseline data from the community-based MAGNUS (milk affecting growth, cognition and the gut in child stunting) trial (ISRCTN13093195), we explored potential correlates of p-cit in Ugandan children with stunting aged 12-59 mo. Using linear regression in univariate and multivariate models, we explored associations with socioeconomics, diet, micronutrient status, and water, sanitation, and hygiene characteristics. The influence of covariates age, fasting, and systemic inflammation were also explored. RESULTS: In 750 children, the mean ± standard deviation age was 32.0 ± 11.7 mo, and height-for-age z-score was -3.02 ± 0.74. P-cit, available for 730 children, differed according to time fasted and was 20.7 ± 8.9, 22.3 ± 10.6 and 24.2 ± 13.1 µmol/L if fasted <2, 2-5 and >5 h, respectively. Positive correlates of p-cit were age [0.07; 95% confidence interval (CI): 0.001, 0.15 µmol/L] and log10 serum insulin-like growth factor-1 (8.88; 95% CI: 5.09, 12.67 µmol/L). With adjustment for systemic inflammation, the association with serum insulin-like growth factor-1 reduced (4.98; 95% CI: 0.94, 9.03 µmol/L). Negative correlates of p-cit included food insecurity, wet season (-3.12; 95% CI: -4.97, -1.26 µmol/L), serum C-reactive protein (-0.15; 95% CI: -0.20, -0.10 µmol/L), serum α1-acid glycoprotein (-5.34; 95% CI: -6.98, -3.70 µmol/L) and anemia (-1.95; 95% CI: -3.72, -0.18 µmol/L). Among the negatively correlated water, sanitation, and hygiene characteristics was lack of soap for handwashing (-2.53; 95% CI: -4.82, -0.25 µmol/L). Many associations attenuated with adjustment for inflammation. CONCLUSIONS: Many of the correlates of p-cit are characteristic of populations with a high EED prevalence. Systemic inflammation is strongly associated with p-cit and is implicated in EED and stunting. Adjustment for systemic inflammation attenuates many associations, reflecting either confounding, mediation, or both. This study highlights the complex interplay between p-cit and systemic inflammation.

Growth and Body Composition 5 y After Treatment for Severe Acute Malnutrition: A 5-y Prospective Matched Cohort Study in Ethiopian Children.

BACKGROUND: Short-term anthropometric outcomes are well documented for children treated for severe acute malnutrition (SAM). However, anthropometric recovery may not indicate restoration of healthy body composition. OBJECTIVES: This study aimed to evaluate long-term associations of SAM with growth and body composition of children 5 y after discharge from community-based management of acute malnutrition (CMAM). METHODS: We conducted a 5-y prospective cohort study, enrolling children aged 6 to 59 mo discharged from CMAM (post-SAM) (n = 203) and nonmalnourished matched controls (n = 202) from Jimma Zone, Ethiopia in 2013. Anthropometry and body composition (bioelectrical impedance) were assessed. Multiple linear regression models tested differences in height-for-age (HAZ), weight-for-age (WAZ), and body mass index-for-age (BAZ) z-scores; height-adjusted fat-free mass index (FFMI); and FM index (FMI) between groups. RESULTS: Post-SAM children had higher stunting prevalence than controls at discharge (82.2% compared with 36.0%; P < 0.001), 1 y (80.2% compared with 53.7%; P < 0.001), and 5 y postdischarge (74.2% compared with 40.8%; P < 0.001). Post-SAM children remained 5 cm shorter throughout follow-up, indicating no HAZ catch-up. No catch-up in WAZ or BAZ was observed. Post-SAM children had lower hip (-2.05 cm; 95% CI: -2.73, -1.36), waist (-0.92 cm; CI: -1.59, -0.23) and mid-upper arm (-0.64 cm; CI: -0.90, -0.42) circumferences and lower-limb length (-1.57 cm; 95% CI: -2.21, -0.94) at 5 y postdischarge. They had larger waist-hip (0.02 cm; 95% CI: 0.008, 0.033) and waist-height (0.013 cm; 95% CI: 0.004, 0.021) ratios, and persistent deficits in FFMI at discharge and 6 mo and 5 y postdischarge (P < 0.001 for all). No difference was detected in head circumference, sitting height, or FMI. CONCLUSIONS: Five y after SAM treatment, children maintained deficits in HAZ, WAZ, BAZ, and FFMI, with preservation of FMI, sitting height, and head circumference at the expense of lower-limb length, indicating a "thrifty growth" pattern. Research is urgently needed to identify effective clinical and public health interventions to mitigate these consequences of malnutrition.

The Associations of Breastfeeding Status at 6 Months with Anthropometry, Body Composition, and Cardiometabolic Markers at 5 Years in the Ethiopian Infant Anthropometry and Body Composition Birth Cohort.

(1) Background: Breastfeeding (BF) has been shown to lower the risk of overweight and cardiometabolic disease later in life. However, evidence from low-income settings remains sparse. We examined the associations of BF status at 6 months with anthropometry, body composition (BC), and cardiometabolic markers at 5 years in Ethiopian children. (2) Methods: Mother-child pairs from the iABC birth cohort were categorised into four BF groups at 6 months: 1. "Exclusive", 2. "Almost exclusive", 3. "Predominantly" and 4. "Partial or none". The associations of BF status with anthropometry, BC, and cardiometabolic markers at 5 years were examined using multiple linear regression analyses in three adjustment models. (3) Results: A total of 306 mother-child pairs were included. Compared with "Exclusive", the nonexclusive BF practices were associated with a lower BMI, blood pressure, and HDL-cholesterol at 5 years. Compared with "Exclusive", "Predominantly" and "Almost exclusive" had shorter stature of -1.7 cm (-3.3, -0.2) and -1.2 cm (-2.9, 0.5) and a lower fat-free mass index of -0.36 kg/m2 (-0.71, -0.005) and -0.38 kg/m2 (-0.76, 0.007), respectively, but a similar fat mass index. Compared with "Exclusive", "Predominantly" had higher insulin of 53% (2.01, 130.49), "Almost exclusive" had lower total and LDL-cholesterol, and "Partial or none" had a lower fat mass index. (5) Conclusions: Our data suggest that children exclusively breastfed at 6 months of age are overall larger at 5 years, with greater stature, higher fat-free mass but similar fat mass, higher HDL-cholesterol and blood pressure, and lower insulin concentrations compared with predominantly breastfed children. Long-term studies of the associations between BF and metabolic health are needed to inform policies.

Micronutrient Status and Other Correlates of Hemoglobin among Children with Stunting: A Cross-Sectional Study in Uganda.

In low-income countries, undernutrition and infections play a major role in childhood anemia. Stunted children may be at particular risk of anemia. In a cross-sectional study nested in a nutrition trial among 12-59-month-old stunted children in eastern Uganda, we measured hemoglobin (Hb) and markers of iron, cobalamin, folate and vitamin A status. We assessed low micronutrient status, socio-demography, stunting severity, inflammation and malaria as correlates of Hb and anemia using linear and logistic regression analyses, respectively. Of 750 stunted children, the mean ± SD age was 32.0 ± 11.7 months and 55% (n = 412) were male. The mean Hb was 104 ± 15 g/L and 65% had anemia, Hb < 110 g/L. In a multivariable model with age, sex and inflammation, the following were associated with lower Hb: serum ferritin < 12 µg/L (-5.6 g/L, 95% CI: -8.6; -2.6), transferrin receptors > 8.3 mg/L (-6.2 g/L, 95% CI: -8.4; -4.0), plasma folate <20 nmol/L (-4.6 g/L, 95% CI: -8.1;-1.1), cobalamin < 222 pmol/L (-3.0 g/L, 95% CI: -5.4; -0.7) and serum retinol-binding protein < 0.7 µmol/L (-2.0 g/L, 95% CI: -4.1; 0.2). In addition, severe stunting, inflammation and malaria were negative correlates. Anemia is common among stunted children in eastern Uganda; micronutrient deficiencies, inflammation and malaria are associated with low Hb.

Association of linear growth velocities between 0 and 6 years with kidney function and size at 10 years: A birth cohort study in Ethiopia.

BACKGROUND: Risk of noncommunicable diseases accrues from fetal life, with early childhood growth having an important role in adult disease risk. There is a need to understand how early-life growth relates to kidney function and size. OBJECTIVES: This study aimed to assess the association of linear growth velocities among children between 0 and 6 y with kidney function and size among children aged 10 y. METHODS: The Ethiopian Anthropometric and Body Composition birth cohort recruited infants born at term to mothers living in Jimma with a birth weight of ≥1500 g and without congenital malformations. Participants were followed up with 13 measurements between birth and 6 y of age. The latest follow-up was at ages 7-12 y with measurement of serum cystatin C as a marker of kidney function and ultrasound assessment of kidney dimensions. Kidney volume was computed using an ellipsoid formula. Linear-spline multilevel modeling was used to compute linear growth velocities between 0 and 6 y. Multiple linear regression modeling was used to examine the associations of linear growth velocities in selected age periods with cystatin C and kidney size. RESULTS: Data were captured from 355 children, at a mean age of 10 (range 7-12) y. The linear growth velocity was high between 0 and 3 mo and then decreased with age. There was no evidence of an association of growth velocity ≤24 mo with cystatin C at 10 y. Between 24 and 48 and 48 and 76 mo, serum cystatin C was higher by 2.3% [95% confidence interval (CI): 0.6, 4.2] and 2.1% (95% CI: 0.3, 4.0) for 1 SD higher linear growth velocity, respectively. We found a positive association between linear growth velocities at all intervals between 0 and 6 y and kidney volume. CONCLUSIONS: Greater linear growth between 0 and 6 y of development was positively associated with kidney size, and greater growth velocity after 2 y was associated with higher serum cystatin C concentrations.

Vitamin B12 Status before and after Outpatient Treatment of Severe Acute Malnutrition in Children Aged 6-59 Months: A Sub-Study of a Randomized Controlled Trial in Burkina Faso.

Severe acute malnutrition (SAM) is treated with ready-to-use therapeutic foods (RUTF) containing a vitamin-mineral premix. Yet little is known about micronutrient status in children with SAM before and after treatment. We aimed to investigate vitamin B12 status in children with uncomplicated SAM, aged 6-59 months in Burkina Faso, before and after treatment with a standard or a reduced dose of RUTF. Blood samples were collected at admission and discharge. Serum B12 was determined with microbiological assay and serum methylmalonic acid (MMA) and total homocysteine (tHcy) were analyzed with gas chromatography-tandem mass spectrometry. B12 status was classified using the combined indicator (3cB12). Among 374 children, the median [interquartile range] age was 11.0 [7.7-16.9] months, and 85.8% were breastfed. Marked or severe B12 deficiency, as judged by 3cB12, decreased from 32% to 9% between admission and discharge (p < 0.05). No differences in B12 status following treatment with either standard (n = 194) or reduced (n = 180) doses of RUTF were observed. Breastfed children showed a lower B12 status (3cB12) than non-breastfed ones (-1.10 vs -0.18, p < 0.001 at admission; -0.44 vs 0.19; p < 0.001 at discharge). In conclusion, treatment of SAM with RUTF improved children's B12 status but did not fully correct B12 deficiency.

Correlates of Iron, Cobalamin, Folate, and Vitamin A Status among Stunted Children: A Cross-Sectional Study in Uganda.

Micronutrient deficiencies and stunting are prevalent. We assessed correlates of iron, cobalamin, folate, and vitamin A biomarkers in a cross-sectional study of stunted children aged 12-59 months in eastern Uganda. The biomarkers measured were serum ferritin (S-FE), soluble transferrin receptor (S-TfR), retinol binding protein (S-RBP), plasma cobalamin (P-Cob), methylmalonic acid (P-MMA), and folate (P-Fol). Using linear regression, we assessed socio-demography, stunting severity, malaria rapid test, and inflammation as correlates of micronutrient biomarkers. Of the 750 children, the mean (SD) age was 32.0 (11.7) months, and 45% were girls. Iron stores were depleted (inflammation-corrected S-FE < 12 µg/L) in 43%, and 62% had tissue iron deficiency (S-TfR > 8.3 mg/L). P-Cob was low (<148 pmol/L) and marginal (148-221 pmol/L) in 3% and 20%, and 16% had high P-MMA (>0.75 µmol/L). Inflammation-corrected S-RBP was low (<0.7 µmol/L) in 21% and P-Fol (<14 nmol/L) in 1%. Age 24-59 months was associated with higher S-FE and P-Fol and lower S-TfR. Breastfeeding beyond infancy was associated with lower iron status and cobalamin status, and malaria was associated with lower cobalamin status and tissue iron deficiency (higher S-TfR) despite iron sequestration in stores (higher S-FE). In conclusion, stunted children have iron, cobalamin, and vitamin A deficiencies. Interventions addressing stunting should target co-existing micronutrient deficiencies.

Effect of Milk Protein and Whey Permeate in Large-Quantity Lipid-Based Nutrient Supplement on Early Child Development among Children with Stunting: A Randomized 2 × 2 Factorial Trial in Uganda.

Stunting affects 22% children globally, putting them at risk of adverse outcomes including delayed development. We investigated the effect of milk protein (MP) vs. soy and whey permeate (WP) vs. maltodextrin in large-quantity, lipid-based nutrient supplement (LNS), and LNS itself vs. no supplementation, on child development and head circumference among stunted children aged 1-5 years. We conducted a randomized, double-blind, community-based 2 × 2 factorial trial in Uganda (ISRCTN1309319). We randomized 600 children to one of four LNS formulations (~535 kcal/d), with or without MP (n = 299 vs. n = 301) or WP (n = 301 vs. n = 299), for 12 weeks or to no supplementation (n = 150). Child development was assessed using the Malawi Development Assessment Tool. Data were analyzed using linear mixed-effects models. Children had a median [interquartile range] age of 30 [23; 41] months and mean ± standard deviation height-for-age z-score of -3.02 ± 0.74. There were no interactions between MP and WP for any of the outcomes. There was no effect of either MP or WP on any developmental domain. Although LNS itself had no impact on development, it resulted in 0.07 (95%CI: 0.004; 0.14) cm higher head circumference. Neither dairy in LNS, nor LNS in itself, had an effect on development among already stunted children.

Associations of weight and body composition at birth with body composition and cardiometabolic markers in children aged 10 y: the Ethiopian infant anthropometry and body composition birth cohort study.

BACKGROUND: Although birth weight (BW) has been associated with later cardiovascular disease and type 2 diabetes, the role of birth fat mass (BFM) and birth fat-free mass (BFFM) on cardiometabolic health is unclear. OBJECTIVES: To examine associations of BW, BFM, and BFFM with later anthropometry, body composition, abdominal fat, and cardiometabolic markers. METHODS: Birth cohort data on standardized exposure variables (BW, BFM, and BFFM) and follow-up information at age 10 y on anthropometry, body composition, abdominal fat, and cardiometabolic markers were included. A linear regression analysis was used to assess associations of exposures with outcome variables, adjusting for maternal and child characteristics at birth and current body size in separate models. RESULTS: Among 353 children, mean (SD) age was 9.8 (1.0) y, and 51.5% were boys. In the fully adjusted model, 1-SD higher BW and BFFM were associated with 0.81 cm (95% CI: 0.21, 1.41 cm) and 1.25 cm (95% CI: 0.64, 1.85 cm) greater height at 10 y, respectively. The 1-SD higher BW and BFM were associated with 0.32 kg/m2 (95% CI: 0.14, 0.51 kg/m2) and 0.42 kg/m2 (95% CI: 0.25, 0.59 kg/m2) greater fat mass index at 10 y, respectively. In addition, 1-SD higher BW and BFFM were associated with 0.22 kg/m2 (95% CI: 0.09, 0.34 kg/m2) greater FFM index, whereas a 1-SD greater BFM was associated with a 0.05 cm greater subcutaneous adipose tissue (95% CI: 0.01, 0.11 cm). Furthermore, 1-SD higher BW and BFFM were associated with 10.3% (95% CI: 1.4%, 20.0%) and 8.3% (95% CI: -0.5%, 17.9%) greater insulin, respectively. Similarly, 1-SD higher BW and BFFM were associated with 10.0% (95% CI: 0.9%, 20.0%) and 8.5% (95% CI: -0.6%, 18.5%) greater homeostasis model assessment of insulin resistance, respectively. CONCLUSIONS: BW and BFFM rather than BFM are predictors of height and FFM index at 10 y. Children with higher BW and BFFM showed higher insulin concentrations and homeostasis model assessment of insulin resistance at 10 y of age. This trial was registered at ISRCTN as ISRCTN46718296.

Dietary patterns and diabetes mellitus among people living with and without HIV: a cross-sectional study in Tanzania.

Background: Due to the complexity of human diets, it is difficult to relate single foods to health outcomes. We aimed to identify the dietary patterns and associated factors and to assess the association of dietary patterns with prediabetes/diabetes among adults living with and without HIV in Tanzania. Methods: Diet data were collected by a food frequency questionnaire (FFQ) and dietary patterns were derived by principal component analysis (PCA) and reduced rank regression (RRR). The associations between dietary patterns and associated factors as well as with prediabetes/diabetes were assessed using multinomial logistic regression and presented by marginal plots. Results: Of 572 recruited, 63% were people living with HIV. The mean (±SD) age was 42.6 (±11.7) years and 60% were females. The PCA identified two major dietary patterns, i.e., vegetable-rich pattern (VRP) and vegetable-poor pattern (VPP) whereas RRR identified one dietary pattern, i.e., carbohydrate-dense pattern (CDP). In comparison to females, males had higher adherence to VPP and CDP, but less to VRP. Higher socioeconomic status was associated with higher adherence to VRP and VPP but low adherence to CDP. Compared to HIV-negative participants, people living with HIV had higher adherence to VRP but less adherence to CDP. Compared to younger people, older people had lower adherence to VPP. High adherence to CDP or VRP was positively associated with prediabetes. Higher adherence to VRP was associated with a borderline decrease in diabetes. No association was observed between VPP with either prediabetes or diabetes. Conclusion: Our findings suggest that dietary patterns may impact the risk of prediabetes and diabetes differently. Awareness of the health benefits of VRP should be encouraged in the community, especially for men who seem to consume fewer vegetables. Longitudinal studies are needed to explore the contribution of dietary patterns to prediabetes/diabetes development in sub-Saharan Africa.

Effect of milk protein and whey permeate in large quantity lipid-based nutrient supplement on linear growth and body composition among stunted children: A randomized 2 × 2 factorial trial in Uganda.

BACKGROUND: Despite possible benefits for growth, milk is costly to include in foods for undernourished children. Furthermore, the relative effects of different milk components, milk protein (MP), and whey permeate (WP) are unclear. We aimed to assess the effects of MP and WP in lipid-based nutrient supplement (LNS), and of LNS itself, on linear growth and body composition among stunted children. METHODS AND FINDINGS: We performed a randomized, double-blind, 2 × 2 factorial trial among 12 to 59 months old stunted children in Uganda. Children were randomized to 4 formulations of LNS with MP or soy protein isolate and WP or maltodextrin (100 g/day for 12 weeks) or no supplementation. Investigators and outcome assessors were blinded; however, participants were only blinded to the ingredients in LNS. Data were analyzed based on intention-to-treat (ITT) using linear mixed-effects models adjusted for age, sex, season, and site. Primary outcomes were change in height and knee-heel length, and secondary outcomes included body composition by bioimpedance analysis (ISRCTN13093195). Between February and September 2020, we enrolled 750 children with a median age of 30 (interquartile range 23 to 41) months, with mean (± standard deviation) height-for-age z-score (HAZ) -3.02 ± 0.74 and 12.7% (95) were breastfed. The 750 children were randomized to LNS (n = 600) with or without MP (n = 299 versus n = 301) and WP (n = 301 versus n = 299), or no supplementation (n = 150); 736 (98.1%), evenly distributed between groups, completed 12-week follow-up. Eleven serious adverse events occurred in 10 (1.3%) children, mainly hospitalization with malaria and anemia, all deemed unrelated to the intervention. Unsupplemented children had 0.06 (95% confidence interval, CI [0.02, 0.10]; p = 0.015) decline in HAZ, accompanied by 0.29 (95% CI [0.20, 0.39]; p < 0.001) kg/m2 increase in fat mass index (FMI), but 0.06 (95% CI [-0.002; 0.12]; p = 0.057) kg/m2 decline in fat-free mass index (FFMI). There were no interactions between MP and WP. The main effects of MP were 0.03 (95% CI [-0.10, 0.16]; p = 0.662) cm in height and 0.2 (95% CI [-0.3, 0.7]; p = 0.389) mm in knee-heel length. The main effects of WP were -0.08 (95% CI [-0.21, 0.05]; p = 220) cm and -0.2 (95% CI [-0.7; 0.3]; p = 403) mm, respectively. Interactions were found between WP and breastfeeding with respect to linear growth (p < 0.02), due to positive effects among breastfed and negative effects among non-breastfed children. Overall, LNS resulted in 0.56 (95% CI [0.42, 0.70]; p < 0.001) cm height increase, corresponding to 0.17 (95% CI [0.13, 0.21]; p < 0.001) HAZ increase, and 0.21 (95% CI [0.14, 0.28]; p < 0.001) kg weight increase, of which 76.5% (95% CI [61.9; 91.1]) was fat-free mass. Using height-adjusted indicators, LNS increased FFMI (0.07 kg/m2, 95% CI [0.0001; 0.13]; p = 0.049), but not FMI (0.01 kg/m2, 95% CI [-0.10, 0.12]; p = 0.800). Main limitations were lack of blinding of caregivers and short study duration. CONCLUSIONS: Adding dairy to LNS has no additional effects on linear growth or body composition in stunted children aged 12 to 59 months. However, supplementation with LNS, irrespective of milk, supports linear catch-up growth and accretion of fat-free mass, but not fat mass. If left untreated, children already on a stunting trajectory gain fat at the expense of fat-free mass, thus nutrition programs to treat such children should be considered. TRIAL REGISTRATION: ISRCTN13093195.

Calibration of Bioelectrical Impedance Analysis Against Deuterium Dilution for Body Composition Assessment in Stunted Ugandan Children.

BACKGROUND: BIA represents an important tool in body composition (BC) assessment, especially in low-income settings in which simple and affordable options are preferred. There is a particular need to measure BC in stunted children, in which cases population-specific BIA estimating equations are lacking. OBJECTIVES: We calibrated an equation to estimate body composition from BIA using deuterium dilution (2H) as the criterion method in stunted children. METHODS: We measured BC with 2H and performed BIA in stunted Ugandan children (n = 50). Multiple linear regression models were constructed to predict 2H-derived FFM from BIA-derived whole-body impedance and other relevant predictors. Model performance was expressed as adjusted R2 and RMSE. Prediction errors were also calculated. RESULTS: Participants were aged 16-59 mo, of whom 46% were girls, and their median (IQR) height-for-age z-score (HAZ) was -2.58 (-2.92 to -2.37) according to the WHO growth standards. Impedance index (height2/impedance measured at 50 kHz) alone explained 89.2% variation in FFM and had an RMSE of 583 g (precision error 6.5%). The final model contained age, sex, impedance index, and height-for-age z-score as predictors and explained 94.5% variation in FFM with an RMSE of 402 g (precision error 4.5%). CONCLUSIONS: We present a BIA calibration equation for a group of stunted children with a relatively low prediction error. This may help evaluate the efficacy of nutritional supplementation in large-scale trials in the same population. J Nutr 20XX;xxx:xx.