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.

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 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.

HIV-Infected and HIV-Uninfected Western Kenyan Women Produce Equivalent Amounts of Breast Milk at 6 Wk and 6 Mo Postpartum: A Prospective Cohort Study Using Deuterium Oxide Dose-to-Mother Technique.

BACKGROUND: Regardless of their HIV serostatus, mothers are advised to exclusively breastfeed infants ≤6 mo postpartum. How this guidance impacts breast milk intake among HIV-exposed infants in varied contexts needs to be better understood. OBJECTIVES: The objective of this study was to compare breast milk intake of HIV-exposed and HIV-unexposed infants at 6 wk and 6 mo of age, as well as the associated factors. METHODS: In a prospective cohort design, which we followed from a western Kenya postnatal clinic, 68 full-term HIV-uninfected infants born to HIV-1-infected mothers (HIV-exposed) and 65 full-term HIV-uninfected infants born to HIV-uninfected mothers were assessed at 6 wk and 6 mo of age. Breast milk intake of infants (51.9% female) weighing 3.0-6.7 kg (at 6 wk of age) was determined using the deuterium oxide dose-to-mother technique. Student t test for independent samples compared the variations in breast milk intake between the 2 groups. Correlation analysis detected the associations between breast milk intake and maternal and infant factors. RESULTS: Daily breast milk intakes by HIV-exposed and HIV-unexposed infants were not significantly different at either 6 wk (721 ± 111 g/d and 719 ± 121 g/d, respectively) or 6 mo (960 ± 121 g/d and 963 ± 107 g/d, respectively) of age. Maternal factors that significantly correlated with infant breast milk intake were FFM at both 6 wk (r = 0.23; P < 0.05) and 6 mo (r = 0.36; P < 0.01) of age and weight at 6 mo postpartum (r = 0.28; P < 0.01). Infant factors that significantly correlated at 6 wk were birth weight (r = 0.27; P < 0.01), present weight (r = 0.47; P < 0.01), length-for-age z-score (r = 0.33; P < 0.01), and weight-for-age (r = 0.42; P > 0.01). At 6 mo, they were infant length-for-age (r = 0.38; P < 0.01), weight-for-length (r = 0.41; P > 0.01), and weight-for-age (r = 0.60; P > 0.01). CONCLUSIONS: Full-term breastfeeding infants born to HIV-1-infected and HIV-1-uninfected women attending standard Kenyan postnatal care clinics ≤6 mo of age in this resource-poor setting consume comparable amounts of breast milk. This trial was registered at clinicaltrials.gov as PACTR201807163544658.

Associations between Stunting, Wasting and Body Composition: A Longitudinal Study in 6- to 15-Month-Old Kenyan Children.

BACKGROUND: Early growth and body composition may influence the risk of obesity and health in adulthood. Few studies have examined how undernutrition is associated with body composition in early life. OBJECTIVES: We assessed stunting and wasting as correlates of body composition in young Kenyan children. METHODS: Nested in a randomized controlled nutrition trial, this longitudinal study assessed fat and fat-free mass (FM, FFM) using deuterium dilution technique among children at age 6 and 15 months. This trial was registered at http://controlled-trials.com/ (ISRCTN30012997). Cross-sectional and longitudinal associations between z-score categories of length-for-age (LAZ) or weight-for-length (WLZ) and FM, FFM, fat mass index (FMI), fat-free mass index (FFMI), triceps, and subscapular skinfolds were analyzed by linear mixed models. RESULTS: Among the 499 children enrolled, breastfeeding declined from 99% to 87%, stunting increased from 13% to 32%, and wasting remained at 2% to 3% between 6 and 15 mo. Compared with LAZ >0, stunted children had a 1.12 kg (95% CI: 0.88, 1.36; P < 0.001) lower FFM at 6 mo and increased to 1.59 kg (95% CI: 1.25, 1.94; P < 0.001) at 15 mo, corresponding to differences of 18% and 17%, respectively. When analyzing FFMI, the deficit in FFM tended to be less than proportional to children's height at 6 mo (P ≤ 0.060) but not at 15 mo (P > 0.40). Stunting was associated with 0.28 kg (95% CI: 0.09, 0.47; P = 0.004) lower FM at 6 mo. However, this association was not significant at 15 mo, and stunting was not associated with FMI at any time point. A lower WLZ was generally associated with lower FM, FFM, FMI, and FFMI at 6 and 15 mo. Differences in FFM, but not FM, increased with time, whereas FFMI differences did not change, and FMI differences generally decreased with time. CONCLUSIONS: Overall, low LAZ and WLZ among young Kenyan children were associated with reduced lean tissue, which may have long-term health consequences.

Measuring the impact of malaria infection on indicators of iron and vitamin A status: a systematic literature review and meta-analysis.

Inflammation and infections such as malaria affect estimates of micronutrient status. Medline, Embase, Web of Science, Scopus and the Cochrane library were searched to identify studies reporting mean concentrations of ferritin, hepcidin, retinol or retinol binding protein in individuals with asymptomatic or clinical malaria and healthy controls. Study quality was assessed using the US National Institute of Health tool. Random effects meta-analyses were used to generate summary mean differences. In total, forty-four studies were included. Mean ferritin concentrations were elevated by: 28·2 µg/l (95 % CI 15·6, 40·9) in children with asymptomatic malaria; 28·5 µg/l (95 % CI 8·1, 48·8) in adults with asymptomatic malaria; and 366 µg/l (95 % CI 162, 570) in children with clinical malaria compared with individuals without malaria infection. Mean hepcidin concentrations were elevated by 1·52 nmol/l (95 % CI 0·92, 2·11) in children with asymptomatic malaria. Mean retinol concentrations were reduced by: 0·11 µmol/l (95 % CI -0·22, -0·01) in children with asymptomatic malaria; 0·43 µmol/l (95 % CI -0·71, -0·16) in children with clinical malaria and 0·73 µmol/l (95 % CI -1·11, -0·36) in adults with clinical malaria. Most of these results were stable in sensitivity analyses. In children with clinical malaria and pregnant women, difference in ferritin concentrations were greater in areas with higher transmission intensity. We conclude that biomarkers of iron and vitamin A status should be statistically adjusted for malaria and the severity of infection. Several studies analysing asymptomatic infections reported elevated ferritin concentrations without noticeable elevation of inflammation markers, indicating a need to adjust for malaria status in addition to inflammation adjustments.

Serum cobalamin in children with moderate acute malnutrition in Burkina Faso: Secondary analysis of a randomized trial.

BACKGROUND: Among children with moderate acute malnutrition (MAM) the level of serum cobalamin (SC) and effect of food supplements are unknown. We aimed to assess prevalence and correlates of low SC in children with MAM, associations with hemoglobin and development, and effects of food supplements on SC. METHODS AND FINDINGS: A randomized 2 × 2 × 3 factorial trial was conducted in Burkina Faso. Children aged 6 to 23 months with MAM received 500 kcal/d as lipid-based nutrient supplement (LNS) or corn-soy blend (CSB), containing dehulled soy (DS) or soy isolate (SI) and 0%, 20%, or 50% of total protein from milk for 3 months. Randomization resulted in baseline equivalence between intervention groups. Data on hemoglobin and development were available at baseline. SC was available at baseline and after 3 and 6 months. SC was available from 1,192 (74.1%) of 1,609 children at baseline. The mean (±SD) age was 12.6 (±5.0) months, and 54% were females. Low mid-upper arm circumference (MUAC; <125 mm) was found in 80.4% (958) of the children and low weight-for-length z-score (WLZ; <-2) in 70.6% (841). Stunting was seen in 38.2% (456). Only 5.9% were not breastfed. Median (IQR) SC was 188 (137; 259) pmol/L. Two-thirds had SC ≤222 pmol/L, which was associated with lower hemoglobin. After age and sex adjustments, very low SC (<112 pmol/L) was associated with 0.21 (95% CI: 0.01; 0.41, p = 0.04) and 0.24 (95% CI: 0.06; 0.42, p = 0.01) z-score lower fine and gross motor development, respectively. SC data were available from 1,330 (85.9%) of 1,548 children followed up after 3 months and 398 (26.5%) of the 1,503 children after 6 months. Based on tobit regression, accounting for left censored data, and adjustments for correlates of missing data, the mean (95% CI) increments in SC from baseline to the 3- and 6-month follow-up were 72 (65; 79, p < 0.001) and 26 (16; 37, p < 0.001) pmol/L, respectively. The changes were similar among the 310 children with SC data at all 3 time points. Yet, the increase was 39 (20; 57, p < 0.001) pmol/L larger in children given LNS compared to CSB if based on SI (interaction, p < 0.001). No effect of milk was found. Four children died, and no child developed an allergic reaction to supplements. The main limitation of this study was that only SC was available as a marker of status and was missing from a quarter of the children. CONCLUSIONS: Low SC is prevalent among children with MAM and may contribute to impaired erythropoiesis and child development. The SC increase during supplementation was inadequate. The bioavailability and adequacy of cobalamin in food supplements should be reconsidered. TRIAL REGISTRATION: ISRCTN Registry ISRCTN42569496.

Association of postnatal severe acute malnutrition with pancreatic exocrine and endocrine function in children and adults: a systematic review.

Severe acute malnutrition may lead both concurrently and subsequently to malabsorption and impaired glucose metabolism from pancreatic dysfunction. We conducted a systematic review to investigate the associations of current and prior postnatal wasting malnutrition with pancreatic endocrine and exocrine functions in humans. We searched PubMed, Google Scholar, Web of Science and reference lists of retrieved articles, limited to articles in English published before 1 February 2022. We included sixty-eight articles, mostly cross-sectional or cohort studies from twenty-nine countries including 592 530 participants, of which 325 998 were from a single study. Many were small clinical studies from decades ago and rated poor quality. Exocrine pancreas function, indicated by duodenal fluid or serum enzymes, or faecal elastase, was generally impaired in malnutrition. Insulin production was usually low in malnourished children and adults. Glucose disappearance during oral and intravenous glucose tolerance tests was variable. Upon treatment of malnutrition, most abnormalities improved but frequently not to control levels. Famine survivors studied decades later showed ongoing impaired glucose tolerance with some evidence of sex differences. The similar findings from anorexia nervosa, famine survivors and poverty- or infection-associated malnutrition in low- and middle-income countries (LMIC) lend credence to results being due to malnutrition itself. Research using large, well-documented cohorts and considering sexes separately, is needed to improve prevention and treatment of exocrine and endocrine pancreas abnormalities in LMIC with a high burden of malnutrition and diabetes.

Anthropometry, body composition, early growth and chronic disease risk factors among Zambian adolescents exposed or not to perinatal maternal HIV.

Early life exposures and growth patterns may affect long-term risk of chronic non-communicable diseases (NCD). We followed up in adolescence two Zambian cohorts (n 322) recruited in infancy to investigate how two early exposures - maternal HIV exposure without HIV infection (HEU) and early growth profile - were associated with later anthropometry, body composition, blood lipids, Hb and HbA1c, blood pressure and grip strength. Although in analyses controlled for age and sex, HEU children were thinner, but not shorter, than HIV-unexposed, uninfected (HUU) children, with further control for socio-demographic factors, these differences were not significant. HEU children had higher HDL-cholesterol than HUU children and marginally lower HbA1c but no other biochemical or clinical differences. We identified three early growth profiles - adequate growth, declining and malnourished - which tracked into adolescence when differences in anthropometry and body fat were still seen. In adolescence, the early malnourished group, compared with the adequate group, had lower blood TAG and higher HDL, lower grip strength (difference: -1·87 kg, 95 % CI -3·47, -0·27; P = 0·02) and higher HbA1c (difference: 0·5 %, 95 % CI 0·2, 0·9; P = 0·005). Lower grip strength and higher HbA1c suggest the early malnourished children could be at increased risk of NCD in later life. Including early growth profile in analyses of HIV exposure reduced the associations between HIV and outcomes. The results suggest that perinatal HIV exposure may have no long-term effects unless accompanied by poor early growth. Reducing the risk of young child malnutrition may lessen children's risk of later NCD.

Anthropometry, body composition and chronic disease risk factors among Zambian school-aged children who experienced severe malnutrition in early childhood.

There is limited information as to whether people who experience severe acute malnutrition (SAM) as young children are at increased risk of overweight, high body fat and associated chronic diseases in later life. We followed up, when aged 7-12 years, 100 Zambian children who were hospitalised for SAM before age 2 years and eighty-five neighbourhood controls who had never experienced SAM. We conducted detailed anthropometry, body composition assessment by bioelectrical impedance and deuterium dilution (D2O) and measured blood lipids, Hb and HbA1c. Groups were compared by linear regression following multiple imputation for missing variables. Children with prior SAM were slightly smaller than controls, but differences, controlling for age, sex, socio-economic status and HIV exposure or infection, were significant only for hip circumference, suprailiac skinfold and fat-free mass index by D2O. Blood lipids and HbA1c did not differ between groups, but Hb was lower by 7·8 (95 % CI 0·8, 14·7) g/l and systolic blood pressure was 3·4 (95 % CI 0·4, 6·4) mmHg higher among the prior SAM group. Both anaemia and high HbA1c were common among both groups, indicating a population at risk for the double burden of over- and undernutrition and associated infectious and chronic diseases. The prior SAM children may have been at slightly greater risk than the controls; this was of little clinical significance at this young age, but the children should be followed when older and chronic diseases manifest.

ß-cell dysfunction and insulin resistance in relation to pre-diabetes and diabetes among adults in north-western Tanzania: a cross-sectional study.

OBJECTIVE: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of ß-cell dysfunction and insulin resistance on pre-diabetes and diabetes. METHODS: We included 1890 participants with mean age of 40.6 (SD11.9) years in a cross-sectional study among male and female adults in Tanzania during 2016 to 2017. Data on C-reactive protein (CRP), alpha-acid glycoprotein (AGP), HIV, oral glucose tolerance test (OGTT), body composition and insulin were collected. Insulinogenic index and HOMA-IR were used to derive an overall marker of ß-cell dysfunction and insulin resistance which was categorised as follows: normal ß-cell function and insulin sensitivity, isolated ß-cell dysfunction, isolated insulin resistance, and combined ß-cell dysfunction and insulin resistance. Pre-diabetes and diabetes were defined as 2-hour OGTT glucose between 7.8-11.0 and ≥ 11.1 mmol/L, respectively. Multinomial regression assessed the association of ß-cell dysfunction and insulin resistance with outcome measures. RESULTS: ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated ß-cell dysfunction (adjusted relative risk ratio (aRRR) 4.8 (95% confidence interval (CI) 2.5, 9.0), isolated insulin resistance (aRRR 3.2 (95% CI 1.5, 6.9), and combined ß-cell dysfunction and insulin resistance (aRRR 35.9 (95% CI 17.2, 75.2) were associated with higher diabetes risk. CRP, AGP and HIV were associated with higher diabetes risk, but fat mass was not. 31%, 10% and 33% of diabetes cases were attributed to ß-cell dysfunction, insulin resistance, and combined ß-cell dysfunction and insulin resistance, respectively. CONCLUSIONS: ß-cell dysfunction seemed to explain most of diabetes cases compared to insulin resistance in this population. Cohort studies on evolution of diabetes in Africa are needed to confirm these results.

Thymus size in children with moderate malnutrition: a cohort study from Burkina Faso.

BACKGROUND: Moderate acute malnutrition (MAM) affects millions of children, increasing their risk of dying from infections. Thymus atrophy may be a marker of malnutrition-associated immunodeficiency, but factors associated with thymus size in children with MAM are unknown, as is the effect of nutritional interventions on thymus size. METHODS: Thymus size was measured by ultrasound in 279 children in Burkina Faso with MAM, diagnosed by low mid-upper arm circumference (MUAC) and/or low weight-for-length z-score (WLZ), who received 12 weeks treatment with different food supplements as part of a randomized trial. Correlates of thymus size and of changes in thymus size after treatment, and after another 12 weeks of follow-up were identified. RESULTS: Thymus size correlated positively with age, anthropometry and blood haemoglobin, and was smaller in children with malaria. Children with malnutrition diagnosed using MUAC had a smaller thymus than children diagnosed based on WLZ. Thymus size increased during and after treatment, similarly across the different food supplement groups. CONCLUSIONS: In children with MAM, the thymus is smaller in children with anaemia or malaria, and grows with recovery. Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low WLZ in children with MAM. IMPACT: Thymus atrophy is known to be a marker of the immunodeficiency associated with malnutrition in children. In children with moderate malnutrition, we found the thymus to be smaller in children with anaemia or malaria. Assuming that thymus size reflects vulnerability, low MUAC seems to identify more vulnerable children than low weight for length. Thymus atrophy appears reversible with recovery from malnutrition, with similar growth seen in children randomized to treatment with different nutritional supplements.

Risk factors for impaired renal function in HIV-infected and HIV-uninfected adults: cross-sectional study in North-Western Tanzania.

BACKGROUND: Although the burden of impaired renal function is rising in sub-Saharan Africa (SSA), little is known about correlates of impaired renal function in the region. We determined factors associated with estimated glomerular filtration rate (eGFR) and impaired renal function in HIV-infected and HIV-uninfected adults. METHODS: We undertook cross-sectional analysis of data from 1947 adults at enrolment for a cohort study on diabetes and associated complications in HIV patients in Mwanza, north-western Tanzania. A structured questionnaire was used to collect data on sociodemography, smoking, alcohol, physical activity, antiretroviral therapy (ART) and anthropometry. We measured blood pressure, tested blood samples for creatinine, glucose and HIV, and performed Kato Katz for Schistosoma mansoni. Correlates of eGFR (mL/min/1.73 m2) and impaired renal function (eGFR< 60 mL/min/1.73 m2) were determined using linear regression and logistic regression, respectively. RESULTS: 655 (34%) participants were HIV-uninfected, 956 (49%) were ART-naive HIV-infected and 336 (17%) were HIV-infected adults on ART. The mean age was 41 years (SD12) and majority (59%) were females. Overall, the mean eGFR was 113.6 mL/min/1.73 m2 but 111.2 mL/min/1.73 m2 in HIV-uninfected, 109.7 mL/min/1.73 m2 in ART-naive HIV-infected and 129.5 mL/min/1.73 m2 in HIV-infected ART-experienced adults, and respective prevalence of impaired renal function was 7.0, 5.7, 8.1 and 6.3%. Correlates of lower eGFR were increasing age, higher socioeconomic status, unhealthy alcohol drinking, higher body mass index and diabetes mellitus. Anaemia was associated with 1.9 (95% Confidence Interval (CI):1.2, 2.7, p = 0.001) higher odds of impaired renal function compared to no anaemia and this effect was modified by HIV status (p value 0.02 for interaction). CONCLUSION: Impaired renal function is prevalent in this middle-aged study population. Interventions for prevention of impaired renal function are needed in the study population with special focus in HIV-infected adults and those with high socioeconomic status. Interventions targeting modifiable risk factors such as alcohol and weight reduction are warranted.

Impact of food supplements on early child development in children with moderate acute malnutrition: A randomised 2 x 2 x 3 factorial trial in Burkina Faso.

BACKGROUND: Lipid-based nutrient supplements (LNS) and corn-soy blends (CSBs) with varying soy and milk content are used in treatment of moderate acute malnutrition (MAM). We assessed the impact of these supplements on child development. METHODS AND FINDINGS: We conducted a randomised 2 × 2 × 3 factorial trial to assess the effectiveness of 12 weeks' supplementation with LNS or CSB, with either soy isolate or dehulled soy, and either 0%, 20%, or 50% of protein from milk, on child development among 6-23-month-old children with MAM. Recruitment took place at 5 health centres in Province du Passoré, Burkina Faso between September 2013 and August 2014. The study was fully blinded with respect to soy quality and milk content, while study participants were not blinded with respect to matrix. This analysis presents secondary trial outcomes: Gross motor, fine motor, and language development were assessed using the Malawi Development Assessment Tool (MDAT). Of 1,609 children enrolled, 54.7% were girls, and median age was 11.3 months (interquartile range [IQR] 8.2-16.0). Twelve weeks follow-up was completed by 1,548 (96.2%), and 24 weeks follow-up was completed by 1,503 (93.4%); follow-up was similar between randomised groups. During the study, 4 children died, and 102 children developed severe acute malnutrition (SAM). There was no difference in adverse events between randomised groups. At 12 weeks, the mean MDAT z-scores in the whole cohort had increased by 0.33 (95% CI: 0.28, 0.37), p < 0.001 for gross motor; 0.26 (0.20, 0.31), p < 0.001 for fine motor; and 0.14 (0.09, 0.20), p < 0.001 for language development. Children had larger improvement in language z-scores if receiving supplements with milk (20%: 0.09 [-0.01, 0.19], p = 0.08 and 50%: 0.11 [0.01, 0.21], p = 0.02), although the difference only reached statistical significance for 50% milk. Post hoc analyses suggested that this effect was specific to boys (interaction p = 0.02). The fine motor z-scores were also improved in children receiving milk, but only when 20% milk was added to CSB (0.18 [0.03, 0.33], p = 0.02). Soy isolate over dehulled soy increased language z-scores by 0.07 (-0.01, 0.15), p = 0.10, although not statistically significant. Post hoc analyses suggested that LNS benefited gross motor development among boys more than did CSB (interaction p = 0.04). Differences between supplement groups did not persist at 24 weeks, but MDAT z-scores continued to increase post-supplementation. The lack of an unsupplemented control group limits us from determining the overall effects of nutritional supplementation for children with MAM. CONCLUSIONS: In this study, we found that child development improved during and after supplementation for treatment of MAM. Milk protein was beneficial for language and fine motor development, while suggested benefits related to soy quality and supplement matrix merit further investigation. Supplement-specific effects were not found post-intervention, but z-scores continued to improve, suggesting a sustained overall effect of supplementation. TRIAL REGISTRATION: ISRCTN42569496.

Early development in children with moderate acute malnutrition: A cross-sectional study in Burkina Faso.

Malnutrition impairs cognitive, communication, and motor development, but it is not known how nutrition and health are associated with development in children with moderate acute malnutrition (MAM). We aimed to describe motor and language development of children with MAM and explore its nutrition and health-related correlates. This cross-sectional study used baseline data from a nutritional trial in children with MAM aged 6-23 months in Burkina Faso. Motor and language skills were assessed using the Malawi Development Assessment Tool (MDAT). Linear mixed models were used to explore potential correlates of MDAT including socio-economic status, anthropometry, body composition, whole-blood polyunsaturated fatty acids (PUFA), haemoglobin (Hb), iron status, and morbidity. We also assessed child and caregiver participation during MDAT procedures and their associations with correlates and development. MDAT data were available for 1.608 children. Mean (95% CI) MDAT z-scores were -0.39 (-0.45, -0.34) for gross motor, 0.54 (0.48, 0.59) for fine motor, and -0.91 (-0.96, -0.86) for language skills. Children with higher mid-upper arm circumference, weight-for-height, height-for-age, fat-free mass, n-3 PUFAs, Hb, and iron status had better MDAT z-scores, whereas children with more fat mass index, anaemia, illness, and inflammation had poorer z-scores. In addition, children living in larger households or with an unmarried mother had poorer MDAT z-scores. Associations between morbidity and z-scores were largely explained by children's poorer participation during MDAT assessment. The identified factors associated with child development may inform interventions needed to stimulate development during or after management of MAM.

Unhealthy Snack Food and Beverage Consumption Is Associated with Lower Dietary Adequacy and Length-for-Age z-Scores among 12-23-Month-Olds in Kathmandu Valley, Nepal.

BACKGROUND: Consumption of unhealthy snack foods and beverages (USFBs) in low- and middle-income countries (LMICs) is rising, with global awareness increasing about risks of overnutrition. However, little is known about the relation between USFB consumption and young children's diet/nutritional outcomes in contexts where nutrient density of complementary foods is often low. OBJECTIVES: This study assessed the association of high USFB consumption, compared with low consumption, with nutrient intakes, dietary adequacy, iron status, and growth in young children in Kathmandu Valley, Nepal. METHODS: A cross-sectional survey was conducted in a representative sample of 745 primary caregivers of children aged 12-23 mo. Food consumption was measured through quantitative 24-h recalls, and child anthropometric measurements and capillary blood samples were collected. Using adjusted linear/logistic regression models, nutrient intakes, dietary adequacy, length-for-age and weight-for-length z-scores (LAZ and WLZ, respectively), and iron status were compared between lowest and highest tertiles of consumption based on the contribution of USFBs to total energy intakes (TEIs). Mediation of the relation between USFB consumption and LAZ via lowered dietary adequacy was explored using structural equations modeling. RESULTS: On average, USFBs contributed 46.9% of TEI among the highest tertile of consumers, compared with 5.2% of TEI among the lowest. Compared with low-USFB consumers, high-USFB consumers had lower nutrient intakes and a greater proportion were at risk of inadequate intakes for 8 nutrients. Mean LAZ was nearly 0.3 SD lower among high-USFB consumers than low consumers (P = 0.003), with this relationship partially mediated through dietary adequacy. No associations were found with stunting prevalence or iron status. Prevalence of overweight/obesity was low. CONCLUSIONS: In this LMIC context, high USFB consumption among young children was associated with inadequate micronutrient intakes, which can contribute to poor growth outcomes. Addressing increased availability of USFBs in LMIC food systems should be a priority for policies and programs aiming to safeguard child nutrition.

Steady Growth in Early Infancy Is Associated with Greater Anthropometry in Indian Children Born Low Birth Weight at Term.

BACKGROUND: Patterns of early growth are associated with later body composition and risk of adult noncommunicable disease but information from low-income countries is limited. OBJECTIVES: The aim of this study was to investigate early growth trajectories and later anthropometric and bone density outcomes among children born term low birth weight (LBW: 1.8-2.5 kg). METHODS: We used data from 902 children from the Delhi Infant Vitamin D Supplementation study of LBW term infants (which collected monthly anthropometry from birth to 6 mo) and who had height, weight, midupper arm circumference (MUAC), midupper arm muscle circumference (MUAMC), subscapular and triceps skinfold thicknesses, tibia and radius bone density measured at age 4-6 y. We investigated how growth in the first 6 mo of life, modeled using the SuperImposition by Translation and Rotation (SITAR) growth curve model, was related to these outcomes. SITAR summarizes each infant's weight and length trajectory in terms of a population mean curve and child-specific growth parameters: size, timing, and intensity. These were included as explanatory variables in linear regression models for the childhood outcomes. RESULTS: Considering the infant weight and length SITAR parameters jointly, childhood weight was strongly associated with infant length timing [estimated regression coefficient ß = 0.25 (95% CI: 0.10, 0.39)] and with weight size, timing, and intensity [ß = 9.01 (6.75, 11.27), ß = -0.25 (-0.43, -0.07), ß = 5.03 (3.22, 6.84), respectively]. Childhood height was associated only with the length parameters [ß = 0.97 (0.71, 1.23), ß = -0.43 (-0.77, -0.09), ß = 11.68 (8.60, 14.75), respectively]; childhood MUAC, MUAMC, and skinfolds with all parameters; and bone density with none. Overall, delayed and sustained growth in infant weight and length resulted in higher values of all outcomes except bone density, with the period up to 15 wk of age appearing critical for setting childhood anthropometry in this population. CONCLUSIONS: The explanation for the effects of delayed growth and length of the period in which trajectories are set is unclear; however, sustained and delayed growth in early infancy appears to be beneficial for these LBW children at least in the short-term. The trial was registered at clinicaltrials.gov as BT/PR7489/PID/20/285/2006.

Stunting, wasting and breast-feeding as correlates of body composition in Cambodian children at 6 and 15 months of age.

The study aimed at assessing stunting, wasting and breast-feeding as correlates of body composition in Cambodian children. As part of a nutrition trial (ISRCTN19918531), fat mass (FM) and fat-free mass (FFM) were measured using 2H dilution at 6 and 15 months of age. Of 419 infants enrolled, 98 % were breastfed, 15 % stunted and 4 % wasted at 6 months. At 15 months, 78 % were breastfed, 24 % stunted and 11 % wasted. Those not breastfed had lower FMI at 6 months but not at 15 months. Stunted children had lower FM at 6 months and lower FFM at 6 and 15 months compared with children with length-for-age z ≥0. Stunting was not associated with height-adjusted indexes fat mass index (FMI) or fat-free mass index (FFMI). Wasted children had lower FM, FFM, FMI and FFMI at 6 and 15 months compared with children with weight-for-length z (WLZ) ≥0. Generally, FFM and FFMI deficits increased with age, whereas FM and FMI deficits decreased, reflecting interactions between age and WLZ. For example, the FFM deficits were -0·99 (95 % CI -1·26, -0·72) kg at 6 months and -1·44 (95 % CI -1·69; -1·19) kg at 15 months (interaction, P<0·05), while the FMI deficits were -2·12 (95 % CI -2·53, -1·72) kg/m2 at 6 months and -1·32 (95 % CI -1·77, -0·87) kg/m2 at 15 months (interaction, P<0·05). This indicates that undernourished children preserve body fat at the detriment of fat-free tissue, which may have long-term consequences for health and working capacity.

Snack food and beverage consumption and young child nutrition in low- and middle-income countries: A systematic review.

Although snacks can provide important nutrients for young children during the complementary feeding period, the increasing availability of snack foods and sugar-sweetened beverages (SSB), often energy-dense and nutrient-poor, in low- and middle-income countries (LMIC) is a concern. Such foods may displace consumption of nutritious foods in contexts where diets are often nutritionally inadequate and the burden of childhood malnutrition is high. This systematic review summarizes literature on the contribution of snack food/SSB consumption to total energy intakes (TEI) of children below 23 months of age in LMIC and associations between this consumption and nutritional outcomes. It also identifies areas where further research is needed. A systematic search of Embase, Global Health, and MEDLINE for literature published in January 1990-July 2018 was conducted. This search yielded 8,299 studies, 13 of which met inclusion criteria: Nine studies assessed % TEI from snack foods/SSB, and four studies assessed associations between snack food/SSB consumption and nutritional outcomes. Average % TEI from snack foods/SSB ranged from 13% to 38%. Findings regarding associations with growth were inconclusive, and no studies assessed associations with nutrient intakes. Variation in measurement of consumption and definitions of snack foods and SSB limited study comparisons. Further research is needed to understand how consumption of energy-dense, nutrient-poor snack foods and SSB influences undernutrition and overnutrition among young children during the complementary feeding period in settings that are experiencing dietary transitions and the double burden of malnutrition.

Energy intake from unhealthy snack food/beverage among 12-23-month-old children in urban Nepal.

Unhealthy snack food and beverage (USFB) consumption among young children has been noted in many low-income and middle-income countries (LMIC), however, there is a lack of information on the contribution of these foods to children's diets in these contexts. This study describes the nutrient profiles and costs of snacks consumed by young children in Kathmandu Valley, Nepal, and assesses the proportion of total energy intake from nonbreastmilk foods (%TEI-NBF) contributed by USFB and factors associated with high USFB consumption. A cross-sectional survey was conducted among 745 randomly sampled primary caregivers of children aged 12-23 months. Of 239 unique snack foods and beverages consumed, 180 (75.3%) were classified as unhealthy based on nutrient profiling, with 158 of these being commercially branded. Median cost/100 kcal of USFB was lower as compared with healthy snacks. Ninety-one percent of children had consumed a USFB in the previous 24 hr, with these foods contributing a mean %TEI-NBF of 24.5 ± 0.7 among all children. Biscuits (10.8%), candy/chocolate (3.5%), and savoury snacks (3.4%) provided the largest %TEI-NBF. Children who were older, female, or from the poorest households had significantly higher odds of high USFB consumption, whereas children whose caregivers were of upper caste/ethnicity or had achieved tertiary education had lower odds of consumption than other children. To reduce USFB consumption, interventions should seek to further understand social/cultural drivers of feeding practices, target disadvantaged populations, and ensure caregivers are fully aware of the nutritional quality of food products they choose for their children.