Nutrition and Health in Arab Adolescents (NaHAR): Study protocol for the determination of ethnic-specific body fat and anthropometric cut-offs to identify metabolic syndrome.

The prevalence of adolescent obesity in the Middle-East is considered among the highest in the world. Obesity in adolescents is associated with several cardiometabolic abnormalities, the constellation of which is referred to as the metabolic syndrome (MetS). This multi-country cross-sectional study aims to determine the optimal cut-off values for body fat (BF); body mass index (BMI) z-score; waist circumference (WC) percentile, and mid-upper arm circumference (MUAC) for the prediction of MetS among adolescents from Kingdom of Saudi-Arabia (KSA), Kuwait, Jordan, Lebanon and Syria. A secondary objective is to examine the validity of Bioelectrical Impendence Vector Analysis (BIVA) in estimating BF against the deuterium dilution technique (DDL). In each country, a sample of 210 adolescents will be recruited. Data collection will include demographics, socioeconomic, lifestyle and dietary data using a multi-component questionnaire; anthropometric measurements will be obtained and body composition will be assessed using the DDL and BIVA; blood pressure and biochemical assessment will be performed for the identification of the MetS. Receiver operating characteristic analyses will be undertaken to determine optimal cut-off values of BMI, WC, MUAC and BF in identifying those with MetS. Odds ratios (OR) and their respective 95% confidence interval (CI) for the association of the anthropometric measurements with MetS will be computed based on multiple logistic regression analysis models. The Bland and Altman approach will be adopted to compare BIVA against the reference DDL method for the determination of body composition parameters. This study responds to the need for ethnic-specific anthropometric cut-offs for the identification of excess adiposity and associated cardiometabolic risks in the adolescent population. The adoption of the generated cut-offs may assist policy makers, public health professionals and clinical practitioners in providing ethnic-specific preventive and curative strategies tailored to adolescents in the region.

Effects of variations in atmospheric temperature and humidity on the estimation of exclusive breastfeeding status using the deuterium oxide dose-to-mother technique.

Background: The deuterium dose-to-mother (DTM) method measures the human milk intake of breastfed children. Recently, the use of this method has been expanded to classify babies objectively as exclusively breast fed (EBF) or not (non-EBF) based on quantification of non-milk oral water intake (NMOI). However, the calculation of NMOI estimates involves atmospheric temperature and humidity. Objective: To evaluate the effects of atmospheric temperature and humidity on NMOI calculation and the classification of exclusive breastfeeding. Methods: The effect of indoor temperature and relative humidity on NMOI and the estimated prevalence of non-EBF were examined in two existing data sets of DTM in children by varying temperature in the range of 15 to 35°C and relative humidity in the range of 20 to 80% representing the maximum span of indoor conditions expected. Population-level estimates of NMOI distributions were derived using the rstan package for R v2.21.2. Results: The NMOI decreased at a rate of -1.15 g/day per °C increase and at a rate of -1.01 g/day per percent increase in relative humidity; this was due to variations in non-oral water intake from the atmosphere, a component of the calculation of NMOI, which is dependent on temperature and humidity. For the various locations considered, the mean calculated NMOI varied between 24.6 and 53.3 g/day using the same input data. In the mixed-fed sample of babies, the prevalence of non-EBF based on the earlier defined NMOI cut-off of 86.6 g/day was reduced by 19% when relative humidity was increased by 60%. Conclusions: Atmospheric conditions are essential factors in the computation of NMOI, used in the objective classification of babies as exclusively breast fed or not, and should be considered when the DTM method is used to classify exclusive breastfeeding.

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.

Predictors of time to recovery and non-response during outpatient treatment of severe acute malnutrition.

BACKGROUND: Every year, over 4 million children are treated for severe acute malnutrition with varying program performance. This study sought to explore the predictors of time to recovery from and non-response to outpatient treatment of SAM. METHODS: Children with weight-for-height z-score (WHZ) <-3 and/or mid-upper arm circumference (MUAC) <115 mm, without medical complications were enrolled in a trial (called MANGO) from outpatient clinics in Burkina Faso. Treatment included a weekly ration of ready-to-use therapeutic foods. Recovery was declared with WHZ ≥-2 and/or MUAC ≥125 mm, for two weeks without illness. Children not recovered by 16 weeks were considered as non-response to treatment. Predictors studied included admission characteristics, morbidity and compliance during treatment and household characteristics. Cox proportional hazard models were fitted and restricted mean time to recovery calculated. Logistic regression was used to analyse non-response to treatment. RESULTS: Fifty-five percent of children recovered and mean time to recovery was eight weeks while 13% ended as non-response to treatment. Independent predictors of longer time to recovery or non-response included low age, being admitted with WHZ <-3, no illness nor anaemia at admission, illness episodes during treatment, skipped or missed visits, low maternal age and not practising open defecation. Eighty-four percent of children had at least one and 59% at least two illness episodes during treatment. This increased treatment duration by 1 to 4 weeks. Thirty-five percent of children missed at least one treatment visit. One missed visit predicted 3 weeks longer and two or more missed visits 5 weeks longer treatment duration. CONCLUSIONS: Both longer time to recovery and higher non-response to treatment seem most strongly associated with illness episodes and missed visits during treatment. This indicates that prevention of illnesses would be key to shortening the treatment duration and that there is a need to seek ways to facilitate adherence.

Characteristics and birth outcomes of pregnant adolescents compared to older women: An analysis of individual level data from 140,000 mothers from 20 RCTs.

BACKGROUND: Adolescence is a critical period of maturation when nutrient needs are high, especially among adolescents entering pregnancy. Using individual-level data from 140,000 participants, we examined socioeconomic, nutrition, and pregnancy and birth outcomes for adolescent mothers (10-19 years) compared to older mothers in low and middle-income countries. METHODS: This study was conducted between March 16, 2018 and May 25, 2021. Data were obtained from 20 randomised controlled trials of micronutrient supplementation in pregnancy. Stratified analyses were conducted by age (10-14 years, 15-17 years, 18-19 years, 20-29 years, 30-39 years, 40+ years) and geographical region (Africa, Asia). Crude and confounder-adjusted means, prevalence and relative risks of pregnancy, nutrition and birth outcomes were estimated using multivariable linear and log-binomial regression models with 95% confidence intervals. FINDINGS: Adolescent mothers comprised 31.6% of our data. Preterm birth, small-for-gestational age (SGA), low birthweight (LBW) and newborn mortality followed a U-shaped trend in which prevalence was highest among the youngest mothers (10-14 years) and then reduced gradually, but increased again for older mothers (40+ years). When compared to mothers aged 20-29 years, there was a 23% increased risk of preterm birth, a 60% increased risk of perinatal mortality, a 63% increased risk of neonatal mortality, a 28% increased risk of LBW, and a 22% increased risk of SGA among mothers 10-14 years. Mothers 40+ years experienced a 22% increased risk of preterm birth and a 103% increased risk of stillbirth when compared to the 20-29 year group. INTERPRETATION: The youngest and oldest mothers suffer most from adverse pregnancy and birth outcomes. Policy and programming agendas should consider both biological and socioeconomic/environmental factors when targeting these populations. FUNDING: Bill and Melinda Gates Foundation (Grant No: OP1137750).

Lipid-based nutrient supplement at initiation of antiretroviral therapy does not substitute energy from habitual diet among HIV patients - a secondary analysis of data from a randomised controlled trial in Ethiopia.

Introduction: Malnutrition is common among people with HIV in sub-Saharan Africa. Nutritional supplementation at initiation of antiretroviral treatment (ART) has shown beneficial effects, but it is not known if supplementation replaces or supplements the habitual energy intake in a context of food insecurity. Methods: As part of a randomised controlled trial among people with HIV initiating ART in Ethiopia, we assessed whether the provision of a lipid-based nutrient supplement (LNS) affected energy intake from the habitual diet. People with HIV aged ≥18 years with a body mass index (BMI) >17 were randomly allocated 2:1 to receive either early (month 1-3 after ART initiation) or delayed (month 4-6 after ART initiation) supplementation with LNS (≈4,600 kJ/day). Participants with BMI 16-17 were all allocated to early supplementation. The daily energy intake from the habitual diet (besides the energy contribution from LNS) was assessed using a 24-h food recall interview at baseline and at monthly follow-up visits. Linear mixed models were used to compare habitual energy intake in (1) early versus delayed supplementation groups and (2) supplemented versus unsupplemented time periods within groups. Results: Of 301 participants included, 67% of the participants were women, mean (±standard deviation [SD]) age was 32.9 (±8.9) years and 68% were living in moderately or severely food insecure households. Mean (±SD) reported habitual energy intake at baseline was 5,357 kJ/day (±2,246) for women and 7,977 kJ/day(±3,557) for men. Among all participants, there were no differences in mean habitual energy intake between supplemented and unsupplemented groups in neither the first 3 (P = 0.72) nor the following 3 months (P = 0.56). Furthermore, habitual energy intake did not differ within groups when comparing periods with or without supplementation (P = 0.15 and P = 0.20). The severity of food insecurity did not modify the effect of supplementation in habitual energy intake (P = 0.55). Findings were similar when participants with BMI 16-17 were excluded. Conclusion: Our findings indicate that the LNS provided after ART initiation supplement, rather than substitute, habitual energy intake among people with HIV, even among those who are food insecure. This supports the feasibility of introducing nutritional supplementation as part of HIV treatment.

Effects of nutritional supplementation on glucose metabolism and insulin function among people with HIV initiating ART.

BACKGROUND: Without high-quality nutritional support, there is a risk that people infected with human immunodeficiency virus (HIV) will replace lost muscle mass with fat mass when initiating antiretroviral therapy (ART). We have shown that lipid-based nutrient supplements (LNS) with whey or soy considerably increases lean mass among Ethiopian people with HIV starting ART. Here, we aim to assess the effects of LNS on insulin function and glucose metabolism. METHODS: This is a secondary analysis of a randomized trial testing the effect of three-month supplementation with LNS containing whey (LNS/whey) or soy (LNS/soy) among people with HIV. LNS/whey and LNS/soy groups were combined and then were compared against the non-supplemented group. The outcomes were change in fasting plasma-glucose (FPG), and 30-min glucose and 120-min glucose after oral glucose tolerance test. We further assessed effect on glycated hemoglobin (HbA1c), fasting insulin, homeostatic model assessment index for beta-cell function (HOMA-B) and insulin resistance (HOMA-IR). RESULTS: Of the 318 patients enrolled, 268 (84.3%) had available FPG and HbA1c and included. After 3 months of ART, HbA1c tended to be 2 mmol/mol higher in the LNS supplemented group, most pronounced among those receiving whey as the protein source. LNS led to higher 30-min glucose (0.5 mmol/L, 95% CI 0.2, 0.8) and 120-min glucose (0.4 mmol/L, 95% CI 0.03, 0.8) and a > 50% increase in fasting insulin, HOMA-B and HOMA-IR compared to the non-supplemented. CONCLUSION: Among Ethiopian people with HIV initiating ART, short-term LNS intake increased glucose and insulin levels, and tended to increase HbA1c, potentially leading to more insulin resistance. Higher intake of carbohydrates with LNS could influence glycemic status. Whether these metabolic changes in early HIV treatment are beneficial or increase long-term risk of metabolic disorders needs to be explored.

New bioelectrical impedance analysis equations for children and adolescents based on the deuterium dilution technique.

BACKGROUND AND AIMS: Body composition in childhood is not only a marker of the prevalence of obesity, but it can also be used to assess associated metabolic complications. Bioelectrical impedance analysis (BIA) shows promise as an easy to use, rapid, and non-invasive tool to evaluate body composition. The objectives of this study were to: (a) develop BIA prediction equations to estimate total body water (TBW) and fat-free mass (FFM) in European children and early adolescents and to validate the analysis with the deuterium dilution as the reference technique and (b) compare our results with previously published paediatric BIA equations. METHODS: The cohort included 266 healthy children and adolescents between 7 and 14 years of age, 46% girls, in five European countries: Bosnia and Herzegovina, Latvia, Montenegro, North Macedonia, and Portugal. TBW and FFM were the target variables in the developed regression models. For model development, the dataset was randomly split into training and test sets, in 70:30 ratio, respectively. Model tuning was performed with 10-fold cross-validation that confirmed the unbiased estimate of its performance. The final regression models were retrained on the whole dataset. RESULTS: Cross-validated regression models were developed using resistance index, weight, and sex as the optimal predictors. The new prediction equations explained 87% variability in both TBW and FFM. Limits of agreement between BIA and reference values, were within ±17% of the mean, (-3.4, 3.7) and (-4.5, 4.8) kg for TBW and FFM, respectively. BIA FFM and TBW estimates were within one standard deviation for approximately 83% of the children. BIA prediction equations underestimated TBW and FFM by 0.2 kg and 0.1 kg respectively with no proportional bias and comparable accuracy among different BMI-for-age subgroups. Comparison with predictive equations from published studies revealed varying discrepancy rates with the deuterium dilution measurements, with only two being equivalent to the equations developed in this study. CONCLUSIONS: The small difference between deuterium dilution and BIA measurements validated by Bland-Altman analysis, supports the application of BIA for epidemiological studies in European children using the developed equations.

Utility of bio-electrical impedance vector analysis for monitoring treatment of severe acute malnutrition in children.

BACKGROUND & AIMS: Change in hydration is common in children with severe acute malnutrition (SAM) including during treatment, but is difficult to assess. We investigated the utility of bio-electrical impedance vector analysis (BIVA), a quick non-invasive method, for indexing hydration during treatment. METHODS: We studied 350 children 0·5-14 years of age with SAM (mid-upper arm circumference <11·0 cm or weight-for-height <70% of median, and/or nutritional oedema) admitted to a hospital nutrition unit, but excluded medically unstable patients. Weight, height (H), resistance (R), reactance (Xc) and phase angle (PA) were measured and oedema assessed. Similar data were collected from 120 healthy infants and preschool/school children for comparison. Means of height-adjusted vectors (R/H, Xc/H) from SAM children were interpreted using tolerance and confidence ellipses of corresponding parameters from the healthy children. RESULTS: SAM children with oedema were less wasted than those without (p < 0·001), but had BIVA parameters that differed more from those of healthy children (P < 0·05) than those non-oedematous. Initially, both oedematous and non-oedematous SAM children had mean vectors outside the reference 95% tolerance ellipse. During treatment, mean vectors migrated differently in the two SAM groups, indicating fluid loss in oedematous patients, and tissue accretion in non-oedematous patients. At admission, R/H was lower (oedematous) or higher (non-oedematous) among children who died than those who exited the hospital alive. CONCLUSIONS: BIVA can be used in children with SAM to distinguish tissue-vs. hydration-related weight changes during treatment, and also identify children at high risk of death enabling early clinical interventions.

Renal function in Ethiopian HIV-positive adults on antiretroviral treatment with and without tenofovir.

BACKGROUND: Limited data are available on the effect of antiretroviral treatment (ART) or Tenofovir disoproxil fumarate (TDF) on renal function in Ethiopians. We aimed to assess factors associated with renal function changes during the first year of ART with special focus on TDF. METHODS: HIV positive persons who were ≥ 18 years of age and eligible for ART initiation were recruited. Creatinine measurement to estimate glomerular filtration rate (eGFR) and spot urine analyses were performed at baseline and after 3, 6 and 12 months of ART. Univariate and multivariate linear regression and univariate logistic regression were used to determine factors associated with eGFR as continuous and categorical variable respectively. A linear mixed model was used to assess 12 month eGFR difference in TDF and non-TDF based regimen. RESULT: Of 340 ART-naïve HIV patients with baseline renal function tests, 82.3% (279/339) were initiated on a TDF based ART regimen. All patients were on non-nucleoside reverse transcriptase inhibitors (NNRTI) based ART regimen. The median (IQR) change in eGFR with 12 months of ART was 0.8 (- 11.1; 10.0) ml/min/1.73m2. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m2 in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m2 within 12 months. Moreover, none of the HIV patients had persistent proteinuria or glycosuria. Older HIV patients especially age > 45 years and those with unsuppressed viral load at 6 month of ART had a significantly lower eGFR at 12 months of ART initiation. However, there was no difference in 12 month eGFR between HIV patients initiated on TDF based regimen and non-TDF based regimen. CONCLUSION: Renal function remained stable with no difference between HIV patients treated with TDF or non-TDF NNRTI based ART regimen over 12 months. However, older HIV patients and those with unsuppressed viral load deserve special focus on renal monitoring. Data on long-term safety of TDF (> 1 year) is still warranted in this population.

Vitamin A and iron status of children before and after treatment of uncomplicated severe acute malnutrition.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) and aims for quick regain of lost body tissues while providing sufficient micronutrients to restore diminished body stores. Little evidence exists on the success of the treatment to establish normal micronutrient status. We aimed to assess the changes in vitamin A and iron status of children treated for SAM with RUTF, and explore the effect of a reduced RUTF dose. METHODS: We collected blood samples from children 6-59 months old with SAM included in a randomised trial at admission to and discharge from treatment and analysed haemoglobin (Hb) and serum concentrations of retinol binding protein (RBP), ferritin (SF), soluble transferrin receptor (sTfR), C-reactive protein (CRP) and α1-acid glycoprotein (AGP). SF, sTfR and RBP were adjusted for inflammation (CRP and AGP) prior to analysis using internal regression coefficients. Vitamin A deficiency (VAD) was defined as RBP < 0.7 µmol/l, anaemia as Hb < 110 g/l, storage iron deficiency (sID) as SF < 12 µg/l, tissue iron deficiency (tID) as sTfR > 8.3 mg/l and iron deficiency anaemia (IDA) as both anaemia and sID. Linear and logistic mixed models were fitted including research team and study site as random effects and adjusting for sex, age and outcome at admission. RESULTS: Children included in the study (n = 801) were on average 13 months of age at admission to treatment and the median treatment duration was 56 days [IQR: 35; 91] in both arms. Vitamin A and iron status markers did not differ between trial arms at admission or at discharge. Only Hb was 1.7 g/l lower (95% CI -0.3, 3.7; p = 0.088) in the reduced dose arm compared to the standard dose, at recovery. Mean concentrations of all biomarkers improved from admission to discharge: Hb increased by 12% or 11.6 g/l (95% CI 10.2, 13.0), RBP increased by 13% or 0.12 µmol/l (95% CI 0.09, 0.15), SF increased by 36% or 4.4 µg/l (95% CI 3.1, 5.7) and sTfR decreased by 16% or 1.5 mg/l (95% CI 1.0, 1.9). However, at discharge, micronutrient deficiencies were still common, as 9% had VAD, 55% had anaemia, 35% had sID, 41% had tID and 21% had IDA. CONCLUSION: Reduced dose of RUTF did not result in poorer vitamin A and iron status of children. Only haemoglobin seemed slightly lower at recovery among children treated with the reduced dose. While improvement was observed, the vitamin A and iron status remained sub-optimal among children treated successfully for SAM with RUTF. There is a need to reconsider RUTF fortification levels or test other potential strategies in order to fully restore the micronutrient status of children treated for SAM.

Body composition during outpatient treatment of severe acute malnutrition: Results from a randomised trial testing different doses of ready-to-use therapeutic foods.

BACKGROUND & AIMS: Treatment of children with uncomplicated severe acute malnutrition (SAM) is based on ready-to-use therapeutic foods (RUTF) prescribed based on body weight and administered at home. Treatment performance is typically monitored through weight gain. We previously reported that a reduced dose of RUTF resulted in weight gain velocity similar to standard dose. Here we investigate the change in body composition of children treated for SAM and compare it to community controls, and describe the effect of a reduced RUTF dose on body composition at recovery. METHODS: Body composition was measured via bio-electrical impedance analysis at admission and recovery among a sub-group of children with SAM participating in a clinical trial and receiving a reduced or a standard dose of RUTF. Non-malnourished children were measured to represent community controls. Linear mixed regression models were fitted. RESULTS: We obtained body composition data from 452 children at admission, 259 at recovery and 97 community controls. During SAM treatment the average weight increased by 1.20 kg of which 0.55 kg (45%) was fat-free mass (FFM) and 0.67 kg (55%) was fat mass (FM). At recovery, children treated for SAM had 1.27 kg lower weight, 0.38 kg lower FFM, and 0.90 kg lower FM compared to community controls. However, their fat-free mass index (FFMI) was not different from community controls (Δ0.2 kg/m2; 95% CI -0.1, 0.4). No differences were observed in FFM, FM or fat mass index (FMI) between the study arms at recovery. However, FFMI was 0.35 kg/m2 higher at recovery with the reduced compared to standard dose (p = 0.007) due to slightly lower height (Δ0.22 cm; p = 0.25) and higher FFM (Δ0.11 kg; p = 0.078) in the reduced dose group. CONCLUSIONS: Almost half of the weight gain during SAM treatment was FFM. Compared to community controls, children recovered from SAM had a lower FM while their height-adjusted FFM was similar. There was no evidence of a differential effect of a reduced RUTF dose on the tissue accretion of treated children when compared to standard treatment.

Setting research priorities on multiple micronutrient supplementation in pregnancy.

Prenatal micronutrient deficiencies are associated with negative maternal and birth outcomes. Multiple micronutrient supplementation (MMS) during pregnancy is a cost-effective intervention to reduce these adverse outcomes. However, important knowledge gaps remain in the implementation of MMS interventions. The Child Health and Nutrition Research Initiative (CHNRI) methodology was applied to inform the direction of research and investments needed to support the implementation of MMS interventions for pregnant women in low- and middle-income countries (LMIC). Following CHNRI methodology guidelines, a group of international experts in nutrition and maternal health provided and ranked the research questions that most urgently need to be resolved for prenatal MMS interventions to be successfully implemented. Seventy-three research questions were received, analyzed, and reorganized, resulting in 35 consolidated research questions. These were scored against four criteria, yielding a priority ranking where the top 10 research options focused on strategies to increase antenatal care attendance and MMS adherence, methods needed to identify populations more likely to benefit from MMS interventions and some discovery issues (e.g., potential benefit of extending MMS through lactation). This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC.

Assessing Breastfeeding Practices Objectively Using Stable Isotope Techniques.

An objective method of assessing breastfeeding practices is required to evaluate progress toward the World Health Organization Global Target 2025: to increase exclusive breastfeeding (EBF) rates in the first 6 months to at least 50% by 2025. Currently, assessment of EBF at the population level is based on mother or caregiver reporting, which risks recall and social desirability bias. A more objective method is the deuterium oxide dose to mother (DTM) technique, in which lactating mothers are given a small amount of deuterium-labeled water. The infant receives deuterium during breastfeeding, and a compartmental model is used to determine the amount of human milk consumed by the infant, and the exclusivity of breastfeeding practices. If the amount of human milk consumed by an infant is determined using the DTM technique and the concentration of nutritional components or potentially toxic contaminants is measured, then the infant's intake of essential nutrients or environmental contaminants can be ascertained.

Body mass index trajectories in early childhood in relation to cardiometabolic risk profile and body composition at 5 years of age.

BACKGROUND: Both impaired and accelerated postnatal growth have been associated with adult risks of obesity and cardiometabolic diseases, like type 2 diabetes and cardiovascular disease. However, the timing of the onset of cardiometabolic changes and the specific growth trajectories linking early growth with later disease risks are not well understood. OBJECTIVES: The aim of this study was to identify distinct trajectories of BMI growth from 0 to 5 y and examine their associations with body composition and markers of cardiometabolic risk at age 5 y. METHODS: In a prospective birth cohort study of 453 healthy and term Ethiopian children with BMIs assessed a median of 9 times during follow-up, we identified subgroups of distinct BMI trajectories in early childhood using latent class trajectory modeling. Associations of the identified growth trajectories with cardiometabolic markers and body composition at 5 y were analyzed using multiple linear regression analyses in 4 adjustment models for each outcome. RESULTS: We identified 4 heterogeneous BMI growth trajectories: stable low BMI (19.2%), normal BMI (48.8%), rapid catch-up to high BMI (17.9%), and slow catch-up to high BMI (14.1%). Compared with the normal BMI trajectory, children in the rapid catch-up to high BMI trajectory had higher triglycerides (TGs) (range of ß-coefficients in Models 1-4: 19-21%), C-peptides (23-25%), fat masses (0.48-0.60 kg), and fat-free masses (0.50-0.77 kg) across the 4 adjustment models. Children in the stable low BMI trajectory had lower LDL cholesterol concentrations (0.14-0.17 mmol/L), HDL cholesterol concentrations (0.05-0.09 mmol/L), fat masses (0.60-0.64 kg), and fat-free masses (0.35-0.49 kg), but higher TGs (11-13%). CONCLUSIONS: The development of obesity and cardiometabolic risks may be established already in early childhood; thus, our data provide a further basis for timely interventions targeted at young children from low-income countries with unfavorable growth patterns. The birth cohort was registered at ISRCTN as ISRCTN46718296.

Impact of reduced dose of ready-to-use therapeutic foods in children with uncomplicated severe acute malnutrition: A randomised non-inferiority trial in Burkina Faso.

BACKGROUND: Children with uncomplicated severe acute malnutrition (SAM) are treated at home with ready-to-use therapeutic foods (RUTFs). The current RUTF dose is prescribed according to the weight of the child to fulfil 100% of their nutritional needs until discharge. However, there is doubt concerning the dose, as it seems to be shared, resulting in suboptimal cost-efficiency of SAM treatment. We investigated the efficacy of a reduced RUTF dose in community-based treatment of uncomplicated SAM. METHODS AND FINDINGS: We undertook a randomised trial testing the non-inferiority of weight gain velocity of children with SAM receiving (a) a standard RUTF dose for two weeks, followed by a reduced dose thereafter (reduced), compared with (b) a standard RUTF dose throughout the treatment (standard). A mean difference of 0.0 g/kg/day was expected, with a non-inferiority margin fixed at -0.5 g/kg/day. Linear and logistic mixed regression analyses were performed, with study site and team as random effects. Between October 2016 and July 2018, 801 children with uncomplicated SAM aged 6-59 months were enrolled from 10 community health centres in Burkina Faso. At admission, the mean age (± standard deviation [SD]) was 13.4 months (±8.7), 49% were male, and the mean weight was 6.2 kg (±1.3). The mean weight gain velocity from admission to discharge was 3.4 g/kg/day and did not differ between study arms (Δ 0.0 g/kg/day; 95% CI -0.4 to 0.4; p = 0.92) confirming non-inferiority (p = 0.013). However, after two weeks, the weight gain velocity was significantly lower in the reduced dose with a mean of 2.3 g/kg/day compared with 2.7 g/kg/day in the standard dose (Δ -0.4 g/kg/day; 95% CI -0.8 to -0.02; p = 0.041). The length of stay (LoS) was not different (p = 0.73) between groups with a median of 56 days (interquartile range [IQR] 35-91) in both arms. No differences were found between reduced and standard arm in recovery (52.7% and 55.4%; p = 0.45), referral (19.2% and 20.1%; p = 0.80), defaulter (12.2% and 8.5%; p = 0.088), non-response (12.7% and 12.5%; p = 0.95), and relapse (2.4% and 1.8%; p = 0.69) rates, respectively. However, the reduced RUTF dose had a small 0.2 mm/week (95% CI 0.04 to 0.4; p = 0.015) negative effect on height gain velocity with a mean height gain of 2.6 mm/week with reduced and 2.8 mm/week with standard RUTF dose. The impact was more pronounced in children under 12 months of age (interaction, p = 0.019) who gained 2.8 mm/week with reduced and 3.1 mm/week with standard dose (Δ -0.4 mm/week; 95% CI -0.6 to -0.2; p < 0.001). Limitations include not blinding participants to the RUTF dose received and excluding all children with negative appetite test. The results are generalisable for relatively food secure contexts with a young SAM population. CONCLUSIONS: Reducing the RUTF dose provided to children with SAM after two weeks of treatment did not reduce overall weight or mid-upper arm circumference (MUAC) gain velocity nor affect recovery or lengthen treatment time. However, it led to a small but significant negative effect on linear growth, especially among the youngest. The potential effect of reducing the RUTF dose in a routine program on treatment outcomes should be evaluated before scaling up. TRIAL REGISTRATION: ISRCTN registry ISRCTN50039021.

Associations of fat mass and fat-free mass accretion in infancy with body composition and cardiometabolic risk markers at 5 years: The Ethiopian iABC birth cohort study.

BACKGROUND: Accelerated growth in early childhood is an established risk factor for later obesity and cardiometabolic disease, but the relative importance of fat mass (FM) and fat-free mass (FFM) accretion is not well understood. We aimed to study how FM and FFM at birth and their accretion during infancy were associated with body composition and cardiometabolic risk markers at 5 years. METHODS AND FINDINGS: Healthy children born at term were enrolled in the Infant Anthropometry and Body Composition (iABC) birth cohort between December 2008 and October 2012 at Jimma University Specialized Hospital in the city of Jimma, Ethiopia. FM and FFM were assessed using air displacement plethysmography a median of 6 times between birth and 6 months of age. In 507 children, we estimated individual FM and FFM at birth and their accretion over 0-3 and 3-6 months of age using linear-spline mixed-effects modelling. We analysed associations of FM and FFM at birth and their accretion in infancy with height, waist circumference, FM, FFM, and cardiometabolic risk markers at 5 years using multiple linear regression analysis. A total of 340 children were studied at the 5-year follow-up (mean age: 60.0 months; girls: 50.3%; mean wealth index: 45.5 out of 100; breastfeeding status at 4.5 to 6 months post-partum: 12.5% exclusive, 21.4% almost exclusive, 60.6% predominant, 5.5% partial/none). Higher FM accretion in infancy was associated with higher FM and waist circumference at 5 years. For instance, 100-g/month higher FM accretion in the periods 0-3 and 3-6 months was associated with 339 g (95% CI: 243-435 g, p < 0.001) and 367 g (95% CI: 250-484 g, p < 0.001) greater FM at 5 years, respectively. Higher FM at birth and FM accretion from 0 to 3 months were associated with higher FFM and cholesterol concentrations at 5 years. Associations for cholesterol were strongest for low-density lipoprotein (LDL)-cholesterol, and remained significant after adjusting for current FM. A 100-g higher FM at birth and 100-g/month higher FM accretion from 0 to 3 months were associated with 0.16 mmol/l (95% CI: 0.05-0.26 mmol/l, p = 0.005) and 0.06 mmol/l (95% CI: 0.01-0.12 mmol/l, p = 0.016) higher LDL-cholesterol at 5 years, respectively. Higher FFM at birth and FFM accretion in infancy were associated with higher FM, FFM, waist circumference, and height at 5 years. For instance, 100-g/month higher FFM accretion in the periods 0-3 and 3-6 months was associated with 1,002 g (95% CI: 815-1,189 g, p < 0.001) and 624 g (95% CI: 419-829 g, p < 0.001) greater FFM at 5 years, respectively. We found no associations of FM and FFM growth with any of the other studied cardiometabolic markers including glucose, HbA1c, insulin, C-peptide, HOMA-IR, triglycerides, and blood pressure. Non-attendance at the 5-year follow-up visit was the main limitation of this study, which may have introduced selection bias and limited the power of the regression analyses. CONCLUSIONS: FM accretion in early life was positively associated with markers of adiposity and lipid metabolism, but not with blood pressure and cardiometabolic markers related to glucose homeostasis. FFM accretion was primarily related to linear growth and FFM at 5 years.

Hyperglycemia and insulin function in antiretroviral treatment-naive HIV patients in Ethiopia: a potential new entity of diabetes in HIV?

BACKGROUND: Although diabetes is more common in HIV patients, the direct link between HIV and diabetes is unknown. Glucose abnormalities should be assessed among antiretroviral treatment (ART)-naive patients to reduce confounding by ART. We assessed diabetes status, insulin function and association with inflammation among Ethiopian ART-naive HIV patients. METHODS: Among HIV patients initiating ART, we used glycosylated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) to define prediabetes and diabetes. Insulin during OGTT was determined to calculate insulin function, and C-reactive protein and α1-acid glycoprotein were used as same-day markers of inflammation. RESULTS: Among 332 HIV patients, mean (SD) age was 32.9 (8.8) years, and 222 (66.9%) were women. None had known diabetes, but we found diabetes prevalence using OGTT and HbA1c to be 7.6 and 8.5%, respectively. C-reactive protein and α1-acid glycoprotein were positively associated with hyperglycemia and insulin deficiency, but not insulin resistance. We found poor correlation between traditional risk factors (age and anthropometry) and diabetes, but participants generally had low BMI and waist circumference. CONCLUSION: ART-naive Ethiopian HIV patients had a high prevalence of prediabetes and diabetes, with a poor agreement between HbA1c and OGTT. Diabetes was associated with inflammation, but not with adiposity and age. Diabetes was linked to insulin deficiency, rather than insulin resistance, which may represent a different entity than type 1 and 2 diabetes. This has implications for choice of drugs, when managing diabetes in African HIV patients.

Higher Weight and Weight Gain after 4 Years of Age Rather than Weight at Birth Are Associated with Adiposity, Markers of Glucose Metabolism, and Blood Pressure in 5-Year-Old Ethiopian Children.

BACKGROUND: Fetal and early life growth is associated with adult risk of obesity and cardiometabolic disease. However, little is known about the relative importance of birth weight and successive periods of weight gain on markers of cardiometabolic risk in childhood in low-income populations. OBJECTIVES: The objective was to study associations of birth weight and weight gain velocities in selected age intervals from birth to 60 mo with height, fat-free mass (FFM), and markers of adiposity and cardiometabolic risk at 60 mo. METHODS: In a prospective cohort study of 375 Ethiopian children aged 60 mo, we estimated individual weight gain velocities in the periods between birth and 3, 6, 24, 48, and 60 mo using linear-spline mixed-effects modeling. Subsequently, we analyzed associations of birth weight, weight gain velocities, and current weight with height, FFM, and markers of adiposity and cardiometabolic risk. RESULTS: Weight gain from 48 to 60 mo and weight at 60 mo rather than birth weight were the strongest correlates of insulin, C-peptide, HOMA-IR, blood pressure, height, FFM, waist circumference, and fat mass at 60 mo. For instance, 1 SD higher (1 SD = 50 g/mo) weight accretion from 48 to 60 mo was associated with a higher insulin of 23.3% (95% CI: 9.6%, 38.8%), C-peptide of 11.4% (2.7%, 20.8%), systolic blood pressure of 1.4 mm Hg (0.6, 2.3 mm Hg), fat mass of 0.72 kg (0.59, 0.85 kg), and FFM of 0.70 kg (0.56, 0.85 kg). Weight gain from 0 to 3 mo was positively associated with LDL cholesterol, systolic blood pressure, height, and the body composition indices, and weight gain from 24 to 48 mo was inversely associated with blood glucose. CONCLUSIONS: In 60-mo-old Ethiopian urban children, weight gain and weight after 48 mo rather than weight at birth may represent a sensitive period for variations in markers of adiposity and glucose metabolism. The birth cohort is registered at https://www.isrctn.com/ as ISRCTN46718296.