Publications by authors named "Henrik Friis"

204 Publications

Inflammatory markers as correlates of body composition and grip strength among adults with and without HIV: A cross-sectional study in Ethiopia.

Eur J Clin Nutr 2022 Jan 13. Epub 2022 Jan 13.

Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

Background: Changes in body composition and muscle strength are common among individuals with HIV. We investigated the associations of inflammation with body composition and grip strength in adults with and without HIV.

Methods: Cross-sectional study among Ethiopian treatment-naïve individuals with and without HIV. Fat mass and fat-free mass adjusted for height (kg/m) were used as indicators of body composition.

Results: 288/100 individuals with/without HIV were included between July 2010 and August 2012. Females with HIV had lower fat mass index (FMI) and fat-free mass index (FFMI) than females without HIV, whereas no difference was seen between males with and without HIV. Males and females with HIV had lower grip strength than their counterparts without HIV. Serum alpha-1-acid glycoprotein (s-AGP) was negatively correlated with FMI (-0.71 kg/m, 95% CI: -1.2; -0.3) among individuals with HIV, and those with HIV and serum C-reactive protein (s-CRP) ≥ 10 mg/l had 0.78 kg/m (95% CI -1.4; -0.2) lower FMI than those with s-CRP < 10 mg/l. In contrast, s-AGP was positively correlated with FMI (2.09 kg/m, 95% CI 0.6; 3.6) in individuals without HIV. S-CRP and AGP were negatively associated with grip strength in individuals with HIV, while no correlation was observed among those without HIV.

Conclusion: Inflammation was positively associated with FMI in individuals without HIV while it was negatively associated with FMI in those with HIV, indicating that inflammation may be one of the drivers of depleting energy reserves among treatment-naïve individuals with HIV. Inflammation was associated with decreased muscle quantity and functional capacity among individuals with HIV, but not in those without HIV.
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http://dx.doi.org/10.1038/s41430-021-01056-4DOI Listing
January 2022

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

BMC Nephrol 2021 10 29;22(1):355. Epub 2021 Oct 29.

Mwanza Intervention Trials Unit/National Institute for Medical Research, Mwanza, 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 m) and impaired renal function (eGFR< 60 mL/min/1.73 m) 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 m but 111.2 mL/min/1.73 m in HIV-uninfected, 109.7 mL/min/1.73 m in ART-naive HIV-infected and 129.5 mL/min/1.73 m 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.
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http://dx.doi.org/10.1186/s12882-021-02563-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8555220PMC
October 2021

Weight-for-Height -score Gain during Inpatient Treatment and Subsequent Linear Growth during Outpatient Treatment of Young Children with Severe Acute Malnutrition: A Prospective Study from Uganda.

Curr Dev Nutr 2021 Oct 25;5(10):nzab118. Epub 2021 Sep 25.

Department of Nutrition, Exercise, and Sports, University of Copenhagen, Frederiksberg C, Denmark.

Background: Linear catch-up growth after treatment of severe acute malnutrition (SAM) is low, and little is known about the association between ponderal and subsequent linear growth.

Objective: The study assessed the association of weight-for-height -score (WHZ) gain with subsequent linear growth during SAM treatment and examined its modifiers.

Methods: This was a prospective study, nested in a trial (ISRCTN16454889), among 6-59-mo-old children treated for SAM in Uganda. Weight, total length (TL), and knee-heel length (KHL) were measured at admission, weekly during inpatient therapeutic care (ITC), at discharge, and fortnightly during outpatient therapeutic care (OTC) for 8 wk. Linear regression was used to assess the association between WHZ gain during ITC and linear growth during OTC.

Results: Of 400 children, 327 were discharged to OTC and 290 were followed up for 8 wk. Mean WHZ gains were 0.45 in ITC and 1.24 in OTC, whereas mean height-for-age -score (HAZ) declined by 0.41 during ITC and increased by 0.14 during OTC. WHZ gain during ITC was positively associated with HAZ, TL, and KHL gains during OTC [regression coefficients (β) (95% CI): 0.12 (0.09, 0.15) -score; 3.1 (2.4, 3.8) mm and 0.5 (0.1, 0.7) mm, respectively]. The regression coefficients were highest for the middle tertile of WHZ gain with respect to HAZ and TL. Admission diarrhea and low plasma citrulline reduced the association between WHZ gain during ITC and HAZ and TL gain during OTC ( < 0.001). In contrast, pneumonia ( = 0.051) and elevated plasma C-reactive protein ( < 0.001) increased the association with TL gain, but reduced the association with KHL gain ( < 0.001).

Conclusions: Among children admitted with SAM, considerable WHZ gain during ITC was followed by very modest linear catch-up growth during OTC, with no indication of a WHZ gain threshold, above which linear growth was higher. To optimize linear growth in these children, early treatment of infections and conditions affecting the gut may be necessary.
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http://dx.doi.org/10.1093/cdn/nzab118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546154PMC
October 2021

Hepatic steatosis is associated with anthropometry, cardio-metabolic disease risk, sex, age and urbanisation, but not with ethnicity in adult Kenyans.

Trop Med Int Health 2022 Jan 7;27(1):49-57. Epub 2021 Nov 7.

Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

Objective: We aimed to determine the associations of non-alcoholic fatty liver disease (NAFLD) with cardio-metabolic risk factors for diabetes in adult Kenyans.

Methods: A cross-sectional study was undertaken among rural and urban Kenyans of different ethnic origin. Ultrasonography scanning (USS) methods were used for the assessment of hepatic fat accumulation for NAFLD assessment and abdominal fat distribution, and simple anthropometry measurements were performed. All participants underwent a 2-h oral glucose tolerance test, and biochemical, haemodynamic and lifestyle data were obtained. Multivariate logistic regression analyses were used to assess sex, age, residency and ethnic differences in the association between NAFLD and various metabolic parameters.

Results: In total, 743 individuals (59.1% women) with a mean age of 38.0 (range 18-68) years participated in the study. Overall, 118 individuals (15.9%) had NAFLD, of whom 94.1% had mild steatosis. Age >40 years was significantly associated with having NAFLD compared with <30 years of age with no difference found in NAFLD between ethnic groups (Luo, Kamba, Maasai). All body composition and clinical measurements were associated with NAFLD (p < 0.045 for OR).

Conclusion: Finding lower odds for NAFLD in men was unexpected, as was the lack of differences in NAFLD among the ethnic groups, while higher odds for NAFLD with increasing age and in urban vs. rural populations was expected. Especially the sex-specific results warrant further studies in black African populations on biology of body composition for having NAFLD, and whether this translates into insulin resistance and higher risk of diabetes and consequently cardiovascular disease in black African women.
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http://dx.doi.org/10.1111/tmi.13696DOI Listing
January 2022

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

BMC Nutr 2021 Oct 18;7(1):60. Epub 2021 Oct 18.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1186/s40795-021-00462-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521983PMC
October 2021

The future of human malnutrition: rebalancing agency for better nutritional health.

Global Health 2021 10 9;17(1):119. Epub 2021 Oct 9.

Charles Perkins Centre, University of Sydney, Sydney, Australia.

The major threat to human societies posed by undernutrition has been recognised for millennia. Despite substantial economic development and scientific innovation, however, progress in addressing this global challenge has been inadequate. Paradoxically, the last half-century also saw the rapid emergence of obesity, first in high-income countries but now also in low- and middle-income countries. Traditionally, these problems were approached separately, but there is increasing recognition that they have common drivers and need integrated responses. The new nutrition reality comprises a global 'double burden' of malnutrition, where the challenges of food insecurity, nutritional deficiencies and undernutrition coexist and interact with obesity, sedentary behaviour, unhealthy diets and environments that foster unhealthy behaviour. Beyond immediate efforts to prevent and treat malnutrition, what must change in order to reduce the future burden? Here, we present a conceptual framework that focuses on the deeper structural drivers of malnutrition embedded in society, and their interaction with biological mechanisms of appetite regulation and physiological homeostasis. Building on a review of malnutrition in past societies, our framework brings to the fore the power dynamics that characterise contemporary human food systems at many levels. We focus on the concept of agency, the ability of individuals or organisations to pursue their goals. In globalized food systems, the agency of individuals is directly confronted by the agency of several other types of actor, including corporations, governments and supranational institutions. The intakes of energy and nutrients by individuals are powerfully shaped by this 'competition of agency', and we therefore argue that the greatest opportunities to reduce malnutrition lie in rebalancing agency across the competing actors. The effect of the COVID-19 pandemic on food systems and individuals illustrates our conceptual framework. Efforts to improve agency must both drive and respond to complementary efforts to promote and maintain equitable societies and planetary health.
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http://dx.doi.org/10.1186/s12992-021-00767-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500827PMC
October 2021

Weight and mid-upper arm circumference gain velocities during treatment of young children with severe acute malnutrition, a prospective study in Uganda.

BMC Nutr 2021 Jun 18;7(1):26. Epub 2021 Jun 18.

Department of Nutrition, Exercise and Sports, University of Copenhagen, 1958, Frederiksberg C, Denmark.

Background: Weight gain is routinely monitored to assess hydration and growth during treatment of children with complicated severe acute malnutrition (SAM). However, changes in weight and mid-upper arm circumference (MUAC) gain velocities over time are scarcely described. We assessed weight and MUAC gain velocities in 6-59 mo-old children with complicated SAM by treatment phase and edema status.

Methods: This was a prospective study, nested in a randomized/probiotic trial ( ISRCTN16454889 ). Weight and MUAC gain velocities were assessed by treatment phase and edema at admission using linear mixed-effects models.

Results: Among 400 children enrolled, the median (IQR) age was 15.0 (11.2;19.2) months, 58% were males, and 65% presented with edema. During inpatient therapeutic care (ITC), children with edema vs no edema at admission had negative weight gain velocity in the stabilization phase [differences at day 3 and 4 were - 11.26 (95% CI: - 20.73; - 1.79) g/kg/d and - 13.09 (95% CI: - 23.15; - 3.02) g/kg/d, respectively]. This gradually changed into positive weight gain velocity in transition and eventually peaked at 12 g/kg/d early in the rehabilitation phase, with no difference by edema status (P > 0.9). During outpatient therapeutic care (OTC), overall, weight gain velocity showed a decreasing trend over time (from 5 to 2 g/kg/d), [difference between edema and non-edema groups at week 2 was 2.1 (95% CI: 1.0;3.2) g/kg/d]. MUAC gain velocity results mirrored those of weight gain velocity [differences were - 2.30 (95% CI: - 3.6; - 0.97) mm/week at week 1 in ITC and 0.65 (95% CI: - 0.07;1.37) mm/week at week 2 in OTC].

Conclusions: Weight and MUAC gain velocities among Ugandan children with complicated SAM showed an increasing trend during transition and early in the rehabilitation phase, and a decreasing trend thereafter, but, overall, catch-up growth was prolonged. Further research to establish specific cut-offs to assess weight and MUAC gain velocities during different periods of rehabilitation is needed.
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http://dx.doi.org/10.1186/s40795-021-00428-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212498PMC
June 2021

The Role of Milk Protein and Whey Permeate in Lipid-based Nutrient Supplements on the Growth and Development of Stunted Children in Uganda: A Randomized Trial Protocol (MAGNUS).

Curr Dev Nutr 2021 May 24;5(5):nzab067. Epub 2021 Apr 24.

Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark.

Stunting is associated with cognitive impairment and later chronic disease. Previous trials to prevent stunting have had little effect, and no trials seem to have provided larger amounts of energy and high-quality proteins to already stunted children. We aimed to assess the effects of milk protein (MP) and whey permeate (WP) in large-quantity lipid-based nutrient supplements (LNS-LQ), among stunted children, on linear growth and child development. This was a randomized, double-blind, 2-by-2 factorial trial. Stunted children aged 12-59 mo from eastern Uganda (= 750) were randomly assigned to receive 100 g LNS-LQ with or without MP and WP (= 4 × 150) or no supplement (= 150) for 3 mo. The primary outcomes were change in knee-heel and total length. Secondary outcomes included child development, body composition, anthropometry, and hemoglobin. Micronutrient status, intestinal function, and microbiota were also assessed. Our findings will contribute to an understanding of the role of milk ingredients and LNS in linear catch-up growth. This trial was registered at www.isrctn.com as ISRCTN13093195.
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http://dx.doi.org/10.1093/cdn/nzab067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128719PMC
May 2021

Correlates of serum IGF-1 in young children with moderate acute malnutrition: a cross-sectional study in Burkina Faso.

Am J Clin Nutr 2021 09;114(3):965-972

Department of Pediatrics and Adolescent Health, Rigshospitalet, Copenhagen, Denmark.

Background: Serum insulin-like growth factor 1 (sIGF-1) is an important growth factor in childhood. However, studies on sIGF-1 among children from low-income countries are few, and the role of body composition is unknown.

Objectives: To assess the associations of anthropometry, body composition, inflammation, and breastfeeding with sIGF-1 among children with moderate acute malnutrition (MAM).

Methods: A cross-sectional study based on admission data from 6- to 23-mo-old children with MAM participating in a nutrition intervention trial (Treatfood) in Burkina Faso. Linear regression analysis was used to identify correlates of sIGF-1.

Results: Among 1546 children, the median (IQR) sIGF-1 was 12 (8.2-18.3) ng/mL. sIGF-1 was highest at 6 mo, with a nadir ∼10-11 mo, and higher in girls than boys. Length-for-age z score (LAZ), weight-for-length z score (WLZ), and midupper arm circumference were positively associated with sIGF-1 (P ≤ 0.001). Fat-free mass (FFM) was also positively associated, as sIGF-1 increased 1.5 (95% CI: 0.5, 2.5) ng/mL for each 1-kg increase in FFM. However, the association disappeared after adjustment for height. Elevated serum C-reactive protein and α1-acid glycoprotein were negatively associated with sIGF-1 (P ≤ 0.001), as was fever (P < 0.001) but not a positive malaria test per se (P = 0.15). Children never breastfed had lower sIGF-1 (-5.1; 95% CI: -9.8, -0.3).

Conclusions: LAZ and WLZ were positively and inflammation negatively associated with sIGF-1. As all children were moderately malnourished and many had inflammation, this probably explains the very low median sIGF-1. The association of FFM with sIGF-1 was fully explained by height. There was a marked age pattern, with a nadir in late infancy, confirming findings from smaller studies from well-nourished populations. There is a need for prospective studies to disentangle the role of sIGF-1 in growth and health. This trial was registered at https://www.isrctn.com as ISRCTN42569496.
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http://dx.doi.org/10.1093/ajcn/nqab120DOI Listing
September 2021

Waist circumference and low high-density lipoprotein cholesterol as markers of cardiometabolic risk in Kenyan adults.

PLoS One 2021 25;16(2):e0247600. Epub 2021 Feb 25.

Department of Public Health, Section of Global Health, University of Copenhagen, Copenhagen, Denmark.

Background: Abdominal obesity predict metabolic syndrome parameters at low levels of waist circumference (WC) in Africans. At the same time, the African lipid profile phenotype of low high-density lipoprotein (HDL) cholesterol without concomitant elevated triglyceride levels renders high triglyceride levels detrimental to cardiometabolic health unsuitable for identifying cardiometabolic risk in black African populations.

Objectives: We aimed to identify simple clinical measures for cardiometabolic risk based on WC and HDL in an adult Kenyan population in order to determine which of the two predictors had the strongest impact.

Methods: We used linear regression analyses to assess the association between the two exposure variables WC and HDL with cardiometabolic risk factors including ultrasound-derived visceral (VAT) and subcutaneous adipose tissue (SAT) accumulation, fasting and 2-h venous glucose, fasting insulin, fasting lipid profile, and blood pressure in adult Kenyans (n = 1 370), and a sub-population with hyperglycaemia (diabetes and pre-diabetes) (n = 196). The same analyses were performed with an interaction between WC and HDL to address potential effect modification. Ultrasound-based, semi-quantitative hepatic steatosis assessment was used as a high-risk measure of cardiometabolic disease.

Results: Mean age was 38.2 (SD 10.7) (range 17-68) years, mean body mass index was 22.3 (SD 4.5) (range 13.0-44.8) kg/m2, and 57.8% were women. Cardiometabolic risk was found in the association between both WC and HDL and all outcome variables (p<0.05) except for HDL and SAT, fasting and 2-h venous glucose. Additive cardiometabolic risk (WC and HDL interaction) was found for SAT, low-density lipoprotein cholesterol, and triglycerides. No differences in the association between WC and HDL and the outcome variables were found when comparing the full study population and the hyperglycaemia sub-population. Increase in WC and HDL were both associated with hepatic steatosis (OR 1.09, p<0.001, and OR 0.46, p = 0.031, respectively).

Conclusion: In adult Kenyans, increasing WC identified more cardiometabolic risk factors compared to HDL.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247600PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906307PMC
August 2021

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

Trop Med Int Health 2021 04 27;26(4):435-443. Epub 2021 Jan 27.

Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

Objective: Studies on phenotypes of diabetes in Africa are inconsistent. We assessed the role of β-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 β-cell dysfunction and insulin resistance which was categorised as follows: normal β-cell function and insulin sensitivity, isolated β-cell dysfunction, isolated insulin resistance, and combined β-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 β-cell dysfunction and insulin resistance with outcome measures.

Results: β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance were associated with higher pre-diabetes risk. Similarly, isolated β-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 β-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 β-cell dysfunction, insulin resistance, and combined β-cell dysfunction and insulin resistance, respectively.

Conclusions: β-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.
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http://dx.doi.org/10.1111/tmi.13545DOI Listing
April 2021

Predictors of glucose metabolism and blood pressure among Ethiopian individuals with HIV/AIDS after one-year of antiretroviral therapy.

Trop Med Int Health 2021 04 2;26(4):428-434. Epub 2021 Feb 2.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

Objective: Better understanding of glucose metabolism in patients with HIV after initiating antiretroviral therapy (ART) is important to target treatment and follow-up for diabetes risk and other non-communicable diseases in resource-limited settings. The aim of this study was to assess the changes and predictors of glucose metabolism and blood pressure among patients with HIV on ART for 12 months.

Methods: One-year follow-up of Ethiopian patients with HIV after initiation of ART was done. Outcomes were changes in fasting plasma glucose (FPG), and 30-minute (30mPG) and 2-hour plasma glucose (2hPG) after oral glucose tolerance test, glycated haemoglobin (HbA1c), fasting plasma insulin (p-insulin), homeostatic model assessment index for insulin resistance (HOMA-IR) and blood pressure.   RESULTS: The mean age was 33 years, and the majority were women. During the first 12 months, levels of all plasma glucose parameters decreased, while p-insulin (10 3.1; 95% CI2.4, 4.0), HOMA-IR (10 3.1; 95% CI2.3, 4.0) and systolic blood pressure (B 4.0; 95% CI2.5, 5.5) increased. Fat-free mass at baseline predicted higher increments in p-insulin, HOMA-IR and blood pressure; whereas, fat mass predicted higher increment in HbA1c.

Conclusions: Among Ethiopian patients with HIV, blood pressure and insulin increased, and all glucose parameters declined during 12-month of ART. Only longer-term follow-up will tell us whether insulin increase is due to insulin resistance or from recovering β-cells.
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http://dx.doi.org/10.1111/tmi.13544DOI Listing
April 2021

Thymus size and its correlates among children admitted with severe acute malnutrition: a cross-sectional study in Uganda.

BMC Pediatr 2021 01 4;21(1). Epub 2021 Jan 4.

Department of Nutrition, Exercise and Sports, University of Copenhagen, DK-1958, Frederiksberg C, Denmark.

Background: Malnutrition continues to be a major cause of mortality and morbidity among children in resource limited settings. Children with severe acute malnutrition (SAM) experience severe thymus atrophy, possibly reflecting poor immune function. This immune dysfunction is responsible for the severe infections they experience which lead to mortality. Since their immune dysfunction is not fully understood and there has been a lapse in research in this field, more research is needed. Knowing the correlates of thymus size may help clinicians identify those with more severe atrophy who might have more severe immune impairment. We aimed to describe thymus size and its correlates at admission among children hospitalized with SAM.

Methods: This cross-sectional study involved children 6-59 months admitted with complicated SAM in Mulago National Referral Hospital. Well-nourished children from same communities were used as a community reference group for thymus size. At admission, thymus size was measured by ultrasound scan. Demographic, clinical and laboratory variables were identified at admission. A linear regression model was used to determine correlates of thymus size among children with SAM.

Results: Among 388 children with SAM, the mean age was 17±8.5 months and 58% were boys. The mean thymus size was 3.14 (95% CI 2.9; 3.4) cm lower than that of the 27 healthy community reference children (1.06 vs 4.2 cm, p<0.001) when controlled for age. Thymus size positively correlated with current breastfeeding (0.14, 95% CI 0.01, 0.26), anthropometric measurements at admission (weight, length, mid-upper-arm circumference, weight-for-height Z scores and length-for-age Z scores) and suspected tuberculosis (0.12, 95% CI 0.01; 0.22). Thymus size negatively correlated with > 2 weeks duration of sickness (-0.10; 95% CI -0.19; -0.01).

Conclusion: The thymus is indeed a barometer for nutrition since all anthropometric measurements and breastfeeding were associated with bigger thymus. The immune benefits of breastfeeding among children with SAM is underscored. Children with longer duration of illness had a smaller thymus gland indicating that infections have a role in the cause or consequence of thymus atrophy.
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http://dx.doi.org/10.1186/s12887-020-02457-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780382PMC
January 2021

Influence of hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency on diagnosis of diabetes by HbA1c among Tanzanian adults with and without HIV: A cross-sectional study.

PLoS One 2020 31;15(12):e0244782. Epub 2020 Dec 31.

Vanderbilt Institute for Global Health and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.

Introduction: Hemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders.

Methods: Blood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT).

Results: The mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26, P < 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+ AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM.

Conclusions: HbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244782PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775052PMC
March 2021

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.

PLoS Med 2020 12 23;17(12):e1003442. Epub 2020 Dec 23.

Department of Pediatrics and Adolescent Health, Rigshospitalet, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1371/journal.pmed.1003442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7757806PMC
December 2020

Reply-Comment on RUTF and correction of anaemia and iron deficiency in severe acute malnutrition.

Clin Nutr 2020 09 23;39(9):2936-2937. Epub 2020 Jul 23.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1016/j.clnu.2020.07.009DOI Listing
September 2020

Association between admission criteria and body composition among young children with moderate acute malnutrition, a cross-sectional study from Burkina Faso.

Sci Rep 2020 08 6;10(1):13266. Epub 2020 Aug 6.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 25, 1958, Frederiksberg, Denmark.

Children with moderate acute malnutrition (MAM) are treated based on low weight-for-length z-score (WLZ), low mid-upper arm circumference (MUAC) or both. This study aimed to assess associations of admission criteria and body composition (BC), to improve treatment of MAM. We undertook a cross-sectional study among 6-23 months old Burkinabe children with MAM. Fat-free (FFM) and fat mass (FM) were determined by deuterium dilution and expressed as FFM (FFMI) and FM index (FMI). Of 1,489 children, 439 (29.5%) were recruited by low MUAC only (MUAC-O), 734 (49.3%) by low WLZ and low MUAC (WLZ-MUAC) and 316 (21.2%) by low WLZ only (WLZ-O). Thus, 1,173 (78.8%) were recruited by low MUAC, with or without low WLZ (ALL-MUAC). After adjustments, WLZ-O had 89 g (95% confidence interval (CI) 5; 172) lower FFM compared to MUAC-O. Similarly, WLZ-O had 0.89 kg/m (95% CI 0.77; 1.01) lower FFMI compared to MUAC-O, whereas there was no difference for FMI. However, boys included by WLZ-O compared to MUAC-O had 0.21 kg/m (95% CI 0.05; 0.38) higher FMI. In contrast, girls included by WLZ-O had 0.17 (95% CI 0.01; 0.33) kg/m lower FMI compared to MUAC-O (interaction, p = 0.002). We found that different criteria for admission into MAM treatment programmes select children with differences in BC, especially FFMI.Trial registration: ISRCTN42569496.
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http://dx.doi.org/10.1038/s41598-020-69987-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413376PMC
August 2020

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

BMC Infect Dis 2020 Aug 6;20(1):582. Epub 2020 Aug 6.

Department of Infectious Diseases, Rigshospitalet, Copenhagen, Denmark.

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/1.73m. About 41 and 26.9% of HIV patients had a drop of greater than 3 and 10 mL/min/1.73 m in eGFR at 12 month, respectively. However, none of the HIV patients declined to < 60 ml/min/1.73m 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.
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http://dx.doi.org/10.1186/s12879-020-05308-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409649PMC
August 2020

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

Clin Nutr 2021 02 24;40(2):624-631. Epub 2020 Jun 24.

Childhood Nutrition Research Centre, UCL Institute of Child Health, London, UK.

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.
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http://dx.doi.org/10.1016/j.clnu.2020.06.012DOI Listing
February 2021

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

Pediatr Res 2021 05 20;89(7):1732-1741. Epub 2020 Jul 20.

Médecins Sans Frontières-Denmark, Strandlodsvej 44, 2. 2300, København S, Denmark.

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.
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http://dx.doi.org/10.1038/s41390-020-1057-5DOI Listing
May 2021

HIV and metabolic syndrome in an Ethiopian population.

Ann Hum Biol 2020 Aug 20;47(5):457-464. Epub 2020 Jul 20.

Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Frederiksberg, Denmark.

Background: The global prevalence of metabolic syndrome (MS) is increasing due to lifestyle changes. Studies have found that MS is associated with human immunodeficiency virus (HIV) and antiretroviral treatment (ART), but controversies still exist on associations between HIV and MS.

Aims: To assess associations between HIV and MS among ART-naïve HIV positive individuals compared to HIV negative individuals.

Subjects And Methods: A cross-sectional study among ART-naïve HIV positive and HIV negative individuals recruited from HIV treatment and testing facilities in Ethiopia. Information was collected on components of MS: waist circumference, triglycerides, high-density lipoprotein cholesterol (HDL-C), blood pressure and fasting plasma glucose (FPG). Data were analysed using logistic and linear regression stratified by sex and adjusted for age, wealth and education.

Results: Data from 329 HIV positive and 100 HIV negative individuals were included. HIV positive status was associated with higher odds of MS in women (OR: 3.56, 95%CI: 1.25; 10.15) ( = 292), but not in men (OR: 0.98, 95%CI: 0.22; 4.30) ( = 137), interaction: = .11. Associations between HIV and components of MS were strongest for HDL-C among women and for FPG among men. The most prevalent components of MS in HIV positive individuals were elevated triglycerides, reduced HDL-C and elevated FPG.

Conclusions: HIV was associated with MS among ART-naïve women, suggesting that MS should be evaluated before initiating ART and monitored during treatment to identify those at risk of developing diabetes and cardiovascular disease (CVD).
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http://dx.doi.org/10.1080/03014460.2020.1781929DOI Listing
August 2020

Diabetes prevalence by HbA1c and oral glucose tolerance test among HIV-infected and uninfected Tanzanian adults.

PLoS One 2020 8;15(4):e0230723. Epub 2020 Apr 8.

Mwanza Research Centre, National Institute for Medical Research, Mwanza, Tanzania.

Background: The burden of diabetes is increasing in sub-Saharan Africa, including among people living with HIV. We assessed the prevalence of diabetes and the roles of HIV, antiretroviral therapy (ART) and traditional risk factors among adults in Tanzania.

Methods: We analysed diabetes-relevant baseline data from 1,947 adult participants in the CICADA study in Mwanza, Tanzania: 655 HIV-uninfected, 956 HIV-infected ART-naïve, and 336 HIV-infected persons on ART. WHO guidelines for haemoglobin A1c (HbA1c) and oral glucose tolerance test (OGTT) were used to define diabetes and prediabetes. Risk factors were evaluated using multinomial logistic regression analysis. Relative risk ratios (RRR) were generated comparing participants with diabetes and prediabetes against the reference of those with no diabetes.

Results: Mean age was 41 (SD 12) years; 59% were women. The prevalence of diabetes was 13% by HbA1c and 6% by OGTT, with partial overlap among participants identified by the two tests. Relative to HIV-uninfected, HIV-infected ART-naïve persons had increased relative risks of diabetes (HbA1c: RRR = 1.95, 95% CI 1.25-3.03; OGTT: RRR = 1.90, 95% CI 0.96-3.73) and prediabetes (HbA1c: RRR = 2.89, 95% CI 1.93-4.34; OGTT: RRR = 1.61, 95% CI 1.22-2.13). HIV-infected participants on ART showed increased risk of prediabetes (RRR 1.80, 95% CI 1.09, 2.94) by HbA1c, but not diabetes. CD4 count < 200 cell/μL at recruitment increased risk and physical activity decreased risk of diabetes by both HbA1c and OGTT.

Conclusions: The prevalence of diabetes was high, especially among HIV-infected ART-naïve adults. Being more physically active was associated with lower risk of diabetes. HbA1c and OGTT identified different participants as having diabetes or prediabetes. Overall, the finding of high burden of diabetes among HIV-infected persons suggests that health systems should consider integrating diabetes screening and treatment in HIV clinics to optimize the care of HIV patients and improve their health outcomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230723PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141607PMC
July 2020

Deworming children for soil-transmitted helminths in low and middle-income countries: systematic review and individual participant data network meta-analysis.

J Dev Effect 2019 6;11(3):288-306. Epub 2019 Dec 6.

Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands.

Intestinal parasites affect millions of children globally. We aimed to assess effects of deworming children on nutritional and cognitive outcomes across potential effect modifiers using individual participant data (IPD). We searched multiple databases to 27 March 2018, grey literature, and other sources. We included randomised and quasi randomised trials of deworming compared to placebo or other nutritional interventions with data on baseline infection. We used a random-effects network meta-analysis with IPD and assessed overall quality, following a pre-specified protocol. We received IPD from 19 trials of STH deworming. Overall risk of bias was low. There were no statistically significant subgroup effects across age, sex, nutritional status or infection intensity for each type of STH. These analyses showed that children with moderate or heavy intensity infections, deworming for STH may increase weight gain (very low certainty). The added value of this review is an exploration of effects on growth and cognition in children with moderate to heavy infections as well as replicating prior systematic review results of small effects at the population level. Policy implications are that complementary public health strategies need to be assessed and considered to achieve growth and cognition benefits for children in helminth endemic areas.
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http://dx.doi.org/10.1080/19439342.2019.1691627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077355PMC
December 2019

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

Clin Nutr 2020 11 24;39(11):3512-3519. Epub 2020 Mar 24.

Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1016/j.clnu.2020.03.016DOI Listing
November 2020

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

Clin Nutr 2020 11 6;39(11):3426-3433. Epub 2020 Mar 6.

Childhood Nutrition Research Centre, UCL Great Ormond Street Institute of Child Health, London, UK; Population, Policy, and Practice Programme, UCL Great Ormond Street Institute of Child Health, London, UK.

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/m; 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/m 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.
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http://dx.doi.org/10.1016/j.clnu.2020.02.038DOI Listing
November 2020

Restitution of gut microbiota in Ugandan children administered with probiotics ( GG and subsp. BB-12) during treatment for severe acute malnutrition.

Gut Microbes 2020 07 20;11(4):855-867. Epub 2020 Jan 20.

Department of Food Science, University of Copenhagen , Frederiksberg C, Denmark.

Severe acute malnutrition (SAM) is a major challenge in low-income countries and gut microbiota (GM) dysbiosis may play a role in its etiology. Here, we determined the GM evolution during rehabilitation from SAM and the impact of probiotics ( GG and subsp. lactis BB-12) supplementation. The GM (16S rRNA gene amplicon sequencing) of children admitted to hospital with SAM showed distinct composition over admission (e.g. spp., and Enterobacteriaceae spp.), discharge (e.g. Clostridiaceae spp., ) and follow-up (e.g. spp., ), reaching similar β- and α-diversity as healthy individuals. Children with diarrhea had reduced distribution of Bacteroidaceae, Lachnospiraceae, increased Enterobacteriaceae and Moraxellaceae, and lower α-diversity. Children suffering from edematous SAM had diminished proportion of Prevotellaceae, Lachnospiraceae, Ruminoccaceae and a higher α-diversity when compared to non-edematous SAM. Supplementation of probiotics did not influence β-diversity upon discharge or follow-up, but it increased ( < .05) the number of observed species [SE: > 4.5]. Children where the probiotic species were detected had lower cumulative incidence ( < .001) of diarrhea during the follow-up period compared to children receiving placebo and children receiving probiotics, but where the probiotics were not detected. The GM of children with non-edematous and edematous SAM differ in composition, which might have implications for future GM targeted treatments. Probiotics treatment reduced the cumulative incidence of diarrhea during the outpatient phase, with the strongest effect in children where the administered probiotics could be detected in the GM.
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http://dx.doi.org/10.1080/19490976.2020.1712982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524335PMC
July 2020

Critical evaluation of the appetite test for children with severe acute malnutrition.

Trop Med Int Health 2020 04 6;25(4):424-432. Epub 2020 Jan 6.

Department of Pediatrics and Child Health, Faculty of Medical Sciences, Jimma University, Jimma, Ethiopia.

Objectives: The appetite test is used to risk stratify for children with severe acute malnutrition (SAM) in inpatient or outpatient care. The test is recommended in guidelines despite lack of evidence. We evaluated its ability to identify children at risk of a poor treatment outcome.

Methods: We conducted an observational study of children diagnosed with SAM at three health facilities in Ethiopia. The appetite test was done independently, and the result did not affect decisions about hospitalisation and clinical care. Data were analysed using mixed linear and logistic regression models.

Results: Appetite was tested in 298 (89%) of 334 children enrolled; 56 (19%) passed. Children failing the appetite test had a 6.6% higher weight gain per day (95% CI: 2.6, 10.8) adjusted for type of treatment, oedema, duration of follow-up and age than children passing the test. We found medical complications in 179 (54%) children. Medical complications were associated with blood markers of metabolic disturbance. Children with medical complications tended to have lower weight gain than those without complications (3.5%, 95% CI: -0.25, 7.0). Neither the appetite test nor medical complications were correlated with bacteraemia or treatment failure.

Conclusions: Our findings question the use of the appetite test to identify children who need inpatient care. An assessment of medical complications alone could be a useful risk indicator but needs to be evaluated in other settings.
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http://dx.doi.org/10.1111/tmi.13360DOI Listing
April 2020

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

Matern Child Nutr 2020 04 11;16(2):e12928. Epub 2019 Dec 11.

Department of Nutrition, Exercise and Sports, SCIENCE, University of Copenhagen, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1111/mcn.12928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083399PMC
April 2020
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