Effects of L-Carnitine Supplementation on the Rate of Weight Gain and Biomarkers of Environmental Enteric Dysfunction in Children with Severe Acute Malnutrition: A Double-Blind Randomized Controlled Clinical Trial.

BACKGROUND: Severe acute malnutrition (SAM) is a major public health concern among low- and middle-income countries, where the majority of the children encountering this acute form of malnutrition suffer from environmental enteric dysfunction (EED). However, evidence regarding the effects of L-carnitine supplementation on the rate of weight gain and EED biomarkers in malnourished children is limited. OBJECTIVES: We aimed to investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with SAM. METHODS: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted at the Nutritional Rehabilitation Unit (NRU) of Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh. Children with SAM aged 9-24 mo were randomly assigned to receive commercial L-carnitine syrup (100 mg/kg/d) or placebo for 15 d in addition to standard of care. A total of 98 children with Weight-for-Length-z-score (WLZ) < -3 Standard deviation were enrolled between October 2021 and March 2023. Analyses were conducted on an intention-to-treat basis. RESULTS: The primary outcome variable, "rate of weight gain," was comparable between L-carnitine and placebo groups (2.09 ± 2.23 compared with 2.07 ± 2.70; P = 0.973), which was consistent even after adjusting for potential covariates (age, sex, Weight-for-Age z-score, asset index, and WASH practices) through linear regression [ß: 0.37; 95% confidence interval (CI): -0.63,1.37; P = 0.465]. The average hospital stay was ∼4 d. The results of adjusted median regression showed that following intervention, there was no significant difference in the EED biomarkers among the treatment arms; Myeloperoxidase (ng/mL) [ß: -1342.29; 95% CI: -2817.35, 132.77; P = 0.074], Neopterin (nmol/L) [ß: -153.33; 95% CI: -556.58, 249.91; P = 0.452], alpha-1-antitrypsin (mg/mL) [ß: 0.05; 95% CI: -0.15, 0.25; P = 0.627]. Initial L-carnitine (µmol/L) levels (median, interquartile range) for L-carnitine compared with placebo were 54.84 (36.0, 112.9) and 59.74 (45.7, 96.0), whereas levels after intervention were 102.05 (60.9, 182.1) and 105.02 (73.1, 203.7). CONCLUSIONS: Although our study findings suggest that L-carnitine bears no additional effect on SAM, we recommend clinical trials with a longer duration of supplementation, possibly with other combinations of interventions, to investigate further into this topic of interest. This trial was registered at clinicaltrials.gov as NCT05083637.

Inpatient Morbidity and Mortality of Severely Underweight Children Was Comparable to That of Severely Wasted Children in Dhaka, Bangladesh.

Both wasting and undernutrition are responsible for multiple morbidities and increased mortality in younger children hospitalized for acute illnesses. The question of whether children who are suffering from severe underweight are as vulnerable as children suffering from severe wasting needs to be researched further. We aimed to compare the morbidity and mortality of severely underweight but not severely wasted (SU-nSW) children with that of severely wasted (SW) children admitted to inpatient wards of a hospital. Data from 12,894 children aged < 5 years were collected using cross-sectional methods from Dhaka Hospital, International Centre for Diarrhoeal Disease Research, Bangladesh between March 2019 and December 2021. After exclusion of non-desired populations (N = 8,834), comparisons between SU-nSW (N = 1,876) and SW (N = 2,184) children were observed. The risk of morbidities and mortality among SU-nSW and SW children was analyzed after adjusting for age and sex. Inpatient morbidities were mostly similar among children with sepsis (adjusted odds ratio [aOR]: 0.90; 95% CI: 0.69, 1.19; P = 0.472) and convulsions (aOR: 0.84; 95% CI: 0.51, 1.37; P = 0.475). Dehydration (aOR: 0.71; 95% CI: 0.62, 0.81; P < 0.001) and hypokalemia (aOR: 0.58; 95% CI: 0.42, 0.79; P = 0.001) were more likely associated with SW children than with SU-nSW children. Pneumonia/severe pneumonia was more likely to affect SU-nSW children (aOR: 1.24; 95% CI: 1.02, 1.48; P = 0.018). Death was comparable between the two groups (aOR: 1.32; 95% CI: 0.70, 2.49; P = 0.386). This study underscores the importance of implementing present treatment guidelines for severe acute malnutrition in the facility-based management of severely underweight children as well.

Nutritional Profiles and Zinc Supplementation among Children with Diarrhea in Bangladesh.

Zinc supplementation is an added intervention with oral rehydration solution (ORS) for treating childhood diarrhea as per World Health Organization recommendations. Our study aimed to determine the prevalence of zinc administration in addition to ORS for childhood diarrhea before hospitalization and the nutritional profile of those children admitted to the outpatient department of the largest diarrheal facility in Bangladesh. This study used a screening dataset of a clinical trial (www.clinicaltrials.gov; NCT04039828) on zinc supplementation at a Dhaka hospital (International Centre for Diarrhoeal Disease Research, Bangladesh) between September 2019 and March 2020. A total of 1,399 children aged 3-59 months were included in our study. Children were divided into two groups (one group received zinc and another did not) and were analyzed accordingly; 39.24% (n = 549) children received zinc along with ORS for the current diarrheal episode prior to hospitalization. Percentages of underweight (weight-for-age z-score < -2 SD), stunting (length/height-for-age z-score < -2 SD), wasting (weight-for-length/height z-score < -2 SD), and overweight (weight-for-age z-score > +2 SD) among these children were 13.87% (n = 194), 14.22% (n = 199), 12.08% (n = 169), and 3.43% (n = 48), respectively. In logistic regression after adjusting age, sex, and nutritional status (underweight, stunting, wasting, and overweight), association of dehydration (adjusted odds ratio [aOR]: 0.06; 95% CI: 0.03-0.11; P < 0.01), bloody diarrhea (aOR: 0.18; 95% CI: 0.11-0.92; P < 0.01), and fever (aOR: 0.27; 95% CI: 0.18-0.41; P < 0.01) were less with children who received zinc at home. Bangladesh is one of the leading zinc coverage areas globally but lags behind the target for zinc coverage in diarrheal illness among under-five children. Policymakers should scale up and formulate guidelines with sustainable strategies to encourage zinc supplementation in diarrheal episodes in Bangladesh and elsewhere.

Role of L-Carnitine supplementation on rate of weight gain and biomarkers of Environmental Enteric Dysfunction in children with severe acute malnutrition: A protocol for a double-blinded randomized controlled trial.

BACKGROUND: Severe acute malnutrition (SAM) and environmental enteric dysfunction (EED) are highly prevalent among children residing in resource-limited countries like Bangladesh. L-carnitine may play a role in improving the growth and ameliorating the EED among nutritionally vulnerable children. OBJECTIVE: To investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with severe acute malnutrition. METHODS: This study is a double-blinded, placebo-controlled, randomized clinical trial aiming to enroll diarrheal children with SAM between 9-24 months of both sexes attending the nutritional rehabilitation unit (NRU) of Dhaka Hospital of icddr,b. It is an ongoing trial including two arms where one arm receives L-carnitine supplementation, and the other arms receive a placebo for 15 days in addition to the existing standard treatment of SAM. The primary outcome is the rate of weight gain, and the secondary outcomes include duration of hospital stay and EED biomarkers. Outcomes are assessed at baseline and 15 days of post-intervention. We hypothesize that the L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED. TRIAL REGISTRATION: ClinicalTrials.gov # NCT05083637. Date of registration: October 19, 2021.

Inadequate Vitamin C Intake and Intestinal Inflammation Are Associated with Multiple Micronutrient Deficiency in Young Children: Results from a Multi-Country Birth Cohort Study.

Children living in resource-limited settings often suffer from multiple micronutrient deficiencies (MMD). However, there lacks evidence on the correlates of MMD in young children. We investigated the role of diets, water, sanitation and hygiene practice, enteric infections, and impaired gut health on MMD in children at 24 months of age using data from the multi-country MAL-ED birth cohort study. Co-existence of more than one micronutrient deficiency (e.g., anemia, iron, zinc, or retinol deficiency) was considered as MMD. We characterized intestinal inflammation by fecal concentrations of myeloperoxidase (MPO) and neopterin (NEO) measured in the non-diarrheal stool samples. Bayesian network analysis was applied to investigate the factors associated with MMD. A total of 1093 children were included in this analysis. Overall, 47.6% of the children had MMD, with the highest prevalence in Pakistan (90.1%) and lowest in Brazil (6.3%). MMD was inversely associated with the female sex [OR: 0.72, 95% CI: 0.54, 0.92]. A greater risk of MMD was associated with lower vitamin C intake [OR: 0.70, 95% CI: 0.48, 0.94] and increased fecal concentrations of MPO [OR: 1.31, 95% CI: 1.08, 1.51]. The study results imply the importance of effective strategies to ameliorate gut health and improve nutrient intake during the early years of life.

New formulation zinc sulphate acceptability and adherence in children with acute diarrhoea: A prospective, open-label, interventional study in Bangladesh.

AIM: Zinc is an adjunct to oral rehydration salts for management of diarrhoea in children. Due to zinc's unpleasant taste, children often develop nausea and/or vomiting. We aimed to assess acceptability (tolerability) and adherence of improvised formulation of zinc tablet among under-five children with acute diarrhoea. METHODS: This was an open-label intervention trial among 3-59 months old diarrhoeal children attending the outpatient department of Dhaka Hospital, who were enrolled in two age strata, 3 to <18 months and 18-59 months. Zinc tablets 10 or 20 mg per day were prescribed for a total of 10 days for <6 months and ≥6 months age children respectively, with follow-up. Diary-cards were used to record events. RESULTS: In stratum 1, 158 (90.8%) children and in stratum 2, 144 (95.4%) children completed the study as per protocol out of 325 enrolled children. Sociodemographic, clinical and anthropometric measurements were comparable in the two strata except admission diarrhoeal duration (median 3 days vs. 2 days, P = 0.001). Adherence to 10 days treatment was 123 (77.8%) in stratum 1 and 127 (88.2%) in stratum 2. Zinc tablets were tolerated very well/well in 280 (92.7%) children. Vomiting, regurgitation and nausea were observed in 99 (32.8%), 59 (19.5%) and 22 (7.4%) children respectively. Caregivers' willingness to use the same drug in future was 300 (99.3%) among all children. CONCLUSION: Our study findings demonstrate that modified taste and formulation zinc tablets were well tolerated, and caregivers' willingness to use this formulation in future supports its acceptability, adherence and palatability.