Complicated Severe Malnutrition Research Articles

Low to high caloric feed transition failure in hospitalized children with complicated severe malnutrition: A secondary analysis of the childhood acute illness nutrition network (CHAIN) Cohort

Low to high caloric feed transition failure in hospitalized children with complicated severe malnutrition: A secondary analysis of the childhood acute illness nutrition network (CHAIN) Cohort

Intestinal disturbances associated with mortality of children with complicated severe malnutrition

BackgroundChildren admitted to hospital with complicated severe malnutrition (CSM) have high mortality despite compliance with standard WHO management guidelines. Limited data suggests a relationship between intestinal dysfunction and poor prognosis in CSM, but this has not been explicitly studied. This study aimed to evaluate the role of intestinal disturbances in CSM mortality.MethodsA case-control study nested within a randomized control trial was conducted among children hospitalized with CSM in Kenya and Malawi. Children who died (cases, n = 68) were compared with those who were discharged, propensity matched to the cases on age, HIV and nutritional status (controls, n = 68) on fecal metabolomics that targeted about 70 commonly measured metabolites, and enteropathy markers: fecal myeloperoxidase (MPO), fecal calprotectin, and circulating intestinal fatty acid binding protein (I-FABP).ResultsThe fecal metabolomes of cases show specific reductions in amino acids, monosaccharides, and microbial fermentation products, when compared to controls. SCFA levels did not differ between groups. The overall fecal metabolomics signature moderately differentiates cases from controls (AUC = 0.72). Enteropathy markers do not differ between groups overall, although serum I-FABP is elevated in cases in a sensitivity analysis among non-edematous children. Integrative analysis with systemic data suggests an indirect role of intestinal inflammation in the causal path of mortality.ConclusionsIntestinal disturbances appear to have an indirect association with acute mortality. Findings of the study improve our understanding of pathophysiological pathways underlying mortality of children with CSM.

Systemic inflammation and metabolic disturbances underlie inpatient mortality among ill children with severe malnutrition.

Children admitted to hospital with an acute illness and concurrent severe malnutrition [complicated severe malnutrition (CSM)] have a high risk of dying. The biological processes underlying their mortality are poorly understood. In this case-control study nested within a multicenter randomized controlled trial among children with CSM in Kenya and Malawi, we found that blood metabolomic and proteomic profiles robustly differentiated children who died (n = 92) from those who survived (n = 92). Fatalities were characterized by increased energetic substrates (tricarboxylic acid cycle metabolites), microbial metabolites (e.g., propionate and isobutyrate), acute phase proteins (e.g., calprotectin and C-reactive protein), and inflammatory markers (e.g., interleukin-8 and tumor necrosis factor–α). These perturbations indicated disruptions in mitochondria-related bioenergetic pathways and sepsis-like responses. This study identified specific biomolecular disturbances associated with CSM mortality, revealing that systemic inflammation and bioenergetic deficits are targetable pathophysiological processes for improving survival of this vulnerable population.

Corrigendum.

Maternal & Child NutritionVolume 16, Issue 3 e13007 CORRIGENDUMOpen Access Corrigendum This article corrects the following: Phenotype is sustained during hospital readmissions following treatment for complicated severe malnutrition among Kenyan children: A retrospective cohort study Gerard Bryan Gonzales, Moses M. Ngari, James M. Njunge, Johnstone Thitiri, Laura Mwalekwa, Neema Mturi, Martha K. Mwangome, Caroline Ogwang, Amek Nyaguara, James A. Berkley, Volume 16Issue 2Maternal & Child Nutrition First Published online: November 22, 2019 First published: 16 June 2020 https://doi.org/10.1111/mcn.13007AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat In the following article (Gonzales et al., 2020), there was a typesetting error in key messages on page 2. The word “readmitted” should have been changed to “admitted” in the sentence. The incorrect sentence reads: Severe malnutrition phenotype was persistent such that a child readmitted for kwashiorkor would be likely to be readmitted with kwashiorkor again. The correct sentence should have read: Severe malnutrition phenotype was persistent such that a child admitted for kwashiorkor would be likely to be readmitted with kwashiorkor again. REFERENCE Gonzales, G. B., Ngari, M. M., Njunge, J. M., Thitiri, J., Mwalekwa, L., Mturi, N., … Berkley, J. A. (2020). Phenotype is sustained during hospital readmissions following treatment for complicated severe malnutrition among Kenyan children: A retrospective cohort study. Maternal and Child Nutrition, 16, e12913. Volume16, Issue3July 2020e13007 ReferencesRelatedInformation

Metabolomic Profiles Associated with Mortality of Children with Complicated Severe Malnutrition: A Nested Case-Control Study

Abstract Objectives Children hospitalized with complicated severe malnutrition (CSM) have unacceptably high mortality rates despite receiving standard nutritional and medical treatment. The underlying pathology of the poor prognosis is not well understood. Growing evidence indicates presence of metabolic dysfunction in CSM. Yet, it is unclear whether and how metabolic dysfunction contributes the poor prognosis. This study aimed to identify metabolic signatures and pathways associated with CSM mortality. Methods A case-control study was performed on CSM patients enrolled to a multicenter (one Malawi and two Kenya hospitals) randomized control trial (NCT02246296). A total of 90 death cases and 90 discharged controls that were propensity score matched by age, HIV and mid-upper arm circumferences were included in the study. Targeted metabolomics was performed on their serum samples collected at admission and on day 3 of hospitalization. In particular, 206 metabolites, including amino acids, acylcarnitines, lipids and organic acids were quantified by LC-MS/MS. Results Discriminant analysis (PLS-DA) showed that metabolomic signatures at admission could differentiate cases from controls, with a cross-validated classification error rate of 21.8%. An increase of homovanillic, isobutyric and propionic acids, and decrease of lipids lysoPC a C18:2, lysoPC a C20:4, PC ae C42:2, SM C26:0, and SM C26:1 were the top 8 significant features characterizing the admission metabolomes of cases. Notably, cases with higher levels of isobutyrate, a microbial fermentation product, had significantly shorter survival time, implying a role of gut integrity in mortality. Pathway analysis revealed that metabolites of the tricarboxylic acid (TCA) cycle pathway differentiated cases from controls. Analysis of day 3 samples showed metabolic differences in response to treatment, especially in the recovery rate of lipids, between cases and controls. Conclusions CSM non-survivors have metabolomes distinct from survivors indicating perturbations in mitochondrial function and nutrition utilization. Perturbed metabolites identified shed light on biological mechanisms of mortality and may serve as targets of nutritional or therapeutic interventions to improve CSM survival. Funding Sources Bill and Melinda Gates Foundation, Thrasher Research Fund, and RESTRACOMP Graduate Scholarship.

Phenotype is sustained during hospital readmissions following treatment for complicated severe malnutrition among Kenyan children: A retrospective cohort study

Hospital readmission is common among children with complicated severe acute malnutrition (cSAM) but not well‐characterised. Two distinct cSAM phenotypes, marasmus and kwashiorkor, exist, but their pathophysiology and whether the same phenotype persists at relapse are unclear. We aimed to test the association between cSAM phenotype at index admission and readmission following recovery. We performed secondary data analysis from a multicentre randomised trial in Kenya with 1‐year active follow‐up. The main outcome was cSAM phenotype upon hospital readmission. Among 1,704 HIV‐negative children with cSAM discharged in the trial, 177 children contributed a total of 246 readmissions with cSAM. cSAM readmission was associated with age<12 months (p = .005), but not site, sex, season, nor cSAM phenotype. Of these, 42 children contributed 44 readmissions with cSAM that occurred after a monthly visit when SAM was confirmed absent (cSAM relapse). cSAM phenotype was sustained during cSAM relapse. The adjusted odds ratio for presenting with kwashiorkor during readmission after kwashiorkor at index admission was 39.3 [95% confidence interval (95% CI) [2.69, 1,326]; p = .01); and for presenting with marasmus during readmission after kwashiorkor at index admission was 0.02 (95% CI [0.001, 0.037]; p = .01). To validate this finding, we examined readmissions to Kilifi County Hospital, Kenya occurring at least 2 months after an admission with cSAM. Among 2,412 children with cSAM discharged alive, there were 206 readmissions with cSAM. Their phenotype at readmission was significantly influenced by their phenotype at index admission (p < .001). This is the first report describing the phenotype and rate of cSAM recurrence.

Linear growth following complicated severe malnutrition: 1-year follow-up cohort of Kenyan children

BackgroundStunting is the most common manifestation of childhood undernutrition worldwide. Children presenting with severe acute malnutrition (SAM) are often also severely stunted. We evaluated linear growth and its determinants after...

Changes in susceptibility to life-threatening infections after treatment for complicated severe malnutrition in Kenya

ABSTRACTBackgroundGoals of treating childhood severe acute malnutrition (SAM), in addition to anthropometric recovery and preventing short-term mortality, include reducing the risks of subsequent serious infections. How quickly and how much the risk of serious illness changes during rehabilitation are unknown but could inform improving the design and scope of interventions.ObjectiveThe aim of this study was to investigate changes in the risk of life-threatening events (LTEs) in relation to anthropometric recovery from SAM.DesignThis was a secondary analysis of a clinical trial including 1778 HIV-uninfected Kenyan children aged 2–59 mo with complicated SAM, enrolled after the inpatient stabilization phase of treatment, and followed for 12 mo. The main outcome was LTEs, defined as infections requiring rehospitalization or causing death. We examined anthropometric variables measured at months 1, 3, and 6 after enrollment in relation to LTEs occurring during the 6 mo after each of these time points.ResultsOver 12 mo, there were 823 LTEs (257 fatal), predominantly severe pneumonia and diarrhea. At months 1, 3, and 6, 557 (34%), 764 (49%), and 842 (56%) children had a weight-for-height or -length z score (WHZ) ≥−2, respectively, which, compared with a WHZ <−3, was associated with lower risks of subsequent LTEs [adjusted HRs (95% CIs): 0.50 (0.40, 0.64), 0.30 (0.23, 0.39), and 0.23 (0.16, 0.32), respectively]. However, children with a WHZ ≥−2 at 1, 3, and 6 mo still had 39 (95% CI: 32, 47), 26 (95% CI: 22, 32), and 15 (95% CI: 12, 20) LTEs/100 child-years of observation during the following 6 mo. WHZ at study enrollment predicted subsequent WHZ but not the risk of LTEs. Changes in height-for-age z score did not predict LTEs.ConclusionsAnthropometric response was associated with a rapid and substantial reduction in risk of LTEs. However, reduction in susceptibility lagged behind anthropometric improvement. Disease events, together with anthropometric assessment, may provide a clearer picture of the effectiveness of interventions. Robust protocols for detecting and treating poor anthropometric recovery and addressing broader vulnerabilities that complicated SAM indicates may save lives. This trial was registered at www.clinicaltrials.gov as NCT00934492.

Population Pharmacokinetics of Gentamicin in Mexican Children With Severe Malnutrition

To develop a population pharmacokinetic model of gentamicin in children with complicated severe malnutrition and to study the influence of covariates (weight and age) on pharmacokinetic indices. In addition, we use the model to perform Monte Carlo simulations to explore the efficacy of several dosage regimens. Twenty-six children with severe complicated malnutrition were studied. Ninety-six samples of gentamicin plasma concentrations, obtained from 0.5 to 8 hours after intravenous dosing, were analyzed. Population pharmacokinetic models were built using the program Monolix 4.2 (Lixoft, Antony, France). Monte Carlo simulations were performed to evaluate optimal dosage regimens, using the final pharmacokinetic model, based on the probability of pharmacokinetic-pharmacodynamic target attainment. The concentration-time data were fitted best to 1-compartment model. The estimated population clearance was 1.1 L/h, and the volume of distribution was 2.23 L, with an interindividual variability of 47.2% and 35.6%, respectively. The final models for the clearance and volume of distribution were as follows: CL (L/h) = CL = 1.15 (age/median age) and V (L) = 2.33 (weight/median weight). In Monte Carlo simulations, gentamicin given in dosages of 7.5 to 15 mg/kg optical density was effective in achieving the pharmacodynamic target Cmax:minimal inhibitory concentration >10 for minimal inhibitory concentrations ≤2.5 mg/L, with a probability lower than 1% for Cmin >1 mg/L. Based on the available evidence, an intravenous dose of 7.5 to 15 mg/kg once daily in children with complicated severe malnutrition and normal renal function ensures high probability of efficacy and low risk of nephrotoxicity, which gives further support to the recommendations issued by the World Health Organization treatment for this patient population.

Inpatient management of children with severe acute malnutrition: a review of WHO guidelines.

ObjectiveTo understand how the World Health Organization’s (WHO’s) guidelines on the inpatient care of children with complicated severe acute malnutrition may be strengthened to improve outcomes.MethodsIn December 2015, we searched Google scholar and WHO’s website for WHO recommendations on severe acute malnutrition management and evaluated the history and cited evidence behind these recommendations. We systematically searched WHO International Clinical Trials Registry Platform, clinicaltrials.gov and the Controlled Trials metaRegister until 10 August 2015 for recently completed, ongoing, or pending trials.FindingsWHO’s guidelines provide 33 recommendations on the topic. However, 16 (48.5%) of these recommendations were based solely on expert opinion – unsupported by published evidence. Another 11 (33.3%) of the recommendations were supported by the results of directly relevant research – i.e. either randomized trials (8) or observational studies (3). The other six recommendations (18.2%) were based on studies that were not conducted among children with complicated severe malnutrition or studies of treatment that were not identical to the recommended intervention. Trials registries included 20 studies related to the topic, including nine trials of alternative feeding regimens. Acute medical management and follow-up care studies were minimally represented.ConclusionWHO’s guidelines on the topic have a weak evidence base and have undergone limited substantive adjustments over the past decades. More trials are needed to make that evidence base more robust. If the mortality associated with severe malnutrition is to be reduced, inpatient and post-discharge management trials, supported by studies on the causes of mortality, are needed.