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Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.

Background: From the 1950s to the mid-1970s, United Nations (UN) agencies were focused on protein malnutrition as the major worldwide nutritional problem. The goal of this review is to examine this era of protein malnutrition, the reasons for its demise, and the aftermath. Summary: The UN Protein Advisory Group was established in 1955. International conferences were largely concerned about protein malnutrition in children. By the early 1970s, UN agencies were ringing the alarm about a ‘protein gap'. In The Lancet in 1974, Donald McLaren branded these efforts as ‘The Great Protein Fiasco', declaring that the ‘protein gap' was a fallacy. The following year, John Waterlow, the scientist who led most of the efforts on protein malnutrition, admitted that a ‘protein gap' did not exist and that young children in developing countries only needed sufficient energy intake. The emphasis on protein malnutrition waned. It is recently apparent that quality protein and essential amino acids are missing in the diet and may have adverse consequences for child growth and the reduction of child stunting. Key Messages: It may be time to re-include protein and return protein malnutrition in the global health agenda using a balanced approach that includes all protective nutrients.

Malnutrition is classified into marasmus and kwashiorkor in children. However, the clinical significance of these aspects is unclear in adult patients with heart failure (HF). We divided 2308 adult patients with HF into four groups according to marasmus type (body mass index < 18.5 kg/m 2 ) and kwashiorkor type (serum albumin < 3.4 g/dL) malnutrition: Group C (no malnutrition, n = 1511, 65.5%), Group M (marasmus type malnutrition, n = 133, 5.8%), Group K (kwashiorkor type malnutrition, n = 554, 24.0%) and Group MK (marasmic-kwashiorkor type malnutrition, n = 110, 4.8%). Group M showed the lowest blood pressure. Groups K and MK showed higher levels of B-type natriuretic peptide. Right atrial pressure was lowest in Groups M and MK. Kaplan-Meir analysis demonstrated that Group MK had the lowest event-free rate of all-cause death and cardiac death. In the multivariable Cox proportional hazard analysis, Groups M, K, and MK were associated with all-cause death (hazard ratio 1.790, 1.657 and 2.313, respectively) and cardiac death (hazard ratio 2.053, 1.855 and 3.001, respectively) compared to Group C as a reference. Marasmus type and kwashiorkor type malnutrition are associated with distinct profiles and high mortality, and marasmic-kwashiorkor type malnutrition has the poorest prognosis.

Severe acute malnutrition in childhood manifests as oedematous (kwashiorkor, marasmic kwashiorkor) and non-oedematous (marasmus) syndromes with very different prognoses. Kwashiorkor differs from marasmus in the patterns of protein, amino acid and lipid metabolism when patients are acutely ill as well as after rehabilitation to ideal weight for height. Metabolic patterns among marasmic patients define them as metabolically thrifty, while kwashiorkor patients function as metabolically profligate. Such differences might underlie syndromic presentation and prognosis. However, no fundamental explanation exists for these differences in metabolism, nor clinical pictures, given similar exposures to undernutrition. We hypothesized that different developmental trajectories underlie these clinical-metabolic phenotypes: if so this would be strong evidence in support of predictive adaptation model of developmental plasticity. We reviewed the records of all children admitted with severe acute malnutrition to the Tropical Metabolism Research Unit Ward of the University Hospital of the West Indies, Kingston, Jamaica during 1962-1992. We used Wellcome criteria to establish the diagnoses of kwashiorkor (n = 391), marasmus (n = 383), and marasmic-kwashiorkor (n = 375). We recorded participants' birth weights, as determined from maternal recall at the time of admission. Those who developed kwashiorkor had 333 g (95% confidence interval 217 to 449, p<0.001) higher mean birthweight than those who developed marasmus. These data are consistent with a model suggesting that plastic mechanisms operative in utero induce potential marasmics to develop with a metabolic physiology more able to adapt to postnatal undernutrition than those of higher birthweight. Given the different mortality risks of these different syndromes, this observation is supportive of the predictive adaptive response hypothesis and is the first empirical demonstration of the advantageous effects of such a response in humans. The study has implications for understanding pathways to obesity and its cardio-metabolic co-morbidities in poor countries and for famine intervention programs.

Background: Long-term impact of different forms of severe acute malnutrition (SAM) in childhood on the emergence of noncommunicable diseases (NCDs) is poorly known. Aim: To explore the association between subtypes of SAM during childhood, NCDs, and cardiovascular risk factors (CVRFs) in young adults 11 to 30 years after post-SAM nutritional rehabilitation. Methods: In this follow-up study, we investigated 524 adults (mean age 22 years) treated for SAM during childhood in eastern Democratic Republic of the Congo (DRC) between 1988 and 2007. Among them, 142 had a history of marasmus, 175 of kwashiorkor, and 207 had mixed-form SAM. These participants were compared to 407 aged- and sex-matched control adults living in the same community without a history of SAM. Our outcomes of interest were cardiometabolic risk markers for NCDs. Logistic and linear regressions models were sued to estimate the association between subtype of SAM in childhood and risk of NCDs. Results: Compared to unexposed, former mixed-type SAM participants had a higher adjusted ORs of metabolic syndrome [2.68 (1.18; 8.07)], central obesity [1.89 (1.11; 3.21)] and low HDL-C (High-density lipoprotein cholesterol) [1.52 (1.08; 2.62)]. However, there was no difference between groups in terms of diabetes, high blood pressure, elevated LDL-C (low-density lipoprotein cholesterol) and hyper TG (hypertriglyceridemia) and overweightness. Former mixed-type SAM participants had higher mean fasting glucose [3.38 mg/dL (0.92; 7.7)], reduced muscle strength [−3.47 kg (−5.82; −1.11)] and smaller hip circumference [−2.27 cm (−4.24; −0.31)] compared to non-exposed. Regardless of subtypes, SAM-exposed participants had higher HbA1c than unexposed (p < 0.001). Those with a history of kwashiorkor had cardiometabolic and nutritional parameters almost superimposable to those of unexposed. Conclusion: The association between childhood SAM, prevalence of NCDs and their CVRFs in adulthood varies according to SAM subtypes, those with mixed form being most at risk. Multicenter studies on larger cohorts of older participants are needed to elucidate the impact of SAM subtypes on NCDs risk.

RationaleSince the first documentation of skin changes in malnutrition in the early 18th century, various hair and skin changes have been reported in severely malnourished children globally. We aimed to describe the frequency and types of skin conditions in children admitted with acute illness to Queen Elizabeth Central Hospital, Blantyre, Malawi across a spectrum of nutritional status and validate an existing skin assessment tool.MethodsChildren between 1 week and 23 months of age with acute illness were enrolled and stratified by anthropometry. Standardised photographs were taken, and three dermatologists assessed skin changes and scored each child according to the SCORDoK tool.ResultsAmong 103 children, median age of 12 months, 31 (30%) had severe wasting, 11 (11%) kwashiorkor (nutritional oedema), 20 (19%) had moderate wasting, 41 (40%) had no nutritional wasting and 18 (17%) a positive HIV antibody test. Six (5.8%) of the included patients died. 51 (50%) of children presented with at least one skin change. Pigmentary changes were the most common, observed in 35 (34%), with hair loss and bullae, erosions and desquamation the second most prevalent skin condition. Common diagnoses were congenital dermal melanocytosis, diaper dermatitis, eczema and postinflammatory hyperpigmentation. Severe skin changes like flaky paint dermatosis were rarely identified. Inter-rater variability calculations showed only fair agreement (overall Fleiss’ kappa 0.25) while intrarater variability had a fair-moderate agreement (Cohen’s kappa score of 0.47–0.58).DiscussionSkin changes in hospitalised children with an acute illness and stratified according to nutritional status were not as prevalent as historically reported. Dermatological assessment by means of the SKORDoK tool using photographs is less reliable than expected.

Objective To determine the prevalence, risk factors, co-morbidities and case fatality rates of Protein Energy Malnutrition (PEM) admissions at the paediatric ward of the University of Nigeria Teaching Hospital Enugu, South-east Nigeria over a 10 year period. Design A retrospective study using case Notes, admission and mortality registers retrieved from the Hospital’s Medical Records Department. Subjects All children aged 0 to 59 months admitted into the hospital on account of PEM between 1996 and 2005. Results A total of 212 children with PEM were admitted during the period under review comprising of 127 (59.9%) males and 85(40.1%) females. The most common age groups with PEM were 6 to 12 months (55.7%) and 13 to 24 months (36.8%). Marasmus (34.9%) was the most common form of PEM noted in this review. Diarrhea and malaria were the most common associated co-morbidities. Majority (64.9%) of the patients were from the lower socio-economic class. The overall case fatality rate was 40.1% which was slightly higher among males (50.9%). Mortality in those with marasmic-kwashiokor and in the unclassified group was 53.3% and 54.5% respectively. Conclusion Most of the admissions and case fatality were noted in those aged 6 to 24 months which coincides with the weaning period. Marasmic-kwashiokor is associated with higher case fatality rate than other forms of PEM. We suggest strengthening of the infant feeding practices by promoting exclusive breastfeeding for the first six months of life, followed by appropriate weaning with continued breast feeding. Under-five children should be screened for PEM at the community level for early diagnosis and prompt management as a way of reducing the high mortality associated with admitted severe cases.

Mortality among African children hospitalized with severe malnutrition remains high, with sudden, unexpected deaths leading to speculation about potential cardiac causes. Malnutrition is considered high risk for cardiac failure, but evidence is limited. To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). A prospective, matched case-control study, the Cardiac Physiology in Malnutrition (CAPMAL) study, of 88 children with SAM (exposed) vs 22 severity-matched patients without SAM (unexposed) was conducted between March 7, 2011, and February 20, 2012; data analysis was performed from October 1, 2012, to March 1, 2016. Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Eighty-eight children (52 with marasmus and 36 with kwashiorkor) of the 418 admitted with SAM and 22 severity-matched controls were studied. A total of 63 children (57%) were boys; median age at admission was 19 months (range, 12-39 months). On admission, abnormalities more common in cases vs controls included severe hypokalemia (potassium <2.5 mEq/L) (18 of 81 [22%] vs 0%), hypoalbuminemia (albumin level <3.4 g/dL) (66 of 88 [75%] vs 4 of 22 [18%]), and hypothyroidism (free thyroxine level <0.70 ng/dL or thyrotropin level >4.2 mU/L) (18 of 74 [24%] vs 1 of 21 [5%]) and were associated with typical electrocardiographic changes (T-wave inversion: odds ratio, 7.3; 95% CI, 1.9-28.0; P = .001), which corrected as potassium levels improved. Fourteen children with SAM (16%) but no controls died. Myocardial mass was lower in cases on admission but not by day 7. Results of the Tei Index, a measure of global cardiac function, were within the reference range and similar in cases (median, 0.37; interquartile range [IQR], 0.26-0.45) and controls (median, 0.36; IQR, 0.28-0.42). Echocardiography detected no evidence of cardiac failure among children with SAM, including those receiving intravenous fluids to correct hypovolemia. Cardiac dysfunction was generally associated with comorbidity and typical of hypovolemia, with low cardiac index (median, 4.9 L/min/m2; IQR, 3.9-6.1 L/min/m2), high systemic vascular resistance index (median, 1333 dyne seconds/cm5/m2; IQR, 1133-1752 dyne seconds/cm5/m2), and with few differences between the marasmus and kwashiorkor manifestations of malnutrition. Seven-day continuous ECG Holter monitoring during the high-risk initial refeeding period demonstrated self-limiting significant ventricular arrhythmias in 33 of 55 cases (60%) and 6 of 18 controls (33%) (P = .049); none were temporally related to adverse events, including fatalities. There is little evidence that African children with SAM are at greater risk of cardiac dysfunction or clinically significant arrhythmias than those without SAM or that marasmus and kwashiorkor differed in cardiovascular profile. These findings should prompt a review of current guidelines.