Risk of Chronic Disease after an Episode of Marasmus, Kwashiorkor or Mixed-Type Severe Acute Malnutrition in the Democratic Republic of Congo: The Lwiro Follow-Up Study.

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.

Dietary intake of sulfur amino acids and risk of kwashiorkor malnutrition in eastern Democratic Republic of the Congo.

BACKGROUND: Kwashiorkor is an often-fatal type of severe acute malnutrition affecting hundreds of thousands of children annually, but whose etiology is still unknown. Evidence suggests inadequate sulfur amino acid (SAA) status may explain many signs of the condition but studies evaluating dietary protein intake in relation to the genesis of kwashiorkor have been conflicting. We know of no studies of kwashiorkor that have measured dietary SAAs. OBJECTIVES: We aimed to determine whether children in a population previously determined to have high prevalence of kwashiorkor [high-prevalence population (HPP)] have lower dietary intakes of SAAs than children in a low-prevalence population (LPP). METHODS: A cross-sectional census survey design of 358 children compared 2 previously identified adjacent populations of children 36-59 mo old in North Kivu Province of the Democratic Republic of the Congo. Data collected included urinary thiocyanate (SCN), cyanogens in cassava-based food products, recent history of illness, and a 24-h quantitative diet recall for the child. RESULTS: The HPP and LPP had kwashiorkor prevalence of 4.5% and 1.7%, respectively. A total of 170 children from 141 households in the LPP and 169 children from 138 households in the HPP completed the study. A higher proportion of HPP children had measurable urinary SCN (44.8% compared with 29.4%, P < 0.01). LPP children were less likely to have been ill recently (26.8% compared with 13.6%, P < 0.01). Median [IQR] intake of SAAs was 32.4 [22.9-49.3] mg/kg for the LPP and 29.6 [18.1-44.3] mg/kg for the HPP (P < 0.05). Methionine was the first limiting amino acid in both populations, with the highest risk of inadequate intake found among HPP children (35.1% compared with 23.6%, P < 0.05). CONCLUSIONS: Children in a population with a higher prevalence of kwashiorkor have lower dietary intake of SAAs than children in a population with a lower prevalence. Trial interventions to reduce incidence of kwashiorkor should consider increasing SAA intake, paying particular attention to methionine.

Understanding the Mothers of Children with Spina Bifida and Hydrocephalus in Tanzania.

OBJECTIVE: To identify if there are cultural, medical, educational, economic, nutritional and geographic barriers to the prevention and treatment of spina bifida and hydrocephalus. METHODS: The mothers of infants with spina bifida and hydrocephalus admitted to Muhimbilli Orthopaedic Institute, Dar Es Salaam, Tanzania, between 2013 and 2014 were asked to complete a questionnaire. A total of 299 infants were identified: 65 with myelomeningoceles, 19 with encephaloceles, and 215 with isolated hydrocephalus. The questionnaire was completed by 294 of the mothers. RESULTS: There was a high variation in the geographic origin of the mothers. Approximately 85% traveled from outside of Dar Es Salaam. The mean age was 29 (15-45) years old with a parity of 3 (1-10). The rates of consanguinity, obesity, antiepileptic medication, HIV seropositivity, and family history were 2%, 13%, 0%, 2%, and 2%, respectively. A maize-based diet was found in 84%, and only 3% of woman took folic acid supplementation, despite 61% of mothers stating that they wished to conceive another baby. Unemployment was high (77%), a low level of education was common (76% not attended any school or obtaining a primary level only), and 20% were single mothers. Hospital only was the preferred method of treatment for 94% of the mothers, and 85% of the babies were born in a hospital. CONCLUSIONS: Our study highlights some of the cultural, educational, geographic, nutritional, and economic difficulties in the prevention and management of spina bifida and hydrocephalus in Tanzania.

Assessment of Myocardial Function in Kenyan Children With Severe, Acute Malnutrition: The Cardiac Physiology in Malnutrition (CAPMAL) Study.

Importance: 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. Objective: To investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM). Design, Setting, and Participants: 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. Exposures: Echocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28. Main Outcomes and Measures: Findings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared. Results: 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. Conclusions and Relevance: 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.

Lost in Aggregation: The Geographic Distribution of Kwashiorkor in Eastern Democratic Republic of the Congo.

BACKGROUND: Kwashiorkor is a major classification of severe acute malnutrition whose etiology remains elusive. It is estimated to affect hundreds of thousands of children annually, but no accurate global prevalence figures are available. Little is known how prevalence varies within populations, an important undocumented aspect of kwashiorkor obscured by the aggregation of prevalence or incidence of the condition across large populations and geographic areas. OBJECTIVE: To estimate the prevalence of kwashiorkor in select neighboring villages of the eastern Democratic Republic of the Congo (DRC) and assess if prevalence can vary dramatically among neighboring villages. METHODS: An anthropometric census survey evaluated 1328 children aged 12 to 59 months within all 19 villages in one health area of eastern DRC, recording all cases of kwashiorkor, diagnosed by bipedal pitting edema. RESULTS: Village-level prevalence of kwashiorkor in the study area varied from 0% to 14.9%. Interviews with health services staff in the study area and across 2 provinces confirmed that current differences in prevalence reflect a long-term pattern and are a common feature of kwashiorkor throughout this region. CONCLUSIONS: Aggregation of kwashiorkor prevalence and incidence data across large populations or geographic regions poses several risks to understanding the epidemiology of kwashiorkor. If clustering of kwashiorkor is not taken into account, (1) nutritional crises in particular villages may go undetected; (2) the real effect of interventions may be underestimated; (3) interventions may be inappropriately targeted, leading to reduced coverage, efficacy, and cost-efficiency; and (4) important insights into the root causes of kwashiorkor may be lost.

Influence of malnutrition upon all-cause mortality among children in Swaziland.

OBJECTIVE: To analyze the effect of the type of malnutrition, sex, age and the presence of edema upon all-cause mortality in children under 5 years of age. MATERIAL AND METHODS: A cross-sectional study was conducted during 2010 and 2011 in Swaziland. Sex, age, weight and height were taken to classify nutritional status according to the 2006 WHO growth standards: stunting (low height for age), wasting (low weight for height or low body mass index for age) and underweight (low weight for age). The sample (309 boys and 244 girls under 5 years of age) was analyzed by sex and age groups (under and equal/over 12 months). The association between variables was evaluated using the χ2 test. Cox regression analysis (HR, 95% CI) was used to assess the likelihood of mortality. RESULTS: The mortality risk in malnourished children under one year of age was lower among females and increased in the presence of severe edema. Wasting combined with underweight increased the mortality risk in children under 12 months of age 5-fold, versus 11-fold in older children. The combination of stunting, wasting and underweight was closely associated to mortality. Stunting alone (not combined with wasting) did not significantly increase the mortality risk. CONCLUSIONS: Sex, severe edema and wasting are predictors of mortality in malnourished children. Regardless of these factors, children with deficiencies referred to weight for height and weight for age present a greater mortality risk in comparison with children who present stunting only.

The Rise and Fall of Protein Malnutrition in Global Health.

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.

Gut microbiomes of Malawian twin pairs discordant for kwashiorkor.

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.

Under-five protein energy malnutrition admitted at the University of Nigeria Teaching Hospital, Enugu: a 10 year retrospective review.

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.

Prenatal factors contribute to the emergence of kwashiorkor or marasmus in severe undernutrition: evidence for the predictive adaptation model.

BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Protein energy malnutrition.

Protein energy malnutrition (PEM) is a common problem worldwide and occurs in both developing and industrialized nations. In the developing world, it is frequently a result of socioeconomic, political, or environmental factors. In contrast, protein energy malnutrition in the developed world usually occurs in the context of chronic disease. There remains much variation in the criteria used to define malnutrition, with each method having its own limitations. Early recognition, prompt management, and robust follow up are critical for best outcomes in preventing and treating PEM.

The use of home-based therapy with ready-to-use therapeutic food to treat malnutrition in a rural area during a food crisis.

When the international community declared a famine in Malawi in January of 2006, emergency food aid reached only populations with pre-existing health care services. To treat the widespread childhood malnutrition in Machinga district, a rural area lacking health care facilities, in February 2006 five outpatient therapeutic programs were implemented that utilized home-based therapy and ready-to-use therapeutic food. Children with severe malnutrition, defined as the presence of edema and/or a weight-for-height less than 70% of the reference standard, were enrolled in the program. Two senior clinical nurses trained village health aides in each of the five communities. Children visited the health aides biweekly. During the visits, health aides collected demographic and anthropometric information and distributed a 2-week supply of ready-to-use therapeutic food, providing 175 kcal/kg/d. Treatment continued for 8 weeks; children were discharged before 8 weeks if they reached a weight-for-height more than 100% of the reference standard, or required admission to the hospital due to systemic infection or recurrence of edema. Of the 826 children enrolled, 775 (93.7%) recovered, 13 (1.8%) remained malnourished, 30 (3.6%) defaulted, and 8 (0.9%) died. Mean weight gained was 2.7+/-3.7 g/kg/d, height gained 0.3+/-0.9 mm/d, and mid-upper arm circumference gained 0.2+/-0.3 mm/d. Home-based therapy with ready-to-use therapeutic food administered by village health aides is an effective approach to treating malnutrition during food crises in areas lacking health services.

Fraction of all hospital admissions and deaths attributable to malnutrition among children in rural Kenya.

BACKGROUND: Malnutrition is common in the developing world and associated with disease and mortality. Because malnutrition frequently occurs among children in the community as well as those with acute illness, and because anthropometric indicators of nutritional status are continuous variables that preclude a single definition of malnutrition, malnutrition-attributable fractions of admissions and deaths cannot be calculated by simply enumerating individual children. OBJECTIVE: We determined the malnutrition-attributable fractions among children admitted to a rural district hospital in Kenya, among inpatient deaths and among children with the major causes of severe disease. DESIGN: We analyzed data from children between 6 and 60 mo of age, comprising 13,307 admissions, 674 deaths, 3068 admissions with severe disease, and 562 community controls by logistic regression, using anthropometric z scores as the independent variable and admission or death as the outcome, to calculate the probability of admission as a result of "true malnutrition" for individual cases. Probabilities were averaged to calculate attributable fractions. RESULTS: Z scores < -3 were insensitive for malnutrition-attributable deaths and admissions, and no single threshold was both specific and sensitive. The overall malnutrition-attributable fraction for in-hospital deaths was 51% (95% CI: 42%, 61%) with midupper arm circumference. Similar malnutrition-attributable fractions were seen for the major causes of severe disease (severe malaria, gastroenteritis, lower respiratory tract infection, HIV, and invasive bacterial disease). CONCLUSIONS: Despite global improvements, malnutrition still underlies half of the inpatient morbidity and mortality rates among children in rural Kenya. This contribution is underestimated by using conventional clinical definitions of severe malnutrition.