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

ABSTRACT: BACKGROUND:Stunting 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 medically complicated SAM. METHODS:We performed secondary analysis of clinical trial data (NCT00934492) from HIV-uninfected Kenyan children aged 2-59 months hospitalised with SAM. Outcome was change in height/length-for-age z-score (HAZ) between enrolment and 12 months later. Exposures were demographic, clinical, anthropometric characteristics and illness episodes during follow-up. RESULTS:Among 1169 children with HAZ values at month 12 (66% of those in original trial), median (IQR) age 11 (7-17) months and mean (SD) HAZ -2.87 (1.6) at enrolment, there was no change in mean HAZ between enrolment and month 12: -0.006Z (95%?CI -0.07 to 0.05Z). While 262 (23%) children experienced minimal HAZ change (within ±0.25 HAZ), 472 (40%) lost >0.25?and 435 (37%) gained >0.25 HAZ. After adjusting for regression to the mean, inpatient or outpatient episodes of diarrhoea and inpatient severe pneumonia during follow-up were associated with HAZ loss. Premature birth and not being cared by the biological parent were associated with HAZ gain. Increases in mid-upper arm circumference and weight-for-age were associated with HAZ gain and protected against HAZ loss. Increase in weight-for-height was not associated with HAZ gain but protected against HAZ loss. No threshold of weight gain preceding linear catch-up growth was observed. CONCLUSIONS:Interventions to improve dietary quality and prevent illness over a longer period may provide opportunities to improve linear growth.

SUBMITTER: Ngari MM

PROVIDER: S-EPMC6556974 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Ngari Moses M MM Ngari Moses M MM Iversen Per Ole PO Thitiri Johnstone J Mwalekwa Laura L Timbwa Molline M Fegan Greg W GW Fegan Greg W GW Berkley James Alexander JA

Archives of disease in childhood 20180928 3

<h4>Background</h4>Stunting 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 medically complicated SAM.<h4>Methods</h4>We performed secondary analysis of clinical trial data <b>(</b>NCT00934492) from HIV-uninfected Kenyan children aged 2-59 months hospitalised with SAM. Outcome was change in height/length-for-age z-score (HAZ) betw ...[more]

PMID: 30266874

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Project description:ImportanceMortality 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.ObjectiveTo investigate the role of cardiovascular dysfunction in African children with severe, acute malnutrition (SAM).Design, setting, and participantsA 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.ExposuresEchocardiographic and electrocardiographic (ECG) recordings (including 7-day Holter monitoring) at admission, day 7, and day 28.Main outcomes and measuresFindings in children with (cases) and without (controls) SAM and in marasmus and kwashiorkor phenotypes were compared.ResultsEighty-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 relevanceThere 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.

Project description: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.

Project description:BACKGROUND:It is well documented that treatment for severe acute malnutrition (SAM) is effective. However, little is known about the long-term outcomes for children treated for SAM. We sought to trace former SAM patients 11 to 30 years after their discharge from hospital, and to describe their longer-term survival and their growth to adulthood. METHODS:A total of 1,981 records of subjects admitted for SAM between 1988 and 2007 were taken from the archives of Lwiro hospital, in South Kivu, DRC. The median age on admission was 41 months. Between December 2017 and June 2018, we set about identifying these subjects (cases) in the health zones of Miti-Murhesa and Katana. For deceased subjects, the cause and year of death were collected. A Cox proportional hazards multivariate regression analysis was used to identify the death-related factors. For the cases seen, age- and gender-matched community controls were selected for a comparison of anthropometric indicators. RESULTS:A total of 600 subjects were traced, and 201 subjects were deceased. Of the deceased subjects, 65·6% were under 10 years old at the time of their death. Of the deaths, 59·2% occurred within 5 years of discharge from hospital. The main causes of death were malaria (14·9%), kwashiorkor (13·9%), respiratory infections (10·4%), and diarrhoeal diseases (8·9%). The risk of death was higher in subjects with SAM, MAM combined with CM, and in male subjects, with HRs* of 1·83 (p = 0·043), 2.35 (p = 0·030) and 1.44 (p = 0·013) respectively. Compared with their controls, the cases had a low weight (-1·7 kg, p = 0·001), short height [sitting (-1·3 cm, p = 0·006) and standing (-1·7 cm, p = 0·003)], short legs (-1·6 cm, p = 0·002), and a small mid-upper arm circumference (-3·2mm, p = 0·051). There was no difference in terms of BMI, thoracic length, or head and thoracic circumference between the two groups. CONCLUSION:SAM during childhood has lasting negative effects on growth to adulthood. In addition, these adults have characteristics that may place them at risk of chronic non-communicable diseases later in life.

Dataset Information

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

Publications

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

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