A meta-analysis of inpatient treatment outcomes of severe acute malnutrition and predictors of mortality among under-five children in Ethiopia

Globally, an estimated 20 million under-five children suffer from severe acute malnutrition (SAM) contributing to 1 million deaths every year, mainly attributable to comorbid and/or consequent infections [1, 2]. SAM is characterized by two clinical parameters: (1) severe wasting; that is, marasmus, defined as middle upper arm circumference (MUAC) < 115 mm for children aged > 6 months or a weight-for-height < − 3 z-scores according to WHO’s growth standards for under-five children; and (2) nutritional edema with kwashiorkor; that is, the presence of clinically confirmed bilateral, pitting edema [2‐4].

Acute malnutrition is a major challenge for achieving sustainable development goals (e.g., Goals 2 and 3–Zero Hunger and Good Health and Wellbeing) as it is associated with major causes of under-five mortality. Moreover, it leads to adverse maternal and child health consequences including retarded school performance and aggravating maternal related problems [5, 6] especially in poorer settings. For instance, 2% of children (nearly 13 million) suffer from SAM in developing countries [7] of which over 90% live in South- East Asia and sub-Saharan Africa [8]. Indeed, SAM is a common indication for pediatric hospital admission and inpatient treatment in these countries. Thus, mortality of children from SAM in inpatient set-ups in sub-Saharan Africa still remains significantly high, with ten-folds higher the risk of death than well-nourished children [9].

Ethiopia has a long history of food insecurity and nutritional disorders aggravated by larger population size, land degradation, and droughts affecting a larger proportion of population [4, 10, 11]. Consequently, the country has been experiencing malnutrition related problems, although both community- and facility-based interventions are in place. For instance, children with SAM had conventionally been managed according to WHO standard in facility set-ups encompassing admission and comprehensive inpatient clinical treatment, although this protocol was first published in 1999 [12] and has guided only inpatient care of complicated SAM patients. Recently (2013 to date), there has been a paradigm shift for treating SAM, using updated WHO treatment guideline published in 2013, with compressive approaches [13]. This includes inpatient, outpatient, and community-based management of acute malnutrition (CMAM) and also provides training for health workers. The main aim of this approach is to decrease over crowdedness by treating non-complicated SAM cases at outpatient treatment programmes (OTP) without admitting to a hospital [7]. Adhering to this protocol has enhanced desired treatment outcomes [14, 15].

In Ethiopia, the health sector has attempted to upgrade nutritional intervention and improve treatment outcomes through health promotion, effective treatment strategy and supplementation of essential micronutrients for children and mothers. Different small scale fragmented studies have been conducted to determine treatment outcomes of children with SAM. However, the evidence base from previous studies on the treatment outcomes of, and factors associated with, SAM are inconsistent, and remain inconclusive. That is, under-five mortality rate in children with SAM ranges from 3.5% [16] to 29% [17] in Ethiopia, depicting a 26% variation between studies. Similarly, recovery rate ranges from 43.5% [16] to 87.6 [18] in different facilities of the country. This suggests that prevention and management of SAM are not uniform and unfinished agendas across the country may be because of lack of access to relevant healthcare, inconsistence use of SAM treatment protocol, etc. In addition, predictors of treatment outcome, particularly mortality, have not been well addressed, although anemia, HIV/AIDS, tuberculosis and diarrhea are reported to be some predictors of time to death [16, 19‐23].

The main aim of the current meta-analysis is to determine treatment outcomes and predictors of mortality among under-five children with SAM in Ethiopia. This will assist decision makers and/or other stakeholders to practice effective and efficient SAM management.

This meta-analysis examined treatment outcomes – death, recovery, defaulter and transfer out plus non-response rates – in under-five children admitted to SAM stabilization centers in Ethiopia. The proportion of children that died and recovered does not achieve the minimum SPHERE standard and WHO management protocol for SAM (i.e., < 10% death rate and > 75%) [60]. This high death rate and low recovery rate could be a result of delay at presentation to a stabilization center, the occurrence of recurrent infections, presence of co-morbidities and non-adherence (by healthcare providers) to the current SAM treatment guideline. The finding was also lower than the previous retrospective review done by Teferi et al. (n = 11,335 children) that revealed 87% cure rate and 3.6% (n = 468) death rate [15]. Likewise, a study from SierraLeone (n = 1987 children) reported 83% recovery rate [61]. This discrepancy might be because of the study characteristics. For instance, previous studies included both moderate and severe forms of acute malnutrition, which might potentially be associated with good treatment outcomes. However, the current analysis reported a recovery rate higher than that reported in Indian study (1130 SAM children) where 51.7% children were discharged from the program upon meeting discharge criteria [62]. Interestingly, the defaulter rate was in parallel with SPHERE report standard stating that the defaulter rate should be less than 15% [60]. By contrast, this finding was lower than a finding in India (47.2% children did not complete their treatment course – defaulters) [62]. The observed variation might be due to sociodemographic characteristics, study period and provision of quality of care, or inefficient use of resources including manpower. Moreover, uncomplicated SAM has occasionally been admitted to Asian stabilization centers [63].

In terms of predictors of mortality in SAM children, the association of diarrhea and SAM is a well-recognized fact [64, 65], although, to the best of our knowledge, the management of children presenting with diarrhea and SAM is limited [66]. This could have a vital role for treatment outcomes. This is supported by several studies [67‐71] that have shown increased mortality rates in children who have both diarrhea and SAM comorbidities. This possibly is attributed by the fact that children with diarrhea have concurrent clinical features including severe dehydration, impaired perfusion, and severe metabolic acidosis that would raise mortality. Moreover, gram-negative bacteremia is normally allied with diarrhea and is the major risk factor for death, nonetheless of HIV or anthropometric status [72].

Furthermore, higher mortality rates amongst dehydrated children is likely to be related to the fact that children develop metabolic disturbance and volume deficit with the high prevalence of bacterial disease. Furthermore, the urgent correction of hypotension by speedy volume expansion may attribute to potential sodium and fluid overload that could be a plausible subsidizing factor to death [73‐75]. We also found that anemia is one of the predictors responsible for increased mortality in SAM children. Consistently, the risk of earlier death for anemic children is reported to be significantly higher than for children without anemia [14, 76, 77]. The higher risk of mortality is because of an increased prevalence of infection and increased probability of heart failure [78].

Enhancing management of inpatient SAM remains an important approach for reducing malnutrition-related complications including mortality. As such, rendering comprehensive outpatient treatment for most SAM patients may diminish inpatient caseloads, decreases the risks of hospital-acquired infections, and thus, leave staff time to inpatient care. This strategy may reduce case-fatality rates, with cost-effective techniques. Indeed, this is recommended by updated WHO SAM management guideline which is meant to be adhered and implemented in respective set ups.

In general, our findings have policy implications for the management of children with SAM. Policymakers should be cognizant of this to strengthen health systems for appropriate management of SAM. Accordingly, in a bid to improve treatment outcomes for children with SAM, the WHO developed a-ten steps guideline for effective management of SAM, which is a widely accepted standard [79]. Indeed, few studies have reported the feasibility and sustainability of the implementation of this guideline in district hospitals with insufficient resources [80, 81]. Thus, further evaluation studies may fill this gap.

However, the findings need to be considered in the context of some important limitations. These included less control for possible confounders as crude hazard ratios were used to estimate some factors associated with treatment outcomes as opposed to adjusted analyses due to scarcity of data. Moreover, although Egger’s test did not show any risk of publication bias, few studies (e.g., Kebede et al., 2015 and Tirore et al., 2017)) showed high heterogeneity that needs to be considered while interpreting these findings.

Desired treatment outcomes in under-five children with SAM are lower than the WHO standard, where mortality is being predicted by comorbidities at admission. Healthcare facilities and providers are strongly advised to adhere to and implement based on the up-to-date inpatient SAM treatment and management protocol.