Length of stay to recover from severe acute malnutrition and associated factors among under-five years children admitted to public hospitals in Aksum, Ethiopia

Background Severe acute malnutrition is defined by <70% weight for length/height, by visible severe wasting, by the presence of pitting edema, and in children 6 to 59 months of age, mid upper arm circumference <110 mm. Severe acute malnutrition remains to be a worldwide problem, claiming lives of millions of children, especially in sub-Saharan Africa and south Asia. Though the Ethiopian national guideline states the total length of stay in therapeutic feeding units should not be more than four weeks, there is huge difference, varying from 8 to 47 days of stay. Therefore, the objective of this study was to assess length of stay to recover from severe acute malnutrition and associated factors among under five children hospitalized to the public hospitals in Aksum Town. Methods Sample size was calculated using STATA version 12.0. A retrospective cohort study was conducted using pretested questionnaire in the public hospitals in Aksum on children aged 0–59 months. Cleaned data was entered to Epi info version 7.1.4 and then exported into SPSS version 21 for analysis. Bivariable and multivariable analyses were performed using Kaplan Meier and Cox regression models. During bivariable analysis, variables with p-value < 0.05 were selected for multivariable analysis to identify independent factors associated with length of stay. Results A total of 564 participants enrolled to the study. The rate of recovery was 56% with median length of stay of 15 days (95% CI: 14.1, 15.9). The independent predictors of length of stay to recovery were presence of diarrhea at admission (AHR = 0.573, 95% CI: 0.415–0.793), being HIV positive (AHR = 0.391, 95% CI: 0.194–0.788), palmar pallor (AHR = 0.575, 95% CI: 0.416–0.794), presence of other co-morbidities at admission (AHR = 0.415, 95% CI: 0.302–0.570) and not being treated with plumpy nut (AHR = 0.368, 95% CI: 0.262–0.518). Conclusions Length of stay is in the acceptable range of the international and national set of standards. Nevertheless, the recovery rate was lower compared to the Sphere standard. Presence of diarrhea, palmar pallor, HIV other co-morbidities and not treated with plumpy nut were found independent protective factors for recovery from sever acute malnutrition.

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Ethical clearance and permission letter were taken from the Ethical Review Committee (ERC) of Aksum University, College of health science. An official letter was written to Selekleka primary hospital requesting facilitation to conduct the research study and this official letter approved and distributed to the respective units of Selekleka primary hospital. Confidentiality and privacy was maintained during data collection, analysis and reporting in which the information obtained from the data will not be shared other than the data collectors and principal investigator and this was assured by obtaining institutional written consent from Selekleka primary hospital and by providing Information sheet which explains the purpose, benefit, and short and long-term effect of the study on the study participants. Yes -all data are fully available without restriction Although SAM usually affects all segments of a population, infants and young children are 53 most vulnerable as they have higher nutritional requirements for growth and development 54 (5). It is one of the leading causes of morbidity and mortality among infants and young 55 children all over the world and more frequently in sub-Saharan Africa and south Asia (6).The 56 peak age for SAM is 6-18 months, time of especially high growth velocity and brain 57 4 development. However, it is increasingly becoming common that SAM may occur in infants 58 less than six months of age with many disadvantaged populations introducing solids to 59 children as young as two months (3).

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The 2013 Ethiopian guideline for SAM management states that the total length of stay (LOS) 61 in therapeutic feeding units (TFUs) should not be more than four weeks (7). But there is huge 62 difference in LOS in studies done in Ethiopia, varying from 8 to 47 days (8-10).

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More than ten million children die before celebrating their fifth birthday each year globally 72 due to SAM. Huge number of severely malnourished children die at their home without any 73 hospital care, but sometimes even hospital care is given, death rates may be high (7). In 74 developing countries, children under five who are severely malnourished and admitted to 75 hospital face a 30 to 50 per cent case fatality rate, which is unacceptably high (14).

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In the developing world, where SAM is the most common reason for pediatric 77 hospitalization, it is associated with higher risk of morbidity & mortality, underlying for 78 more than 50 per cent of the ten to eleven million children under 5 years old who die every year from avoidable causes (2,15,16). Despite of such worldwide significance, child recovery 80 programs have not given the required attention for facility based management of SAM (2).

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According to studies from Kenya and Niger, recovery rate and LOS are affected by co-82 morbidities like pneumonia, malaria, altered consciousness, weak pulse, inability to drink, 83 temperature gradient, chest in-drawing, diarrhea & severe pallor (17,18).

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Horn of Africa has identified 6.6 per cent of children less than five years old as wasted. With 85 estimated 10%, Ethiopia has highest rate of wasting (acute malnutrition) in this region (19).

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Even though it was not well known in this particular study area, some studies in Ethiopia 87 indicated that there is a big variation in LOS in Ethiopia, ranging from 8 to 47 days (8-10), 88 that is not congruent with the National SAM management protocol that states the total LOS 89 in TFUs should not be more than four weeks (7). A study in northwest Ethiopia also revealed 90 that patients admitted with SAM had a case fatality and defaulter rates of 18%, and 9% 91 respectively (20).

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UNICEF has conducted an evaluation study in Ethiopia (21) and identified gaps and 93 management errors in the services like not giving routine medicines such as Amoxicillin, 94 children who should be managed in phase two were managed in phase one, and those who 95 could be treated in OTP were being treated in TFU, poor medical record handling, late 96 transfer of cases from phase to phase & to discharge, and limited area allowed to the TFU 97 that increase cross infection and raised risk of death, especially for HIV infected children as.

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Though the Federal Ministry of Health (FMoH) jointly with its partners is taking promising 99 actions in reducing SAM, the Ethiopian national underweight and wasting rates among under 100 6 five children are still high, 24 and 10 % respectively. The same is true in Tigray region as the 101 underweight & wasting rates are 23 and 11% respectively (22,23).

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There were couples of researches conducted on malnutrition in the study area, but none of 103 them attempted to assess the length of stay to recover from SAM and associated factors 104 among under five children hospitalized to public hospitals in Aksum town, northern Ethiopia.  The purpose of this study was to assess the length of stay to recover from SAM and  (7).

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The study was carried out on those admitted with SAM from September 11, 2016 to February   This study has excluded children whose admission and discharge date not recorded as this 157 will not show the outcome variable (LOS), those with congenital anomalies like cleft lip and 158 developmental disorders such as Down's syndrome as these can be a confounding with LOS 159 for SAM and those whose medical records were not found or incomplete for type of SAM. the assumption of number of study subjects required to achieve a study power of 80% and 166 10% incompleteness, the overall sample become 585 (Table 1).

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All selected children aged 0-59 months with severe acute malnutrition admitted to NRUs of Defaulters: those who were not found in the NRU for two successive days, or who leave the 205 ward against professional advice while the child is not cured (7,13,32).

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Death: when the SAM child die while receiving treatment in the TFU and registered as dead 207 in the treatment logbook (7). sciences for the partial fulfillment of master of public health nutrition. It will also be 257 disseminated to both hospitals. I will make an attempt to submit it for publication in one 258 reputable journal as well.

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Out of total 585 eligible severely malnourished children hospitalized to the NRUs of public 261 hospitals in Aksum, 564 children were followed from September 11, 2016 to February 10, 262 2019 with retrieval rate of 96.4%. Out of the total followed children, 56% were recovered 263 from SAM and recovery times for the remaining 44% were considered to be censored at the   Table 2). 282 At admission, pneumonia was the most commonly observed co-morbidity (38.6%) followed 283 by anemia (16.2%) and TB (9.4%). The presence of co-morbidity contributed to the delay in  Almost all (98.8%) received antibiotics like amoxicillin, ampicillin and gentamycin and 321 higher numbers of children were supplemented folic acid and iron (68.1% and 61.9% 322 respectively). Regarding feedings, F75 was offered for almost all patients (99.8%) followed 323 by F100 (for 81% of participants) and half of them were given plumpy nut. Meanwhile, 31.9 324 per cent were fed with NG tube. As receiving folic acid, vitamin A, F100, plumpy nut and 325 not being fed with NG tube were suggestive of shorter recovery time in bivariate analysis, 326 these all were selected for further multivariable analysis using Cox regression model (Table   327 3). For those discharged cured, the average weight gain was 10.1g/kg/day. The overall 328 median recovery time from SAM was also determined to be 15 days with a 95% confidence 329 interval between 14.1 and 15.9 days (Figure 2).

Predictors of length of stay 331
After ascertaining validity of the model assumptions and adjustment, eight independent 332 significant predictors of LOS for nutritional recovery were found, which are; diarrhea, HIV 333 sero status, palmar pallor, co-morbidity, blood transfusion, IV fluid infusion, provision of 334 plumpy nut and feeding with the help of NG tube.

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Patients with diarrhea at admission were 42.7% (AHR = 0.573; 95% CI: 0.415-0.793) less 336 likely to recover quickly from SAM as compared to those without diarrhea while those HIV 337 positive found to be 60.9% (AHR = 0.391; 95% CI: 0.194-0.788) less likely to get cured fast 338 in comparison with those whose sero-status is unknown. However, no significant difference 339 was obtained in the hazards of non-recovery for children with Non-reactive (AHR = 0.937; 340 95% CI: 0.714-1.231) and unknown HIV status. The difference in chance of recovery 341 between reactive and non-reactive patients stays significant at 5% level of significance.

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Unsurprisingly, the highest difference in median LOS was observed in patients who were not 351 transfused, 1.9 times (AHR = 1.905; 95% CI: 1.158-3.135) more likely to recover than their 352 counter parts who were transfused.   In this enquiry, the median LOS till recovery from SAM was estimated to be 15 days (95% 368 CI: 14.1, 15.9), which is in the acceptable range of international standards set by the 369 SPHERE project (15). This is similar with the findings from institution based researches in days. It is also better (lower LOS) than multiple studies in the country (1,8,11,35,37) and 373 than that of Yemen (28). However, it is longer than some study reports from some parts of 374 Ethiopia (31,32,44), Ghana (20) and India (26). This could be due to the differences in 375 underlying co-morbidities, caring practice of healthcare providers, health facility set up and 376 variation in socioeconomic status of the population in these different study areas. In this 377 study, as it also was in recent studies in Ethiopia (40,42,43), type of SAM was not associated 378 with statistically significant difference in recovery time among edematous and severely 379 wasted children, in contrary to the current finding from southern region of Ethiopia which 380 shows marasmic ones were less likely to recover earlier compared to their edematous counter 381 parts (41).

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The overall rate of recovery from SAM was found to be 56%, that is consistent with findings 383 from Debrebrhan University that revealed 55.9% rate of recovery (31). It is better than that of  This study shows death rate of 6% from the total participants enrolled, which is acceptable by 394 the SPHERE project minimum international standards for managing SAM in NRU/TFU, and 395 This is not the way a scientific discussion should be 20 better than the recent study findings from University of Gondar (40) and Hawassa University 396 (43) comprehensive specialized hospitals which found mortality rates of 10.8 % for each. It is 397 similar with the findings of two studies done in Ethiopia (31,32) and one conducted in 398 Nigeria (38). But the mortality rate is greater than that of some studies done in Ethiopia 399 (11,13,33),India (25,26), Ghana (20) and Yemen (28). This could be due to lack of close 400 follow up of patients with strict adherence to the national or international SAM management 401 protocols and socioeconomic differences in the different areas.

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The average weight gain in this thesis was in line with the international/national set of 403 standards, unlike the recent finding from southern Ethiopia, Sidama zone, that found an 404 average weight gain of 5.4 g/kg/day (41). This variation could be due to the study setting, as  Similarly, not receiving plumpy nut (AHR = 0.368; 95% CI: 0.262-0.518) was observed as 413 strong independent predictor of recovery time in this thesis, which also is consistent with 414 report from Bahirdar (13). But other related studies from Ethiopia (9,32) reported that neither 415 palmar pallor nor plumpy nut as independent predictor of LOS till recovery. This could be 416 due to inter institutional differences in strictly adhering to the national SAM management 417 guideline.

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In line with this research findings, studies from different parts of the country (1,10,32) and 419 studies from Malawi and Uganda (29,30) reported that children presented with retroviral 420 infection at hospitalization were less likely to recover from SAM, as being reactive for HIV 421 serostatus among the study participants had negatively affected LOS to recover from SAM 422 (AHR = 0.391; 95% CI: 0.194-0.788) in this particular thesis work.

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Probability of getting cured fast was reduced by 58.5% (AHR = 0.415; 95% CI: 0.302-0.570) 424 in those admitted with co-morbidity. Consistent with this report, a hospital based 425 retrospective cross-sectional study from Bahirdar and retrospective cohort study in similar 426 setting in Jimma University found less recovery rate of SAM in co-morbid children (1,37).

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Another finding from this research is that those not fed with NG tube had 1.9 times (AHR = 428 1.861; 95% CI: 1.335-2.593) higher chance of faster recovery in reference to those fed with 429 NG tube, that is in agreement with study finding in Gedeo zone of southern Ethiopia (35).

Limitations of the study 431
Even though the strength of this thesis paper comes from its study design (cohort), it totally 432 was based on patients' secondary data, in which incompleteness was observed to some 433 extent, and lacked control over the quality of measurements taken during hospitalization. It 434 was also impossible to analyze socio-economic characteristics of parents/guardians and 435 factors related to patient treatment (medical/pharmaceutical supplies and healthcare provider 436 expertise) that could have influenced the outcome variable in a desirable or undesirable way.   Confidentiality and privacy was maintained during data collection, analysis and reporting in 466 which the information obtained from the data will not be shared other than the data collectors 467 and principal investigator and this was assured by obtaining institutional written consent 468 from Selekleka primary hospital and by providing Information sheet which explains the 469 purpose, benefit, and short and long-term effect of the study on the study participants.    Where P = Prevalence of non-recovery (at third week)