Comorbidities Associated with Mortality among Children under Five Years Admitted with Severe Acute M

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IAA Journal of Scientific Research 9(1):1 16, 2022.

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ISSN: 2736 7319

Comorbidities Associated with Mortality among Children under Five Years Admitted with Severe Acute Malnutrition in the Nutritional Unit of Jinja Regional Referral Hospital

DepartmentofMedicine,PaediatricsandChildHealthofKampalaInternationalUniversity Uganda.

ABSTRACT

Mortality among children with severe acute malnutrition remains an immense health concern in the hospitals in Africa, but its attributes are not fully known to various hospital settings This study determined the comorbidities associated with in hospital mortality among children under five years of age admitted with severe acute malnutrition at Jinja Regional Referral Hospital. This was a hospitalbased analytical descriptive prospective cohort study conducted at in the nutritional unit of Jinja Regional Referral Hospital. This study was performed from July to October 2019 with children under five years of age admitted with severe acute malnutrition and their caregivers from and their caregivers. A total of 338 children and their caretakers who met the criteria were consecutively enrolled into the study. Children were followed until discharge from the nutritional unit or until death. Data collected from questionnaires, WHO chart and culture media were entered into Microsoft Excel version 10 and imported into Stata 12 for data analysis. Descriptive statistics were used to each of the independent comorbidities were subjected to Chisquare test followed by logistic regression analysis to assess its association incidence of mortality among children. All independent variables with p values ≤0.05 were entered into a multivariate model for comorbidities independently Comorbidities with p values ≤0.05 were considered as associates of mortality of mortality among children. Although the majority children were diagnosed with dehydration, 128(37.9%) and pneumonia, 127(37.6%) and malaria, 87(25.7%).Anemia (aRR=2.9, 95%CI: 1.23 6.62, p=0.01), bacteremia (aRR=10.0, 95%CI: 3.6229.01, p=0.01), HIV (aRR=4.8, 95%CI: 1.42 16.30, p<0.01), TB (aRR=4.3, 95%CI: 1.2814.49, p <0.02) and shock (aRR=60.9, 95%CI: 9.05410.28, p <0.01) were the Comorbidities significantly associated with a likelihood of mortality. In conclusion, the mostimportantcomorbiditiesassociatedwithmortalitywereacuteanemia,bacteremia,HIV, TBandshock.

Keywords:Comorbidities,Mortality,ChildrenandSevereAcuteMalnutrition.

INTRODUCTION

Hypoglycemia is one of the comorbidities associated with SAM and a risk factor of inhospital mortality in children admitted with severe acute malnutrition. In a retrospective longitudinal study on the incidence and predictors of mortality among severe acute malnourished under five children admitted to Dilla University Referral hospital in Sudan, the highest incidence rate of death was observed in the first two days with 8.4/1000 person day, when stratified in days; then decreased in the subsequent days and weeks of enrolment with the peak incidence of death shortly after admission may have several explanations, since the risk of early death is associated with Comorbidities such as hypoglycemia [1] In these patients,severalfactors suchas a shortage in the exogenous nutritional

intake, the reduced absorption of sugars resulting from intestinal villous atrophy, or a generalized augment in oxidative stress may compromise glucose homeostasis [2]. The rigorous application of the WHO management of malnutrition guidelines significantly improves the prognosis in these patients. This is likely inrelationtothefactthattheseguidelines take into special consideration the prevention and early treatment of sepsis and hypoglycemia [2]. Hypoglycemia suggests that the homeostatic mechanisms are under stress or have failed a great deal to evaluate the underlying problems. In this study, random blood sugar levels of the children was taken using a glaucometer during recruitment of study participants to determine whether they have

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hypoglycaemia oor not. Hypothermia is also a clinical risk factor associated with mortality in children with SAM. [3] in Ethiopia found that children with hypothermiahad11.8timesincreasedrisk of dying when compared to children with complicated SAM with normal temperature. The study by [1] revealed that the risk of earlier death was 6.94 timeshigherforchildrenwhohavealtered body temperature than children who have normal body temperature. A study carried out in Northern Uganda showed that very low body temperature also had a significantly increased association with mortality. In that study, children with hypothermia were about five times more likely to die [4] Regular temperature monitoring poses a major challenge and has implications for use of scarce human resources in areas where malnutrition is common. Current guidelines recommend 2 4 hourly monitoring during the stabilization phase until the transition to F100feedsandthepatientisstable.Inour setting, where staffing is limited, we suggest a reduction in routine temperature and more targeted use of temperature monitoring of severely malnourished children. This study involved temperature monitoring every 2 hours and determined whether hypothermia was also a predictor of mortality in severely malnourished children.

A study by [5] in the Eastern Cape, South Africa, found that high death rates were attributable to avoidable errors by clinical staff. Avoidable causes of death included sepsis due to failure to prescribe appropriate antibiotics, dehydration and overhydration due to poor fluid management and failure to correct electrolyte imbalances. Another study done in Ethiopia revealed that diarrhea was the most comorbidity associated with severe acute malnutrition among children aged 059 months in 44.6% [6]. A study by Irena, [7] in Zambia revealed that children with severe acute malnutrition with diarrhea had two and ahalf times higher risks of mortality than those without diarrhea (Adjusted OR = 2.5 (95% CI 1.50 4.09, P < 0.001)) Another study by [8] in Kenyashowedthatweakpulse,inabilityto drink, and diarrhea were associated with increased mortality with OR=3.79 (3.02,5.06), OR=3.6(2.9,4.3), OR : 1.90(1.60,2.27), respectively. In Uganda, [9] showed that diarrhea was a strong

predictor of mortality with a Hazard Ratio = 2.19 (1.06,4.51). Diarrhea leads to loss of electrolytes and dehydration which leaves the child weak. Severely malnourished diarrheal children who present with a history of lack of adequate foodandfluidintakeathomeareproneto deaths. Identification of these simple clinical predicting factors may help in early management of these children with ReSoMal during diarrhea in order to reduce their risk of death. A number of observational studies have indicated that children with SAM may have radiologic evidence of pneumonia without one or all of what clinicians would consider to be the typical clinical features of pneumonia as defined by WHO and others [10]. [11] have found respiratory tract infections to be the second most frequent cause of infection in children admitted with severe acute malnutrition. A study by [12] among the malnourished children admitted to SOS hospital in Somalia, revealed that bronchopneumonia was the most common comorbidities associated with SAM with a proportion of 62.2%. Another study done in Uganda by [9] showed that pneumonia was a major contributor of mortality in children with SAM with Hazard Ratio=1.84(0.9,3.72).Pneumoniaiscaused byvirusesorbacteriaandaspiration.Most serious episodes are caused by bacteria. Children with severe acute malnutrition have a weak immune system which hide the natural course of the disease, pneumonia, and mislead the clinician. Antibiotic therapy is needed in all cases. Severe pneumonia requires additional treatment, such as oxygen, to be given in hospital. The HIV pandemic has changed the epidemiology, pathophysiology and mortality of SAM in many parts of sub Saharan Africa and other areas of the world. Currently, there are very few evidencebased recommendations for managing children with SAM and HIV infection any differently to children with SAM without HIV infection. Drug toxicity, antimicrobial use, fungal infections and persistent diarrhea are likely to require extra consideration amongst HIVinfected children with SAM [10]. [13] in their study on morbidity and mortality pattern in children under 5 years with severe acute malnutrition in Zambia found that HIV infected children were 80% more likely to die than those who were HIV uninfected (OR=1.8, 95% CI 1.6 2.0, P < 0.001). In Uganda, a study done by [4] on treatment

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outcome among children under five years hospitalized with severe acute malnutrition in St. Mary’s hospital Lacor, revealed that HIV was significantly associated with mortality in 18.6% versus 9.6% in children HIV negative with OR=3.087(1.3077.292). [4] study was a retrospective study making use of patients’ medical records in the facility whichcouldhaveresultedintobiasdueto incomplete or missing records though the strength of their study was that they used bivariate logistic regression to establish the association between the outcome variable and the exposure variable. Meanwhile the use of multivariate logistic regression helped them to take in consideration the effect of confounding factors. Malaria is a comorbidity which can accompany severe acute malnutrition. A study done by [14] on malaria and nutritional status of children with severe acute malnutrition in Niger revealed that malaria was an important co morbidity with 55.3% in children with severe acute malnutrition. Another study carried out in Niger to assess mortality and causes of mortality in children 6 59 months of age admitted in inpatient therapeutic feeding centers showed that the high mortality due to malaria in Madaoua was probably linked to the timing of the malaria season during the study period [15] A study by [16] in Ghana revealed that malaria was associated with low chance of recovery, weight gain and default among children withSAM,while those withoutmalariahad a higher chance of recovery with OR=30 (95% 333 CI: 10.02, 92.13, p<0.001) compared with those who had malaria. All these studies were done in different African countries with different study settings but the results were similar. We sought to understand whether the results ofthiscurrentstudy wasalso in linewith those past studies since children with malaria coinfection were seen to have less odds of surviving as compared to those without malaria. Anemia is one of the co morbidities associated with severe acute malnutrition and increases the risk of mortality. A study on Malnutrition and anemia among hospitalized children in Vavuniya showed that the mean hemoglobin concentration among the studysamplewas10.7g/dl,andofthe284 malnourished children, 55.5% had mean hemoglobin concentration less than 11 g/dl and were classified as anemic [10] A study by [17] in Ethiopia showed that

anemia was an independent predictor of mortality among children with SAM (AHR=2.3, 95%CI: 1.2 4.5). Among malnourished infants aged 6 12 months, the prevalence of anemia was 68.3% , compared to 55.9% among malnourished children aged 13 years and 39.1% among malnourishedchildrenaged3 5years[18]. Another study by [19] in Burkina Faso revealed that 85.3% of included malnourished children had anemia (Hb ≤ 11 g/dl) and 10.6% severely anemic (Hb < 6 g/dl). However, mortality rate did not differ significantly from severely malnourished children with anemia (12.4%) and without anemia (22.2%), p = 0.12 and Kaplan Meir survival curves did not differ significantly between the two groups, (pLog Rank = 0.11). If not adequately managed, anemia can be a leading cause of mortality in severely malnourished children. The latter study was in disagreement with other studies as it argued that anemia was not statistically associated with mortality of the children admitted with SAM. In this study, all the severely malnourished children with severe anemia who were transfused were followedup to find whether anemia and its management were the predictors of mortalityinthiscategory

Aim of the study

To assess the comorbidities associated with in hospital mortality among children under five years of age admitted with severeacutemalnutritionatJinjaRegional ReferralHospital.

Specific objective

Todeterminethecomorbiditiesassociated with in hospital mortality among children underfive years ofage admitted withSAM in the nutritional unit of Jinja Regional Referralhospital.

Research question

What are the Comorbidities associated with in hospital mortality among children underfive years ofage admitted withSAM in the nutritional unit of Jinja Regional ReferralHospital?

Scope of the study

Geographical scope

Thestudy was conductedatJinja Regional Referral Hospital (JRRH), Kampala International University Teaching Hospital (KIUTH) satellite hospital. JRRH is located in Southeastern Uganda, approximately 87 kilometers east of Kampala, the capital city of Uganda. The hospital is located in the center of Jinja Municipality with coordinates of Jinja hospital as: 00 25 52

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N, 33 12 18E (Latitude; 0.4310; Longitude 33.2050). Jinja district sits along the northern shores of Lake Victoria, near the source of the White Nile and has an average elevation of 1,204 meters above sea level. It is bordered by Kamuli district to the north, Luuka district to the east, Buvuma district to the south, and Buikwe district to the northwest. An estimated 65.8 sq.km of the district’s total land area (767.8 sq.km) is covered by water. The main economic activity in Jinja District is agriculture,engagingthemajority(85%)of the district population. Administratively, the district is constituted by 12 sub

Study design

counties including three town councils, three divisions under Jinja municipality and six rural sub counties with a total of 53 parishes and wards and 386 villages. According to the 2014 census data, Jinja RRH serves a population of 471,242 in Jinja district, and the hospital also serves Bugiri, Kamuli, Iganga, Mayuge, Namutumba, Kaliro, Buyende, Luuka, Namiyongo and Jinja district. The nutritional unit of JRRH where this study was conducted is located in pediatric ward, around 1 km from the main hospital.

METHODOLOGY

This was an analytical descriptive prospective cohort study to determine the proportion of mortality, demographic, biological, socioeconomic factors and Comorbidities associated with mortality among children below 5 years admitted with severe acute malnutrition in the nutritional unit of Jinja Regional Referral Hospital.

Study site

The study was conducted at Jinja RRH. Jinja RRH is located in Southeastern Uganda, approximately 87 kilometers East of Kampala, the capital of Uganda. The coordinates of Jinja hospital are; 00 25 52 N, 33 12 18E (Latitude; 0.4310; Longitude 33.2050). Jinja district sits along the northern shores of Lake Victoria, near the source of the White Nile and has an average elevation of 1,204 meters above sea level. It is bordered by Kamuli district to the north, Luuka district to the east, Buvuma district to the south, and Buikwe district to the north west. It is a designated internship hospital where medical graduate internship centre and has several consultant staff and specialists in medical and surgical disciplines. Jinja RRH, also provides comprehensive HIV/AIDS services. It is also a KIU Satellite Teaching Hospital aimed at training undergraduates and postgraduate students including postgraduate in Pediatrics The nutritional unit is in pediatric ward, around 1 km fromthemainhospital,ithas 32bedsand 3 trained nurses assigned for the ward. Patients are categorized into moderate acute malnutrition, severe acute malnutrition, and edematous and non edematous malnutrition with a minimum of60admissionspermonth.

Study population

The study included all children under five years of age admitted with SAM in the nutritional unit of Jinja Regional Referral Hospitalandtheircaregivers.Accordingto the 2014 census data, Jinja RRH serves a population of 471,242 in Jinja district,and the hospital also serves Bugiri, Kamuli, Iganga, Mayuge, Namutumba, Kaliro, Buyende, Luuka, Namiyongo and Jinja district.

Selection criteria

Inclusion criteria

All children under five years of age admittedwithsevereacutemalnutritionin the nutritional unit of Jinja Regional Referral Hospital and their caregivers who consentedwereincludedinthisstudy.

Exclusion criteria

Those who were referred for further management were excluded from this study Also, children with pre existing congenital malformations, and cerebral palsywereexcludedfromthisstudy.

Sample size estimation

Sample size calculation was done using a formula for estimating a population proportion[20]

n = Zα/2 2 *p*(1 p) / MOE2 , And

Zα/2 is the critical value of the Normal distribution at α/2 (e.g. for a confidence level of 95%, α is 0.05 and the critical valueis1.96), MOE is the margin of error, estimated at 0.05

P is the estimated proportion of children withSAMthatdiedinhospital=0.33based on a study done in Kenya that reported 33%[21].

n= 1.962 x 0.33 (10.33) /0.052 = 339.7 = 340 children with Severe Acute Malnutrition.

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Estimating the sample size for the socio demographic, biological and economic factors associated with mortality among children under five years of age with severe acute malnutrition in the nutritionalunitcare.

Using the modified Daniel’s formula n = Zα/2 2 *1 /R*P (1 P)/ d2 Where; n=desiredsamplesize Z= value corresponding to 95% confidence interval=1.96

R= Odds ratio for the SAM mortality according to the socio demographic factors associated with mortality in children under five years of age with SAM that died in hospital based on a study done in Uganda (Mulago) that reported an OR=1infemales[22]

P= proportion of mortality among females under five years admitted with SAM based ontheabovestudywas0.25. d=degree of error to be accepted which is 5%.

n= 1.962 *1 /1*0.25 (10.25)/ 0.052 =147 children under five years of age admitted withSAM.

Estimating the sample size for the co morbidities associated with mortality of children under five years of age admitted withSAMinthenutritionalunitcare.

Using the same modified Daniel’s formula n = Zα/2 2 *1 /R*P (1 P)/ d2 Where n=desiredsamplesize Z= value corresponding to 95% confidence interval=1.96

R= Odds ratio for children with SAM mortality according to the associated co morbidities based on a study done in Mulago that reported an OR=3.62 of childrenwithHIVthatdiedofSAM[9].

P= proportion of mortality among HIV patients with SAM in the nutritional unit basedontheabovestudywas0.34.

d= degree oferror to beaccepted whichis 5%

n =1.962 *1/3.62*0.34(10.34)/0.052 =95 children under five years of age admitted withSAM.

The overall sample size is 340 children under five years of age admitted with SAM.

Sampling technique

All children under five years of age admitted with SAM in the nutritional unit of Jinja Regional Referral hospital, who met our inclusion criteria were consecutivelyenrolledintothestudyuntil

when the required sample size has been attained.

Data collection tools

The following tools will be used to collect data: questionnaires, tape measure, thermometer, pediatric size stethoscope, stadiometer, infantometer, WHO chart, vacutainers, gloves, and syringes, culture medium.

Study procedures

Screening for eligibility

Screening and inclusion were performed upon admission of the child in the paediatric ward as long as they met inclusion criteria. The principal investigator explained the purpose and the process of the study to the patient and/or guardian and a written consent wasobtained.

Demographic information and biological information

Information regarding the place of residence, sex, age and date of birth and relationshipofthechildwiththecaretaker were collected by the principal investigator using the data collection tool. Complaints of diarrhea, vomiting, loss of appetite, fever, cough and others were alsorecordedinthedatacollectiontoolas well as the child’s immunization history, nutrition history, HIV status, occupation of the caretaker. All information obtained was entered in the data collection tool. The emergency cases were managed first; information from them was collected later

Clinical examination

Children underwent general examination with special emphasis on temperature, presence of visible wasting, presence of edema, dehydration, eye signs of vitamin A deficiency and pallor, respiratory distress, tachypnea, some dehydration was distinguished from septic shock according to the WHO protocol Systemic examination was done with special emphasis on the respiratory, cardiovascular system where pulse rate, capillary refill time, temperature gradient in thelimbs were assessedandthecentral nervous system where the level of consciousness was noted. Pulse rate and oxygen saturation were taken using a pulse oximeter. Findings on clinical exam were enteredin thedata collection tool by the principal investigator; they helped to diagnose some comorbidities. All the patients were followed up from admission to the discharge with the clinical care pathwayform(AppendixV).

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Sample collection and laboratory procedures

Blood sample was collected during insertion of IV cannula for measurement of full blood count, blood glucose, blood slide for malaria and HIV test and culture. Prior to drawing of blood, the area will be swabbed with cotton dipped in ethyl alcohol 70% and iodine to prevent contamination. Three to four milliliters of blood were drawn for blood culture, determination of blood glucose, full blood count,HIVtestandbloodslideformalaria and serum electrolytes. The blood sample for culture was taken and analyzed using AutomatedBloodCultureSystem(BACTEC) in the main hospital laboratory of JRRH. These laboratory investigations were done on admission except serum electrolytes thatwasdoneduringtransitionphase.For the HIV test, pre and post test counseling were done. A first Determine® HIV rapid test was performed and confirmed with a 2nd rapid test StatPak®. In case of discordance, a Unigold® test will be done. Children under 18 months with positive rapid tests will be referred for DNA PCR test in the HIV clinic in the Jinja RRH. Blood samples will be taken off only once atadmission.

Full blood count was analyzed using Sysmex® Automated Hematology Analyser at Jinja RRH. Blood glucose was measured using Freestyle optium glucometer by the principal investigator at admission. Thick blood smears for malaria parasites was done using Field stains A&B and examined by a Laboratory technician using the microscope in the pediatric ward laboratory. Early morning gastric aspirate was collected in a sterile for gene expert atadmission.Thesample was taken tothe pediatric ward laboratory of JRRH for analysisatadmission.

Comorbidities

After getting the history, clinical assessment coupled with laboratory investigations were done to diagnose the comorbidities related to Severe Acute Malnutrition. Those comorbidities were defined according to WHO protocol (2013) asfollow:

Hypoglycemia by the blood sugar < 3mmol/litre (54mg/dl); hypothermia by the axillary temperature below 35 degree Celsius and when the axillary temperature did not register on a normal temperature, we assumed that the child had hypothermia. All the participants with SAM who had watery diarrhea or reduced

urine output were assumed to have some dehydration. However, electrolyte imbalance was defined by the serum electrolytes below or above the normal ranges. Bacteremia was defined by the bacterial growth in the blood sampled collected using Automated Blood Culture system. Severe pneumonia was defined by cough or difficulty in breathing with oxygen saturation < 90% or central cyanosis, severe respiratory distress or signs of pneumonia with a general danger sigh like inability to breastfeed, lethargy or altered level of consciousness with decreased breath sound, bronchial breath sound, crackles, pleural rub on auscultation of the chest .Pneumonia was defined by cough with fast breathing for the age, chest in drawing. Severe anemia wasdefinedbyhemoglobinbelow4g/dlor 46g/dl in a child with respiratory distress. Shock was defined by lethargy or unconsciousness with cold extremities, capillary refill above 3 seconds, and a weak or fast pulse or a low or immeasurable systolic blood pressure. Confirmed tuberculosis was defined by a positivegeneexpert.

Patient management

Children with severe acute malnutrition were treated according to updated WHO guidelines. Prescription of treatments for the participants was done by doctors and clinical officers who were availed with guidelines on treating children with SAM. The role of the principal investigator was limited on recommendations. All children were routinely treated with IV Ampicillin and IV Gentamycin that was modified according to the blood culture and sensitivity results. They were also routinely started on a feeding program with F75 formula feeds. Caretakers took the responsibility for the feeding of the children under the supervision of the hospital Nutritionist. Children with diarrhea were routinely given Zinc tablets in addition to the routine deworming tablet that was given to all the enrolled patients. Those with some dehydration were given ReSoMal solution while those with septic shock were given IV half strength Darrow’s and 5% Dextrose solution. All patients were followedup fromadmissiontothedischargeaccording totheWHOprotocol

Data management

Hard copy questionnaires were kept in lockablesafes.Datawascheckedmanually by the principle investigator to verify the

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completeness of information. Where missing information was found, the principle investigator cross checked to find out whether the information was indeed missing from the field. The data was entered and cleaned using EPI info version 7and was exportedto STATA 12.0 for further analysis. The data was kept in a password protected computer to avoid unauthorized persons from accessing it. The data was made accessible to authorizedpersonslikethebiostatistician, research supervisors, hospital administrators and any other authorized person. Descriptive statistics like frequencies, percentages and means was calculated.

Data analysis

Characteristics of study participants: Socio demographic were summarized descriptively as frequencies, percentages (categoricalvariables). The proportion of comorbidities was assessed for association with in hospital mortality using frequencies and percentages and their association with mortality were assessed using logistic regression to obtain the relative risk of mortality. Both Bivariate and Multivariate analysis were carried out. Data was presented using a table. Statistical significancewasconsideredat α ≤ 0.05.

Ethical considerations

Forthestudytobeethical,thefollowing wasconsidered

Institutional consent

Approval was sought from the Research and Ethics Committee of Kampala

International University and also by the hospitaladministrationofJinjaRRHwhere theresearchwascarriedout.

Privacy and confidentiality

Allquestionnairesdidnothaveprovisions for participant’s names, and participants willbeinterviewedseparatelyfromother clientstomaintainprivacyand confidentiality.

Informed consent

Written consent was obtained from the parents or caretakers of the participants. For parent or caretaker who does not know how to read and write, the consent form was translated in local language (Lusoga) and we identified a witness who had to explain the consent form to him/her after which the parent/caretaker gave consent using his/her thumbprint. Mothers who were emancipated minors gave their consent after being clearly informed about the risks and benefits of the study by the principal investigator. Pre andposttestcounsellingforHIVwere performed separately by the Research nurse. Written consent for HIV testing was obtainedonaspecificform.Therefusalof HIV test by the parent/caretaker did not stop the participant from getting care Informed consent was sought from the attendant of the participants after clearly explaining the purpose of the study. Participation wasvoluntaryandparentsor guardians were free to refuse to participate or withdraw from the study withoutanypenalties

PRESENTATIONANDINTERPRETATIONOFTHERESULTS

Study profile of study participants

Overall, 340 participants under 5 years of age with severe acute malnutrition were consecutively enrolled in the study in the nutritional unit of Jinja Regional Referral Hospital after an informed consent of their caregivers from July to September 2019. Of the 340 participants, 2 participants wereexcludedfrom thestudy because of refusal to consent. A total of 338 participants were followed up from admission to discharge A total of 49 participants died and 289 participants survived.

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Figure 1: Study profile of study participants

Socio demographic characteristics of children under five years of age admitted with SAM in the nutritional unit of Jinja Regional Referral Hospital

Table 1 shows that of the 338 children under five years of age studied, majority were males,208(61.5%) aged 13 24 months with a mean age of 18.months (SD = 10.7) Most of children had complete

immunization status, 177 (52.4%) presented with fever 229(67.8%) and cough 204(60.4%). Most of the children hadcompletedimmunization,177(52.4%) Majority of the children were not exclusively breastfed up to 6 months, 229 (67.7%). Almost all the children had a hospital stay/duration of admission of at least72hours.

Table 1: Socio demographic and biological characteristics children under five years of age admitted with SAM in the nutritional unit of Jinja Regional Referral Hospital (n = 338)

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Variable n(%) Sex Males 208(61.5) Females 130(38.5) Age in months ≤12 107(31.66) 1324 179(52.96) >24 52(15.38) Immunisation Status Complete 177(52.4) Incomplete 154(45.6) No 7(2.1) Duration of admission <24hours 5(1.5) 2448hours 12(3.6) >48hours 321(95.0) Exclusive breast feeding up to 6 months Yes 109(32.3) No 229(67.7)
died
338 participants under five years enrolled
the
340
49
289 recovered. 2 Participants were excluded as caregivers did not consent.
in
study.
Participants under 5 years of age admitted with Severe Acute Malnutrition

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Socio-demographic characteristics of the caretakers of children under five years of age admitted with SAM in the nutritional unit of Jinja Regional Referral Hospital

Table 2 shows that of the 338 caregivers, themajorityweremothers,237(70.1%)and

were from rural settings, 274(81.1). Most of caregivers were aged 20 29 years, 165(48.8%). Most of the caregivers had attained primary education, 188(55.6%) and were engaged in business, 205(60.7%) although they earned less than 100,000 Ugx,259(76.6%).

Table 2: Socio demographic characteristics of the caretakers of children under five years of age admittedwithSAM inthe nutritionalunit ofJinjaRegionalReferralHospital(n = 338)

Variable n(%) Relationship with child

Mother 237(70.1) Father 28(8.3) Grandparent 55(16.3) Others 16(5.3)

Age in years

<20years 25(7.4) 2029years 165(48.8) 3049years 121(35.8) 50+years 27(8.0)

Residence

Urban 64(18.9) Rural 274(81.1)

Highest education level Noformal 79(23.4) Primary 188(55.6) Secondary 69(20.4) Tertiary 02(0.59)

Occupation

Peasant 56(16.6) Business 205(60.7) Civilservant 71(21.0) Other 6(1.78)

Average monthly income of caregiver (Ugx)

<100,000Ushs 259(76.6) 100,000500,000Ushs 72(21.3) >500,000Ushs 7(2.1)

Comorbidities among children under 5 years admitted with SAM in the nutritional unit of JRRH Figure 2 shows that of the 338 children under 5 years of age admitted with SAM,

the majority were diagnosed with dehydration, 128(37.9%) and pneumonia, 127(37.6%)andmalaria,87(25.7%).

9

120

100

80

60

40

140 Frequency (%)

20

128(37.9) 127(37.6) 87(25.7) 73(21.6) 61(18.5)

23(6.8) 20(5.9) 17(5.0) 14(4.1) 12(3.6) 6(1.8) 3(0.9) 0

Complications

Figure 2: Comorbidities among children under 5 years admitted with SAM in the nutritional unit of JRRH

Comorbidities associated with in hospital mortality among children under 5 years admitted with SAM in the nutritional unit of Jinja Regional Referral hospital.

Table 3 shows that in absence of other comorbidities,allthecomorbiditiesexcept malaria, pneumonia, electrolyte imbalance andcardiacfailurewereassociatedwithin hospital mortality of children under 5 years of age admitted with SAM in the nutritional unit of JRRH (p≤0.05). In the multivariate model in which only Comorbidities with p value ≤ 0.05 were entered, acute diarrhea, bacteremia, HIV, TB and shock remained significant Comorbidities associated with in hospital mortality. Specifically, children who had acutediarrheawere0.2timeslesslikelyto experience mortality than those who had

no acute diarrhea (aRR=0.2, 95%CI: 0.04 0.88, p = 0.03). Children who had anemia were 2.9 times more likely to die than thosewhohadnoanemia(aRR=2.9,95%CI: 1.236.62, p=0.01). Children who had bacteremia were 10 times more likely to die than those who had no bacteremia (aRR=10.0, 95%CI: 3.6229.01, p=0.01). Children who had HIV were 4.8 times at risk of dying compared with participants who had no HIV (aRR=4.8, 95%CI: 1.42 16.30, p<0.01). Children who had TB were 4.3 times more likely to die compared to participants who had no tuberculosis (aRR=4.3, 95%CI: 1.2814.49, p <0.02). Children withshockhad60.9 times higher risk of death compared to participants who had no shock (aRR=60.9, 95%CI: 9.05 410.28, p <0.01).

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Table 3: Comorbidities associated with in the mortality among children below 5 years admitted with Severe Acute Malnutrition in the nutritional unit of JRRH Complication Mortality cRR(95%CI) P aRR(95%CI) P Yes No

Dehydration

No 33(17.62) 173(82.38) 1.0 Yes 12(9.38) 116(90.63) 0.48(0.240.96 0.04 0.8(0.312.20) 0.71

Pneumonia

No 29(13.74) 182(86.26) 1.0 Yes 20(15.75) 105(84.25) 1.17(0.632.18) 0.61

Malaria No 34(13.55) 217(84.45) 1.0 Yes 15(17.24) 72(82.76) 1.3(0.682.68) 0.40

Acutediarrhea No 44(16.6) 221(83.4) 1.0 Yes 5(6.85) 68(93.15) 0.4(0.140.96) 0.04 0.2(0.040.88) 0.03

Anaemia No 32(11.55) 245(88.45) 1.0 Yes 17(27.87) 44(72.13) 2.9(1.55.8) 0.01 2.9(1.236.62) 0.01

Bacteremia

No 36(11.43) 279(88.57) 1.0 Yes 13(56.52) 10(43.48) 10.1(4.11 24.64) 0.01 10.0(3.62 29.01) 0.01

HIV+ No 42(13.21) 279(86.79) 1.0 Yes 7(35.0) 13(65.0) 3.5(1.339.37) 0.01 4.8(1.4216.30) 0.01 TB No 42(13.08) 279(86.92) 1.0 Yes 7(41.21) 10(58.82) 4.6(1.6712.88) 0.01 4.3(1.2814.49) 0.02

ElectrolyteImbalance

No 48(14.81) 276(85.19) 1.0 Yes 1(7.14) 13(92.86) 0.4(0.563.45) 0.44

Shock No 39(11.96) 287(88.04) 1.0 Yes 10(83.33) 2(16.67) 36.7(7.77 174.15) 0.01 60.9(9.05 410.28) 0.01

Hypothermia

No 46(13.86) 286(86.14) 1.0 Yes 3(50.00) 3(50.00) 6.2(1.2131.74) 0.03 0.9(0.098.80) 0.94

Cardiacfailure

No 49(14.63) 286(85.37) Yes 0(0.00) 3(100.00)

cRR=crude Relative Risk, aRR = adjusted Relative Risk CI = Confidence Interval, P value is significantat 0.05

DISCUSSION

The objective of the present study was to determine the comorbidities associated with in hospital mortality among children underfive years ofage admitted withSAM in the nutritional unit of Jinja Regional Referral hospital. It was found out that anemia, bacteremia, HIV shock and TB were the comorbidities associated with mortality. Such comorbidities partly explain why malnutrition continues to be a major cause of mortality especially in lowincome countries killing millions of children [23]. In this study it was found out that shock was found to be an

independent predictor of mortality among children under five years of age admitted with severe acute malnutrition in the study site with children who had shock having 60.9 folds the risk of death than children who never had shock. Shock is definedbytheWHOinseveremalnutrition as all of the following: altered conscious level, capillary refill time more than 3 seconds, a weak and fast pulse plus a temperature gradient (cool hands and/or feet). For the diagnosis of shock the presence three features are required (cold feet or hands, weak and fast pulse), which

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have resulted in limited numbers identified for which fatal outcome is almost universal [24]. The result of the present study is in line with the result of an institution based retrospective cohort study done among underfive children with severe acute malnutrition in Northwest Ethiopia (AHR: 7.9, 95% CI: 3.7, 16.7).Muchascoxregressionanalysiswas usedin theprevious study, the magnitude of the risk of mortality is similar in both the present study and the previous study [25].

The finding of the present study is also in accordance with the finding of [27] which demonstrated that children with shock were more likely to have hazard of death as compared to their counterparts though shock was significant only at bivariate analysis(CHR:6.0,95%CI:1.77,20.45)but was not found to be significant at the multivariable Cox regression analysis (AHR: 2, 95% CI: 0.51, 7.84).The result of this study is further supported by a study doneby [27] who foundthat children with fatal outcome were 11.29 times more likely to have shock (p = 0.001). Contrary to this study, [9] in their study done at Mulago National Referral Hospital excluded all the children who had shock from their study and yet there is a possibility that they could have found some association between mortality and shock as it has been the case in the present study. The similarity of our result with others could be explained by the poor response of the medical intervention to patients with Severe Acute Malnutrition whose metabolism has completely changed because of the reductive adaptation. This study revealed that anemia was one of the comorbidities with anincreasedlikelihoodofriskofmortality among children with SAM at JRRH. This finding coincides with that of [25] in Ethiopia in which anemia was an independent predictor of mortality among children with SAM (AHR=2.3, 95%CI: 1.2 4.5).However,[19]inBurkinaFasodidnot find a difference in mortality among severely malnourished children with anemia (12.4%) and those without anemia (22.2%, p = 0.12. This implies that anemia leads to death when not adequately managed. The latter study was in disagreement with other studies as it argued that anemia was not statistically associated with mortality of the children admitted with SAM This could be explained by the study design or the

different response to the medical intervention.

In thepresentstudy,theriskofdeath was 4.8 times higher in children who had HIV than children who never had HIV. The possible reason for the high magnitude of risk of death among malnourished children with HIV could be because HIV infection increases susceptibility to persistent diarrhoea and opportunistic infections which can greatly impact the health of severely malnourished children and HIVinfected children with severe acute malnutrition are nearly three times more likely to die during treatment (for severe acute malnutrition), compared to their HIVnegative counterparts [28] Currently, there are very few evidence based recommendations for managing children with SAM and HIV infection any differently to children with SAM without HIV infection. [9] found an association between HIV status of the children and mortality on bivariate analysis but unfortunately the association disappeared on multivariate analysis after adjusting for age and sex of the children which is a clear indicator that the association between HIV status and mortality was being masked by the sex and age of the children. Therefore in the previous study HIV status of the children was not an independent risk factor associated with mortality of the children unlike in the present study where HIV status was an independent risk factor for mortality. [29] studied risk factors for death in children during inpatient treatment of severe acute malnutrition using a prospective cohort study design and they found that HIV infected study participants were 3 times morehazardofdeathcomparedtotheHIV noninfected study participants but unfortunately they found no statistically significant association between HIV status and mortality among the study participantscontrarytowhatwasfoundin thepresentstudy.Also,[13] in theirstudy on morbidity and mortality pattern in children under 5 years with severe acute malnutrition in Zambia found that HIV infected children were 1.8 times more likely to die than those who were HIV uninfected (OR=1.8, 95% CI 1.6 2.0, p < 0.001) which is in line with what was found in the present study. In Uganda, a study done by [4] on treatment outcome among children under five years hospitalized with severe acute malnutrition in St. Mary’s hospital Lacor,

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revealed that HIV was significantly associated with mortality in 18.6% versus 9.6% in children HIV negative with OR=3.1(1.3077.292) of which this study finding is consistent with the findings of the present study. Finally, a prospective descriptive study done among Kenyan children by [21] revealed that HIV status of the study participants was statistically associated with mortality. Study participants who were not tested for HIV had 2.2 higher odds of dying than study participants who were HIV negative (OR 2.2, 95%CI 1.3 3.7, P=0.0042). Drug toxicity, antimicrobial use, fungal infections and persistent diarrhea are likely to require extra consideration amongst HIVinfected children with SAM [10]. Contrary to what was found in this study, an institution based retrospective cohort study done in Northwest Ethiopia by [25] found no statistically significant association between HIV status of the study participants and mortality. Possible reason for the disagreement in the study findings could be because of the difference in the geographical regions where the 2 studies were conducted and the study designs used in that the previous study was retrospective whereas thepresentstudywasprospective.

This study shows that TB is a contributor to mortality among hospitalized children with severe acute malnutrition. The study participants who had tuberculosis were have 4.3 times risk of death than study participants who had no tuberculosis. Tuberculosis contributes significantly to mortality among children with SAM in high TB and HIV prevalence settings [13] In Northwest Ethiopia, contrary to the findings of the present study, [17] found no significant statistical association between Tuberculosis and mortality amongthestudyparticipants.Muchasthe sample size in the previous study was almost doubling the sample size in the present study, still it did not generate for them enough evidence to reject the null hypothesis, the disagreement in the results of the previous study and the present study can then be explained by the difference in the study settings, difference in study designs and difference in clinical profiles of the study participants. [26] retrospectively reviewed records of children with SAM admitted in three selected hospitals from Ethiopia and they found 5.3% of the study participants to be having Tuberculosis but they never

went ahead to do regression analysis to establish whether there was any association between Tuberculosis and mortality of the study participants. Bacteremia was found to have a high likelihood of mortality. Severe acute malnutrition severely suppresses every component of the immune system leading to increased susceptibility and severity to infection. However, symptoms and signs of infections are often unapparent making prompt clinical diagnosis and early treatment very difficult. In the present study, children with bacteremia had 3.8 folds the risk of death compared to their counter parts who never had bacteremia. A prospective study from Uganda was done to determine predictors of mortality among hospitalized children with severe acute malnutrition. On bivariate analysis, results showed an association between bacteremia and mortality of the study participants (OR 2.23, 95%CI 1.18 4.24, P=0.01) but on multivariate analysis the association was lost (OR 0.3, 95%CI 0.04 2.24, P=0.20) which implies that on bivariate analysis the association between bacteremia and mortality was being masked by some confounding factors although both the previous study and the current study were also prospective cohort studies [9] Similarly in a study done by [30] to confirm whether children with severe malnutrition at highest risk of death can be identified with the WHO protocol, they observed that bacteremia complicated 27% of all death and bacteremia had a significant P value of 0.03. Similarly, a study done from rural district hospital in southern Mozambique revealed that bacteremia was independently associated with an increased risk of in hospital mortality which is consistent with what was found inthisstudy[31].Ontheotherhand,case control study was conducted in the Dhaka Hospital to identify the risk factors of mortality in severely malnourished children whowerehospitalized.Resultsof the study revealed that study participants who had the presence of clinical septicaemia were 8.8 times the odds of death than study participants who never had septicaemia (AOR 8.8, 95%CI 3.7 21.1, p=0.01). The magnitude of risk of death of study participants with bacteremia in the present study is low compared to the previous study [32,33,34]. The difference in the magnitude of risks could have arisen

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because the previous study was a case control study meanwhile the present study was a prospectivecohortstudy.The findingsofthisstudyisfurthersupported by the findings of a study done by [33,35] to study bacteremia in severely malnourished children in an HIV endemic setting and they found significant association between bacteremia and

mortality of the study participants. Similarly, the results of a study done by Talbert et al., revealed that children who had bacteremia had 4.3 times the odds of death than the children who never had bacteremia (AOR 4.3, 95%CI 2.3 8.1, P<0.001) which happens to be in agreementwiththefindingsofthepresent study

CONCLUSION

Themostimportantcomorbiditiesassociatedwithmortality wereacuteanemia,bacteremia, HIV,TBandshock.

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