Mortality during and following hospital admission among school-aged children: a cohort study

Introduction

Despite a remarkable decline in global child mortality, more than 6 million children died in 2018, of which 0.9 million (15%) deaths occurred among children aged 5 to 14 years, mostly in low- and middle-income countries (LMICs)^1,2. Public health efforts to improve survival are generally directed towards children <5 years old^2–4. Despite there being no specific new health interventions targeting children aged 5 to 14 years, their mortality risk from 1990 to 2016 declined by 51% globally⁴. However, since 2000, the annual rate of mortality reduction in this group (2.7%) has been lower than amongst children <5 years old (4.0%)⁴.

Children ≥5 years old may be admitted to hospital with different conditions than younger children and their risks for inpatient or post-discharge mortality may also differ. However, there are only limited data describing reasons for admission and mortality-patterns in LMICs. Among school-aged children admitted to six Kenyan hospitals in 2013, 3.5% of children aged 5 to 9 years and 5.0% of children 10 to 14 years died⁵. Infectious diseases such as malaria were the main reported causes of death in children ≥5 years^2,5,6.

Post-discharge mortality is increasingly recognized as a significant contributor to the burden of mortality among under-fives in LMICs and adults in resource-rich settings^7–9. The most recent systematic review (2018) of paediatric post-discharge mortality in LMICs did not identify any studies focusing specifically on school-aged children^7,8. Of 24 studies reviewed, four included children ≥5 years old. A study in Bangladesh with a sample size of 74 children aged 24 to 72 months did not report the number of children who were ≥5 years old¹⁰. A large study in Kenya among children 0 to 15 years old (N=14,971) reported that 16% (88/535) of all post-hospital discharge deaths were among children aged 5 to 14 years¹¹ and two studies from Uganda with children aged 2 months to 12 years reported ~1% and 3.8% children dying after discharge, respectively, but were not disaggregated by age group^12,13. Since the latest systematic review (2018)⁷, four more studies have evaluated paediatric post-discharge mortality in LMICs^3,14–16. Hau et al. included children aged 2 to 12 years followed-up for 12 months after discharge from two hospitals in Tanzania and found that 16% (26/161) of children aged 5 to 12 years died after hospital discharge³. Post-discharge mortality risk was reported to be higher than that of children <5 years (hazard ratio 2.44 (95%CI, 1.37 to 4.34)³. The commonest diagnoses at admission were malaria and sickle cell disease³. The second study from southern Mozambique included 18,023 children aged <15 years, of which 83/3,816 (2.2%) aged ≥5 years died within three months after discharge¹⁴. The third study was from Kenya, but excluded children ≥5 years old¹⁵. The fourth study from Tanzania included children aged 2 to 12 years, of whom 47/466 (10%) died one year after hospital discharge, but deaths were not disaggregated by age¹⁶. Two of the four studies from Tanzania, used same study participants to evaluate overall one-year post-discharge mortality based on admission diagnosis³ and on levels of haemoglobin¹⁶ respectively.

In this retrospective cohort study, we aimed to describe the reasons for hospitalisation, underlying illnesses, and the clinical characteristics and features associated with mortality during hospitalisation and for one year after discharge among children 5 to 12 years old admitted to a rural hospital in Kenya.

Methods

Results

From 2007 to 2016, there were 41,107 paediatric admissions to KCH, of which 7,063 (17%) were aged 5 to 12 years (Figure 1). Of these, 3,907 (55%) admissions among 3,196 children were KHDSS residents and were included in this analysis (Figure 1). Their median age was 92 (IQR 74−116) months and 1,673 (43%) were female. Of the 3,907 admissions, 792 (20%) presented with severe anaemia, 749 (19%) with malaria, 408 (10%) with sickle cell disease (known at admission or diagnosed during admission), 408 (10%) had suffered trauma, 340 (8.7%) with severe pneumonia and 194 (5.0%) with diarrhoea.

Figure 1. Study participant recruitment and follow-up.

KHDSS, Kilifi Health Demographic Surveillance System.

Underlying chronic conditions included stunting in 1,143 (29%), severe stunting in 90 (2.3%), severe wasting (MUACZ <-3) in 623 (16%), HIV infection in 194 (5.0%), and nutritional oedema in 90 (2.3%) (Table 1, Table 2 and Extended data Table S2).

A total of 138 (3.5%) children had detectable bacteraemia (Table 1). The commonest bacteria isolated were: Streptococcus pneumoniae (47/138, 34%), Staphylococcus aureus (32/138, 23%) and non-typhi Salmonella species (21/138, 15%) (Extended data Table S3). The final diagnoses assigned by clinicians are shown in Table 2.

There were 132 (3.4%) inpatient deaths. The median (IQR) time to inpatient death was one (1−4) days, while median (IQR) time to discharge among the survivors was three (2−6) days. There were 44 (5.6%), 30 (4.0%), 45 (13%), 23 (17%), 9 (17%), and 10 (5.2%) deaths among those admitted with severe anaemia, malaria, severe pneumonia, bacteraemia, meningitis and diarrhoea, respectively. There were 21 (11%), 34 (5.5%), 10 (2.5%) and 4 (1.2%) deaths among children who were HIV-infected, severely wasted, had sickle cell disease and Epilepsy/convulsion, respectively (Table 2 and Extended data Table S2).

Post-discharge mortality

Among the 3,064 children who were discharged alive, follow-up data were missing for 67 (2.2%) children (Figure 1). We therefore analysed data from 2,997 children who accrued 2,853 child-years of observation. Eighty-nine (3.0%) children died during follow-up; 63 (71%), 80 (90%) and 84 (94%) of post-discharge deaths occurred within three, six and nine months of discharge, respectively. The overall mortality rate was 31.2 (95%CI, 25.3 to 38.4) per 1,000 child-years. During the first three, six and nine months after discharge, mortality rate was 244 (95%CI, 190.3 to 311.8), 89.6 (95%CI, 72.0 to 111.6), and 53.2 (95%CI, 43.0 to 65.9) per 1000 child-years, respectively. Forty (45%) deaths occurred at home, 26 (29%) during readmission to KCH and 23 (26%) in other health facilities. Among the 26 deaths at KCH, the leading estimated causes of death were: malaria (8, 31%), anaemia (3, 12%) and heart disease (3, 12%) (Extended data Table S6).

Some signs of disease severity at admission (elevated respiratory rate and presence of weak pulse), HIV infection, severe anaemia and severe wasting were positively associated with post-discharge death (Table 3 and Figure 2). Malaria was negatively associated with post-discharge death (Table 3 and Figure 2). Hospital admission duration was not independently associated with post-discharge death (Extended data Table S4). Thirteen (0.43%) children absconded from hospital and all of them were alive after one year post-discharge.

Figure 2. Cumulative hazard curves for post-discharge mortality:

A) by HIV status; B) by anaemia categories; C) by malaria status and D) by mid-upper arm circumference (MUAC)-for-age z-scores groups. The broken lines are 95% confidence intervals, where there is overlap in 95%CI some lower or upper confidence intervals may not be visible.

There was no evidence that the effect of HIV infection on post-discharge mortality was modified by age (P=0.95), anaemia (P=0.25), malaria (P=0.37) or severe wasting (P=0.88). The effect of malaria on post-discharge mortality was not modified by anaemia (P=0.33) but was modified by severe wasting (P=0.007) and weak evidence of being modified by age (P=0.05). Compared to MUACZ ≥-2 with a negative malaria slide, the groups of MUACZ -3 to -2 with a negative malaria slide (HR 3.60 [95%CI, 1.75 to 7.39]) and MUACz<-3 with a negative malaria slide (HR 6.36 [95%CI, 3.10 to 13.1]) had greater post-discharge mortality. Among children with positive slide results, MUACZ was not associated with post-discharge mortality.

In the exploratory analysis of biochemical variables, hyperkalaemia and elevated creatinine were associated with post-discharge mortality (Extended data Table S7).

Discussion

In this large study of school-aged children admitted to hospital and systematically followed-up during admission and for one year after discharge, we observed that anaemia, malaria, sickle cell disease and trauma were the leading reasons for admission. This profile is unlike that reported among under-fives, in whom pneumonia and diarrhoea are the leading reasons for admission, accounting for more than two-thirds of hospital admission in Kenya and South Africa^26–28. All-cause inpatient case fatality was 3.4%, which was similar to the 3.5% previously reported in six hospitals in Kenya among children 5 to 17 years old in 2013⁵. Markers of disease severity at admission were the main predictors of inpatient mortality despite following WHO care guidelines, suggesting that current management strategies and resources may be insufficient for the sickest school-aged children. Surprisingly, epilepsy/convulsion appeared ‘protective’ compared to other reasons for admission in this hospitalised population, but would not be expected to be protective if compared to children in the community.

The 3.0% one-year post-discharge mortality, with almost three-quarters occurring within three months, broadly concurs with that observed in rural Mozambique three months after hospital-discharge (2.2%) among children 5 to 15 years old¹⁴, but was much lower than one-year post-discharge mortality (16%) observed among children 5 to 12 years old in Tanzania³. However, the Tanzanian study did not stratify results by age above or below 5 years and it seems likely that a higher prevalence of non-communicable diseases including cancer and heart disease reported in that population may have contributed to the higher risk of post-discharge death. However, the mortality rate of 31.2 deaths/1000 child-years observed was >34 fold higher than 0.91 deaths/1000 child-years within KHDSS among this age-group (unpublished data). The leading cause of death among the 26 children who died during readmission at KCH was malaria, similar to the leading cause assigned through verbal autopsies to children 1 to 4 years old who died in the community, but differing from that in infants among whom pneumonia was the leading causes of death in KHDSS²⁹

Tachypnoea, which may be associated with anaemia, hypoxia, sepsis or pneumonia, and weak pulse, a sign of circulatory insufficiency, were independently associated with post-discharge mortality which would suggest some children may be discharged with ongoing unstable vital signs that may lead to post-discharge deaths. Undernutrition was associated with post-discharge mortality, similar to most previous studies, which have identified nutritional status as a major risk-factor for post-discharge mortality in under-fives^{3,7,14,15,17,30}. We previously showed that MUACZ is valuable in predicting post-discharge mortality among children >5 years in a model only adjusted for age, sex and HIV status²².

We found severe anaemia was independently associated with post-discharge mortality; however, prior evidence of the effect of haemoglobin concentration on post-discharge mortality has been inconsistent, and may be influenced by the predominant causes of anaemia and local transfusion policies^{3,14,16,31–34}. Interestingly, we found no significant effect modification by anaemia on the effect of malaria on post-discharge mortality. The finding that children with malaria had lower post-discharge mortality than other reasons for admission is consistent with previous reports from this site among children <5 years of age where malaria parasitaemia had an apparently ‘protective’ effect on post-discharge mortality¹¹. This likely reflects the fact that when appropriately treated, mortality risk in children with malaria may be lower than in children with other causes of a similar apparent severity of illness.

In exploratory analyses, elevated creatine and hyperkalaemia, markers of impaired kidney function, were identified as predictors of both inpatient and post-discharge mortality. One study among children aged 2 to 12 years in Tanzania identified estimated glomerular filtration rate <60 ml/min/1·73m² as a predictor of one-year post-discharge mortality³. This is an important finding since dehydration and sepsis are common and associated with acute kidney injury³⁵, and current guidelines recommend potentially nephrotoxic empiric gentamicin, without capacity for monitoring levels³⁶. However, clinical trials that could delineate attributable nephrotoxicity from background risks from renal disease, serious illness and dehydration have not yet been done.

Overall, our findings add to previous data in under-fives suggesting that hospitalisation marks an extended period of vulnerability, and reports suggesting that significant post-discharge mortality occurs outside hospital even among school-age children^7,11,17. The transition from inpatient to home care in the immediate three-month period following hospital discharge appears to be a critical period of risk. Risk stratification and targeted interventions for this population during this period might improve survival⁴. However, current services, such as for the management of malnutrition in the community or those to manage anaemia, largely focus on children <5 years of age and may not operate in a way that fully addresses the mortality risk in this population^37,38.

Strengths of this study include the large sample size, high rates of follow-up and the detailed longitudinal data available. However, this study also had some limitations. We used data from a single hospital, including only children resident within the nearby KHDSS, thus our results may not be generalizable to other sites or children living further away from the main road. Biochemical features were not systematically collected and could not be included in the primary analysis. We were not able to ascertain whether HIV infected children and malnourished children attended and complied with treatments from comprehensive care and nutrition clinics after discharge from hospital. We did not have access to causes of deaths among children who died at home or in other health facilities. Moreover, this study did not include data on caregiver or household characteristics, socio-economic situation or access to care.

Conclusion

This study highlights important differences in reasons for hospitalisation among school-aged children compared to younger children, and high rates of inpatient and post-discharge mortality among subgroups of school-aged children. To improve survival, active risk stratification and targeting intervention and follow-up in the early months after hospital discharge are needed, along with expansion of services that normally focus on the under-fives to vulnerable over-fives. The large proportion of deaths outside hospital suggests that facilitating access to healthcare among the most vulnerable, and priority clinical evaluation if unwell may be important measures.

Data availability