The authors have declared that no competing interests exist.
Conceived and designed the experiments: MOW CL JS SP. Performed the experiments: MOW SP. Analyzed the data: MOW CL JMA NK SP EK AN. Wrote the paper: MOW NK CL JMA EK AN SP JS.
Mortality following hospital discharge is an important and under-recognized contributor to overall child mortality in developing countries. The primary objective of this systematic review was to identify all studies reporting post-discharge mortality in children, estimate likelihood of death, and determine the most important risk factors for death.
MEDLINE and EMBASE were systematically searched using MeSH terms and keywords from the inception date to October, 2012. Key word searches using Google Scholar™ and hand searching of references of retrieved articles was also performed. Studies from developing countries reporting mortality following hospital discharge among a pediatric population were considered for inclusion.
Thirteen studies that reported mortality rates following discharge were identified. Studies varied significantly according to design, underlying characteristics of study population and duration of follow-up. Mortality rates following discharge varied significantly between studies (1%–18%). When reported, post-discharge mortality rates often exceeded in-hospital mortality rates. The most important baseline variables associated with post-discharge mortality were young age, malnutrition, multiple previous hospitalizations, HIV infection and pneumonia. Most post-discharge deaths occurred early during the post-discharge period. Follow-up care was examined in only one study examining malaria prophylaxis in children discharged following an admission secondary to malaria, which showed no significant benefit on post-discharge mortality.
The months following hospital discharge carry significant risk for morbidity and mortality. While several characteristics are strongly associated with post-discharge mortality, no validated tools are available to aid health workers or policy makers in the systematic identification of children at high risk of post-discharge mortality. Future research must focus on both the creation of tools to aid in defining groups of children most likely to benefit from post-discharge interventions, and formal assessment of the effectiveness of such interventions in reducing morbidity and mortality in the first few months following hospital discharge.
Acute diseases leading to death and significant morbidity continue to plague children in resource limited areas of the developing world disproportionately. About 70% of deaths are due to infectious diseases. While effort has been made to address diagnosis and treatment during the acute episode, care following discharge from hospital is an important aspect of management that is often neglected by both policy makers and health researchers. Reasons for this neglect are likely multifactorial and include a tremendous burden and high costs to provide care for acute illness, which in regions with limited resources poses significant system challenges. Furthermore, failure to recognize and document the burden of post-discharge morbidity and mortality contributes to a lack of awareness by health care workers of potentially avoidable adverse outcomes. Therefore, the attempt to improve care following discharge is viewed as a low priority by both health care workers and policy makers. Lack of attention to post-discharge issues has tremendous adverse implications because the scant available evidence strongly suggests that in developing countries post-discharge deaths may be of similar (or higher) magnitude than deaths during hospitalization
While current evidence clearly points to the significant burden of post-discharge mortality, the estimates of this burden vary widely between studies. Factors such as age, co-morbidities, disease severity, healthcare resources, length of follow-up, and social disparities are likely to play a significant role in determining outcome. Using the guidelines set forth by the Meta-analysis of Observational Studies in Epidemiology Group
We conducted a systematic computerized search from the inception date (1946 in MEDLINE and 1974 in EMBASE) to October, 2012 to identify all potentially eligible studies. One investigator (SP) trained in database searching independently carried out an initial systematic search. A study was defined as an analysis of post-hospitalization mortality in a pediatric population. We applied the following algorithm in both medical subject heading (MeSH) and free text words. In MEDLINE, the MeSH terms “follow-up studies,” “hospitalization,” OR “longitudinal studies” were combined with “developing countries,” “Africa,” “Bangladesh,” “Haiti,” “Afghanistan,” “Yemen,” “Papua New Guinea,” “Myanmar,” “Pakistan,” OR “Solomon Islands.” MeSH terms were exploded where appropriate. The MeSH term “Africa” included the names of all African countries when exploded. Free text words including “post-discharge mortality” and “long-term outcomes” were also used to increase capture of relevant articles. In EMBASE, the MeSH terms “follow-up,” “hospitalization,” OR “longitudinal study” were combined with “developing country,” “Bangladesh,” “Haiti,” “Afghanistan,” “Yemen,” “Papua New Guinea,” “Burma,” “Pakistan,” “Solomon Islands” OR “Melanesia” AND “Pediatrics.” Free text word “Burma” was also included in the search as this was not a MeSH term. Google Scholar™ was also searched and references of relevant publications were reviewed to identify any articles not captured during initial search. All retrieved articles were independently reviewed by a second author (MW) to determine if they met inclusion criteria.
Studies were included if: (i) they presented original data from randomized-controlled trials, cohort studies, or retrospective analyses; (ii) the data on post-discharge mortality in pediatric patients of any age was clearly defined and length of follow-up was reported; (iii) data was collected from pediatric patients living in developing countries. Developing countries were defined for the purposes of this review as those countries currently classified by the United Nations Development Program (UNDP) as having a low Human Development Index (HDI)
Studies were excluded if: (i) there was no pediatric data or pediatric data could not be differentiated for adult data; (ii) there was no post-hospital discharge information or patients were not discharged from a hospital setting; (iii) discharge was following a non-admission (i.e. following birth); (iv) studies represented a surgical population since post-discharge care following surgery would likely be very different from care following acute illness and; (v) if the study was unpublished, published in a language other than English or if published only in abstract form.
Data was collected systematically onto a computerized spreadsheet developed
While a validated quality scoring system for studies on post-discharge mortality has not been developed, several variables likely to contribute to study quality were collected and reported including: proportion of subjects successfully followed-up, method of follow-up, study design and presence of an intervention.
Since significant heterogeneity between studies was observed studies were not pooled. Studies were organized based on underlying etiology in the study sample. Descriptive statistics were generated using Microsoft Excel (Redmond, WA).
Thirteen studies met both inclusion and exclusion criteria and were included in the final analysis; four randomized controlled trials
Ref. | Design | Period | Country | Age Range | Population | Locale* | N | FU Proportion | FU Method | FU Times | IP Mortality | PD Mortality | PD deaths in hospital | PD hospitalization | Obs. Period | ||||||||||||||||||
(14) | Retrospective Cohort | 1991–1996 | Guinea-Bissau | (81%<5y) | All Admits | NR | 3373 | NA | Surveillance | NA | 12.10% | 6.10% | 23.10% | 11.60% | 12 m | ||||||||||||||||||
(15) | Retrospective Cohort | 2003–2008 | Kenya | 0–15y | All Admits | Mixed | 14,971 | NA | Surveillance | NA | NR | 4.50% | NR | NR | 12 m | ||||||||||||||||||
(1) | Prospective Cohort | 1991 | Kenya | 0–5y | All Admits | Mixed | 1223 | 96% | CV & HV | 4, 8 w | 10% | 13% | NR | NR | 8 w | ||||||||||||||||||
(2) | CC with longitudinal FU | 2002–2004 | Malawi | 6–60 m | Anemia (Hg<50g/L) | Mixed | 377 | 82.20% | CV | 1, 3, 6, 12,18 m | 6.4% | 11.6% | NR ("most") | 17.20% | 18 m | ||||||||||||||||||
7–60 m | Any other condition | Mixed | 373 | 80.40% | CV | 1, 3, 6, 12,18 m | 0.0% | 2.7% | NR ("most") | 9.40% | 18 m | ||||||||||||||||||||||
(9) | RCT | 2006–2009 | Malawi | 4–59 m | IPTpd | Mixed | 706 | 95% | PCD | 1, 2, 3, 6m | NA | 2.6% | NR | 19% | 6 m | ||||||||||||||||||
5–59 m | Placebo | Mixed | 708 | 95% | PCD | 1, 2, 3, 6m | NA | 2.4% | NR | 19% | 7 m | ||||||||||||||||||||||
(10) | RCT | 2004–2006 | Guinea–Bissau | 3–60 m | Severe malaria | NR | 951 | 95% | CV & HV | 28 d after admission | 7.20% | 2.0% | NR | NR | 28d after admission | ||||||||||||||||||
(12) | Prospective cohort | 1979 | Bangladesh | 3 m–3y | Diarrhea | Rural | 551 | NR | NR | NR | NA | 4.2% | NR | NR | 12 m | ||||||||||||||||||
(11) | Prospective cohort | 199–1992 | Bangladesh | 1–23 m | Diarrhea | Urban | 500 | 85% at 6w, 80% at 12w | HV | 6, 12 w | NA | 7% | 53% | NR | 12 w | ||||||||||||||||||
(16) | Retrospective cohort | 1983–1983 | Bangladesh | 24–72 m | Diarrhea | Urban | 74 | 93% | HV | Approx. 4m | NR | 2.9% | NR | NR | Approx. 4m | ||||||||||||||||||
(3) | RCT | 1993–1997 | Tanzania | 6–60 m | Pneumonia | NR | 687 | 89% | CV | Monthly | 3% | 10% | NR | NR | 24 m | ||||||||||||||||||
(4) | RCT | 2006–2008 | Bangladesh | 2–59 m | Severe pneumonia | Urban | 180 | 90% | CV | Every 2 w | 0% | 1% | NR | 6% | 3 m | ||||||||||||||||||
(17) | CC with longitudinal FU | 1992–1997 | The Gambia | 0–5 m | LRTI, SpO2 <90 | Mixed | 83 | 64% | CV & HV | Once | NR | 15% | NR | NR | mean 41 m | ||||||||||||||||||
LRTI, SpO2 ≥90 | Mixed | 107 | 61% | CV & HV | Once | NR | 6% | NR | NR | mean 34 m | |||||||||||||||||||||||
(13) | Prospective cohort | 1970 | DRC | NR | PEM | NR | 171 | 76 | CV | Annually | NA | 18% | NR | NR | 5y |
Study | Population | Obs. period | Time-point for 50% of PD deaths | Other mortality statistic |
(11) | 1–23 m with diarrhea | 12 w | 10d | |
(12) | 3 m-3y with diarrhea | 12 m | 30d | |
(14) | All pediatric admissions | 12 m | 60d | |
(1) | 0–5y all admissions | 8 w | 82% PD deaths at 4 w | |
(3) | 6–60 m with pneumonia | 24 m | 80% PD deaths at 12 m | |
(13) | malnutrition | 5y | >50% PD deaths at 1y | |
(2) | 6–60 m with anemia | 18 m | 71% at PD deaths at 6 m* |
Ref. | Population | Risk factors for post-discharge mortality | Adjusted RR or HR (95% CI) |
(15) | All admissions | Age 1–5 m | 1.34 (0.93–1.92) |
Age 6–11 m | 0.82 (0.57–1.18) | ||
Age 2–5 y | 0.57 (0.36–0.90) | ||
Weight-for-age Z score <−3 | 3.42 (2.5–4.68) | ||
Weight-for-age Z score <−4 | 6.53 (4.85–8.80) | ||
Parasitemia | 0.45 (0.29–0.71) | ||
Hypoxia | 2.30 (1.64–3.23) | ||
Bacteremia | 1.77 (1.15–2.74) | ||
Jaundice | 1.77 (1.08–2.91) | ||
Hepatomegaly | 2.34 (1.60–3.42) | ||
Hospitalization >13d | 1.83 (1.33) | ||
1 prior discharge | 2.83 (2.04) | ||
2 prior discharges | 7.06 (4.09–12.21) | ||
≥3 prior discharges | 23.55 (10.70–51.84) | ||
Mild pneumonia | 2.30 (1.00–5.28) | ||
Severe pneumonia | 1.37 (1.05–1.79) | ||
Very severe pneumonia | 4.09 (2.25–7.46) | ||
Severe malnutrition | 4.37 (2.73–7.01) | ||
Meningitis | 2.29 (1.57–3.32) | ||
Sick young infant | 2.67 (1.98–3.58) | ||
HIV | 2.22 p = 0.19 | ||
Absconded | 2.06 p = 0.95 | ||
(14) | All admissions | Mother educated | 0.74 (0.55–0.99) |
Discharged against medical advice | 8.51 (5.32–13.59) | ||
Anemia (vs. malaria) | 1.97 (1.07–3.63) | ||
Diarrhea (vs. malaria) | 1.82 (1.21–2.74) | ||
Pneumonia (vs. malaria) | 0.98 (0.65–1.51) | ||
Measles (vs. malaria) | 0.77 (0.36–1.64) | ||
≥5y (vs. 1–12 m) | 0.15 (0.07–0.30) | ||
4–5y (vs. 1–12 m) | 0.23 (0.10–0.59) | ||
3–4y (vs. 1–12 m) | 0.14 (0.06–0.35) | ||
2–3y (vs. 1–12 m) | 0.52 (0.33–0.81) | ||
1–2y (vs. 1–12 m) | 0.82 (0.59–1.13) | ||
Neonatal (vs. 1–12 m) | 0.69 (0.31–1.55) | ||
(2) | Anemia (Hg<50 g/L) admissions | Increase in age (months) | 0.92 (0.87–0.97) |
Rural (vs. urban) | 1.63 (0.63–3.52) | ||
Male (vs. female) | 1.54 (0.68–3.52) | ||
Parental unemployment | 4.15 (1.61–10.74) | ||
Splenomegaly | 0.36 (0.16–0.80) | ||
HIV | 10.49 (4.05–27.20) | ||
Bacteremia | 2.17 (0.84–5.64) |
Ref. | Population | Risk factors for post-discharge mortality | Adjusted RR or HR (95% CI) |
Studies of diarrhea admissions | |||
(11) | Diarrhea admissions | Age (1–6 m vs. 6–24 m) | 4.57 (2.90–7.18) |
Sex (Female) | 1.73 (1.14–2.65) | ||
Maternal Education (none vs. ≥1y) | 2.12 (1.37–3.28) | ||
Child was not breastfed | 2.35 (1.44–3.84) | ||
Weight-for-age median <60% vs. ≥60% | 1.04 (0.57–1.89) | ||
Length-for-age median <85% vs. ≥85% | 2.97 (1.43–6.16) | ||
(17) | Pneumonia admissions | Weight-for-age Z-Score <−2 | 3.2 (1.03–10.29) |
Length of stay | SS* (RR not reported) |
Three studies (two from Kenya and one from Guinea-Bissau) included all children regardless of admission diagnosis. The first Kenyan study, a prospective cohort study conducted in 1991, enrolled 1223 children between 0 and 5 years of age at the time of admission and followed these children until 8 weeks following discharge
Two studies of children with malaria, both of which were randomized trials, were identified. The first study, conducted in Malawi between 2006 and 2009, randomized children with severe malaria to receive intermittent preventative therapy (IPTpd) or placebo following hospital discharge
Three studies investigating outcomes following diarrhea were identified, all of which were conducted in Bangladesh between the late 1970 s and the early 1990 s. The most recent study conducted between 1991 and 1992 enrolled 500 urban children who were admitted and treated for diarrhea
Three studies of outcomes following pneumonia were identified, two of which were randomized trials. The first study was a secondary analysis of a trial of vitamin A supplementation in children 6–60 months of age with pneumonia
One study aiming to determine the short and long term effects of severe anemia in children conducted in Malawi in 2008 was identified
One study assessed survival following successful hospital treatment of protein energy malnutrition in the Democratic Republic of Congo (formerly Zaire)
Thirteen studies that reported post-discharge mortality rates were identified. Studies varied in design, length of follow-up, location and in study population. The majority of studies were from African countries. In these studies we found a consistent trend of mortality rates similar to those seen in hospital. Of the six studies that reported both in-patient and post-discharge mortality, four reported mortality rates higher following discharge than during hospitalization.
The term “post-hospital syndrome” has recently been introduced and describes an acquired, transient period of vulnerability following discharge
Ideally, all children discharged from hospital should be followed-up to ensure identification of children suffering re-emergence of an acute illness; however in an already over-burdened health system this is neither feasible nor cost-effective. Therefore, the identification of risk factors for post-discharge mortality is an important starting point for interventions aiming to reduce morbidity and mortality following discharge. In those studies which identified such risk factors, nutritional indicators (such as weight–for-age), young age, and previous hospitalizations as well as disease specific factors such as HIV infection and pneumonia were consistently associated with a poor prognosis following discharge. The only study identified which actively addressed post-discharge mortality built upon previous research indicating anemia was an important predictor of mortality after discharge. Unfortunately, however, the intervention of providing malaria prophylaxis did not substantially reduce 6 month post-discharge mortality. The timing of post-discharge deaths is also an important consideration since this may aid in determining the period during which post-discharge interventions should be applied. While the duration of follow-up varied significantly between studies (28 days – 5 years), the probability of death was substantially higher during the first several months, indicating that post-discharge interventions during this period may offer the highest probability of success.
The integrated management of childhood illness (IMCI) program developed by the World Health Organization (WHO) is an attempt to compile the best available evidence for treatment of common pediatric diseases and facilitate the uptake of a standardized approach to these diseases in resource poor countries
In addition to specific risk factors for, and timing of, post-discharge mortality, we also observed that in several studies many children who died did not die during a re-admission but rather died at home
One limitation of this review was that the studies that were identified often did not have post-discharge mortality as a primary outcome. It is therefore possible that other similar studies, further removed from the search terms used, were not identified. However, the systematic search utilized was intended to be sufficiently broad to identify most of such studies. Another limitation was that several studies had follow-up rates below 90%. It is unlikely, however, that the reported mortality rates would be lower since losses to follow-up likely represent a more vulnerable population with higher rates of post-discharge mortality. A further limitation was the lack of a valid quality scoring system. As most studies were not specifically designed to assess post-discharge mortality a scoring system based on general study features could also not be created. The reason was that most of the study features in various statements (CONSORT, STROBE etc.) are for determining validity for drawing specific inferences according to the objectives of the study. Presence (or lack) of these characteristics does not necessarily mean that inferences for post-discharge mortality estimates are good (such as blinding in an RCT).
Pediatric post-discharge mortality is a significant and generally unrecognized problem in developing countries. While several characteristics are strongly associated with post-discharge mortality, no validated tools are available to aid health workers or policy makers in the systematic identification of children at high risk of post-discharge mortality. Global health policy and research must focus on both the creation of tools to aid in defining groups of children most likely to benefit from post-discharge interventions, formal assessment such interventions, followed by the scale-up of effective interventions.