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Prioritizing Health Care Strategies to Reduce Childhood Mortality

Key Points Question Which public health care improvements could have prevented the most deaths among children younger than 5 years? Findings In this cross-sectional study of 3390 deaths investigated at sites with high child mortality rates in sub-Saharan Africa and Southern Asia, 77% were deemed potentially preventable. Recommended measures to prevent deaths were improvements in antenatal and obstetric care, clinical management and quality of care, health-seeking behavior, and health education. Meaning These findings suggest that investments in interventions that reduce child mortality should focus on health system improvement, including improved antenatal care and higher quality of pediatric care.


Introduction
The global mortality rate among children younger than 5 years decreased by 59% from 1990 to 2019. 1 However, high mortality among children younger than 5 years persists across regions and countries, with sub-Saharan Africa and Southern Asia accounting for 81% of the 5.0 (95% CI, 4. 8-5.5) million deaths among children younger than 5 years in 2020. 2 The United Nations adopted the Sustainable Development Goals (SDGs) in 2015 to promote healthy lives for children and eliminate preventable deaths among newborns and children younger than 5 years by 2030. 3 SDG 3.2.1 specifically aims to reduce newborn mortality to fewer than 12 per 1000 live births and mortality among children younger than 5 years to fewer than 25 per 1000 live births in every country. 3 Furthermore, the World Health Organization (WHO) and United Nations Children's Fund launched the Every Newborn Action Plan as a blueprint for improving newborn health and ending preventable stillbirths by 2035. 4 High mortality among children younger than 5 years in sub-Saharan Africa and Southern Asia has been attributed to suboptimal health care quality, 5 long distances from home and access challenges to health care facilities, 6,7 and delays in seeking timely health care. 8 Interventions that could substantially reduce mortality among children younger than 5 years include better quality of clinical and antenatal care (ANC), access to emergency obstetrical procedures, enhanced triage and risk-stratification, immunization coverage, and infection control measures. 9 However, a comprehensive analysis of public health and clinical interventions that would produce the greatest reduction of mortality among children younger than 5 years in sub-Saharan Africa and Southern Asia is lacking.
We analyzed data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network, which currently operates in 7 sites in Africa and Southern Asia to track causes of stillbirths and deaths among children younger than 5 years. A core objective of this is to increase child survival, and for this, the assessment of each individual death includes evaluation of its potential preventability and which actions would have been needed to prevent it. This assessment of pathological and modifiable causes of deaths by a multidisciplinary expert review panel could result in broad understanding of health system deficiencies that may inform targeted interventions to decrease stillbirths and childhood mortality.

Data Sources
CHAMPS collects standardized, population-based, surveillance data from sites with high child mortality to understand and track preventable causes of death. CHAMPS currently includes sites in 7 countries: Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa. CHAMPS is not intended to be representative of entire countries but rather focuses on regions where mortality rates are known to be highest. To that end, understanding causes of death (and what it would take to prevent them) at these sites could have the greatest impact in terms of reducing mortality. By design, CHAMPS does not reflect low mortality areas. The CHAMPS database contains comprehensive data on all stillbirths and deaths among children younger than 5 years enrolled at each of the surveillance sites. These data include demographic characteristics, extensive postmortem diagnostic results, clinical medical record abstraction data for each child and, when appropriate, maternal antenatal records and verbal autopsy data (as well as social autopsy data in Sierra Leone). Site characteristics, selection criteria, catchment areas, death notification methods, eligibility screening, and specimen and data collection methods have been previously described. 10,11 Limitations of the CHAMPS methodology have been documented elsewhere 10,12,13 and include the inability to include all deaths within catchment areas, disparate population characteristics between sites, and overrepresentation of health care facility-based deaths. Ethical approval was obtained for use of CHAMPS data by each site's ethical review board and by the Emory University Rollins School of Public Health. Parents or guardians of stillborn fetuses or deceased children provided written informed consent before collection of data, specimens, or information on the mothers. All cases were anonymized prior to review. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines for cross-sectional studies were followed.

Causes of Death
Details regarding the cause of death determination and standardization across sites processes have been described elsewhere. 11,12 Briefly, deaths are investigated with minimally invasive tissue sampling (MITS), a postmortem approach using biopsy needles for sampling key organs and body fluids. The samples undergo testing using conventional microbiology and multiplexed polymerase chain reaction (PCR) assays using TaqMan array cards; tissues are also examined by pathologists and subject to more advanced histopathological tests. Any available data regarding the terminal events are abstracted from medical records and verbal autopsy and recorded from caregiver recollection. A determination of cause of death (DECODE) panel consisting of pediatricians, obstetricians, epidemiologists, pathologists, microbiologists, and other health care professionals review case data at each surveillance site to assign causes of death. CHAMPS uses the WHO International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) and the WHO application of ICD-10 deaths during the perinatal period (ICD-PM). 14,15 For deaths in which only a single cause led to death, that cause is listed as the underlying cause. For deaths in which multiple causes led to the death, the panel determines the causal chain including the underlying, antecedent, and immediate causes leading to death. 13 The underlying cause usually occurred before immediate or antecedent conditions and may have predisposed the child to an immediate cause or comorbid illnesses that then led to death; the immediate cause was closest to the death, and the antecedent causes were in between the underlying and immediate causes. Each death has only 1 underlying cause, zero or 1 immediate cause, and zero or more antecedent causes. At the site level, a subset of cases that underwent DECODE review are shared with the other sites for secondary review as a quality control measure.

Health System Improvements
For each death, the DECODE panel determined whether the death was preventable (yes, no, or under certain circumstances) by considering all the information available for each case, which may include demographic, clinical, pathological, microbiological, verbal autopsy, photography, and anthropometric measurements. The definition of preventability mainly captures the conditions immediately surrounding the death of that particular child and not the broader global political, financial, and social influences. If the death was deemed potentially preventable, the panel identified death, the panel also had the option to provide specific public health action recommendations beyond the 10 categories in an open text field, which were subsequently categorized as well.
There were 10 high-level categories of health system improvements (Table), and each death could have multiple prevention categories listed. Although some health system improvement categories primarily target specific age groups (eg, improvements in antenatal and obstetric care), any category implemented at a given site may affect children in other age groups to varying degrees. We evaluated health system improvement categories across all sites by age group. We defined stillbirths as the death of a baby before or at delivery, neonates as those aged 0 to 27 days, and infants and children as those aged 28 days to younger than 5 years. 16

Statistical Analysis
To determine which health system improvements could have prevented the most deaths regardless of cause, we generated every combination of 1 to 10 categories (1023 combinations) and calculated how many deaths could have been prevented for each combination under the assumption (A1) that all health system improvement categories recommended for a single death are necessary to prevent that death. We also conducted sensitivity analyses assuming (A2) deaths would be reduced proportionally to the number of categories implemented for deaths with multiple health system improvement categories noted, and (A3) any single category among categories recommended for each death is sufficient to prevent the death. For example, if 4 health system improvement categories were recommended for a set of deaths and only 1 was implemented, we calculated that, according to the 3 assumptions: (A1) those deaths would not be prevented, (A2) 25% of those deaths would be prevented, and (A3) 100% of those deaths would be prevented (eMethods in Supplement 1). All analyses were done in R version 4.1.2 (R Foundation for Statistical Computing).

Results
Between  We examined which single health system improvement category could have prevented the most deaths across all sites assuming all improvement categories recommended for a single death are necessary to prevent that death (Figure 2).  This figure assumes (1) all recommendations given for a single death are necessary to prevent that death, (2) for every category implemented for deaths with multiple categories, deaths would be reduced proportionally, and (3) any single category among all categories recommended for each death is sufficient to prevent that death. Categories appear in the Table. ANC indicates antenatal care.

Discussion
From an analysis of 3390 deaths in 7 countries with high mortality rates among children younger Prior studies suggest maternal undernutrition, obesity, diabetes, stress, depression, smoking, alcohol use, or drug consumption may increase risk of infections, preterm birth, and/or congenital malformations. 17 Our study demonstrates that regular ANC visits may be the most critical measure to prevent the most stillbirths and neonatal deaths. At least 4 ANC visits may reduce leading causes of neonatal deaths. 18,19 Ultrasonography access, timely caesarian delivery, trained staff for parturition, fetal heart rate monitoring, and improving maternal nutrition were among recommendations to improve ANC and obstetric care in our study, which is consistent with other studies. 20 Beyond what can be prevented with existing modalities, CHAMPS data also provide insights into what new tools are needed. Considering the contribution of neonatal sepsis to mortality, it is likely that development and use of interventions including maternal immunization, rapid diagnostics, and novel therapeutics would substantially reduce neonatal mortality. A systematic review highlighted measures to reduce mortality among preterm and low-birth-weight neonates in low-and middle-income countries. 21 WHO adopted 10 main recommendations to improve preterm birth outcomes, which include when This figure assumes all recommendations given for a single death are necessary to prevent that death. None indicates no health system improvements and represents the actual number of deaths over time.

Limitations
This study has several limitations. First, it focused on broad health system improvement categories, which included a range of interventions. For example, improvements in HIV prevention and control include greater maternal access to testing and antiretroviral therapy, therapy for neonatal infections, and others. The categories were developed from recommendations from the first DECODE panels and are being refined to be more specific. Second, despite efforts to standardize procedures, myriad factors preclude our ability to make direct comparisons between sites, including differences in catchment area populations, consent rates, clinical care, and diagnostic capabilities, and others.