Background

Infant mortality refers to “the death of a live-born infant before their first birthday” [1, 2]. This mortality rate reflect as not only a measure of the risk of infant death but it is used more broadly as a crude indicator of Community health status, Poverty and socioeconomic status levels in a community, Availability and quality of health services and medical technology [3]. It is, therefore, recognized as a uniquely vulnerable to several factors that impact health, represents a long-standing concern of public health and an important marker of the overall health of a society [2].

Globally, around 44% of all under-five deaths occurred during the neonatal period [4] and 75% occurred within the first year of life–with an estimated 4.1 million infants die in 2017 [5]. More than 98% of these deaths occur in developing countries [6], and roughly half of those deaths occurred in sub-Saharan Africa [6, 7]. In worldwide, infant mortality rate has shown decline from the rate of 63 deaths per 1000 live births in 1990 to 29 deaths per 1000 live births in 2017 [5], yet the rate is at highest level in developing world [5, 6].

Evidence showed that Ethiopia has shown a remarkable improvement in the reduction of infant mortality [8–10]. Despite this improvement, however, the death rate of infant is still at the highest level which stands at (59 deaths per 1000 live births) with disproportionately higher amongst population of some regions [9]. Afar and Oromia regions are among the highest in infant mortality. Information on cause of Infant mortality pattern is very much limited, and the available studies were mainly conducted in the hospitals and demographic and health surveillance sites, which make difficulties to understand the cause of death situation in local settings. If these conditions remain as such, proper measures could not be taken and ultimately more Ethiopian children will die. Attention to this condition is important if the Sustainable Development Goal (SDG)-goal 3 target 3.2 (to reduce childhood mortality) is ever to be achieved by 2030 [11].

Infant deaths are intrinsically linked to several causes and factors which need extensive studies. Without addressing this, it’s going to be hard to see the same level of progress that has been made in the reduction of infant mortality in last decade. Cause leads directly to a death, while a contributor is a risk factor that makes the death more likely to occur [12]. Cause of infant death information are critical for formulating good public health policy [13]. Emphatically, detecting and generating empirical information on cause of infant death and patterns of association factors on cause-specific mortality at population level is the first priority and basically utmost essential to take evidence-based measures. This ultimately contributes in reducing infant morbidity and mortality. However, determination of causes of death is a global concern as around half of the world’s children deaths pass without any formal registration of the cause of death [14]. Such situation leads to a major problem for understanding the infant’s health problems in general and difficult for planning the best solutions.

Developing countries have been the worst and serious concern in determining the cause of infant death, and yet little is known about cause of death in sub-Saharan Africa [15]. Ethiopia is one of a nation with lack of consistent cause of death information [16, 17] and understanding the cause of infant death in any setting is still challenging. This is for the reason that most people die at home [16, 18–20] and lost their life without having had contact with the health system [19, 21]. The civil registration systems in general do not exist and there is limited in medical capacity to produce death certificates for the population [16]. As an option, Verbal autopsy is the only available tool and best solution to determine cause of death in a setting where the majority of deaths occur at home and civil registration systems incomplete [13, 22]. For many years, researchers and policy-makers have been undertaking Verbal Autopsy interviews to ascertain the cause of death [23]. But there remains a problem on how to interpret VA interviews reliably and consistently in order to arrive at cause of death. For this effect, InterVA is a suite of computer models for interpreting verbal autopsy data, which recognize a range of indicators relating to a particular death, processes them in a mathematical model based on Bayes’ theorem, and produces as its output likely cause(s) of death [24]. Taking its limitation into account from a validation studies, the 2014 WHO VA instrument is developed to ascertain all individuals cause of death and describes cause-specific mortality fractions at population level [25].

Investigating cause of infant mortality at population level and analyzing the factors contributing to the major cause-specific mortality risk is crucial. There are limited studies on detecting cause of infant mortality at population level and many studies established the risk of dying factors data among those who did not die. No study have been conducted in any sort of settings on the patterns of maternal and infant characteristical factors associated with the most common cause-specific infant deaths against all other cause of death. The objective of the present study, therefore, was to determine causes of infant death using InterVA-4 model and investigate the patterns of maternal and infant characteristics factors on the major cause-specific mortality as compared to mortality from all-causes in Eastern Ethiopia. This study contributes to be filling the knowledge gaps that exist on the pattern of the associated factors among the most common cause-specific infant death against deaths from all other causes. This uniquely would help to better understand the factors that largely have an effect on multiplying infant’s risk of death from specific cause of illness or conditions. This could be important for developing effective and efficient public health strategies and interventions, which will ultimately be reduce the burden of infant mortality.

Materials and methods

Results

General characteristics of respondents and study population

During the study period, a total of 362 deceased infants’ mothers/caretakers were interviewed, yielded 97.8% response rate. The highest proportion (90.4%) of the respondents was parents to the deceased infants.’ The mean age (± SD) of the respondent was 27.3 (±4.3) years old. The age distribution of the deceased infants’ mothers/care taker was highest in the age category of 20–34 years old (86.7%). The majority of the respondents were married at 91.2%. More than four-fifths (87.9%) of the respondents were reported not to have been attended formal education at some point in their lives. Almost 88.6% of respondent’s economic activity was home-maker (housewife) in a year prior to infant’s death.

Of the overall recorded infant deaths, about 192 (53.0%) deaths were occurred during neonatal life while 170 (47.0%) in the post-neonatal period. The deceased infant comprised of 205 (56.6%) males and 157 (43.4%) females with an overall sex ratio of 1.31:1. Over half (55.4%) of the infant death were occurred in the wet season. Almost seven out of nine deaths (77.1%) took place outside of health facilities, of which the majority (71.8%) was died at home. A large proportion of the deceased infants reported from districts of the study area in Oromia region at 87.8% (see Table 1).

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Table 1. Frequency distribution of the respondents and the deceased infant characteristics in Eastern Ethiopia, 2016–18.

https://doi.org/10.1371/journal.pone.0270245.t001

Specific cause of infant deaths: Result from verbal autopsy (interVA-4)

Based on the result of the InterVA-4 model, the mean (± SD) of the likelihood value for the assigned cause of death across cases was 96.5% (±4.8%). The likelihood rate across cases varied with the range between 85–100%. In this analysis, the probable causes of infant deaths were classified into an age group of neonatal (<1month) and post-neonatal (1-11months). The analysis revealed that there were considerable major differences in the causes of infant death structure by age group.

Neonatal cause of death (n = 192).

Across all the study area, nearly half of neonatal deaths (47.0%) occurred within 24 hours of birth, and about 10.4% die more than 24 hours after birth but within 48 hours from birth. For a further 14.6% deaths occurred more than 48 hours from birth but within the first week of life and for the rest 28.0% deaths were after the first week, but within first 28 days.

Among neonatal deaths, the three major causes of deaths were neonatal pneumonia (33.3%), followed by birth asphyxia (30.9%) and prematurity (13.9%). The fourth leading cause of death was meningitis and encephalitis which was responsible for 5.2 percent of death under this age group. Congenital malformation and neonatal sepsis were found to be another cause of neonatal mortality with 4.5 percent and 3.7 percent respectively. Diarrhea diseases caused about 2.0 percent of neonate death and for the remaining 1.8 percent no cause could be determined which concluded under other and unspecified neonatal cause of death.

Post-neonatal cause of death (n = 170).

In the post-neonatal age group, the leading cause of death was acute respiratory infection including pneumonia, which is responsible for 44.2% of all deaths in this age category. Close to one-third (32.5%) of death were due to diarrheal diseases which accredited to the second largest cause of deaths and malaria positioned at the third major cause of death, which accounted for one of every ten deaths (9.2%).

The result revealed that about 2.8 percent of deaths were due to severe malnutrition. The other illness that attributed to death under this age group was measles, which took a toll of 2.2 percent followed by pulmonary tuberculosis (1.6%) and non-obstetric sepsis (1.1%). Few deaths were ascertained due to HIV/AIDs related and meningitis and encephalitis each accounted for 0.6% of death. Deaths due to accidents found to be 2.4%, typically from contact with venomous animals and plants (1.8%) and accidental poisoning and exposure to noxious substance (0.6%). The remaining (0.6%) appeared to be other and unspecified infectious disease cause of death.

Overall cause of infant death (n = 362).

Of the total infant did, the findings indicate the highest mortality load among infants was diseases of respiratory system, particularly acute respiratory infection including pneumonia in post-neonate and neonatal pneumonia, which accounted for 20.7% and 17.7% respectively and causing in a combination of 38.4 percent infant deaths in the study area.

The mortality risk due to birth asphyxia was the next leading cause of deaths, accounted for 16.4% of infant death. Almost one-sixth (16.3%) of the infant were died as a result of diarrheal diseases. About 7.4% of deaths were associated with prematurity. Deaths due to malaria, meningitis and encephalitis, and sepsis appeared to be another identified cause of death conditions that contributed to 4.3%, 3.0%, and 2.5% of infant death, respectively. Moreover, congenital malformation (2.4%), severe malnutrition (1.3%) and measles (1.0%) were also observed as causes that directly lead to infant deaths. Pulmonary tuberculosis (0.8%) and HIV/AIDS related death (0.3%) were the least ranked conditions among the deceased infant, and further 1.1% was causes due to accidents.

As per consolidated into a broad WHO cause category, Infectious and parasitic diseases causes exhibited 46.7 percent—with a high burden on post neonate age group, followed by neonatal cause of death (45.9%), nutritional and endocrine disorder (1.3%), external causes of death (1.1%) and the remaining (1.3%) were reportedly unknown cause (see Table 2).

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Table 2. Cause-specific infant mortality fraction by WHO VA category and age group in Eastern Ethiopia, 2016–18.

https://doi.org/10.1371/journal.pone.0270245.t002

Pattern of associated factors with specific-causes of deaths against all-causes of death

Independent factors in multivariable analysis have been identified through pattern of selected factors associated with each leading specific-causes of infant death (ARTI including pneumonia, diarrheal death, birth asphyxia, prematurity and malaria) as compared to those infant who died from all other cause of death in combined.

Result from ARI-specific mortality model showed that, infant mortality from Acute respiratory infection, including pneumonia shows a strong significant association with younger maternal age (<20 years old), deaths out of heath facilities and unmarried women than all other causes of infant death. Lower maternal age (<20 Years old) was almost 5 times more likely to die of Acute respiratory infection, including pneumonia than all other causes of infant death combined (P = 0.001, AOR: 4.82, 95% CI: 1.88, 12.3). Infants being died out of health facilities were also associated with nearly 3 times higher risk of ARTI death as compared to mortality from all other causes (P = 0.007, AOR: 2.85, 95% CI: 1.33, 6.12). Significant interaction were observed for those died infants with unmarried mothers, but resulted in lower chance (P = 0.041, AOR: 0.46, 95% CI: 0.22, 0.97) of ARTI-related death than those who died from other all-causes (see Table 3).

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Table 3. Multivariable logistic regression analysis of factors associated with cause-specific mortality against all other cause of infant death in Eastern Ethiopia, 2016–18.

https://doi.org/10.1371/journal.pone.0270245.t003

Analysis from diarrhea-specific mortality model indicated that post-neonates period and wet seasons have more pronounced significant association with diarrhea death than all-cause of death. The post-neonatal period had almost 16 times higher risk of diarrhea death than non-diarrheal deaths (P = 0.000, AOR: 15.5, 95% CI: 6.35, 37.8). Wet seasons had significantly 2 times higher chance of infant death due to diarrhea than other cause of death (P = 0.006, AOR: 2.38, 95% CI: 1.28, 4.44) (see Table 3).

Infant mortality from birth asphyxia shows a statistical significant relationship, but less likely to occur, with male sex (P = 0.039, AOR: 0.52, 95% CI: 0.28, 0.97) and being died out of heath facilities (P = 0.002, AOR: 0.32, 95% CI: 0.16, 0.66), as compared to mortality from all other causes. Infant died out of health facilities was the only associated factor with prematurity death, but lower odds (P = 0.001, AOR: 0.24, 95% CI: 0.10, 0.57) (see Table 3).

Infant who died from malaria is more closely associated with age of mothers between 20–35 years old and infant who resided in districts of Afar region. Infant with age of mothers between 20–35 years old were 4 times (P = 0.024, AOR: 4.44, 95% CI: 1.22, 16.2) higher to die of malaria than malaria-unrelated death. Similarly, infant who resided in districts of Afar region were 4 times higher to die of Malaria than non-malaria death (P = 0.013, AOR: 4.08, 95% CI: 1.35, 12.4). Significant association is observed on the risk of death from malaria in wet season, but the likelihood of dying resulted less (P = 0.024, AOR: 0.22, 95% CI: 0.06, 0.82) (see Table 3).

Discussion

The exact cause of death is ascertained by postmortem autopsy [32]. However, this is not practically applicable in most developing countries and, as an alternative Verbal Autopsy has become one of the major sources of data for causes of death, which also used for identification of major health problems and comparison of local and national mortality ratio differences [33]. Most of the published on cause of death using verbal Autopsy data was interpreted by physician review, and this approach is time-consuming, costly and inconvenient [22, 34]. In recent years, the electronically determination of death cause has been introduced and provide an analysis solution that is more convenient, consistent, and rapid ways to interpret VA data [34]. In our study context, InterVA-4 model is preferred to use for assigning cause of infant death as this model is relatively better than other available models (SmartVA/Tarrif, InSilicoVA), particularly for neonate and children death, when contrasting in terms of the degree of chance corrected concordance (CCC), CCVA (Computerized coding of verbal Autopsy) population Accuracy, PCVA (Physician-certified verbal autopsy) performance [35, 36]. In view of that, the present study was undertaken to determine the cause of death using InterVA-4 model and analyze the pattern of associated factors between the most leading cause-specific mortality against all-causes of death.

In this study, many different causes of infant death were observed, from infection to birth defects or accidents. The study result revealed that the proportion of death in the neonatal stage was higher in contrast to post-neonatal period. Similar view was seen in other studies [29, 37–39]. These findings clearly proven as neonatal period is the most vulnerable time for a child death [40]. The most common causes of infant death in the neonatal period are different from those that occur in the post-neonatal. Analyses in the interpretation of specific causes of infant mortality indicated that neonatal pneumonia, birth asphyxia and prematurity were the three major causes of deaths during the neonatal period. Regardless of proportional differences, Birth Asphyxia and Prematurity as a common appeared to be leading causes, which have similarity to those of studies conducted in some parts of Ethiopia [10, 41–43]—and other developing countries [37]. Some studies described Infections diseases (sepsis, pneumonia, meningitis, tetanus and diarrhea) are the leading cause [10, 41, 44], which had methodologically and/or application tools differences with this study. Evidences from several studies conducted in Ethiopia reported that Prematurity, Birth asphyxia, and Neonatal sepsis were the leading causes for neonatal death [29, 45]. These results are consistent to the present study except neonatal sepsis as the proportion of deaths due to sepsis appeared to be less in the study area.

Neonatal Pneumonia is a devastating condition [46] and remained one of the most cause of death in Ethiopians children [47]. It is a serious respiratory infectious disease in a neonate which can be prevented by simple measures such as treatment of maternal infections, careful obstetric care and general infection control measures in neonatal facilities. The higher risks of death from birth asphyxia might be due to lower institutional delivery coverage and mother’s education is essential which might be expected in large reduction in some circumstances. The burden of prematurity seemed to be mostly due to caregivers failed to recognize the danger signs related to prematurity and its consequences. It has been recognized that behaviors that encourage a healthy pregnancy plays an important role in preventing premature labour.

In the post-neonatal period, acute respiratory infection including pneumonia, diarrheal diseases and malaria were the most common causes of death. Despite means of verification and proportional differences, these results showed a similar pattern with the finding of other studies within nationwide [47]. Acute respiratory infection including pneumonia and Diarrheal diseases were mostly appeared as a common cause during post-neonate period, which showed in other inland studies [29, 47], and somewhere else [37–39, 48]. The present study indicated as Malaria was the third major cause of death in this age category, which are quite different from deaths identified in other studies of the country as bacterial sepsis were observed in one of the top three causes of post-neonate death [29] as well as malnutrition [49]. Similar view was observed in studies conducted in other countries [37–39]. As per consolidation into a broad cause category, Infectious and parasitic disease causes were the leading causes of death during the post-neonatal period, which is in agreement with previous studies [29, 47].

In overall infant death, acute respiratory infection including pneumonia, birth asphyxia and diarrhea disease were the most common caused in the present study. Apart from magnitude and rank order disparity, the findings of acute respiratory infection including pneumonia and diarrhea disease as a major probable cause of infant death has similarity with those of the results reported in other parts of the country [10, 47, 49–51], and elsewhere [37, 52]. It can be observed that Prematurity, Malaria, Meningitis and encephalitis, Sepsis and Congenital malformation were other condition resulting deaths of Eastern Ethiopia children, which are more or less the same with causes occurred in most parts of developing countries [48, 53, 54].

The higher risk of death due to acute respiratory infection in the current study might be due to less awareness of the disease transmission and prevention, weak case management in health services, less understanding on early recognition of pneumonia cases and inappropriate care-taking by the parents [55]. Acute respiratory infection including pneumonia may exist due to lack of adequate through and cross ventilation system in the dwelling [56], overcrowding or suffocation in bedroom and weak maternal health, which have a potential favors to transmit the infection [57].

Diarrheal diseases were another most important cause of infant death as reflected by the facts that almost one-sixth of infants reported to have been dead. Infant and children are more likely to die due to lack of safe water and sanitation, along with poor hygiene practices, that result in deteriorative synergy that leads to diarrheal disease [58]. Health seeking behavior such as poor early sough of health care, less measure to diarrhea disease management including oral rehydration therapy (ORT) for rehydration were responsible for diarrhea-related mortality [59]. Other deaths due to severe malnutrition, Measles, Pulmonary tuberculosis and HIV/AIDS appeared to be tribulation of infant’s survival on the basis of the present study result. However, deaths due to tetanus were not observed. This disease was remained as a noticeable death causes of Ethiopian children [8, 47, 51, 60]. The nonappearance of death due to tetanus is most likely associated with being controlled through tetanus toxoid (TT) routine immunization program. Likewise, the less infant death from malnutrition attributed to high-impact nutrition interventions delivery through an integrated package by government and non-governmental organization.

The present study also compares the patterns of factors associated with the leading specific cause of infant death against all other cause of death. Our finding revealed that the patterns of association among each cause-specific mortality were quite different when evaluate with that of its comparison group (all-cause of death in combined). Infants with lower maternal age (<20 years old) were five-fold an increased risk of death from ARI, including pneumonia in contrast to infant with higher maternal age (≥35 years old). This finding suggested as lower maternal age group has largely contributed to multiplying ARI-specific infant mortality risk than all other causes of death. Studies revealed that children having adolescent mother was a strong risk factor for ARI-related death [55, 61]. This could be possibly due to the assumption that lower aged mothers tend to have lower experience in pneumonia-related health care of children and, therefore, greater susceptibility to severe forms of infections that could be drives to mortality. The risk of infant death due to ARI again rises with those infant who died out of heath facilities, which shows three-fold at an increase risk of ARTI, including pneumonia death than ARTI-unrelated infant death. This, in turn, indicated the contribution of death that occurred at home, which might probably due to lack or delay in seeking appropriate medical care utilization. This showed to be highly increases risk of dying from pneumonia than died from other causes [62].

Another important finding was that, the post-neonatal period is the most predominant factor in contributing to the greater elevated by nearly sixteen times of diarrheal death risk than the corresponding risk of all-causes of death. The strong influence of this age period on diarrhea-related death had been examined in other studies [63, 64]. Our study also revealed that wet seasons are strong significant risk factors by twice for diarrhea-related death than all other causes. The study conducted in India and Mexico where largely confirmed that deaths caused by diarrhea are strongly linked to seasons of death with more pronounced during cooler months [64, 65]. This might be due to the fact that diarrhea diseases had more potential to transmit in wet seasons, and increase its incidence that initiated the series of events leading to death.

Our study has also found that being male sex is significantly association with death from birth asphyxia; however, the risk of dying has been less likely as compared to other cause of death. This linkage could be attributed to behavioral, biological, socio-cultural, and genetic factors, which needs further study. We also observed that male is the most predominance in dying from birth asphyxia; similar finding was observed in various studies [66, 67]. Our analysis indeed showed significant association in place of death that occurred out of health facilities for birth asphyxia against other causes; though the likelihood of its effect is less. The study similarly demonstrated that place of death in out of health facilities are the only significant factor with lower chance for premature death as compared to all-cause mortality.

It has been also observed that infant mortality resulted from malaria significantly related to infant’s mothers/care takers age group of 20–34 years with four times highest-risk chance in contrast to maternal age ≥35 years old, as evaluated from that of all-causes of death. A study on the link between early childhood mortality and malaria in Malawi reported that children were significantly at greater risk if the mother was lower age relative to older age [68]. The geographical administration division are appears to be statistically significant to the risk of malaria-specific infant death. Infants resided in the study area of districts in Afar region were four times substantial raised risk of malaria deaths as compared to districts in Oromia region, as evaluated against all other causes. A study in Burkina Faso has demonstrated the significant variations in all-cause and malaria-specific mortality across village clusters [69]. The differences by geographical administrative division might be due to variability in socio-demographic and economic factors, the prevalence of malaria incidence, weather condition, and variability of quality of health care service. However, further studies are needed to better understand for these disparities. Significant interaction was seen between wet seasons of infant death with the risk of malarial-specific death. However, this risk is less likely as observed in comparison to the all-cause of death. A study in West Africa indicated that malaria-specific infant death had significant seasonal trends and higher in the rainy seasons [70].

Supporting information

Acknowledgments

We would like to thank the West Harargehe zonal health department and the overall districts (Chiro, Mieso, Gemechis, Tullo, Amibara and Awash Fentale) health offices for their dedication and commitment in providing information and facilitate the study. We also thank for the study participants such as data collectors, supervisors and the respondents. We are our deep sense of gratitude to Addis Ababa University, EIWR and Care Ethiopia- West Hararghe Field Office for their technical and resources assistant.