https://orcid.org/0009-0005-8597-0042
Figures
Abstract
Background
The neonatal period is the most vulnerable time for an infant’s survival, particularly for preterm neonates. Preterm birth is among the leading causes of neonatal mortality. Many neonatal complications can be prevented, but preterm birth remains a leading cause of admission, death, and long-term complications, highlighting the need for further research on outcome and survival disparities across populations and settings. Therefore, this study aimed to assess survival status and predictors of mortality among preterm neonates admitted to neonatal intensive care units at public hospitals in the Harari region and Dire Dawa administration, Eastern Ethiopia, from November 1, 2021 to October 30, 2024.
Methods
The hospital-based retrospective cohort study was conducted among preterm neonates admitted to the neonatal intensive care unit at public hospitals of the Harari region and Dire Dawa administration, Eastern Ethiopia. A simple random sampling technique was used, and data were extracted from neonates’ medical records and registration formats using a structured checklist prepared in English. Descriptive statistics, life table, Kaplan-Meier curves, and Log-rank test were used to estimate and compare survival time. Predictors of mortality were identified using the Cox Proportional Hazard model.
Results
Out of 612 preterm neonates, 205 (33.5%; 95% CI: 29.76–37.39) died, corresponding to an incidence rate of 52.76 deaths per 1,000 preterm neonate-days (95% CI: 46.01–60.50), with a median survival time of 18 days. As multivariable cox-regression result, ≥ 4 antenatal care contact (AHR = 0.56; 95% CI: 0.36–0.89), receiving KMC (AHR = 0.16; 95% CI: 0.09–0.27), 5th minute APGAR score <7 (AHR = 1.80; 95% CI: 1.22–2.66), PNA (AHR = 1.55; 95 CI: 1.08–2.22), resuscitation with bag and mask at birth (AHR = 1.59; 95% CI: 1.10–2.29), RDS (AHR = 1.75; 95% CI: 1.22–2.51), born in non-cephalic presentation (AHR = 1.68; 95% CI: 1.12–2.53), and neonatal sepsis (AHR = 1.58; 95% CI: 1.09–2.28) were identified as significant predictors of preterm neonates mortality.
Conclusion
The incidence of preterm neonatal mortality was high in this study. Adequate Antenatal care (ANC) and kangaroo mother care (KMC) significantly improved preterm survival, while low APGAR score, resuscitation with bag and mask, neonatal sepsis, PNA, and RDS were major predictors of preterm neonatal death. Emphasis should be placed on strengthening antenatal and perinatal care, along with early detection and management of identified neonatal complications.
Citation: Ebsa BA, Tefera M, Tamiru D, Negash A, Oda N, Dheresa M (2026) Survival status and predictors of mortality among preterm neonates admitted to the neonatal intensive care unit at public hospitals of Harari region and Dire Dawa administration, eastern Ethiopia: Retrospective cohort study 2025. PLoS One 21(4): e0347244. https://doi.org/10.1371/journal.pone.0347244
Editor: Ricardo Q. Gurgel, Federal University of Sergipe, BRAZIL
Received: March 2, 2026; Accepted: March 25, 2026; Published: April 17, 2026
Copyright: © 2026 Ebsa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: The dataset used for this study is not publicly available due to ethical and confidentiality considerations. However, it can be accessed upon reasonable request from the Institutional Health Research Ethics Review Committee (IHRERC) at Haramaya University, which oversees data governance and ensures that data sharing complies with ethical standards. Requests for data access may be directed to Negga Baraki, Chairperson of the IHRERC, via email at neggalemash@gmail.com or through the Office of IHRERC (Tel: +251254662011; Fax: +251256668081; P.O. Box: 235, Harar, Ethiopia).
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: ANC, Antenatal Care; AHR, Adjusted Hazard Ratio; APGAR, Appearance, Pulse, Grimace, Activity, Respiration; CPAP, Continuous Positive Airway Pressure; KMC, Kangaroo Mother Care; NICU, Neonatal Intensive Care Unit; PNA, Perinatal Asphyxia; RDS, Respiratory Distress Syndrome; WHO, World Health Organization
Introduction
Preterm birth is defined as a live birth born before 37 completed weeks of pregnancy or less than 259 days from the first date of the woman’s last normal menstrual period [1,2]. Preterm birth is classified as very preterm (28 to < 32 weeks), moderate preterm (32 to <34 weeks), and late preterm (34 to <37 completed weeks) based on gestational age [1,3]. The majority of preterm births occur spontaneously, while others are caused by medical conditions like infections or other pregnancy complications that require early labor induction or cesarean delivery [1].
Globally, the preterm birth rate was reduced slightly from 10.6% in 2014 to 9.9% in 2020, with 15% of all preterm births occurring at <32 weeks of gestation [2,4]. Despite this reduction, the burden is disproportionately high, as over 50% of all preterm births occurred in eight countries. Highest in India, followed by Pakistan, Nigeria, China, Ethiopia, Bangladesh, the Democratic Republic of the Congo, and the USA [4]. Southern Asia and sub-Saharan Africa contributed to approximately 65% of all preterm births globally in 2020 [4]. The majority of preterm births and related mortality occur in low- and middle-income countries, and their burden is high in sub-Saharan Africa and South Asia [5].
Preterm birth is a major global health challenge, significantly contributing to neonatal and under-five mortality. Preterm birth affects an estimated 13.4 million newborns annually, accounting for 9.9% of all births [1,4] and it is the leading cause of death in children under five, responsible for 1 million deaths, or 35% of neonatal deaths and 18% of under-five deaths worldwide [1,5].
Preterm birth remains a health problem both in developed and developing countries, with notable disparities. In developed settings, such as the USA, the preterm mortality rate is 22.35 per 1000 births [6]. In middle-income countries like China, regional disparities are observed, with preterm-related neonatal deaths accounting for 51.3% in eastern and 44.5% in western regions [7]. Developing countries carry the highest burden of preterm mortality. India alone accounts for nearly one-third (33%) of global preterm deaths [5].
Sub-Saharan Africa bears the highest burden of neonatal mortality, as the 2022 World Health Organization (WHO) report identified the region as having neonatal mortality of 27 per 1000 live births [8]. Evidence from the Alliance for Maternal and Newborn Health Improvement (AMANHI) study further highlights that preterm birth accounts for 46% of neonatal mortality, of which 40% occurs in sub-Saharan Africa [9]. Country-level evidence reported the severity of the problem, with preterm birth complications responsible for 36% of neonatal deaths in South Africa and ranking as the second major cause in Kenya (28%) [10].
In East Africa, preterm neonatal mortality remains unacceptably high, with Uganda reporting a rate of 31.6% [11]. Ethiopia ranks among the top five globally for both preterm births and neonatal deaths, with a preterm birth prevalence of 10.48% [4,12,13]. The country’s national neonatal mortality rate (33 per 1000 live births) in 2019 exceeded the regional averages of Sub-Saharan Africa and Central and Southern Asia [8,14,15]. Regional variations within Ethiopia also demonstrate a preterm neonatal mortality rate ranging from 22.7% to 36.1% [16,17]. Specifically, in eastern Ethiopia, preterm complications contribute to 28.8% of neonatal deaths [18].
Beyond survival, preterm birth has lasting health, social, and economic consequences. Affected newborns face neurodevelopmental delays, sensory and cognitive impairments, and behavioral challenges [19,20]. Mothers experience disrupted early bonding, postpartum health issues, and reduced emotional well-being [19]. Economically, preterm births impose heavy costs on families, including medical expenses and caregiving demands, special education needs, lost work time, and reduced productivity [21].
Ethiopia’s current neonatal mortality rate remains unacceptably high, falling short of the Health Sector Transformation Plan-II (HSTP-II) target of 21 per 1,000 live births by 2024/25 and raising uncertainty about achieving the Sustainable Development Goal target (SDG) of 12 per 1,000 live births by 2030 [8,15,22]. Despite national strategies and interventions, preterm-related mortality remains persistently high. However, evidence on the survival status and predictors of mortality among preterm neonates remains limited, particularly in the current study area. Most existing studies have been conducted in the northern, southwestern, and central regions, leaving a significant geographic gap. Additionally, findings from previous studies are often inconsistent, with neonatal outcomes varying across regions, facilities, and time periods. To address these gaps, the present study uses a larger sample size than previous research and aims to provide context-specific evidence on preterm neonatal survival. Specifically, it seeks to assess the survival status and predictors of mortality among preterm neonates admitted to Neonatal Intensive Care Units (NICUs) at public hospitals in the Harar region and Dire Dawa Administration, Eastern Ethiopia.
Methods and materials
Study setting
The study was conducted at public hospitals in the Harar region and the Dire Dawa Administration, Eastern Ethiopia. The Harari region is one of Ethiopia’s regional states, with an estimated population of 283,000, comprising 143,000 males and 140,000 females [23]. The capital city of the Harari region is Harar, an ancient city situated on a hilltop in eastern Ethiopia, approximately 526 kilometers from Addis Ababa. The region has two public hospitals: Hiwot Fana Comprehensive Specialized University Hospital (HFCSUH) and Jugal General Hospital (JGH). The Dire Dawa administration is located 515 kilometers northeast of Addis Ababa, the capital of Ethiopia. It is one of the two chartered cities in the country, with an estimated population of 551,000, including 278,000 males and 273,000 females [23]. The two public hospitals in Dire Dawa are Dilchora Referral Hospital and Sabian General Hospital.
Study period
This study was conducted among preterm neonates admitted to the NICU of public hospitals in the Harari region and Dire Dawa administration from November 1, 2021 to October 31, 2024, and the preterm neonates’ medical charts and registers were reviewed from January 1–31, 2025.
Population
Source population.
All preterm neonates admitted to the NICU at public hospitals in the Harar region and the Dire Dawa administration.
Study population.
All randomly selected preterm neonates who were admitted to the NICU at public hospitals in the Harar region and the Dire Dawa administration from November 1, 2021, to October 31, 2024. A preterm neonate’s medical card with incomplete records of date of admission, date of discharge, gestational age, and unknown status was excluded.
Sample size and sampling procedure
The sample size was calculated using the STATA statistical package (version 17.0) for Cox PH regression, considering assumptions such as a hazard ratio (1.54) for selected covariates (having respiratory distress syndrome (RDS) and a failure (death) probability of 29.7%, based on a previous study conducted at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. [24]. Assuming a type I error (α) of 0.05, a study power of 80%, and a 10% rate of withdrawals or incomplete records. RDS was selected among five covariates because it yielded the largest sample size. Consequently, the calculated maximum sample size for this study was 630. The medical cards of preterm neonates were identified using their Medical Record Number (MRN) through the NICU registration as the sampling frame. Then, a simple random sampling method was applied, and the number of medical charts was generated using Excel to proportionally select 630 preterm neonate charts from each hospital for the study.
Variables of the study
Survival status of preterm neonates is the study’s dependent variable. Socio-demographic characteristics, obstetrics and gynecological related factors, maternal medical conditions, and preterm neonate-related characteristics are all independent variables.
Operational definitions
Censored:.
preterm neonates those alive beyond 28 days after birth, discharged with parental refusal, discharged with improvement, and referred to other health institutions.
Time to death:.
is the time in days from admission to NICU until death/transfer/discharge of neonates in the first 28 days of life.
Preterm neonatal sepsis.
: defined as clinical signs and symptoms with the presence of risk factors, lab tests, or confirmed by blood culture or diagnosed by a physician as the presence of sepsis [25].
Bad obstetric history: implies previous unfavorable fetal outcome in terms of two or more consecutive spontaneous abortions, early neonatal deaths, stillbirths, intrauterine fetal deaths, and intrauterine growth retardation [26].
Data collection instrument
The data collection checklist includes information on socio-demographic characteristics, obstetrics and gynecological related factors, maternal medical conditions, preterm neonatal status, and characteristics related to preterm neonates. Research assistants were trained for two days so that they became familiar with the objectives of the study, its contents, sampling procedure, data extraction tools, and the issue of confidentiality. The data extraction checklist was adapted by reviewing various literature from similar studies and modified using preterm neonates’ medical records and NICU health management information system (HMIS) registration format [24,25,27–30]. Two bachelor’s degree-holder Midwives, data collectors, were used as data extractors from the neonate’s medical card and logbook, and supervised by an MSc holder Midwife. During the data extractions, regular supportive supervision and discussions with data collectors and the supervisor were conducted. On-site checking and review of the completed checklist were done by the responsible body.
Data management and quality
Before actual data collection, the records were reviewed, and preterm neonatal cards were identified by medical record number. Then, the data were extracted from each preterm neonate’s medical records and health management information system (HMIS) registration format, using a structured checklist prepared in English from those preterm neonates’ medical records that fulfilled the inclusion criteria. A pretest was conducted on 5% of the total sample size using neonates’ medical records and register books at Hiwot Fana Comprehensive Specialized Hospital during a period outside the main study. Following the pre-test, checklist modifications were made to improve the instrument’s clarity, consistency, and reliability.
Methods of data processing and analysis
The data were coded and exported into STATA version 17.0 for analysis. The Kaplan–Meier survival curve was used to estimate the median survival time and cumulative survival probability, and to compare survival experiences across different covariates. The log-rank test was applied to statistically assess differences in survival across categories of the explanatory variables. A life table was employed to estimate the cumulative survival probability at different time intervals.
A bivariable analysis using crude hazard ratios was performed to identify candidate variables (p < 0.25) for inclusion in the multivariable Cox regression to identify predictors of preterm neonatal death. The proportional hazards assumption was evaluated using the Schoenfeld residuals test (global test), and the overall model fitness was checked graphically by using the Cox-Snell residual plot.
The Cox proportional hazards model was used to identify significant predictors of mortality and time to death among preterm neonates. The Adjusted Hazard Ratios (AHR) with 95% Confidence Intervals (CI) were used to evaluate the association between predictors and preterm neonatal death. Statistical significance was reported at p-value < 0.05.
Ethical considerations
Ethical approval was obtained from the Institutional Health Research Ethical Review Committee (IHRERC) (Ref. No. IHRERC/227/2024) of Haramaya University, College of Health and Medical Sciences. After approval, an official letter was sent from Haramaya University, College of Health and Medical Sciences, to the director of HFCSUH, Jugal General Hospital, and the Dire Dawa Administration health bureau. Informed, voluntary, written, and signed consent was secured from each hospital’s head. The confidentiality of neonates was preserved through anonymous data collection.
Results
Socio-demographic characteristics
In the final analysis, 612 (97.14%) medical records of preterm neonates meeting the inclusion criteria were reviewed, whereas 18 (2.86%) records were excluded due to incomplete data. Out of incomplete cards, 6 had no date of admission, 7 had no date of discharge, and 5 were not available during card review. The average maternal age was 26.90 years with a standard deviation of ±5.50 years. More than two-thirds (488; 79.74%) of the maternal ages were between 20 and 34 years. Slightly more than half (315; 51.47%) of preterm neonates were male (Table 1).
Obstetrics and medical-related factors
Among the 612 mothers of preterm neonates, 474 (77.45%) had antenatal care follow-up, of whom 299 (48.86%) had fewer than four ANC contacts. Nearly half of the neonates were born to multiparous mothers 274 (44.77%), and labor started spontaneously in 427 (69.77%) cases. Most neonates were from singleton pregnancies 506 (82.68%) and were delivered at hospitals (88.56%). Spontaneous vaginal delivery accounted for 437 (71.41%) births, with a median labor duration of 6 hours. Preeclampsia was present in 140 (22.88%) mothers, preterm premature rupture of membranes occurred in 217 (35.46%), and 179 (29.25%) mothers received antenatal corticosteroids. Additionally, anemia was observed in 61 (9.97%) mothers (Table 2).
Neonatal related characteristics
Among the 612 preterm neonates included in the study, the majority were late preterm (34 to <37 weeks, 46.08%), followed by moderate preterm (32 to <34 weeks, 29.90%) and very preterm (28 to <32 weeks, 24.02%). Most neonates were appropriate weight for gestational age (70.59%), with nearly two-thirds classified as low birth weight (64.54%). The majority had a 5-minute APGAR score ≥7 (73.04%), while nearly one-third required resuscitation at birth (30.23%). Common clinical conditions included respiratory distress syndrome (50.49%), hypothermia (76.47%), and neonatal sepsis (63.73%), with a smaller proportion developing perinatal asphyxia (15.69%). Most neonates had a cephalic presentation at birth (85.46%), and supportive interventions included kangaroo mother care (38.56%) and CPAP (57.52%) (Table 3).
Major causes of preterm neonatal death in the NICU of public hospitals
The findings of this study revealed that multiple comorbidities were observed among deceased preterm neonates, significantly contributing to the overall burden of morbidity, resulting in preterm neonate mortality. The major causes of death among preterm neonates were hypothermia (25.65%), neonatal sepsis (25.04%), and respiratory distress syndrome (23.50%), together accounting for the majority of reported deaths (Fig 1).
Survival status of preterm neonate
Among admitted preterm neonates, 205 (33.50%; 95% CI: 29.76–37.39) died, 342 (55.88%) were discharged home alive, 47 (7.68%) had loss to follow up, 8 (1.31%) were referred to other health institutions, and 10 (1.63%) survived beyond 28 days (Fig 2).
The overall incidence rate of mortality was 52.76 deaths per 1,000 neonate-days (95% CI: 46.01–60.50), with a total follow-up time of 3,885.35 neonate-days among 612 preterm neonates. The median survival time was 18 days, while the median length of hospital stay was 4 days (IQR: 2–9 days).
The Kaplan–Meier survival analysis showed that 65 (31.71%) of all preterm neonatal deaths occurred on the first day of follow-up. The cumulative survival probabilities at 1, 4, and 28 days were 89.16% (95% CI: 86.39–91.40), 73.17% (95% CI: 69.22–76.70), and 44.38% (95% CI: 35.84–52.57), respectively (Table 4).
The Kaplan-Meier curve illustrates the probabilities of survival and failure during follow-up time, indicating that these probabilities changed over time (Fig 3).
The Nelson-Aalen cumulative hazard estimate shows the accumulation of mortality risk over time among preterm neonates admitted to NICUs at public hospitals in the Harari region and Dire Dawa administration, up to 28 days of follow-up (Fig 4).
The log-rank test was used for comparisons of survival time differences between different groups of categorical covariates. In this study, the log-rank test was statistically significant which shows the differences between groups in ANC follow up (Pr > X2 = 0.0000), 5th minute APGAR score (Pr > X2 = 0.0000), resuscitation with bag and mask at birth (Pr > X2 = 0.0000), PNA (Pr > X2 = 0.0000), RDS (Pr > X2 = 0.0000), neonatal sepsis (Pr > chi2 = 0.0001), presentation during birth (Pr > X2 = 0.0184) and using KM (Pr > X2 = 0.0000), as compared to their counterparts (Figs 5 and 6).
Cox proportional hazards assumption test and model fitness test
The proportional hazards assumption of the Cox model was evaluated using Schoenfeld residuals and a global test of proportionality. The global test was not statistically significant (Prob > χ² = 0.6401), indicating no evidence of violation of the proportional hazard assumption. Model adequacy was further assessed using Cox–Snell residuals, and the cumulative hazard plot closely followed the 45° reference line, suggesting good model fit (Fig 7).
Predictor of preterm neonates’ mortality
As bivariable cox-regression at <5% significance level having of ANC contacts ≥ 4, grand multipara, having eclampsia, taking antenatal steroid, gestational age between 28 to < 32 and 32- < 34 weeks, < 1000gm weight of neonate, small weight for gestational age at birth, APGAR score at 1st and 5th minute < 7, diagnosed hypothermia with at admission, bag and mask resuscitation at birth, having perinatal asphyxia, having respiratory distress syndrome, having neonatal sepsis, non-cephalic presentation, neonates diagnosed with NEC, kangaroo mother care usage, and receiving CPAP were significantly predictors of mortality among preterm neonates compared to their counterparts. However, the multivariable Cox proportional hazards regression analysis identified having ≥ 4 ANC contacts, a fifth-minute APGAR score < 7, resuscitation with bag and mask at birth, perinatal asphyxia, respiratory distress syndrome, non-cephalic presentation, sepsis, and kangaroo mother care utilization as significant predictors of preterm neonatal mortality (Table 5).
Findings from the multivariable Cox proportional hazards regression analysis revealed that the hazard of death among preterm neonates born to mothers with ≥ 4 ANC contacts was 41% lower compared to those born to mothers who had no ANC contacts (AHR = 0.59; 95% CI: 0.36–0.96). The hazards of death among preterm neonates with APGAR score at 5th minute <7 were 1.80 times higher than those with APGAR score at 5th minute ≥7 (AHR = 1.80; 95% CI: (1.22–2.66). Preterm neonates who were resuscitated with bag and mask at birth had 1.59 times higher risk of mortality compared to those who were not resuscitated (AHR = 1.59; 95% CI: 1.10–2.29). The risk of death of preterm neonates with perinatal asphyxia (PNA) was 1.55 times higher than that of those who had no PNA (AHR = 1.55; 95% CI: 1.08–2.22).
Similarly, preterm neonates diagnosed with respiratory distress syndrome (RDS) had a 75% higher risk of mortality compared to those without RDS (AHR = 1.75; 95% CI: 1.22–2.51). Preterm neonates with non-cephalic presentation at birth had 1.68 times higher risk of death compared to those with cephalic presentation (AHR = 1.68; 95% CI: 1.12–2.53). The hazard of death of preterm neonates with neonatal sepsis was 1.58 times higher than that of those without sepsis (AHR = 1.58; 95% CI: 1.09–2.28). Likewise, preterm neonates who received KMC had an 84% lower risk of death compared to those who did not receive KMC (AHR = 0.16; 95% CI: (0.09–0.27) (Table 5).
Discussion
This study found that the cumulative incidence of preterm neonatal mortality rate at the end of the follow-up period was 33.50% (95% CI: 29.76–37.39), with an incidence rate of 52.76 (95% CI: 46.01–60.50) deaths per 1000 preterm neonate-days. The median survival time for preterm neonates was 18 days.
The incidence of preterm neonatal mortality observed in this study was consistent with findings from various hospitals across Ethiopia and other regions. Similar results were documented in studies conducted in Addis Ababa [31], Bench Sheko Zone, Sheka Zone and Keffa Zone [30], and Mizan-Tepi University Teaching Hospital [28], Tigray region hospital [32], Felege Hiwot Hospital in Bahir Dar city [33], and Fort Portal Regional Referral Hospital in Uganda [11].
However, this finding was higher than the study conducted in those upper-middle- and high-income countries, including in China [34,35], Iran [36] and Saudi Arabia [37]. The distinction could be due to economic and sociodemographic differences between Ethiopia and those nations. Infants born preterm in those countries have received improved care during the pre-pregnancy, antenatal, intrapartum, and postnatal periods [38]. These economic and sociodemographic differences may lead to differences in the quality-of-service provision in preterm neonatal care, and developed countries might be better equipped with skilled professionals, a support labor force, and advanced equipment necessary for preterm neonatal care [24,27].
The findings of this study revealed a higher incidence of preterm neonatal mortality compared to studies conducted in Uganda [39], western Sierra Leone [40], Nigeria [41], Jordan [42], and a multicenter study in India and Pakistan [43]. Similarly, within Ethiopia, lower preterm mortality rates were reported from Aksum Referral and General Specialty Hospital [44], a multicenter study conducted in five hospitals [16], Jimma University Medical Center [45], public hospitals in the west Guji and Borena zones [27], the University of Gondar Comprehensive Specialized Hospital [25], and Tikur Anbesa Specialized Hospital [24]. The variation in findings compared to studies from Jordan and a multicenter study in India and Pakistan may be due to differences in economic status, healthcare facilities, study settings, and quality of services [45]. Differences within studies from Ethiopia, Nigeria, Sierra Leone, and Uganda could also reflect variations in service quality among hospitals, with some offering more specialized care [28,30]. Additionally, the larger sample size in the current study may have contributed to the higher reported mortality rate.
In this study, the overall incidence rate of preterm neonatal death was 52.76 (95% CI: 46.01–60.50) per 1,000 preterm neonate-days, with a median survival time of 18 days. This finding is comparable to a previous study conducted in public hospitals in the West Guji and Borena zones, which also reported a median survival time of 18 days [27]. This may be due to similarities in study populations, designs, and healthcare settings across the regions.
The incidence rate of preterm neonatal mortality in this study was higher than that reported in the Busoga region of Uganda [39], two specialized hospitals in the Tigray region [32], Tikur Anbesa Specialized Hospital, with a median survival time of 21 days [24], Nigist Eleni Mohammed Memorial Hospital [46], and Jimma University Medical Center [45]. This variation could be explained by differences in health care quality, patient demographics, referral patterns, or availability of neonatal intensive care services across the various study sites.
Conversely, the incidence rate observed in this study was lower than that reported in studies conducted in Bench Sheko, Sheka, and Keffa Zones [30] and at Mizan Tepi University Teaching Hospital [28]. The lower discrepancy may be explained by variations in study setting, design, quality of care, and healthcare access among those hospitals and the current study hospitals.
This study also identified predictors of mortality among preterm neonates. Accordingly, preterm neonates born to mothers who had four or more ANC contacts had a 44% lower risk of death compared to those whose mothers had fewer than four ANC contacts (AHR = 0.56; 95% CI: 0.36–0.89). This finding is supported by studies conducted at the University Teaching Hospital of Butare in Rwanda [47] and in South Western Uganda [48]. This might be because of the protective effect of adequate antenatal care, likely due to improved maternal health monitoring, early detection of complications, and timely interventions [49]. Additionally, regular ANC visits enhance maternal awareness of danger signs and promote maternal and fetal health in reducing antenatal pregnancy complications, which were associated with preterm neonatal death [50].
In this study, preterm neonates who had a fifth-minute APGAR score of <7 were 1.80 times more likely at hazard of death than those who had an APGAR score of ≥7 (AHR = 1.80; 95% CI: 1.22–2.66). This finding is supported by studies conducted in tertiary hospitals in Ghana [51] and Sierra Leone [40], as well as in multiple hospitals in China [34] and Iran [36,52]. Similarly, studies from Ethiopian facilities, including Mizan Tepi University Teaching Hospital [28] and Tikur Anbessa Specialized Hospital in Addis Ababa aligns with the current finding [24]. This may be attributed to the fact that the 5-minute APGAR score assesses how well the newborn is adapting to the extrauterine environment. A low score at this stage suggests poor physiological adaptation, which increases the risk of neonatal mortality [53]. Moreover, neonates with a fifth-minute APGAR score below 7 often require intensive and specialized care. In settings where timely and advanced medical support from skilled professionals equipped with appropriate resources is lacking, these newborns are at a substantially increased risk of mortality compared to those with higher APGAR scores [28,51].
From the current study, preterm neonates who had perinatal asphyxia (PNA) were 1.55 times more at risk of mortality compared to their counterparts (AHR = 1.55; 95% CI: 1.08–2.22). This finding is consistent with previous studies conducted in China [7,34], at Mbarara Regional Referral Hospital in Southwestern Uganda [48] and in several Ethiopian institutions, including the University of Gondar Comprehensive Specialized Hospital [25], and comprehensive specialized hospitals in the Tigray region [32]. The possible explanation was that perinatal asphyxia remains a major cause of neonatal death in the country due to poor-quality and limited emergency obstetric and newborn care services. Perinatal asphyxia can also damage vital organs, disrupt gas exchange, and worsen organ immaturity in preterm neonates, increasing the risk of death. Additionally, it often leads to severe complications like hypoxic-ischemic encephalopathy and intraventricular hemorrhage, especially in preterm infants [16,53].
In the current study, preterm neonates who received bag-and-mask resuscitation at birth had a 59% higher hazard of death compared to those who were not resuscitated (AHR = 1.59; 95% CI: 1.10–2.29). This finding is supported by evidence from studies conducted in public hospitals in southern Ethiopia [27], Kenya [54], and western Uganda [11]. The possible reason is that the need for resuscitation often indicates serious underlying conditions linked to poor neonatal outcomes, and in low-resource settings, inadequate resuscitation quality and limited post-care contribute to higher mortality in resuscitated preterm neonates. Moreover, resuscitation may act as a pathway for microbial entry, leading to infection, as preterm neonates generally have weak immune defenses, which can lead to neonatal sepsis, which is significantly associated with preterm neonatal mortality [11,55,56].
In this study, preterm neonates diagnosed with RDS had a 1.75 times higher hazard of mortality compared to those without RDS (AHR = 1.75; 95% CI: 1.22–2.51). This finding is supported by studies conducted in southwestern and western Uganda [11,48] and is consistent with research from various parts of Ethiopia, including Addis Ababa [24], Bahir Dar [33], Gondar [25], and Mizan Tepi [28]. The reason is that the increased risk of mortality among preterm neonates with RDS can be attributed to the immaturity of the lungs, particularly due to insufficient production of pulmonary surfactant, a crucial substance that reduces surface tension and prevents alveolar collapse at the end of expiration [53,57].
The hazard of death among preterm neonates born in a non-cephalic presentation was 1.7 times higher than that of those born in cephalic presentation (AHR = 1.68; 95% CI: 1.12–2.53). This finding is supported by studies conducted in various countries and settings, with similar results reported in Uganda [48], in Iran [58], Mizan-Tepi University Teaching Hospital in Ethiopia [28], and a multicenter study in Ethiopian public hospitals [59]. This could be attributed to the increased risk of trauma during delivery, asphyxia, and meconium aspiration syndrome among preterm neonates delivered in a non-cephalic presentation at an early gestational age, which may subsequently result in complications and death in preterm neonates [16,28].
Furthermore, in this study, preterm neonates with neonatal sepsis had a 58% higher risk of mortality compared to those without sepsis (AHR = 1.58; 95% CI: 1.09–2.28). This finding is supported by studies conducted at Tikur Anbessa Specialized Hospital in Addis Ababa [24] and Jimma University Medical Center [45]. This may be attributed to the increased susceptibility of preterm neonates to infections, as their immature immune systems, coupled with inadequate calorie intake, make them more vulnerable and potentially raise the risk of death [60].
Moreover, in the current study, preterm neonates who received kangaroo mother care had an 84% lower hazard of mortality compared to those who did not receive it (AHR = 0.16; 95% CI: 0.09–0.27). This finding is consistent with studies conducted in the southwestern and Busoga regions of Uganda [39,48], Jimma [45], Southwest Ethiopia [30], Addis Ababa [31], Gondar [25], and the Tigray region [32]. This might be because most preterm neonates in those studies did not receive KMC. KMC plays a vital role in protecting neonates from infections, effectively managing hypothermia, enhancing gastrointestinal function and cardiorespiratory stability, and promoting the initiation and continuation of breastfeeding [61].
Strengths and limitations
This study showed survival status and indicated important predictors of mortality among preterm neonates, contributing to the evidence for early identification and management of preterm neonates with identified complications. Since this study involved time-to-event analysis, it allowed for the inclusion of censored study subjects in assessing their contributions. It was conducted in two major cities in eastern Ethiopia with a relatively large sample size. The limitation of this study is follow-up is only limited until discharge. Some events may occur after discharge. Due to the incomplete records, certain major predictors of preterm mortality, such as all maternal demographics, nutritional conditions, and institutional factors, were not addressed.
Conclusion
The study found a high incidence of preterm neonatal mortality, with most deaths occurring in the early neonatal period. The main contributing conditions were hypothermia, neonatal sepsis, and respiratory distress syndrome (RDS). Key predictors of mortality included fewer than four ANC visits, lack of kangaroo mother care (KMC), non-cephalic presentation, neonatal sepsis, RDS, perinatal asphyxia, low APGAR score, and need for bag-and-mask resuscitation at birth.
Most predictors are preventable with available facility resources. Strengthening ANC attendance, promoting KMC, and improving integrated neonatal care, particularly resuscitation, infection prevention, and management of asphyxia, RDS, and sepsis, are essential. Further research should investigate maternal, socioeconomic, nutritional, and institutional factors affecting preterm neonatal survival.
Acknowledgments
We want to express our great appreciation to the heads of public hospitals in the Harari Region and the Dire Dawa Administration, and to the data collectors, for their selfless provision of continuous support and facilitation during the data collection process.
References
- 1.
WHO. World Health Organization, Preterm birth; 2023. Available from: https://www.who.int/en/news-room/fact-sheets/detail/preterm-birth
- 2. Chawanpaiboon S, Vogel JP, Moller A-B, Lumbiganon P, Petzold M, Hogan D, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019;7(1):e37–46. pmid:30389451
- 3. Vogel JP, Chawanpaiboon S, Watananirun K, Lumbiganon P, Petzold M, Moller A-B, et al. Global, regional and national levels and trends of preterm birth rates for 1990 to 2014: protocol for development of World Health Organization estimates. Reprod Health. 2016;13(1):76. pmid:27317125
- 4. Ohuma EO, Moller A-B, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 2023;402(10409):1261–71. pmid:37805217
- 5. Walani SR. Global burden of preterm birth. Int J Gynaecol Obstet. 2020;150(1):31–3. pmid:32524596
- 6. Venkatesan T, Rees P, Gardiner J, Battersby C, Purkayastha M, Gale C. National trends in preterm infant mortality in the United States by race and socioeconomic status, 1995-2020. JAMA Pediatrics. 2023;177(10):1085–95.
- 7. Yu X, He C, Wang Y, Kang L, Miao L, Chen J, et al. Preterm neonatal mortality in China during 2009-2018: a retrospective study. PLoS One. 2021;16(12):e0260611. pmid:34879099
- 8.
WHO. World Health Organization, Newborn mortality; 2024. Available from: https://www.who.int/news-room/fact-sheets/detail/newborn-mortality#:~:text=There%20are%20approximately%206500%20newborn,to%202.3%20million%20in%202022
- 9. AMANHI (Alliance for Maternal and Newborn Health Improvement GA Study Group). Population-based rates, risk factors and consequences of preterm births in South-Asia and sub-Saharan Africa: a multi-country prospective cohort study. J Glob Health. 2022;12:04011. pmid:35198148
- 10. Masaba BB, Mmusi-Phetoe RM. Neonatal survival in sub-Saharan Africa: a review of Kenya and South Africa. J Multidiscip Healthc. 2020;13:709–16. pmid:32801733
- 11. Egesa WI, Odong RJ, Kalubi P, Ortiz Yamile EA, Atwine D, Turyasiima M, et al. Preterm neonatal mortality and its determinants at a tertiary hospital in western uganda: a prospective cohort study. Pediatric Health Med Ther. 2020;11:409–20. pmid:33117056
- 12. Muchie KF, Lakew AM, Teshome DF, Yenit MK, Sisay MM, Mekonnen FA, et al. Epidemiology of preterm birth in Ethiopia: systematic review and meta-analysis. BMC Pregnancy Childbirth. 2020;20(1):574. pmid:32993555
- 13.
WHO. World Health Organization. Newborns: improving survival and well-being; 2020. Available from: https://www.who.int/westernpacific/news-room/fact-sheets/detail/newborns-reducing-mortality
- 14.
EMDHS Ethiopian Public Health Institute. Ethiopia Mini Demographic and Health Survey 2019: Final Report. Rockville (MD): EPHI and ICF; 2019.
- 15.
EMoH (Ministry of Health, Federal Democratic Republic of Ethiopia). Ethiopia Health Sector Transformation Plan-II (HSTP-II); 2021. Available from: https://www.globalfinancingfacility.org/sites/default/files/Ethiopia-HSTP-II.pdf
- 16. Muhe LM, McClure EM, Nigussie AK, Mekasha A, Worku B, Worku A, et al. Major causes of death in preterm infants in selected hospitals in Ethiopia (SIP): a prospective, cross-sectional, observational study. Lancet Glob Health. 2019;7(8):e1130–8. pmid:31303299
- 17. Tamene A, Abeje G, Addis Z. Survival and associated factors of mortality of preterm neonates admitted to Felege Hiwot specialized hospital, Bahir Dar, Ethiopia. SAGE Open Med. 2020;8:2050312120953646. pmid:32922788
- 18. Desalew A, Sintayehu Y, Teferi N, Amare F, Geda B, Worku T, et al. Cause and predictors of neonatal mortality among neonates admitted to neonatal intensive care units of public hospitals in eastern Ethiopia: a facility-based prospective follow-up study. BMC Pediatr. 2020;20(1):160. pmid:32290819
- 19. Henderson J, Carson C, Redshaw M. Impact of preterm birth on maternal well-being and women’s perceptions of their baby: a population-based survey. BMJ Open. 2016;6(10):e012676. pmid:27855105
- 20. Chen Z, Xiong C, Liu H, Duan J, Kang C, Yao C, et al. Impact of early term and late preterm birth on infants’ neurodevelopment: evidence from a cohort study in Wuhan, China. BMC Pediatr. 2022;22(1):251. pmid:35513822
- 21.
Waitzman NJ, Jalali A, Grosse SD. Preterm birth lifetime costs in the United States in 2016: an update. In: Seminars in perinatology. Elsevier; 2021.
- 22.
UNICEF. Neonatal mortality; 2024. Available from: https://data.unicef.org/topic/child-survival/neonatal-mortality/#:~:text=Globally%2C%202.3%20million%20children%20died,6%2C300%20neonatal%20deaths%20every%20day
- 23.
ESS (Ethiopian Statistical Service). Population size by sex, region, zone and wereda: July 2023. Census, population projection; 2023. Available from: https://www.statsethiopia.gov.et/population-projection/
- 24. Aynalem YA, Mekonen H, Akalu TY, Gebremichael B, Shiferaw WS. Preterm neonatal mortality and its predictors in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia: a retrospective cohort study. Ethiop J Health Sci. 2021;31(1):43–54. pmid:34158751
- 25. Yismaw AE, Gelagay AA, Sisay MM. Survival and predictors among preterm neonates admitted at University of Gondar comprehensive specialized hospital neonatal intensive care unit, Northwest Ethiopia. Ital J Pediatr. 2019;45(1):4. pmid:30616641
- 26. Singh G, Sidhu K. Bad obstetric history: a prospective study. Med J Armed Forces India. 2010;66(2):117–20. pmid:27365723
- 27. Huka AE, Oljira L, Weldesenbet AB, Bushra AA, Ahmed IA, Tura AK, et al. Predictors of time to death among preterm neonates admitted to neonatal intensive care units at public hospitals in southern Ethiopia: a cohort study. PLoS One. 2023;18(10):e0283143. pmid:37824535
- 28. Bereka B, Demeke T, Fenta B, Dagnaw Y. Survival status and predictors of mortality among preterm neonates admitted to Mizan Tepi University Teaching Hospital, South West Ethiopia. Pediatric Health Med Ther. 2021;12:439–49. pmid:34512074
- 29. Toma T, Merga H, Dube L. Incidence and predictors of mortality among preterm neonates admitted to Jimma University Medical Center, Southwest Ethiopia: a retrospective follow-up study. Int J Public Health. 2021;69:1606897.
- 30. Mihretu E, Genie YD, Adugnaw E, Shibabaw AT. Survival status and predictors of mortality among preterm neonates admitted in Bench Sheko Zone, Sheka Zone and Keffa Zone Governmental Hospitals, Southwest Ethiopia: prospective follow-up study. BMJ Open. 2024;14(4):e083897.
- 31. Birhanu D, Gebremichael B, Tesfaye T, Tadesse M, Belege F, Godie Y, et al. Survival status and predictors of mortality among preterm neonates admitted to neonatal intensive care unit of Addis Ababa public hospitals, Ethiopia, 2021. A prospective cohort study. BMC Pediatr. 2022;22(1):153. pmid:35321673
- 32. Girma B, Berhe H, Mekonnen F, Nigussie J. Survival and predictors of mortality among preterm neonates in Northern Ethiopia: a retrospective follow-up study. Front Pediatr. 2023;10:1083749. pmid:36714659
- 33. Belay DM, Worku WZ, Wondim A, Hailemeskel HS, Bayih WA. Predictors of survival among preterm neonates admitted to Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia. Front Pediatr. 2022;10:800300. pmid:35372165
- 34. Xu F, Kong X, Duan S, Lv H, Ju R, Li Z, et al. Care practices, morbidity and mortality of preterm neonates in China, 2013-2014: a retrospective study. Sci Rep. 2019;9(1):19863. pmid:31882629
- 35. Yan J-M, Huang H, Li Q-Q, Deng X-Y. A single-center study on the incidence and mortality of preterm infants from 2006 to 2016. Zhongguo Dang Dai Er Ke Za Zhi. 2018;20(5):368–72. pmid:29764572
- 36. Basiri B, Esna Ashari F, Shokouhi M, Sabzehei MK. Neonatal mortality and its main determinants in premature infants hospitalized in neonatal intensive care unit in Fatemieh Hospital, Hamadan, Iran. J Compr Ped. 2015;6(3):e26965.
- 37. Alghadier M, Alasraj M, Elnaggar R, Alazmi M, Aldawsari A, Alnadah S, et al. A cross-sectional analysis of preterm birth incidence and survival in Al Kharj, Saudi Arabia. Saudi Med J. 2024;45(7):710.
- 38. Kikuchi K, Okawa S, Zamawe COF, Shibanuma A, Nanishi K, Iwamoto A, et al. Effectiveness of continuum of care-linking pre-pregnancy care and pregnancy care to improve neonatal and perinatal mortality: a systematic review and meta-analysis. PLoS One. 2016;11(10):e0164965. pmid:27788176
- 39. Opio C, Malumba R, Kagaayi J, Ajumobi O, Kamya C, Mukose A, et al. Survival time and its predictors among preterms in the neonatal period post-discharge in Busoga region-Uganda June – July 2017. JIEPH. 2018;2(2).
- 40. Luke RD, Akhigbe IE, Bell NV, Sovula HS, Koroma MJ, Jonjo DA. Survival status and predictors of mortality among preterm neonates admitted to a tertiary hospital in Sierra Leone. JAN. 2024;2(4):89–96.
- 41. Du M, Ozoiza TB, Danjuma SD, Olushola DO, Joy BF, Collins J. Prevalence and determinants of mortality among preterm infants in Jos University Teaching Hospital, Jos, Nigeria. Int J Sci Study. 2021;9(6).
- 42. Abdel Razeq NM, Khader YS, Batieha AM. The incidence, risk factors, and mortality of preterm neonates: a prospective study from Jordan (2012-2013). Turk J Obstet Gynecol. 2017;14(1):28–36. pmid:28913132
- 43. Dhaded SM, Saleem S, Goudar SS, Tikmani SS, Hwang K, Guruprasad G, et al. The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study. Lancet Glob Health. 2022;10(11):e1575–81. pmid:36240824
- 44. Gebremeskel TG, Mamo S, Berhe E. Proportion and factors of death among preterm neonates admitted in Aksum University compressive specialized hospital neonatal intensive care unit northern Ethiopia 2019. Asian J Biomed Pharm Sci. 2020.
- 45. Toma TM, Merga H, Dube L. Survival status and predictors of mortality among preterm neonates in Southwest Ethiopia: a retrospective cohort study. Res Sq. 2021.
- 46. Tirore LL, Erkalo D, Abose S, Melaku LM, Mulugeta E, Shiferaw A, et al. Incidence of mortality and its predictors among preterm neonates in nigist eleni mohammed memmorial comprehensive specialized hospital, Hossana, Ethiopia: a prospective follow-up study. BMC Pediatr. 2024;24(1):511. pmid:39123147
- 47. Habimana S, Okova R, Janvier D, Mivumbi JP. Predictors of survival of preterm newborns admitted in neonatology unit at the University Teaching Hospital of Butare, Rwanda. RPHB. 2023;4(2):30–8.
- 48. Tibaijuka L, Bawakanya SM, Owaraganise A, Kyasimire L, Kumbakumba E, Boatin AA, et al. Incidence and predictors of preterm neonatal mortality at Mbarara Regional Referral Hospital in South Western Uganda. PLoS One. 2021;16(11):e0259310. pmid:34727140
- 49.
WHO. World Health Organization recommendations on antenatal care for a positive pregnancy experience; 2016. 152 p.
- 50. Kuhnt J, Vollmer S. Antenatal care services and its implications for vital and health outcomes of children: evidence from 193 surveys in 69 low-income and middle-income countries. BMJ Open. 2017;7(11):e017122. pmid:29146636
- 51. Agbeno EK, Osarfo J, Ashong J, Anane-Fenin B, Okai E, Ofori AA, et al. Determinants of preterm survival in a tertiary hospital in Ghana: a ten-year review. PLoS One. 2021;16(1):e0246005. pmid:33481960
- 52. Ghorbani F, Heidarzadeh M, Dastgiri S, Ghazi M, Rahkar Farshi M. Survival of premature and low birth weight infants: a multicenter, prospective, cohort study in Iran. Iran J Neonatol. 2017;8(1):16–22.
- 53.
FMHE (Federal Ministry of Health of Ethiopia). Neonatal Intensive Care Unit (NICU) training participants’ manual. Addis Ababa; 2021. Available from: https://www.scribd.com/document/563672756/NICU-Manual-2021-1#:~:text=2021,Addis%20Ababa
- 54. Mwangi A, Okube OT, Kamau J. Maternal and neonatal factors associated with mortality of preterm babies admitted in Newborn Unit of Kenyatta National Hospital, Kenya. OJOG. 2022;12(12):1219–36.
- 55. Weldearegay HG, Abrha MW, Hilawe EH, Gebrekidan BA, Medhanyie AA. Quality of neonatal resuscitation in Ethiopia: implications for the survival of neonates. BMC Pediatr. 2020;20(1):129. pmid:32192449
- 56. Jabiri A, Wella HL, Semiono A, Saria A, Protas J. Prevalence and factors associated with neonatal sepsis among neonates in Temeke and Mwananyamala Hospitals in Dar es Salaam, Tanzania. Tanzania J Hlth Res. 2016;18(4).
- 57. Wang H, Gao X, Liu C, Yan C, Lin X, Dong Y, et al. Surfactant reduced the mortality of neonates with birth weight ⩾1500 g and hypoxemic respiratory failure: a survey from an emerging NICU network. J Perinatol. 2017;37(6):645–51. pmid:28151493
- 58. Haghighi L, Nojomi M, Mohabbatian B, Najmi Z. Survival predictors of preterm neonates: hospital based study in Iran (2010-2011). Iran J Reprod Med. 2013;11(12):957–64. pmid:24639721
- 59. Hailemeskel HS, Dagnaw FT, Demis S, Birhane BM, Azanaw MM, Chanie ES, et al. Neonatal outcomes of preterm neonates and its predictors in Ethiopian public hospitals: Multicenter prospective follow-up study. Heliyon. 2023;9(8):e18534. pmid:37576212
- 60. Collins A, Weitkamp JH, Wynn JL. Why are preterm newborns at increased risk of infection? Arch Dis Child - Fetal Neonatal Ed. 2018;103(4):F391–4.
- 61.
WHO. World Health Organization recommendations on interventions to improve preterm birth outcomes. WHO Library; 2015.