Does neonatal resuscitation associated with neonatal death in low-resource settings? A follow-up study

Abstract

Background

The newborn period is the most vulnerable phase for a child’s survival, with around half of all under-five deaths worldwide occurring during this time. Despite existing policies and measures, Ethiopia ranks among the top 10 African countries in terms of newborn mortality. In spite of many studies being carried out in the country, the incidence and predictors of neonatal mortality in the Pastoralist and agro-pastoralist parts of the country’s southern still remain unidentified. Therefore, this study aimed to identify the predictors of neonatal mortality in selected public Hospitals in southern Ethiopia.

Materials and methods

An institution-based retrospective cohort study was conducted among 568 neonates admitted to the neonatal intensive care unit at Bule Hora University teaching Hospital and Yabelo General Hospital, Southern Ethiopia from 1 January 2020–31 December 2021. A simple random sampling technique was used to select records of neonates. Data entry was performed using Epidata version 3.1 and the analysis was performed using STATA version 14.1 Kaplan Meir curve and Log-rank test were used to estimate the survival time and compare survival curves between variables. Hazard Ratios with 95% CI were computed and all the predictors associated with the outcome variable at p-value 0.05 in the multivariable cox proportional hazards analysis were declared as a significant predictor of neonatal death.

Results

Out of 565 neonates enrolled, 54(9.56%) neonates died at the end of the follow-up period. The overall incidence rate of death was 17.29 (95% CI: 13.24, 22.57) per 1000 neonatal days with a restricted mean follow-up period of 20 days. Of all deaths, 64.15% of neonates died within the first week of life. In the multivariable cox-proportional hazard model, neonatal age < 7 days (AHR: 9.17, 95% CI: (4.17, 20.13), place of delivery (AHR: 2.48, 95% CI: (1.38, 4.47), Initiation of breastfeeding after 1 h of birth (AHR: 6.46, 95% CI: (2.24, 18.59), neonates’ body temperature <36.5 °C (AHR: 2.14, 95% CI: (1.19, 3.83), and resuscitated neonates (AHR: 2.15, 95% CI: (1.20, 3.82) were independent predictors of neonatal death.

Conclusion

In the research setting, the incidence of neonatal death was high, especially during the first week of life. The study found that neonatal age < 7 days, place of delivery, Initiation of breastfeeding after 1 h of birth, neonates’ body temperature <36.5 °C, and resuscitated neonates were predictors of neonatal death. To improve newborn survival, significant neonatal problems, improved resuscitation, and other relevant factors should be addressed.

Keywords:

• Resuscitation
• nICU
• neonates
• Bule Hora
• Ethiopia

Introduction

Neonatal mortality (NM) is defined as the death of a baby during the neonatal period (within the first 28 days of life) which is the most vulnerable time for survival in which children face the highest risk of dying in their life. The neonatal period is the most risky time for a child’s survival [1] and the newborn period is when they are more vulnerable to survival potential hazards.

Globally, neonatal death accounts for about half of all under-five mortality and is anticipated to rise by more than half (52%) by 2030 [2]. Almost all newborn deaths occur in low-income and middle-income countries (LMICs) where access to health care, including resuscitation at birth, is limited [3,4]. Notably, studies suggest that the systematic implementation of low-cost and effective newborn resuscitation programs in low-resource settings (LRSs) has the potential to avert nearly 200,000 of these intrapartum-related deaths each year [5,6].

The neonatal mortality rate in Ethiopia is among the highest in Sub-Saharan Africa. Neonatal death in Ethiopia decreased non-significantly from 37 deaths per 1000 live births in the national survey report from 2011 to 29 deaths per 1000 live births in the Demographic Health Survey (DHS) of 2016 [7].

Since 2015, Ethiopia has implemented a number of measures in order to meet the target of the Sustainable Development Goals (SDGs). These nationally designed measures are in place to make certain that integrated management of neonates and children illnesses (IMNCI), neonatal intensive care units (NICU), and kangaroo mother care (KMC) are accessible and available at all District Hospitals. Similarly, boosting primary health care (PHC) services is a national strategy plan to accomplish the SDGs’ targets of ending preventable newborn deaths, with all nations aiming to reduce NM to at least 12 per 1,000 live births by 2030 [8–10]. Despite all of these efforts, in Ethiopia the NMR is still far behind national and international goals. Moreover, the incidence and predictors of neonatal mortality have not been well-known in the Pastoralist and Semi-pastoralist areas of the southern part of the country. Therefore, the aim of this study was to identify the incidence and predictors of death among neonates admitted to the NICU at Bule Hora University teaching hospital and Yabelo general hospital in Southern Ethiopia.

Materials and methods

Study area and period

This study was conducted at Bule Hora University Teaching Hospital and Yabelo General Hospital, Oromia Regional State, Southern Ethiopia. These areas are located 467 km and 567 km far from Addis Ababa, the capital city of Ethiopia, respectively. These two hospitals provided a delivery service, and also have NICU wards. Bule Hora University Teaching Hospital and Yabelo General Hospital currently have a 3 and 4 incubator capacities NICU with 2 and 4-bed kangaroo mother care units attached to it respectively. The study period was from 1 January 2020–31 December 2021 among neonates admitted to NICU at the selected hospitals with a maximum follow-up period of 28 days.

Study design, population, and eligibility criteria

An institution-based retrospective cohort study was conducted. The study population was all neonates’ admission records at the NICU at Bule Hora University Teaching Hospital and Yabelo General Hospital admitted from 1 January 2020–31 December 2021. All neonates’ admission records at the NICU at Bule Hora University Teaching Hospital and Yabelo General Hospital during the study period were included in the study; whereas neonates’ admission records with incomplete information, and any neonates’ records with withdrawal from treatment were excluded from the study.

Sample size and sampling procedure

To determine the representativeness of the population, the sample size for the cohort study was estimated using the double population proportion formula in EPI INFO version 7 considering the following assumptions: 95% CI: 1.96; 80% power. The ratio of the population exposed to non-exposed was 1:1. Finally, the low birth weight as exposure variable was chosen for estimating the sample size (AHR) =2.59 from a previous study [11] and then, 10% for loss to follow up was added to the estimated sample size, yielding a final sample size of 568. Using their unique medical registration number (obtained from the admission record) as a sampling frame, a predetermined sample size was selected using a simple random sampling technique.

Data collection procedure and instruments

The checklist for this study was taken from the medical card and record of neonates, with modifications based on a review of the literature [12,13]. A standardized checklist was used to retrieve data from each neonate’s medical card and logbook. The checklist included information on maternal and newborn characteristics and obstetric-related factors.

Data collectors received training on how to extract acceptable data from neonates’ medical cards, and the data collection on the spot was closely monitored and supervised on a daily basis.

Variables and measurements

The outcome variable of this study was neonatal mortality and which was the event of the study. Neonatal mortality is the death of neonates during the first 28 days after birth [14]. The neonates that did not develop an event [15] were recorded as censored. Censored includes neonates who survived the first 28 completed days after birth and were alive at the end of the study, lost from follow-up, and transferred to other health institutions. Time-to-death is defined as a time in days from starting of observation (admission to NICU) until the occurrence of the outcome of observation and calculated by subtracting the date of admission from the date of the event [16]. The neonatal period refers to the period of less than 28 days after birth, the early neonatal period refers to the period before 7 days of age, and the late neonatal period refers to the period from the completion of 7 days up to 28 days of life.

Several covariates were considered in this study to identify the major predictors of neonatal death as independent variables. Maternal-related factors such as the number of pregnancy, onset of labor, duration of labor, ANC follow-up, place of delivery, mode of delivery, and TT injection. Neonatal-related factors such as the weight of the neonate at admission, sex of neonates, Apgar score, the temperature of neonates, gestational age, early initiation of breastfeeding, and Resuscitation were also included.

Data management and analysis

After data collection, each questionnaire was checked for completeness and consistency. Data were cleaned, edited, coded, and entered into Epi data version 3.1 and then exported to STATA version 14 for further analysis. The distribution of survival time was estimated using descriptive survival analysis, such as Kaplan-Meier survival function calculation. Person-days of observation were computed by subtracting the date of an event or censoring from the date of admission to the NICU ward to determine the total days of follow-up for all neonates in the study.

Kaplan Meier survival curve together with the log-rank test was fitted to test for the presence of difference in the occurrence of death among the covariates. The overall survival function and separate estimates for the stratum of covariates were considered statistically significant at a p-value of 0.05 in the Log-rank test. Cox proportional hazards regression model was used to determine predictors of mortality by controlling confounding. The potential candidate predictors to the full model were selected by Bivariable Cox proportional hazard regression with a cutoff point p ≤ 0.25. Multi-collinearity was checked using variance inflation factor (VIF < 10) indicating the nonexistence of multicollinearity. Hazard Ratios (HR) with 95% Confidence Intervals (CI) were used to assess the relationship between predictors associated with the occurrence of preterm neonatal death. Statistical significance was declared at p-value < 0.05. Proportional hazard assumption was assessed both graphically and Schoenfeld residual global test and PH assumption was met. Cox–Snell residual plot was used to assess the overall goodness of fit of the proportional hazard model.

Results

Socio-demographic and Obstetric characteristics

Out of 568 selected records of neonates, 565 complete medical records were extracted with a retrieval rate of 99% included in the data analysis. The mean (±SD) age of the neonate’s mother age was 28 (±6.1SD) years (Table 1).

Table 1. Obstetric characteristics of mothers of neonates admitted to the NICU at Bule Hora University Teaching Hospital and Yabelo General Hospital, Southern Ethiopia, 2022.

Variables	Category	Frequency	Percentage (%)
Family residence	Urban	241	42.65
	Rural	324	57.35
Parity	Primipara	172	30.40
	Multipara	289	51
	Grand multipara	104	18.40
Gravidity	Primi-gravida	168	29.70
	Pregnancy two	111	19.65
	≥3 Pregnancy	284	50.20
Onset of labor	Induced	41	7.26
	Spontaneous	524	92.74
Duration of Labor	≤ 6 h	195	36.40
	7-12 h	253	47.20
	>12 h	87	16.20
Mode of Delivery	Spontaneous Vaginal delivery	496	87.79
	Instrumental	8	1.42
	Cesarean section	61	10.80

Neonatal characteristics

Out of 568 reviewed records, 565(99%) were included in the data analysis. More than half, 339(60%) of the neonates enrolled in the study were males and 303(53.6%) of the neonates belonged to the age group less than 7 days. The median age of the neonates was 6 days. The median admission weight and gestational age of neonates were 2800 g (IQR: 2000 g-3290g) and 37 weeks (IQR: 36–38 weeks) respectively. About 91(16.11%) of neonates were resuscitated and 208(36%) neonates were hypothermic upon admission (Table 2).

Table 2. Characteristics of neonates admitted to NICU at Bule Hora University Teaching Hospital and Yabelo General Hospital, Southern Ethiopia, 2022.

Variables	Category	Frequency	Percentage (%)
Age	< 7 days	303	53.63
	≥ 7 days	262	46.37
Sex	Male	339	60
	Female	226	40
Gestational age	< 37 weeks	355	62.83
	≥ 37 weeks	210	37.7
APGAR score at 5^th minutes	< 5	193	51.47
	≥ 5	182	48.53
Weight of Neonate at admission	< 2500 g	211	37.35
	≥ 2500 g	354	62.65
Temperature of neonates at admission	< 36.5 °C	406	71.86
	≥ 36.5 °C	159	28.14
Early Initiation of breastfeeding	Within 1 h	253	44.78
	After 1 h	312	55.22
Resuscitated	Yes	91	16.11
	No	474	83.89

Healthcare seeking and utilization

Among 565 neonates enrolled in the study, three hundred seventy-five (66.3%) mothers gave birth at the health facility. One hundred fifty-eight (27%), were born from a mother who had antenatal care follow-up (ANC), in which only 24(14%) of them had four or above ANC visits. The majority of neonates were delivered in healthcare institutions, and about seventy-four (74%) of them did not receive a TT injection.

Causes of neonatal admission and mortality

The major cause of neonatal admission were neonatal sepsis, 314(55.5%) followed by preterm 122(21.5%), Prenatal asphyxia 75(13) and Congenital malformation 7(1.24%). In this study, 54(9.56%) of neonates died, in which the leading causes of neonatal mortality were, neonatal sepsis 21(38.9%), preterm 19(35.1%), and prenatal asphyxia 12(22.59%) leading causes of mortality.

Survival analysis and outcome of the follow-up

A total of 565 neonates were followed for a mean follow-up period of 20 days. During a follow-up time, a total of 3124 person day observations were detected with a minimum and maximum follow-up time of 1 and 26 days, respectively. The overall incidence of neonatal mortality was 17.29 (95% CI: 13.24, 22.57) per 1000 neonatal days of observation. Of all deaths, 34 (64.15%) of neonates died in the first week of life and 20(35.85%) died in the late neonatal period (after one week of life) (Table 3).

Table 3. Incidence of neonatal mortality admitted to NICU at Bule Hora University Teaching Hospital and Yabelo general hospital, Southern Ethiopia, 2022.

Variables	Category	Neonatal days	Number of events	Rate (95% CI)
Total neonatal days		3124	54	0.02(0.01, 0.02)
Sex	Male	1869	32	0.02(0.01, 0.02)
	Female	1255	22	0.02(0.01, 0.03)
Neonatal age	< 7 days	1071	34	0.03(0.02, 0.04)
	≥ 7 days	1994	20	0.01(0.01, 0.01)
Residence	Urban	1292	18	0.01(0.01, 0.01)
	Rural	1832	36	0.02(0.01, 0.03)
5^th minutes Apgar score	< 5 score	515	14	0.03(0.02, 0.04)
	≥ 5 score	2609	40	0.02(0.01, 0.02)
Initiation of exclusive breast feeding	Within 1 h	1283	4	0.003(0.001, 0.01)
	After 1 h	1841	50	0.02(0.01, 0.02)
Resuscitated	No	2624	33	0.01(0.01, 0.02)
	Yes	500	21	0.04(0.03, 0.06)
Weight at admission	< 2500 g	1223	27	0.02(0.01, 0.03)
	≥ 2500 g	1901	27	0.01(0.01, 0.02)

Survival function of time to death

Kaplan Meier survival estimate indicates that, as follow-up time increase the probability of neonatal survival increase. During the first ten days of follow-up, the graph went down rapidly which shows a higher proportion of neonates were dying and there was a lower probability of neonatal survival (Figure 1).

Figure 1. Probability of survival estimate of neonates admitted to NICU at Bule Hora University Teaching Hospital and Yabelo General Hospital from January 2020 to December 2021 (n = 565).

Comparison of the survival function

The log-rank test revealed that neonates born at health facility had higher survival experience compared to their counterparts (Log-rank test, X²=8.85, P-value = 0.003) while neonates who were not resuscitated had a higher survival experience than neonates who have undergone resuscitation (Log-rank test, X² = 22.71, P-value = 0.001) (Figure 2).

Figure 2. Kaplan-Meier survival curves of time to death among exposed and unexposed neonates admitted to NICU at Bule Hora University Teaching Hospital and Yabelo General Hospital from January 2020 to December 2021 (n = 565).

Predictors of death among neonates

In cox regression analysis, residence, maternal age, neonatal age, mode of delivery, place of delivery, early initiation of breastfeeding, resuscitation, ANC follow-up, TT injection, low admission weight, Temperature, Apgar score at fifth minute and pregnancy complication were selected for multivariable cox regression. Finally, five of the predictors (neonatal age, place of delivery, initiation of breastfeeding, neonate body temperature, and neonate resuscitation) were found to have a statistically significant association with neonatal mortality during multivariable cox proportional regression analysis.

In this study, the hazard of death at early neonatal period is higher, in which the risk of death among neonate less than 7 days were 9 times higher as compared with the neonatal age of 7 days and above (AHR: 9.17, 95% CI: (4.17, 20.13). The risk of death among those neonates born at home was 2.4 times higher as compared to neonates born at health facilities (AHR: 2.48, 95% CI: (1.38, 4.47). The risk of neonatal death among those whose exclusive breastfeeding was not initiated within 1 h of birth was 6 times higher than neonates who start within 1 h (AHR: 6.46, 95% CI: (2.24, 18.59). The hazard of neonatal death among neonates with body temperature less than 36.5 °C was 2 times higher as compared with those with body temperature greater than or equal to 36.5 °C (AHR: 2.14, 95% CI: (1.19, 3.83). The hazard of death among neonates resuscitated in NICU has 2 times higher risk of death compared to their counterparts (AHR: 2.15, 95% CI: (1.20, 3.82) (Table 4).

Table 4. Predictors of neonatal mortality among neonates admitted to NICU at Bule Hora University Teaching Hospital and Yabelo General Hospital from January 2020 to December 2021 (n = 565).

		Survival status
Variable	Category	Died(n)	Censored (n)	CHR 95% CI	AHR 95% CI
Neonatal age	<7 days	34	269	6.65 (3.10, 14.27)	9.17(4.17, 20.14)**
	≥7 days	20	242	1	1
Mode of delivery	SVD	52	444	1	1
	Instrumental	2	67	0.28(0.07, 1.16)	0.36 (0.09, 1.55)
Place of delivery	Home	28	162	2.19(1.28, 3.75)	2.48(1.37, 4.47)**
	Health facility	26	349	1	1
Temperature at Admission	<36.5 °C	30	129	3.38(1.96, 5.84)	2.14(1.19, 3.83)*
	≥36.5 °C	24	382	1	1
Pregnancy complication	Yes	7	38	1.67 (0.75, 3.71)	1.86(0.76,4.54)
	No	47	473	1	1
Time breastfeeding initiated	Within 1 h	4	249	1	1
	After 1 h	50	262	8.69(3.13,24.11)	6.46(2.24,18.59)
ANC follow up	Yes	10	158	1	1
	No	44	407	1.66(0.83,3.30)	1.72(0.82,3.62)
Resuscitation	Yes	21	70	3.46(2.00,6.01)	2.15(1.20,3.83)**
	No	33	441	1	1
Neonate weight	≥2500g	27	327	1	1
	<2500g	27	184	1.53(0.90,2.62)	0.94(0.53,1.69)

SVD: Spontaneous vaginal delivery; CHR: crude hazard ratio; AHR: Adjusted hazard ratio; CI: confidence interval *p-value <0.05 **p-value < 0.01.

Discussion

Despite the fact that the government and non-governmental stakeholders remain strongly committed to reducing newborn mortality, developing countries like Ethiopia continue to face difficulties. Therefore, this study aimed to identify predictors of neonatal death among neonates admitted to the neonatal intensive care unit at Bule Hora University Teaching Hospital and Yabelo General Hospital, Southern Ethiopia. The results showed that 9.56% of the neonates died during the follow-up period., of which 64.15% of neonates died in the first week of life and 35.85% died later (after one week of life). The overall incidence rate of neonatal mortality was 17.29 deaths per 1000 neonatal days with a restricted mean survival time of 20 days. This finding was lower than EDHS 2019 (30 deaths per 1000 live birth) [17] and the study conducted in Northern and Southern parts of Ethiopia [11–13]. However, it is higher than the studies conducted in Butajira and Wolega University referral Hospitals [18,19]. The reason for these discrepancies could be that previous studies used data from only one department, such as the delivery room, while others included data from both the delivery and neonatal intensive care units, whereas this study included only data from neonates admitted to the neonatal intensive care unit while taking into account very important predictors such as neonatal, maternal, and health service utilization. Furthermore, these disparities may be attributed to the quality of service offered, study sites, and time frame.

In this study, the majority of newborn deaths (64%) occurred in the first week of life, indicating that the hazard of death among neonates in the early neonatal period was 9.17 times higher than those neonates in the late neonatal period. This finding is consistent with findings of studies conducted in Northern, Southern, and Western areas of Ethiopia [11–13, 19,20]. This could be because the newborn period, particularly the early neonatal period, is the most vulnerable period for a child’s life. Similarly, poor antenatal care visits, a delay in diagnosis, and inadequate handling of difficulties during pregnancy and delivery by health care personnel, as well as the advancement of institutions where those neonates are admitted to.

Neonates born at home were 2.4 times more likely to die than those born at a health facility at any given time. This could be due to the perceived poor quality of healthcare services, unwelcoming attitudes of health workers, home deliveries as a social norm, and distance and limited access to transportation as causes for home delivery in the study area. These variables may also have a negative impact on pregnant women’s attitudes toward healthcare delivery, leading them to choose home delivery.

The hazard of death was 6.46 times higher for neonates who did not start breastfeeding within one hour of birth than their counterparts at any given time. This is consistent with findings from other studies in the country [11, 21–23]. This implies that breastfeeding should be started as soon as possible to prevent neonatal mortality. However, in the current study, starting breastfeeding within one hour of birth appears to be underutilized and under-promoted. It is important to highlight that unwell newborns may not be able to suck breast milk as well as healthy neonates.

The risk of death among neonates with a body temperature less than 36.5 °C was twice higher as compared with those with a body temperature greater than and equal to 36.5 °C at any given time. This is due to the fact that these neonates are exposed to the risk of dying from hypothermia. This shows that if the warm delivery room procedures were continued and neonatal infections were detected and treated early, the majority of newborn babies’ lives would have been saved.

The hazard of death among neonates who were resuscitated at birth was twice more likely than those who were not resuscitated at birth at any given time. This is consistent with several studies conducted in Ethiopia and other African countries [12, 23–26]. However, it is against a study conducted in the Eastern part of Ethiopia [27] where resuscitation was found to be one of the protective factors. This might be related to the fact that neonates being transferred to NICU might be at increased risk of neonatal complications or it might be related to using improper procedures to resuscitate and also may be the inadequate skill of health care providers. According to International Liaison Committee on Resuscitation, rapid advances in neonatal resuscitation research and implementations of various resuscitation training programs have resulted in a decrease in global neonatal mortality by almost half in the last three decades.

Limitations of the study

First, there is a potential to exclude neonatal deaths particularly those registries considered as incomplete. Second, the current study was limited to health facilities providing neonatal intensive care services. Due to all the above-mentioned factors overall neonatal mortality would be underestimated. The other limitation is that because of the nature of the study design some important predictors of neonatal mortality were not explored.

Conclusions

In the research setting, the incidence of neonatal death was high, especially during the first week of life. The study found that neonatal age < 7 days, place of delivery, Initiation of breastfeeding after 1 h of birth, neonates’ body temperature <36.5 °C, and resuscitated neonates were predictors of neonatal death. Therefore, attention has to be given to boosting the skill of healthcare providers and equipping healthcare facilities with appropriate resuscitation materials in the NICU and community-based neonatal survival strategies, particularly for rural mothers. Furthermore, neonates should get special attention during their early neonatal period. Finally, we would recommend future researchers to conduct prospective follow-up study on why resuscitated neonates are more likely to die than their counterparts in resource-limited countries.

Ethical approval and consent to participate

Ethical clearance was obtained from the Institutional Review Board of Bule Hora University with Ref.no BHU/RPD/817/13. The necessary explanation regarding the purpose of the study was informed to data collectors and the concerned official body in the hospital. Confidentiality of the information was assured by not recording any personal identifiers from the chart. Furthermore, the research procedures were conducted in accordance with the principle expressed in the World Medical Association’s Declaration of Helsinki.

Authors’ contributions

AA, SA, DJ, AE, and EA conceived the idea and designed the study, led the data analysis and interpretation, developed the first draft of the manuscript, and made all revisions. AA and AE critically revised the manuscript for important intellectual content and ensured that the requirements for submission of the manuscript were met. AA, SA, DJ, AE, and EA contributed to the analysis and data interpretation and revised and edited the manuscript. AA and AE reviewed the expert opinions and revised the manuscript for important intellectual content. AA, SA, DJ, AE, and EA supervised the study design and wrote the manuscript. All the authors have read and agreed to the final version of the manuscript for publication.

Acknowledgments

First, the authors thank Bule Hora University for supporting our data collection. The authors also like to thank facilities heads, data collectors, and supervisors for their invaluable support and cooperation throughout the data collection.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

All data analyzed during this study are included in the manuscript.

Additional information

Funding

No funding was obtained for this study.