Neonatal mortality and associated factors among neonates admitted to neonatal intensive care unit at public hospitals of Somali Regional State, Eastern Ethiopia: A multicenter retrospective analysis.

BACKGROUND: Neonatal mortality remains a public health problem in the developing world. Globally, around 2.5 million neonatal deaths are reported annually with the highest mortality concentrated in sub-Saharan Africa and South Asia. In comparison with countries demonstrating the lowest neonatal mortality, the risk of mortality is over 30 times higher in sub-Saharan Africa. Ethiopia is among the countries with a high neonatal mortality rate, and the burden of this mortality remains unreported in many pastoralist areas such as Somali Regional State, Eastern Ethiopia. We aimed to investigate factors associated with neonatal mortality in public Hospitals of the Somali Regional State in Eastern Ethiopia.
METHODS: A facility-based cross-sectional study was conducted from May 1st to 30th, 2020 in three public Hospitals of Somali Regional State in Eastern Ethiopia. A total of 510 neonates admitted to neonatal intensive care units from January 2018 to December 2019 were enrolled in the study. The charts of neonates were randomly selected and retrieved. Data were collected using a pretested and validated structured questionnaire. The collected were entered into Epidata version 3.1 and exported to SPSS version 22 (IBM SPSS Statistics, 2013) for further analysis. Descriptive statistics were carried out using frequency tables, proportions, and summary measures. Predictors were assessed using a multivariable logistic regression analysis model and reported using adjusted odds ratio (AOR) with 95% Confidence Interval (CI). Statistical significance was considered at a p-value <0.05.
RESULTS: Overall, the neonatal mortality was 18.6% [95%CI (15.31, 22.30)], equating to a rate of 186 per 1000 live births. The most common causes of mortality were prematurity (44.6%), low birth weight (33.5%), and birth asphyxia (27.6%). In the final model of multivariable analysis, predictors such as: lack of antenatal care follow-up[AOR = 3.71, 95%CI (2.13, 6.44)], neonatal sepsis [AOR = 1.84, 95%CI (1.07, 3.19], preterm birth [AOR = 2.20, 95%CI (1.02, 4.29], and birth asphyxia [AOR = 2.40, 95%CI(1.26,4.43)], and birth weight of less than 2500gms[AOR = 3.40, 95%CI(1.92, 6.01)] were statistically associated with neonatal mortality.
CONCLUSION: In this study, the neonatal mortality rate was high compared to national and global targets because one in five neonates dies due to preventable causes. Modifiable and non-modifiable risk factors were identified as predictors. This result calls for all stakeholders to provide due attention to low birth weight and premature babies. Early identification and management of birth asphyxia and neonatal sepsis are also very crucial to reduce the risks of neonatal deaths.

Introduction

Neonatal mortality (NM) continues to be a public health problem in the developing world. The first 28 days of life is the most susceptible time for children’s life because they face the highest risk of dying in their first month of life [1,2]. Worldwide, about half of the global under-five mortality are due to neonatal deaths, making the neonatal period the most deadly in a child’s life [3,4]. For example, in 2019, 2.4 million neonates died, with an average of 6700 deaths occurring per day in the first month of life [5,6].

Globally, most regions have made substantial progress in reducing neonatal mortality since 1990. However, the mortality rate continued to be high in developing regions. In other words, despite the global burden of neonatal deaths declined by 51%, from 5 million deaths in 1990 to 2·5 million deaths in 2017, sub-Saharan Africa(SSA) and South Asian countries have shown slow progress in reduction of the neonatal mortality. For instance, in 2017, South Asia and sub-Saharan Africa alone accounted for 79% of the global neonatal mortality [7,8]. Similarly, studies have shown that the risk of neonatal mortality is over 30 times higher in sub-Saharan Africa than in the lowest mortality country in the world [9].

Furthermore, neonatal mortality rates (NMRs) vary significantly among the countries, with a huge toll of deaths attributed to the low-income countries. For instance, in 2019, the NMR was 522/1000 in India, 270/1000 in Nigeria, 248/1000 in Pakistan, and 97/1000 in the Democratic Republic of Congo [5,8]. Ethiopia is among the countries with the highest neonatal mortality in SSA. According to the Demographic Health Survey(DHS) of 2016, in Ethiopia, the neonatal mortality rate was 29 deaths per 1000 live births, which showed a non-significant decline from 37 deaths per 1000 live births in the 2011 national survey report [10].

Furthermore, studies have shown that around 60% to 80% of neonatal deaths are attributed to prematurity and small for gestational age [5]. In addition, researchers have indicated that numerous risk factors like parents’ lower educational level, lack of basic prenatal care [11], post-term pregnancy [12], low birth weight [13], congenital malformations [14], perinatal asphyxia [15,16], preterm birth [17,18], neonatal infections [13,17,19-21], hypothermia, respiratory distress syndrome [13,22], and low Apgar score(less than 7 score) [23] are associated with neonatal deaths. Moreover, assisted vaginal delivery [20], and maternal age less than 20 years old [24] are significant predictors of neonatal deaths. Three-fourths of newborn deaths can be prevented by effective interventions such as antenatal care (ANC) during pregnancy, intrapartum care (skin-to-skin contact, early initiation of breastfeeding, newborn resuscitation, and kangaroo mother care), and postnatal care. In addition, providing the continuum of care for small and sick newborns, and good nutrition can reduce these burdens of neonatal deaths [25,26].

Ethiopia has developed various interventions since 2015 to achieve the target of sustainable development goals (SDGs). These nationally devised interventions are established to ensure the accessibility and availability of integrated management of newborns and childhood illnesses (IMNCI), neonatal intensive care units (NICU), and kangaroo mother care (KMC) at all District Hospitals. Likewise, strengthening the primary health care (PHC) services is also a national strategic plan to meet the targets of SDGs, which aimed to end preventable deaths of newborns with all countries aiming to reduce NM to at least 12 per 1,000 live-births in 2030 [27-29].

Furthermore, the Federal Ministry of Health (FMoH) has also introduced new programs such as health extension program (HEP), community health insurance program (CHIP), and community-based newborn care (CBNC) to ensure the accessibility of basic healthcare services to the rural community of Pastoralist and Semi-Pastoralist areas such as Afar and Somali regions [29,30]. With all these efforts are being implemented, still, the NMR is far from the national and global targets. Moreover, although limited studies have been conducted in Eastern Ethiopia [31-33], still, the magnitude and predictors of neonatal mortality have not been well known in the Pastoralist and Semi-pastoralist areas of the Somali Region. Therefore, we aimed to investigate the associated risk factors of neonatal mortality in selected public Hospitals of Somali Regional State, Eastern Ethiopia.

Materials and methods

Study setting, period, and design

A facility-based cross-sectional study (a multicenter retrospective chart review) was conducted from May 1st to 30th, 2020 in three public hospitals (Kebri-Dahar General Hospital, Dhegahbur Zonal Hospital, and Godey General hospital) in Eastern Ethiopia. Kebri-Dahar is one of the Districts in the Somali Regional State. According to the 2007 national census, the District has a total population of 136,142, of whom 77,685 are males and 58,457 females. It has one zonal hospital, one general hospital, two health centers, and four health posts. Deghbur Zonal Hospital is found in Degahbur town in the eastern part of Ethiopia, 780 Km from Addis Ababa and 171km from Jigjiga, the Regional capital. The town has an estimated total population of 42,360 of whom 9679 are reproductive age and 1339 are pregnant women. It has one Hospital, two health centers, and four health posts. Godey General Hospital is located in Godey town, 630Km from Jigjiga, Regional capital. The Godey town consists of 10 the smallest administrative unit called Kebeles. It has a total population of 75,000 (33,000 males and 42,000 females). The town has one public Hospital, one private clinic, and four health posts [34].

Population and sampling technique

All neonates aged 0-28days admitted to NICU of selected public Hospitals of the Somali Regional State from January 2018 to December 2019 were considered as source population. All eligible and randomly selected medical records of neonates were included in the analysis. However, medical records of neonates with incomplete and lack of pertinent information, and neonates who were initially admitted, but immediately referred to the specialized health facilities for further management were excluded from the study. The sample size of this study was calculated using the statistical software of Epi-info (Version 7.0). Thus, from the predictor variables, maternal ANC follow-up was considered as the exposure variable. This proportion was taken from a previous study report conducted in Gondar, Northern Ethiopia [20]. The proportions of neonatal deaths among mothers of a neonate who had no ANC follow-up were considered as an exposed group, and the proportions of neonatal deaths among those women who had ANC follow-up were considered as the unexposed group. Based on the above information, the following assumptions were made: Accordingly, the proportion of outcomes among unexposed group (had ANC follow-up, p = 30.8%), the proportion of outcomes among an exposed group (had no ANC follow-up, p = 13.4%), two-sided confidence level = 95%, a tolerable margin of error = 5%, power of 80%, the ratio of unexposed to exposed = 1.0, and by adding 10% contingency for non-response rate, the final sample size of the study was 514.

In the Somali Regional State, three public hospitals (Kebri-Dahar General Hospital, Degahbur Zonal Hospital, and Godey General Hospital) were purposely selected. The total number of neonates admitted to the NICU of all three Hospitals (from January 2018 to December 2019) was 830. The sample size (n = 514) was proportionally allocated to all selected public Hospitals by considering the number of admitted neonates in the last two years. Lists of medical records of neonates were taken from each Hospital and a sampling frame was developed. Medical records of neonates were selected using a simple random sampling (SRS) technique. Finally, the patients’ charts were retrieved and pertinent information was obtained until the required sample size was achieved (

Data collection tools and procedures

Data were collected using validated structured questionnaires and checklists adapted and customized from Ethiopian Demographic and Health Survey (EDHS) data collection tools [10] and developed by reviewing related literature [13,14,20]. Initially, three pediatricians and one neonatologist expert validated the content of the questionnaire. The questionnaire pretest was conducted in a similar setting and refined accordingly. Data were collected by four diploma (10+3) nurses, who had data collection experiences. Three supervisors (Bachelor of Sciences degree in nursing) were recruited and assigned to each selected Hospital for close supervision of data collectors and data collection process. Informed, voluntary, and signed consent was obtained from all authorized bodies of the selected Hospitals. All eligible medical records of neonates were manually searched from where they were previously stored and filed in the board cabinet. Eligible charts were searched, and allocated using patients’ medical record numbers (MRNs). Finally, data were collected until the required sample was obtained.

Variables and measurements

In this study, the dependent variable was neonatal mortality. This dependent variable was dichotomized as binary outcomes. Accordingly, if neonate was not survived after admission to NICU, it was recoded as “1”, and if neonate was survived after admission to NICU, it was recoded as “0”. Moreover, the explanatory variables were categorized as: socio-demographic variables (age of the mother, age of the neonate, sex of the neonate, residence), neonatal related factors(neonatal respiratory distress, Apgar score, congenital malformation, birth asphyxia, low birth weight, neonatal sepsis, preterm birth, hypothermia, and early and late admission), and maternal related factors (parity, place of birth, ANC follow-up, home delivery, vaginal delivery, cesarean delivery, and instrumental delivery).

Operational definitions

Neonatal mortality: the probability of dying of neonates within the first 28days of life [35]. The magnitude of neonatal mortality: is the proportion of neonatal death among neonates admitted to NICU. Neonatal mortality rate: Probability of dying during the first 28 days of life, expressed per 1,000 live births [10]. Neonatal sepsis: Record of infection or sepsis diagnosed either clinically or with culture by professionals during admission of the neonate and as possible causes of death and designated or recorded on the chart [12]. Hypothermia: defined as when the neonatal axillary temperature of less than 36.5°c [36]. Apgar score is a simple evaluation system including five easily identifiable components such as heart rate, respiratory effort, muscle tone, reflex/activity, and color. A score of 0, 1, or 2 is assigned to each component, and the sum of scores of the five components is the total score [37]. Prematurity: defined as when a live-born neonate is delivered before 37 completed weeks of gestation [20]. Birth asphyxia: is diagnosed whenever a neonate had an Apgar score ≤ 6 at the 1st and 5th minutes and did not cry immediately after birth; had respiratory distress, and loss of neonatal reflexes [20]. Antenatal care (ANC): If the pregnant woman attended the ANC unit during her pregnancy at least once. ANC follow-up: history of one to four antenatal follow-up during current or index pregnancy at any health facility for pregnancy check-ups and chart designation or recording [38].

Data quality control

Data collectors and supervisors were trained for two days. The main contents of the training were the following: the purpose of the study, data collection procedures, and data handling and storage. The pretest was conducted on 25 samples (5% of the total samples) of the questionnaire in Warder Hospital to ensure the validity of the tool, and the correction was made accordingly. The principal investigator and supervisors were monitored and supervised the data collection process. Data were checked for completeness and consistency, and any missed data or blank were sent back to the data collectors for correction. was conducted before data entry and analysis. The collected data were entered by two independent data clerks. Simple frequencies were run to check any missing values and outliers and crosschecked with hard copies of the questionnaire before further analysis.

Data processing and analysis

The collected data were cleaned, coded, and entered into Epidata version 3.1 and exported to SPSS version 22 (IBM SPSS Statistics, 2013) for further analysis. Descriptive statistics were computed using frequency tables, proportion, and summary measures. Bi-variable logistic regression analysis was carried out to identify the association between each independent variable and neonatal mortality. All variables having a p-value ≤ 0.25 in the bi-variable analysis were included in the final model of multivariable based on the assumption of selection criteria. Multi-collinearity was checked using variance inflation factor (VIF) and tolerance. Hosmer-Lemeshow goodness of fitness test was used to check for model fitness and the result was found to be insignificant (p-value = 0.501, R2 = 0.241) which indicates the model was fitted. The multivariable logistic regression analysis was performed to identify the true effects of the selected predictor variables on neonatal mortality. In the final model of multivariable logistic regression analysis, the adjusted odds ratio (AOR) with 95% confidence interval (CI) were computed to estimate the true effect of independent variables on the outcome variable. The level of statistical significance was declared at a p-value <0.05.

Ethical consideration and consent to participate

The ethical clearance was approved by the Institutional Health Research Review Committee (IHRRC) of the College of Medicine and Health Sciences, Jigjiga University (Ref.IHRRC0012/2020). Supportive letters were written to all three public Hospitals of the study sites. Hence, all data were previously anonymized, no informed consent was sought from the participants (mothers of neonates). Medical records of neonates who sought treatment from January 2018 to December 2019 were selected. These medical records of neonates were manually searched, and accessed from May 1st to 30th, 2020. Confidentiality of the patient information was assured by omitting their names and using card numbers instead.

Results

Socio-demographic characteristics of the study participants

A total of five hundred fourteen (514) charts of the neonates who were admitted to the NICU of selected public Hospitals were retrieved and five hundred ten (510) were successfully extracted making the response of 99%. Four charts were excluded from the analysis because of incompleteness and lack of pertinent information. The mean age of mothers of the neonates was 26.81 years (SD = ±6.226) ranged from 16 to 42 years. Four-hundred-fifty-two (88.8%) of the mothers’ neonates were from a rural setting. The mean age of neonates was 2.43days (± 4.019) and ranged from one day to twenty-seven days. More than two-thirds of the neonates (480, 94.1%) were aged 0-7days (

Maternal and neonatal related factors

The findings of this study revealed that more than half of the neonates 318(62.4%) were of normal birth weight of 2500-4000grams with a mean weight of 2909.22grams (SD = ±784.685) while around 161(31.6%) neonates were low birth weights (less than 2500gms). Concerning neonatal Apgar score, more than half of the neonates, 287(56.3%) had low Apgar scores (less than 7 scores), and more than two-thirds (64.7%) had neonatal sepsis. Around 213(41.8%) and 87(17.1%) of the neonates had a history of respiratory distress syndrome and birth asphyxia respectively. More than three-fourths of the neonates, 402(78.8%) were admitted within the first 24hoursrs (one day) and the majority, 455(89.2%) were term neonates (born between 37–42 weeks). Concerning maternal-related factors, a majority of the mothers were multipara 421(82.5%), and more than half, 275(53.9%) of them were not utilized antenatal care during current pregnancy and only 74(29.7%) of them had more than three ANC visits. The majority, 456(89.4%) of the neonates were delivered through spontaneous vaginal delivery (SVD) followed by operative delivery 54(10.6%). Regarding the place of delivery, a vast majority of the neonates, 478(93.7%) were given birth at health institutions (

The magnitude of neonatal mortality

In this study, the magnitude of neonatal deaths in selected public Hospitals in the Somali Regional State was found to be 18.6% [95%CI (15.3, 22.3)], equating to a rate of 186 deaths per 1000 live births. In contrast, of 510 neonates admitted to NICU of selected public Hospitals of the Somali Region who were enrolled in the study, four hundred fifteen neonates (81.4%) were discharged alive (

Factors associated with neonatal mortality

In bi-variable analysis, all predictor variables having a p-value ≤ 0.25 were entered in the final model of multivariable analysis. Thus, from all tested predictor variables lack of ANC follow-up [COR = 3.49, 95%CI (2.09, 5.85)], low Apgar score[COR = 2.04, 95%CI(1.22, 3.40)], preterm birth [COR = 4.42, 95%CI (2.45, 7.94)], neonatal sepsis [COR = 1.66, 95%CI (1.01, 2.74)] and birth asphyxia [COR = 1.88, 95%CI (1.10, 3.22)], birth weight of less 2500gm(COR = 4.10, 95%CI(2.53, 6.59)] were significantly associated with neonatal mortality (

In the final model of multivariable logistic regression analysis, predictor variables such as having no ANC follow-up, preterm birth, neonatal sepsis, and birth asphyxia, and low birth weight were remained statistically associated with neonatal mortality. Accordingly, the odds of neonatal mortality were 3.71 times higher among mothers who had no ANC follow-up during pregnancy compared to those neonates whose mothers had ANC follow-up during their current pregnancy[AOR = 3.71, 95%CI (2.13, 6.44)]. Preterm neonates (born before 37weeks) were 2.2 times more likely to die compared to term neonates (born after 37 weeks of pregnancy) [AOR = 2.20, (95%CI (1.02, 4.29)]. The odds of neonates who had sepsis were nearly two times [AOR = 1.84, 95%CI (1.07, 3.19)] have a higher risk of death compared to those who had not sepsis during the first month of life. Concerning birth asphyxia, those neonates who had a history of birth asphyxia were 2.41`times [AOR = 2.41, 95%CI (1.26, 4.43)] more likely to die compared to those who had not asphyxia at the time of birth. Finally, the odds of neonatal mortality were more than three times higher among neonates whose birth weight was less than 2500gm compared to normal birth weight [AOR = 3.40, 95%CI(1.92, 6.01)] (Table 4).

Table 4

Multivariable logistic regression analysis of factors associated with neonatal mortality among neonates admitted to NICU of selected public hospitals in Somali Regional State, Eastern Ethiopia, 2020.

Characteristics	Categories	Neonatal outcome		COR(CI = 95%)	AOR(CI = 95%)	P-values at AOR
		Not survivedN (%)	survivedN (%)
ANC follow up	Yes	22(9.4)	213(90.6)	1	1	-
	No	73(26.5)	202(73.5)	3.49(2.09,5.85)	3.71(2.13, 6.44)	0.0001
Birth weight	Low BW(<2500gm)	54(33.5)	107(66.5)	4.10(2.53, 6.59)	3.40(1.92, 6.01)	0.0001
	Normal BW (2500-4000gm)	35(11.0)	283(89.0)	1	1	-
	Macrosomia (>4000gm)	6(19.4)	25(80.6)	1.94(0.74, 5.06)	1.82(0.67, 4.94)	0.24
preterm birth	Yes	25(44.6)	31(55.4)	4.42(2.45,7.94)	2.20(1.02, 4.29)	0.04
	No	70(15.4)	384(84.6)	1	1	-
Respiratory distress	Yes	47(22.1)	166(77.9)	1.46(0.93,2.29)	1.32(0.79, 2.15)	0.30
	No	75(16.6)	377(83.4)	1	1	-
Neonatal sepsis	Yes	70(21.2)	260(78.8)	1.66(1.01,2.74)	1.84(1.07, 3.19)	0.03
	No	25(13.9)	155(86.1)	1	1	-
Apgar score	<7 score	65(22.6)	222(77.4)	2.04(1.22, 3.40)	1.54(0.87, 2.73)	0.140
	Unknown	6(18.8)	26(81.3)	1.61(0.60, 4.31)	1.26(0.42, 3.79)	0.68
	≥7 scores	30(13.5)	193(86.5)	1	1	-
Residence	Rural	75(16.6)	377(83.4)	0.35(1.45,4.79)	0.26(0.44, 2.07)	0.34
	Urban	21(35.1)	37(64.9)	1	1	-
Birth asphyxia	Yes	24(27.6)	63(72.4)	1.68 (0.97,2.91)	2.41(1.26, 4.43)	0.007
	No	71(16.8)	352(83.2)	1	1	-
Mode of delivery	SVD	81(17.8)	375(82.2)	1	1	-
	OD	14(25.9)	40(74.1)	0.61 (0.32,1.18)	1.61(0.77, 3.36)	0.20

Key: BW = Birth weight, SVD = Spontaneous Vaginal Delivery, OD = Operative Delivery, COR = Crude Odds Ratio, AOR = Adjusted Odds Ratio, 1 = Reference categories.

Discussion

In this study, the magnitude of neonatal mortality was 18.6% (equating to a rate of 186 deaths per 1000 live births). Besides, predictor variables like lack of ANC follow-up, prematurity, neonatal sepsis, birth asphyxia and low birth weight were identified as risk factors of neonatal mortality.

In this study, the proportion of neonatal is relatively comparable with previous studies conducted in Jigjiga Referral Hospital(20.5%) [31], Arba Minch General Hospital (20.2%) [39], Hawassa referral Hospital (16.5%) [15], a semi-urban Hospital in Cameroon (15.7%) [23], Democratic Republic of Congo (19.7%) [40], Ayder specialized hospital in northern Ethiopia (16.7%) [12], and Debre Markos referral Hospital in Northwest Ethiopia (21.3%) [41]. However, the current proportion of neonatal death was higher than studies conducted in different parts of the world such as Karamara General Hospital(5.7%) [22], Jimma Referral Hospital, southwest Ethiopia(13.3%) [14], Felege Hiwot referral Hospital, Northern Ethiopia (13.29%) [42], and Asmara city, Eritrea [13]. The possible justification for this discrepancy might be the difference in socio-demographic characteristics of the study participants. Moreover, health service accessibility and exposure to information might be lower in the former study population because the current study participants were from a highly marginalized pastoralist community in Eastern Ethiopia.

In contrast, the finding of this study is lower than the neonatal mortality reported in the Ashanti region of Ghana (51.8%) [43], Bench Maji Zone of South-West Ethiopia (22.8%) [44], and Hospital-based study in Egypt (58.8%) [45]. The difference is might be due to the methods of assessment and the difference in the sample size of the study. In addition, the difference in estimates might be attributed to the time gap between study periods, geographical setting of the study population. Another possible explanation is because currently the government is increasing the number of health extension workers in the rural community and introducing community health insurance programs that are motivating communities towards health services utilization.

In the final model of this study, we found that lack of ANC follow-up during pregnancy was significantly associated with neonatal mortality. Thus, those neonates whose mothers had no history of ANC follow-up during pregnancy were 3.71 times more likely to die compared to neonates born from mothers who had ANC follow-up during their pregnancy. This finding is consistent with several studies conducted in different parts of Ethiopia such as Debre-Marcos, Northern Ethiopia [41], and Hawassa Southern Ethiopia [15]. The possible explanation is because women who have not antenatal care follow-up during pregnancy are at risk of developing complications related to pregnancy and childbirth that can put the newborn at risk of death during the first month of life. In contrast, women with adequate antenatal care visits have a better chance of early detection and management of birth-related problems. This is also supported by the scientific finding of different kinds of literature that recommend ANC utilization is helpful in the identification of risk pregnancy, management of pregnancy-related complications, or prevention and treatment of concurrent diseases.

Likewise, early onset of neonatal sepsis was found to be an independent predictor of neonatal mortality. Thus, the odds of neonatal mortality were nearly two times higher among neonates who had early onset of neonatal sepsis compared to those who had not asepsis. This result is incongruent with the previous hospital-based studies conducted in the capital city of Addis Ababa, central Ethiopia [46], and Cameroon [23]. It is also supported by a previous research report from Kersa Demographic Health Surveillance site in Ethiopia [32] in which a higher proportion of neonatal deaths was observed among neonates admitted with sepsis. The possible explanation could be justified by those neonates who had sepsis in the neonatal period are at risk of dying in the first of month life because their immunity can be extensively affected by disease progress.

Moreover, in this study, neonatal birth-asphyxia was statistically associated with neonatal mortality. Thus, the odds of neonatal mortality were 2.41 times higher among neonates admitted with birth asphyxia compared to those neonates who were not asphyxiated. This result is also supported by a study conducted in Jimma, Northern Ethiopia which indicated higher odds of death among neonates who had birth asphyxia compared to their counterparts (those neonates had no asphyxia) [14]. Similar findings were also reported from two Hospitals (Gondar Hospital and Ayder referral Hospital) in Northern Ethiopia, in which a higher odds of neonatal deaths was reported in asphyxiated newborns [12,20]. The possible explanation might be because the difficulty of breathing at the time of birth can lead to neonatal hypoxia as a result, neonates can be died because of oxygen deficiency.

Furthermore, prematurity was also independently associated with neonatal mortality. Accordingly, the odds of neonatal deaths were more than two times higher among preterm babies compared to term neonates. This also is in line with studies conducted in a semi-urban Hospital in Cameroon [17] and Guadalajara of central Mexico [47]. The possible explanation is because preterm babies had suppressed immune systems and other body defense mechanisms so that they can easily be exposed and infected with a bacterial infection. In addition, unlike term babies, preterm neonates are also prone to develop respiratory distress syndrome because their lungs are not matured like that of term babies. Finally, low birth weight was also independently associated with neonatal mortality. Thus, the odds of neonatal deaths were 4.1 times higher among neonates whose birth weight was less than 2500gms compared to normal birth weight. This finding is also supported by studies conducted elsewhere [12,13], in which high proportion of neonatal deaths was observed in low birth weight babies. The possible reason is that low birth weight babies are at a greater risk of neonatal sepsis than normal birth weight newborns because they are highly susceptible to bacterial infections. In addition, small size babies are at increased risk of hypoglycemia because of poor feeding, and even, they can easily develop hypothermia because of their susceptibility to cold environments. All these can increase the risk of neonatal deaths in low birth weight babies.

Limitation of the study

Since we used a chart review cross-sectional study design, no causal association could have been made. The data were collected from a secondary source; some independent variables could have been missed. In addition, the study was conducted only in public health institutions; neonates who were admitted to private health facilities were not included in the study.

Conclusion

In conclusion, the magnitude of neonatal mortality was unacceptably high compared to national and global targets. Lack of ANC follow-up during pregnancy, neonatal sepsis, preterm births, birth asphyxia and low birth weights were positively and statistically associated with neonatal mortality. Therefore, this result calls for all stakeholders to give due consideration to mitigating this neonatal mortality, especially in the Pastoralist community. In addition, due attention should be given to low birth weight and premature babies. Healthcare providers and other stakeholders should also give more emphasis on early identification and management of birth asphyxia, and early onset of neonatal sepsis to reduce risks of neonatal deaths. Moreover, further studies such as longitudinal prospective studies are needed to identify the true effects of factors associated with neonatal mortality.

Dataset used for the analysis of Neonatal mortality (SPSS.data).

(SAV)

Click here for additional data file.

27 May 2021

PONE-D-21-13372

Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A two years’ retrospective Analysis

PLOS ONE

Dear Dr. Abdurke Kure

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

ACADEMIC EDITOR:

Your manuscript was reviewed by 3 experts in the field. The majority identified many important problems in your submission and provided copious comments.

Please revise the manuscript as per the reviewers' comments especially the  results section was difficult to follow.

Please consider the reviewers' comments and provide point-by-point responses.

Please upload the figures again.

We have noticed that you did not upload your data,  Plos one allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

Please submit your revised manuscript by  July 10 2021 11:59PM.  If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see:  http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at  https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Ammal Mokhtar Metwally, Ph.D (MD)

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study, including: a) whether all data were fully anonymized before you accessed them; b) the date range (month and year) during which patients' medical records were accessed; c) the date range (month and year) during which patients whose medical records were selected for this study sought treatment. If the ethics committee waived the need for informed consent, or patients provided informed written consent to have data from their medical records used in research, please include this information.

3. Thank you for stating the following in the Funding Section of your manuscript:

[ This study w as funded by Jigjiga University and the Ethiopian Ministry of Science and Higher Education. The funding organizations had no role in the study design, data collection, data analysis, and writing up of the manuscript. ]

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

[The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.]

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

4. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions.

In your revised cover letter, please address the following prompts:

a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent.

b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. Please see http://www.bmj.com/content/340/bmj.c181.long for guidelines on how to de-identify and prepare clinical data for publication. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories.

We will update your Data Availability statement on your behalf to reflect the information you provide.

5. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the opportunity to read your paper examining predictors and incidence of neonatal mortality in Eastern Ethiopia.

I read your paper with interest and think examining these cohorts, especially in the developing world, is important. Generally, I believe the conclusions are fair, albeit limited by the cross-sectional design.

My major comment is with respect to “Reviewer Question 4” which relates to clear, correct and unambiguous language, without typographical or grammatical errors.

Generally, given multiple errors in syntax & frequent repetition, the manuscript is difficult to read and as such the specifics around methodology are difficult to follow. There are multiple paragraphs of information that could readily be condensed into 2-3 sentences. I have included some of my feedback below, but this is not all-encompassing as these errors are present throughout the manuscript.

General comments:

1. A punchier title may be considered – perhaps revise to “Neonatal mortality and Associated Factors among Neonates Admitted to the Neonatal Intensive Care Unit in Eastern Ethiopia”.

2. In tables, precise p values should be stated instead of <0.25 or <0.05.

3. Figure 2 is likely unnecessary as it represents only a binary pie chart.

4. Generally, I’d suggest removing “died” and replacing with “mortality” where possible.

Introduction

5. Line 23: Insert “a” between “remains” and “public health challenge”

6. Line 25-26: Suggest replace sentence with “In comparison with countries demonstrating the lowest neonatal mortality, the risk of mortality is over 30 times higher in Sub-Saharan Africa”.

7. Line 35-36 can be simplified to “identify the effect of predictors on mortality”

8. Abstract results – suggest include p values

9. Line 52-53 in which year? 2017? Consider rewording

10. Line 63 – neonatal mortality in India and Pakistan not relevant given not in Africa. Listing rates in these countries is not necessary in this sentence. Also, is this intended to be 38 / 1000 live births, or 38% of neonatal admissions? The sentence reads as all-cause neonatal mortality.

11. Line 72 change declined to decline and clarify “but not met national target” as this doesn’t read well & doesn’t make sense here.

12. Line 83-90 from editorial point of view try to delete some of the “for instance” and “for example”

13. The introduction is overall a bit wordy and repetitious and could be shortened.

Methods

14. Need to define “Woredas” and “Kebeles” for international readers.

15. Line 109 – delete “and”

16. Line 114 – “woreda” is not capitalised as previously done.

17. Line 122 delete “and”

The methods are particularly difficult to follow given multiple typographical and grammatical errors. I have listed only a few of them above and would suggest a thorough proof reading and rephrasing in many places for clarity.

Results

18. Line 242 – replace “in” with of”

19. Again multiple typographical errors (including above) which should be proof read and corrected.

Discussion

The discussion revolves primarily around comparisons with mortality in other regions and countries. Line 289 – 315 is entirely dedicated to comparator cohorts, of which > 10 are listed. Consider abbreviating this list and condensing this to one paragraph discussing similar cohorts.

Minor comments:

20. Line 294 – How is Turkey relevant here? Suggest removing.

21. Line 301-302 remove the assertion regarding difference due to time of the study and sample size as this is stated in the following sentence anyway.

22. Line 351 delete “Strengths of the study” and “Limitation of the study”. This section needs revising. Standardised checklists and questionnaires are not necessarily a strength.

23. Lines 352-354 is poorly worded.

Conclusion

Conclusions are appropriate but again need to be reworded for simplicity.

While I think the results of this study are interesting and relevant to both the scientific community in Ethiopia and the international community, this paper requires major revision, primarily from a language point of view to reduce repetition, simplify the methodology for the reader, and reduce the burden of language errors.

Reviewer #2: The authors studied predictors of neonatal mortality in 3 public hospitals in the Somali region, Eastern Ethiopia. The research is original, it was the first in this region which is mainly a rural area. The data presented supported the conclusion and fitted with the study objective. The sample size was calculated appropriately, the sample was randomly selected and the satatistical analysis were rigorously performed. The results were properly discussed and the limitations of the study were mentioned.

However, I have some suggestions to improve the manuscripts :

1. There are some grammer and spelling mistakes

2. The p-value of the Hosmer-Lemeshow goodness of fitness test is a result and should be included with the table of the final model in the results section with the determination coefficient R2.

3. I suggest to present the final model only of the multivariable regression with the goodness of fit criteria.

Reviewer #3: The article provides a very nice picture on neonatal mortality and relevant risk factors for neonatal mortality in Ethiopia. It is worthwhile to be published. However, the article is not written carefully, abbreviations are not introduced, and country specific situation are not explained for an international readership and one citation is misleading.

General remarks:

Abbreviation need to be introduced once when used first time, and then this abbreviation shall be used through the whole text. I believe NMR is introduce three times, however ANC, NM, and NICU is not explained at all. Due to the tremendous use of abbreviation, I also suggest providing an abbreviation list where all abbreviations are explained. Please check the correct use of all abbreviation in the text.

Introduction:

The introduction explains the importance of the research question and uses relevant literature. However, the rates from neonatal mortality seems to be wrong, (line 61 ff: information of neonatal mortality is normally given in number per 1000 and not in %; the relevant cited source is connected to under 5 years mortality which does not make sense in this context; and the numbers are not repeatable. Please correct these numbers and cite a correct source.

Furthermore, I suggest introducing shortly the Apgar-score as well as ANC and ANC follow up in the introduction. You cannot expect that the international readership knows this words/abbreviations.

Method:

In the study population sample size, data collection and data analysis are presented carefully. However, the sample size calculation can be presented more condensed. And the coding of neonatal mortality can be dropped from the explanation.

Furthermore, under analysis it was mentioned that collinearity analysis was done, but the results were not presented. I expect a high collinearity between apgar-score and asphyxia (which is defined via apgar score) and ANC follow up and No of ANC-visits. Therefore, the results are important to present.

Result:

Result presentation is nice and carefully done.

As small remark to some tables:

• Table 2:, I suggest to present for binary variables only one line. If you know that 8.6 (n=44) have Hypothermia, then it is implicitly given that the rest do not have hyperthermia this line can be dropped from the table. However, that is relevant only for binary/dichotomous variables. On the other hand, there is one variable (number of ANC visits) which is not dichotomous/binary, but only presented in this form, clarification is necessary.

• Table 4: significant results are only marked under AOR but not under COR. Please add this. Furthermore, both abbreviations need to be introduced under the table.

• Figure 1. The arrow text line “Simple random sampling (SRS)” can be dropped. The line above contains 196+178+140 which gives exactly 514. No random sampling took place at this stage of sampling procedure.

• Figure 2 can be deleted, The results of this figure can be added in table 2

Discussion:

The discussion is nicely done, good work.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Hedia Bellali

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

20 Jul 2021

Authors’ Response to the editor’s and Reviewers’ comments and Suggestions

Manuscript ID: PONE-D-21-13372

Journal: PLOS ONE

Dear Editors and Reviewers,

Thank you so much for giving us an opportunity to submit a revised draft of our manuscript entitled “Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A two years’ retrospective Analysis” to this high visibility impact factor and peer reviewed Journal. We appreciate the time and effort that you and the reviewers dedicated to providing feedback on our manuscript. We are very grateful for the insightful comments and valuable improvements to our premature paper. We have incorporated most of the suggestions and comments made by handling editor, and reviewers. All comments and suggestions forwarded by Editor and reviewers were clearly stated and well addressed (a point-by-point to the Editor's and reviewers' comments and concerns) in the separated letter of "Response to Reviewers". All newly changes were highlighted in Red font color within the clean revised manuscript. Thank for your countless effort.

Authors’ Response to Editor’s Comments and Suggestions:

Title: Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A two years’ retrospective Analysis

Authors: 1.Hamda Ahmed Mohamed(First author),

2.Zemenu Shiferaw (Co-author),

3.Abdurahman Kedir Roble(Co-author)

4.Mohammed Abdurke Kure(Co-author & Corresponding author)

To: Handling Editor(s)

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

First, we thank you for your constructive comments and helpful suggestions that helped us to improve and enrich our manuscript. Here under in the table below, we have pointed out how authors incorporated your valuable comments, suggestions and concerns one by one.

1.Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

AUTHORS' RESPONSE:

Great! We are very happy and overjoyed. Thank you very much for giving us an opportunity to submit our revised manuscript to such legitimate and high visibility impact factor Journal (PLOS ONE).

2.Your manuscript was reviewed by 3 experts in the field. The majority identified many important problems in your submission and provided copious comments. Please revise the manuscript as per the reviewers' comments especially the results section was difficult to follow.

AUTHORS' RESPONSE:

Ok, accepted with thanks. We appreciate the time and effort that you and the reviewers dedicated to providing feedback on our manuscript.

3.Please consider the reviewers' comments and provide point-by-point responses.

AUTHORS' RESPONSE:

Thanks a lot. Dear editor, the authors critically reviewed all comments and suggestions raised during review process and corrected all necessary modifications. The newly modified change were highlighted with red font color in the clean revised main manuscript.

4.We have noticed that you did not upload your data, Plos one allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly.

AUTHORS' RESPONSE:

Ok, great! No legal restrictions for our data set. We decided to upload all data sets used for analysis in this study without any restrictions. Thanks a lot!

Academic Editor’s Specific Comments (Journal Requirements)

5.Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found athttps://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

AUTHORS' RESPONSE:

Thank you so much. You are perfect. These are very important comments. Even it is the authors mandatory to stick to Journal’s format guidelines. Now, the authors addressed this critical issues based on your valuable suggestion. We downloaded all formats templates (PLOS Affiliations Formatting and Manuscript body formatting guidelines) from Journal’s Website, and critically read and corrected all necessary formatting. Newly changed and corrected were highlighted with red font color in the clean revised manuscript.

6.In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records used in your retrospective study.

AUTHORS' RESPONSE:

Thanks. You are perfect. This valid comment was addressed based on your valuable suggestion. Newly changed and corrected was highlighted with red font color in the clean revised manuscript (on page11, Lines=226-232)

7.Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement.

AUTHORS' RESPONSE:

Ok, thanks. The editor is correct. We are very sorry; this is against PLOS ONE authors’ guideline. The authors critically reviewed this valid comment and corrected the necessary modification. The newly modified change was highlighted with red font color in the clean revised manuscript

8.If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files. We will update your data availability statement on your behalf to reflect the information you provide.

AUTHORS' RESPONSE:

Thank you very much. In fact, this is a valid concern. We critically considered this point, and we decided to upload data set used for analysis, and we aploaded it as supplementary File(S1)

9.Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

AUTHORS' RESPONSE:

Thank you a lot for such a technical input. Now, authors considered the raised issue. After thoroughly and critically revised this important comment, we removed from previously it appeared in Acknowledgment part. Thanks!

End of authors’ responses for Handling Editor(s)

Authors’ Response to Reviewer 1’s Comments and Suggestions:

Title: Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A two years’ retrospective Analysis

Authors: 1.Hamda Ahmed Mohamed(First author),

2.Zemenu Shiferaw (Co-author),

3.Abdurahman Kedir Roble(Co-author)

4.Mohammed Abdurke Kure(Co-author & Corresponding author)

To: Reviewer 1

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

First and foremost, we would like to thank you for your constructive and valuable comments and helpful suggestions that helped us to improve and enrich our premature manuscript. Here under in the table we have pointed out how authors incorporated your valuable comments, suggestions and concerns one by one.

5. Specific Review’s Comments to the Authors

1.Reviewer #1: Thank you for the opportunity to read your paper examining predictors and incidence of neonatal mortality in Eastern Ethiopia.

Authors' Response: Thank you very much for countless effort to review our premature manuscript.

2.I read your paper with interest and think examining these cohorts, especially in the developing world, is important. Generally, I believe the conclusions are fair, albeit limited by the cross-sectional design

Authors' Response:

Great! Thanks a lot. You are perfect. In the cross-sectional study design, the researchers cannot draw a conclusion of cause-effect relationship, thanks.

3.My major comment is with respect to “Reviewer Question 4” which relates to clear, correct and unambiguous language, without typographical or grammatical errors.

Authors' Response:

Thank you so much. Authors critically considered this input. Authors acknowledged your efforts. We critically considered and incorporated all raised issues, comments, suggestions and concerns in this manuscript. Moreover, we thoroughly revised and edited the whole parts of our manuscript and extensively corrected all copy-editing errors in the clean revised manuscript. Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

4.Generally, given multiple errors in syntax & frequent repetition, the manuscript is difficult to read and as such the specifics around methodology are difficult to follow.

Authors' Response:

Thank very much. The reviewer is perfect. At initial submission, the manuscript was not written in concise manner. We critically considered this point. We took a long time, thoroughly and extensively revised and edited the whole manuscript both technically and editorially. The document was also arranged and organized as per journal template. Even we removed all previously written non-sense paragraphs and sentences and replace them with new texts both in ‘Introduction’ part and ‘Methods’ part. The newly modified change were highlighted with red font color in the clean revised manuscript.

5.There are multiple paragraphs of information that could readily be condensed into 2-3 sentences. I have included some of my feedback below, but this is not all-encompassing as these errors are present throughout the manuscript.

Authors' Response:

Thank you a lot. We appreciated your observation. We considered your deep concern and explicitly incorporated your input both technically and editorially. The document was newly arranged and organized, even we removed all previously written non-sense paragraphs and sentences, clauses and poorly worded text and replaced them with new texts both in ‘Introduction’ part and ‘Methods’ part. The newly modified change were highlighted with red font color in the clean revised manuscript.

6. A punchier title may be considered – perhaps revise to “Neonatal mortality and Associated Factors among Neonates Admitted to the Neonatal Intensive Care Unit in Eastern Ethiopia”.

Authors' Response:

Dear, reviewer, thank you very much. The authors could not understand this suggestion. Do you mean to modify the title of the paper?

7.In tables, precise p values should be stated instead of <0.25 or <0.05

Authors Response:

Ok! Thank you reviewer. We really appreciate this valid observation. Is it better to put both p-values and ORs simultaneously? But currently, many researchers recommend only ORs instead of using both estimators simultaneously. Anyways, we incorporate this important suggestion based on your recommendation in the tables of bi-variable and multivariable analysis.

8.Figure 2 is likely unnecessary as it represents only a binary pie chart.

Authors' Response:

Thank you very much. In fact, this is a valid concern. We critically considered this important suggestion, and removed previously appeared binary chart, and web substitute it with bar-chart because it is the most appropriate graphical representation for this binary outcome.

9.Generally, I’d suggest removing “died” and replacing with “mortality” where possible.

Authors' Response:

Exactly! Thanks. It is not good to use the word “died” to indicate mortality. Based on this important suggestion, we made necessary changes throughout the whole document where possible!

INTRODUCTION

10.Line 23: Insert “a” between “remains” and “public health challenge”

Authors Response:

Thank you so much. This was grammatical error. We corrected this on page 2, line 41 of the main manuscript based on your recommendation.

11.Line 25-26: Suggest replace sentence with “In comparison with countries demonstrating the lowest neonatal mortality, the risk of mortality is over 30 times higher in Sub-Saharan Africa”.

Authors Response:

Thank you very much. The reviewer is correct. We considered this valid concern. Authors carefully considered your valid comments and modified based on your insightful suggestion on page 2, line 24-25

12.Line 35-36 can be simplified to “identify the effect of predictors on mortality”

Authors Response:

Thank you a lot. We appreciated your observation. Now authors considered your valid concern and explicitly incorporated your input in the clean revised manuscript and highlighted with red font color.

13.Abstract results – suggest include p values

Authors Response:

Thank a lot. Dear editor, we appreciate your valid suggestion. Is it better to put both p-values and ORs simultaneously in the abstract? Most of Biomedical researchers recommend AOR with CIs,(AOR, 95%CI). In previous comment, we incorporate p-value in the tables of bi-variable and multivariable analysis. However, here if add p-value with AOR and 95%CIs, the abstract may become bulk and distorted. Abstract should be short and concise.

14.Line 52-53 in which year? 2017? Consider rewording

Authors Response:

Definitely! Thank you so much. This important comment was modified and highlighted with red font color in the clean revised main manuscript. Thanks.

15.Line 63 – neonatal mortality in India and Pakistan not relevant given not in Africa. Listing rates in these countries is not necessary in this sentence. Also, is this intended to be 38 / 1000 live births, or 38% of neonatal admissions? The sentence reads as all-cause neonatal mortality.

Authors' Responses:

OK! Thank you. Here we found 2 important comments. First. Neonata Mortality in Indian and Pakistan: Exactly, you are perfect. We are very sorry! This was unintentionally introduced error during first draft. Actually, the paragraph started with indicating both Africa and Asian regions. However, “Asia” was missed unintentionally. This was editorial error. Now, we corrected this comment on page 3, line 59-60. Thank you!

Second: NMR should be per 1000 live births. The reviewer is correct. What you are suggesting is the standards. We appreciate this valid observation. Normally, Neonatal mortality can expressed 1000 per live births Rate (NMR=per 1000 live births). However, in small-scale research, we can estimate neonatal death in “magnitude” or “proportion” to show the prevalence. Based on your recommendation, we corrected this valid comment, and corrected on page 3, line 61-66.

16.Line 72 change declined to decline and clarify “but not met national target” as this does not read well & doesn’t make sense here.

Authors Response:

Thank you a lot. We appreciated your observation. Now authors considered your valid concern and explicitly incorporated your input in the clean revised manuscript and highlighted with red font color.

17.Line 83-90 from editorial point of view try to delete some of the “for instance” and “for example”

Authors' Response:

Thank you a lot. We appreciated your observation. Now authors considered your valid concern and explicitly incorporated your input in the clean revised manuscript and highlighted with red font color.

18.The introduction is overall a bit wordy and repetitious and could be shortened

Authors Response:

Great! Thank very much. We have corrected and rephrased based on your recommendation. Even the authors explicitly and critically reviewed this valid comment and rewrote. The previous bulk paragraphs were removed and organized in concise manner. We highlighted the change in red font in the main clean revised manuscript.

METHODS

19.Need to define “Woredas” and “Kebeles” for international readers.

Authors' Response:

Thanks. Thank you a lot for such technical input. This lacks standards, and difficult to understand by scientific community. We made the correction accordingly. (Woreda=District, Kebeles=The smallest administrative unit in Ethiopia. Thank you very much!

20.Line=109–delete“and”

Authors Response:

Great, thanks a lot. This was editorial error, and we corrected this on page 5, line 106-108 in the clean revised manuscript.

21.Line 114 – “woreda” is not capitalised as previously done.

Authors Responses:

Thank you. The authors have corrected such a language and editing errors. We corrected this grammatical based your insightful comment error here and elsewhere in the clean revised manuscript.

22.. Line 122 delete “and”

Authors Response:

Thank you so much. This was editorial and grammatical error. We corrected this on page 5, lines 124-126.

23.The methods are particularly difficult to follow given multiple typographical and grammatical errors. I have listed only a few of them above and would suggest a thorough proof reading and rephrasing in many places for clarity.

Authors Response:

Thank you a lot for such a technical input. You are perfect. Previously, there were bulky paragraphs and sentences in the methods part of this manuscript. Now, the authors considered the raised issue. After thoroughly and critically revised this important comment, we removed all previous bulky texts and long paragraphs/sentences and replaced it with newly corrected one, and all changes were highlighted with red font color in the clean revised manuscript from page 5-9.

RESULTS

24.Line 242 – replace “in” with of”

Authors Response:

Important, Thank you. We have corrected these unnecessary editing errors based on your valuable recommendations and suggestions.

25.Again multiple typographical errors (including above) which should be proof read and corrected.

Authors Responses:

Great! Thanks a lot for such implicit and critical review for our premature paper. We are very sorry for such unnecessary full of editorial errors for the whole manuscript. Authors critically considered this input. Now, we thoroughly revised and edited the whole parts of our manuscript and extensively corrected all copy-editing errors in the clean revised manuscript. Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

Important, Thank you. We have corrected these unnecessary editing errors based on your valuable recommendations and suggestions.

DISCUSSION

26.The discussion revolves primarily around comparisons with mortality in other regions and countries. Line 289 – 315 is entirely dedicated to comparator cohorts, of which > 10 are listed. Consider abbreviating this list and condensing this to one paragraph discussing similar cohorts.

Authors' Response:

Thank you so much. We appreciated your observation. The authors critically reviewed this important comment. We condensed and shortened previously bulky long paragraphs based on your valuable suggestions.

27.Line 294 – How is Turkey relevant here? Suggest removing.

AUTHORS' RESPONSE:

Thank you very much. In fact, this is a valid concern. We critically considered this point, and modified accordingly.

28.Line 301-302 remove the assertion regarding difference due to time of the study and sample size as this is stated in the following sentence anyway.

Authors' Response:

Thanks a lot. You are perfect. This valid comment was incorporated based on your valuable suggestion. Newly changed and corrected was highlighted with Red font color in the Clean revised manuscript.

29.Line 351 delete “Strengths of the study” and “Limitation of the study”. This section needs revising. Standardized+ checklists and questionnaires are not necessarily a strength.

Authors' Response:

Thank you again. You are correct. This is editorial errors and Technical errors. We have corrected this valid concern based on your important implicit suggestion. We delete unnecessary text and highlighted with red font color in the clean revised manuscript.

30.Lines 352-354 is poorly worded.

Authors Response:

Great, Thank you so much. Very appreciable comment and suggestion. We have corrected these unnecessary poorly worded following your insightful recommendations and suggestions.

CONCLUSION

31.Conclusions are appropriate but again need to be reworded for simplicity.While I think the results of this study are interesting and relevant to both the scientific community in Ethiopia and the international community, this paper requires major revision, primarily from a language point of view to reduce repetition, simplify the methodology for the reader, and reduce the burden of language errors.

Authors Response:

Thank you very much for such valuable intellectual input. Authors critically considered this input. Now, we thoroughly revised and edited the whole parts of our manuscript and extensively corrected all copy-editing errors in the clean revised manuscript. Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

NB: New notification for reviewer 1

Dear, reviewer, thank you very much for your countless effort. Finally, we kindly notify you that during revision of our manuscript, we revised the final model of multivariable analysis and we checked one predictor variable (Birth weight of newborn). The BW was categorized as:

1.LBW= less than 2500mg , 2.Normal BW= 2500-4000mg

3.Macrosomia: >4000mg. In SPSS analysis, initially we used the “Macrosomia” as Ref. category, and no significant association was found in multivariable analysis. However, in current revision, the authors critically revise this issue and shifted/substituted the previous Ref. category (>4000mg) to “Normal BW(2500-400mg)”, considering the remaining two categories as exposure. As a result, LBW becomes significant predictor of Neonatal mortality. For further details, we submitted SPSS data used for analysis to the Journal as Supplementary File 1(S1). We highlighted newly modified changes with red font color in the Table 3 and 4, and elsewhere in the text. Thank you very much for your time and consideration.

End of authors responses for Reviewer 1

Authors’ Response to Reviewer 2’s Comments and Suggestions:

Title: Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A two years’ retrospective Analysis

Authors: 1.Hamda Ahmed Mohamed(First author),

2.Zemenu Shiferaw (Co-author),

3.Abdurahman Kedir Roble(Co-author)

4.Mohammed Abdurke Kure(Co-author & Corresponding author)

To: Reviewer 2

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

First and foremost, we would like to acknowledge you for your constructive and valuable comments and helpful suggestions that helped us to improve and enrich our manuscript. Here under in the table we have pointed out how authors incorporated your valuable comments, suggestions and concerns one by one.

1.Reviewer #2: The authors studied predictors of neonatal mortality in 3 public hospitals in the Somali region, Eastern Ethiopia. The research is original; it was the first in this region, which is mainly a rural area. The data presented supported the conclusion and fitted with the study objective. The sample size was calculated appropriately, the sample was randomly selected and the satatistical analysis were rigorously performed. The results were properly discussed and the limitations of the study were mentioned.

Authors Response:

Thank you very much. We would like to thank you for your appreciation and constructive suggestion. Further, we revised and enriched the paper after previous initial submission to the journal.

2.Reviewer #2 However, I have some suggestions to improve the manuscripts :

Authors Response:

Thank you a lot. We accepted all your valid suggestion and concern in this paper, and correct accordingly.

3.There are some grammar and spelling mistakes

Authors' Response:

Thank you so much. Authors critically considered this input. Now, we thoroughly revised and edited the whole parts of our manuscript and extensively corrected all copy-editing errors in the clean revised manuscript. Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

4.The p-value of the Hosmer-Lemeshow goodness of fitness test is a result and should be included with the table of the final model in the results section with the determination coefficient R2.

Authors Response:

Ok, thanks! We really appreciate this valid suggestion. Dear reviewer, is it better to put H-L goodness of fitness test result and R2 in Final model of Multivariable analysis? Where do we put this result in table? Do we create its own column? Most of biomedical researchers put the results of H-L goodness test, VIF and tolerance in methods part. Anyways, we incorporate this important suggestion in the clean revised manuscript in the method part.

5. I suggest to present the final model only of the multivariable regression with the goodness of fit criteria.

Authors' Response:

Ok! Thank you so much, reviewer. We also put this for only multivariable logistic regression analysis.

NB: New Notification for Reviewer 2

Dear, reviewer, thank you very much for your countless effort. Finally, we kindly notify you that during revision of our manuscript, we revised the final model of multivariable analysis and we checked one predictor variable (Birth weight of newborn). The BW was categorized as:

1.LBW= less than 2500mg , 2.Normal BW= 2500-4000mg

3.Macrosomia: >4000mg. In SPSS analysis, initially we used the “Macrosomia” as Ref. category, and no significant association was found in multivariable analysis. However, in current revision, the authors critically revise this issue and shifted/substituted the previous Ref. category (>4000mg) to “Normal BW(2500-400mg)”, considering the remaining two categories as exposure. As a result, LBW becomes significant predictor of Neonatal mortality. For further details, we submitted SPSS data used for analysis to the Journal as Supplementary File 1(S1). We highlighted newly modified changes with red font color in the Table 3 and 4, and elsewhere in the text. Thank you very much for your time and consideration

End of authors responses to Reviewer 2!!!

Authors’ Response to Reviewer 3’s Comments and Suggestions:

Title: Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A two years’ retrospective Analysis

Authors: 1. Hamda Ahmed Mohamed(First author),

2. Zemenu Shiferaw (Co-author),

3. Abdurahman Kedir Roble(Co-author)

4. Mohammed Abdurke Kure(Co-author & Corresponding author)

To: Reviewer 3

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

First and foremost, we would like to thank you for your insightful comments and helpful suggestions that helped us to improve and enrich our manuscript. Here under in the table we have pointed out how authors incorporated your valuable comments, suggestions and concerns one by one.

1.Reviewer #3: The article provides a very nice picture on neonatal mortality and relevant risk factors for neonatal mortality in Ethiopia. It is worthwhile to be published. However, the article is not written carefully, abbreviations are not introduced, and country specific situation are not explained for an international readership and one citation is misleading.

Authors' Response:

Great, Thank you so much. Very appreciable comment and suggestion. Authors acknowledge for your constructive suggestions!

2.Abbreviation need to be introduced once when used first time, and then this abbreviation shall be used through the whole text. I believe NMR is introduce three times, however ANC, NM, and NICU is not explained at all. Due to the tremendous use of abbreviation, I also suggest providing an abbreviation list where all abbreviations are explained. Please check the correct use of all abbreviation in the text.

Authors' Response:

Thanks a lot. You are perfect. These are very important observation. These valid comments and suggestions were addressed based on your insightful suggestion in the introduction part and elsewhere. All abbreviations/Acronyms (appear at least 3 or more in the document) were critically revised and corrected based on your valuable suggestions. Newly changed and corrected were highlighted with red font color in the clean revised manuscript.

INTRODUCTION

3.-The introduction explains the importance of the research question and uses relevant literature. However, the rates from neonatal mortality seems to be wrong, (line 61 ff: information of neonatal mortality is normally given in number per 1000 and not in %; the relevant cited source is connected to under 5 years mortality which does not make sense in this context; and the numbers are not repeatable. Please correct these numbers and cite a correct source.

Authors' Response:

Thank you so much. The reviewer is correct. We considered this valid concern. Authors carefully considered these important comments. We took a long time and extensively reviewed, edited and revised these bolded technical errors. Here we found 2 important comments.

1.NMR: You are perfect. What you are suggesting is the standards. NMR should be per 1000 live births. The reviewer is correct. What you are suggesting is the standards. We appreciate this valid observation. Normally, Neonatal mortality can expressed 1000 per live births Rate (NMR=per 1000 live births). However, some times, in small-scale research, we can estimate these neonatal death in “magnitude” or “proportion” to show the prevalence. Based on your recommendation, we corrected this valid comment, and corrected on page 3, line 61-64.

2. Incorrect citation: Thanks a lot. Dear reviewer, we are very sorry! This misused citation was unintentionally introduced during manuscript drafting. Now, we critically considered, and revised our endnote library to solve the issues. The newly modified changes were highlighted with red font color in the clean revised main manuscript.

4.-Furthermore, I suggest introducing shortly the Apgar-score as well as ANC and ANC follow up in the introduction. You cannot expect that the international readership knows this words/abbreviations.

Authors' response:

Thank you a lot. We appreciated your valid observation. Now authors considered your valid concern and explicitly incorporated your input in the operational definition (in the methods) (APGAR Score, ANC and ANC follow up) and the newly modified changes were highlighted with red font color in the clean revised manuscript.

METHODS

5.-In the study population sample size, data collection and data analysis are presented carefully. However, the sample size calculation can be presented more condensed. And the coding of neonatal mortality can be dropped from the explanation.

AUTHORS' RESPONSE:

Thank you a lot for such a technical input. Now, authors considered the raised issue. After thoroughly and critically revised this important comment, we removed previous bulky and long sentence and replaced with newly corrected one.

6.Furthermore, under analysis it was mentioned that collinearity analysis was done, but the results were not presented. I expect a high collinearity between apgar-score and asphyxia (which is defined via apgar score) and ANC follow up and No of ANC-visits. Therefore, the results are important to present.

AUTHORS' RESPONSE:

Great, thanks a lot for such important intellectual input. These are very critical and concerns issues in the final models of multivariable analysis. Dear, reviewer, really we appreciate your insightful and logical input. You are perfect. Usually we expect similar predictor variables to have collinearity effect(highly correlation). For example,( primiparity Vs multiparity, Apga score Vs Birth asphyxia, Grand multipara Vs Advance maternal etc..). However, in our case, we didn’t encounter any collinearity effect between “Apgar score” and “Birth asphyxia” in using both VIF and Tolerance. All VIF results were less than 5 and All tolerance results were greater than 0.1. For instance, in our case=

1.Apgar score (VIF= 1.44, Tolerance=0.70), 2.Ashyxia(VIF= 1.024, Tolerance=0.97)

3.ANC follow(VIF=1.012, Tolerance=0.98)

7.Result presentation is nice and carefully done.

Authors response:

Thank you so much. Authors greatly acknowledge for your countless effort.

8.Table 2: I suggest to present for binary variables only one line. If you know that 8.6 (n=44) have Hypothermia, then it is implicitly given that the rest do not have hyperthermia this line can be dropped from the table. However, that is relevant only for binary/dichotomous variables.

AUTHORS' RESPONSE:

Great, Thanks a lot for such implicit and critical review for our premature paper. Dear reviewer, you are perfect. We really appreciate this valid observation. However, in our case, the questionnaire/tool was prepared in binary response to assess neonatal conditions(Yes or No). Here, our intention is assess presence or absence of hypothermia. Thus. we prepared questions for hypothermia as: Does the neonate have Hypothermia at admission? 1. Yes 2. No, However, there was no question to assess hyperthermia. Thank a lot for your insightful suggestion and recommendation.

9.On the other hand, there is one variable (number of ANC visits) which is not dichotomous/binary, but only presented in this form, clarification is necessary.

AUTHORS' RESPONSE:

Thanks a lot. Number of ANC visits were presented in Table 2 as 1. 1-3 visits, 2.>3visits….However, we didn’t consider it for regression analysis, instead we selected Presence or absence of ANC follow up. Actually, this is very important concern.

10.Table 4: significant results are only marked under AOR but not under COR. Please add this. Furthermore, both abbreviations need to be introduced under the table.

AUTHORS' RESPONSE:

Thanks a lot. You are perfect. These are very important observation. These valid comments and suggestions were addressed based on your insightful suggestion in both tables 3 and 4.

11.Figure 1. The arrow text line “Simple random sampling (SRS)” can be dropped. The line above contains 196+178+140 which gives exactly 514. No random sampling took place at this stage of sampling procedure.

AUTHORS' RESPONSE:

Thank you very much. In fact, this is a valid concern. We critically considered this point, and dropped arrow text line from fig1 based on your valid suggestion. Thank you.

12.Figure 2: Can be deleted, The results of this figure can be added in table 2

AUTHORS' RESPONSE:

Great! Thanks a lot. Since it is pie-chat, the binary outcome is not suitable for this figure. Thank you for this intellectual input. Based on your insightful suggestion and your co-reviewers, we modified this figure from previous pie-chart to simple bar-chat. Since it is the major finding of our study, All authors critically discussed on this issue, and decided to change the figure 2 to simple bar-chart for simplicity of the readers(for easily capturing of the magnitude of NM).

13.The discussion is nicely done, good work.

AUTHORS' RESPONSE:

Thank you so much. Authors acknowledged you for your countless effort to review our paper.

NB: New notification for Reviewer 3

Dear, reviewer, thank you very much for your countless effort. Finally, we kindly notify you that during revision of our manuscript, we revised the final model of multivariable analysis and we checked one predictor variable (Birth weight of newborn). The BW was categorized as:

1.LBW= less than 2500mg , 2.Normal BW= 2500-4000mg

3.Macrosomia: >4000mg. In SPSS analysis, initially we used the “Macrosomia” as Ref. category, and no significant association was found in multivariable analysis. However, in current revision, the authors critically revise this issue and shifted/substituted the previous Ref. category (>4000mg) to “Normal BW(2500-400mg)”, considering the remaining two categories as exposure. As a result, LBW becomes significant predictor of Neonatal mortality. For further details, we submitted SPSS data used for analysis to the Journal as Supplementary File 1(S1). We highlighted newly modified changes with red font color in the Table 3 and 4, and elsewhere in the text. Thank you very much for your time and consideration.

End of authors’ responses to Reviewer 3

Submitted filename: 2.Response to reviewers.docx

Click here for additional data file.

18 Oct 2021

In lines 55-60, there is some overlap with http://www.kma.org.kw/uploads/versions/EEQGAXUUOAQIGLDPHVORFANO.pdf (pages113-114)

In lines 81-85 there is some overlap with https://documents1.worldbank.org/curated/en/384721537219780286/pdf/129971-AR-PUBLIC-UN-IGME-Child-Mortality-Report-2018.pdf?fbclid=IwAR2X1_3wyyZFl_v1-6yrBvZgIM0jMjnw4cJL4JxRBou8XV_eJfo2oGOyg20 (page 12)

Please review the entire manuscript, especially the abovementioned sections to ensure that you rephrase any duplicated text and cite your sources in full. In addition, please review the manuscript again to check for any remaining typographical and grammatical errors, particularly in the Abstract.

Thank you for your attention to these requests.

Please submit your revised manuscript by Nov 29 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

23 Oct 2021

Authors’ response to the editor’s minor comments and suggestions:

• Manuscript ID: PONE-D-21-13372

• MS title: Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A multicenter retrospective Analysis

• Authors: Hamda Ahmed Mohamed1, Zemenu Shiferaw2, Abdurahman Kedir Roble3, Mohammed Abdurke Kure4

• Journal’s name: PLOS ONE

• Date: October 20, 2021

Dear editor(s), your Excellency!

First and foremost, we would like to thank PLOS ONE Journal’s editorial office for giving us an opportunity to submit a revised draft of our manuscript entitled “Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A multicenter retrospective Analysis” to this high visibility impact factor and peer reviewed Journal. We appreciate the time and effort that you and the reviewers dedicated to providing feedback on our manuscript. We are also very grateful for the insightful comments and suggestions to our paper. We have incorporated minor comments made by handling editor. Newly modified changes were highlighted in red font color in the specific part of the revised manuscript.

Subject: Authors’ Response to Specific Comments and Suggestion of Academic Editor

To: Handling Editor(s)

From: Mohammed Abdurke Kure (Corresponding Author)

Above all, authors thank you for your insightful constructive comments and suggestions that helped us to improve and enrich our manuscript to this status. Next, here in the table below, we tried to address your valuable comments, suggestions and concerns one by one.

Editor’s Comments and suggestion to the Authors

Editor’s General Comments and Suggestions

Authors’ Responses: Overall, thank you so much for your cooperation to handle our manuscript. Handling paper is really needs dedication and strong commitment. Thanks a lot!

1.Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Authors’ Responses: Great! We are very grateful for the entire editorial office in general, and respective editorial team in particular.

• Further, above all, we would like to extend our deepest appreciation to the handling academic editor, for the time and countless effort that she/he dedicated to handle our paper as academic editor (handling editor). We understand that handling paper is really needs dedication and strong commitment.

• Finally, authors thank you for giving us an opportunity to submit our revised manuscript to such legitimate and high visibility impact factor Journal (PLOS ONE).

2. Thank you for your response to the reviewer comments. The reviewers consider the manuscript to be much improved. However, some additional editorial concerns must be addressed before the manuscript can be considered for publication.

Authors’ Responses: Ok, we accepted with thanks. We appreciate the time and effort that you and the reviewers have dedicated to providing feedback on our manuscript.

• We critically revised all editor’s concerns and comments, and we addressed all accordingly(on respective page numbers).

3. Specifically, we found a degree of text overlap between your submission and the following previously published works:

a. In lines 55-60, there is some overlap with http://www.kma.org.kw/uploads/versions/EEQGAXUUOAQIGLDPHVORFANO.pdf (pages113-114)

b. In lines 81-85 there is some overlap with https://documents1.worldbank.org/curated/en/384721537219780286/pdf/129971-AR-PUBLIC-UN-IGME-Child-Mortality-Report-2018.pdf?fbclid=IwAR2X1_3wyyZFl_v1-6yrBvZgIM0jMjnw4cJL4JxRBou8XV_eJfo2oGOyg20 (page 12)

Authors’ Responses: Thanks a lot. Really, this is very critical concerns. Dear editor, we are very sorry for such unnecessary bolded mistake made in the previous last submission. In this regard, we observed two important suggestion:

a. overlap issues of lines 55-60:

• Dear editor, these overlapping/similarity texts were unintentionally introduced during the 2nd round of revised submission. It’s all our fault and therefore, we sincerely apologize for all these an unintentionally introduced technical errors.

• These valid comments were extensively revised, and addressed based on your implicit and valuable suggestion. Newly changed and corrected parts were highlighted with red font color in the clean revised manuscript (please see page=3, lines: 54-64). Thank you once again.

b. overlap issues of lines 81-85:

• Thank you so much: The editor is perfect.

• Similarly, this valid observation was also critically revised and rephrased based on your insightful suggestions. The newly modified change were highlighted with a red-font color in the clean revised manuscript.(Please see, page 4 & 5, lines: 83-97).

4. Please review the entire manuscript, especially the abovementioned sections to ensure that you rephrase any duplicated text and cite your sources in full. In addition, please review the manuscript again to check for any remaining typographical and grammatical errors, particularly in the Abstract.

Authors’ Responses: Thank you very much. In fact, this is very important suggestion. We are very grateful for this implicit comment and suggestion. Thank you so much for such a valuable intellectual input. Authors critically considered this valid input.

• Accordingly, we thoroughly revised and edited not only the abstract, but also the whole parts of our manuscript.

• In addition, we extensively corrected all copy-editing errors made in the previous submission. Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

• Finally, the newly modified change were highlighted with red font color in the clean revised manuscript (Page 2).

5. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Authors’ Responses: Thank you so much. You are perfect. The issues of reference are very critical, and have to be revised and corrected before any decision for the acceptance of the Manuscript for publication.

• Even it is the authors mandatory to critically review the references styles and its relevancy (Both in text-citation and Bibliography) to avoid any inconsistence and wrong citations across the document.

• We took a long time, thoroughly and critically revised our endnote library. Moreover, any wrong citations were checked in the word document and refined accordingly.

• Further, in the document citation, we checked the references for any repetition, incompleteness, and inconsistences.

• Finally, we addressed these important concerns based on your insightful suggestions. Newly corrected references were highlighted with red font color in the clean revised manuscript.

In summary:

Overall, thank you all for your unquantified effort to enrich this manuscript by forwarding your insightful intellectual input. We are very grateful for all reviewers and the entire editorial office in general and respective academic editor in particular. Dear editor, we learned a lot from all steps of review process made in this manuscript. Really, publications process is learning forum.

=All we can is thanks!!

End of authors’ responses for Handling Editor(s)

Submitted filename: 3.Response to Editor= NM.docx

Click here for additional data file.

4 May 2022

Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit in Public Hospitals of Somali Regional State, Eastern Ethiopia: A multicenter retrospective Analysis

PONE-D-21-13372R2

Dear Dr. Kure,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

George Vousden

Deputy Editor-in-Chief

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: The authors have adressed all the reviewer's comments. However, the paper layout is still to be improved, there are some mistakes of presentation: spaces between references and text...

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #2: Yes: Prof Hedia Bellali

19 May 2022

PONE-D-21-13372R2

Neonatal mortality and Associated Factors among Neonates Admitted to Neonatal Intensive Care Unit at Public Hospitals of Somali Regional State, Eastern Ethiopia: A multicenter retrospective Analysis

Dear Dr. Kure:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. George Vousden

Staff Editor

PLOS ONE

Table 1

Socio-demographic characteristics of neonates admitted to NICU of selected public Hospitals in Somali Regional State, Eastern Ethiopia, 2020.

Characteristics	Category	Frequency (n)	Percentage (%)
Age of mother	<20 years	119	23.3
	20–35 years	332	65.1
	>35 years	59	11.6
Maternal residence	Rural	452	88.8
	Urban	58	11.2
Age of neonate	0–7 days	480	94.1
	8–28 days	30	5.9
Sex of neonate	Male	285	55.9
	Female	225	44.1

Table 2

Maternal and neonatal related factors among mothers and neonates who admitted to NICU of the selected public Hospitals in Somali Regional State, Eastern Ethiopia, 2020.

Characteristics	Categories	Frequency (n)	Percentage (%)
Birth weight	Low BW (<2500gm)	161	31.6
	Normal BW (2500-4000gm)	318	62.4
	Macrosomia (>4000gm)	31	6.0
Apgar score	<7 score	287	56.3
	≥7 score	191	37.5
	Unknown	32	6.2
Neonatal sepsis	Yes	330	64.7
	No	180	35.3
Preterm birth	Yes	56	11.0
	No	454	89.0
Hypothermia	Yes	44	8.60
	No	466	91.4
Birth asphyxia	Yes	87	17.1
	No	423	82.9
Respiratory distress	Yes	213	41.8
	No	297	58.2
Admission time	Early admission (≤ 24hours)	402	78.8
	late admission (>24hours)	108	21.2
ANC follow-up	Yes	235	46.1
	No	275	53.9
Number of ANC visit	1–3 visits	208	85.2
	>3visits	36	14.8
Parity	Primipara	89	17.5
	Multipara	421	82.5
Place of delivery	Home delivery	32	6.3
	Institutional delivery	478	93.7
Mode of delivery	Spontaneous vaginal delivery	456	89.4
	Operative delivery*	54	10.6

Key: APGAR = A-Appearance, P-pulse, G-Grimace, Activity, Respiration; ANC = Antenatal care; BW = Birth Weight

* = Instrumental delivery, C/S delivery.

Table 3

Bi-variable logistic regression analysis of factors associated with neonatal mortality at selected public hospitals in Somali Regional State, Eastern Ethiopia, 2020.

Characteristics	Category	Neonatal outcome		COR(CI = 95%)	P-value
		Not survivedN (%)	SurvivedN (%)
Age of mother(years)	≤20	25(21.0)	94(79.0	1.04(0.48,2.25)	0.39
	21–35	58(17.5)	274(82.5)	0.82(0.41,1.66)	0.580
	>35	12(20.3)	47(79.7)	1	-
Age of neonate(days)	0–7 days	89(18.5)	391(81.5)	0.91(0.36,2.29)	0.840
	8–28 days	6(20.0)	24(80.0)	1	-
Birth weight	Low BW<2500gm	54(33.5)	107(66.5)	4.10(2.53, 6.59)	0.0001
	Normal BW (2500-4000gm)	35(11.0)	283(89.0)	1	-
	Macrosomia (>4000gm)	6(19.4)	25(80.6)	1.94(0.74, 5.06)	0.175
Apgar score	<7 score	65(22.6)	222(77.4)	2.04(1.22, 3.40)	0.006
	Unknown	6(18.8)	26(81.3)	1.61(0.60, 4.31)	0.35
	≥7 scores	30(13.5)	193(86.5)	1	-
Preterm Birth	Yes	25(44.6)	31(55.4)	4.42(2.45,7.94)	0.0001
	No	70(15.4)	384(84.6)	1
Neonatal sepsis	Yes	70(21.2)	260(78.8)	1.67(1.01, 2.75)	0.044
	No	25(13.9)	155(86.1)	1	-
Hypothermia	Yes	8(18.2)	36(81.8)	0.96(0.43,2.15)	0.94
	No	87(18.7)	379(81.3)	1	-
Birth asphyxia	Yes	24(27.6)	63(72.4)	1.68(0.97, 2.91)	0.062
	No	71(16.8)	352(83.2)	1	-
Residence	Rural	75(16.6)	377(83.4)	0.35(1.45,4.79)	0.038
	Urban	21(35.1)	37(64.9)	1	-
Respiratory distress	Yes	47(22.1)	166(77.9)	1.47(0.94, 2.29)	0.092
	No	48(16.2)	249(83.8)	1	-
ANC follow-up	Yes	22(9.4)	213(90.6)	1	-
	No	73(26.5)	202(73.5)	3.49(2.09,5.85)	0.0001
Parity	Primipara	19(21.3)	70(78.7)	1.23(0.70,2.16)	0.47
	Multipara	76(18.1)	345(81.9)	1	-
Place of birth	Home	5(15.6)	27(84.4)	0.79(0.29,2.13)	0.65
	Health facility	90(18.8)	388(81.2)	1	-
Mode of delivery	SDV	81(17.8)	375(82.2)	1	-
	Operative delivery	14(25.9)	40(74.1)	0.61(0.32,1.18)*	0.15

Key: APGAR: A-Appearance, P-pulse, G-Grimace, Activity, Respiration; SVD: Spontaneous Vaginal Delivery, ANC: Antenatal care, BW = Birth weight, LBW: Low Birth Weight, COR = Crude Odds Ratio.