Literature DB >> 35245309

The magnitude of neonatal asphyxia and its associated factors among newborns in public hospitals of North Gondar Zone, Northwest Ethiopia: A cross-sectional study.

Fitalew Tadele Admasu1, Biruk Demssie Melese2, Tadeg Jemere Amare3, Edget Abebe Zewude3, Chalachew Yenew Denku4, Tadesse Asmamaw Dejenie5.   

Abstract

INTRODUCTION: Birth asphyxia is a prominent and avoidable cause of infant illness and death worldwide, particularly in underdeveloped countries such as Ethiopia. Early identification and control of the underlying contributory factors would help to alleviate the situation. As a result, the goal of this study was to assess the magnitude and determinants of neonatal asphyxia among live newborns at the northern Gondar public Hospitals in northwest Ethiopia.
MATERIALS AND METHODS: From April 1 to May 2, 2020, 357 newborns were studied in an institution-based cross-sectional study. The sample size was proportionally distributed among three public hospitals, namely Gondar referral teaching hospital, Debark general hospital, and Kola-Diba District Hospital, which was chosen at random. The number of deliveries given at each hospital six months prior to the data collecting period was used to allocate the hospitals. To get all participants, a systematic random sampling approach was adopted based on hospital delivery registration. The physicians' evaluation of an APGAR score of 7 in the first and fifth minutes of birth was used as the confirmation of birth asphyxia. Data was collected using a standardized and pretested questionnaire. Variables having p-values less than 0.25 were entered into a multivariable logistic regression analysis in the bivariable analysis. At a p-value of 0.05, a statistically significant level was reported.
RESULTS: As per the study, the total prevalence of neonatal asphyxia was found to be 27.1 (95% CI: 21.4, 32.7). In a multivariable logistic regression analysis, neonates born to rural mothers (AOR = 2.441, 95% CI: 1.137, 5.241), primiparity (AOR = 5.521 95%CI: 1.691, 8.026), premature rupture of membrane, (AOR = 3.202, 95% CI: 1.484, 6.909) and low birth weight (< 2.5kg) (AOR = 3.706, 95%CI: 3.307, 4.152) were all found to be independent predictors of birth asphyxia.
CONCLUSION: This study identified that rural residence, primiparity, premature rupture of membrane, and birth weight were found to be the independent predictors of birth asphyxia. The majority of variables that cause birth asphyxia can be controlled.

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Year:  2022        PMID: 35245309      PMCID: PMC8896710          DOI: 10.1371/journal.pone.0264816

Source DB:  PubMed          Journal:  PLoS One        ISSN: 1932-6203            Impact factor:   3.240


Introduction

The first four weeks of a child’s life are the most susceptible for survival, with more than one-third of all child fatalities occurring during this period [1]. The neonatal period accounts for 45 percent of all deaths in children under the age of five worldwide [2]. Perinatal asphyxia is responsible for around a quarter of all newborn fatalities globally. Perinatal asphyxia is also responsible for 23% of newborn mortality in low-income countries, with Sub-Saharan Africa accounting for more than two-thirds (38%) of these deaths [2-5]. Birth asphyxia is described by the World Health Organization (WHO) as "the inability to begin and sustain breathing or spontaneous respiration at birth" [6]. It causes the baby to be deprived of oxygen, causing physical injury to essential organs, most commonly the brain [7-9]. The immature newborn brain is highly susceptible to dangerous situations [10]. In most instances, birth asphyxia is not treatable, and those who survive usually suffer from untreatable neurodevelopmental sequelae, like cognitive and motor disabilities, in the short and long term. Around 25% of asphyxia survivors develop hypoxic-ischemic encephalopathy and neurological disorders [11-13]. Perinatal asphyxia has played a significant role in infant morbidity and death across the world [14]. In underdeveloped nations, it is the primary cause of newborn morbidity and mortality, with an estimated incidence of 100-250/1000 live births, contrasted to 5-10/1000 in industrialized countries [15]. Around 4 million babies are born asphyxiated each year, resulting in 2 million neonatal fatalities and intrapartum stillbirths. 23% of all neonatal fatalities and 8% of all deaths in children under the age of 5 are associated with signs of neonatal asphyxia at birth. Almost all newborn mortality occurs in poorer nations, where the majority of babies are born at home with little or no prenatal care and inadequate perinatal care [10]. Various international studies found that multiple risk factors: socio-demographic (mother’s age, residence, mother’s marital status, educational status, occupation), antepartum (ANC follow up, parity, history of prior neonatal death, pre-eclampsia), intrapartum (prolonged labor, status of amniotic fluid, cephalopelvic disproportion, nature of amniotic fluid), neonatal (pre-term babies, birth weight, gestational age are associated with neonatal asphyxia [16, 17]. In underdeveloped nations like Ethiopia, maternity and child health services might avert infant deaths if providing professional care to mothers during pregnancy, as well as during and after birth. To avoid birth asphyxia, minimize mortality, and enhance infant quality of life, it is critical to recognize and manage the factors of birth asphyxia early. However, data on determinants of birth asphyxia are limited in Ethiopia in general, and in the study area in particular and the majority of past research has been conducted at a single institution. Although studies have been conducted in hospitals in the northeastern portion of Amhara, Ethiopia, to the best of our knowledge, no studies have been conducted in hospitals in the northwestern part of Amhara, Ethiopia. As a result, the purpose of this study was to determine the magnitude and determinants of birth asphyxia in neonates delivered at public hospitals in northwest Ethiopia’s north Gondar zone.

Materials and methods

Study settings and participants

An institutional-based cross-sectional study was conducted in three hospitals namely (Gondar referral and teaching hospital, Debark general hospital, and Kola Diba District hospital) from April 1 to May 2, 2020. The hospitals are 727, 812, and 757 kilometers from Ethiopia’s capital city, Addis Ababa, respectively. These hospitals serve a total of over 2 million people in the catchment regions. All neonates born with a gestational age of ≥ 28 weeks and with their mother were evaluated for eligibility. Newborns with life-threatening abnormalities such as hydrops and cyanotic congenital heart defects were excluded as are already predisposed for asphyxia. Furthermore, preterm babies <28 weeks, those who were seriously ill during the study period, and those neonates who were transferred to advanced care before assessment of APGAR score were also excluded. A single population proportion formula was used to calculate the sample size. Based on a previous study done in Jimma, Southwest Ethiopia [18], the prevalence of perinatal asphyxia was estimated to be 33%. With a 95% confidence level (the Critical value Zα/2 = 1.96), a 5% margin of error, and adding a 5% non-response rate, the final sample size was (3400.05 + 340) = 357. Where: n = the required sample size, Z α/2 = the standardized normal distribution curve value for the 95% confidence level, P = the proportion of birth asphyxia among the general population, and d = degree of precision (the margin of error between the sample and population). Three hospitals were chosen at random from the zone’s eight hospitals for this study. The number of study participants was proportionally assigned to each hospital based on the monthly average number of deliveries. In each hospital’s delivery unit, a systematic sampling technique with every fifth interval was used to enroll study participants.

Data collection tools and procedures

Data were collected by using structured questionnaires from both primary and secondary (chart review) sources. A pre-tested structured interviewer based questionnaire was used to collect data on maternal sociodemographic (age, marital status, ethnicity, religion, residence, educational, and occupational status), antepartum (parity, antepartum hemorrhage, co-existing obstetric/medical diseases, and antenatal visits), intrapartum (duration of labor, fetal presentation, mode of delivery, labor attendant, meconium-stained amniotic fluid and premature rupture of membranes), and neonatal related factors (asphyxia, gestational age, birth weight, sex, and birth type) were abstracted using a pre-tested structured checklist from the medical records of pregnant women who gave birth during the data collection period. In each hospital, data was collected by qualified BSc holding midwives and supervised by an MSc holder nurse. The data collection process was evaluated on a daily basis by the primary investigator and supervisor to ensure data quality and to check for missing information or potential errors. The physicians’ evaluation of an APGAR score of 7 in the first and fifth minutes of birth was used as the confirmation of birth asphyxia. The APGAR score was obtained in the birth ward and operation room throughout both day and night. Data collectors received two days of training on how to gather and record data. The questionnaires were translated into Amharic and then retranslated into English for consistency under the supervision of a pediatrician, and the supervisors and principal investigator checked them daily for accuracy, consistency, and completeness. One week before the actual data collection, the questionnaire was pretested on 17 eligible mother-newborn dyads (5% of the sample size) in Alfa primary hospital.

Data management and analysis

The data was cleaned up and double-checked before being input into Epi data version 3.1 and exported to SPSS version 20 for analysis. The outcomes of the maternal socio-demographic, antepartum, intrapartum, and neonatal studies were described using descriptive statistics. The degree of relationship between independent and dependent variables was determined using the odds ratio (OR) and confidence interval (CI). Using odds ratios, bivariate logistic regression was used to rank the relative relevance of each exposure variable with the outcome variables. Variables with a P value of less than 0.25 in the bivariate logistic regression analysis were chosen and fitted to the multiple logistic regression analysis to determine the independent effects of each variable. Finally, the Adjusted Odds Ratio with 95% confidence intervals (CI) was used to assess the existence and strength of relationships, with statistical significance reported if p ≤ 0.05.

Results

In this study, all 357 mothers agreed to participate, with a 100% response rate. More than half of the respondents, 238(66.67%) were rural inhabitants. The mean age was 26.92 years (SD ± 4.7) of whom 122 (34.17%) belonged to the age category of 20–24 years. Three hundred (84.1%) women were married. In addition, 123 (34.45%) were housewives and only 102 (28.6%) of mothers attended tertiary education. A small number of mothers 23 (6.4%) had a history of adverse pregnancy outcomes (Table 1).
Table 1

Socio-demographic factors of mothers who gave live birth at public hospitals of North Gondar zone, 2020 (n = 357).

FactorsResponseFrequency%
ResidenceUrban11933.33
Rural23866.67
Age (years)15–19298.1
20–2412234.17
25–2911131.1
30–346618.48
35 and above298.1
Marital statusSeparated257.0
Widowed328.9
Married30084.1
ReligionOrthodox30785.99
Muslim4011.2
Others*102.8
OccupationHousewife12334.45
Self-employee8624.1
Government employee9927.7
Merchant4512.6
Others**41.1
Educational StatusNo formal education8022.4
primary8323.2
secondary9225.7
Tertiary and above10228.6
ParityPrimiparous16546.2
Multiparous19253.8
History of adverse pregnancy outcomeYes236.4
No33493.6

Antepartum related factors

322(90.2%)] had attended antenatal care at either public hospitals or public health centers. However, only 196(54.9%) moms had four and above antenatal care visits. Of the total respondents, 83(23.2%) of women had Obstetric complications during pregnancy. About 61(17.1%) mothers ever used substances during their gestation (Table 2).
Table 2

Factors related to the antepartum period among mothers who gave live birth at public hospitals of North Gondar zone, 2020 (n = 357).

FactorResponseFrequency%
ANC follow upNo, follow up359.8
1 time339.2
2–3 times9326.1
4 times and above19654.9
Obstetric complication during pregnancyNo, complication27476.8
Preeclampsia/eclampsia226.1
Antepartum hemorrhage143.9
Anemia3810.6
Infections71.9
Gestational diabetes20.6
Any medical illness during pregnancyYes246.7
No33393.3
Substance used during pregnancyYes6117.1
No29682.9

Intrapartum related characteristics

In our study, 303 (84.87%) of newborns were of vertex presentation, 20 (5.6%) were born by assisted vaginal delivery. The majority 253(70.9%) of the mothers had intrapartum rupture of fetal membranes whereas 104 (29.1%) premature rupture of the membrane was reported among mothers. Finally, 32 (9%) mothers had complicated labor and 103 (28.9%) of births were meconium-stained amniotic fluid following membrane rupture (Table 3).
Table 3

Intra-partum related characteristics among mothers who gave live birth at public hospitals of North Gondar zone, 2020 (n = 357).

FactorResponseFrequency%
Fetal presentationVertex30384.87
Malpresentation5415.13
Mode of deliverySpontaneous vaginal delivery29081.2
Cesarean section4713.2
Assisted vaginal delivery205.6
labor InductionYes143.9
no34390.1
Labor durationNormal16546.2
Prolonged14239.8
Precipitated5014
Time of membrane rupturePROM10429.1
Intrapartum25370.9
Duration of ROMNormal30986.5
Prolonged4813.5
Status of amniotic fluid at birthClear24769.2
Meconium stained10328.9
Bloodstained71.9
Complicated laborYes329
no32591

Neonatal related characteristics

189 (53%) of the newborns were males. The mean gestational age at birth was 38.5 (±2.4) weeks and the majority of the newborns 242(67.8%) were term. Moreover, 58(16.3%) of the newborns had low birth weight. At birth, there were 71(19.9%) newborns with health problems. There were 15 (4.2%) twin newborns (Table 4).
Table 4

Newborn related characteristics among mothers who gave live birth at public hospitals of North Gondar zone, 2020 (n = 357).

FactorResponsefrequency%
SexMale18953
Female16847
Gestational age at birthPreterm7821.8
Term24267.8
Post-term371.1
Birth weight2.5–4 kg27677.3
<2.5kg5816.3
> 4 kg236.4
Birth outcomeSingleton34295.8
Twin154.2
The neonatal medical problem at birth other than asphyxiaNo medical problems28680.1
Neonatal sepsis4111.5
Birth injury195.3
Congenital malformation113.1

The magnitude of birth asphyxia

The magnitude of birth asphyxia was found to be 97 (27.2%) [95% CI: 21.4%, 32.7%] based on APGAR scoring less than 7 persistently for more than 5 minutes after birth. Most of the asphyxiated neonates had moderate asphyxia 76 (78.4%) whereas 21 (21.2%) neonates had severe birth asphyxia.

Determinate factors of birth asphyxia

The Bi-variable logistic regression analysis showed that 7 factors namely, residence, gestational age, parity, premature rupture of membrane, birth weight of neonates, antenatal obstetrics complication, mode of delivery were crudely associated with birth asphyxia. However, after statistical adjustments in the final model, gestational age, Antenatal obstetric complications, and mode of delivery were not significant. Neonates of women from the rural residences had 2.4(AOR = 2.4: 95% CI: 1.4, 5.2) more likelihood of being asphyxiated at birth as compared to the urban residence. Neonates born from primipara mothers were 5.5times (AOR = 5.5: 95%CI: 1.7, 8.1) more prone to be asphyxiated at birth when compared to Multiparous mothers. Furthermore, Neonates born to mothers with premature rupture of fetal membranes were 3.2 times (AOR = 3.2: 95% CI: 1.9, 6.9) more prone to be asphyxiated at birth as compared to those with intrapartum rupture of membranes. Birth asphyxia was 3.8 times (AOR = 3.8, 95%CI: 3.3, 4.2) higher among low-birth-weight neonates than those normal weight neonates (Table 5).
Table 5

Bivariable and multivariable logistic regression analysis of factors associated with birth asphyxia among live births at public hospitals of North Gondar zone, 2020 (n = 357).

FactorBirth asphyxia95% CIP-value
Asphyxiated (n = 97)Not asphyxiated (n = 260)COR (95%CI)AOR (95%CI)
Residence
Urban382001.01.0
Rural59601.8(0.9, 3.4)2.4(1.4, 5.2)0.036
parity
Primiparous571084.7(1.7, 12.8)5.5(1.7, 8.1)0.001
Multiparous401521.01.0
Birth weight
< 2.5 kg451313.5(1.5,23.7)3.8(3.3, 4.2)0.011
2.5-4kg392371.01.0
> 4 kg13105.3(0.7, 42.3)2.7(1.1,5.9)
Membrane rupture
PROM63412.4(1.2, 4.5)3.2(1.9, 6.9)0.031
Intrapartum342191.01.0
Gestational age
Preterm36423.8(0.4, 33.1)8.7(0.6, 13.76)0.098
Term471951.01.0
Post-term14231.8(0.2, 16.6)3.6(0.2, 52.9)0.779
Antenatal obstetric complications
Yes651816.8(10.5,26.8)6.5 (0.6, 1.6)0.08
No322421.01.0
Mode of delivery
SVD452451.01.0
Assisted vaginal1373.9 (2.4, 6.3)6.2 (2.4, 14.6)0.517
CS3989.5 (5.5, 15.1)6.7 (0.7, 2.0)0.065

CS = Cesarean section.

CS = Cesarean section.

Discussion

In this study, the prevalence, and predictors of birth asphyxia amongst live births at public hospitals in the south Gondar zone are explored in depth. Birth asphyxia was found to be significantly associated with rural residency, primiparity, preterm ruptures of the membranes, and low birth weight. In the study, the Perinatal asphyxia was found to be lower (27.1%) than in a study conducted at Dilla Referral Hospital in Southern Ethiopia (32.8%) [19]. However, it was found to be higher than other studies, particularly in India (6.6%), Nigeria (21.1%), Cameroon (8.5%), and also in Ethiopian hospitals of Dire Dawa (12.5%) and Addis Ababa (16.2%) [20, 21]. This discrepancy could be explained by differences in sociocultural characteristics among the study participants. Furthermore, the prevalence of birth asphyxia in our setting was lower than in an Iranian study (58.8%) [22], which could be due to differences in sample size, study setting, and, most importantly, case definition, as our study only used the fifth minute APGAR score less than 7, whereas the Iranian study used more laboratory-based results as diagnostic criteria for birth asphyxia. Despite the fact that prenatal asphyxia contributes significantly to neonatal morbidity and mortality in underdeveloped countries, evidence is scarce on the factors that predict perinatal asphyxia. There isn’t enough evidence to say whether maternal or neonatal variables play a role in the occurrence of birth asphyxia [23, 24]. In an analysis of associated factors, newborns born to women who reside in rural areas had a 2.5 higher risk of having birth asphyxia than those born to women who live in the city. This finding is in line with research was undertaken in Nepal [24], Gondar [25], Dire Dawa [26], and Wollo [27], which found that moms in rural areas had poorer birth outcomes than mothers in urban areas. This could be because the research locations are similar in terms of socioeconomic and lifestyle conditions. The discrepancy between urban and rural residents could be due to a lack of quality pregnancy-related antenatal and prenatal care in rural areas, as well as the availability and distance of health facilities, a lack of information about antenatal and prenatal care, transportation issues, and a high load of housework. In comparison to multiparous women, neonates delivered to primiparous mothers were shown to be five times more likely to be asphyxiated at delivery. The finding is consistent with research conducted in Pakistan, Nigeria, and central Tigray, which found that being primipara is one of the independent factors of newborn asphyxia [28, 29]. The consistency can be justified by the fact that primipara mothers are more likely to be found at a younger age and may be more prone to malpresentation, prolonged obstructed labor, and the mother who is experiencing labor and delivery for the first time may take longer to negotiate with the pelvic brim and may fail to progress in labor, resulting in the delivery of an asphyxiated neonate. In this study, low birth weight was also founded to be a major factor of birth asphyxia. Low—birth—weight neonates were 3.72 times more likely than normal birth weight neonates to suffer from birth asphyxia. These findings matched those of research undertaken at Gondar Referral Hospital [12], Jimma hospital [18], and Iran [30]. This could be explained by the fact that a high proportion of small babies are born prematurely and lack sufficient surfactant, resulting in breathing difficulties, and low-birth-weight neonates typically have pulmonary immaturity and weak respiratory muscle strength. Furthermore, compared to those delivered to mothers with intrapartum rupture, neonates born to mothers with premature rupture of fetal membranes (PROM) were 3.2 times more likely to be asphyxiated at birth. This finding is in line with studies in Cameroon [31], Uganda [32], and Al-Diwaniya Teaching Hospital in Saudi Arabia [33]. A prospective case-control study on term newborns in Yaoundé, Cameroon, found a link between premature ruptured membranes and delivery hypoxia [34].

Conclusions

In conclusion, the prevalence of birth asphyxia is comparable to previous studies in underdeveloped nations. Rural inhabitants, primiparity, preterm rupture of membranes, and low birth weight were all found to be independent predictors of birth asphyxia. As a result, health care personnel, particularly those in labor and delivery wards, must pay more attention to complex labors to foresee and prevent birth asphyxia. 13 Jan 2022
PONE-D-21-24852
The magnitude of Neonatal Asphyxia and its Associated Factors among newborns; A cross-sectional study
PLOS ONE Dear Dr. Dejenie 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.
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Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author. https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0226891 https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-020-03348-2 We would like to make you aware that copying extracts from previous publications, especially outside the methods section, word-for-word is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. Please revise the manuscript to rephrase the duplicated text, cite your sources, and provide details as to how the current manuscript advances on previous work. 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Nevertheless, authors should clarify some points and improve the discussion, as suggested below. Authors should consider the following recommendations: - Manuscript should be further revised in order to correct some typos and improve style. - I would recommend to highlight clearly other conditions that may cause adverse obstetric outcomes, including neonatal asphyxia, such as advanced maternal age (PMID: 25027820), pre-eclampsia (PMID: 26512423; PMID: 32283429) and obstructed labor (PMID: 31823037; PMID: 32307556 ). Reviewer #2: This is a cross sectional study analyzing cases of fetal asphyxia in northwest Ethiopia. The article has some inconsistencies. The most evident are: - In the abstract you say " The diagnosis of birth asphyxia was confirmed based on the physician’s diagnosis of an APGAR score < 7 in the 1 st and 5 th minutes of birth". IN the text you say "The diagnosis of birth asphyxia was made based on the fifth-minute APGAR scores of < 7 ". Please correct - Regarding the antepartal visits, you reported in the text that 59.1% of patients had 4 or more visits, while in the table they are 54.09% - Married women are 325 (91.1%) in the text and 32 (8.9%) in the table I recommend reviewing all correspondences between text and tables. In table 4 you wrote about "Neonatal medical problem at birth" that 286 babies had no problems, 41 sepsis, 19 birth injury and 11 congenital malformation. It is not clear where the 97 cases of childbirth asphyxia fit in. In lines 192-193 In lines 192-193 you divide fetal asphyxia into moderate and severe but it is not defined by what criteria this subdivision is carried out. 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. 9 Feb 2022 January 28, 2022 Rebuttal letter PONE-D-21-24852 The magnitude of neonatal asphyxia and its associated factors among newborns; a cross-sectional study Dear Editors and Reviewers, We are grateful for the critical review and constructive suggestions to improve our manuscript. Based on the comments and suggestions, we have made corrections and modifications and provided point-by-point responses to comments and suggestions. Please, find our responses in a green mark to comments/suggestions presented by academic editors and reviewers marked in yellow. Below are our responses to each point raised by the academic editor and reviewers. Best regards! Tadesse Asmamaw Dejenie, on behave of all authors Response to academic editor’s comment Comment 1: Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming Author response: Thank you so much for sending the link to the PLOS ONE style templates; we have taken your advice and updated our manuscript to meet the style requirements of PLOS ONE. Please double-check it in the revised manuscript. Comment 2: Thank you for submitting the above manuscript to PLOS ONE. During our internal evaluation of the manuscript, we found significant text overlap between your submission and the following previously published works, some of which you are an author. Author response: We'd like to thank you for your input. We've taken your advice and thoroughly reread our amended manuscript. Please see the revised manuscript for further information. Comment 3: We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide. Author response: We'd want to thank you one more for alerting us. Please correct, as the datasets used in this work are available upon reasonable request from the corresponding author. Response to Reviewers’ comment Reviewer #1: I read with great interest the manuscript, which falls within the aim of this Journal. In my honest opinion, the topic is interesting enough to attract the readers’ attention. Nevertheless, authors should clarify some points and improve the discussion, as suggested below. Authors should consider the following recommendations: - Manuscript should be further revised in order to correct some typos and improve style. - I would recommend highlighting clearly other conditions that may cause adverse obstetric outcomes, including neonatal asphyxia, such as advanced maternal age (PMID: 25027820), pre-eclampsia (PMID: 26512423; PMID: 32283429) and obstructed labor (PMID: 31823037; PMID: 32307556 ). Author response: We are really grateful for your suggestions. We have acknowledged and adjusted your helpful suggestions. Tables 3 and 4 of the revised manuscript address some of your issues. For further information, please kindly check the revised manuscript. Reviewer #2: Comment 1: The article has some inconsistencies. The most evident are: - In the abstract you say " The diagnosis of birth asphyxia was confirmed based on the physician’s diagnosis of an APGAR score < 7 in the 1st and 5th minutes of birth". IN the text you say "The diagnosis of birth asphyxia was made based on the fifth-minute APGAR scores of < 7 ". Please correct Author response: We'd like to express our gratitude for your insightful remarks and suggestions. We've taken note of the suggestions and made the necessary revisions. Comment 2: Regarding the antepartal visits, you reported in the text that 59.1% of patients had 4 or more visits, while in the table they are 54.09% Author response: We appreciate your thoughtful and helpful remarks once again. We are perplexed as to why this issue has arisen. This is most likely due to a technical glitch. In any case, we took your suggestions and made the necessary changes. Comment 3: Married women are 325 (91.1%) in the text and 32 (8.9%) in the table I recommend reviewing all correspondences between text and tables. In table 4 you wrote about "Neonatal medical problem at birth" that 286 babies had no problems, 41 sepsis, 19 birth injury and 11 congenital malformation. It is not clear where the 97 cases of childbirth asphyxia fit in. Author response: We value your critical opinion. In fact, when we assessed the neonatal medical condition at birth, we did not consider neonatal asphyxia; instead, we assessed medical problems other than asphyxia. Comment 4: In lines 192-193 you divide fetal asphyxia into moderate and severe but it is not defined by what criteria this subdivision is carried out. Author response: Fetal asphyxia was classified using the Standard Treatment Protocol for Management of Common Newborn Conditions in Small Hospitals, which is based on WHO Guidelines. Submitted filename: Response to Reviewers.rtf Click here for additional data file. 18 Feb 2022 The magnitude of neonatal asphyxia and its associated factors among newborns in public hospitals of North Gondar Zone, Northwest Ethiopia: A cross-sectional study PONE-D-21-24852R1 Dear Dr. Tadesse Asmamaw, 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, Francesca Crovetto Academic Editor PLOS ONE 22 Feb 2022 PONE-D-21-24852R1 The magnitude of neonatal asphyxia and its associated factors among newborns in public hospitals of North Gondar Zone, Northwest Ethiopia: A cross-sectional study Dear Dr. Dejenie: 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. Francesca Crovetto Academic Editor PLOS ONE
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1.  Antenatal and intrapartum risk factors for birth asphyxia among emergency obstetric referrals in Mulago Hospital, Kampala, Uganda.

Authors:  D Kaye
Journal:  East Afr Med J       Date:  2003-03

2.  The Apgar score.

Authors: 
Journal:  Pediatrics       Date:  2006-04       Impact factor: 7.124

3.  4 million neonatal deaths: when? Where? Why?

Authors:  Joy E Lawn; Simon Cousens; Jelka Zupan
Journal:  Lancet       Date:  2005 Mar 5-11       Impact factor: 79.321

4.  Risk factors for neonatal mortality due to birth asphyxia in southern Nepal: a prospective, community-based cohort study.

Authors:  Anne C C Lee; Luke C Mullany; James M Tielsch; Joanne Katz; Subarna K Khatry; Steven C LeClerq; Ramesh K Adhikari; Shardaram R Shrestha; Gary L Darmstadt
Journal:  Pediatrics       Date:  2008-05       Impact factor: 7.124

Review 5.  Two million intrapartum-related stillbirths and neonatal deaths: where, why, and what can be done?

Authors:  Joy E Lawn; Anne C C Lee; Mary Kinney; Lynn Sibley; Wally A Carlo; Vinod K Paul; Robert Pattinson; Gary L Darmstadt
Journal:  Int J Gynaecol Obstet       Date:  2009-10       Impact factor: 3.561

Review 6.  Could Perinatal Asphyxia Induce a Synaptopathy? New Highlights from an Experimental Model.

Authors:  María Inés Herrera; Matilde Otero-Losada; Lucas Daniel Udovin; Carlos Kusnier; Rodolfo Kölliker-Frers; Wanderley de Souza; Francisco Capani
Journal:  Neural Plast       Date:  2017-02-23       Impact factor: 3.599

7.  Determinants of birth asphyxia among live birth newborns in University of Gondar referral hospital, northwest Ethiopia: A case-control study.

Authors:  Lisanu Wosenu; Abebaw Gebeyehu Worku; Destaw Fetene Teshome; Abebaw Addis Gelagay
Journal:  PLoS One       Date:  2018-09-07       Impact factor: 3.240

8.  Prevalence and associated factors of perinatal asphyxia among newborns in Dilla University referral hospital, Southern Ethiopia- 2017.

Authors:  Abebe Alemu; Getnet Melaku; Gerezgiher Buruh Abera; Ashenafi Damte
Journal:  Pediatric Health Med Ther       Date:  2019-07-24

9.  Perinatal mortality and associated risk factors: a case control study.

Authors:  Getachew Bayou; Yifru Berhan
Journal:  Ethiop J Health Sci       Date:  2012-11

10.  Risk factors for birth asphyxia in an urban health facility in cameroon.

Authors:  Andreas Chiabi; Seraphin Nguefack; Evelyne Mah; Sostenne Nodem; Lawrence Mbuagbaw; Elie Mbonda; Pierre-Fernand Tchokoteu; Anderson Doh Frcog
Journal:  Iran J Child Neurol       Date:  2013
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  1 in total

1.  Perinatal maternal characteristics predict a high risk of neonatal asphyxia: A multi-center retrospective cohort study in China.

Authors:  Yi Yu; Jinsong Gao; Juntao Liu; Yabing Tang; Mei Zhong; Jing He; Shixiu Liao; Xietong Wang; Xinghui Liu; Yinli Cao; Caixia Liu; Jingxia Sun
Journal:  Front Med (Lausanne)       Date:  2022-08-08
  1 in total

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