Incidence of respiratory distress and its predictors among neonates admitted to the neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia.

BACKGROUND: Although respiratory distress is one of the major causes of neonatal morbidity and mortality throughout the globe, it is a particularly serious concern for nations like Ethiopia that have significant resource limitations. Additionally, few studies have looked at neonatal respiratory distress and its predictors in developing countries, and thus we sought to investigate this issue in neonates who were admitted to the Neonatal Intensive Care Unit at Black Lion Specialized Hospital, Ethiopia.
METHODS: An institution-based retrospective follow-up study was conducted with 571 neonates from January 2013 to March 2018. Data were collected by reviewing patients' charts using a systematic sampling technique with a pretested checklist. The data was then entered using Epi-data 4.2 and analyzed with STATA 14. Median time, Kaplan-Meier survival estimation curves, and log-rank tests were then computed. Bivariable and multivariable Gompertz parametric hazard models were fitted to detect the determinants of respiratory distress. The hazard ratio with a 95% confidence interval was subsequently calculated. Variables with reported p-values < 0.05 were considered statistically significant.
RESULTS: The proportion of neonates with respiratory distress among those admitted to the Black Lion Specialized Hospital neonatal intensive care unit was 42.9% (95%CI: 39.3-46.1%) The incidence rate was 8.1/100 (95%CI: 7.3, 8.9). Significant predictors of respiratory distress in neonates included being male [Adjusted hazard ratio (HR): 2.4 (95%CI: 1.1, 3.1)], born via caesarean section [AHR: 1.9 (95%CI: 1.6, 2.3)], home delivery [AHR: 2.9 (95%CI: 1.5, 5,2)], maternal diabetes mellitus (AHR: 2.3 (95%CI: 1.4, 3.6)), preterm birth [AHR: 2.9 (95%CI: 1.6, 5.1)], and having an Apgar score of less than 7 [AHR: 3.1 (95%CI: 1.8, 5.0)].
CONCLUSIONS: In this study, the proportion of respiratory distress (RD) was high. Preterm birth, delivery by caesarean section, Apgar score < 7, sepsis, maternal diabetes mellitus, and home delivery were all significant predictors of this condition. Based on our findings this would likely include encouraging more hospital births, better control of diabetes in pregnancy, improved neonatal resuscitation and addressing ways to decrease the need for frequent caesarean sections.

Background

Respiratory distress (RD) is a common problem for newborns immediately following birth. It is often seen during the transition from fetal to neonatal life. RD typically manifests in newborns as tachypnea, intercostal retractions, nasal flaring, audible grunting, and cyanosis. The successful transition from fetal to neonatal life requires a series of rapid physiologic changes in the cardiorespiratory systems. These changes result in a redirection of gas exchange from the placenta to the lungs and requires the replacement of alveolar fluid with air and the onset of regular breathing [1]. Although RD may be transient in some newborns, if it persists, then there is a need for proper diagnostic and therapeutic interventions to optimize outcomes and minimize morbidity.

RD is one of the most common reasons for neonates to be admitted to the neonatal intensive care unit (NICU) [2, 3]. Fifteen percent of term infants and 29% of late preterm infants admitted to the NICU develop significant respiratory morbidity [4]. This incidence is even higher for infants born before 34 weeks’ gestation [5]

Certain risk factors increase the likelihood of neonatal RD. Recognized causes of RD in other low and high resource countries includes; prematurity, low first and fifth minute Apgar scores, meconium aspiration syndrome, caesarian section delivery, gestational diabetes, maternal chorioamnionitis, premature rupture of membranes [6], and oligohydramnios, as well as structural lung abnormalities are some predictors identified in previous studies [5, 7–10]. Other common causes include transient tachypnea of the newborn, meconium aspiration syndrome, pneumonia, sepsis, pneumothorax, and persistent pulmonary hypertension of the newborn [11]. In contrast, the risk decreases with each advancing week of gestation and birth through spontaneous vaginal delivery [12].

Regardless of the cause, if not recognized and managed quickly, RD can escalate to respiratory failure, cardiopulmonary arrest, and even death. Therefore, it is imperative that any health care practitioner caring for newborn infants be able to readily recognize the signs and symptoms of RD, differentiate the various causes, and initiate management strategies to prevent significant complications or death. Consequently, neonates in need of critical medical attention are usually admitted to the NICU. These infants tend to be preterm, have a low birth weight, or have serious medical conditions including RD [13, 14].

Globally, there are different policies, strategies, and programs which work on or advocate for the prevention and care of preterm neonates and their birth outcomes, including RD, like the Sustainable Development Goals (SDGs) and the Every Women and Every Child initiative [15, 16]. Despite these efforts, RD remains among the leading causes of neonatal mortality and morbidity [17-21]. Indeed, in Ethiopia, RD is the most common cause of neonatal mortality and morbidity [17-22], resulting in exponentially increasing neonatal care costs within the first 28 day of life. Additionally, few studies have been conducted in developing countries to assess RD in these regions, including Ethiopia. Therefore, this study we aimed to determine the incidence and predictors of RD among neonates who were admitted to the NICU at Black Lion Specialized Hospital, Ethiopia.

Methods

Study design, setting, and population

An institution-based retrospective follow-up study was conducted among a cohort of neonates from the previous consecutive five years (from January 2013 to March 2018). The study was conducted in Addis Ababa, a capital city of Ethiopia at NICU of black lion hospital. Addis Ababa has ten sub-cities in which the City lies at an altitude of 7,546 feet (2,300metres). It has twelve governmental and nine nongovernmental hospitals. The NICU of black lion hospital ward is able to accommodate a maximum of 60 patients with average of 20–40 patients’ daily admission. There are on average 5000–6000 annual admissions. The study was conducted from March to April 1, 2018. The neonatal chart number were taken from the HMIS- data base. The total patients admitted to NICU from January 2013-last of March 2018 were 5000. We have found the number of admissions for each year. The samples were proportionally allocated for each year, and with systematics sampling; the study participants of each year were selected as follows. First, numbering the units of each year on the frame from 1 to N (N = total admission of each year), then we determine the sampling interval (K) by dividing the number of units in the population by the desired sample size of each year (n = sample size of each year) which gives 8. Then number between one and 8 at random was selected (2 were selected). This number is called the random start and the first number included in the sample. Then later Selection was conducted every 8th unit after that first number. Our source population was all neonates admitted to the NICU at the Black Lion Specialized Hospital, Ethiopia. All neonates who were admitted to the NICU in the previous five consecutive years (from January 2013 to March 2018) were considered as the study population.

Eligibility criteria

All targeted neonates’ medical cards documented in the previous five years from the study period were recruited and those with incomplete cards were excluded.

Sample size determination and sampling procedure

The sample size was determined via the double population proportion formula using Epi-Info Version 7 by assuming a one-to-one ratio of exposed to non-exposed, 95% level of confidence, and a power of 80%. We considered four significantly associated factors to calculate the sample size; the largest sample size was 522. After adding a 10% non-response rate, the total sample size became 604. The neonates’ cards were accessed using the systematic random sampling technique after determining the sampling fraction (k = 6) and the first card was selected by the lottery method.

Study variables

Dependent variable

Incidence of RD

Independent variables

Socio-demographic factors. Neonatal-related variables included age at admission, gestational age, sex, the weight of the neonate, date of NICU admission and discharge. Maternal-related variables were age and residency.

Gynecologic-obstetric related factors. Antenatal care (ANC) follow up, gravidity, parity, mode of delivery, multiple pregnancies, PROM, preeclampsia, abruption placenta, and breastfeeding initiation.

Medical disorders in mother. Hypertension, diabetes mellitus (DM), human immune virus/acquired immune deficiency syndrome (HIV)/(AIDS).

Neonatal outcome condition. Apgar score, sepsis, jaundice, hypothermia, prenatal asphyxia (PNA), hypoglycemia, meningitis, esophageal atresia.

Data collection tools. A pretested checklist was used to collect the required data from the neonates’ charts. The checklist was translated to the local language of Amharic and back to English. The consistency of this translation was checked to ensure its accuracy. Data were collected by reviewing the complete patients’ cards from the previous five consecutive years from the study period. RD was confirmed by reviewing neonate medical charts.

Data quality control. Data quality was assured by designing proper data abstraction tools. The checklist was evaluated by experienced researchers. The data collection instrument was pretested on 5% of the sample size. Rigorous training was given regarding the data abstraction checklist and data collection process for both data collectors and supervisors. During the data collection time, close supervision and monitoring were carried out by the supervisors and investigator. Double data entry was also done using Epi Data 4.2.0 software.

Data processing, analysis, and presentation. Before analysis, data was cleaned, edited, and coded. Any errors identified at this time were corrected after review of the original data using the code numbers that we had assigned during the data collection period. Data were entered using Epi-Data version 4.2.0 and analyzed using STATA 14 statistical software. Incidence density rate (IDR) was calculated for the entire study period. Subsequently, the number of cases of RD within the follow-up period was divided by the total person-time at risk on follow-up and reported per 100-person day. Kaplan-Meier survival curves were used to estimate the mean survival time and the log-rank tests were used to compare survival curves. Proportional hazard assumption was tested both graphically and through the Schoenfeld residual test for all predictors, revealing that the proportional hazard assumption was met. After checking this assumption, by comparing models, a more effective hazard model was selected using the log likelihood ratio (LR) test and the Akaike Information Criterion (AIC). In this parametric approach, the baseline hazard and the vector of its parameters were assessed together with the regression coefficients. The best-fit model was chosen using AIC; selecting those having the smallest AIC. Subsequently, parametric models were completed for neonates to ascertain the possible predictors. Variables having a p-value less than or equal to 0.05 in the bivariate analysis were fitted to the multivariable Gompertz hazard distribution regression model with a 95% confidence interval. A p-value less than 0.05 was considered statistically significant.

Ethical consideration. Ethical clearance was obtained from Addis Ababa University, College of health science ethical review board. Letters of cooperation were written to Black Lion Specialized Hospital by the ethical review board members and subsequently permission was obtained from the clinical director and relevant department and unit heads of the hospital. Since the study was conducted by taking appropriate information from medical chart, it will not inflict any harm on the patients. The name or any other identifying information was not be recorded on the checklist and all information that was taken from the chart was kept strictly confidential and in a safe place.

Following these approvals, access to the medical charts was provided and we did our utmost to maintain participant confidentiality by storing in a file cabinet and kept in a key and locked system with computer pass ward.

Operational definition

Event (neonatal RD)

The presence of two or more of the following signs: an abnormal respiratory rate (tachypnea > 60 breaths/min, bradypnea < 30 breaths/minute, respiratory pauses, or apnea) or signs of labored breathing (expiratory grunting, nasal flaring, intercostal recessions, xyphoid recessions), with or without cyanosis.

RD

presence of two or more of the following signs: an abnormal respiratory rate, expiratory grunting, nasal flaring, chest wall recessions, and cyanosis as per patient chart information.

Results

Characteristics of neonates

Among 604 neonatal charts reviewed, 571 (94.5%) records met the enrollment criteria and were included in the final analysis. Of this group, 299 (52.34%) of the study participants were males. Neonates in the late neonatal period accounted for more than half of the study participants. The mean age of the cohort at the time of admission to the NICU was 3 days ± 3.72 standard deviation (SD). More than half of the neonates admitted to the NICU were diagnosed with neonatal sepsis, but other common causes of admission were jaundice, hypothermia, and PNA (Table 1). In addition, the common types of RD for neonatal admission were RDS or hyaline membrane diseases (Fig 1).

Table 1

Characteristics of neonates admitted to the NICU at Black Lion Specialized Hospital, Ethiopia, (n = 571).

Characteristics	Category	Frequency (%)
Sex	Male	299 (52.34)
	Female	272 (47.66)
Gestational age (weeks)	<37	239 (41.8)
	≥37	332 (58.2)
Neonates weight (g)	<2500	243 (42.6)
	≥2500	328 (57.4)
Hypothermia	Yes	180 (31.5)
	No	391 (68.5)
Sepsis	Yes	260 (45.5)
	No	247(43.3)
Jaundice	Yes	202 (35.4)
	No	369 (64.6)
1st minute Apgar	<7	337 (59.0)
	≥7	234 (41)

Fig 1

Common types of neonatal RD at Black Lion Specialized Hospital, Ethiopia.

Socio-demographic and obstetric characteristics of mothers

In the current study, most mothers were found to be between the ages of 20–34. The mean age of mothers was found to be 28 years ± 5.42 SD. Among all mothers enrolled in this study, 336 (58.9%) experienced spontaneous vaginal delivery. Regarding obstetric, gynecological, and medical diagnosis of maternal diseases, 250 (43.8%) had PROM, (43.8%) had HIV/AIDS (13.5%), and (10.7%) had DM. The results of this study also indicated that the majority [402 (70.4%)] of neonates were born to mothers who had an ANC follow-up. (Table 2).

Table 2

Socio-demographic and obstetric characteristics of mothers of neonates admitted to the NICU at Black Lion Specialized Hospital, Ethiopia, (n = 571).

Characteristics	Category	Frequency (%)
ANC follow-up	Yes	402(70.4)
	No	169(29.6)
Maternal age (years)	<20	61(10.9)
	20–34	426 (74.6)
	>34	84 (14.7)
Place of delivery	Home	194(34)
	Health institution	377(66.0)
Multiple pregnancy	Yes	49(8.5)
	No	522(91.5)
PROM	Yes	250(43.8)
	No	321(56.2)
HIV/AIDS	Yes	76(13.3)
	No	495(86.7)
Maternal DM	Yes	61(10.7)
	No	510(89.3)

Overall proportion and incidence rate of RD in neonates

The overall proportion of neonates that develop RD was found to be 42.9% (95%CI: 39.3–46.1). The overall incidence rate of RD was found to be 8.1 per 100 neonate day (95%CI: 7.29, 8.9) with 4331-person day observation.

Time to discharge of neonates with RD

The overall median length of hospital stay for neonates with RD in this study was 9 days (95%CI: 8–10) and the overall length of hospital stay were 28 neonates’ days (IQR5, 30 neonate-days). The cumulative probability of neonates not developing RD at the end of the first day in the NICU was 94.4%, between the fifth and 10th days was 41.3%, and between 20–28 days in the NICU was 19.14% (Fig 2).

Fig 2

Overall Kaplan-Meier survival estimate of neonates with RD admitted to the NICU at Black Lion Specialized Hospital, Ethiopia.

The proportional hazard assumption was evaluated using Kaplan-Meier survival curves and the Sheffield residual global test and was found to be met (x2 = 5.11; p value = 0.08) (Fig 3).

Fig 3

Kaplan-Meier survival curves of neonates with RD with respect to A) PROM, B) PNA, C) maternal HIV/AIDS, and D) mode of delivery.

Model comparison criteria

The goodness of fit model was checked using the Cox-Snell residual test. Based on the AIC, the univariate Gompertz hazard distribution (AIC = 435.8) model was more efficient than the parametric exponential (AIC = 987.5) and Weibull (AIC = 686.9) semi-parametric Cox-proportional hazard (AIC = 1123.54) models (Fig 4).

Fig 4

The Cox-Snell residual Nelson-Aalen cumulative hazard graph on neonates with RDS admitted to the NICU at Black Lion Specialized Hospital, Ethiopia.

Predictors of RD

The univariate and multivariable parametric Gompertz hazard distribution regression model was used to identify predictors of RD in neonates from admission to discharge in the NICU. Findings from the bivariate analysis showed that gestational weight, being male, having no antenatal follow-up, multiple pregnancies, neonates born via caesarean section, home delivery, PROM, maternal DM, maternal HIV/AIDS, preterm birth, neonatal sepsis, and an Apgar score of less than 7 were significantly associated with the time to discharge of neonates with RD. However, in the multivariable analysis, being male, neonates born via caesarean section, home delivery, maternal DM, preterm birth, neonatal sepsis, PROM, and an Apgar score of less than 7 were the factors which continued as statistically significant predictors of RD. The hazard ratio for RD in male neonates was 2.4 times higher than their female counterparts [AHR: 2.4 (95%CI: 1.1, 3.1)]. The current study also showed that the hazard ratio for RD among neonates born via caesarean section had nearly two times the risk compared to neonates born vaginally [AHR: 1.9 (95%CI: 1.6, 2.3)]. In this study, the risk of RD in neonates born at home was almost three times higher than those delivered at a health institution [AHR: 2.9 (95%CI: 1.5, 5,2)]. This result also indicated that neonates delivered from mothers who had DM had a 2.3 times higher risk of RD as compared with their non-DM counterparts [AHR 2.3 (95%CI: 1.4, 3.6)]. Moreover, as the gestational age increases by one week the rate of RD decreased by 10% [AHR: 2.9 (95%CI: 1.6, 5.1)]. The risk of RD also increased threefold for a neonate who had an Apgar score of less than 7 as compared with one having an Apgar score greater than or equal to 7 [AHR: 3.1 (95%CI: 1.8, 5.0)]. Additionally, neonatal sepsis increases the risk of RD by 60% [AHR: 1.6 (95%CI: 1.1, 2.4)]. The last predictor for RD was to be born from mothers experiencing PROM, with neonates having a 1.11.1(1.8,1.5) times higher risk of RD than their counterparts not experiencing PROM [AHR: 1.1 (95%CI: 1.8, 1.5)] (Table 3).

Table 3

Gompertz hazard model for predictors of RD among neonates admitted to the NICU at Black Lion Specialized Hospital, Ethiopia (N = 571).

Predictor	Category	RD (n, %)	Censored (%)	Total (%)	CHR (95%CI)	AHR (95%CI)
Mother’s age (years)	<20	50 (20.4)	69 (21.2)	119 (10.9)	1.5 (0.97, 2.4)	1.4 (1.3, 1.9)
	20–34	107 (43.7)	44 (13.5)	151 (74.6)	1
	≥34	88 (35.9)	213 (78.4)	301 (14.7)	2.7 (1.18, 3.4)	2.8(1.8, 3.3)
Sex	Female	171 (48.6)	101 (46.2.)	272 (47.6)	1
	Male	181 (51.4)	118 (53.8)	299 (52.4)	1.7 (1.2, 2.3) **	2.4 (1.1, 3.1) *
Place of delivery	Home				3.14 (2.3, 5.2)	2.9 (1.5, 5.2) *
	Health institution				1
ANC follow up	Yes	56 (22.8)	113 (34.7)	169 (29.6)	0.4 (0.3, 0.5) **	0.8 (0.54, 1.19)
	No	189 (77.2)	213 (65.3)	402 (70.4)	1
Multiple pregnancy	Yes	23 (9.4)	26 (8)	49 (8.5)	1.6 (1.1, 2.1) **	1.1 (0.9, 1.6)
	No	22 (90.6)	300 (92)	351 (91.5)	1
PROM	Yes	143 (58.4)	107 (32.8)	250 (43.8)	1.5 (1.1, 2.0) *	1.1(1.8, 1.5) *
	No	102 (41.6)	219 (67.2)	321 (56.2)	1
Mode of delivery	Caesarean section	132 (53.8)	103 (31.6)	235 (41.2)	1.6 (1.2, 2.2) **	1.9 (1.6, 2.3)
	Vaginal Caesarean section	113 (46.2)	223 (68.4)	336 (58.8)	1
HIV/AIDS	Yes	35 (14.3)	41 (12.6)	76 (13.3)	1.9 (1.3, 2.7) **	1.5(0.9, 2.5)
	No	210 (85.7)	285 (87.4)	495 (86.7)	1
Maternal DM	Yes	39 (15.9)	22 (6.7)	61 (10.7)	2.4 (1.6, 3.5) **	2.3 (1.4, 3.6) **
	No	206 (84.1)	304 (93.3)	510 (89.3)	1
Sepsis	Yes	189 (77.1)	122 (37.4)	311 (54.5)	2.2 (1.6, 3.1) **	1.6 (1.1, 2.4) **
	No	56 (22.9)	204 (62.6)	260 (45.5)	1
GA	<37	23 (13.5)	8	31 (5.4)	6.3 (3.9, 10.2) **	2.9 (1.6, 5.1) **
	≥37	61 (35.9)	271 (67.6)	332 (58.1)	1
Neonatal weight (g)	<1000	22 (12.9)	11	33 (5.8)	3.8 (1.9, 7.5) **	1.9 (0.9, 4.3)
	1000–1500	56 (32.9)	99 (24.7)	155 (27.1)	1.3 (0.7, 2.4)	0.8 (0.41, 1.6)
	1500–2500	84 (49.4)	257 (64.1)	341 (59.7)	1.1 (0.6, 1.9)	0.8 (0.4, 1.4)
	≥2500	8	34 (8.5)	42 (7.4)	1
First minute Apgar Score	<7	154 (90.6)	283 (70.5)	437 (76.5)	3.2 (1.9, 5.4) *	3.1 (1.8, 5.0) *
	≥7	16	118 (29.5)	134 (23.5)	1
Fifth minute Apgar score	<7	128 (75.2)	131 (32.7)	259 (45.4)	3.8 (2.7, 5.4) **	1.81 (1.3, 4.8) **
	≥7	42 (24.8)	270 (67.3)	312 (54.6)	1

Discussion

In the current study, the overall proportion of neonates with RD admitted to the Black Lion Specialized Hospital NICU was 42.9% (95%CI: 39.3–46.1%). This finding is in line with a study conducted in the Republic of China [23]. However, our finding is higher than studies conducted in several countries including Nepal (34%) [24], India (33.4%) [10], Egypt (34.3%) [25], Pakistan (4.6%) [26], Northern Italy (20.1%) [27], and Portugal (8.83%) [28]. Variance noted in these studies may have been due to differences in the study settings which maybe more advanced maternal newborn care services in some locations than in others. Additionally, sample size, study design, and population socio-demographic characteristics may also lead to the differences observed between studies. Interestingly, the prevalence of RD found in this study was lower than studies from Saudi Arabia (54.7%) [8], Cameroon (47.5%) [7], and Poland (54.29%) [29]. These differences may reflect the quality/qualifications of staff, public awareness to attended births, and cultural beliefs.

Based on the current finding, the overall incidence of RD was 8.1 per 100 neonate-days (95%CI: 7.3, 8.9). The common causes of RD in our study were RDS and meconium aspiration, which is similar to previous findings from Nepal and Egypt [24, 25].

This study found that there were multiple predictors of RD in neonates from Ethiopia, including preterm birth, caesarean section delivery, Apgar score < 7, sepsis, PROM, maternal DM, and home delivery. The risk of RD in male neonates was 2.4 times higher than their female counterparts; a finding which was also found in studies done in China [28] and Cameroon [7]. This aligns with the fact that male neonates have higher levels of circulating testosterone than females, which may be associated with differences in pulmonary biomechanics and vascular development. For those neonates delivered via caesarean section there was a nearly two times higher risk of developing RD than in non-caesarean births. This was also found in neonate studies from China [23], Cameroon [7], and Italy [30]. Moreover, we found that the risk of RD for neonates born at home was almost three times higher than those delivered at a health institution.

Mothers with DM bore infants 2.3 times more likely to develop RD than non-DM mothers, which is 2again a finding supported by research done in China [31]. It is possible that this relates to the fact that these neonates have plentiful glucose stores, but develop hypoglycemia because of high insulin secretion induced by maternal and fetal hyperglycemia.

Our study also found that preterm neonates had a threefold greater likelihood of RD than those who were term births, which aligns with work from Cameron [7] and Italy [30]. This finding seems to coincide with the positive association between gestational age and fetal development, thereby reducing complications as the level of prematurity is lessened. Additionally, those neonates born premature often have immature lung structures which might delay intrapulmonary fluid absorption, a deficiency in pulmonary surfactant, and inefficient gas exchange. The risk of RD was also increased by threefold in neonates who had an Apgar score less than 7, which has been previously reported in other studies [7]. Finally, neonatal sepsis was significantly associated with the risk of developing RD as was found in Nepal and Egypt, [24, 25].

Limitations

Since the data were collected from secondary source; some important predictors such as socioeconomic factors like nutritional status of mother, educational level, birth interval might be missed which will have a significant on RD. The study area covers only TASH; its generalizability to all hospitals of the city and Ethiopia is may not be possible and this might also decrease our precision.

Conclusion

RD was found to be a major public health problem for neonates that were admitted to NICU of Black Lion Specialized Hospital. Those neonates delivered at home, delivered through caesarean section, born preterm, who had an Apgar score < 7, or were born from diabetic mothers were most likely to develop RD. Thus, to actively reduce the risk of the development of RD in neonates, medical professionals should support pregnant mother’s health wherever possible and encourage those mothers to give birth in health care institutions, especially in premature birth situations.

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Checklist used to assess incidence of RD and its predictors.

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9 Feb 2020

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4 May 2020

PONE-D-20-01297

Incidence of respiratory distress and its predictors among neonates admitted at neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia

PLOS ONE

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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.

6. Thank you for stating the following financial disclosure:

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

At this time, please address the following queries:

Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

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If you did not receive any funding for this study, please state: “The authors received no specific funding for this work.”

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

7. Please amend the manuscript submission data (via Edit Submission) to include author Pammla Margaret Petrucka.

8. Please amend your list of authors on the manuscript to ensure that each author is linked to an affiliation. Authors’ affiliations should reflect the institution where the work was done (if authors moved subsequently, you can also list the new affiliation stating “current affiliation:….” as necessary).

9. Please include your tables as part of your main manuscript and remove the individual files.

Please note that supplementary tables should be uploaded as separate "supporting information" files

10. Your ethics statement must appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please also ensure that your ethics statement is included in your manuscript, as the ethics section of your online submission will not be published alongside your manuscript.

[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

**********

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

Reviewer #1: 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

**********

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: 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: The revised manuscript is much improved with the exception of the abstract. The topic is important. As the authors have correctly noted without knowing what causes respiratory distress in their setting you cannot develop an effective strategy to reduce the incidence and I congratulate them for this.

The abstract still needs major work. The same things are repeated 3-4 times in the abstract's result and conclusion sections and don't need to be. The first sentence of the abstract needs to be deleted as that is said in the results section. The 3rd and 4th sentences need to be revised and combined again so they are not mostly a revision of the results section. Authors might consider something like Concerned bodies Ethiopia and other low-resource nurseries with similar risk factors should develop a strategy to decrease respiratory distress in their nurseries. Based on our findings this would likely include encouraging more hospital births, better control of diabetes in pregnancy, improved neonatal resuscitation and addressing ways to decrease the need for frequent caesarean sections.

Background has been improved.

In second paragraph still have missing reference develop significant morbidity ?? source----need to add reference.

In 3rd paragraph eliminate Meconium stained amniotic fluid OR combine meconium stained amniotic fluid with meconium aspiration syndrome as that is the real cause of RD i.e. meconium stained amniotic fluid leading to meconium aspiration syndrome

Could be improved by better lead in as to why these results would be helpful and how they relate to other locales. In third paragraph of background would start paragraph off something like--Recognized causes of RD in other low and high resource countries include.......

Sentence starting with In contrast needs to be combined with 3rd paragraph and not be free standing.

In the paragraph just above table 2 the sentence half of the neonates that was delivered should read and half the neonates that were delivered via caesarean section

Tables and Graphs are approrpiate

Discussion

Would clarify the sentence beginning with such variance. I think you mean Variance noted in these studies may have been due to differences in the study settings which maybe more advanced in some locations than in others.

Would strengthen your conclusion similar to what I did in the abstract i.e. how do the results of this study inform what you and others in similar nurseries need to do to decrease the incidence of respiratory distress.

**********

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

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

5 Jun 2020

Dear Academic Editor!

PLOS ONE

Response to Academic Editor and Reviewers

I am pleased to resubmit for publication version of “Incidence of respiratory distress and its predictors among neonates admitted to the neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia” for a review as original research in PLOS ONE.

The comments of the editor and the reviewers were highly insightful and enabled us to greatly improve the quality of our manuscript. Therefore, based on the editor’s and the reviewers’ concerns we have made extensive edition in our manuscript. The comments of the editor and the reviewers were highly insightful and enabled us to greatly improve the quality of our manuscript. Therefore, based on the editor’s and the reviewers’ concerns we have made extensive edition in our manuscript. Especially we have extensively edited the manuscript by a professional language editor, at Excision Editing (a fluent, native Australian, English-language speaker thoroughly edited the manuscript for language usage, spelling, and grammar) before submitting the revised version. The formatting of the text and document (text sizes and grammatical errors) were also edited. His name is called Dr. Ryan Bell(CEO and Chief Editor Excision Editing)

In the following pages, we have addressed yours’ concerns in a point by point format.

We look forward to hearing from you at your earliest convenience.

Thank you for your consideration of this manuscript!

Kind regards,

Yared Asmare Aynalem.

On behalf of authors

Editors comment

PONE-D-20-01297

Incidence of respiratory distress and its predictors among neonates admitted at neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia

PLOS ONE

Dear Yared Asmare Aynalem,

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.

Response: thank you very much for consideration.

We would appreciate receiving your revised manuscript by Jun 18 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Please include the following items when submitting your revised manuscript:

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• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.

• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Response: thank you very much. We have sent the revised manuscript as based on the plose one guideline and as per editors comment

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Georg M. Schmölzer

Academic Editor

PLOS ONE

Response: thank you very much

additional Editor Comments:

Thank you for your submission,

Response: thank you very much

In addition to the reviewers comments, please see below:

Please add the STROBE - Statement checklist for cohort studies when you upload the revisions.

Response: thank you very much for reminding us to include the STROBE statement checklist.as per your suggestion we have include it.

Journal requirements:

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

Response: thank you very much

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

Response: thank you .we have correct our manuscript based one PLOS ONE's style requirements including the file naming. We have correct all the intended correction based on the line that the editor provided to us(plose one submission guideline)

2. Thank you for including your ethics statement:

'Ethical clearance was obtained from Addis Ababa University, College of Nursing and Midwifery Research Committee. The full name of the ethical committee/institutional review board(s) that approved our specific study is “ College of health science ethical review bord ,Addis Ababa Universty”

Letters of cooperation were written to Black Lion Specialized Hospital and subsequently permission was obtained from the clinical director and relevant department and unit heads of the hospital. Following these approvals, access to the medical charts was undertaken with due diligence to maintain participant confidentiality.'

Response: thank you for acknowledging that

a. Please amend your current ethics statement to include the full name of the ethics committee/institutional review board(s) that approved your specific study and confirm that your named institutional review board or ethics committee specifically approved this study.

from Addis Ababa University, College of Nursing and Midwifery Research Committee. Letters

Response: thank you this concern .The full name of the ethical committee/institutional review board(s) that approved our specific study is “ College of health science ethical review bord ,Addis Ababa Universty”

b. Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”).

Response: thank you .we have edited that

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

Specifically, please ensure that you have discussed whether all data were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent.

If patients provided informed written consent to have data from their medical records used in research, please include this information.

For additional information about PLOS ONE ethical requirements for human subjects research, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-human-subjects-research

Response: we acknowledge for the issue. since the data were taken from the neonatal record, what we have done is that providing the ethical review bord letters to the hospital manager, particularly to the pediatric ward directors. then they provide to us a later permission. then we try to retrieve their data by using their card number. since it didn’t have a direct effect/harm on the neonate because of chart review. the patient was not able to gave the written informed consent. because we have reviewed the last 5 years chart of their new born. rather we try to keep the confidentiality issue by coding without listing their name.

4. In your Methods section, please provide additional information about the participant recruitment method and the demographic details of your participants.

Response: thank you very much. the demographic detail of the participants is stated as follows; study was conducted in Addis Ababa, a capital city of Ethiopia at black lion hospital. Addis Ababa has ten sub-cities in which the City lies at an altitude of 7,546 feet (2,300metres). It has twelve governmental and nine nongovernmental hospitals. The NICU of black lion hospital ward is able to accommodate a maximum of 60 patients with average of 20-40 patient’s daily admission. There are on average 5000-6000 annual admissions of neonates and 75% of admissions are from referral of different birth centers. The study was conducted from March to April 1, 2018.

Please ensure you have provided sufficient details to replicate the analyses such as:

a) the recruitment date range (month and year),

Response: thank you very much. the recruitment date range were from January 2013 to the last of March 2018

b) a description of how participants were recruited, and

Response: thank you very much .The neonatal chart number were taken from the HMIS- data base. The total patient admitted to NICU from January 2013-last of March 2018 were 5000. We have found the number of admissions for each year. The sample were proportionally allocated for each year, and with systematics sampling; the study participants of each year were selected as follows. First, numbering the units of each year on the frame from 1 to N (N=total admission of each year), then we determine the sampling interval(K) by dividing the number of units in the population by the desired sample size of each year (n=sample size of each year) which gives 8. Then number between one and 8 at random was selected (2 were selected). This number is called the random start and the first number included in the sample. Then later Selection was conducted every 8th unit after that first number.

c) descriptions of where participants were recruited and where the research took place."

Response: thank you .The study were conducted in NICU of Black Lion hospital, the larger and the most known referal hospital of Ethiopia ,located in the capital of Ethiopia ,Addis abba .

5. 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.

Response: thank you.Sorry for the inconivenec.it is to mean all data are accessible on online.

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.

Response: thank you.all data can be accessed on online

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.

upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information file

Response: thank you We have upload the minimal anonymized data set necessary to replicate our study findings as a either Supporting Information file. upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information file

6. Thank you for stating the following financial disclosure:

Response: thank you for acknowledging that

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

At this time, please address the following queries:

a. Please clarify the sources of funding (financial or material support) for your study. List the grants or organizations that supported your study, including funding received from your institution.

Response: thank you for response.it was self-sponsored /we the authors were the source of the funding . The authors have also confirmed that no financial funding was received for the study, authorship, and publication of this article

b. State what role the funders took in the study. If the funders had no role in your study, please state: “The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

Response: thank you. we haven’t any source of the fund. We all the authors participate in select the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

c. If any authors received a salary from any of your funders, please state which authors and which funders.

Response: thank you. None of the authors received a salary .because it were self-sponsored

d. If you did not receive any funding for this study, please state: “The authors Response: thank you .The authors received no specific funding for this work.”

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

Response: thank you.we included it to the cover latter

7. Please amend the manuscript submission data (via Edit Submission) to include author Pammla Margaret Petrucka.

Response: thank you.we have included author Pammla Margaret Petrucka in the manuscript submission data via Edit Submission

8. Please amend your list of authors on the manuscript to ensure that each author is linked to an affiliation. Authors’ affiliations should reflect the institution where the work was done (if authors moved subsequently, you can also list the new affiliation stating “current affiliation:….” as necessary).

Response: thank you. We have amended the list of authors on the manuscript that each author is linked to an affiliation. But there is no any new affiliation stating “current affiliation.

9. Please include your tables as part of your main manuscript and remove the individual files.

Response: thank you. We included the table as a part of the main manuscript

Please note that supplementary tables should be uploaded as separate "supporting information" files

Response: thank you.we have attached supplementary tables as a separate "supporting information" files

10. Your ethics statement must appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please move it to the Methods section and delete it from any other section. Please also ensure that your ethics statement is included in your manuscript, as the ethics section of your online submission will not be published alongside your manuscript.

Response: thank you.we have moved the ethical statement in the Methods section of our manuscript and we have incorporating it in the manuscript.

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

Response: thank you for acknowledgment

________________________________________

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

Reviewer #1: Yes

Response: thank you for acknowledgment

________________________________________

________________________________________

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

Response: thank you for acknowledgment

________________________________________

________________________________________

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: Yes

Response: thank you for acknowledgment

________________________________________

________________________________________

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)

Response: thank you .we took our time to correct all the concern of the reviewers

________________________________________

Reviewer #1: The revised manuscript is much improved with the exception of the abstract. The topic is important. As the authors have correctly noted without knowing what causes respiratory distress in their setting you cannot develop an effective strategy to reduce the incidence and I congratulate them for this.

Response: thank you for acknowledgment

________________________________________

The abstract still needs major work. The same things are repeated 3-4 times in the abstract's result and conclusion sections and don't need to be. The first sentence of the abstract needs to be deleted as that is said in the results section. The 3rd and 4th sentences need to be revised and combined again so they are not mostly a revision of the results section. Authors might consider something like Concerned bodies Ethiopia and other low-resource nurseries with similar risk factors should develop a strategy to decrease respiratory distress in their nurseries. Based on our findings this would likely include encouraging more hospital births, better control of diabetes in pregnancy, improved neonatal resuscitation and addressing ways to decrease the need for frequent caesarean sections.

Response: thank you for your concern. We have included all your contractive feedback to our papers. See the highlight. Additionally, a professional language editor (Dr. Ryan Bell CEO and Chief Editor Excision Editing)was edited the paper for the second round.

Background has been improved.

In second paragraph still have missing reference develop significant morbidity ?? source----need to add reference.

Response: thank you for your concern. We would like to excuse for the inconvenience. we have cited it and highlighted

In 3rd paragraph eliminate Meconium stained amniotic fluid OR combine meconium stained amniotic fluid with meconium aspiration syndrome as that is the real cause of RD i.e. meconium stained amniotic fluid leading to meconium aspiration syndrome

Response: thank you for your concern. we correct it as meconium aspiration syndrome per your recommendation. thanks once again

Could be improved by better lead in as to why these results would be helpful and how they relate to other locales. In third paragraph of background would start paragraph off something like--Recognized causes of RD in other low and high resource countries include.......

Response: thank you for your concern.we have modified it. Also see the highlights

Sentence starting with In contrast needs to be combined with 3rd paragraph and not be free standing.

Response: thank you for your critical revision. We have combined it as per your request and contractive feedback

In the paragraph just above table 2 the sentence half of the neonates that was delivered should read and half the neonates that were delivered via caesarean section

Response: thank you for your critical revision. we edited it.

Tables and Graphs are appropriate

Response: thank you for acknowledgment

Discussion

Would clarify the sentence beginning with such variance. I think you mean Variance noted in these studies may have been due to differences in the study settings which maybe more advanced in some locations than in others.

Response: thank you for your critical revision.we have include the suggestion given by our reviewer.

Would strengthen your conclusion similar to what I did in the abstract i.e. how do the results of this study inform what you and others in similar nurseries need to do to decrease the incidence of respiratory distress.

Response: We thank you very much for this important recommendation. Based on your recommendations, we rearranged it

________________________________________

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

Response: We thank you for reminding us to publish peer review history of their article. sorry for the inconvenience. we the authors are happy to published it.

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 us at figures@plos.org. Please note that Supporting Information files do not need this s

Response: We thank you for reminding us to use PACE for uploading our figures. We have attached the figures with PACE as per your recommendation

Thank you

Submitted filename: Response to editor.docx

Click here for additional data file.

16 Jun 2020

PONE-D-20-01297R1

Incidence of respiratory distress and its predictors among neonates admitted to the neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia

PLOS ONE

Dear Dr. Yared Asmare Aynalem,

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.

Please submit your revised manuscript by July 31 2020. 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

We look forward to receiving your revised manuscript.

Kind regards,

Georg M. Schmölzer

Academic Editor

PLOS ONE

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

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 #1: 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 #1: Yes

**********

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

Reviewer #1: 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 #1: 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 #1: 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 #1: Under Background

Probably more correct to say. “It is often seen during the transition from fetal to neonatal life”. Not triggered by

**********

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 #1: No

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16 Jun 2020

Dear Academic Editor!

PLOS ONE

A letter Accompanying Revision in Response to editor and Reviewers Comment

I am pleased to resubmit for publication version of “Incidence of respiratory distress and its predictors among neonates admitted to the neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia” for a review as original research in PLOS ONE.

financial disclosure: The authors confirmed that no financial funding was received for the study. None of the authors received specific funding for this work.

The comments of the editor and reviewers were highly insightful and enabled us to greatly improve the quality of our manuscript. Therefore, based on the editor and reviewers’ concerns we have made extensive edition in our manuscript. In the following pages, we have addressed yours’ concerns in a point by point format.

We look forward to hearing from you at your earliest convenience.

Thank you for your consideration of this manuscript!

Sincerely,

Yared Asmare Aynalem

On behalf of authors

PONE-D-20-01297R1

Incidence of respiratory distress and its predictors among neonates admitted to the neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia

PLOS ONE

Dear Dr. Yared Asmare Aynalem,

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.

Response: We thank you very much for consideration

Please submit your revised manuscript by July 31 2020. 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.

Response: We thank you very much. We have submitted it.

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Response: We thank you very much. We have submitted Response to Reviewers, Revised Manuscript with Track Changes and Manuscript separately

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.

Response: We thank you. We have included the financial disclosure as The authors have also confirmed that no financial funding was received for the study, authorship, and publication of this article.

the figures were uploaded with the plos one guide line

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

Response. Thank you. We think that it is not applicable

We look forward to receiving your revised manuscript.

Kind regards,

Georg M. Schmölzer

Academic Editor

PLOS ONE

Response. Big thanks. We will send it as soon as possible

Response

Reviewer #

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 #1: All comments have been addressed

________________________________________

Response: thank you very much for acknowledging it

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

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Reviewer #1: Yes

Response: thank you very much.

________________________________________

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

Reviewer #1: Yes

Response: thank you very much.

________________________________________

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Reviewer #1: Yes

Response: thank you very much.

________________________________________

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Reviewer #1: Yes

Response: thank you very much.

________________________________________

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Reviewer #1: Under Background

Probably more correct to say. “It is often seen during the transition from fetal to neonatal life”. Not triggered by

Response: thank you very much. Response: Based on your recommendations, we have addressed the issue. See the track change

________________________________________

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Reviewer #1: No

Response: Thank you

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.

Response: thank you. We have uploaded figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool.

thank you

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

18 Jun 2020

Incidence of respiratory distress and its predictors among neonates admitted to the neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia

PONE-D-20-01297R2

Dear Dr. Yared Asmare Aynalem,

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.

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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,

Georg M. Schmölzer

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

22 Jun 2020

PONE-D-20-01297R2

Incidence of respiratory distress and its predictors among neonates admitted to the neonatal intensive care unit, Black Lion Specialized Hospital, Addis Ababa, Ethiopia

Dear Dr. Aynalem:

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.

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

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Georg M. Schmölzer

Academic Editor

PLOS ONE