Outcome of induction and associated factors among induced labours in public Hospitals of Harari Regional State, Eastern Ethiopia: A two years’ retrospective analysis

Yimer Mohammed Beshir; Mohammed Abdurke Kure; Gudina Egata; Kedir Teji Roba

doi:10.1371/journal.pone.0259723

. 2021 Nov 9;16(11):e0259723. doi: 10.1371/journal.pone.0259723

Outcome of induction and associated factors among induced labours in public Hospitals of Harari Regional State, Eastern Ethiopia: A two years’ retrospective analysis

Yimer Mohammed Beshir ¹, Mohammed Abdurke Kure ^2,^*, Gudina Egata ³, Kedir Teji Roba ²

Editor: Subash Chandra Gupta⁴

PMCID: PMC8577748 PMID: 34752507

Abstract

Background

Induction of labor (IOL) is an essential intervention to reduce adverse maternal and neonatal outcomes. It is also improved pregnancy outcomes, especially in resource-limited countries, where maternal and perinatal mortality is unacceptably high. However, there is a scarcity of evidence regarding the outcome of induction of labor and its predictors in low-income countries like Sub-Saharan Africa. Therefore, this study was aimed at assessing the outcome of induction of labor and associated factors among mothers who underwent labor induction in public Hospitals of Harari Regional State, Estern Ethiopia.

Methods

A facility-based cross-sectional study was conducted from 1 to 30 March, 2019 in Harari Regional State, Eastern Ethiopia. A total of 717 mothers who underwent induction of labor in public Hospitals of Harari Regional State, Eastern Ethiopia from January 2017 to December 2018 were enrolled in the study. Data were collected using a pretested structured questionnaire. The collected data were entered into Epi-data version 3.1 and exported to SPSS version 24 (IBM SPSS Statistics, 2016) for further analysis. A multivariable logistic regression analysis was performed to estimate the effects of each predictor variable on the outcome of induction of labor after controlling for potential confounders. Statistical significance was declared at p-value <0.05.

Results

Overall, the prevalence of success of induction of labor was 65% [95% CI (61.5, 68.5)]. Pre-eclampsia/eclampsia was found to be the most common indication for induction of labor (46.70%) followed by pre-labor rupture of fetal membrane (33.5%). In the final model of multivariable analysis, predictors such as: maternal age < 24 years old [AOR = 1.93, 95%CI(1.14, 3.26)], nulliparity[AOR = 0.34, 95%CI(0.19, 0.59)], unfavorable Bishop score [AOR = 0.06, 95%CI(0.03, 0.12)], intermediate Bishop score [AOR = 0.08, 95%CI(0.04, 0.14)], misoprostol only method [AOR = 2.29, 95%CI(1.01, 5.19)], nonreassuring fetal heart beat pattern [AOR = 0.14, 95%CI (0.07, 0.25)] and Birth weight 3500 grams and above[AOR = 0.32, 95% CI (0.17, 0.59)] were statistically associated with the successful outcome of induction of labor.

Conclusion

The prevalence of successful of induction of labor was relatively low in this study area because only two-thirds of the mothers who underwent induction of labor had a successful of induction. Therefore, this result calls for all stakeholders to give more emphasis on locally available induction protocols and guidelines. In addition, pre-induction conditions must be taken into consideration to avoid unwanted effect of failed induction of labour.

Introduction

Induction of labor (IOL) is an artificial initiation of labour or uterine contraction before the onset of spontaneous true labour in situations when the benefits of delivery of the fetus are outweighing the continuity of the pregnancy [1, 2]. The main aim of initiation of labor without its true time is to have the health of the mother and unborn fetus and to minimize severe obstetric complications related to unnecessary cesarean section [1]. However, sometimes this artificial initiation of labour may result in failure of achieving a good uterine contractions leading to failed induction. This failed IOL is associated with an increased risk of numerous adverse maternal and perinatal outcomes [3, 4].

Globally, the prevalence of success of induction of labor varies across the continents. A secondary analysis of World Health Organization (WHO) on the outcomes of induction of labor in sixteen Asian and African countries indicated the average success of IOL in Asian countries was 81.6%, ranging from 67.9% in China to 90.10% in Cambodia, and 83.4% in African countries ranging from 57.3% in Uganda to the highest range 95% in Angola [5]. Besides, the analysis showed the most common type of induction method in both continents was oxytocin only method which accounts an average proportion of 86.1% and 82.4% in African and Asian countries respectively [5]. In Ethiopia, the success of IOL was lower than the average rate of Asian and African countries. For instance; a previous few studies conducted in Ethiopia have shown a success of induction of labor as 65.7% in Jimma, Northern Ethiopia [6], 61.6% in Hawassa, Southern Ethiopia [7], and 62.2% in Addis Ababa Army referral Hospital, central Ethiopia [8].

Although induction of labor for termination of pregnancy is acceptable and effective, sometimes it has adverse consequences on the health of the mother and unborn fetus [9]. For instance; a previous studies have shown that the effects of outcomes of IOL are not only on the modes of delivery but also causes adverse maternal and perinatal outcomes such as postpartum hemorrhage [10], hyperstimulation of the uterus that results in uterine rupture, chorioamnionitis, endometritis [11], fetal hypoxia, maternal fluid intoxication [12], stillbirth [13] and severe birth asphyxia [14].

Furthermore, researchers have found that post-term pregnancy, hypertensive disorders (pre-eclampsia/eclampsia) during pregnancy, pre-labor rupture of membrane (PROM) [15], post-term pregnancy [16], intrauterine growth restriction(IUGR), intrauterine fetal death (IUFD) [3], abruption placenta, fetal congenital anomalies [9], and other medical disorders are some indications for the intervention of induction of labor and may influence the success of induction of labor [9, 17]. Moreover, studies have shown that several factors are associated with the success of IOL to achieve vaginal delivery. This success rate IOL can affected by factors such as methods of induction of labour, methods of cervical ripening either by surgical methods (artificial rapture of the membrane, balloon catheter, laminar) or pharmacological methods (Oxytocin, misoprostol) [18–20]. For example; factors like maternal age, gestational age of a pregnancy [21–23], multiparity [4], birth weight of less than 3500gm [24], and favorable cervical status [25] increase the likelihood of success rate of induction of labour.

In Ethiopia, although rare studies have been identified with different study types, still there is a scarcity of locally generated evidence regarding outcome of induction of labour and its predictors in Eastern Ethiopia [6, 8]. In Ethiopia, although few studies have been conducted in the last five years, almost all previous researchers were selective to central and Northern parts of the country(Addis Ababa, Amhara, and Tigray regions) [26–28], rarely to the Southern and Oromia regions [15, 29], and neglecting other parts of the country, particularly Afar, Harari, and Somali regions. Furthermore, to the best knowledge of the researchers, the outcomes of induction of labor has not been studied in this study area. Therefore, this study was aimed to fill this gap by assessing the outcome of induction of labor and its associated factors among mothers who underwent labor induction in public Hospitals of Harari Regional State, Eastern Ethiopia.

Methods and materials

Study setting, period, and design

A facility-based cross-sectional study (retrospective chart review) was conducted from 1 to 30 March, 2019 in two public Hospitals (Jugal Regional Hospital, and Hiwot Fana Specialized University Hospital) found in Harari Regional State, Eastern Ethiopia. Harari Region is one of the nine regional states of the Federal Democratic Republic of Ethiopia and covers an area of 334km². The Region is located in the Eastern part of Ethiopia at a distance of 526 km from the capital, Addis Ababa. According to the 2007 census conducted by the Central Statistics Agency (CSA) of Ethiopia, the total population of the Region was 183,415 (92,316 males and 91, 099 females) [30]. In the Region, there are 45 health facilities (34 health posts, 8 health centers, and 5 hospitals). Among the 5 hospitals found in the Regional State, only two of them are giving service as public hospitals. This study was conducted in these public hospitals, where different and multidimensional health care services being provided to the patient.

Population and sampling technique

All randomly selected women who delivered after induction of labor, and whose gestational age of pregnancy was greater than or equal to 28weeks in the selected public hospitals of Harari Regional State from January 2017 to December 2018 were enrolled in the study. However, mothers’ medical records/charts with incomplete documentation and lacking pertinent information were excluded from the study. In this study, the sample size was determined by considering different factors associated with the outcome of induction of labor using EPI-Info version 7.0 (USA, 2016). Thus, from the predictor variables, maternal parity was considered because it produces a maximum sample size. Thus, we took a previous research report from Suadi Arabia [31]. In this regard, we considered nulliparity as exposure because we follow the assumption that the success of induction of labor would be better in multiparous women than nulliparous. Thus, the success of induction of labor among nulliparous was considered as exposed and the success of induction of labor among multiparous women was considered as unexposed. Based on this information, the following assumptions were made. Proportion of outcome among nulliparous (p = 59%), the proportion of outcome among multiparous (p = 47.8%), two-sided confidence level = 95%, a tolerable margin = 5%, power of 80%, the ratio of unexposed to expose = 1.0 and by adding 10% contingency for non-response rate, the final sample size for the study was 726.

Sampling techniques and procedures

Initially, the Harari Regional State was selected purposely as the study site. In the Harari Region, there are only two public Hospitals (Jugal Regional Hospital (JRH) and Hiwot Fana Specialized University Hospital (HFSUH)). HFSUH is the only referral Hospital hosted by Haramaya University in Eastern Ethiopia. Currently, both hospitals are providing different health services including labor and delivery services to the laboring mothers and newborns in maternity wards. According to the health management and information system (HMIS), the annual numbers of delivery reports were 2463 in Jugal Regional Hospital and 4256 in Hiwot Fana Specialized University Hospital. Similarly, previous information obtained from the hospitals’ delivery and discharge registration logbooks revealed that the annual number of women who managed with the induction of labor in 2018 was 307 in Jugal Regional Hospital and 552 in Hiwot Specialized University Hospital. Based on the above information, we reviewed two years data of the Hospitals’ registration logbooks of the labor ward. Thus, a total of 628 and 1134 mothers who underwent IOL at the gestational age of 28 weeks and more in JRH and HFSUH from January 2017 to December 2018 were identified respectively. We used a simple random sampling (SRS) technique to select study participants using a list frame of the delivery registar. The total sample size (n = 726) was proportionally allocated to both Hospitals. Accordingly, 256 charts were allocated for Jugal Regional Hospital and 470 charts were allocated for Hiwot Fana Specialized University Hospital. Finally, the patients’ charts were retrieved and pertinent information was obtained until the required sample size was achieved (Fig 1).

Data collection tools and procedures

Data were collected through a review of medical records using a structured questionnaire, which was prepared and customized after reviewing different relevant kinds of literature [6, 15, 26]. Clients’ charts, labor ward logbooks, discharge logbooks, and operation room logbooks were reviewed to collect the required data. Data were collected by six diploma Midwives who were trained on data collection tools and procedures under the supervision of three Bachelor of Science (BSc) nurses, and the principal investigator. Informed voluntary consent was sought from all authorized bodies of the Hospitals. All eligible medical records were manually and exhaustively searched from where they previously stored and filed in the board cabinets. Eligible charts were searched and allocated using patients’ Medical Record Numbers (MRNs) from the listed frames. All collected data were reviewed and checked by supervisor and the principal investigator for completeness, consistency, and if any missing blanks was found, corrective measures were taken immediately.

Study variables and measurements

In this study, the dependent variable was the outcome of induction of labor. This dependent variable was dichotomized into binary outcomes as 0 and 1. Thus, the successful of induction of labor was recoded as 1 and failed of induction of labor was recoded as 0. Success of induction of labor is defined as if a woman delivered vaginally either spontaneously or by instrument after induction and failed induction can be defined as if a woman delivered by cesarean section(C/S) due to failure to acquire either adequate uterine contraction (≥3 contractions or contractions lasting ≥40 seconds in 10 minutes period) or failed to show favorable cervical changes (reach at least 4cm in dilatation and fully effaced) despite being on oxytocin drip for at least eight hours or diagnosed as failed induction by any indications for any indication of cesarean section or it is diagnosed if adequate uterine contractions are not achieved after 6 to 8 hours of oxytocin administration and use of the maximum dose for at least one hours [6, 18].

The explanatory variables were categorized as socio-demographic factors (age and residency), obstetrics related factors (ANC follow-up, previous bad obstetrics history, gravity and parity, gestational age status, and Bishop Score status), obstetric indications related factors((preeclampsia/eclampsia, post-term pregnancy, the pre-labor rapture of the membrane (PROM), polyhydramnios, oligohydramnios, abruptio placenta, and intrauterine fetal death (IUFD)), fetal-related factors(nonreassuring fetal heartbeat pattern (NRFHBP), meconium passage, fetal weight, and fetal sex), methods of IOL related factors (Induction methods (oxytocin only, misoprostol only, oxytocin and artificial rupture of the membrane (ARM)), the time interval from initiation of induction till delivery of the fetus, and type of induction (elective and emergency)).

Measurements

Bishop Score System: The Bishop Score predicts the likelihood of vaginal delivery after induction with Oxytocin. With this scoring system, a number ranging from 0–13 is given to rate the condition of the cervix and fetal station. Interpretation of the Bishop’s score: Score<4: Unfavorable cervix is unlikely to yield for induction; cervical ripening is needed for success with induction. Postpone induction for next week if possible or use cervical ripening and plan induction for the next day. Score 5–8: Intermediate, Score = 9: Favorable cervical condition and induction is likely to succeed and there is no need for cervical ripening. Induction using Oxytocin can be planned for the next day [2, 18]. Oxytocin dosage protocol: According to Ethiopia FMOH, the national induction protocol was adopted and modified based on the WHO recommendation for induction of labor. According to this protocol, the oxytocin dosage is given in three doses for both primigravida and multigravida. This was identified in supplementary file one (S1 File).

Data quality control

A structured checklist, which consists of five sections, was prepared in the English language. Data collectors along with the supervisors were trained for one-day. The training was conducted regarding purpose of the study, data collection tool, data collection procedures, and data handling. A pretest was conducted on 30 mothers’ records (5% of the total sample) to ensure the validity of the tool, and the correction was made before the actual data collection. The principal investigator and supervisors checked on the spot and reviewed the checklists to ensure completeness and consistency of the information and immediate action was taken accordingly. Double data entry was done by two data clerks and the consistency of the entered data was cross-checked. Simple frequencies and cross-tabulations were done for missing values and outliers. The crosschecked was undertaken with hard copies of the collected data.

Data processing and analysis

The collected data were checked, coded, and entered into Epi data version 3.1 to minimize logical errors and design skipping patterns. Then, they were exported to SPSS windows version 24 (IBM SPSS Statistics, 2016) for further analysis. Descriptive statistics were carried out using simple frequency tables, proportions and summary measures. A bi-variable logistic regression analysis was used to identify the association between each independent variable and the outcome variable by using binary logistic regression. All variables having p-value ≤ 0.25 in the bi-variable analysis were included in the final model of multivariable analysis to control for potential confounders. Multi-collinearity was checked using variance inflation factor (VIF) and tolerance, and no collinearities were detected. Likewise, Hosmer-Lemeshow goodness of fitness test was used to check for model fitness and the result was found to be insignificant (p = 0.489), which indicates the model was well fitted. In the final model of multivariable logistic regression analysis, the Adjusted Odds Ratios (AOR) with 95%CI were estimated to identify the effects of independent variables on the outcome of induction of labor. Level of statistical significance was declared at a p-value <0.05.

Ethical considerations and consent to participate

Ethical clearance was obtained from Institutional Health Research Ethics Review Committee (IHRERC) of College of Health and Medical Sciences, Haramaya University. Supportive letters were written to Jugal Regional Hospital and Hiwot Fana Specialized University Hospital. All patient data were previously anonymized before consent was sought from the authorized bodies. Medical records of mothers who underwent labor induction from January 2017 to December 2018 were selected. These medical records of mothers were manually searched, and accessed from March 1^st to 30^th, 2019. Data confidentiality was maintained through anonymity by removing any personal identifiers. Confidentiality of the patient information was assured by omitting their names and using card numbers instead.

Results

Socio-demographic and obstetrics related characteristics of the participants

In this study, a total of 726 records of mothers who underwent induction of labor in selected public hospitals of Harari Regional State were retrieved and 717 charts were successfully extracted making the response rate of 98.80%. Nine charts were excluded from the analysis because of incompleteness and lack of pertinent information. The mean age of the mothers was 24.5 years (SD = ±6.86) ranged from 16 to 44 years. The majority 464 (64.70%) of the study participants were from rural setting. More than two-thirds (508, 70.85%) of the respondents had a history of antenatal care follow-up in the previous pregnancy. The mean gestational age was 36.63 weeks (SD ±3.35) and more than half (51.90%) of the mothers were within 37–40 weeks gestational age of a pregnancy (Table 1).

Table 1. Socio-demographic and obstetric related characteristics of mothers who delivered after induction of labor in public Hospitals of Harari Regional State, Eastern Ethiopia, 2019.

Characteristics	Categories	Frequency (n)	Percentage (%)
Age (years)	16–19	92	12.83
	20–24	214	29.85
	25–29	198	27.62
	30–34	101	14.08
	≥35	112	15.62
Residency	Rural	464	64.70
Residency	Urban	253	35.30
Has ANC follow up	Yes	508	70.85
Has ANC follow up	No	209	29.15
Gestational age (in weeks)	≤36	294	41.00
	37–40	372	51.88
	≥41	51	7.12
Parity	Nulli-para	344	47.98
	Primi-para	82	11.44
	Multi-para	291	40.58
Bad obstetrics history	Yes	107	14.92
Bad obstetrics history	No	610	85.08
Pre-induction Bishop score	Unfavorable	226	31.52
	Intermediate	206	28.73
	Favorable	285	39.70
Pre-labor rapture of Membrane	Yes	240	33.50
Pre-labor rapture of Membrane	No	477	66.50
Non-reassuring fetal heartbeat pattern	Yes	133	18.55
Non-reassuring fetal heartbeat pattern	No	584	81.45
Duration of IOL to till delivery	≤10hrs	500	69.70
Duration of IOL to till delivery	>10hrs	217	30.30

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Magnitude of the outcome of induction, and indications of induction

In this study, the proportion of success of induction of labor was 65% [95%CI (61.5,68.6) (Fig 2).

Regarding the indication of induction, the most common indication for induction of labor was pre-eclampsia/eclampsia which accounted for 335(46.70%), followed by pre-labor rupture of membrane 240 (33.50%) and intrauterine fetal death 54(7.5%) (Fig 3).

Methods of induction of labor, and mode of delivery

Of 717 mothers who underwent labor induction and enrolled in the study, 278(38.77%) of them underwent cervical ripening. Regarding the methods of induction of labor, the most common type of induction method was oxytocin intravenous drip regimen only 633(88.3%) followed by jointly oxytocin and misoprostol regimens 45(6.30%). Concerning the mode of delivery, of the seven-hundred-seventeen study participants included in the study, more than half 411(57.32%) of them gave birth through spontaneous vaginal delivery followed by cesarean section 251(35.01%) and operative vaginal delivery 51(7.67%) (Table 2).

Table 2. Methods of induction of labor and mode of delivery among mothers who delivered after induction of labor in public Hospitals, Harari Regional State, Eastern Ethiopia, 2019.

Variables	Categories	Frequency (n)	Percentage (%)
Cervical Ripening (N = 717)	Yes	278	38.77
Cervical Ripening (N = 717)	No	439	61.23
Ripening Methods (N = 278)	Misoprostol	139	50.00
	Dinoprostone	19	6.83
	Balloon Catheter	120	43.17
Methods of IOL (N = 717)	Oxytocin only	633	88.30
	ARM + Oxytocin	39	5.40
	Oxytocin+ misoprostol	45	6.30
Phases of IOL (N = 672)	First	70	10.42
	Second	103	15.33
	Third	499	74.25
Oxytocin drop per Minutes per 1L in Normal saline(N = 672)	20	19	2.83
	40	50	7.44
	60	119	17.71
	80	484	72.02
Route for misoprostol(N = 45)	Vaginal	31	68.89
	Oral	8	17.78
	Sublingual	6	13.33
Mode of delivery (N = 717)	SVD	411	57.32
	OVD	55	7.67
	C/S	251	35.01

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Key: ARM- Artificial Rupture of Membrane; SVD: Spontaneous Vaginal delivery; OVD: Operative Vaginal Delivery; C/S: Caesarean Section.

Factors associated with the outcome of induction of labor

In bi-variable logistic regression analysis (age, residency, parity, pre-induction Bishop score, PROM, methods of induction, nonreassuring fetal heartbeat pattern, neonatal weight) were significantly associated with outcomes of induction of labor (Table 3).

Table 3. Bivariable logistic regression analysis of factors associated with the outcome of induction of labor among mothers who delivered after IOL in public hospitals of Harari Regional State, Eastern Ethiopia, 2019.

Variables	Categories	Outcome of IOL		COR(95% CI)
Variables	Categories	Success (%)	Fail (%)	COR(95% CI)
Age (Years)	≤24	207(67.60)	99(32.40)	1.23(0.9, 1.7)^*
Age (Years)	>24	259(63.00)	152(37.00)	1.00
Residency	Rural	319(68.80)	145(31.20)	1.58(1.15, 2.18)^**
Residency	Urban	148(58.10)	106(41.90)	1.00
ANC follow up	Yes	325(64.00)	183(36.00)	0.86(0.61, 1.21)
ANC follow up	No	141(67.50)	68(32.50)	1.00
Gestational age	≤36	199(67.70)	95(32.30)	1.11(0.8, 1.53)
	37–40	243(65.30)	129(34.70)	1.00
	≥41	24(47.10)	27(52.90)	0.47(0.26, 0.85)
Parity	Nulli-Para	207(60.20)	137(39.80)	0.59(0.42, 0.83)^**
	Primi-para	50(61.00)	32(39.00)	0.61(0.37, 1.02)
	Multi-para	209(71.80)	82(28.20)	1.00
Bad obstetric history	Yes	66(61.70)	41(38.30)	0.85(0.55, 1.29)
Bad obstetric history	No	400(65.60)	210(334.40)	1.00
Pre-induction Bishop score	Unfavorable	116(51.30)	110(48.70)	0.15(0.10, 0.24)^**
	Intermediate	101(49.00)	105(51.00)	0.14(0.09, 0.22)^**
	Favorable	249(87.40)	36(12.60)	1.00
Pre-labor rupture of fetal membrane	Yes	176(73.30)	64(26.70)	1.77(1.26,2.49)^**
Pre-labor rupture of fetal membrane	No	290(60.80)	187(39.20)	1.00
Duration of of IOL till delivery	≤10 hours	323(64.60)	177(35.40)	0.94(0.68, 1.32)
Duration of of IOL till delivery	>10 hours	143(65.90)	74(34.10)	1.00
Methods of Induction	Oxytocin only	405(64.00)	228(36.00)	1.00
	ARM+oxytocin	28(71.80)	11(28.20)	1.43(0.70, 2.93)^*
	Oxytocin+Misoprostol	33(73.30)	12(26.70)	1.55(0.78, 3.06)^*
Nonreassuring fetal heartbeat pattern	Yes	35(26.30)	98(73.70)	0.13(0.08, 0.19)^**
Nonreassuring fetal heartbeat pattern	No	431(73.80)	153(26.20)	1.00
Birth weight of the newborn	<2500	158(70.90)	65(29.10)	1.18(0.83, 1.69)
	2500–3499	265(67.30)	129(32.70)	1.00
	≥3500	41(42.30)	56(57.70)	0.36(0.23, 0.56)^**

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Key: ARM-Artificial Rupture of Membrane, IOL-Induction of Labor;

* = p-value < 0.25,

** = statistically significant.

In the final model of multivariable logistic regression analysis, variables such as age, parity, pre-induction Bishop score, methods of induction of labor, nonreassuring fetal heartbeat pattern, and birth weight of the newborn were remained significantly associated with the outcomes of induction of labor. Accordingly, the odds of successful of induction of labor were two times higher among mothers whose age ≤24 years of age than those whose age was greater than 24years [AOR = 1.96, 95%CI (1.16, 3.31)]. Likewise, the odds of successful of induction of labor were 67% times lower among nullipara mothers compared to their counterparts (multipara women) [AOR = 0.33, 95%CI (0.19, 0.59)]. Moreover, the likelihood of successful of IOL was decreased by 94% among mothers who had unfavorable cervical status than those who had favorable cervix [AOR = 0.06, 95% CI (0.03, 0.12)]. Similarly, the likelihood of successful of induction of labor was 92% times lower among mothers who had intermediate cervical status than those who had a favorable cervix [AOR = 0.08, 95%CI (0.04, 0.14)]. Regarding the method of induction of labor, the odds of successful of IOL were 2.36 times higher among mothers who were induced by jointly oxytocin and misoprostol than those who were induced by oxytocin only method [AOR = 2.36, 95% CI(1.04, 5.32). Likewise, the likelihood of having successful of IOL was 86% times lower among mothers whose fetuses experienced nonreassuring fetal heartbeat patterns than those whose fetuses had no non-reassuring fetal heartbeat pattern [AOR = 0.14, 95% CI(0.07, 0.25)]. In addition, the weight of infant was independently associated with successful of IOL. Thus, the successful of IOL was decreased by 68% among mothers whose fetal weight greater than 3500 grams compared to those whose fetal weight was 25000–3499 grams [AOR = 0.32, 95%CI(0.17, 0.60)] (Table 4).

Table 4. Multivariable logistic regression analysis of factors associated with the success of induction of labor among mothers who delivered after induction of labor in public Hospitals of Harari Regional State, Eastern Ethiopia, 2019.

Variables	Categories	Outcome of IOL		COR(95%CI)	AOR (95%CI)
Variables	Categories	Success (%)	Fail (%)	COR(95%CI)	AOR (95%CI)
Age (years)	≤24	207(67.60)	99(32.40)	1.23(0.90, 1.70)	1.96(1.16, 3.31)*
Age (years)	>24	259(63.00)	152(37.00)	1.00	1.0
Residence	Rural	319(68.80)	145(31.20)	1.58(1.15, 2.18)	1.22(O.86, 1.27)
Residence	Urban	148(58.10)	106(41.90)	1.00	1.0
Parity	Nulli-Para	207(60.20)	137(39.80)	0.59(0.42, 0.80)	0.33(0.19, 0.59)^**
	Primi-para	50(61.00)	32(39.00)	0.61(0.37, 1.02)	0.51(0.26, 1.02)
	Multi-para	209(71.80)	82(28.20)	1.00	1.0
Pre-induction Bishop score	Unfavorable	116(51.30)	110(48.70)	0.15(0.10, 0.24)	0.06(0.03, 0.12)^**
	Intermediate	101(49.00)	105(51.00)	0.14(0.09, 0.22)	0.08(0.04, 0.14)^**
	Favorable	249(87.40)	36(12.60)	1.00	1.0
PROM	Yes	176(73.30)	64(26.70)	1.77(1.26, 2.49)^**	1.51(0.92, 2.13)
PROM	No	290(60.80)	187(39.20)	1.00	1.0
Methods of Induction	Oxytocin only	405(64.00)	228(36.00)	1.00	1.0
	ARM+oxytocin	28(71.80)	11(28.20)	1.43(0.70, 2.93)	1.35(0.49, 3.23)
	Oxytocin+Misoprostol	33(73.30)	12(26.70)	1.55(0.78, 3.06)	2.36(1.04, 5.32)^***
NRFHBP	Yes	35(26.30)	98(73.70)	0.13(0.08, 0.19)	0.14(0.08, 0.25)^***
NRFHBP	No	431(73.80)	153(26.20)	1.00	1.0
Birth weight	<2500	158(70.90)	65(29.10)	1.18(0.83, 1.69)	1.46(0.88, 2.42)
	≥3500	41(42.30)	56(57.70)	0.36(0.23, 0.56)	0.32(0.17, 0.60)^***
	2500–3499	265(67.30)	129(32.70)	1.00	1.0

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Keys: 1 = reference, p-values:

**≤ 0.01,

***≤0.001,

COR = Crude Odds Ratio, AOR = Adjusted, NRFHBP = Nonreassuring fetal heartbeat pattern, PROM = Pre-labor rupture of fetal membrane.

Discussion

In this study, the overall proportion of success of induction of labor was found to be 65%. Pre-eclampsia/eclampsia and prelabour rupture of the membrane were the most common indications for induction of labor. Age of the mother, parity, pre-induction Bishop score, method of induction, nonreassuring fetal heartbeat pattern, and weight of the newborn were factors significantly associated with outcomes of induction of labor.

In this study, the prevalence of success of induction of labor was relatively low. This result is in line with previous studies conducted in Ethiopia like Jimma University Teaching Hospital(65.7%) [6], Hawassa public health facilities(61.56%) [32], and Addis Ababa Army Referral Hospital(62.2%) [8]. Moreover, the finding is also nearly comparable with the cross-sectional studies conducted in South Africa (59.76%) [17], and Nigeria (63.5%) [16]. The possible justification for these similarities might be because of the definition of time interval for failed IOL (from six to eight hours) for intravenous oxytocin drips. Another possible explanation might be because using a similar standard protocol for induction of labor as the majority of the reports were from similar settings (limited resource countries). However, the current study finding is lower than the studies conducted in different countries like Ethiopia (80.3%) [26], China(76.9%) [33], Pakistan (82%) [34], Saudi Arabia(84%) [31], India (86.32%) [35] and Nigeria (82.2%) [36]. The possible justification for this discrepancy might be due to differences in socio-demographic characteristics of the study participants, the nature of study designs, and methods of data collections techniques. The other differences in estimate are due to the time gap between study periods, the geographical setting of the study population, and the difference in the sample size of the studies. In addition, definitions of failed induction per protocol might be attributed for these observed variations. For instance, type of methods of inductions, cervical ripening methods, maintaining the oxytocin concentration and dose adjustment while changing the infusion of bag might different per protocol.

In the final model of multivariable analysis, maternal age was independently associated with the success of induction of labor. Thus, the odds of successful of IOL were two times higher among mothers less than or equal to 24 years of age than those whose age greater than 24years. This is in line with studies conducted by Batinelli et al in Italy and Sara in Addis Ababa, central Ethiopia [4, 8]. This association might be due to maternal anatomical stability in the age group of lower than 25 years old. Reversely, the sacral promontory, ischial spine, and coccyx bone deformity increase (becoming shrink inward to the pelvic cavity that leads to decreasing of pelvic diameter) as age increases. Likewise, the success of induction of labor was affected by maternal parity. Thus, the likelihood having successful of IOL was reduced by more than two-thirds among nulliparous mothers when compared to multiparous women. This finding is also supported by previous studies conducted elsewhere such as King Khalid Hospital in Saudi Arabia, Kenyatta National Hospital in Kenya, and Hawassa Referral Hospital in southern Ethiopia [7, 31, 37]. This is might be due to direct induction before cervical ripening, undoing of cervical sweeping, and amniotomy after the active phase of the first stage of labor in nullipara mothers leads to failed induction. Other possible justifications might be attributed to multiparity because as the parity of the mother increases, the likelihood of failed induction of labor decreases as uterine muscles can be easily stimulated and contracted in multipara women.

Moreover, pre-induction cervical status (Bishop score) was found to be independent predictor of success of IOL. Accordingly, the successful of labor induction was lower in mothers who had unfavorable and intermediate Bishop scores. Thus, the likelihood of success of induction of labor was greater than ninety-percent among mothers who had a favorable Bishop score compared to those mothers who had unfavorable and intermediate Bishop Scores. This result is supported by studies conducted in Jimma University Specialized Hospital and Hawassa Town Health facilities which reported failed induction of labor in mothers with unfavorable and intermediate Bishop Score [6, 7]. This finding is supported by another study conducted in Addis Ababa, in which higher success of IOL was observed in mothers who had higher cervical Bishop Scores [8]. It is also supported by the scientific finding of different kinds of literature that the condition of the cervix is an important predictor, with the modified Bishop score which is a widely used scoring system that includes four cervical parameters (cervical consistency, effacement, position, and dilatation) and the station of presenting part of the fetus. This indicates that the un-ripened cervix is highly associated with failed induction. This is also might be because un-ripened cervical status (unfavorable cervix) is less likely to be affected by uterine muscle contractility and pressure of the fetal present part compared to the favorable cervix.

In this study, the type of method for induction was found to be an independent predictor of the success of induction of labor. Thus, the odds of successful of IOL were 2.36 times higher among mothers who were induced by jointly oxytocin and misoprostol than those who were induced by oxytocin only method. This result is in line with the previous studies conducted in Brazil, Zimbabwe, and Nigeria [16, 38, 39], which indicated higher success of IOL in combination of oxytocin and misoprostol than using either of the medication a lone. The possible explanation might be attributed to the nature of the regimen used for induction. This is because misoprostol does not need special storage and it is less likely to be affected by high temperature than oxytocin. The difference in the time interval, optimal dose, and mechanism of action on the uterus are also some possibilities.

Furthermore, the presence of fetal heartbeat abnormalities during labor induction was negatively associated with the success rate of induction of labor. Thus, mothers whose fetuses experienced nonreassuring fetal heartbeat patterns were 86% times less likely to have a successful IOL than those whose fetuses had a normal fetal heartbeat pattern. This is in line with the study conducted in South Carolina and in Addis Ababa Military Hospital, central Ethiopia [8, 40]. It is also supported by other studies conducted in Jordan and Ethiopia (Wolliso St. Luke Catholic Hospital), which explained that the absence of fetal heartbeat abnormality had a higher success rate than those who developed abnormal fetal heartbeat pattern [15]. The possible reason might be because the presence of fetal heartbeat abnormalities can cause fetal distress that leads to an increment of failure of induction of labor.

Finally, in this study, the birth weight was independently associated with success of IOL. Accordingly, those mothers whose fetal weight 3500 grams and greater were 68% times less likely to have a success rate IOL than those whose fetal weight was 2500–3499 grams. This finding is supported by studies conducted by Bertinelli et al in University Hospital ‘Le Scotte’ of Siena, Italy and in Kenyatta National Hospital by Rashida [4, 37]. The possible reason could be explained by when the weight of the fetus is greater than 3500 grams it causes cephalo-pelvic disproportion, which leads to the difficulty of vaginal delivery and hence it increases the failure rate of induction of labor.

Limitations of the study

Since we used a chart review cross-sectional study design, no causal association could have made. Moreover, the data were collected from a secondary source; some independent variables might be missed. The study was conducted only in public health institutions; pregnant women who underwent IOL at private health facilities were not included in the study.

Conclusion

Overall, the proportion of success of induction of labor was relatively low in this study area. Pre-eclampsia/eclampsia and prelabour rupture of the membrane were the most common indications of induction of labor in the study area. Maternal age, maternal parity, Bishop score, method of induction of labor, presence of nonreassuring fetal heartbeat pattern, and newborn weight at birth were independently and significantly associated with the success of induction of labor. Therefore, further work is needed to improve the success of induction of labor by assessing and monitoring maternal and fetal status before the initiation of induction of labor. Moreover, cue due attention should be given to induction protocols and standard guidelines for better outcomes of the success of induction of labor. Moreover, longitudinal studies are needed to identify the causal association of outcomes of induction of labor and its predictors.

Supporting information

S1 File. Induction protocol for induction of labour.

(PDF)

Click here for additional data file.^{(568.7KB, pdf)}

S1 Data. Data set used for analysis of the study conducted on IOL in Eastern Ethiopia, 2019.

(ZIP)

Click here for additional data file.^{(25.5KB, zip)}

Acknowledgments

The authors thank the data collectors, data collectors’ supervisors and administrative staff of Harari Regional Health Bureau for their cooperation to conduct this research paper. We also extend our deepest gratitude to clinical staff of Hiwot Fana Specialized University Hospital and Jugal Hospital for their unreserved support, and without them, this work would not be realized.

Data Availability

All relevant data are within the paper and its Supporting information files.

Funding Statement

This study was funded by Haramaya University. The funders had no role in a study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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PLoS One. doi: 10.1371/journal.pone.0259723.r001

Decision Letter 0

Subash Chandra Gupta

17 Jun 2021

PONE-D-21-06515

Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harar Town, Eastern Ethiopia: A two Years’ Retrospective Analysis

PLOS ONE

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Reviewer #1: 1.The authors have conducted the research in an ethical fashion and collected all the data using approprate mechanisms to ensure the quality remains appropriate for the subject. The authors have duly cited their peers and prior art and also conducted statistical analysis with rigour. However, the experitmental setup does not indicate how this study is different from the prior studies and therfore provides no indication of why the outcomes might be expected to be different. If the setup was the same the output can be safely assumed to be the same.

2. Based on the current analysis shows no significant improvement in outcomes while utilizing IoL, further analysis is meritted for the use case.

a. The paper seems to describe the effect of the parameters in isolation. The data representation, and therefore results, does not describe the effect of the combination of factors. Authors must conduct this analysis and clearly represent the significance of individual parameters and the various permutations and combinations

b. A detailed description of the control sample (patients not receving IOL) is requried. The current manuscript does not provide details on this.

c. Based on the results provided, the bishops score has a significantly higher effect on the outcome. While this may well turn out to be true, the analysis needs to be provide an analysis while holding the bishops score as a constant. This would allow a better study of the effect of each variable. Without this analysis the effect of the IOL on parameters beyond the bishops score are nebulous at best. A similar analysis should be conducted while holding each parameter constant. This would provide an exhaustive analysis that helps differentiate the output from prior work.

3. Authors should maintain unformity while describing results. Eg: Line 259 describes the paramenter as "more likely" based on the cut off; but the subsequent parameters are described as "less likely" at the cut off. The authors should construct the sentences to describe in one of two ways (either less or more). Switching between positive and negative effect of the cut off can create confusion for the readers.

4. The discussion section focusses more on prior work than an analysis of the results. Perhaps correlation while holding parameters constant would provide more content for discussion.

4. Significant sections of the paper need to be re-written to correct for sentence construction.

5. Suggestion: Some of the tables could be converted to graphical representation for easier interpretation.

Overall the work conducted has potential for significant impact, but a more detailed analysis is needed. In the current fommt the manuscript does not give any indication of differentiation from prior art. However, given the nature of the problem being addressed, I recommend the authors be give a chance to conduct a more details analysis and submit a renewed manuscript.

Reviewer #2: 1 Abstract is written well and comprehensive

2. In the Introduction section, Authors may give more information about advantages and disadvantages of induction of labor (IOL) citing more literature

3. Study design, Study population, Eligibility criteria, and Sample size calculations are well planned and presented; sampling procedure is done well with good selection of variables.

4 The presentation of results obtained is very clear with facts of of many pregnant women having indications of pre-eclampsia/eclampsia and pre-labor rupture of membrane. The state of conditions are worrying in this part Ethiopia reported by the Authors. Parity of the mothers, nullipara and multipara mothers is also taken care in this study

5. The results obtained are discussed well citing references.

6. As an another parameter, in the discussion, the Authors would have touched upon socio-economic and nutritional status of pregnant women compared to those in other countries/Ethiopia.

7. In this study Authors established that success of induction of labor was relatively low in study area

**********

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Reviewer #1: Yes: Kiran Aatre

Reviewer #2: No

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PLoS One. 2021 Nov 9;16(11):e0259723. doi: 10.1371/journal.pone.0259723.r002

Author response to Decision Letter 0

29 Aug 2021

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

Manuscript ID: PONE-D-21-06515

Journal: PLOS ONE

Dear Editors and Reviewers,

Thank you so much for giving us an opportunity to submit a revised draft of our manuscript entitled “Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harar Town, Eastern Ethiopia: A two Years’ Retrospective Analysis” to this high visibility impact factor and peer reviewed Journal. We appreciate the time and effort that you and the reviewers dedicated to providing feedback on our manuscript. We are very grateful for the insightful comments and valuable improvements to our premature paper. We have incorporated most of the suggestions and comments made by handling editor, reviewers. All comments and suggestions are clearly stated and well addressed (a point-by-point to the reviewer’s comments and concerns). These changes are highlighted in Red font color within the clean revised manuscript.

Authors’ Response to Editor’s Comments and Suggestions

Title: Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

Authors: Yimer Mohammed Beshir, Gudina Egata, Mohammed Abdurke Kure, Kedir Teji Roba,

To: Handling Editor(s)

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

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

Editor’s Comments to the Authors

A.Editor’s General Comments and Suggestions

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

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

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

Academic Editor’s Specific Comments (Journal Requirements)

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

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

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

Authors' Response: Thanks. You are perfect. This valid comment was addressed based on your valuable suggestion. Newly changed and corrected was highlighted with red font color in the clean revised manuscript (on page, Lines= )

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

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

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

Authors' Response: Thank you very much. In fact, this is a valid concern. We critically considered this point, and we decided to upload data set used for analysis with revised submission as supplementary File 2(S2)

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

Authors' Response: Thank you a lot for such a technical input. Now, authors considered the raised issue. We are very sorry! In fact, this authors responsibility to follow and adhere Journal’s format guidelines. After thoroughly and critically revised this important comment, we removed from previously it appeared in Acknowledgment part. Thanks!

End of authors’ responses for Handling Editor(s)

A. Authors’ Response to Reviewer 1’s Comments and Suggestions

Title: Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

Authors: Yimer Mohammed Beshir, Gudina Egata, Mohammed Abdurke Kure, Kedir Teji Roba

To: Reviewer 1

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

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

Reviewer’s Comments to the Authors

Reviewer’s General Comments

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

Reviewer #1: partly

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

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

Reviewer #1: No

Authors' Response: Thank you so much. Authors acknowledge you for your countless effort. We also appreciate this valuable response. Dear, reviewer, in this study, the authors followed standard methods of data collections and analysis. We used validated data collection tool, which was developed and customized from Ethiopian Demographic and Health Survey (EDHS) data collection tool, and by reviewing related published literature. We also used strong statistical software (Epi-Data version-3.1) for data entry. Further, data were exported to SPSS version 24 (IBM SPSS Statistics, 2016) for further analysis. Now, we revised the paper after initial submission. We took a long time, thoroughly revised and corrected the whole parts of our manuscript to make it more scientifically robust. Further, we also critically revised the statistical analysis of all descriptive statistics, Bi-variable and multivariable logistic regression models to correct any systematic errors introduced during analysis sage.

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

Reviewer #1: Yes

Authors' Response: Thanks a lot! Authors acknowledged your countless efforts. Now, authors agreed to upload SPSS data set used for analysis as supplementary file 2(S2) with revised submission.

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

Reviewer #1: Yes

Authors' Response: Thank you very much. Even after initially submission, we thoroughly revised and edited the whole parts of our manuscript and extensively corrected all copy-editing errors in the clean revised manuscript. Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

5. Specific Review’s Comments to the Authors

1.The authors have conducted the research in an ethical fashion and collected all the data using appropriate mechanisms to ensure the quality remains appropriate for the subject. The authors have duly cited their peers and prior art and also conducted statistical analysis with rigour. However, the experimental setup does not indicate how this study is different from the prior studies and therefore provides no indication of why the outcomes might be expected to be different. If the setup was the same the output can be safely assumed to be the same.

Authors' Response: Thank you very much. We would like to thank you for your appreciation and constructive suggestion. We really appreciate this valid observation. Based on your insightful suggestion, we took a long time and critical revised the paper to enrich it after previous initial submission to the journal. Dear, reviewer, in the introduction part, we clearly stated that no studies have conducted in the eastern Ethiopia, and even there were very few reports from other part of the country. Further, this study was conducted in eastern part of Ethiopia, particularly, Harari Regional State, where majority of the people are not accessed to health care services. This region has boundary with Somali Regional State, where marginalized and pastoralist community are inhibited, and many of laboring mothers referred to Hiwot Fana Specialized University Hospital for better care because it is the only Referral Hospital in eastern Ethiopia.

2. Based on the current analysis shows no significant improvement in outcomes while utilizing IoL, further analysis is merited for the use case.

Authors' Response: Great! Thanks a lot. Dear, reviewer, we really appreciate your valid concern. Initially, we followed standard methods of data collections and analysis. We also used strong statistical software (Epi-Data version-3.1) for data entry. Further, data were exported to SPSS version 24 (IBM SPSS Statistics, 2016) for further analysis. We used all statistical analysis steps required for comparison cross-sectional study (Descriptive statistics, Bi-variable analysis, Multivariable analysis). We performed regression analysis after critically considered assumption of logistic regression. Our outcome variable was “Binary outcome” and we dichotomized it accordingly. It is obvious that there would be limitation for “cross-sectional study” because no causal-association can be estimated. In this study, we used “Facility-based Cross-sectional study with internal comparison”, and we tried to increase our sample size (n=717) to have representative sample. Moreover, because of limited resource, we could not conduct, prospective longitudinal study to see the true causal-effect relationship (to estimate the true effect of predictor variables on the outcome of IOL).

2a. The paper seems to describe the effect of the parameters in isolation. The data representation, and therefore results, does not describe the effect of the combination of factors. Authors must conduct this analysis and clearly represent the significance of individual parameters and the various permutations and combinations

Authors' Response: Thank you so much. Authors critically considered this input. Authors acknowledged your efforts. We critically considered and incorporated these raised issues. Dear reviewer, from the beginning, we followed all steps of statistical analysis as follows:

1.Questionnaire template was prepared using Epi-Dat version 3.1 for data entry

2.Double data entry was conducted by independent data clerk

3.After verification, entered data were exported to SPSS version 24 (IBM SPSS Statistics, 2016) for further analysis.

4. In SPSS analysis, imported data were cleaned and checked for outliers using (ascending and descending, simple frequency, Plot chat…etc).

5.Descript statistics were done using frequency tables, proportions and summary measures

6.Bivariable Analysis was conducted using Binary logistic regression analysis after dichotomizing of “outcome of induction as ‘Failed IOL’ and ‘Successful IOL’ ”. Thus, Failed IOL= 0 and Successful IOL= 1. Accordingly, around 12 predictors were run independently in respect with outcome of IOL.(See Table 3)

7. Multivariable analysis was performed after all assumptions of Logistic regression were fulfilled. Here, around 8 variables with p-value < 0.25 in Bivariable analysis were considered for multivariable analysis based on selection criteria(after model fitness and multicollineaity were checked).(See Table 4)

2b. A detailed description of the control sample (patients not receiving IOL) is required. The current manuscript does not provide details on this.

Authors' Response: Thanks a lot. Authors appreciate your insightful concern. Dear, reviewer, in this study, we used the method of “Cross-sectional study design with internal comparison” which has been conducted in point in time or “Snapshot”. We have conducted retrospective chart-review of 2 years (January 2017 to December 2018). Moreover, in its nature, cross-section study does not have comparative group like case-control (Diseased Vs Non-diseased), Cohort study (Exposed Vs Unexposed group), RCT (Placebo Vs Interventional group). Therefore, In our case, we didn’t have control group, and our study subjects were “Laboring mother who underwent IOL”. Accordingly, the charts of mothers admitted to selected Public Hospitals in Eastern Ethiopia, who underwent labor induction(January 2017 to December 2018) were retrieved.

2c.Based on the results provided, the bishops score has a significantly higher effect on the outcome. While this may well turn out to be true, the analysis needs to be provide an analysis while holding the bishops score as a constant. This would allow a better study of the effect of each variable. Without this analysis the effect of the IOL on parameters beyond the bishops score are nebulous at best. A similar analysis should be conducted while holding each parameter constant. This would provide an exhaustive analysis that helps differentiate the output from prior work.

Authors' Response: Thank you a lot. We appreciated your observation. We considered this deep and insightful concern. Dear, reviewer, initially, we followed all steps of statistical analysis. In the final model, multivariable analysis was performed after all assumptions of Logistic regression analysis were fulfilled. Accordingly, around 8 variables with p-value<0.25 in Bi-variable analysis were considered for multivariable analysis based on selection criteria (after model fitness and multicollineaity were checked). These variables include (maternal age, residence, parity, Bishop score, PROM, NRFHBP, Methods of induction, Birth wt). In this final model analysis, all reference categories were held constant to estimate the effect of each predictor on outcome of IOL. In the previous submission, the Bishop score was also incorporated in both Bi-variable and multivariable analysis.

(See Table 4)

Authors' Response: Thank you so much. You are perfect. In fact, this is very important comment. This valid comment was addressed based on your insightful suggestion. Newly changed and corrected were highlighted with red font color in the clean revised manuscript (page , lines ).

4. The discussion section focusses more on prior work than an analysis of the results. Perhaps correlation while holding parameters constant would provide more content for discussion.

Authors' Response: Great, Thanks a lot for such implicit and critical review for our premature paper. You are perfect. We really appreciate this valid observation. Now, the authors critically reviewed this valid comment and corrected the necessary modification. The newly modified changes were highlighted with red font color in the clean revised manuscript

5. Significant sections of the paper need to be re-written to correct for sentence construction.

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

6. Suggestion: Some of the tables could be converted to graphical representation for easier interpretation.

Authors' Response: Ok, Great! Thanks a lot. In fact, this is valid concern. It is obvious that graphs/bars are easier to capture the information about presenting data. In this study, we used 3 figures and 4 tables, and most Biomedical researchers recommend minimum number figures than tables. However, if is mandatory to put the data in the figure, we will modify based on your specific recommendation. Thanks!

Overall the work conducted has potential for significant impact, but a more detailed analysis is needed. In the current format the manuscript does not give any indication of differentiation from prior art. However, given the nature of the problem being addressed, I recommend the authors be give a chance to conduct a more details analysis and submit a renewed manuscript.

Authors' Response: Thank you very much. Authors thank for your countless effort to enrich our paper. We also appreciate this valuable suggestion. Dear, reviewer, we tried to address your deep concern about the analysis of the data in the previous questions. Based on your insightful comments, the authors critically reviewed, and checked the SPSS archived data to correct any bolded errors or misleading results. However, the authors didn’t found any systematic errors that may introduced unintentionally. Moreover, we took a long time, critically revised the whole manuscript, and modified previously bulky paragraphs, poorly worded, and other copy-editing errors. All newly modified/changes were highlighted with red font color with in the revised main manuscript. For further details, we submitted SPSS data (used for analysis) to the Journal as supplementary file 2(S2) with the revised submission.

End of authors responses for Reviewer 1

B. Authors’ Response to Reviewer 2’s Comments and Suggestions

Title: Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

Authors: Yimer Mohammed Beshir, Gudina Egata, Mohammed Abdurke Kure, Kedir Teji Roba

To: Reviewer 2

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

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

Reviewer’s Comments to the Authors

Reviewer’s General Comments

Authors' Response: Overall, thank you very much for your positive and constructive suggestions

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

Reviewer #1: Yes

Authors' Response: Thank you very much! We appreciate your valuable response.

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

Reviewer #1: Yes

Authors' Response: Thank you very much. Authors acknowledged your countless efforts, positive and constructive suggestion! Further, we frequently revised the statistical analysis, and results to enrich the manuscript than previous its status.

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

Reviewer #1: Yes

Authors' Response: Thank you reviewer! We are very grateful for your positive response.

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

Reviewer #1: Yes

Authors' Response: Thanks a lot! Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

5. Specific Review’s Comments to the Authors

1 Abstract is written well and comprehensive

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

2. In the Introduction section, Authors may give more information about advantages and disadvantages of induction of labor (IOL) citing more literature

Authors' Response: Thank you a lot. We accepted all your valid suggestion and concern in this paper, and correct accordingly. The newly modified part were highlighted with red-font color in the main manuscript.

3. Study design, Study population, Eligibility criteria, and Sample size calculations are well planned and presented; sampling procedure is done well with good selection of variables.

4 The presentation of results obtained is very clear with facts of many pregnant women having indications of pre eclampsia/eclampsia and pre-labor rupture of membrane. The state of conditions are worrying in this part Ethiopia reported by the Authors. Parity of the mothers, nullipara and multipara mothers is also taken care in this study

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

5. The results obtained are discussed well citing references.

Authors' Response: Ok! Thank you so much for your countless effort to review our paper.

6. As another parameter, in the discussion, the Authors would have touched upon socio-economic and nutritional status of pregnant women compared to those in other countries/Ethiopia.

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

7. In this study Authors established that success of induction of labor was relatively low in study area

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

End of authors responses to Reviewer 2

Attachment

Submitted filename: 3.Response to reviewers.docx

Click here for additional data file.^{(37.8KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0259723.r003

Decision Letter 1

Subash Chandra Gupta

20 Sep 2021

PONE-D-21-06515R1Outcome of Induction and Associated Factors among Induced Labours in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective AnalysisPLOS ONE

Dear Dr. Kure,

Please revise the manuscript considering the comments from reviewer.

Please submit your revised manuscript by Nov 04 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If 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: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Subash Chandra Gupta, Ph.D.

Academic Editor

PLOS ONE

Journal Requirements:

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

Additional Editor Comments (if provided):

Please revise the manuscript considering the comments from reviewer.

[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: (No Response)

Reviewer #2: All comments have been addressed

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Reviewer #1: Most comments have been addressed. However, the merit of conducting a study using identical parameters is debatable. I understand that the socio-economic and geographic settings of this study were different, but all previous studies on the same topic with varying socio-economic studies indicated the same output as the authors. This begs the question, is the study truly unique enough to add to a body of scientific knowledge. What was the scientific hypothesis to indicate that the outcome may be different in Ethiopia. What was the rationale for expecting a different outcome? This needs to be highlighted somehwere, else it is merely a repetition of the previous studies.

Reviewer #2: Authors have corrected and modified the manuscript as per suggestions of reviewers, no more corrections

**********

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.

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

Reviewer #1: No

Reviewer #2: No

PLoS One. 2021 Nov 9;16(11):e0259723. doi: 10.1371/journal.pone.0259723.r004

Author response to Decision Letter 1

3 Oct 2021

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

Manuscript ID: PONE-D-21-06515

Journal: PLOS ONE

Dear Editors and Reviewers,

Authors’ Response to Editor’s Comments and Suggestions

Title: Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

Authors: Yimer Mohammed Beshir, Gudina Egata, Mohammed Abdurke Kure, Kedir Teji Roba,

To: Handling Editor(s)

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

Editor’s Comments to the Authors

Editor’s General Comments and Suggestions

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

Authors' response: Thank you so much. We are very grateful for giving us an opportunity to submit our revised manuscript to such legitimate and high visibility impact factor Journal (PLOS ONE). Thank you editor.

Academic Editor’s Specific Comments (Journal Requirements)

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

Authors' response: Thank you so much. You are perfect. These are very important suggestions. Even it is the authors mandatory to critically review references issue (Both in text-citation and Bibliography) to avoid any inconsistence and wrong citations across the document. Now, the authors addressed this critical issues based on your valuable suggestions. Newly changed and corrected References were highlighted with red font color in the clean revised manuscript.

End of authors’ responses for Handling Editor(s)

Authors’ Response to Reviewer 1’s Comments and Suggestions

Title: Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

Authors: Yimer Mohammed Beshir, Gudina Egata, Mohammed Abdurke Kure, Kedir Teji Roba

To: Reviewer 1

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of 3rd Round Incorporated Comments and Suggestions

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

Reviewer’s Comments to the Authors Authors’ Responses to Reviewer’s comments

Reviewer’s General Comments Overall, thank you very much for your positive and constructive suggestions

Reviewer #1: (No Response)

Authors' response: Ok, great! Thank you so much. We revised and enriched the paper after previous 2nd round submission to the journal. Authors critically discussed on this reviewers suggestion (not endorsed for previous addressed comments) to the Journal’s query to enrich our paper to be scientifically sound, and we took a long time, implicitly revised for the reviewers concerns. Thus, now we clearly stated and addressed the this reviewer’s deep concern(particularly, the issue of novelty and duplication), in the question number 5 below(next page). Thank you a lot, reviewer.

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

Reviewer #1: Yes

Authors' response: Thank you. Authors appreciate your positive response.

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

Reviewer #1: Yes

Authors' response: Thank you so much. Authors acknowledge you for your countless effort. We also appreciate this valuable response.

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

Reviewer #1: Yes

Authors' response: Great! Dear reviewer, we thank you again for constructive suggestion.

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

Reviewer #1: Yes

Authors' response: Thank you very much. Even after revised 2nd submission, we corrected all copy-editing errors in the clean revised manuscript after previous submission.

5. Specific Review’s Comments to the Authors

1. Most comments have been addressed. However, the merit of conducting a study using identical parameters is debatable. I understand that the socio-economic and geographic settings of this study were different, but all previous studies on the same topic with varying socio-economic studies indicated the same output as the authors. This begs the question, is the study truly unique enough to add to a body of scientific knowledge. What was the scientific hypothesis to indicate that the outcome may be different in Ethiopia? What was the rationale for expecting a different outcome? This needs to be highlighted somewhere, else it is merely a repetition of the previous studies.

Authors' response: Thank you very much. We would like to thank you for your appreciation and constructive suggestion.

Coming to the specific concern: Really, this is an important intellectual suggestion. Dear, reviewer, authors really appreciate your implicit and deep concern about the novelty and repetition of this research paper. In this regard, we tried to indicate in the 2nd round submission of the revised manuscript and review letter response.

Dear, reviewer, in the introduction part of this paper, we clearly stated that no studies have been conducted in the eastern part of Ethiopia, and even there were very few reports from other part of the country. Further, this study was conducted in eastern part of Ethiopia, particularly, Harari Regional State, where majority of the people are less accessed to health care services. Moreover, this Harari Reginal State has boundary with Somali Regional State, where marginalized and pastoralist community are inhibited, and many of laboring mothers referred to Hiwot Fana Specialized University Hospital for better care because it is the only Referral Hospital in eastern Ethiopia. Furthermore, in Ethiopia, eastern part of Ethiopia is one of the most neglected area of the country, particularly, Harari regional state which is located at periphery( at 526Km distance from capital Addis Aba) of the country, and has a boundary with Somali regional, where highly marginalized community(Pastoralists and semi pastoralist) communities are largely inhibited and seeking healthcare services from Harari regional state, Eastern Ethiopia.

- In Ethiopia, although few studies have been conducted in the last five years, almost all previous researchers were selective to central and Northern parts(Addis Ababa, Amhara, and Tigray regions), neglecting other regions of the country, particularly Afar, Harari, and Somali regions.

Further, the authors added researcher gaps that indicate the reasons why this study has been conducted in Eastern part of Ethiopia. The newly modified changes were highlighted within the clean revised manuscript on page (page 5, lines 87-94). Thank you once again.

Dear, reviewer, really publication is learning forum because we learned a lot from your insightful comments and suggestions throughout the review process our paper.

End of authors responses for Reviewer 1

Authors’ Response to Reviewer 2’s Comments and Suggestions

Title: Outcome of Induction and Associated Factors among Induced Labors in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

Authors: Yimer Mohammed Beshir, Gudina Egata, Mohammed Abdurke Kure, Kedir Teji Roba

To: Reviewer 2

From: Mohammed Abdurke Kure (Corresponding Author)

Subject: Submission of Incorporated Comments and Suggestions

Reviewer’s Comments to the Authors

Reviewer’s General Comments

Authors' response: Overall, thank you very much for your positive and constructive suggestions

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

Reviewer #2: All comments have been addressed Great!

Authors' response: We are very grateful for your unquantified effort throughout the review process of our manuscript. Thank you so much.

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

Reviewer #2: Yes

Authors' response: Thank you very much! We appreciate your valuable response and constructive suggestion.

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

Reviewer #2: Yes

Authors' response: Thanks a lot. Authors acknowledged your countless efforts, positive and constructive suggestion!

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

Reviewer #2: Yes

Authors' response: Thank you reviewer! We are very grateful for your appreciation and constructive intellects.

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

Reviewer #2: Yes

Authors' response: Thank you so much! Authors also sent the manuscript to language expert/editor who critically reviewed, edited and corrected all language related errors made in a submitted manuscript.

5. Specific Review’s Comments to the Authors

Reviewer #2: Authors have corrected and modified the manuscript as per suggestions of reviewers, no more corrections

Thank you very much. We would like to thank you for your appreciation and constructive suggestion. Further, we revised and enriched the paper after previous 2nd round submission to the PLOS ONE Journal.

In conclusion:

Really, the publication is leaning forum. Overall, we learned a lot from your comments and suggestion throughout the review process of this manuscript. Thank you so much once again.

End of authors responses to Reviewer 2

Attachment

Submitted filename: 3.Response to reviewers.docx

Click here for additional data file.^{(32.5KB, docx)}

PLoS One. doi: 10.1371/journal.pone.0259723.r005

Decision Letter 2

Subash Chandra Gupta

26 Oct 2021

Outcome of Induction and Associated Factors among Induced Labours in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

PONE-D-21-06515R2

Dear Dr. Kure,

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

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PLoS One. doi: 10.1371/journal.pone.0259723.r006

Acceptance letter

Subash Chandra Gupta

29 Oct 2021

PONE-D-21-06515R2

Outcome of Induction and Associated Factors among Induced Labours in Public Hospitals of Harari Regional State, Eastern Ethiopia: A two Years’ Retrospective Analysis

Dear Dr. Kure:

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

S1 File. Induction protocol for induction of labour.

(PDF)

Click here for additional data file.^{(568.7KB, pdf)}

S1 Data. Data set used for analysis of the study conducted on IOL in Eastern Ethiopia, 2019.

(ZIP)

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Attachment

Submitted filename: 3.Response to reviewers.docx

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Attachment

Submitted filename: 3.Response to reviewers.docx

Click here for additional data file.^{(32.5KB, docx)}

Data Availability Statement

All relevant data are within the paper and its Supporting information files.

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PERMALINK

Outcome of induction and associated factors among induced labours in public Hospitals of Harari Regional State, Eastern Ethiopia: A two years’ retrospective analysis

Yimer Mohammed Beshir

Mohammed Abdurke Kure

Gudina Egata

Kedir Teji Roba

Roles

Abstract

Background

Methods

Results

Conclusion

Introduction

Methods and materials

Study setting, period, and design

Population and sampling technique

Sampling techniques and procedures

Fig 1. Schematic presentation of sampling procedure among mothers who delivered after induction of labor in public Hospitals of Harari Regional State, Eastern Ethiopia, 2019.

Data collection tools and procedures

Study variables and measurements

Measurements

Data quality control

Data processing and analysis

Ethical considerations and consent to participate

Results

Socio-demographic and obstetrics related characteristics of the participants

Table 1. Socio-demographic and obstetric related characteristics of mothers who delivered after induction of labor in public Hospitals of Harari Regional State, Eastern Ethiopia, 2019.

Magnitude of the outcome of induction, and indications of induction

Fig 2. Magnitude of the outcomes after induction of labor among mothers who delivered after induction of labor in public Hospitals of Harar town, Eastern Ethiopia, 2019.

Fig 3. Indications for induction of labor among mothers who delivered after induction of labor in public Hospitals in Harari Regional, Eastern Ethiopia, 2019.

Methods of induction of labor, and mode of delivery

Table 2. Methods of induction of labor and mode of delivery among mothers who delivered after induction of labor in public Hospitals, Harari Regional State, Eastern Ethiopia, 2019.

Factors associated with the outcome of induction of labor

Table 3. Bivariable logistic regression analysis of factors associated with the outcome of induction of labor among mothers who delivered after IOL in public hospitals of Harari Regional State, Eastern Ethiopia, 2019.

Table 4. Multivariable logistic regression analysis of factors associated with the success of induction of labor among mothers who delivered after induction of labor in public Hospitals of Harari Regional State, Eastern Ethiopia, 2019.

Discussion

Limitations of the study

Conclusion

Supporting information

Acknowledgments

Data Availability

Funding Statement

References

Decision Letter 0

Subash Chandra Gupta

Roles

Author response to Decision Letter 0

Decision Letter 1

Subash Chandra Gupta

Roles

Author response to Decision Letter 1

Decision Letter 2

Subash Chandra Gupta

Roles

Acceptance letter

Subash Chandra Gupta

Roles

Associated Data

Supplementary Materials

Data Availability Statement

ACTIONS

PERMALINK

RESOURCES

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