Perinatal outcome of meconium stained amniotic fluid among labouring mothers at teaching referral hospital in urban Ethiopia.

OBJECTIVE: To determine the perinatal outcome of labouring mothers with meconium-stained amniotic fluid (MSAF) compared with clear amniotic fluid at teaching referral hospital in urban Ethiopia.
METHODS: A prospective cohort study was conducted among labouring mothers with meconium-stained amniotic fluid from July 1 to December 30, 2019. Data was collected with pretested structured questionnaires. A Chi-square test used to check statistical associations between variables. Those variables with a p-value of less than 0.05 were selected for cross-tabulation and binary logistic regression. P-value set at 0.05, and 95% CI was used to determine the significance of the association. Relative risk was used to determine the strength and direction of the association. RESULT: Among 438 participants, there where 75(52.1%) primigravida in a stained fluid group compared to112 (38.5%) of the non-stained fluid group. Labour was induced in 25 (17.4%) of the stained fluid group compared to 25(8.6%) of a non-stained fluid group and has a statistically significant association with meconium staining. The stained fluid group was twice more likely to undergo operative delivery compared with a non-stained fluid group. There were more low Apgar scores at birth (36.8% versus 13.2%), birth asphyxias (9% versus 2.4%), neonatal sepsis (1% versus 5.6%), neonatal death (1% versus 9%), and increased admissions to neonatal intensive care unit (6.2% versus 21.5%) among the meconium-stained group as compared to the non-stained group. Meconium aspiration syndrome was seen in 9(6.3%) of the stained fluid group.
CONCLUSION: Meconium-stained amniotic fluid is associated with increased frequency of operative delivery, birth asphyxia, neonatal sepsis, and neonatal intensive care unit admissions compared to clear amniotic fluid.

Introduction

Meconium stained amniotic fluid(MSAF) is usually seen in 12 to 16% of deliveries [1]. Meconium passage is less common before 37 weeks of gestational age and increases steadily with gestational age [2]. It may represent the normal gastrointestinal maturation, or it may indicate an acute or chronic hypoxic event, thereby making it a potential warning sign of a fetal Compromise [3, 4]. Though its controversial to differentiate physiologic or pathologic meconium staining of amniotic fluid, there are few shreds of evidence that indicates its association with increased meconium aspiration syndrome, operative delivery, respiratory distress, neonatal sepsis, need for resuscitation, neonatal intensive care admission, and low Apgar score [5-8]. Besides, infants born through a meconium-stained amniotic fluid are more likely to develop respiratory distress and are at increased risk of perinatal death [1, 9]. Meconium aspiration syndrome (MAS) is characterized by the presence of respiratory distress with radiographic evidence of aspiration pneumonitis in the presence of meconium-stained amniotic fluid [4, 10]. MAS occurs in about 5% of deliveries with meconium-stained amniotic fluid [11], and death occurs in about 12% of infants with MAS [12].

The evidence of poor perinatal outcome associated with meconium-stained amniotic fluid mandates a well-designed study. Still, there is no well-designed comparative study in our country in general and no study at all in our hospital on the subject matter. The present study was, therefore, aimed at determining perinatal outcomes among laboring mothers with MSAF compared with clear amniotic fluid at teaching referral hospital in urban Ethiopia.

Materials and methods

This was a hospital-based prospective cohort study. The study was conducted at Saint Paul’s Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia from July 1 to December 30, 2019. SPHMMC is a tertiary teaching referral hospital providing maternity service. The current prospective cohort study was conducted to determine the perinatal outcome of meconium-stained amniotic fluid (MSAF) compared with clear amniotic fluid among pregnant mothers in labour at Saint Paul's Hospital Millennium Medical College.

All consented pregnant women in labour who had completed more than 37 weeks of gestation, with viable singleton pregnancies with cephalic presentations and with no known fetal congenital anomalies were included. Twin pregnancy was excluded because of difficulty to determine chorionicity in labour and finding chorionicity and gestational age-matched twins. Gestational age was calculated from reliable last normal menstrual period or early ultrasound done before 24 weeks and those with an unknown date or without early ultrasound were excluded. Those with MSAF were exposed group referred to as "Stained fluid group", and those with clear amniotic fluid were non-exposed groups referred to as "non-stained fluid group" in our study.

Meconium stained amniotic fluid is the exposure variable of interest and classified into three:

Grade one meconium-stained liquor: small amount of meconium diluted in a plentiful amount of amniotic fluid. The fluid has only a slightly greenish or yellowish discoloration.

Grade two meconium-stained liquor: moderate meconium staining, when there is a fair amount of amniotic fluid, but it is stained with meconium. In this case, it will be 'khaki green' or brownish.

Grade three meconium-stained liquor: heavy staining, when there is reduced amniotic fluid and a large amount of meconium, making the staining quite thick, with 'pea soup' consistency.

Outcome variables were: 1st and 5th minute Apgar score, MAS, Birth asphyxia, NICU admission, early-onset neonatal sepsis (EONS), early neonatal death (END), and Operative delivery (CS or instrumental delivery). Covariates were parity, mode of delivery, duration of labour, duration of rupture of membrane, obstetric or medical complications like antepartum hemorrhage, pregnancy-induced hypertension, growth restriction, oligohydramnios, intra-amniotic infection(chorioamnionitis) and diabetes.

Operational definitions

Perinatal outcome: in our study were used to describe composite of outcome variables.

Perinatal mortality: in our study means neonatal death within seven days of post-natal life per thousands of live births because all antenatal still-birth was excluded in the study.

Early neonatal death (END): neonatal death within seven days of post-natal life.

Operative delivery: in our study is meant for cesarean section or instrumental (vacuum or forceps delivery).

Birth asphyxia: in our study defined as 1st and 5th minute Apgar score of less than six and clinical diagnosis of perinatal asphyxia (PNA) at NICU.

MAS: in our study is a clinical diagnosis of respiratory distress in a neonate born through MSAF with a sign of meconium aspiration and was diagnosis put at NICU.

Open Epi version 3 was used to calculate the sample size for a matched cohort study. If 5% of patients with MSAF will develop MAS and 0.1% of patients with clear amniotic fluid will develop MAS and selection of two, clear amniotic fluids for one MSAF. By using the power of 80% and CI of 95%, the calculated sample size was 399 and adding 10% non-response rate total sample size was 438, so 146 stained fluid was collected consecutively and 292 non-stained who was in labour at the same time and who has close gestational age within one week were selected for comparison.

Trained midwives collected the data at the labour ward in pretested proforma. Data about the mode of delivery and outcome of birth were collected upon delivery in terms of apparent health, 1st and 5th minute Apgar score, early neonatal death (END), and referral to neonatal intensive care unit (NICU). Neonates who were referred to NICU were checked for admission diagnosis to NICU and their outcome on the seventh postnatal day from the neonatal chart and NICU logbook and those who are not referred to NICU and discharged home safely with mother were checked with a cell phone interview with mothers.

Data were entered and analyzed using SPSS version 23. Chi-square test was used to check statistical associations between meconium-stained amniotic fluid and outcome variables and covariates. Outcome variables with P value less than 0.05 were selected, and cross-tabulation was done to determine the strength and direction of the association between meconium staining of amniotic fluid and each outcome variable. All covariates with P value less than 0.05(covariates associated with exposure variable) were selected for binary logistic regression to determine their association with each outcome variable. Statistical significance of the association between exposure and outcome variables were determined by a 95% confidence interval and p-value set at 0.05. Adjusted relative risk (RR) was used to determine the strength and direction of the association between exposure and outcome variables.

Ethical consideration

Ethical approval was obtained from Saint Paul’s Hospital Millennium Medical College ethical review committee. Written informed consent was obtained from patient and confidentiality was maintained during data collection, analysis, and interpretation. All the datasets used and/or analyzed during the current study are included in the manuscript and supplementary material.

Results

According to the statistics office of the hospital, nearly 50,000 attended antenatal care, and around 9000 deliveries were attended in 2019, 35% of births were by cesarean section. A total of 438 pregnant women were included in this study, with a response rate of 99.3%. Three of post-partum women couldn't be traced on the seventh postpartum day for a phone interview and were lost to follow up. The meconium was described as grade I in 51 (35%) patients, grade-II in 48 (33%) patients, and grade-III 45 (32%) patients (Fig 1).

Fig 1

Flow diagram of study participants.

Among 144 of the stained fluid group, 129 (89.6%) women were of 20-35-year age-group compared to 251(86.3%) of the non-stained fluid group. There is no statistically significant difference in the sociodemographic characteristics of participants (Table 1).

Table 1

Sociodemographic characteristics of laboring mothers at SPHMMC from July 1 to December 30, 2018.

Variables.	Category.	Non-stained fluid.		Stained fluid.		Chi-square(p-value)
		Frequency	%	Frequency	%
Age	<20	18	6.2	10	6.9
	20–35	251	86.3	129	89.6	2.802(0.241)
	>35	22	7.5	5	3.5
Level of education	Illiterate	21	7.2	10	6.9
	primary school	120	41.2	63	43.8	0.281(0.962)
	high school	106	36.4	51	35.4
	College and above.	44	15.1	20	13.9
Religion	Orthodox Christian	173	59.5	96	66.7
	Protestant Christian	45	15.5	10	6.9
	Muslim	73	25.1	38	26.4	6.405(0.063)
Occupation status	Daily laborer	3	1.0	0	0.0
	Student	2	0.7	1	0.7
	Employed	62	21.3	35	24.3	2.065(0.721)
	Housewife	216	74.2	105	72.9
	Others	8	2.7	3	2.1
Marital status	Single	3	1.0	2	1.4
	Married	287	98.6	140	97.2
	Divorced	0	0.0	2	1.4	4.663(0.193)
	Widowed	1	0.3	0	0.0

All participants had antenatal care (ANC) follow up except one patient in the non-stained fluid group. Fetal heart rate (FHR) monitoring was done with continuous cardiotocography (CTG) in 286 (98.3%) of the non-stained fluid group and 142(98.6%) of the stained fluid group. There where 75(52.1%) primigravida in a stained fluid group compared to112 (38.5%) of the non-stained fluid group and only 9 (6.3%) of them are gravida five and above compared with 13(4.5%) non-stained fluid group (Table 2).

Table 2

Antepartum and intrapartum events of laboring mothers at SPHMMC from July 1 to December 30, 2018.

Character	Non-stained fluid.		Stained fluid.		Chi square (P-value)
	Frequency	%	Frequency	%
Attended Antenatal care (ANC)	290	99.7	144	100	4.532(0.482)
Parity.					14.682(0.005)
Primigravida	112	38.5	75	52.1
Gravid two	88	30.2	39	22.1
Gravid three	48	16.5	18	12.5
Gravid four	30	10.3	3	2.1
Gravid five and above.	13	4.5	9	9.3
Duration of labour
<12 hours.	181	62.4	80	55.6
12–24 hours.	96	33.1	53	36.8	2.870(0.238)
>24 hours.	13	4.5	11	7.6
Onset of labour					.
Spontaneous	266	91.4	119	82.6
Induced	25	8.6	25	17.4	7.283(0.007)
Duration of rupture of membrane.
<12 hours.	220	75.6	112	77.8
12–24 hours.	50	17.2	23	16.0	0.274(0.872)
>24 hours.	21	7.2	9	6.3
An obstetric or medical complication
Chorioamnionitis	3	4.8	4	7.5
Abruptio placenta	14	22.6	7	13.2
PIH*	22	35.5	26	49.1	8.237(0.144)
Growth restriction	11	17.7	7	13.2
Pregestational Diabetes Mellitus	7	11.3	1	1.9
Oligohydramnios	5	8.1	8	15.1
FHB** follow up method
Continuous cardiotocography.	286	98.3	142	98.6
Pinard fetoscope	4	1.4	2	1.4	0.496(0.780)
Mixed both methods	1	0.3	0	0.0

*pregnancy-induced hypertension

** Fetal heartbeat.

Pregnancy-induced hypertension (PIH) was seen 26(49.1%) of the stained fluid group compared with 22(35.5%) of the non-stained fluid group. Labour started spontaneously in 266(91.4%) of the non-stained fluid group compared with 119(82.6%) stained fluid group and induced in 25(17.4%) of the stained fluid group compared to 25(8.6%) of the non-stained fluid group. Induced labour is seven times more likely to have meconium-stained fluid compared to spontaneous onset of labour (Table 2). Prolonged rupture of membrane above 12 hours was seen in 32(19.3%) of the stained fluid group and 71(24.4%) of the non-stained fluid group. Duration of labour above 24 hours was seen in 11(7.6%) of the stained fluid group compared to13 (4.5%) of the non-stained fluid group. There was no statistically significant difference in terms of duration of the rupture of membrane and labour between the two groups (Table 2).

Cesarean section was the mode of delivery in 64(44.5%) stained fluid group as compared to 66(22.6%) non-stained fluid group. Sixteen (10.6%) of the stained fluid group had instrumental deliveries compared to 13(4.5%) non-stained fluid group. Merging cesarean and instrumental delivery as operative delivery; 80(55.6%) stained fluid group undergoes operative delivery compared to 79(27.1%) of the non-stained fluid group. All thin (grade one) stained fluid gave birth vaginally, while 80(86%) of thick (grade two and three) group underwent operative delivery. All cesarean section are emergency operations for the indication of thick meconium, fetal distress and poor progress of labour in 30,20 and 14 of stained fluid group respectively compared to poor progress of labour, previous scar in labour, fetal distress and active bleeding in 35,15,10 and 6 non-stained fluid respectively. The stained fluid group was twice more likely to undergo operative delivery compared with the non-stained fluid group (Table 3).

Table 3

Mode of delivery of laboring mothers at SPHMMC from July 1 to December 30, 2018.

	Stained fluid.	Non-stained fluid.
Mode of delivery	Frequency (%)	Frequency (%)	Total.	RR (95% CI)
Vaginally delivery	64(44.4)	212(72.8)	276	0.640(0.546–0.766)
Operative delivery.	80(55.6)	79(27.1)	159	2.170(1.666–2.827)
Total.	144(100)	291(100)	435(100)

Infants with MSAF had low 5th minute Apgar scores and 31(21.5%) stained fluid group needed intensive care unit admissions compared to 18(6.2%) of the non-stained group. Meconium aspiration syndrome was seen in 9(6.3%), stained fluid group. Neonates born to stained fluid were 2.5 times at risk of death in the first seven post-natal life as compared to those born to the non-stained fluid. Incidence of birth asphyxia, neonatal sepsis, and NICU admissions was statistically higher among babies born to the stained fluid as compared to those who were born to non-stained fluid (Table 4).

Table 4

Perinatal outcome of laboring mothers at SPHMMC from July 1 to December 30, 2018.

Parameter	Non-stained fluid	Stained fluid	Chi-square (P-value)	RR (95% CI)
	Frequency (%)	Frequency (%)
Meconium sucked from Oro-pharynx	2(0.7)	56(38.9)	21.657(0.001)	4.136(3.423–4.998)
5th minute Apgar score (<7)	40(13.7)	53(36.8)	30.475(0.001)	2.142(1.669–2.748)
Perinatal asphyxia	7(2.4)	13(9)	9.631(0.002)	2.059(1.449–2.926)
Early-onset neonatal sepsis	3(1)	8(5.6)	8.001(0.005)	2.267(1.539–3.340)
Admission to NICU	18(6.2)	31(21.5)	22.685(0.001)	2.161(1.660–2.813)
Early neonatal death	3(1)	13(9)	17.388(0.001)	2.598(1.972–3.424)

Meconium stained amniotic fluid has a positive clinically significant association with a primigravida, induction of labour (Table 2), and Operative delivery (Table 3). So binary logistic regression was done to see the effect of those independent variables which are associated with meconium staining on perinatal outcome. None of those independent variables has an association with perinatal outcome, and the adverse perinatal outcomes are solely associated with MSAF (Table 5).

Table 5

Binary logistic regression of variables associated with meconium staining and perinatal outcomes.

Perinatal outcome	Independent variable	P-value	RR (95% CI)
5th minute Apgar score	Mode of delivery	0.391	2.009(0.409–9.878)
	The onset of labour.	0.815	0.865(0.090–52.439)
	Parity.	0.773	1.023(0.124–3.336)
Early neonatal death	Mode of delivery	0.998	2.583(0.007–73941)
	The onset of labour.	0.496	3.407(0.100–11.590)
	Parity	0.855	1.000(0,048–61.884)
Perinatal asphyxia	Mode of delivery	0.998	7.443(0.704–4.951)
	The onset of labour.	0.998	2.2730.412–368.583)
	Parity	0.921	1.000(0.219–16.886)
Meconium aspiration syndrome	Mode of delivery	0.998	1.000(0.257–2.917)
	The onset of labour.	0.998	1.000(0.090–32.439)
	Parity	0.921	1.000(0.072–63.987)
Early onset neonatal sepsis	Mode of delivery	0.200	0.200(0.024–1.683)
	The onset of labour.	0.953	0.953(0.140–6.483)
	Parity	0.430	0.430(0.063–4.505)
NICU admission	Mode of delivery	0.142	4.640(0.597–36.061)
	The onset of labour.	0.225	2.509(0.568–11.079)
	Parity	0.745	0.425(0.219–16.886)

Discussion

In the current study, participants had similar baseline characteristics except for primigravida and induced labour which are associated more with MSAF. This might be because of slow and protracted progress of labour among primigravida’s increasing the possibility of meconium development. Saunders et al. [13] reported that cesarean sections were performed twice as frequently in subjects with meconium-stained amniotic fluid. Naveen S et al. [14] also reported a cesarean section rate of 49.1% in MSAF. The current study also showed the stained fluid group was two times more likely to undergo operative delivery compared to the non-stained fluid group. Our study also highlighted that 86% of the thick stained amniotic fluid group (grades two and three) undergoes operative delivery which indicates the risk of fetal heart rate abnormality with meconium staining and cesarean section being used as a rescue for infants who are about to develop MASThis is in line with other studies showing a higher risk of complications with thick meconium staining [5, 15].

In the current study, 36.8% stained fluid group had Apgar score less than seven, and stained fluid was 2.1 times more likely to have low 5th minute Apgar score compared to the non-stained fluid group. This is much lower than the study conducted by Sori DA et al. [16] at JUSH, which shows an Apgar score of less than seven in 88% of the exposed group. But the outcome is high compared to, Patil et al. [17] study, which reported that 19% of babies with MSAF had poor Apgar scores and other studies [9, 17]. The difference can be explained by the high incidence of operative deliveries for cephalon-pelvic disproportion (CPD) and non-reassuring fetal heart rate patterns in Sori DA et al. and the current study, which can be a cause and sign of intrauterine fetal distress and asphyxia, respectively.

Several investigators have demonstrated an association of meconium staining and poor perinatal outcome [1, 7, 18, 19]. There is no intrapartum death in our study, but the stained fluid group was at increased risk of END13 (9%) compared with non-stained fluid group 3(1%). PNA occurs almost twice in the stained fluid group (9%) compared to the non- stained fluid group (2.4%) and newborns born to MSAF were twice more likely to require NICU admission compared to those born to mothers with a clear amniotic fluid.

In the current research, MAS was diagnosed in 6.3% of babies in stained fluid group. MAS was diagnosed in 12.8% of babies born through MSAF in the study done by Patil et al. [17]. Meconium aspiration syndrome develops in only 2 of every 1000 live-born infants and 2% of those new-borns born through MSAF [20]. Ninety-five percent of infants with inhaled meconium clear the lungs spontaneously [9, 20]. A study by Sori DA et al. [16] showed meconium aspiration syndrome was diagnosed in 18.5% of the neonates born through MSAF, which is very high and they explained as the possibility of overdiagnosis since the diagnosis of MAS in their study was made only with clinical judgment without Chest X-ray. Moreover, the current study was conducted at tertiary hospital located in the capital city of Ethiopia compared to study by Sori DA et al. conducted at Jimma University Hospital which is serving the rural population. The possible limited access to health care in rural population might result in late presentation despite poor progress of labour resulting in high MAS. Therefore, since the current study was conducted at tertiary urban based hospital with relatively good obstetric care among relatively literate and wealth population with easy access to care might limit its generalizability to other centers and the wider population. This highlights that it is imperative to conduct multicenter study incorporating all levels of care.

Conclusions

Meconium stained amniotic fluid is worrisome as it is associated with increased frequency of operative delivery, birth asphyxia, neonatal sepsis, and neonatal intensive care unit admissions compared to clear amniotic fluid which was seen in the current study. Therefore, management requires appropriate intrapartum care with a continuous or strict one to one fetal heartbeat follow up. Furthermore, knowing the high risk of early neonatal death we advise early postnatal follow up should be considered for infants born to mothers with thick MSAF. Finally, we recommend well-controlled studies comparing the perinatal outcome of thick and thin stained amniotic fluid to stratify management accordingly.

Strobe checklist: Describes a completed strobe checklist for an observational study.

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9 Jul 2020

PONE-D-20-13739

Perinatal Outcome of Meconium Stained Amniotic Fluid among labouring mothers at teaching referral hospital in urban Ethiopia.

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Reviewer #1: Comments and Suggestions for Authors

A well thought study looking at the perinatal outcome of meconium stained amniotic fluid(MSAF) among laboring mothers at teaching hospital in Ethiopia. This study brings out important information regarding the outcomes of MSAF in Ethiopia.

Corrections:

Line 42 –Can be corrected as: Meconium stained amniotic fluid is usually seen in 12 to 16% of deliveries.

Line 47- Can be corrected as: Though its controversial to differentiate physiologic or pathologic meconium staining of amniotic fluid, there are few shreds of evidence that indicates its association (instead of associated) with increased meconium aspiration syndrome, respiratory distress, neonatal sepsis and perinatal mortality.

Line 77: Gestational age was (instead of is) calculated from reliable last normal menstrual period or early ultrasound done before 24 weeks and those with an unknown date or without early ultrasound were (where) excluded.

Line 168: All thin (grade one) stained fluid gave birth vaginally, while 80(86%) of thick (grade two and three) group underwent (instead of undergone) operative delivery.

Line 190 : Our study also highlighted that 86% of (thich )thick stained 190 amniotic fluid group (grade two and three) undergoes operative delivery which indicates the risk of fetal heart rate abnormality with meconium staining

Line 202 : Several investigators

Line 209 : In the current research, MAS was (has) diagnosed in 6.3 % a baby of the stained fluid group, which is 2.3 times compared to a non-stained fluid group

Table :2 P value is not in line for prim gravida and Induced labor.

Suggestions

1.It is unclear what the primary objective of this study was in the introduction. To determine the outcomes for physiologic v pathologic meconium staining or to compare MSAF outcomes with clear amniotic fluid. My recommendation is to have a clear objective in your introduction.

2.My suggestion is to compare Meconium aspiration syndrome between different types of MSAF and not with clear amniotic fluid and also to analyze the outcome differences between different types of MSAF

3. Were there any other conflicting variables like scheduled repeat C- section? Were those mothers excluded

4. My suggestion is also to compare the outcomes based on different Gestational age (Early term, term and post term).

Reviewer #2: Dear Editor,

Thank you for the opportunity to review this paper. The author present epidemiology of MAS in Ethiopia. There is paucity of any epidemiological data for Africa and this paper is worth publishing.

General notes: The text should be proofread for spelling, spacing and grammatical mistakes. The overall readability is borderline, but in several spots it is very difficult to understand what the authors mean. Please have the text proofread and edited. I appreciate the authors efforts to have the text proofread by a professional service, but it seems the editing service used by authors was substandard.

Specific comments:

Line 68 and 69 do not belong to methods since you report the results. Please move it to the result section.

Line 158. You define prolonged rupture of membranes as longer than 12h. It seems to be different from 18 hours used in the US. Can you explain somewhere the choice of this particular interval?

Lines 172-174. By definition, MSAF is one of the requirements to establish MAS diagnosis (your lines 105-106). How the patients with no MSAF were diagnosed with MAS?

In the description of demography (Table 1), the religion part might be misunderstood by some readers. Please specify if the Orthodox religion means Orthodox Judaism or Orthodox Christianity. I would spell out religions as Christian with subgroups of Eastern Orthodox and Protestant. Alternatively, I would spell out Orthodox Judaism and Christian (Protestant).

Table 2. Please specify if the diabetes was type one or pregnancy-induced.

It is interesting, that the follow-up was performed via a cell phone connection. Please, comment if the population of the woman included in the study or admitted to the hospital truly represent the population of Addis-Ababa. I would expect that only small proportion of the population could afford cell phones. Please clarify if I am wrong.

Good luck.

**********

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

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

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

Reviewer #1: No

Reviewer #2: No

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

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

9 Jul 2020

July 10, 2020

To: PLOS ONE Editor in chief.

Dear Editor in chief.

We would like to thank the editor and reviewers for their thoughtful review of the manuscript. They raise important issues and their inputs are very helpful for improving the manuscript. We agree with almost all their comments and we have revised our manuscript accordingly. We respond below in detail to each of the editor comments. We hope that you find our responses satisfactory and that the manuscript is now acceptable for publication

Looking forward hearing from you soon

Sincerely,

Lemi B Tolu (MD, Assistant prof of obstetrics and gynecology).

Saint Paul’s Millennium Medical College (SPHMMC)

Department of Obstetrics and Gynecology

Addis Ababa, Ethiopia.

Email: lemi.belay@gmail.com

Dear editor

Thanks for thoughtful review of the manuscript. Below is point by point response to raised concerns and how we changed the manuscript according to the comments.

#Editor

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Response: Dear editor thank you very much manuscript revised according to the journal requirement.

2. We noticed you have some minor occurrence of overlapping text with the following previous publication(s), which needs to be addressed:

Response: Thank you a lot, concern addressed (line 42-62)

Reviewer #1:

A well thought study looking at the perinatal outcome of meconium stained amniotic fluid (MSAF) among laboring mothers at teaching hospital in Ethiopia. This study brings out important information regarding the outcomes of MSAF in Ethiopia.

Response: Thank you very much for energizing comment, below is the line by line response to concerns.

#Corrections:

1. Line 42 –Can be corrected as: Meconium stained amniotic fluid is usually seen in 12 to 16% of deliveries.

Response: Corrected (Line 42)

2. Line 47- Can be corrected as: Though its controversial to differentiate physiologic or pathologic meconium staining of amniotic fluid, there are few shreds of evidence that indicates its association (instead of associated) with increased meconium aspiration syndrome, respiratory distress, neonatal sepsis and perinatal mortality.

Response: Corrected (line47)

3. Line 77: Gestational age was (instead of is) calculated from reliable last normal menstrual period or early ultrasound done before 24 weeks and those with an unknown date or without early ultrasound were (where) excluded.

Response: Corrected (line 85)

4. Line 168: All thin (grade one) stained fluid gave birth vaginally, while 80(86%) of thick (grade two and three) group underwent (instead of undergone) operative delivery.

Response: Corrected (Line 178)

5. Line 190: Our study also highlighted that 86% of (thich) thick stained 190 amniotic fluid group (grade two and three) undergoes operative delivery which indicates the risk of fetal heart rate abnormality with meconium staining

Response: Corrected (Line 199)

6. Line 202: Several investigators

Response: Corrected (Line 212)

7. Line 209: In the current research, MAS was (has) diagnosed in 6.3 % a baby of the stained fluid group, which is 2.3 times compared to a non-stained fluid group

8. Table :2 P value is not in line for prim gravida and Induced labor.

Response: corrected (table 2)

#Suggestions

1.It is unclear what the primary objective of this study was in the introduction. To determine the outcomes for physiologic v pathologic meconium staining or to compare MSAF outcomes with clear amniotic fluid. My recommendation is to have a clear objective in your introduction.

Response: Thank you, suggestion addressed (68-69)

2.My suggestion is to compare Meconium aspiration syndrome between different types of MSAF and not with clear amniotic fluid and to analyze the outcome differences between different types of MSAF

Response: Dear reviewer thank you very much, the wrong comparison with clear amniotic fluid is corrected as Meconium aspiration syndrome was seen in 9(6.3%) stained fluid group (line 183-184). Unfortunately, among those 9 (6.3%) who developed MAS we didn’t collected the subgroups on thickness of amniotic fluid.

3. Were there any other conflicting variables like scheduled repeat C- section? Were those mothers excluded

Response: Dear reviewer our population are those in labour, admitted to labour ward.

4. My suggestion is also to compare the outcomes based on different Gestational age (Early term, term and post term).

Response: Dear reviewer we did gestational age matched data collection to control possibility of gestational age confounding the outcomes.

Reviewer #2:

#General notes: The text should be proofread for spelling, spacing and grammatical mistakes. The overall readability is borderline, but in several spots, it is very difficult to understand what the authors mean. Please have the text proofread and edited. I appreciate the authors efforts to have the text proofread by a professional service, but it seems the editing service used by authors was substandard.

Response: Dear reviewer, thank you very much. We reviewed the whole manuscript to address the spelling, spacing and grammatical mistakes concern.

#Specific comments:

1. Line 68 and 69 do not belong to methods since you report the results. Please move it to the result section.

Response: Concern addressed (line 76-77 and line 144-145)

2. Line 158. You define prolonged rupture of membranes as longer than 12h. It seems to be different from 18 hours used in the US. Can you explain somewhere the choice of this interval?

Response: Dear reviewer yes, it is true different definitions is used for prolonged rupture of membrane. Pediatrics commonly use 18 hrs. in our hospital to consider for risky of neonatal sepsis. In Obstetrics 12 hrs. is commonly used

3. Lines 172-174. MSAF is one of the requirements to establish MAS diagnosis (your lines 105-106). How the patients with no MSAF were diagnosed with MAS?

Response: Thank you the wrong comparison corrected as Meconium aspiration syndrome was seen in 9(6.3%) stained fluid group (line 183-184)

4. In the description of demography (Table 1), the religion part might be misunderstood by some readers. Please specify if the Orthodox religion means Orthodox Judaism or Orthodox Christianity. I would spell out religions as Christian with subgroups of Eastern Orthodox and Protestant. Alternatively, I would spell out Orthodox Judaism and Christian (Protestant).

Response: Thanks, concern addressed as Orthodox Christian (Table 1)

5. Table 2. Please specify if the diabetes was type one or pregnancy-induced.

Response: Thanks, concern addressed as pregestational DM (Table 2)

It is interesting, that the follow-up was performed via a cell phone connection. Please, comment if the population of the woman included in the study or admitted to the hospital truly represent the population of Addis-Ababa. I would expect that only small proportion of the population could afford cell phones. Please clarify if I am wrong.

Response: Dear reviewer currently most Ethiopians, even rural one had cell phone. The fact that our study is in Addis Ababa, capital city makes the follow up easy as our study population were from Addis Ababa or surrounding city.

Submitted filename: Reviewer.docx

Click here for additional data file.

26 Aug 2020

PONE-D-20-13739R1

Perinatal Outcome of Meconium Stained Amniotic Fluid among labouring mothers at teaching referral hospital in urban Ethiopia.

PLOS ONE

Dear Dr. Tolu,

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. Manuscript does need minor revision.

Please address all concerns raised by Reviewer 2.  We will look forward to your submission.

Please submit your revised manuscript by Oct 10 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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

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

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

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

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

We look forward to receiving your revised manuscript.

Kind regards,

Abhishek Makkar, M.D.

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

Reviewer #2: All comments have been addressed

**********

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

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

Reviewer #1: (No Response)

Reviewer #2: Partly

**********

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

Reviewer #1: (No Response)

Reviewer #2: I Don't Know

**********

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: (No Response)

Reviewer #2: Yes

**********

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

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

Reviewer #1: (No Response)

Reviewer #2: No

**********

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: (No Response)

Reviewer #2: Dear Authors,

Sorry for delay with my review – it is crazy around here (in my part of the planet).

I would like to stress it again, I like the idea of your paper and this data should be published in the best possible form.

I am still not satisfied with the English part. I see the other reviewer helped you with some of that, but the text still needs a major proofreading. For example, your home city is misspelled on the first page. It is spelled as “Addis ababa” �. The title has words started with capital letters in random order. Chose one style. Capitalize them all or none. Obviously, the first word in the sentence and the name of the country should be capitalized, should you chose not capitalizing all the words. And so on and so on for the entire paper including papers.

Your result part of the summary is too descriptive. The readers will be looking for specific numbers of incidence of MAS in MSAF, Apgar scores, NICU admission rates and so on. Your description what was higher or lower is not enough. Please, provide the data of the incidence of MSAF and MAS in the summary. Please add the proportion of primigravida mothers in your population to the summary, if the space allows. Actually, you could cut out a big proportion of the statistics part form the summary to include more data.

It is interesting, that most of your patient population were primigravida. Perhaps you may explain this in discussion, why your group is so different from the rest of the country with average fertility rate over 4. Also, your group is very different form the rest of the country in regard of the literacy. You report that 6-8% of your mothers were illiterate, while in general illiteracy rate in Ethiopia is reported to be more than 50%. Perhaps you would like to mention this and explain why your group is different. Could it be explained by better education in Addis Ababa or just the population your hospital serves? My primary concern is that you group is not true representative of population of the country in terms of education, wealth and accessibility to health care. This in turn could result in different accessibility and desire to use the health care services. With all value of your data it is important to mention the limitations.

Perhaps I have missed it, but I was not able to see the reason for Cesarean section delivery in your patients. It is important to indicate whether it was scheduled or the obstetricians had to do it emergently for any reason. Perhaps you also could discuss if the Cesarean section delivery places a baby at risk of MAS or the Cesarean section serves as a rescue for infants who are about to develop MAS.

Table 4 – I do not see a reason for removal of the MAS incidence from this table. Isn’t it the main outcome?

Good luck.

**********

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

Reviewer #2: No

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

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

27 Aug 2020

August 27, 2020

To: PLOS ONE Editor in chief.

Dear Editor in chief.

We would like to thank the editor and reviewers for their thoughtful review of the manuscript. They raise important issues and their inputs are very helpful for improving the manuscript. We agree with almost all their comments and we have revised our manuscript accordingly. We respond below in detail to each of the editor comments. We hope that you find our responses satisfactory and that the manuscript is now acceptable for publication

Looking forward hearing from you soon

Sincerely,

Lemi B Tolu (MD, Assistant prof of obstetrics and gynecology).

Saint Paul’s Millennium Medical College (SPHMMC)

Department of Obstetrics and Gynecology

Addis Ababa, Ethiopia.

Email: lemi.belay@gmail.com

Dear editor

Thanks for thoughtful review of the manuscript. Below is point by point response to raised concerns by reviewer#2.

Reviewer #2: Dear Authors,

1. I would like to stress it again, I like the idea of your paper and this data should be published in the best possible form.

Response: dear reviewer thanks a lot. We will also do our best to extent of our potential and consult people in our network.

2. I am still not satisfied with the English part. I see the other reviewer helped you with some of that, but the text still needs a major proofreading. For example, your home city is misspelled on the first page. It is spelled as “Addis ababa” �. The title has words started with capital letters in random order. Choose one style. Capitalize them all or none. Obviously, the first word in the sentence and the name of the country should be capitalized, should you chose not capitalizing all the words. And so on and so on for the entire paper including papers.

Response: Dear Reviewer thanks for the comment. Title edited accordingly and the whole text proofreading done by two authors (me and Garumma Tolu Feyissa). However, “Addis Ababa” is normally spelled like that though we might find “Addis Abeba” in some texts.

3. Your result part of the summary is too descriptive. The readers will be looking for specific numbers of incidence of MAS in MSAF, Apgar scores, NICU admission rates and so on. Your description what was higher or lower is not enough. Please, provide the data of the incidence of MSAF and MAS in the summary. Please add the proportion of primigravida mothers in your population to the summary, if the space allows. You could cut out a big proportion of the statistics part form the summary to include more data.

Response: Dear reviewer the abstract section was edited accordingly (lines 31-40)

4. It is interesting, that most of your patient population were primigravida. Perhaps you may explain this in discussion, why your group is so different from the rest of the country with average fertility rate over 4. Also, your group is very different form the rest of the country in regard of the literacy. You report that 6-8% of your mothers were illiterate, while in general illiteracy rate in Ethiopia is reported to be more than 50%. Perhaps you would like to mention this and explain why your group is different. Could it be explained by better education in Addis Ababa or just the population your hospital serves? My primary concern is that you group is not true representative of population of the country in terms of education, wealth and accessibility to health care. This in turn could result in different accessibility and desire to use the health care services. With all value of your data it is important to mention the limitations.

Response: Dear reviewer thank you very much for the input, the concerns where addressed (lines 192-193 and lines 225-232).

5. Perhaps I have missed it, but I was not able to see the reason for Cesarean section delivery in your patients. It is important to indicate whether it was scheduled, or the obstetricians had to do it emergently for any reason. Perhaps you also could discuss if the Cesarean section delivery places a baby at risk of MAS or the Cesarean section serves as a rescue for infants who are about to develop MAS.

Response: Included with indications for both groups (lines 171-175 and lines 198-199)

6. Table 4 – I do not see a reason for removal of the MAS incidence from this table. Isn’t it the main outcome?

Response: Dear reviewer MAS was removed from table because of the contradiction of MAS among clear amniotic fluid group and expressed in sentences (lines 178-179) as “Meconium aspiration syndrome was seen in 9(6.3%), stained fluid

Submitted filename: Response to reviewers .docx

Click here for additional data file.

4 Sep 2020

PONE-D-20-13739R2

Perinatal outcome of meconium-stained amniotic fluid among labouring mothers at teaching referral hospital in urban Ethiopia.

PLOS ONE

Dear Dr. Tolu,

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.

Concerns raised by reviewers still need to be addressed to present manuscript that is clear and easy to read. Your submission still requires substantial editing for English grammar and usage

We would recommend that you have your manuscript copy-edited by either a native-English speaking colleague or a professional copy-editing service. While you may approach any qualified individual or any professional scientific editing service of your choice, PLOS has partnered with American Journal Experts (AJE) to provide discounted services to PLOS authors. AJE has extensive experience helping authors meet PLOS guidelines and can provide language editing, translation, manuscript formatting, and figure formatting to ensure your manuscript meets our submission guidelines. If there are still language issues in text that AJE has edited, AJE will re-edit the text for free. To take advantage of this special partnership, visit the AJE website and enter referral code PLOS15 on the registration page for a 15% discount off AJE services (http://www.aje.com/c/plos15). If you are already registered with AJE, please log in and enter PLOS15 at the bottom of your researcher dashboard under ‘Join a Group.’ Please note that PLOS ONE does not receive any compensation in relation to services completed by AJE and that having the manuscript copyedited by AJE or any other editing services does not guarantee selection for peer review"

Please submit your revised manuscript by Oct 19 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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

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

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

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

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

We look forward to receiving your revised manuscript.

Kind regards,

Abhishek Makkar, M.D.

Academic Editor

PLOS ONE

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

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

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

15 Sep 2020

September 2020, 2020

To: PLOS ONE Editor in chief.

Dear Editor in chief.

We would like to thank the editor and reviewers for their thoughtful review of the manuscript. They raise important issues and their inputs are very helpful for improving the manuscript. We agree that the manuscript requires editing for English grammar and usage. Hence, the manuscript was copy edited by two authors (one research fellow at Drexel university/USA) and Pre-Publication Support Service (PRESS). PRESS is Michigan University/USA based publication support organization providing manuscript preparation and copy editing. We hope that you find our revision satisfactory and that the manuscript is now acceptable for publication

Looking forward hearing from you soon

Sincerely,

Lemi B Tolu (MD, Assistant prof of obstetrics and gynecology).

Saint Paul’s Millennium Medical College (SPHMMC)

Department of Obstetrics and Gynecology

Addis Ababa, Ethiopia.

Email: lemi.belay@gmail.com

Submitted filename: Editor respons.docx

Click here for additional data file.

25 Sep 2020

PONE-D-20-13739R3

Perinatal outcome of meconium-stained amniotic fluid among labouring mothers at teaching referral hospital in urban Ethiopia.

PLOS ONE

Dear Dr. Tolu,

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.

I want to compliment authors for making significant improvement to last version. There are some minor issues that need addressed. Please address the following:

In Results section: Line 156: Either add  women or patients after pregnant.

Line 156: Add Patients after postpartum

Line 157: add and after interview.

Discussion:

236:you have typo, I think you mean to say non-stained

238: take out similar, its redundant.

239: Please rephrase the line, its not clear. Do you mean to state " 6.3% of babies in stained fluid group"

Conclusion: 260: I would advise making line more generalized than giving specific timeline, the way its worded is a strong statement to make. I am assuming you are concluding it based on limited data you mentioned in line 234 and 235 in discussion.

Please consider changing it to " Knowing the high risk of early neonatal death we advise early postnatal follow up should be considered for infants born to mothers with thick MSAF."

Please submit your revised manuscript by September 30th. 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,

Abhishek Makkar, M.D.

Academic Editor

PLOS ONE

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

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

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

25 Sep 2020

September 25, 2020

To: PLOS ONE Editor in chief.

Dear Editor in chief.

We would like to thank the editor for the thoughtful review of the manuscript. They raise important issues and their inputs are very helpful for improving the manuscript. We agree with all points raised and modified the manuscript accordingly. We hope that you find our revision satisfactory and that the manuscript is now acceptable for publication

Looking forward hearing from you soon

Sincerely,

Lemi B Tolu (MD, Assistant prof of obstetrics and gynecology).

Saint Paul’s Millennium Medical College (SPHMMC)

Department of Obstetrics and Gynecology

Addis Ababa, Ethiopia.

Email: lemi.belay@gmail.com

Dear Editor

Thank you very much. Please see the point by point response to raised concerns

1. In Results section: Line 156: Either add women or patients after pregnant.

Response: Done line 136

Line 156: Add Patients after postpartum

Response: Done line 137

2. Line 157: add and after interview.

Response: Done line 137

3. Discussion:236: you have typo, I think you mean to say non-stained

Response: thank you very much, yes, it is to mean non-stained, corrected line 212

4. 238: take out similar, its redundant.

Response: Done, line 214

5. 239: Please rephrase the line, it’s not clear. Do you mean to state " 6.3% of babies in stained fluid group"

Response: Done, line 215 to 216

6. Conclusion: 260: I would advise making line more generalized than giving specific timeline, the way its worded is a strong statement to make. I am assuming you are concluding it based on limited data you mentioned in line 234 and 235 in discussion. Please consider changing it to " Knowing the high risk of early neonatal death we advise early postnatal follow up should be considered for infants born to mothers with thick MSAF."

Response: Dear editor thank you very much for such beautiful thought and input, it means a lot. Corrected as “knowing the high risk of early neonatal death we advise early postnatal follow up should be considered for infants born to mothers with thick MSAF”, line 236-237

Submitted filename: Editor respons.docx

Click here for additional data file.

26 Oct 2020

Perinatal outcome of meconium-stained amniotic fluid among labouring mothers at teaching referral hospital in urban Ethiopia.

PONE-D-20-13739R4

Dear Dr. Tolu,

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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Additional Editor Comments (optional):

Reviewers' comments:

5 Nov 2020

PONE-D-20-13739R4

Perinatal outcome of meconium stained amniotic fluid among labouring mothers at teaching referral hospital in urban Ethiopia.

Dear Dr. Tolu:

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on behalf of

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Academic Editor

PLOS ONE