Effectiveness of utilizing the WHO safe childbirth checklist on improving essential childbirth practices and maternal and perinatal outcome: A systematic review and meta-analysis.

INTRODUCTION: The World Health Organization (WHO) Safe Childbirth Checklist (SCC) is a 29-item checklist based on essential childbirth practices to help health-care workers to deliver consistently high quality maternal and perinatal care. The Checklist was intended to reduce maternal and perinatal mortality and address the primary cause of maternal death, intrapartum stillbirth, and early neonatal death. The objective of this review was to locate international literature reporting on the effectiveness of utilizing the WHO safe childbirth checklist on improving essential childbirth practices, early neonatal death, stillbirth, maternal mortality, and morbidity.
METHODS: We searched MEDLINE, google scholar, Cochrane Central Register of Controlled Trials (CENTRAL), met-Register of Controlled Trials (m-RCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/stop/search/en) to retrieve all available comparative studieshttp://www.opengrey.eu/ published in English after 2008. Two reviewers did study selection, critical appraisal, and data extraction independently. We did a random or fixed-effect meta-analysis to pool studies together and effect estimates were expressed as an odds ratio. Quality of evidence for major outcomes was assessed using the Grading of Recommendations, Assessment, development, and evaluation(GRADE).
RESULTS: We retained three cluster randomized trials and six pre-and-post intervention studies reporting on WHO SCC's. The WHO SCC utilization improved quality of preeclampsia management(moderate quality of evidence) (OR = 7.05 [95% CI 2.34-21.29]), maternal infection management(moderate quality of evidence) (OR = 7.29[95%CI 2.29-23.27]), Partograph utilization(moderate quality of evidence) (OR = 3.81 [95% 1.72-8.43]), postpartum counselling(low quality of evidence) (RR = 132.51[95% 49.27-356.36]) and still birth(moderate quality of evidence) (OR = 0.92[95% CI 0.87-0.96]). However, the utilization of the checklist had no impact on early neonatal death (very low quality of evidence) (OR = 1.07[95%CI [1.01-1.13]) and maternal death (low quality of evidence) (OR = 1.06[95% CI 0.77-1.45]).
CONCLUSIONS: Moderate quality of evidence indicates that WHO SCC utilization is effective in reducing stillbirth and Improving preeclampsia management, maternal infection management and partograph utilization Low quality of evidence indicates that WHO SCC is effective in enhancing postpartum danger sign counseling. Low and very low quality of evidence suggests that WHO SCC has no impact on maternal and early neonatal death, respectively.

Introduction

From more than 130 million births per year, the World Health Organization (WHO) estimates nearly 2,87,000 maternal deaths, 1 million intrapartum related stillbirths, and 3 million newborn deaths during the neonatal period [1]. The majority of maternal and perinatal deaths are clustered around the time of birth, with the highest number of deaths occurring within the first 24 hours after childbirth [1]. As a solution to reduce this high perinatal mortality the World Health Organization (WHO) has introduced a safe childbirth checklist(SCC) in 2008, a 29-item evidence-based essential childbirth practice to help health-care workers to deliver consistently high quality maternal and perinatal care [2]. The WHO Safe Childbirth Checklist (SCC) incorporates major causes of maternal death, intrapartum stillbirth, and early neonatal death and expected to have an impact on maternal and perinatal morbidity and mortality [3]. These practices are organized on admission, just before birth, soon after birth, and on discharge to confirm health care workers have completed essential birth practices at each point for every birth event [4].

A pre and post-intervention pilot studies in India reported a two-fold increased delivery of evidence-based essential birth practices after the introduction of SCC compared to practices before the introduction of the SCC at each birth event [5]. However, some studies report that SCC has no impact on perinatal or maternal mortality [3]. Another study in a tertiary center in Sri Lanka stated that the SCC tool uptake by healthcare workers was higher and has resulted in improved delivery of evidence-based birth practices [6].

Observational studies reported significant improvement in WHO SCC targeted essential maternal and newborn care practices [7-11]. The studies indicate that women delivering in WHO SCC program intervention facilities received more safe childbirth practices as compared to women receiving care in the control facilities [7-11].

A prospective interventional study conducted at a tertiary care hospital in India found that implementation of a safe childbirth checklist has no impact on maternal or neonatal mortality reduction. However, there was increased partograph use, antibiotic administration, and active management of the third stage of labour [12]. The Better-Birth trial in north India, where peer coaching was used to increase adherence of workers to WHO SCC at sub-district and primary health care facilities, reported a significant increase in health care worker's adherence to essential practices. However, the study indicated that the utilization of the tool didn't reduce perinatal and maternal death [13]. A recent quasi-experimental study conducted in the Rajasthan district of India found out that implementation of SCC program potential averts 40,000 intrapartum deaths per year, the most reduction being from prevention of stillbirths [14].

Contradicting results from different studies on WHO SCC's impact on maternal and perinatal death despite an improvement of essential practices mandates searching for robust evidence on the effectiveness of SCC implementation on improving essential childbirth practices and reduction of maternal and perinatal deaths. In our review, Therefore, this systematic review aimed to investigate the effectiveness of utilizing the WHO safe childbirth checklist on improving essential childbirth practices and maternal and perinatal outcomes.

Review question(s)

The review sought to locate international literature reporting on the impact of WHO SCC utilization. Specifically, the review questions were:

What is the effectiveness of the WHO safe childbirth checklist on improving essential childbirth practices?

What are the effectiveness of the WHO safe childbirth checklist on reducing maternal and perinatal morbidity and mortality?

Methods

This systematic review was prepared using PRISMA reporting guidelines (S1 Checklist) for systematic reviews [15]. The review was conducted per Cochrane handbook for a systematic review of interventions [16], and a prior protocol registered in PROSPERO 2019 CRD42019137092(available at https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=137092). During the conduct of the review, we considered the following inclusion criteria:

Participants

For the sake of this review, we considered health professionals directly involved in the care for mothers and newborns during labour, delivery, and post-partum periods and mothers and newborns in any health care settings.

Intervention

The intervention we considered for this review was the utilization of the WHO safe childbirth checklist by health professionals.

Comparator

The comparator considered for this review was labouring mothers and newborn care without WHO safe childbirth or any other structured checklist.

Outcomes

The outcomes considered for this review were the incidence of essential childbirth practices, early neonatal death, stillbirth, maternal death, and maternal morbidity.

Essential childbirth practices considered in this review were:

Partograph use.

Maternal infection management upon admission: Evaluation of mothers for the necessity of antibiotics by temperature measurement and looking for the sign of intra-amniotic infection like prolonged foul-smelling vaginal discharge, uterine tenderness, and maternal tachycardia.

Preeclampsia management: Evaluation of mothers for the necessity of Mgso4 and anti-hypertensive administration by measuring blood pressure upon admission.

Active management the third stage of labour (AMTSL): Oxytocin administration within one minute of delivery of baby, controlled cord traction, and uterine massage.

Maternal postpartum bleeding assessment.

Breastfeeding started within one hour.

Newborn feeding assessment upon discharge.

Postpartum danger signs counseling.

Counseling on family planning.

Early Neonatal Death (END)

Death of newborn within seven days of delivery.

Stillbirth

Intrapartum fetal death after the admission of the patient for labour and delivery. Studies that included fetal death before admission of the patient to a health facility were excluded. For this review, we defined perinatal mortality as intrapartum stillbirth and newborn death within seven days of delivery

Maternal death

the death of mothers caused by obstetric related events within the health facilities.

Maternal morbidity

blood transfusion, hysterectomy, maternal sepsis, postpartum bleeding, and maternal seizure.

Types of studies

This review considered all studies with comparative designs, such as randomized controlled trials (RCTs), and, before and after studies published from 2008 to November 11/2019(the day literature search was done) in English. This date range was selected because the WHO safe childbirth checklist was introduced in 2008 [2].

Search strategy

We did a preliminary search of PROSPERO, MEDLINE, the Cochrane Database of Systematic Reviews, and the JBI Database of Systematic Reviews and Implementation Reports, and no published or ongoing systematic reviews on the topic were identified. The search strategy aimed to locate both published and unpublished studies. An initial limited search of MEDLINE was undertaken, followed by an examination of the text words contained in the titles and abstracts of relevant articles, and the index terms used to describe the articles. A second search using all identified keywords and index terms was then undertaken across all included databases. Thirdly, the reference list of all identified reports and articles was searched for additional studies. The data basis searched were: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), met-Register of Controlled Trials (m-RCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). Likewise, a search for grey literature was conducted using Google Scholar, Open-Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), and WHO websites. A detailed search strategy for MEDLINE was provided in a supplementary file (S1 Table).

Study selection

Following the search, all identified citations were loaded into EndNote, and duplicates were removed. Two independent reviewers screened titles and abstracts for assessment against the inclusion criteria for the review. The full texts of potentially eligible studies were retrieved and assessed in detail against the inclusion criteria by two independent reviewers.

Assessment of methodological quality

Eligible studies were critically appraised by two independent reviewers for methodological quality, using Cochrane risk of bias assessment tool from Rev man [16]. All disagreements that arose were resolved through discussion and, there was no requirement for a third reviewer. All studies regardless of the results of their methodological quality were undergone data extraction, and the results of critical appraisal were reported in narrative form and a table.

Data extraction and synthesis

We extracted data using the Rev Man version 5.3. The relevant information such as population characteristics, authors, study setting, study design, publication year, interventions, and summary of the findings was extracted. Where necessary, we asked primary authors to provide additional information on the articles. Studies were pooled in a statistical meta-analysis using Rev Man version 5.3. Effect sizes were expressed as odds ratios (for dichotomous data), and their 95% confidence intervals were calculated for analysis. We assessed heterogeneity statistically using the Tau2 and I2 tests. We considered I2 tests above 50% as indicative of significant heterogeneity. Besides, the statistical heterogeneity among studies was checked in terms of study settings, sample size, and study design. We conducted leave out analyses by excluding studies with very large or very low effect estimates and different study designs. Also, we compared the random and fixed-effects model, and the decision was made based on the best-fitting model to the data [17].

The certainty of the quality of evidence was assessed using a software package (Grade pro) developed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) [18], group for the following outcomes: Partograph use, preeclampsia management, maternal infection management, postpartum counseling, neonatal death, stillbirth, and maternal death.

Results

The search yielded a total of 458 records. After removing duplicates, 130 documents were retained for further examination. After screening the titles and abstracts, 13 papers were retained for full-text review. Based on pre-defined inclusion criteria, nine records were included in the systemic review (Fig 1).

Fig 1

The prisma flow diagram showing the study selection process.

From four studies excluded by reason, two (Delaney et al. [19] and Kara et al. [5]) reported on the impact of peer coaching on adherence to WHO SCC and one study (Patabendige, M and Senanayake, H. [20]) reported effects of Sri-Lanka context-specific modified WHO Safe Childbirth Checklist on adherence to WHO SCC. One cross-sectional study was excluded because of the non-comparative nature of the study (Patabendige, M and Senanayake, H. [8]) (S1 Document).

Characteristics of included studies

All the nine studies included compared WHO SCC use to none use of WHO SCC. Among the nine studies included in this review, Varghese et al. [14], Semrau et al. [21], and Kumar et al. [7] reported on the finding of a randomized cluster trial conducted in India. Also, another two pre-and-post intervention studies were conducted in India (Spector et al. [3], and Varaganti et al. [12]). The other four pre-and-post intervention studies were conducted in Italy (Albolino et al. [22]), Namibia (Kabongo et al. [9]), Bangladesh (Nababan et al. [11]), and Rwanda (Tuyishim et al. [10]) respectively. Two studies were conducted at a tertiary health facility (Albolino et al. [22] and Varaganti et al. [12]) whereas four (Kabongo et al. [9], Nababan et al. [11], Tuyishim et al. [10], and Varghese et al. [14]) at the district health facility, two (Semrau et al. [21] and Spector et al. [3]) at the subdistrict health facility and one (Kumara et al. [7]) at both district and subdistrict health facility (Table 1).

Table 1

Characteristics of included studies.

Study ID.	Study design	Setting/country.	Participants	Number of participants in Intervention (WHO SCC)/comparison (Without WHO SCC) groups	Outcomes
Albolino et al. 2018[22]	pre-and-post intervention.	Tertiary hospital/Italy.	Labouring mothers.	Intervention: 98	Essential childbirth practices.
				Comparasion:141.
Kabongo et al. 2018[9]	pre-and-post intervention	District hospital /Namibia	Labouring mothers and newborns.	Intervention: 1526	Essential childbirth practices.
				Comparasion:1401	Perinatal outcome.
Kumar et al.2016[7].	Cluster randomized.	District and subdistrict hospital and health centers/India.	Labouring mothers.	Intervention: 240	Essential childbirth practices.
				Comparasion:240.
Nababan et al., 2017[11].	pre-and-post intervention	District Hospital/	Uncomplicated vaginal deliveries.	Intervention: 157	Essential childbirth practices.
		Bangladesh.		Comparasion:153.
Semrau et al., 2017[21].	Cluster randomized	Subdistrict hospital and primary and community health centers/India.	Labouring mothers and newborns.	Intervention: 1048	Essential childbirth practices, perinatal outcome, maternal death, and morbidity.
				Comparasion:1090
Spector et al. 2012[3].	pre-and-post intervention	Subdistrict hospital/India.	Labouring mothers and newborns.	Intervention: 639	Essential childbirth practices.
				Comparasion:405	Perinatal outcome.
					Maternal death.
Tuyishim et al. 2018[10]	pre-and-post intervention	District hospital/Rwanda	Labouring mothers.	Intervention: 95	Essential childbirth practices.
				Comparasion:106
Varaganti et al. 2018[12].	pre-and-post intervention.	Tertiary hospital/India.	Labouring mothers and newborns.	Intervention: 620	Essential childbirth practices.
				Comparasion:635	Maternal death.
					Perinatal outcome.
Varghese et al., 2019[14].	Cluster-randomized.	District/secondary level facility/India.	Labouring mothers and newborns.	Intervention: 77231	-Stillbirth.
				Comparasion:59800	-Early neonatal death.

The methodological quality of the included studies

Eight and one of the Included studies were judged to be high and low risk for allocation concealment respectively, whereas seven and two of included studies were judged to be high and low risk for random allocation respectively (Fig 2).

Fig 2

Risk of bias graph, review authors' judgments about each risk of bias item presented as percentages across all included studies.

Allocation

Three studies were cluster-randomized (Varghese et al. [14], Semrau et al. [21], and Kumar et al. [7]). Six studies were-random pre-and-post intervention study (Albolino et al. [22], Kabongo et al. [9], Nababan et al. [11], Spector et al. [3], Varaganti et al. [12] and Tuyishime et al. [10]). Only the study by Kumar et al. (2016) was concealed by central allocation (Fig 3).

Fig 3

Risk of bias summary: Review authors' judgments about each risk of bias item for each included study.

Incomplete outcome data (Attrition Bias)

Only the study by Nababan et al. [11] was felt to have incomplete outcome data potentially, but they did sensitivity analysis by excluding incomplete reports (Fig 3).

Blinding of participants (performance Bias)

Blinding of health professionals is not possible in all studies as it involves training and introduction of the checklist. Still, three of the studies are cluster randomized with similar data collection for both control and intervention facilities (Varghese et al. [14], Semrau et al. [21] and Kumar et al. [7]) and one study collected retrospectively from documents (Albolino et al. [22]). Five studies collected data by observation of health workers practice which might have introduced hawthorn effect (Albolino et al. [22], Kabongo et al. [9], Nababan et al. [11], Spector et al. [3], Varaganti et al. [12] and Tuyishime et al. [10]) (Fig 3).

Blinding of outcome assessment

Data collectors didn’t know intervention and control facilities in three studies (Varghese et al. [14], Semrua et al. [21], and Kumar et al. [7]). Four studies were not blinded but used a pre-defined checklist and unlikely to affect the outcome of the study (Albolino et al. [22], Kabongo et al. [9], Nababan et al. [11], Spector et al. [3], and Tuyishime et al. [10]). In one study, investigators were involved in data collection (Kabongo et al. [9]), and one study didn't report data collection methods (Varaganti et al. [12]) (Fig 3).

Selective reporting (reporting bias)

Eight studies used a pre-defined data collection protocol, and all outcomes of interest were reported. One study didn’t use a clear study protocol (Varaganti et al. [12]) (Fig 3).

Other potential sources of bias

Three cluster-randomized studies considered design effect during a sample size calculation, had a control group, and had similar baseline similarity in terms of health professionals (Varghese et al. [14], Semrua et al. [21] and Kumar et al. [7]). Five of the studies were pre-and-post-intervention without a control group and didn't consider the design effect. Still, all had similar baseline health professionals (Albolino et al. [22], Kabongo et al. [9], Nababan et al. [11], Spector et al. [3], Varaganti et al. [12] and Tuyishime et al. [10]) (Fig 3).

Review findings

1. Preeclampsia management

There were seven times more likelihood of evaluating labouring mothers for preeclampsia and administration of MgSo4 and antihypertensive drugs (OR,7.05, 95% CI 2.34–21.29, seven studies, 5667 participants) among professionals utilizing WHO SCC (Moderate quality of evidence). Random effect meta-analysis was used for this outcome because of significant heterogeneity (I2 = 97% and Tau2 = 1.97). The substantial heterogeneity indicates that treatment effects vary between studies, so we investigated the factors affecting treatment effects by a subgroup analysis of study design. A meta-analysis of cluster-randomized studies showed 20 times more likelihood of evaluation and management of labouring mothers for preeclampsia among professionals utilizing WHO SCC (OR,20, CI 15.19–26.32, I2 18% and Tau2 0.01, two studies, 2618 participants (Fig 4).

Fig 4

Forest plot of comparison: 1 WHO SCC use and None use, outcome: 1.1 Preeclampsia management.

2. Maternal infection management

Professionals utilizing WHO SCC were 17 times more likely to evaluate and manage maternal infection compared to none use of WHO SCC (OR,17.46, 95% CI 3.62–84.24, seven studies, 5667 participants) (Moderate quality of evidence). Random effect meta-analysis was utilized for this outcome because of significant heterogeneity (I2 = 98% and Tau2 = 4.27). The substantial heterogeneity indicates that treatment effects vary between studies, so we investigated the factors affecting treatment effects by a subgroup analysis of study design. A meta-analysis of cluster-randomized studies showed 214 times more likely maternal infection evaluation and management among professionals utilizing WHO SCC (OR 214.85, CI 93.36–494.41, I2 33% and Tau2 0.02, two studies, 2618 participants) (Fig 5).

Fig 5

Forest plot of comparison: 1 WHO SCC use and none use., outcome: 1.2 Maternal infection management.

3. Partograph

Professionals utilizing WHO SCC was five times more likely to use partograph compared to none use of WHO SCC (OR 5.48, 95% CI 2.21–13.62, six studies, 5323 participants) (Moderate quality of evidence). Random effect meta-analysis was utilized for this outcome because of significant heterogeneity (I2 = 95% and Tau2 = 1.10) The substantial heterogeneity indicates that treatment effects vary between studies, so we investigated the factors affecting treatment effects by a subgroup analysis of study design. A meta-analysis of cluster-randomized studies showed twelve times more partograph use among professionals utilizing WHO SCC (OR 12.25, CI 7.29–20.59, I2 0%, two studies, 2618 participants) (Fig 6).

Fig 6

Forest plot of comparison: 1 WHO SCC use and none use., outcome: 1.3 Partograph.

4. Active Management of the Third Stage of Labour (AMTSL)

Six studies reported on AMTSL (Kumar et al. [7], Nababan et al. [11], Spector et al. [3], Tuyishim et al. [10], Varaganti et al. [12] and Semrau et al. [21]). We didn't perform a meta-analysis because of significant heterogeneity that did not resolve by planned sensitivity analysis. Four studies uniformly reported significant improvement in AMTSL with WHO SCC utilization (Kumar et al. [7], Spector et al. [3], Varaganti et al. [12], and Semrau et al. [21]). In contrast, two studies reported statistically non-significant improvement (Nababan et al. [11] and Tuyishim et al. [10]) (Table 2).

Table 2

AMTSL with and without WHO SCC utilization.

Study	AMTSL without WHO SCC (Number / total and %)	AMTSL with WHO SCC (Number/ total and %)	P-value
1. Kumar et al. [7]	58/240(24%)	211/240(88%)	<0.001
2. Nababan et al. [11]	134/153(88%)	156/157(99%)	<0.001
3. Semrau et al. [21]	154/1041(14.8%)	549/1019(53.9%)	<0.001
4. Spector et al. [3]	33/338(8.4%)	402/583(68.9%)	<0.001
5. Tuyishim et al. [10]	76/92(77.6%)	84/98(84.8%)	0.206
6. Varaganti et al. [12]	600/635(94.5%)	601/620(96.9%)	0.032

5. Maternal postpartum bleeding assessment

Four studies reported on maternal postpartum bleeding assessment (Kumar et al. [7], Nababan et al. [11], Spector et al. [3], and Varaganti et al. [12]). We didn't perform a meta-analysis because of significant heterogeneity that did not resolve by planned sensitivity analysis. Two studies uniformly reported significant improvement in postpartum bleeding assessment with WHO SCC utilization (Kumar et al. [7] and Spector et al. [3]). In contrast, two studies reported statistically non-significant improvement (Varaganti et al. [12] and Nababan et al. [11]) (Table 3).

Table 3

Maternal postpartum bleeding assessment with or without WHO SCC utilization.

Study	Maternal postpartum bleeding assessment without WHO SCC (Number and %)	Maternal postpartum bleeding assessment with WHO SCC (Number and %)	P-value
1. Kumar et al. [7]	84/240(35%)	218/240(91%)	<0.001
2. Nababan et al. [11]	152/153(99%)	157/157(100%)	0.318
3. Spector et al. [3]	58/388(15%)	577/583(99%)	<0.001
4. Varaganti et al. [12]	25/635(3.94%)	20/620(3.22%)	0.498

6. Breastfeeding started within one hour

Mothers handled by professionals utilizing WHO SCC was 17 times more likely to initiate breastfeeding within one hour compared to none use of WHO SCC (OR 21.18, 95% CI 17.54–25.57, five studies, 4050 participants). Random effect meta-analysis was utilized for this outcome because of significant heterogeneity (I2 = 89%). The substantial heterogeneity indicates that treatment effects vary between studies, so we investigated the factors affecting treatment effects by subgroup analysis using study design as a grouping variable. A meta-analysis of pre-and-post-intervention studies showed twenty times more likely initiation of breastfeeding among mothers handled by professionals utilizing WHO SCC (OR 20.03, 95%CI 13.38–29.97, I2 48%, three studies, 1462 participants) (Fig 7).

Fig 7

Forest plot of comparison: 1 WHO SCC use and none use., outcome: 1.4 breastfeeding started within one hour.

7. Newborn assessment for sepsis

Five studies reported on newborn assessment for sepsis (Kumar et al. [7], Nababan et al. [11], Spector et al. [3], Tuyishim et al. [10] and Varaganti et al. [12]). We didn't perform a meta-analysis because of significant heterogeneity that did not resolve by planned sensitivity analysis. Two studies uniformly reported significant improvement in newborn assessment for sepsis with WHO SCC utilization (Kumar et al. [7] and Spector et al. [3]). In contrast, two studies reported statistically non-significant improvement (Varaganti et al. [12] and Tuyishim et al. [10]). Nababan et al. [11] reported that there is no difference in newborn assessment for sepsis with or without WHO SCC utilization (0.65% versus 0.64% with a p-value of 0.985) (Table 4).

Table 4

Newborn assessment for sepsis with or without WHO SCC.

Study	Newborn assessment for sepsis without WHO SCC (Number and %)	Newborn evaluation for sepsis with WHO SCC (Number and %)	P-value
1. Kumar et al. [7]	2/240(1%)	103/240(43%)	<0.001
2. Nababan et al. [11]	1/153(0.65%)	1/157(0.64%)	0.985
3. Spector et al. [3]	0/338	279/489(57.1%)	<0.001
4. Tuyishim et al. [10]	1/101(1%)	5/98(5.1%)	0.115
5. Varaganti et al. [12]	100/635(15.7%)	98/620(15.8%)	0.977

8. Newborn feeding assessment upon discharge

Six studies reported on newborn feeding assessment upon discharge (Kumar et al. [7], Nababan et al. [11], Spector et al. [3], Tuyishim et al. [10], Varaganti et al. [12] and Semrau et al. [21]). We didn't perform a meta-analysis because of significant heterogeneity that did not resolve by planned sensitivity analysis. Three studies uniformly reported significant improvement in newborn feeding assessment upon discharge with WHO SCC utilization (Kumar et al. [7], Spector et al. [3], and Semrau et al. [21]). In contrast, three studies reported statistically non-significant improvement in newborn feeding assessment upon discharge by WHO SCC utilization (Varaganti et al. [12], Nababan et al. [11], and Tuyishim et al. [10]) (Table 5).

Table 5

Newborn feeding assessment upon discharge with or without WHO SCC.

Study	Newborn feeding assessment upon discharge without WHO SCC (Number and %)	Newborn feeding assessment with WHO SCC (Number and %)	P-value
1. Kumar et al. [7]	31/240(13%)	194/240(81%)	<0.001
2. Nababan et al. [11]	152/153(99%)	157/157(100%)	0.318
3. Semrau et al. [21]	2/1041(0.2%)	225/1019(22.5%)	<0.001
4. Tuyishim et al. [10]	89/101(88.1%)	84/98(84.8%)	0.540
5. Varaganti et al. [12]	451/635(71.1%)	458/620(73.8%)	0.259
6. Spector et al. [3]	211/338(62.5%)	448/488(91.8%)	<0.001

9. Postpartum counseling

There was 73 times more likelihood of counseling mothers on postpartum danger signs among professionals utilizing WHO SCC (OR 73.9, 95% CI 37–142.31, four studies, 1876 participants) (Low quality of evidence). Random effect meta-analysis was used for this outcome because of significant heterogeneity (I2 = 65%). The substantial heterogeneity indicates that treatment effects vary between studies, so we investigated the factors affecting treatment effects by a subgroup analysis of study design. Fixed effect meta-analysis of pre-and-post-intervention studies showed 132 times more postpartum danger sign counseling among professionals utilizing WHO SCC (OR 132.51, 95% CI 49.27–356.36, I2 0%, three studies, 1396 participants) (Fig 8).

Fig 8

Forest plot of comparison: 1 WHO SCC use and none use., outcome: 1.5 postpartum counseling.

10. Counseling on family planning

Five studies reported on counseling on family planning (Kumar et al. [7], Nababan et al. [11], Tuyishim et al. [10], Spector et al. [3], and Varaganti et al. [12]). We didn't perform a meta-analysis because of significant heterogeneity that did not resolve by planned sensitivity analysis. Two studies uniformly reported significant improvement in counseling for family planning with WHO SCC utilization (Kumar et al. [7] and Spector et al. [3]). In contrast, two studies reported that there is no difference in counseling for postpartum family planning with or without WHO SCC (Varaganti et al. [12] and Tuyishim et al. [10]). Nababan et al. [11] reported that there is a statistically non-significant improvement in counseling for family planning with WHO SCC utilization (Table 6).

Table 6

Counselling on family planning with or without WHO SCC utilization.

Study	Counseling on family planning without WHO SCC (Number and %)	Counseling on family planning with WHO SCC (Number and %)	P-value
1. Kumar et al. [7]	12/240(5%)	103/240(43%)	<0.001
2. Nababan et al. [11]	152/153(99%)	157/157(100%)	0.318
3. Spector et al. [3]	1/338(0.3%)	466/489(95%)	<0.001
4. Tuyishim et al. [10]	94/100(93.1%)	88/98(88.9%)	0.333
5. Varaganti et al. [12]	635/635(100%)	620/620(100%)	-

11. Stillbirth

Utilization of WHO SCC by health professionals reduces fresh stillbirth by 8% compared to none use of WHO SCC (OR 0.92, 95% CI 0.87–0.96, I2 = 0%, five studies, 299,952 participants, moderate quality of evidence) (Fig 9).

Fig 9

Forest plot of comparison: 1 WHO SCC use and none use., outcome: 1.6 stillbirth.

12. Early neonatal death

There is no statistically significant difference in early neonatal death with or without WHO SCC utilization (OR 1.07,95% 0.01–1.13, I2 = 50% five studies, 293,467 participants, very low quality of evidence). Random effect meta-analysis was utilized for this outcome because of heterogeneity (I2 = 50%) (Fig 10).

Fig 10

Forest plot of comparison: 1 WHO SCC use and none use., outcome: 1.7 early neonatal death.

13. Maternal death

There is no statistically significant difference in maternal death with or without WHO SCC utilization (OR 1.06,95% 0.77–1.57, I2 = 0% three studies, 159,934 participants, low quality of evidence) (Fig 11).

Fig 11

Forest plot of comparison: 1 WHO SCC use and none use. Outcome: 1.7 maternal death.

14. Maternal morbidity

One study (Semrau et.al [21]) reported that WHO SCC utilization has no statistical significant impact on maternal seizure (OR 0.93,95% 0.66–1.30), PPH (OR 0.94,95% 0.91–0.98), maternal sepsis (OR 1.02,95% 0.98–1.07), peri partum hysterectomy (OR 1.02,0.54–1.95) and blood transfusion (OR 0.99,0.89–1.11).

Methodological quality was assessed for seven outcomes using the GRADE approach (Shown in Table 7 below). The outcomes preeclampsia management, maternal infection management, partograph use, and stillbirth were assigned moderate-quality evidence scores. The outcomes postpartum danger sign counseling and maternal death were assigned low-quality evidence scores, where-as early neonatal death outcomes were assigned very low-quality evidence scores. The WHO SCC utilization was effective in improving the quality of essential childbirth practices like preeclampsia management, maternal infection management, post-partum danger sign counseling, partograph use, and breastfeeding practice within one hour of delivery.

Table 7

Summary of Findings(SOF).

WHO SCC compared to Usual care without WHO SCC for laboring mothers and newborn evaluation and management
Patient or population: health professionals, laboring mothers, and newborns.
Setting: sub-district, district, and tertiary health care.
Intervention: WHO SCC
Comparison: Usual care without WHO SCC
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	The certainty of the evidence (GRADE)
	The risk with Usual care without WHO SCC	The risk with WHO SCC
Preeclampsia management.	195 per 1,000	631 per 1,000 (362 to 838)	OR 7.05 (2.34 to 21.29)	5667 (7 RCTs)	⨁⨁⨁◯ MODERATE a
Maternal infection management.	110 per 1,000	805 per 1,000 (253 to 1,000)	RR 7.29 (2.29 to 23.27)	5667 (7 RCTs)	⨁⨁⨁◯ MODERATE a
Partograph.	190 per 1,000	472 per 1,000 (287 to 664)	OR 3.81 (1.72 to 8.43)	5357 (6 RCTs)	⨁⨁⨁◯ MODERATE a
Still birth.	21 per 1,000	20 per 1,000 (19 to 21)	OR 0.92 (0.87 to 0.96)	299952 (5 RCTs)	⨁⨁⨁◯ MODERATE b
Early neonatal death.	19 per 1,000	20 per 1,000 (19 to 21)	OR 1.07 (1.01 to 1.13)	293467 (5 RCTs)	⨁◯◯◯ VERY LOW b, c, d
Maternal death.	1 per 1,000	1 per 1,000 (1 to 1)	OR 1.06 (0.77 to 1.45)	159936 (3 RCTs)	⨁⨁◯◯ LOW d, e
Postpartum counselling.	5 per 1,000	601 per 1,000 (223 to 1,000)	RR 132.51 (49.27 to 356.36)	1876 (4 observational studies)	⨁⨁◯◯ LOW f, g

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; OR: Odds ratio; RR: Risk ratio.

GRADE Working Group grades of evidence.

High certainty: We are very confident that the actual effect lies close to that of the estimate of the impact.

Moderate certainty: We are moderately confident in the effect estimate: The real impact is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

Low certainty: Our confidence in the effect estimate is limited: The actual impact may be significantly different from the estimate of the effect.

Very low certainty: We have very little confidence in the effect estimate: The exact result is likely to be substantially different from the estimate of effect.

Explanations

a. Five studies are pre-and -post-intervention studies and two cluster -randomized trials were included. Downgraded one level for risk of bias of included studies.

b. Two clusters -randomized, three pre-and-post intervention studies were included. Downgraded one level for risk of bias of included studies.

c. Lowered one level for inconsistent outcomes across studies.

d. Wide and statistically non-significant confidence interval.

e. One cluster-randomized trial and two pre-and -post-intervention studies were included. Downgraded one level for risk of bias of included studies.

f. One cluster-randomized and three pre-and -post-intervention studies were involved. Lowered one level for risk of included studies.

g. Wider confidence interval.

Discussion

This systematic review attempted to locate available evidence on the impact of WHO SCC utilization on essential childbirth practices and maternal and perinatal outcomes. Studies included in the review were three cluster randomized trials and six pre-and-post intervention studies. The pre- and -post-intervention studies did not undergo proper random allocation and allocation concealment and were judged to be at high risk of bias because of poor design. The effect estimates were also found to be high in most outcomes which might be reflecting underlying heterogeneity in set up and study design. However, the cluster-randomized studies and pre and post-intervention studies' results were consistent.

Moderate quality of evidence indicates that there was seven times more likelihood of evaluating labouring mothers for preeclampsia and administration of MgSo4 and antihypertensive drugs, 17 times more likely to evaluate and manage maternal infection, five times more likely to use partograph and 73 times more likelihood of counseling mothers on postpartum danger signs among professionals utilizing WHO SCC. Moderate quality of evidence also indicated that utilization of WHO SCC by health professionals reduces fresh stillbirth by 8% compared to none use of WHO SCC.

Low quality of evidence indicates that the utilization of WHO SCC has no impact on maternal death. Further studies are needed as only three primary studies were combined which might not reveal small changes since maternal death is a rare event. Very low quality of evidence indicates that the utilization of WHO SCC has no impact on early neonatal death. However, the primary studies included are of poor quality and moderately heterogeneous with I2 = 50% mandating further well-designed studies.

Given the significant heterogeneity, combining of the outcomes active management of the third stage of labour, newborn assessment for sepsis, newborn feeding assessment upon discharge, maternal postpartum bleeding assessment, and postnatal family planning counseling was not possible. So, further well-designed studies are needed to generate evidence on those essential childbirth practices. Four studies uniformly reported significant improvement in AMTSL with WHO SCC utilization (Kumar et al. [7], Spector et al. [3], Varaganti et al. [12] and Semrau et al. [21]). In contrast, two studies reported statistically non-significant improvement (Nababan et al. [11] and Tuyishim et al. [10]). Two studies uniformly reported significant improvement in postpartum bleeding assessment with WHO SCC utilization (Kumar et al. [7] and Spector et al. [3]). In contrast, two studies reported statistically non-significant improvement (Varaganti et al. [12] and Nababan et al. [11]).

Two studies uniformly reported significant improvement in newborn assessment for sepsis with WHO SCC utilization (Kumar et al. [7] and Spector et al. [3]). In contrast, two studies reported statistically non-significant improvement (Varaganti et al. [12] and Tuyishim et al. [10]). Nababan et al. [11] reported that there is no difference in newborn assessment for sepsis with or without WHO SCC utilization (0.65% versus 0.64% with a p-value of 0.985). Three studies uniformly reported significant improvement in newborn feeding assessment upon discharge with WHO SCC utilization (Kumar et al. [7], Spector et al. [3], and Semrau et al. [21]). In contrast, three studies reported statistically non-significant improvement in newborn feeding assessment upon discharge by WHO SCC utilization (Varaganti et al. [12], Nababan et al. [11], and Tuyishim et al. [10]).

Two studies uniformly reported significant improvement in counseling for family planning with WHO SCC utilization (Kumar et al. [7] and Spector et al. [3]). In contrast, two studies reported that there is no difference in counseling for postpartum family planning with or without WHO SCC (Varaganti et al. [12] and Tuyishim et al. [10]). Nababan et al. [11] reported that there is a statistically non-significant improvement in counseling for family planning with WHO SCC utilization.

Only one randomized cluster study (Semrau et al. [21]) reported that WHO SCC utilization has no statistically significant impact on maternal seizure, PPH, maternal sepsis, peripartum hysterectomy, and blood transfusion. This mandates further study to provide evidence on the impact of WHO SCC on maternal morbidity reduction.

Conclusions

Implications for practice

WHO SCC was effective in improving some of the essential child health practices and reducing stillbirth. Moderate quality of evidence indicates that WHO SCC is effective in) improving preeclampsia management b) improving maternal infection management c) improving partograph utilization d) reducing stillbirth. Low quality of evidence indicates that WHO SCC is effective in enhancing postpartum danger sign counseling. Low and very low quality of evidence suggests that WHO SCC has no impact on maternal and early neonatal death, respectively.

Recommendations for research

The evidence regarding the effect of utilizing WHO SCC on active management of the third stage of labour, newborn assessment for sepsis, newborn feeding assessment before discharge, and postpartum family planning counseling is limited, heterogeneous, and of poor quality. Hence, further well-designed studies are needed to provide evidence on WHO SCC's impact on the above essential childbirth practices, and perinatal mortality, maternal death, and maternal morbidity.

Studies excluded and reasons for their exclusion.

It indicates excluded studies and reasons for their exclusion.

(DOCX)

Click here for additional data file.

Search strategy for the MEDLINE database.

It indicates a detailed search strategy for PubMed.

(DOCX)

Click here for additional data file.

PRISMA checklist.

It describes the review against the checklist for the PRISMA reporting guideline.

(DOCX)

Click here for additional data file.

8 Apr 2020

PONE-D-20-00206

Effectiveness of utilizing the WHO Safe Childbirth Checklist on improving essential childbirth practices and maternal and perinatal outcome: A systematic review and meta-analysis.

PLOS ONE

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**********

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Reviewer #2: I Don't Know

Reviewer #3: Yes

**********

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Reviewer #1: I would like to mention the following comments:

1- Abstract is too long. The URLs are better not to present in abstract.

2- There is a confusion across the whole article. It is not known if it is a systematic review or prospective interventional study. It seems that the authors combined these two types of studies.

3- In the whole article, methods and inclusion/exclusion criteria of these two types of studies are confusing.

4- The version of EndNote is missing.

5- Figure 1: The details of databases (241) and other sources (217) are missing. In addition, the name of figure is not correct.

6- Table 1: Quality check of studies can be presented at a new column (last).

7- Only the quality of 8 studies has been discussed.

8- The studies with high percentage of Bias need more explanation for the solution.

9- Only two groups of "WHO SCC use and None use" have been presented in this article. How about the other methods?

10- Table 7: It is not known that the data in this table belong to systematic review or prospective interventional study.

Good Luck

Reviewer #2: This study presents a systematic review of the effectiveness of the using the WHO safe childbirth checklist (SCC) to improve child, maternal and perinatal outcomes. This study addresses an important research topic that would be of high interest. It would benefit from a more concise description of the research question and more critical discussion of the strengths and limitations of the study.

• Abstract – in the results are the measures of effect reported pooled estimates? If so, the meta-analysis process and pooling needs to be described.

• Abstract – the study outcomes need to be described in the research question

• Abstract – reference to the SOF table is not helpful in the abstract and it would be better if the results of the SOF could be summarized.

• Intro – the methods described at the bottom of page 4 and start of page 5 should be moved to the methods (not intro).

• Was the systematic review registered or is there a published protocol?

• The research question should clearly define the eligible study outcomes

• The two research questions are overlapping and it is unclear what the distinctions are? Is it the effectiveness vs efficacy or the different wording to describe the outcomes? The research question is more clearly described in the original PROSPERO registration. If it did not change after registration, I recommend using the registered question here.

• Under participants it would be helpful to know if there were any age, language, or country restrictions.

• The comparator section suggests use of other checklists was excluded. Were there any studies that compared two checklists that were excluded?

• Were the outcomes defined a priori and searched for or was this the list of outcomes that emerged from the search?

• Figure 1 requires a more detailed title and the reasons for exclusions should be provided.

• Lines 231 -235 are unclear

• What are the numbers in Table 1, column 5?

• Line 263. What is quasi-randomized? Do you mean quasi-experimental and non-randomized?

• Many of the effect estimates in the meta-analysis are incredibly large. Could this be discussed, and some context given?

• Why were meta-analyses not conducted for some of the outcomes with significant heterogeneity? It would be helpful to see all outcomes as meta-analysis when data are available.

• The discussion would benefit from some more critical review of the strengths and limitations of this study.

Reviewer #3: Abstract:it is not clear if authors included RCTs only or not

If not, as in methods, it is not clear if they pooled results from observational studies evalauted with multivariate analysis or not

methods (page 14): what does quasi xperimental studies mean?

methods: Sensitivity analyses were conducted by excluding studies with very large or very low effect estimates. Maybe authors should perform isntrad leave out analysis?

methods/results; in all analyss, despite inconsisency of 50% or more, authors used fixed effect. This should be changed into random.

results: authors should say that in all analysis rct and observational studies were consistent (it is a point of strenght)

**********

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Reviewer #3: Yes: Fabrizio D'Ascenzo

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7 May 2020

May 5, 2020

To: PLOS ONE Editor in chief.

Dear Editor in chief.

We would like to thank the 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 reviewer’s 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 and reviewer

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 comments:

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

Authors: Dear Editor thanks for the comment, the manuscript was revised accordingly, the grammar was editing further by two persons (almost rewritten).

2. We noticed you have some minor occurrence(s) of overlapping text with the following previous publication: https://doi.org/10.2147/JMDH.S228951, https://doi.org/10.1371/journal.pone.0211298,https://doi.org/10.1002/14651858.CD007892.pub5.

Authors: Dear Editor thank you very much those areas are rewritten, and reference was provided.

3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request.

Authors: Dear Editor the comment is well noted, all the data used in the analysis of the manuscript were included in manuscript and we revised accordingly.

Reviewer #1:

1- Abstract is too long. The URLs are better not to present in abstract.

Authors: Dear reviewer this comment is well noted, and we revised abstract accordingly and removed URL.

2- There is a confusion across the whole article. It is not known if it is a systematic review or prospective interventional study. It seems that the authors combined these two types of studies.

3- In the whole article, methods and inclusion/exclusion criteria of these two types of studies are confusing.

Authors: Dear reviewer thank you very much for concerns on number 2 and 3 above, the comment made us to reevaluate our work and we have done a lot of changes throughout the manuscript especially on inclusion criteria’s and English editing’s. Regarding tables it’s our plan from the beginning to describe heterogeneous data’s by tables and narratively.

4- The version of EndNote is missing.

Authors: Dear reviewer the mistake well noted, and correction made (Line 74 and 76)

5- Figure 1: The details of databases (241) and other sources (217) are missing. In addition, the name of figure is not correct.

Authors: Dear reviewer thanks for the comment, we have revised the title of the figure, in this standard Prisma flow diagram we just indicated the source of our studies, the details of the source were included under search strategy.

6- Table 1: Quality check of studies can be presented at a new column (last).

Authors: Dear reviewer, comment is well noted, and we tried to do (add last column) but it goes beyond page and violates the journal requirement. We decided to narrate under methodological quality, thank you very much for understanding us.

7- Only the quality of 8 studies has been discussed.

Authors: Dear reviewer noted and corrected (Page 15, line 274-276).

8- The studies with high percentage of Bias need more explanation for the solution.

Authors: Dear reviewer the methodology of all studies were explained under six domains in detail (page 15-17, lines 274-318).

9- Only two groups of "WHO SCC use and None use" have been presented in this article. How about the other methods?

Authors: Dear reviewer we found WHO SCC is the one widely used, especially in low and middle-income countries and we didn’t come across studies that report on other checklist fulfilling our inclusion criteria (Page 13, line 256).

10- Table 7: It is not known that the data in this table belong to systematic review or prospective interventional study.

Authors: Dear Reviewer Table 7 is summary of finding table, generated by online Gradepro (we exported data directly from Revman to Gradepro). We have included health professionals under participants in the table considering the comment. Thank you very much for understanding.

Reviewer #2

This study presents a systematic review of the effectiveness of the using the WHO safe childbirth checklist (SCC) to improve child, maternal and perinatal outcomes. This study addresses an important research topic that would be of high interest. It would benefit from a more concise description of the research question and more critical discussion of the strengths and limitations of the study.

Authors: thank you very much dear reviewer, we have addressed your comments accordingly to make the manuscript much better.

1. Abstract – in the results are the measures of effect reported pooled estimates? If so, the meta-analysis process and pooling needs to be described.

2- Abstract – the study outcomes need to be described in the research question

3- Abstract – reference to the SOF table is not helpful in the abstract and it would be better if the results of the SOF could be summarized.

Authors: Dear reviewer the above three comments are on abstract. The concerns were addressed, SOF table reference removed, the study outcomes included in research question and method of meta-analysis was described (Page 1-2, lines 22-24,31-32,25-46)

4- Intro – the methods described at the bottom of page 4 and start of page 5 should be moved to the methods (not intro).

Authors: Dear reviewer comment accepted and modified accordingly (Page 5and 6, lines 109-117)

5- Was the systematic review registered or is there a published protocol?

Authors: yes, registered on Prospero ( available at : https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=137092)

6- The research question should clearly define the eligible study outcomes

7- The two research questions are overlapping, and it is unclear what the distinctions are? Is it the effectiveness vs efficacy or the different wording to describe the outcomes? The research question is more clearly described in the original PROSPERO registration. If it did not change after registration, I recommend using the registered question here.

Authors: Dear reviewer the concerns on research questions (Concern 6 and7) were valid and good input for us, we revised accordingly (Page 6, lines 124 and 127)

8- Under participants it would be helpful to know if there were any age, language, or country restrictions.

Authors: Dear reviewer we included studies published in English (doesn’t matter whatever language they speak if the study was published in English).

9- The comparator section suggests use of other checklists was excluded. Were there any studies that compared two checklists that were excluded?

Authors: Dear reviewer we didn’t come across checklist other than WHO SCC, the studies excluded were among WHO SCC who has no outcome of our interest and study design has no comparator.

10- Were the outcomes defined a priori and searched for or was this the list of outcomes that emerged from the search?

Authors: Dear reviewer all are predefined in the protocol, except some edits and minor modifications as we come across different evidences and literatures.

11- Figure 1 requires a more detailed title and the reasons for exclusions should be provided.

Authors: Thanks, dear Reviewer, title corrected and reason for exclusion added (Page 12, line 241-244).

12- Lines 231 -235 are unclear

Authors: Dear reviewer the certainty of level of quality of evidence was assessed using Gradepro. We did grading for seven outcomes. We have made change to the sentences to make clearer (Page 11, lines 231-235)

13- What are the numbers in Table 1, column 5?

Authors: Dear Reviewer, its number of participants in the intervention and comparator group, we made the statement clearer.

14- Line 263. What is quasi-randomized? Do you mean quasi-experimental and non-randomized?

Authors: Dear reviewer yes, it’s to mean non-randomized, its corrected as cluster randomized.

15- Many of the effect estimates in the meta-analysis are incredibly large. Could this be discussed, and some context given?

Authors: Dear reviewer we tried to address in the discussion part as might be because of heterogeneity (Line 511-513)

16- Why were meta-analyses not conducted for some of the outcomes with significant heterogeneity? It would be helpful to see all outcomes as meta-analysis when data are available.

Authors: Dear reviewer we planned to pull together those without significant heterogeneity (I2 < 50%), as pulling together significant heterogenous studies for getting statistics might be introducing more bias to the evidence synthesis. That’s why we didn’t do pull them together, thanks for understanding.

17- The discussion would benefit from some more critical review of the strengths and limitations of this study.

Authors: Dear reviewer thank you very much the, we added sentence to make it clearer to first paragraph of discussion which has strength and limitations (Page 30, lines 505-508 and lines 524-528).

Reviewer#3

2. Abstract: it is not clear if authors included RCTs only or not. If not, as in methods, it is not clear if they pooled results from observational studies evaluated with multivariate analysis or not

Authors: Dear reviewer we have included types of studies. They were cluster randomized and pre and post intervention studies.

3. Methods (page 14): what does quasi experimental studies mean?

Authors: Dear reviewer It was to describe cluster randomized studies and corrected like that (Line 281).

4. methods: Sensitivity analyses were conducted by excluding studies with very large or very low effect estimates. Maybe authors should perform instead leave out analysis?

Authors: Dear reviewer what we did is like leave out analysis, we excluded and see its impact on the heterogeneity (corrected line 227).

5. methods/results; in all analyses, despite inconsistency of 50% or more, authors used fixed effect. This should be changed into random.

Authors: Dear reviewer thank you very much, we have noted the mistake and corrected (Figure 8 on page 26 and Figure 10 on page 28)

6. results: authors should say that in all analysis rct and observational studies were consistent (it is a point of strenght)

Authors: Dear Reviewer thank you very much, included in the discussion part (page 30, Lines 509)

Submitted filename: Reviewer response May 4.docx

Click here for additional data file.

26 May 2020

Effectiveness of utilizing the WHO Safe Childbirth Checklist on improving essential childbirth practices and maternal and perinatal outcome: A systematic review and meta-analysis.

PONE-D-20-00206R1

Dear Dr. Tolu,

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Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

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Reviewer #3: (No Response)

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Reviewer #1: Yes

Reviewer #3: (No Response)

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Reviewer #3: (No Response)

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Reviewer #1: Yes: Masoud Amiri

Reviewer #3: Yes: Fabrizio D'Ascenzo

28 May 2020

PONE-D-20-00206R1

Effectiveness of utilizing the WHO Safe Childbirth Checklist on improving essential childbirth practices and maternal and perinatal outcome: A systematic review and meta-analysis

Dear Dr. Tolu:

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